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The physical performance of climbers, those making high-altitude ascensions up to 8000 m, without additional oxygen was measured. Some functional criteria of the organism adaptation to exhausting physical loading at the high altitudes were selected. It was established that the forecasting of a successful ascension could be improved if the potential maximal oxygen uptake was added to the standard definition parameters of aerobic metabolism such as the maximal oxygen uptake and anaerobic threshold of oxygen uptake. The potential maximal oxygen uptake is considered to be the parameter of maximal oxygen uptake reserve growing in condition of realization of adaptive reaction to hypoxia.

Using a quantitative sensitive HPLC fluorometric assay for the measurement of plasma and urine porphyrins, we have calculated the renal clearance of uro- and coproporphyrin in normal volunteers and in patients with congenital erythropoietic porphyria and hereditary coproporphyria (HCP). In patients with porphyria cutanea tarda (PCT), only uroporphyrin clearance was calculated. Plasma porphyrin concentrations were measured in patients with chronic renal failure (CRF). All our CRF patients on haemodialysis (10) had raised plasma uroporphyrin, 4 had raised plasma heptacarboxyporphyrins and 2 had raised plasma coproporphyrin, unchanged by haemodialysis. CRF patients with raised uroporphyrins and 7-carboxyporphyrins could be distinguished from PCT in patients with normal renal function, by their higher uro/7-carboxyporphyrin ratio (8.0 vs. 1.7). Renal clearance of coproporphyrin was much greater in HCP than in any of the other groups studied. Since coproporphyrin clearance was less than creatinine clearance in most normal subjects, and because 2 patients with CRF had raised plasma coproporphyrin concentrations, we argue that the kidney is probably not a major source of coproporphyrin, as previously reported. Furthermore, the variability and degree of abnormality in plasma porphyrins in CRF would suggest caution in diagnosing chronic porphyria in patients with renal impairment.

OBJECTIVE: To describe the morphological variation of pointed teeth of buccal armature of Sergentomyia nankingensis in a supplementary study.METHODS: The morphology of Sergentomyia nankingensis was observed and the specimens included S. nankingensis captured from the field as well as the female ones bred in the laboratory and their offspring of first generation.RESULTS: The buccal armature of females and males, consists of about 10-19 and 8-15 pointed teeth and the pigmented plate is polymorphous. In the nature, the number of pointed teeth of buccal armature of Sergentomyia is unstable, varying in more than 10 teeth in the same species sometimes.CONCLUSION: Identification of species needs large amount of specimens for comparative observation. Sergentomyia sandfly should be raised separately and individually for morphological observation of its newly emerged offspring, especially when the sandfly specimens and data collected in the field were not sufficient.

PURPOSE: To compare the effectiveness of sonographically guided and palpation-guided steroid injection for the treatment of proximal plantar fasciitis.PATIENTS AND METHODS: Twenty-five consecutive patients with unilateral proximal plantar fasciitis were recruited and randomly divided into a sonographically guided group (n = 12) and palpation-guided group (n = 13). Proximal plantar fascia was assessed with a 5- to 12-MHz linear-array transducer. Pain intensity was quantified using a "tenderness threshold" (TT) and a visual analog scale (VAS). Injection of 7 mg (1 ml) of betamethasone and 0.5 ml of 1% lidocaine into the inflamed proximal plantar fascia was performed under the guidance of sonography or palpation. Patients were evaluated clinically and sonographically before injection and at 2 weeks, 2 months, and 1 year after injection. VAS- and TT-measured pain intensity, thickness, and echogenicity of the proximal plantar fascia, as well as the recurrence of heel pain, were assessed.RESULTS: Both VAS- and TT-measured levels of pain improved significantly after steroid injection in both groups (p < 0.001). Also, the thickness decreased significantly after injection (p < 0.01 in the palpation-guided group; p < 0.001 in the sonographically guided group). The number of patients with hypoechogenicity at the proximal plantar fascia decreased after steroid injection in both groups (p < 0.01 for both groups). The recurrence rate of plantar fasciitis in patients of the palpation-guided group (6/13) was significantly higher than that of the sonographically guided group (1/12) (p < 0.05).CONCLUSIONS: Steroid injection can be an effective way to treat plantar fasciitis, and injection under sonographic guidance is associated with lower recurrence of heel pain.

Plants of the genus Senna (formerly Cassia) are poisonous to livestock and other laboratory animals, leading to a syndrome of a widespread muscle degeneration, incoordination, recumbence, and death. The main histologic lesion is necrosis of skeletal muscle fibers. Recently, a mitochondrial myopathy with ragged-red and cytochrome oxidase (COX)-negative muscle fibers was recognized in hens chronically intoxicated with parts of seeds of S. occidentalis. The purpose of the present work was to investigate if there was peripheral nerve involvement in the acute intoxication of chicks with S. occidentalis seeds. Teasing of individual fibers revealed signs of extensive axonal damage with myelin ovoids. Ultrathin sections confirmed the axonal damage. Axons were filled with membranes, some residual disorganized filaments, and enlarged mitochondria. In some instances the axon disappeared and there was secondary degeneration of the myelin sheath. The present work is the first description of the neurotoxic effect of S. occidentalis intoxication. Future work should attempt to determine the mechanisms involved in this neuropathy.

We describe a patient with a pulsatile nasopharyngeal tumour. The diagnostic methods such as endoscopy, computed tomography and NMR are illustrated as well as the anatomical details of encephaloceles. Correct diagnosis prevents complications which can occur as a result of mistaking this lesion for a cyst or adenoids.

AIMS: This retrospective study evaluates early and midterm results in patients with severe left ventricular dysfunction.TECHNIQUE: Ninety-seven consecutive patients with coronary artery disease and ejection fraction of left ventricle (LVEF) less or equal to 25 % underwent elective coronary artery bypass graft procedure between September 1998 and December 2001. Mean age at operation was 66 (47-86) years. The main symptoms were angina class III-IV Canadian Cardiovascular Society (CCS) in 78 patients (80 %) and dyspnoea class III-IV New York Heart Association (NYHA) in 43 patients (44 %). The major indications for surgery were severe angina, dyspnoea in 90 patients (93 %). Cardiac index (CI), echocardiography (ECHO), planimetry, end-diastolic pressure of left ventricle (LVEDP), end-diastolic diameter of left ventricle (LVEDd) were used to access left ventricular function preoperatively. ECHO was also used to access left ventricular function postoperatively.RESULTS: Early postoperative (30 days) mortality was 4.1 %. Complications had 25 patients (26 %) postoperatively. Two years survival was 95.7 %. Class III-IV CCS and/or NYHA had 17 patients (17.5 %) two years after surgery. LVEF (assessed by ECHO) improved from 23.1 % preoperatively to 36.0 % postoperatively (p < 0.05).CONCLUSION: The study showed that elective myocardial revascularisation in patients with severe left ventricular dysfunction and signs of myocardial viability is not necessarily associated with high operative mortality. It can be performed safely with respectable midterm survival in concordance with left ventricular function improvement, symptom relief and quality of life improvement.

Early in the development of multiple sclerosis (MS) and its mouse model experimental autoimmune encephalomyelitis (EAE), vascular integrity is compromised. This is accompanied by a marked vascular remodeling response, though it is currently unclear whether this is an adaptive vascular repair mechanism or is part of the pathogenic process. In light of the well-described angiogenic role for the á5â1 integrin, the goal of this study was to evaluate how genetic deletion of endothelial á5 integrin (á5-EC-KO mice) impacts vascular remodeling and repair following vascular disruption during EAE pathogenesis, and how this subsequently influences clinical progression and inflammatory demyelination. Immunofluorescence staining revealed that fibronectin and á5 integrin expression were strongly upregulated on spinal cord blood vessels during the pre-symptomatic phase of EAE. Interestingly, á5-EC-KO mice showed much earlier onset and faster progression of EAE, though peak disease severity and chronic disease activity were no different from wild-type mice. At the histological level, earlier disease onset in á5-EC-KO mice correlated with accelerated vascular disruption and increased leukocyte infiltration into the spinal cord. Significantly, spinal cord blood vessels in á5-EC-KO mice showed attenuated endothelial proliferation during the pre-symptomatic phase of EAE which resulted in reduced vascular density at later time-points. Under pro-inflammatory conditions, primary cultures of á5KO brain endothelial cells showed reduced proliferation potential. These findings suggest that á5â1 integrin-mediated angiogenic remodeling represents an important repair mechanism that counteracts vascular disruption during the early stages of EAE development.

It has been reported that diabetes-induced inappropriate apoptosis in embryos during neurulation may be one of the mechanisms leading to neural tube defects. We studied apoptosis and the apoptotic pathway occurring in early post-implantation period embryos of non-diabetic and streptozotocin (STZ)-induced diabetic rats. In quantitative RT-PCR, bax mRNA was constantly expressed to similar degree in embryos of non-diabetic and diabetic rats, while the expression of bcl-2 mRNA was significantly decreased in diabetic rat embryos compared to non-diabetic rat embryos. The increased number of terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL)-positive cells occurred selectively in the primitive brains of diabetic rat embryos compared to non-diabetic rat embryos. Immunohistochemical studies revealed that, in mirror sections, the staining of Bax and activated caspase-3 were observed in the TUNEL-positive cell area, but the expression of Bcl-2 in these apoptotic cells was generally too low to be detected. These results suggest that a Bax-regulated mitochondrial cytochrome c-mediated caspase-3 activation pathway might be involved in the diabetic embryopathy.

To assess compliance with accepted principles, the use of prophylaxis with systemic antibiotics in selected specialty procedures was examined. The operations reviewed were aortofemoral bypass, pulmonary resections, open-hip procedures, and head-neck cancer procedures that involve the oropharyngeal cavity. Of all patients, 74% received antibiotics preoperatively and 79% received prophylaxis with antibiotics longer than 24 hours postoperatively. Evaluated against the criteria of preoperative initiation and limited postoperative administration (less than 24 hours) only 10% of the patients received appropriate prophylaxis. A 3% incidence of drug-associated complications was identified; each patient with complications had received antibiotics for a prolonged time postoperatively. Reduction in the length of postoperative prophylaxis with systemic antibiotics will reduce (1) the number of drug-associated complications, (2) selection pressures on the hospital microbial population, and (3) needless expense in hospitalized patients.

The kinetics of transfer of [3H]cholesterol between human erythrocytes and plasma at 37 degrees C in physiological buffer had these features. 1) Cholesterol transfer was strikingly similar in both directions. 2) Transfer progressed to isotopic equilibrium in a monotonic, apparently first order fashion, except for a minor rapid component (approximately 15%) observed in the transfer of cholesterol from cells to plasma. 3) The mechanism of transfer was not via transient collisions in that the rate of the reaction was quite insensitive to the concentration of reactants over a wide range. 4) The mechanism of transfer did not involve specific, stable complex formation in that there was little difference in the behavior of erythrocytes and inside-out plasma membrane vesicles derived therefrom or between plasma and sonicated liposomes as acceptors. Furthermore, transfer was not affected by vigorous proteolysis of either the cells or the plasma. 5) The kinetics of transfer were fully compatible with diffusion of cholesterol through the aqueous compartment. This was shown by fitting our data to a rigorous model for diffusion equilibrium between three compartments. 6) The partition coefficient of [3H]cholesterol between red cells and buffer was shown to be 10(7). 7) The rate constants for cholesterol release from both red cells and plasma were approximately 1 X 10(-4) s-1 (t 1/2 approximately 2 h). The rate constant for cholesterol uptake into red cells was approximately 1 X 10(3) s-1 (t 1/2 approximately 1 ms). 8) The similarity of the corresponding kinetic constants among red cells, plasma, and liposomes suggests that phospholipids in a variety of physical forms are equivalent solvents for cholesterol. We conclude that despite its extremely low solubility in water, cholesterol moves between lipid compartments by aqueous diffusion.

Eighty patients having anaesthesia for oral surgery requiring nasal intubation were randomly allocated to be intubated with either a plain Magill red rubber or cuffed polyethylene endotracheal tube and in a double blind manner, to receive xylometazoline 0.1% vasoconstrictor nasal spray. The extent of any epistaxis occurring was assessed by an independent observer. With the Magill tube there was bleeding in one out of twenty patients in both the vasoconstrictor group and non vasoconstrictor group at intubation and no bleeding in either of the two groups at extubation. With the polyethylene tube sixteen out of twenty patients had bleeding in the non vasoconstrictor group. This improved to seven out of twenty with the administration of vasoconstrictor drops at intubation (chi square 10.2; p < 0.01) in the polyethylene tube group. At extubation ten out of twenty patients had bleeding in the non vasoconstrictor group improving to two out of twenty with the administration of the vasoconstrictor (chi square 9.6; p,0.01). The use of the vasoconstrictor xylometazoline helped to reduce epistaxis that occurred during nasal intubation and further study into the type of endotracheal tube is recommended.

PURPOSE: Multinodular and vacuolating neuronal tumor (MVNT) have been recently added to the WHO classification of CNS tumors and has not been extensively reported upon in the radiological literature. We report the first radiological and the largest series of cases, aiming to highlight the natural history of lesions with the imaging appearance of MVNT with long follow-up time.METHODS: In this retrospective study, we collected cases with the imaging appearance of MVNT. All lesions were evaluated by using routine MR imaging, with follow-up of up to 93 months. Patient demographics, clinical course, and MRI features of the lesions were recorded.RESULTS: Twenty-four subjects were enrolled, f/m = 16:8, age range 24-59 years, with a median age of 45 years. The patients' symptoms were often episodic and most frequently due to headaches in 12 (50%), visual symptoms in 6 (25%), seizures in 5 ± 1 (20-25%), paresthesia in 4 (~17%), cognitive difficulties in 4 (~17%), in addition to other variable neurological symptoms, or incidental. A total of 30 lesions identified, 77% of the lesions had gadolinium-enhanced MRI and only 13% showed enhancement. A 6.7% of the lesions that had MRI followed up showed progression, while the rest remained stable up to 93 months interval. All patients had intact neurological examinations (except one case that was diagnosed with optic neuritis), were managed conservatively, and did well.CONCLUSION: The natural history of lesions with imaging features of MVNT is overall stable from a clinical and imaging appearance over time.

Novel amidino-derivatives of phenylene-bisbenzothiazoles were synthesized and tested for their antiproliferative activity against several human cancer cell lines, as well as DNA-binding properties. The synthetic approach used for preparation of isomeric amidino substituted-phenylene-bis-benzothyazoles 3a-3f was achieved by condensation reaction of isophthaloyl dichloride 1a and terephthaloyl dichloride 1b or with phthalic acid 1c with 5-amidinium-2-aminobenzothiolate 2a and 5-(imidazolinium-2-yl)-2-aminobenzothiolate 2b in good yields. The targeted compounds were converted in the desired water soluble dihydrochloride salts by reaction of appropriate free base with concd HCl in ethanol or acetic acid. All tested compounds (3a-3f) showed antiproliferative effects on tumour cells in a concentration-dependant manner. The strongest activity and cytotoxicity was observed for diimidazolinyl substituted phenylene-bisbenzothiazole compound 3b. These effects were shown to be related to DNA-binding properties, topoisomerase I and II poisoning effects and apoptosis induction. The highest tested selectivity towards tumour cells was observed for the imidazolyl substituted phenylene-benzothiazole 3d that showed no cytotoxic effects on normal fibroblasts making it an excellent candidate for further chemical optimization and preclinical evaluation.

OBJECTIVE: The objective was to assess the extent of concordance between self-reported contraceptive use and the presence of contraceptive progestins in serum.STUDY DESIGN: We evaluated self-reported contraceptive use by using radioimmunoassay to examine baseline serum levels of medroxyprogesterone acetate (MPA) and levonorgestrel (LNG) among 97 Malawian women enrolling in a contraceptive trial.RESULTS: Twelve percent (12/97) of study participants who reported no hormonal contraceptive use in the previous 6months had either MPA or LNG detected in their serum.CONCLUSIONS: The observed discordance between self-report and detection of exogenous hormones in serum indicates that caution is warranted when drawing conclusions based on self-reported contraceptive use.

College undergraduates were identified as alexithymic or control, based on their scores on the Toronto Alexithymia Scale (TAS; Taylor, Ryan, & Bagby, 1985). All subjects were presented standardized emotion-eliciting color slides for 6 s while facial muscle, heart rate, and skin conductance activity were recorded. Stimuli were presented a second time while subjects were asked to provide emotion self-reports using a paper-and-pencil version of the Self-Assessment Manikin (SAM; Lang, 1980) and to generate a list of words describing their emotional reaction to each slide. Consistent with the definition of alexithymia as a syndrome characterized, in part, by a deficit in the identification of emotion states, high TAS subjects supplied fewer emotion-related words than did controls to describe their response to the slides. Alexithymics also indicated less variation along the arousal dimension of the SAM, produced fewer specific skin conductance responses and showed less heart rate deceleration to the slides, regardless of category. No valence-related differences between alexithymic and control subjects were noted.

OBJECTIVES: In 1996, the new Swiss law on health care insurance (KVG) introduced the coverage of certain preventive measures. This provided an opportunity to include research-based public health issues in federal health policy. The present article examines the problems with which the realization of those goals in a Federalist health care system with strong cantonal autonomy as it is found in Switzerland was confronted.METHOD: Comparative qualitative case studies design (vaccination of school age children and screening-mammography).RESULTS: Switzerland's federalist health care system strongly hinders the realisation of the Confederation's public health goals. Prevention falls into the cantons' autonomy and the federal KVG (Krankenversicherungsgesetz; Health insurance law) only regulates the coverage of the services provided, but does not contain any instruments to assure implementation in consistency with the policy goals. Under those circumstances, conflicts of interest between the implementing actors, varying cantonal preferences, and scarce resources block the implementation of public health goals.CONCLUSIONS: The results imply stronger leadership of the Confederation in prevention policy and an improved consideration of implementation aspects in approving new measures to obligatory insurance coverage.

A gap in the leptospirosis field remains the lack of well-characterized sample collections that allow for comparison of new methods to standard ones. In the context of a flood-related outbreak of leptospirosis evaluated in Anuradhapura, Sri Lanka, a specimen bank was obtained with detailed metadata accompanied by gold standard diagnostic test results. Blood samples collected on admission and 14 days later from suspected cases of leptospirosis were tested using microscopic agglutination test (MAT) (17 serovars), an in-house enzyme-linked immunosorbent assay (ELISA) using a locally obtained strain of Leptospira kirschneri as sonicated antigen, a commercially available ELISA based on sonicated Leptospira biflexa, and a quantitative polymerase chain reaction (qPCR) assay targeting the pathogenic Leptospira-specific 16S rRNA gene. Of 62 patients presenting within the first 2 days of illness, 31 had confirmed leptospirosis based either on paired-sample MAT or qPCR. During the acute phase, qPCR was most sensitive, detecting 74% of definitively diagnosed cases; immunoglobulin G (IgG) ELISA (in-house), IgG ELISA (commercial), and MAT had sensitivities of 35.5%, 12.0%, and 22.6%, respectively, in detecting definitively diagnosed cases using acute phase serum. Of 40 patients with paired sera, 10 were qPCR positive. Of these, five samples were negative by paired-sample MAT. Of the 11 MAT-positive samples, only five were detected using qPCR confirming that both tests are needed for maximal sensitivity. Regional leptospiral serovar-specific IgG ELISA was superior to MAT. Knowing the regionally dominant serovars improves serological sensitivity in the analysis of acute specimens by ELISA, but qPCR was most sensitive in this patient population.

Since a 1997 regulatory shift on the part of the US Food and Drug Administration (FDA), there has been an explosion of televised direct-to-consumer (DTC) pharmaceutical advertising in the United States. The introduction and growth of this form of advertising, as well as other recent evolutions in the health care arena, have altered relationships among key countervailing powers in the health care system, suggesting the need to recast countervailing powers theory so as to account for these changes. Coming from the perspective that the news media play an important role in reflecting the balance of power among the various countervailing powers, the paper advances this theoretical framework through an empirical assessment of the relative prominence of those entities in print news media coverage of the DTC advertising phenomenon. The study finds that ;corporate sellers' (pharmaceutical industry) are accorded more prominence in news coverage than are providers, consumers, corporate purchasers, or state players and that DTC critics, in particular, have minimal representation. In addition, the findings point toward two modifications for countervailing powers theory: (1) an incorporation of the role of academic/research organizations, and (2) a consideration of the universe of possibilities with respect to each of the countervailing powers.

When dark-grown aurea mutant tomato seedlings which lack more than 95% of the phytochrome present in isogenic wild-type seedlings are kept in white or blue light, four nuclear-encoded transcripts coding for plastidic proteins (the light-harvesting chlorophyll a/b-binding protein of photosystem I and II [cab-PSII], plastocyanin and subunit 2 of photosystem I) are present in comparable amounts. These transcript levels in red light are strongly reduced in aurea seedlings when compared with those of wild type. Thus, blue light is required for normal expression of these genes in the mutant, while red light alone is not sufficient. Red light-grown aurea seedlings are very sensitive to blue light, even 10 minutes of blue light every day suffices to cause a measurable increase in cab-PSII transcript level. The action of blue light on the expression of cab-PSII in the mutant is under phytochrome control. After 8 days of blue light, phytochrome is almost as effective in inducing cab-PSII mRNA as in the isogenic wild type, whereas after 8 days of red light, only a small phytochrome response was observed in the mutant. It is concluded that blue light sensitizes the mutant to the residual phytochrome which allows normal gene expression and survival of the mutant under daylight conditions.

We report a 21-month-old child with spontaneous pneumomediastinum (PM), emphysema, and pulmonary bullae caused by Mycoplasma pneumonia (M. pneumoniae) pneumonia. The patient presented with stubborn dyspnea and wheezing although received integrated treatment, including anti-infection, anti-inflammation, and intravenous immunoglobulin. This case was unique in that pulmonary bullae kept increasing. PM and emphysema were refractory in our patient, which have been reported as benign and limited. Surgical intervention was implemented to ultimately cure the case. Clinicians should be aware of air leaks in patients with M. pneumoniae pneumonia since this complication may be fatal.

Using a newly developed isotopic tracer technique for the measurement of 32P-labelled intermediates in glycolysis and nucleotide metabolism in platelets, we studied the variations in 32P-labelled intermediates during activation of the glycolytic flux by cyanide and platelet-activating agents. The major variations occurred in [32P]Fru-1,6-P2, dihydroxy acetone phosphate, ATP and Pi. There was a quantitative covariance between the increase in lactate production and the rise in [32P]Fru-1,6-P2 induced by different platelet-activating agents. In contrast, cyanide induced weaker activation of the flux and greater accumulation of [32P]Fru-1,6-P2. Variations in 32P-labelled intermediates were apparent 5 s after flux activation, but the major changes in [32P]Fru-1,6-P2 occurred much later and fell in periods in which a constant lactate formation was maintained. The cyanide-induced changes in 32P-labelled intermediates depended on the extracellular level of glucose, showing a predominant ATP----Pi conversion in glucose-depleted medium that shifted to an ATP----Fru-1,6-P2 conversion at excess glucose. At about 50 microM glucose, flux activation occurred without major changes in [32P]Fru-1,6-P2, dihydroxy acetone phosphate and Pi, with only a small fall in [32P]ATP. The data provide evidence for a role of the aldolase reaction in flux control and demonstrate rapid changes in Fru-1,6-P2 and ATP during flux activation with an additional role for Fru-1,6-P2 as an energy buffer during post-activation periods.

1 Acebutolol or diacetolol were added to fresh human plasma in varying concentrations and their extent of binding at 25 degrees C measureed by an equilibrium dialysis technique. 2 The extent of binding for both compounds was shown to be very low, being 11-19% for acebutolol and 6-9% for diacetolol. 3 Partition coefficients were measured in an n- octanol/phosphate buffer (0.05M, pH 7.4) solvent system. For a cebutolol, P = 0.62 and for diacetol, P = 0.08. 4 The very low plasma binding is in accord with the hydrophilic partition coefficients of these compounds.

Renal lymphangioma typically manifests as a unilocular or multilocular cystic mass in the parapelvic or perirenal spaces. A solid mass-like lymphangioma rarely occurs and thus is hard to differentiate from a renal cell carcinoma. We encountered a case of a solid mass-like renal lymphangioma that was confirmed using percutaneous biopsy. The purpose of our case report was to describe magnetic resonance imaging features, to show the differential diagnoses, and to discuss the role of percutaneous renal mass biopsy.

The binding of mithramycin A to the d(A1T2G3C4A5T6) duplex was investigated by 1H NMR and found to be similar to that of its analogue chromomycin A3. In the presence of Mg2+, mithramycin binds strongly to d(ATGCAT)2. On the basis of the two-dimensional NOESY spectrum, the complex formed possesses C2 symmetry at a stoichiometry of two drugs per duplex (2:1) and is in slow chemical exchange on the NMR time scale. NOESY experiments reveal contacts from the E-pyranose of mithramycin to the terminal and nonterminal adenine H2 proton of DNA and from the drug hydroxyl proton to both G3NH2 protons, C4H1' proton, and A5H1' proton. These data place the drug chromophore and E pyranose on the minor groove side of d(ATGCAT)2. NOE contacts from the A-, B-, C-, and D-pyranoses of mithramycin to several deoxyribose protons suggest that the A- and B-rings are oriented along the sugar-phosphate backbone of G3-C4, while the C- and D-rings are located along the sugar-phosphate backbone of A5-T6. These drug-DNA contacts are very similar to those found for chromomycin binding to d(ATGCAT)2. Unlike chromomycin, the NOESY spectrum of mithramycin at the molar ratio of one drug per duplex reveals several chemical exchange cross-peaks corresponding to the drug-free and drug-bound proton resonances. From the intensity of these cross-peaks and the corresponding diagonal peaks, the off-rate constant was estimated to be 0.4 s-1. These data suggest that the exchange rate of mithramycin binding to d(ATGCAT)2 is faster than that of chromomycin.

A small set of isoprenoid bisphosphonates ethers has been tested in the K562 chronic myelogenous leukemia cell line to determine their impact on isoprenoid biosynthesis. Five of these compounds inhibit geranylgeranyl diphosphate synthase (GGDPS) with IC50 values below 1 ìM in enzyme assays, but in cells their apparent activity is more varied. In particular, the isomeric C-geranyl-O-prenyl and C-prenyl-O-geranyl bisphosphonates are quite different in their activity with the former consistently demonstrating greater impairment of geranylgeranylation in cells but the latter showing greater impact in the enzyme assays with GGDPS. Together, these findings suggest an organized binding of these inhibitors in the two hydrophobic channels of the geranylgeranyl diphosphate synthase enzyme.

In this article, the authors consider the opportunities for learning in health research that adopts a participatory learning and action (PLA) approach. Much attention has been given to the participation and action components of PLA, but there has been less practical and theoretical consideration of the learning component. Using the research conducted as part of a local Sure Start evaluation in England, the authors reflect on the learning that takes place between participants in the research process. They draw on two models of adult learning styles to frame their reflections and argue that to improve the rigor of participatory research, and to maximize the emancipatory potential of PLA, it is useful for researchers to be explicit about the learning that takes place during participatory research. Furthermore, that learning will be promoted by establishing a dialogue of colearning between different worlds across boundaries.

As access to computational resources continues to increase, free-energy calculations have emerged as a powerful tool that can play a predictive role in a wide range of research areas. Yet, the reliability of these calculations can often be improved significantly if a number of precepts, or good practices, are followed. Although the theory upon which these good practices rely has largely been known for many years, it is often overlooked or simply ignored. In other cases, the theoretical developments are too recent for their potential to be fully grasped and merged into popular platforms for the computation of free-energy differences. In this contribution, the current best practices for carrying out free-energy calculations using free energy perturbation and nonequilibrium work methods are discussed, demonstrating that at little to no additional cost, free-energy estimates could be markedly improved and bounded by meaningful error estimates. Monitoring the probability distributions that underlie the transformation between the states of interest, performing the calculation bidirectionally, stratifying the reaction pathway, and choosing the most appropriate paradigms and algorithms for transforming between states offer significant gains in both accuracy and precision.

We previously cloned ZNF74, a developmentally expressed zinc finger gene commonly deleted in DiGeorge syndrome. Here, the intron/exon organization of the human gene and the functional properties of the expressed protein are presented. This zinc finger gene from the transcription factor IIIA/Kruppel family contains three exons. A truncated Kruppel-associated box (KRAB) located at the N terminus of the predicted 64-kDa zinc finger protein is encoded by exon 2. The remainder of the protein including the zinc finger domain as well as the 3'-untranslated region (UTR) is encoded by exon 3. Both 5'-UTR (exon 1) and 3'-UTR contain repetitive Alu elements. In vitro translation of a cDNA encoding the entire ZNF74 coding region produced a 63-kDa protein as determined on sodium dodecyl sulfate-polyacrylamide gel. A bacterially expressed fusion protein shown to bind tightly to 65zinc was used to test the nucleic acid binding properties of ZNF74. By RNA binding assays, ZNF74 was found to bind specifically to poly(U) and poly(G) RNA homopolymers. The restricted binding to these homopolymers and not to poly(A) and poly(C) suggested that ZNF74 displays RNA sequence preferences. RNA binding was mediated by the zinc finger domain. Immunofluorescence studies on transfected cells revealed ZNF74 nuclear localization. The labeling pattern observed in the nuclei clearly excluded the nucleoli. The zinc finger region lacks a classical nuclear localization signal but was found to be responsible for nuclear targeting. Subcellular and in situ sequential fractionations further showed that ZNF74 is associated with the nuclear matrix. The RNA binding properties of this protein and its tight association with the nuclear matrix, a subnuclear compartment involved in DNA replication as well as RNA synthesis and processing, suggest a role for ZNF74 in RNA metabolism.

Stimulation of the amygdala in rats is known to elicit increases in heart rate (HR) and blood pressure (BP) as well as locomotor activity associated with emotional arousal. The present study was conducted to localize and characterize the role of the GABA system of the amygdala in regulating these cardiovascular responses. Male Sprague-Dawley rats with arterial catheters placed for physiological measurements were implanted with chronic microinjection cannulae in the anterior basolateral (BLA) and central (Ce) amygdaloid nuclei under pentobarbital anesthesia. After recovering, rats were microinjected bilaterally with saline (250 nl) and bicuculline methiodide (BMI, 5-25 ng/250 nl), a selective GABAA antagonist. Microinjection of BMI in the BLA caused significant increases in HR and BP as well as locomotor stimulation while saline had no effect. The cardiovascular response to BMI was blocked by pentobarbital anesthesia. Microinjection of equimolar concentrations of (+)-baclofen HCl (GABAB agonist), phaclofen (GABAB antagonist), or strychnine (glycine antagonist) into the BLA or BMI into the Ce had no significant cardiovascular effects. The cardiovascular effects of BMI injection in the BLA does not appear to be secondary to generalized seizure activity. These results suggest that endogenous GABA, acting on GABAA receptors in the region of the BLA, may be involved in cardiovascular regulation.

Musca domestica flies that were exposed to a uniform vertical 10 Hz electric square-wave field of 1 kVm(-1) changed the period length of their circadian locomotor activity rhythm. Under constant conditions, the clock of short-period flies was slowed down by the field, whereas the clock of long-period flies either was affected only scarcely (experiments at about 19 degrees C) or ran faster (experiments at 25 degrees C). If the field was applied for only 12 h daily, then 30-40 percent of the flies were synchronized. Thus, the field could function as a weak "Zeitgeber" (synchronizer). If the field was increased to 10 kVm(-1), then 50-70 percent of the flies were synchronized. Flies avoided becoming active around the onset of the 12 h period of exposure to a 10 Hz field. The results of these experiments are discussed with respect to similar experiments by Wever on the effects of exposure to a 10 Hz field on the circadian system of man.

The use of optical microscope remains the most commonly used technique for microplastic identification and quantification despite major limitations with misidentifications and biases. We evaluated the use of the 1% Rose Bengal stain in improving the identification of microplastics after a standard microplastic isolation process. The stain discriminated organic materials from potential microplastics with significant differences between numbers observed before (6.65 ± 5.73) and after staining (2.91 ± 3.43). Numbers of potential microplastics observed under the conventional method (without staining) in sediment, feacal matter of shorebirds and the lagoon water were respectively 3.55 g-1, 0.8 g-1 and 0.13 ml-1 but reduced to 1.85 g-1 of sediment, 0.35 g-1 of feacal material and 0.09 ml-1 of water after staining. Colour composition of potential microplastics under the conventional method was brown (31.0%), black (26.5%), white (20.2%), translucent (16.7%) and red (5.6%). After staining, brown (49,2%), black (30.5%) white (2.3%) and translucent (18.0%) were retained but distinction could not be made between stained organic items and red-coloured microplastics. It was clear that the stain has the potential in improving microplastic identification but requires further investigations.

Worldwide, the DNA mismatch repair genes MSH2 and MLH1 account for a major share and almost equal proportions of hereditary nonpolyposis colorectal cancer (HNPCC). Furthermore, the predisposing mutation usually varies from kindred to kindred. In this study, we screen 29 verified or putative HNPCC kindreds from Finland for mutations in these two genes and found 8 different mutations, 7 in MLH1 and 1 in MSH2, occurring in 13 families. Four of these mutations were novel. Altogether, we have to date studied 81 kindreds for mutations and 12 different mutations in 52 families have been identified, 10 in MLH1 and 2 in MSH2. These data show that Finnish HNPCC kindreds are characterized by the predominant involvement of MLH1 (49/52, 94% of the families) and a high rate of shared mutations (5/12, 42%) offering unique possibilities for mutation screening for both research and diagnostic purposes.

AIM: The value of turbo-spin-echo (TSE) sequences was compared with conventional spin-echo (SE) and inversion-recovery (IR) sequences for cerebral MRT in 70 children at 0.5 T and 1.5 T. In addition we evaluated whether proton weighted sequences (PD) were diagnostically important and in what proportion of cases.METHOD: Conventional T1 and T2 weighted SE and T2 weighted TSE sequences were used in all children. An IR sequence was performed in 39 patients. The various sequences were analysed semiquantitatively with regard to image quality, artifacts and the demonstration of normal and anatomical structures and pathological findings.RESULTS: By any criteria, TSE sequences were superior to conventional T2 weighted SE sequences at 0.5T and 1.5 T, requiring a shorter examination time (35-53%). In 8.6% the pathological finding was best seen on PD-SE sequences (5 glial scars, 1 tumor).CONCLUSION: Although TSE sequences are better than T2 SE sequences with regard to image quality and the demonstration of abnormalities, conventional double-echo SE sequences (with PD and T2 weighted images) cannot be entirely replaced by T2 weighted TSE sequences in children.

Failure to follow asthma management guidelines may result in poor asthma control for many patients. The Asthma Insights and Reality in Europe (AIRE) survey, a multi-national survey assessing the level of asthma control from the patients perspective in seven Western European countries, previously demonstrated that the Global Initiative for Asthma (GINA) guideline goals were not achieved in Western Europe and that both adults and children with asthma were poorly controlled. Using additional data on asthma management practices from each of the seven countries in the AIRE survey, we compared variations in asthma morbidity and asthma management practices across countries to provide insight into the reasons for poor asthma control. Asthma management practices and asthma control among adults and children with current asthma were suboptimal in each of seven countries surveyed. Among patients with symptoms of severe persistent asthma, over 40% reported their asthma was well or completely controlled. School absence due to asthma was reported by upto 52.7% of children and up to 27.6% of adult reported work absence due to asthma. Lung function testing in the past year was uncommon: ranging from 13.5% of children in the U.K. to 68.8% of adults in Germany. Written asthma management plans were used by less than 50% of adults and less than 61% of children in all seven countries. Most adults (49.5-73.0%) and a large proportion of children (38.4-70.6%) had follow-up visits for their asthma only when problems developed. The ratio of recent inhaled corticosteroid use to recent short-acting beta-agonist use was inappropriate (<1) among patients with symptoms of severe asthma in all countries. This disparity was greatest among adults in Italy and France, where recent inhaled corticosteroid use was reported by less than one in nine patients reporting recent use of short-acting bronchodialators (IS:SAB <0.11). Management practices differ between countries and additional public health interventions and resources may be necessary to reduce patient suffering. Further efforts to fully implement asthma management guidelines are required to improve asthma control in Europe.

Neural mechanisms that integrate posture with movement are widespread throughout the central nervous system (CNS), and they are recruited in patterns that are both task- and context-dependent. Scientists from several countries who were born in the 19th century provided essential groundwork for these modern-day concepts. Here, the focus is on three of this group with each selected for a somewhat different reason. Charles Sherrington (1857-1952) had innumerable contributions that were certainly needed in the subsequent study of posture and movement: inhibition as an active coordinative mechanism, the functional anatomy of spinal cord-muscle connectivity, and helping set the stage for modern work on the sensorimotor cortex and the corticospinal tract. Sadly, however, by not championing the work of his trainee and collaborator, Thomas Graham Brown (1882-1965), he delayed progress on two key motor control mechanisms: central programming and pattern generation. Walter Hess (1881-1973), a self-taught experimentalist, is now best known for his work on CNS coordination of autonomic (visceral) and emotional behavior. His contributions to posture and movement, however, were also far-reaching: the coordination of eye movements and integration of goal-directed and "framework" (anticipatory set) motor behavior. Nikolai Bernstein (1896-1966), the quintessence of an interdisciplinary, self-taught movement neuroscientist, made far-reaching contributions that were barely recognized by Western workers prior to the 1960s. Today, he is widely praised for showing that the CNS's hierarchy of control mechanisms for posture and movement is organized hand-in-hand with distributed and parallel processing, with all three subject to evolutionary pressures. He also made important observations, like those of several previous workers, on the goal focus of voluntary movements. The contributions of Sherrington, Hess, and Bernstein are enduring. They prompt thought on the philosophical axioms that appear to have driven their research, and the continual need for emphasis on interdisciplinary, comparative, and transnational approaches to advance movement neuroscience.

The V-beam pulsed-dye laser (PDL) (595 nm) has gained popularity in the treatment of port wine stains (PWS). It uses longer pulse durations than the standard flashlamp-pumped pulsed-dye laser (FPDL) (585 nm) and has an in-built cooling system to protect the epidermis. This should, theoretically, reduce the treatment-associated side effects, including discomfort. The aim of this questionnaire-based study was to confirm the clinical impression that V-beam PDL is well tolerated. The results were compared with a historical group of 62 PWS patients treated with FPDL. Fifty-one patients took part in the current study. Only 35.7% (vs. 81% in the historical comparison group) required topical anaesthetic prior to laser treatment. A shortening in the duration of bruising (8 vs. 10 days) and of symptoms such as burning and tightness (3 vs. 10 days) was recorded. Lifestyle change after treatment was recorded by fewer patients (39 vs. 57%). We conclude that V-beam PDL is better tolerated than FPDL when used at therapeutic levels in patients with PWS.

Creating perfect direct composite restorations has been for long time a strict challenge due to many materials' limitations impacting either shade integration or surface quality, and possibly colour stability. Next to technological drawbacks, a certain complexity and lack of predictability in clinical application was inherent to the technique and made it elitist for a long time. Shading and layering concepts then progressively evolved from a simplistic, non histo-anatomical, bilaminar technique to a multi-layering approach (3 to 4 or more layers), following the Vita Classic™ system. One of the most achieved concepts is polychromatic layering which makes use of a variable number of layers (basically VITA™ or non-VITA™ opacious dentin, chromatic enamel and translucent/opalescent enamel), driven by the natural tooth optical composition. In parallel with this evolution, a simplified, non-VITA shading system was developed with a reduced number of layers (basically dentin &enamel layer, plus effect shades if required) known as the natural layering concept, aiming to the same optimal esthetic integration and natural colour reproduction/emulation. The latest improvements appear all driven by the same view of improved reliability and clinical simplification.

OBJECTIVE: To determine the prevalence and appearance of magnetic resonance imaging (MRI) signal changes that occur in local bone marrow after radiation therapy (RT) and/or chemotherapy for extremity soft tissue sarcoma (STS).MATERIALS AND METHODS: Seventy patients with primary STS at the level of a long bone who also had undergone pretreatment MRI and at least one post-treatment MRI of the tumor bed were identified. MRIs of each patient were retrospectively reviewed for new changes in marrow signal in the region of the tumor bed and for the morphology, relative signal intensities, heterogeneity, and progression or regression of changes over time.RESULTS: Focal signal changes in marrow were observed in 26/70 patients (37%) at a median of 9.5 months after RT and/or chemotherapy and diffuse changes in seven (10%) at a median of 8 months. Patients who received neither RT nor chemotherapy did not develop marrow changes. Mean RT doses in patients with changes and those without were 5,867 and 6,076 cGy, respectively. In most patients with focal changes, changes were seen in all sequences and were linear-curvilinear, patchy, or mixed at the level of the tumor bed. Predominant signal intensity of changes was between muscle and fat at T1WI and between muscle and fluid at fat-saturated T2WI or short tau inversion recovery. Most focal changes enhanced heterogeneously and increased or fluctuated in size over time.CONCLUSION: Changes in MRI appearance of long bone marrow frequently are evident after combined RT and chemotherapy for STS and most commonly increase or fluctuate in size over time. These changes have various non-mass-like configurations and often show signal intensities similar to those of red marrow and thus should not be mistaken for metastases. The marrow changes might represent an early stage of gelatinous transformation of marrow.

OBJECTIVE: To assess different measures of socioeconomic status (SES) as predictors of incident depression among women with systemic lupus erythematosus (SLE).METHODS: Data were derived from the 2010-2015 waves of the Lupus Outcomes Study, where individuals with confirmed SLE were interviewed annually by telephone. Depression was assessed using the Center for Epidemiologic Studies Depression Scale, using a validated lupus-specific cutoff (?23) for major depressive disorder. Women interviewed in ?2 consecutive waves, with scores <23 in the first wave (T1), were included. The level of financial strain was classified as high, moderate, or none based on responses to 3 questions. Generalized estimating equations were used to assess the impact of poverty status, income, education, and financial strain at T1 on the risk of incident depression the next year (T2), with adjustment for sociodemographic and disease status measures. Individuals could contribute more than one 2-year dyad to the analysis.RESULTS: In total, 682 women contributed 2,097 observations, with 19% having high financial strain, 47% moderate strain, and 34% no strain. There were 166 women who had 184 episodes of incident depression (rate = 8.8/100 person-years). In bivariate analysis, poverty, lower income and education, disease activity, and high financial strain were associated with depression onset; race/ethnicity was not. Poverty, income, and education were not significant in multivariate analyses, but disease activity and high financial strain were (odds ratio 1.85 [95% confidence interval 1.06-3.23]).CONCLUSION: High financial strain was a significant predictor of new-onset depression in women with SLE, controlling for disease factors and other SES measures. Determining specific, modifiable sources of financial strain may help prevent the development of depression.

The paramyxovirus fusion (F) protein mediates membrane fusion. The biologically active F protein consists of a membrane distal subunit F2 and a membrane anchored subunit F1. A highly stable structure has been identified comprised of peptides derived from the simian virus 5 (SV5) F1 heptad repeat A, which abuts the hydrophobic fusion peptide (peptide N-1), and the SV5 F1 heptad repeat B, located 270 residues downstream and adjacent to the transmembrane domain (peptides C-1 and C-2). In isolation, peptide N-1 is 47% alpha-helical and peptide C-1 and C-2 are unfolded. When mixed together, peptides N1 + C1 form a thermostable (Tm > 90 degrees C), 82% alpha-helical, discrete trimer of heterodimers (mass 31,300 M(r)) that is resistant to denaturation by 2% SDS at 40 degrees C. The authors suggest that this alpha-helical trimeric complex represents the core most stable form of the F protein that is either fusion competent or forms after fusion has occurred. Peptide C-1 is a potent inhibitor of both the lipid mixing and aqueous content mixing fusion activity of the SV5 F protein. In contrast, peptide N-1 inhibits cytoplasmic content mixing but not lipid mixing, leading to a stable hemifusion state. Thus, these peptides define functionally different steps in the fusion process. The parallels among both the fusion processes and the protein structures of paramyxovirus F proteins, HIV gp41 and influenza virus haemagglutinin are discussed, as the analogies are indicative of a conserved paradigm for fusion promotion among fusion proteins from widely disparate viruses.

Vascular dysfunction in patients with diabetes mellitus is related to advanced glycation end product (AGE) formation. We previously showed that AGEs produce an increase in vascular permeability and generated an oxidant stress after binding to the receptor (RAGE) present on endothelium. RAGE, a 35-kDa protein that belongs to the immunoglobulin superfamily, has been cloned from a rat lung cDNA library, and recombinant rat soluble RAGE (rR-RAGE) has been produced in insect cells. The sequence of RAGE is highly conserved between human and rat. We studied the biological effect of rR-RAGE and pharmacokinetics of 125I-rR-RAGE after intravenous or intraperitoneal administration in normal and streptozotocin-induced diabetic rats. rR-RAGE prevented albumin or inulin transfer through a bovine aortic endothelial cell monolayer, restored the hyperpermeability observed in diabetic rats or induced in normal rats by diabetic rat red blood cells, and corrected the reactive oxygen intermediate production after intravenous or intraperitoneal administration. After intravenous injection of 125I-rR-RAGE, the distribution half-life was longer (p < or = 0.01) in diabetic (0.15 and 4.01 hr) than in normal (0.02 and 0.21 hr) rats, as was the case for the elimination half-lives (diabetic, 57.17 hr; normal, 26.02 hr; p < or = 0.01). Distribution volume was higher in diabetic than in normal rats (6.94 and 3.24 liter/kg, respectively; p = 0.049). Our study showed that rR-RAGE was biologically active in vivo and slowly cleared, which suggests it could be considered as a potential therapy.

Iron has been proposed to promote oxidative tissue damage in multiple sclerosis (MS). In order to gain insights about how iron gets processed during MS, the deposition of iron was investigated in the CNS of mice with experimental allergic encephalomyelitis (EAE), which is a commonly used animal model of MS. Control mice (adjuvant only) and EAE mice (myelin basic protein plus adjuvant), were sacrificed at 4-8 days (preclinical phase), 10-13 days (clinical phase), or 18 days (recovery phase) post injection. Sections from the cerebrum, hindbrain, and cervical, thoracic and lumbar spinal cord were stained as previously described (J. Neurosci. Res. 29:413, 1991), and scored blindly for histopathological staining. There was minimal histopathological staining at any age in control animals or during the preclinical stage in EAE animals. At the clinical stage of EAE, stained pathological features (macrophages, extravasated RBC and granular staining) were significantly increased compared to the preclinical stage. In the recovery phase, macrophage and granular staining persisted but there was loss of extravasated RBC. Dual labeling studies revealed that granular deposits were present in astrocytes and in locations that appeared to be extracellular. In order to gain insights about the origin of iron deposits in EAE mice, additional studies were performed on brains of mice with extravasated blood lesions. These brains had granular, macrophage and RBC staining. Thus, each of the stained features in EAE animals could be due to the extravasation of blood which occurs in the SJL model of EAE, although some of the iron could have originated from myelin and oligodendrocytes damaged during EAE.

The ability to detect single protein molecules in blood could accelerate the discovery and use of more sensitive diagnostic biomarkers. To detect low-abundance proteins in blood, we captured them on microscopic beads decorated with specific antibodies and then labeled the immunocomplexes (one or zero labeled target protein molecules per bead) with an enzymatic reporter capable of generating a fluorescent product. After isolating the beads in 50-fl reaction chambers designed to hold only a single bead, we used fluorescence imaging to detect single protein molecules. Our single-molecule enzyme-linked immunosorbent assay (digital ELISA) approach detected as few as approximately 10-20 enzyme-labeled complexes in 100 microl of sample (approximately 10(-19) M) and routinely allowed detection of clinically relevant proteins in serum at concentrations (<10(-15) M) much lower than conventional ELISA. Digital ELISA detected prostate-specific antigen (PSA) in sera from patients who had undergone radical prostatectomy at concentrations as low as 14 fg/ml (0.4 fM).

Quality assurance is an essential part of health care and nursing. While many nurses are familiar with the words "quality assurance," most are not directly involved in the process. Because of increased requirements for licensure and accreditation, and an increased desire for cost-containment, more nurses will become active participants in quality assurance programs. Some institutions are making participation in quality assurance part of the "clinical ladder/advancement" process.

Consultation-referral is a part of everyday family practice. Although the process is taken for granted, it is a complex phenomenon. Neither the practice nor the process always meet the expectations of the referring physician or the consultant, and the patient may be the worse because of this discrepany. Studies of the practice and the process support this view. A model of the process is elaborated which can be used for the teaching of medical students or residents and which the practicing physician may use to improve his/her consultation-referral practices.

172 patients with impotence symptoms were investigated by SBBBV-test, orthostatic blood pressure, Doppler examination of the superficial and deep penile arteries, penile-brachial index, visual sexual stimulation, papaverin test, and measurement of bulbocavernous reflex latency time. Visual sexual stimulation and papaverin test correlated well with each other, and so did papaverin test and PBI in cases of arterial insufficiency. SBBBV was simple to perform and useful in detecting autonomic neuropathy. There were characteristic differences in the pattern of erectile failure between young and old patients. The differentiation to organic or psychogenic erectile failure was easier in the young age groups, whereas the old patients more often had a combination of vascular and psychogenic aetiology.

INTRODUCTION: Do cigarette smokers really want to quit smoking or do they simply say they do in order to placate others and avoid criticism? In surveys of smokers, stated quit intentions and reports of quit attempts may be biased by social desirability concerns. This makes it difficult to interpret large-scale state and national surveys of smoking behavior that collect data through telephone and face-to-face interviews, methods that tend to evoke high levels of socially desirable responding.METHODS: The 2007 Health Information National Trends Survey used a dual-frame design to query smokers' quit intentions and past quit attempts in 1 of 2 ways: A self-administered mail survey (low pressure for socially desirable responding; n = 563), or an interviewer-administered telephone survey (high pressure for socially desirable responding; n = 499). Estimates derived from the 2 formats were compared to test for social desirability effects.RESULTS: In both survey modes, approximately two thirds of smokers reported seriously considering quitting in the next 6 months (mail: 64.9%; telephone: 68.9%), and approximately half reported making a quit attempt in the past year (mail: 54.9%; telephone: 52.3%). Neither difference approached significance in logistic regressions controlling for demographics (ps > .24).CONCLUSIONS: It appears that a large proportion of smokers in the United States aspire to live smoke-free lives and are not simply responding in a socially desirable manner to deflect criticism in an antismoking social climate. Future research should (1) replicate this study with greater statistical power, (2) examine the possible effects of survey context (e.g., health survey vs. smoking pleasure survey), and (3) explore survey mode effects in specific subpopulations.

BACKGROUND: There is a role for brief assessment instruments in detection and management of major depression in MS. However, candidate scales have rarely been validated against a validated diagnostic interview. In this study, we evaluated the performance of several candidate scales: Patient Health Questionnaire (PHQ)-9, PHQ-2, Center for Epidemiologic Studies Depression rating scale (CES-D), and Hospital Anxiety and Depression Scale (HADS-D) in relation to the Structured Clinical Interview for DSM-IV (SCID).METHODS: The sample was an unselected series of 152 patients attending a multiple sclerosis (MS) clinic. Participants completed the scales during a clinic visit or returned them by mail. The SCID was administered by telephone within two weeks. The diagnosis of major depressive episode, according to the SCID, was used as a reference standard. Receiver-operator curves (ROC) were fitted and indices of measurement accuracy were calculated.RESULTS: All of the scales performed well, each having an area under the ROC > 90%. For example, the PHQ-9 had 95% sensitivity and 88.3% specificity when scored with a cut-point of 11. This cut-point achieved a 56% positive predictive value for major depression.CONCLUSIONS: While all of the scales performed well in terms of their sensitivity and specificity, the availability of the PHQ-9 in the public domain and its brevity may enhance the feasibility of its use.

This study examined the vulnerability of infants' reactivated memories to modification. In three experiments, one hundred eight 3-month-olds learned to move a distinctive mobile by kicking. After the operant task was forgotten, its memory was recovered by a reactivation treatment. Immediately afterward, attempts were made to modify the reactivated memory by exposing infants to a novel mobile. Exposing the novel mobile immediately after the reactivation treatment did not affect the reactivated memory (Experiment 1). When exposure to the novel mobile was delayed for 24 hr, the novel mobile temporarily interfered with recognition of the original mobile, but did not modify the reactivated memory (Experiment 2). Only when the contingency was briefly associated with the novel mobile (an active-exposure procedure) was the reactivated memory modified (Experiment 3). These data reveal that infants' recently reactivated memories are surprisingly resistant to updating unless the operant contingency that established the original memory accompanies the new information.

Renin and aldosterone values were measured in 20 patients undergoing coronary bypass surgery. Renin activity rose to a peak during bypass, falling a little after bypass and surgery. Aldosterone levels rose significantly during bypass, and continued to do so afterwards. This demonstrates a typical physiological stress response, evoking hormonal changes.

A method for assaying hybrid ribonuclease has been devised which utilizes as substrate the synthetic hybrid [3H]polyriboadenylic acid [poly(rA)]:polydeoxythymidylic acid [poly(dT)] immobilized on the solid matrix of nitrocellulose filters. The hybridization on filter of [3H]poly(rA) to poly(dT) has been explored in terms of efficacy of the process and the response of the product to RNase H. A pulse of uv irradiation of poly(dT) while in dry state on the filter increased its firm binding to the filter in a concentration-dependent manner, resulting in a concomitant increase of the yield of hybrid formation. The filter-immobilized hybrid was 95% resistant to RNase A but sensitive to RNase H. When stored in toluene in the cold the hybrid maintained its stability for over 6 months, as judged by its resistance to RNase A. The method offers a number of advantages over assays that use solution hybrids as substrates and was readily applicable in the screening of leukemic patients, in the leukocytes of which it has demonstrated increased RNase H levels.

Tumor necrosis factor (TNF)-alpha, a major proinflammatory cytokine, triggers endothelial cell activation and barrier dysfunction which are implicated in the pathogenesis of pulmonary edema associated with acute lung injury syndromes. The mechanisms of TNF-alpha-induced vascular permeability are not completely understood. Our initial experiments demonstrated that TNF-alpha-induced decreases in transendothelial electrical resistance across human pulmonary artery endothelial cells are independent of myosin light chain phosphorylation catalyzed by either myosin light chain kinase or Rho kinase. We next assessed the involvement of another cytoskeletal component, the tubulin-based microtubule network, and found TNF-alpha to induce a decrease in stable tubulin content and partial dissolution of peripheral microtubule network as evidenced by anti-acetylated tubulin and anti-beta-tubulin immunofluorescent staining, respectively. Microtubule-stabilizing agents, paclitaxel and epothilone B, significantly attenuated TNF-alpha-induced decreases in transendothelial electrical resistance, inhibited the cytokine-induced increases in actin stress fibers, formation of intercellular gap, and restored the TNF-alpha-compromised vascular endothelial (VE)-cadherin-based cell-cell junctions. Importantly, neither TNF-alpha nor paclitaxel treatment was associated with endothelial cell apoptosis. Inhibition of p38 mitogen-activated protein kinase by SB203580 significantly attenuated TNF-alpha-induced microtubule destabilization, actin rearrangement, and endothelial barrier dysfunction. These results strongly suggest the involvement of microtubule rearrangement in TNF-alpha-induced endothelial cell permeability via p38 mitogen-activated protein kinase activation.

BACKGROUND: Y-Box-binding protein-1 (YB-1) acts as a transcription factor for multiple genes and is linked to DNA replication and repair, cell proliferation and resistance to cytostatic drugs.PATIENTS AND METHODS: The prognostic value of YB-1 expression in primarily untreated malignant non-Hodgkin's lymphomas (NHLs) was examined using immunohistochemistry.RESULTS: Expression of YB-1 was detected in 48 out of 56 NHLs, and the immunohistochemical reaction was localized exclusively in the cytoplasm. Expression of YB-1 did not correlate with clinicopathological variables. Patients with higher YB-1 expression had shorter progression-free survival during the entire period of observation (p=0.0434), as well as in the course of 30 months' observation (p=0.0253). Additionally, in the course of 50 months' observation, patients with higher expression of YB-1 demonstrated a shorter overall survival time (p=0.0383) and a shorter progression-free survival (p=0.0309).CONCLUSION: Elevated YB-1 expression may represent a new unfavorable prognostic factor.

Accumulation of Cu, Zn, Mn, Ni, Pb, Cd in biologic materials causes microelements imbalance and metabolic disorders affecting also redox reactions, immune system and respiratory organs and functions, therefore leading to chronic pulmonary diseases. The authors suggested a hypothesis on links between environmental pollution, disorders of microelements metabolism and chronic pulmonary diseases pathogenesis in North region dwellers.

Nonproteolytic ubiquitylation of chromatin surrounding deoxyribonucleic acid double-strand breaks (DSBs), mediated by the RNF8/RNF168 ubiquitin ligases, plays a key role in recruiting repair factors, including 53BP1 and BRCA1, to reestablish genome integrity. In this paper, we show that human RNF169, an uncharacterized E3 ubiquitin ligase paralogous to RNF168, accumulated in DSB repair foci through recognition of RNF168-catalyzed ubiquitylation products by its motif interacting with ubiquitin domain. Unexpectedly, RNF169 was dispensable for chromatin ubiquitylation and ubiquitin-dependent accumulation of repair factors at DSB sites. Instead, RNF169 functionally competed with 53BP1 and RAP80-BRCA1 for association with RNF168-modified chromatin independent of its catalytic activity, limiting the magnitude of their recruitment to DSB sites. By delaying accumulation of 53BP1 and RAP80 at damaged chromatin, RNF169 stimulated homologous recombination and restrained nonhomologous end joining, affecting cell survival after DSB infliction. Our results show that RNF169 functions in a noncanonical fashion to harness RNF168-mediated protein recruitment to DSB-containing chromatin, thereby contributing to regulation of DSB repair pathway utilization.

Afferent signal transduction in the urinary bladder is still not clearly understood. An increasing body of evidence supports the view of complex interactions between urothelium, suburothelial myofibroblasts, and sensory nerves. Bladder tissue from tumour patients was used in this study. Methods included confocal immunofluorescence, polymerase chain reaction, calcium imaging, and fluorescence recovery after photobleaching (FRAP).Myofibroblasts express muscarinic and purinergic receptors. They show constitutive spontaneous activity in calcium imaging, which completely depends on extracellular calcium. Stimulation with carbachol and ATP-evoked intracellular calcium transients also depend on extracellular calcium. The intensive coupling between the cells is significantly diminished by incubation with TGF-beta 1. Myofibroblasts form an important cellular element within the afferent signalling of the urinary bladder. They possess all features required to take part in the complex interactions with urothelial cells and sensory nerves. Modulation of their function by cytokines may provide a pathomechanism for bladder dysfunction.

A subpopulation of thymocytes from adult mice that is nonadherent to macrophage monolayers showed dramatically increased syngeneic mixed leukocyte responses (SMLR). Cloned cells were derived by limiting dilution from these SMLR-primed BALB/c thymocytes and were maintained and subcloned by repeated stimulation with syngeneic BALB/c spleen cells without the addition of exogenous interleukins. The cloned thymocytes were tested for their reactivities against H-2- and Mls-identical BALB/c and B10.D2 spleen cells (H-2d, Mlsb). We found that BALB/c and B10.D2 stimulator cells differed significantly in their capacity to restimulate the cloned BALB/c thymocytes. In addition, polyclonal syngeneic mixed leukocyte cultures (SMLC) of BALB/c thymocytes also showed differential restimulation by BALB/c and B10.D2 stimulators. Taken together, our data indicate a role for the product(s) specified by non-MHC and non-Mls gene(s) in the autorecognition by thymocytes.

In an attempt to induce an immune response against tumour antigens, several groups are transfecting cytokine and other genes into autologous tumour cells which are given to the patient as a vaccine. This process is labour-intensive, time-consuming and expensive. Allogeneic cells would offer a more convenient vehicle for the delivery of cytokines and other molecules. However, current dogma suggests that MHC-matched cells are a prerequisite for an effective immune response. Using murine melanoma models we compared allogeneic and autologous vaccination and showed that the survival of C56BL/6 mice (H-2b) was prolonged with some degree of protection achieved against an autologous B15-F10 (H-2b) cell challenge when the mice were vaccinated with allogeneic K1735-M2 (H-2k) cells but not when immunized with autologous B16-F10 cells. Both vaccination with live and irradiated allogeneic cells induced an anti-tumour effect using only one immunization and no boost or adjuvant. Protection was not observed after vaccination with another melanoma (S91; H-2d) or with a carcinoma (A9HT; H-2k). Allogeneic vaccination promoted a cytotoxic cellular response against both the allogeneic and the syngeneic melanomas. This allogeneic vaccination model will be useful for studying the underlying mechanisms of protection, in both pre- and post-challenge settings, as well as for developing whole cell vaccination systems using genetically modified allogeneic tumour cells.

â-Thalassemia and pseudoxanthoma elasticum (PXE) are distinct genetic disorders. Yet, a dystrophic mineralization phenotype similar to PXE has frequently been associated with â-thalassemia or sickle cell anemia patients of Mediterranean descent. These calcifications are clinically and structurally identical to inherited PXE. As we previously excluded the presence of PXE-causing mutations in the ABCC6 gene of â-thalassemia patients with PXE manifestations, we hypothesized that a molecular mechanism independent of gene mutations either altered the ABCC6 gene expression or disrupted the biologic properties of its product in the liver or kidneys, which are the tissues with the highest levels of expression. To test this possibility, we investigated Abcc6 synthesis in the liver and kidneys of a â-thalassemia mouse model (Hbb(th3/+)). We found a progressive liver-specific down-regulation of the Abcc6 gene expression and protein levels by quantitative PCR, Western blotting, and immunofluorescence. The levels of Abcc6 protein decreased significantly at 6 months of age and stabilized at 10 months and older ages at ?25% of the wild-type protein levels. We studied the transcriptional regulation of the Abcc6 gene in wild-type and Hbb(th3/+) mice, and we identified the erythroid transcription factor NF-E2 as the main cause of the transcriptional down-regulation using transcription factor arrays and chromatin immunoprecipitation. The Hbb(th3/+) mice did not develop spontaneous calcification as seen in the Abcc6(-/-) mice probably because the Abcc6 protein decrease occurred late in life and was probably insufficient to promote mineralization in the Hbb(th3/+) mouse C57BL/6J genetic background. Nevertheless, our result suggested that a similar decrease of ABCC6 expression occurs in the liver of â-thalassemia patients and may be responsible for their frequent PXE-like manifestations.

alpha-1-antitrypsin, the major inhibitor of proteolytic enzymes in human serum, was isolated from normal individuals (protease inhibitor type MM) and from those with an inherited deficiency (protease inhibitor type ZZ) of circulatory protein. The two proteins were compared by circular dichroism spectroscopy, and by fluorescence quenching experiments using anionic (I-), and neutral (acrylamide) probes. Both proteins share a similar secondary structure, i.e. approximately 45--50% alpha-helix and 15--20% beta-structure. Evidence was accumulated to show that the microenvironment in the vicinity of the three tryptophanyl residues is altered in Z form as compared to the M form as shown by (a) the absence of the positive dichroic band in the region 290--300 nm of the circular dichroism spectra, (b) a greater than 50% increase in quantum yield in the tryptophanyl fluorescence emission spectra, (c) an increased accessibility of tryptophan to quenching by iodide, and (d) acrylamide quenching experiments which indicate that all tryptophanyl residues in the Z protein are quenched equally or that quenching is dominated by a single residue, while in the M protein, heterogeneous quenching occurs. The potential significance of these findings in terms of alpha-1-antitrypsin deficiency state are discussed.

A 16-year-old woman suffering from bronchial asthma since 2 years previously was admitted to the hospital because of high grade fever, dyspnea, skin eruption and arthralgia. Laboratory data revealed pronounced eosinophilia with elevated immunoglobulin E value. A chest X-ray film showed cardiomegaly with pulmonary congestion. Left ventriculograms showed diffusely reduced motion of the left ventricle (LV). Various clinical symptoms and laboratory data were resolved shortly after the administration of corticosteroids, but the LV dysfunction persisted for at least three months. Left ventriculograms 2 years later disclosed a marked improvement of the LV wall motion. In both the acute and the chronic phase, endomyocardial biopsy of both ventricles revealed non-specific histological findings comprising disarrangement of myocytes and interstitial fibrosis, suggesting post-myocarditis. This case was characterized by LV dysfunction possibly due to eosinophilic myocarditis associated with hypereosinophilic syndrome, and by its functional improvement with long-term corticosteroid therapy.

Budding yeast Mec1, homolog of mammalian ATR, is an essential protein that mediates S-phase checkpoint responses and meiotic recombination. Elimination of Mec1 function leads to genomewide fork stalling followed by chromosome breakage. Breaks do not result from stochastic collapse of stalled forks or other incidental lesions; instead, they occur in specific regions of the genome during a G2 chromosomal transition. Break regions are found to be genetically encoded replication slow zones (RSZs), a newly discovered yeast chromosomal determinant. Thus, Mec1 has important functions in normal S phase and the genome instability of mec1 (and, analogously, ATR-/-) mutants stems from defects in these basic roles.

BACKGROUND: Mobile health (mHealth) has continuously been used as a method in behavioral research to improve self-management in patients with chronic diseases. However, the evidence of its effectiveness in chronic disease management in the adult population is still lacking. We conducted a systematic review to examine the effectiveness of mHealth interventions on process measures as well as health outcomes in randomized controlled trials (RCTs) to improve chronic disease management.METHODS: Relevant randomized controlled studies that were published between January 2005 and March 2016 were searched in six databases: PubMed, CINAHL, EMBASE, the Cochrane Library, PsycINFO, and Web of Science. The inclusion criteria were RCTs that conducted an intervention using mobile devices such as smartphones or tablets for adult patients with chronic diseases to examine disease management or health promotion.RESULTS: Of the 12 RCTs reviewed, 10 of the mHealth interventions demonstrated statistically significant improvement in some health outcomes. The most common features of mHealth systems used in the reviewed RCTs were real-time or regular basis symptom assessments, pre-programed reminders, or feedbacks tailored specifically to the data provided by participants via mHealth devices. Most studies developed their own mHealth systems including mobile apps. Training of mHealth systems was provided to participants in person or through paper-based instructions. None of the studies reported the relationship between health outcomes and patient engagement levels on the mHealth system.CONCLUSIONS: Findings from mHealth intervention studies for chronic disease management have shown promising aspects, particularly in improving self-management and some health outcomes.

The attachment of tendons and ligaments to massive endoprostheses remains a clinical challenge due to the difficulty in achieving a soft tissue implant interface with a mechanical strength sufficient to transmit the forces necessary for locomotion. We have used an in vivo animal model to study patellar tendon attachment to an implant surface. The interface generated when the patellar tendon was attached to a hydroxyapatite (HA) coated implant was examined using light microscopy and a quantitative histomorphological analysis was performed. In the Autograft Group, the interface was augmented with autogenous cancellous bone and marrow graft, and at six weeks an indirect-like insertion was observed. At twelve weeks, the interface was observed to be a layered neo-enthesis, whose morphology was similar to a normal direct tendon insertion. In the HA Group, the tendon-implant interface was not augmented, and the implant was enveloped by a dense collagenous fibrous tissue. This study shows that a tendon-implant neo-enthesis can develop in situ by employing a suitable implant surface in association with biological augmentation.

We hypothesized that a factor may circulate in serum early during sepsis, modulating apoptosis of monocytes and lymphocytes. Serum was collected from 20 healthy volunteers and from 48 patients with severe sepsis/shock within 12 h from signs of the first failing organ. PBMCs were isolated from 20 healthy volunteers and incubated with collected sera. Apoptosis and expression of CD95 were determined by flow cytometry; experiments were run in the presence of caspase-8 and caspase-9 inhibitors and of CaCl(2). Activity of caspase-3 was determined in cell lysates by a chromogenic kinetic assay. Incubation with serum of patients induced apoptosis of CD4 lymphocytes and inhibited apoptosis of CD14 monocytes. This was attenuated after diluting serum or mixing with healthy serum. Activity of caspase-3 was consistent with these findings. Induced apoptosis of CD4 lymphocytes was greater among nonsurvivors, and it was inhibited in the presence of caspase inhibitors. Inhibitors did not modify the effect of patients' serum on apoptosis of CD14 monocytes. CaCl(2) reversed the inhibitory effect on apoptosis of CD14 moncytes. The above findings support the hypothesis for the existence of an early circulating factor in severe sepsis/shock, modulating apoptosis of CD4 lymphocytes and of CD14 monocytes by interaction with the two apoptotic pathways.

This communication describes developmental changes in myelin proteins prepared from control, hypothyroid, and hyperthyroid rat brain. In the 10- to 37-day postnatal period studied, total myelin protein was found to double, and this change mainly reflected the increase in proteolipid and basic protein constituents. Thyroid states affect differentially the various myelin proteins. Hypothyroidism decreases the proteolipid and slow-moving basic protein, but has no effect on the fast basic or minor proteins. In hyperthyroidism, an increase was observed in proteolipid as well as both slow- and fast-moving proteins. The protein alterations were correlated to the changes previously found in lipid composition of myelin consequent upon hypo- and hyperthyroidism, and the role of thyroid hormones in brain development.

The present study investigated the physiological characteristics of eight world-class (WC) and eight national-class (NC) Norwegian sprint cross country skiers. To measure the physiological response and treadmill performance, the skiers performed a submaximal test, a peak aerobic capacity (VO2peak) test, and a peak treadmill speed (V(peak)) test in the skating G3 technique. Moreover, the skiers were tested for G3 acceleration outdoors on asphalt and maximal strength in the lab. The standard of sprint skating performance level on snow was determined by International Ski Federation points, and the training distribution was quantified. WC skiers showed 8% higher VO2peak and twice as long a VO(2) plateau time at the VO2peak test, and a higher gross efficiency at the submaximal test (all P<0.05). Furthermore, WC skiers showed 8% higher V(peak) (P<0.05), but did not differ from NC skiers in acceleration and maximal strength. WC skiers performed more low- and moderate-intensity endurance training and speed training (both P<0.05). The current results show that aerobic capacity, efficiency, and high speed capacity differentiate WC and NC sprint skiers and it is suggested that these variables determine sprint skiing performance.

OBJECTIVE: To investigate endometrial scratch injury (ESI) as an intervention to improve IVF outcome in women undergoing a first ET.DESIGN: Systematic review and meta-analysis.SETTING: Not applicable.PATIENT(S): Infertile women undergoing a first fresh/frozen embryo transfer.INTERVENTION(S): We included published and unpublished data from randomized controlled trials in which the intervention group received ESI and controls received placebo or no intervention. Pooled results were expressed as relative risk (RR) with 95% confidence interval (CI). The review protocol was registered in PROSPERO to start the data extraction (CRD42018087786).MAIN OUTCOME MEASURE(S): Ongoing pregnancy/live birth rate (OPR/LBR), clinical pregnancy rate (CPR), multiple pregnancy rate (MPR), miscarriage rate (MR), and ectopic pregnancy rate (EPR).RESULT(S): Seven studies were included (1,354 participants). We found a nonsignificant difference between groups in terms of OPR/LBR, CPR, MR, MPR, and EPR. Subgroup analysis found that ESI on the day of oocyte retrieval (achieved by a Novak curette) reduced OPR/LBR (RR 0.31, 95% CI 0.14-0.69) and CPR (RR 0.36, 95% CI 0.18-0.71), whereas ESI during the cycle preceding ET (performed through soft devices) had no effect on OPR/LBR and CPR. No difference in the impact of ESI was observed between fresh and frozen embryo transfer.CONCLUSION(S): Current evidence does not support performing ESI with the purpose of improving the success of a first ET attempt.

This main focus of this study was to evaluate the thermal degradation kinetics and the phytochemical characterization of the elderberries extract. Pelargonidin-3-sophoroside and delphinidin-3-glucoside were identified as the major anthocyanin compounds and catechin hydrate as the major flavonoid compound. In order to further understand the action of the heat treatment on the bioactive compounds from elderberry extract, fluorescence studies were also carried out. In general, heating at temperatures ranging from 100 to 150 ? for up to 90 min caused a decrease in fluorescence intensity, simultaneously with significant redshifts in ëmax suggesting important molecular changes inside the anthocyanins structure, affecting the antioxidant activity. Increasing the heating time up to 120 min, the elderberry extract peaked at about 88 nm shifted toward higher wavelengths with respect to that of untreated solutions (peak at 442 nm). The kinetics studies of anthocyanins, fluorescence intensity, and antioxidant activity evidenced a decrease of the degradation rate constants with increased temperature while the activation energies for heat-induced fluorescence intensity, monomeric anthocyanins, and antioxidant activity were 39.62 ± 9.60, 49.97 ± 5.61, and 31.04 ± 19.92 kJ/mol, respectively. Our results can be valuable in terms of establishing the appropriate processing and formulation protocols that could lead to a more efficient utilization of these pigments in actual food products and/or nutraceuticals.

Precursor proteins containing mitochondrial peptide signals are cleaved after import by a mitochondrial processing peptidase. In yeast (Saccharomyces cerevisiae) and human (Homo sapiens), intermediate cleavage peptidase55 (ICP55) plays a role in stabilizing mitochondrial proteins by the removal of single amino acids from mitochondrial processing peptidase-processed proteins. We have investigated the role of a metallopeptidase (At1g09300) from Arabidopsis (Arabidopsis thaliana) that has sequence similarity to yeast ICP55. We identified this protein in mitochondria by mass spectrometry and have studied its function in a transfer DNA insertion line (icp55). Monitoring of amino-terminal peptides showed that Arabidopsis ICP55 was responsible for the removal of single amino acids, and its action explained the -3 arginine processing motif of a number of mitochondrial proteins. ICP55 also removed single amino acids from mitochondrial proteins known to be cleaved at nonconserved arginine sites, a subset of mitochondrial proteins specific to plants. Faster mitochondrial protein degradation rates not only for ICP55 cleaved protein but also for some non-ICP55 cleaved proteins were observed in Arabidopsis mitochondrial samples isolated from icp55 than from the wild type, indicating that a complicated protease degradation network has been affected. The lower protein stability of isolated mitochondria and the lack of processing of target proteins in icp55 were complemented by transformation with the full-length ICP55. Analysis of in vitro degradation rates and protein turnover rates in vivo of specific proteins indicated that serine hydroxymethyltransferase was affected in icp55. The maturation of serine hydroxymethyltransferase by ICP55 is unusual, as it involves breaking an amino-terminal diserine that is not known as an ICP55 substrate in other organisms and that is typically considered a sequence that stabilizes rather than destabilizes a protein.

Inadequate quality of care in healthcare facilities is one of the primary causes of patient mortality in low- and middle-income countries, and understanding the behavior of healthcare providers is key to addressing it. Much of the existing research concentrates on improving resource-focused issues, such as staffing or training, but these interventions do not fully close the gaps in quality of care. By contrast, there is a lack of knowledge regarding the full contextual and internal drivers-such as social norms, beliefs, and emotions-that influence the clinical behaviors of healthcare providers. We aimed to provide two conceptual frameworks to identify such drivers, and investigate them in a facility setting where inadequate quality of care is pronounced. Using immersion interviews and a novel decision-making game incorporating concepts from behavioral science, we systematically and qualitatively identified an extensive set of contextual and internal behavioral drivers in staff nurses working in reproductive, maternal, newborn, and child health (RMNCH) in government public health facilities in Uttar Pradesh, India. We found that the nurses operate in an environment of stress, blame, and lack of control, which appears to influence their perception of their role as often significantly different from the RMNCH program's perspective. That context influences their perceptions of risk for themselves and for their patients, as well as self-efficacy beliefs, which could lead to avoidance of responsibility, or incorrect care. A limitation of the study is its use of only qualitative methods, which provide depth, rather than prevalence estimates of findings. This exploratory study identified previously under-researched contextual and internal drivers influencing the care-related behavior of staff nurses in public facilities in Uttar Pradesh. We recommend four types of interventions to close the gap between actual and target behaviors: structural improvements, systemic changes, community-level shifts, and interventions within healthcare facilities.

We examined the effects of intracerebroventricular (icv) administration of neuromedin U (NMU) on plasma arginine vasopressin (AVP), oxytocin (OXT), and ACTH in rats, using RIA. The induction of c-fos protein (Fos) was examined by immunohistochemical study, and in situ hybridization histochemistry was used to detect c-fos gene expression in the paraventricular (PVN) and supraoptic nuclei (SON). Plasma AVP, OXT, and ACTH were increased in a dose-related manner 15 min after icv administration of NMU. The icv administration of NMU caused a marked induction of Fos-like immunoreactivity (LI) in the SON and the magnocellular and parvocellular divisions of the PVN. In the SON and the magnocellular divisions of the PVN, OXT-LI cells predominantly exhibited nuclear Fos-LI in comparison with AVP-LI cells. The marked induction of the expression of c-fos gene in the PVN and SON was observed 15, 30, and 60 min after icv administration of NMU. Neurosecretion and induction of c-fos gene expression after centrally administered NMU were significantly reduced by pretreatment with anti-NMU IgG. These results suggest that centrally administered NMU activates OXTergic cells in the PVN and SON predominantly as well as hypothalamo-pituitary adrenal axis.

UNLABELLED: 1.LIVING DONOR KIDNEY TRANSPLANTS: Using 1996-2001 UNOS Registry data, we assessed the joint influence of center, 19 pre- and 5 posttransplant factors on renal allograft function in 21,830 patients transplanted with living donor kidneys. During an initial risk period, 21,033 recipients were projected to keep their grafts through one year (an average 96.4% one-year graft survival), and, in a second risk period, 17,775 recipients were projected to keep their grafts through 5 years (84.5% conditional 5-year graft survival after surviving one year posttransplant). 2. CENTER EFFECTS: Following multivariate log-linear analysis, 57.5% and 26.5% of assignable variation in one- and 5-year living-donor graft survival rates were due to the variation across 234 transplant centers. Center effect dominated other factors in influencing early outcomes among living kidney donor transplants. A program's size was associated with this center effect since all large centers (400+ living donor kidneys) had better-than-average one-year graft survival rates, whereas smaller centers (< or = 100 grafts) had wide ranges in short-term outcomes (87-100%). Center size did not play a role in explaining long-term variation, and the extent to which uniformity in care remains the responsibility of the original center needs to be investigated. 3.PRETRANSPLANT FACTOR EFFECTS: The impact of the 19 pretransplant cofactors on short-term outcomes among living donor transplants was clinically small--adjusted one-year graft survival rates across all categories exceeded 94%. However, their long-term effects were stronger and more typical of cadaveric results. The following 4 factors, each explaining > 10% of the assignable variation in conditional 5-year graft survival, were ranked and independently yielded poor results: 1) kidneys from parental donors; 2) grafts in male recipients; 3) teenage/adult recipients (> 12 years); and 4) black recipients. Recipient's original disease and body mass index, donor's race and age, and HLA matching were highly significant factors, but their impact on long-term graft survival was less than those observed previously in cadaveric renal transplants. 4.POSTTRANSPLANT FACTOR EFFECTS: Short- and long-term outcomes were relatively stable regardless of the maintenance drug initiated at hospital discharge. Living donor transplant outcomes were similar for Neoral versus Tacrolimus and for MMF versus azathioprine. Kidney graft survival among living donor transplants was strongly affected by delays in graft function or acute rejection episodes. 5.CONCLUSIONS: During the first year posttransplant, the benefits of receiving a living donor kidney (versus a cadaver kidney) mitigate negative cofactor risks of graft failure. Beyond one-year, recipients of living donor kidneys are subjected to the same deleterious effects from cofactors and early posttransplant events that impact the long-term graft survival following cadaveric transplantation.

Diarrheal illness is a major cause of morbidity and mortality throughout the world, yet the etiologic agent of many cases of gastrointestinal illness remains unspecified, often due to the lack of convenient, timely, and sensitive diagnostic testing. Although bulk fecal specimens remain the recommended specimen type for enteric culture, rectal swabs may be an option preferred by clinicians and patients due to the convenience and timing of collection. However, the lack of data evaluating the sensitivity of rectal swabs compared to fecal specimens for detection of enteric pathogens precludes this specimen type from being recommended by national guidelines. In this study, we retrospectively reviewed 480 paired rectal swab and fecal specimens submitted for enteric culture to the Barnes-Jewish Hospital and St. Louis Children's Hospital microbiology laboratories in St. Louis, MO, from 2002 to 2017. We report 32% positivity of paired specimens with an overall agreement of 93% and Cohen's ê of 0.84 (95% confidence interval, 0.78 to 0.89). Additionally, we evaluated the time to result from the time of patient presentation to the health care setting and demonstrate that rectal swabs have a significantly shorter time to an actionable result than bulk fecal specimens (median, 67.4 h versus 78.4 h, respectively; P < 0.001). These findings indicate that rectal swabs facilitate on-demand culture-based testing with a sensitivity comparable to that of fecal specimens and thus should be recommended for enteric bacterial culture when bulk fecal specimens are unavailable.

BACKGROUND: Time-resolved three-dimensional, three-directional phase-contrast magnetic resonance velocity mapping (4D PC-MRI) is a powerful technique to depict dynamic blood flow patterns in the human body. However, the impact of phase background effects on flow visualizations has not been thoroughly studied previously, and it has not yet been experimentally demonstrated to what degree phase offsets affect flow visualizations and create errors such as inaccurate particle traces.PURPOSE: To quantify background phase offsets and their subsequent impact on particle trace visualizations in a 4D PC-MRI sequence. Additionally, we sought to investigate to what degree visualization errors are reduced by background phase correction.MATERIAL AND METHODS: A rotating phantom with a known velocity field was used to quantify background phase of 4D PC-MRI sequences accelerated with SENSE as well as different k-t BLAST speed-up factors. The deviation in end positions between particle traces in the measured velocity fields were compared before and after the application of two different phase correction methods.RESULTS: Phantom measurements revealed background velocity offsets up to 7 cm/s (7% of velocity encoding sensitivity) in the central slice, increasing with distance from the center. Background offsets remained constant with increasing k-t BLAST speed-up factors. End deviations of up to 5.3 mm (1.8 voxels) in the direction perpendicular to the rotating disc were found between particle traces and the seeding plane of the traces. Phase correction by subtraction of the data from the stationary phantom reduced the average deviation by up to 56%, while correcting the data-set with a first-order polynomial fit to stationary regions decreased average deviation up to 78%.CONCLUSION: Pathline visualizations can be significantly affected by background phase errors, highlighting the importance of dedicated and robust phase correction methods. Our results show that pathline deviation can be substantial if adequate phase background errors are not minimized.

BACKGROUND: Alopecia is a common dermatological condition with mostly cosmetic consequences that, nevertheless, has significant psychological and psychosocial impact.OBJECTIVE: To assess the impact of alopecia on quality of life and certain psychological domains and to compare it between scarring and non-scarring alopecia in Greek adult women.PATIENTS AND METHODS: Forty-four women, aged 18-70 years, with scarring (n = 19) or non-scarring alopecia (n = 25) were recruited. All patients were evaluated by Dermatology Life Quality Index (DLQI), Hospital Anxiety and Depression Scale (HADS), Rosenberg Self-esteem Scale (RSES) and UCLA Loneliness Scale (UCLA-LS).RESULTS: Women with scarring alopecia had higher scores in DLQI, HADS and UCLA- LS and lower scores in RSES, compared to women with non-scarring alopecia. A statistically significant difference between the two groups was documented for DLQI (p = 0.0067), HADS (p = 0.0008), and HADS-Anxiety (HADS-A) (p < 0.05) and HADS-Depression (HADS-D) (p < 0.01) subscales.CONCLUSIONS: The psychological burden is heavier and quality of life is more severely impaired among women with scarring alopecia compared with non-scarring alopecia, probably depicting the poorer prognosis of the former.

Pure sensory stroke (PSS) is typically caused by a lacunar infarct located in the ventral-posterior (VP) thalamic nucleus contralateral to the paresthetic symptoms. The lesion is usually so small that it cannot be seen on computerized tomography (CT), as illustrated by our case. In our moderately hypertensive, 72-year-old patient with PSS, CT scanning and conventional nuclear magnetic resonance imaging (NMRI) scanning using a 7-mm-thick slice on a 1.5 Tesla instrument all failed to visualize the thalamic infarct. Using the high-resolution mode with 2-mm slice thickness it was, however, clearly seen. In addition, NMRI unexpectedly showed diffuse periventricular demyelinization as well as three other lacunar infarcts, i.e., findings characteristic of subcortical arteriosclerotic encephalopathy (SAE). This prompted psychometric testing, which revealed signs of mild (subclinical) dementia, in particular involving visiospatial apraxia; this pointed to decreased function of the right parietal cortex, which was structurally intact on CT and NMRI. Single photon emission computerized tomography by Xenon-133 injection and by hexamethyl-propyleneamine-oxim labeled with Technetium-99m showed asymmetric distribution of cerebral blood flow (CBF), with an 18% lower value in the right parietal cortex compared to the left side; this indicated asymmetric disconnection of the cortex by the SAE. Thus, the tomograms of the functional parameter, CBF, correlated better with the deficits revealed by neuropsychological testing than by CT or NMRI.

BACKGROUND/PURPOSE: To image subretinal neovascularization in proliferative macular telangiectasia Type 2 (MacTel2) using swept source optical coherence tomography based microangiography (OMAG).METHODS: Patients with macular telangiectasia Type 2 were enrolled in a prospective, observational study known as the MacTel Project and evaluated using a high-speed 1,050 nm swept-source OCT prototype system. The OMAG algorithm generated en face flow images from three retinal layers, and the region bounded by the outer retina and Bruch membrane, the choriocapillaris, and the remaining choroidal vasculature. The en face OMAG images were compared with images from fluorescein angiography and indocyanine green angiography.RESULTS: Three eyes with neovascular macular telangiectasia Type 2 were imaged. The neovascularization was best identified from the en face OMAG images that included a layer between the outer retinal boundary and Bruch membrane. Optical coherence tomography based microangiography images identified these abnormal vessels better than fluorescein angiography and were comparable to the images obtained using indocyanine green angiography. In all 3 cases, OMAG identified choroidal vessels communicating with the neovascularization, and these choroidal vessels were evident in the 2 cases with indocyanine green angiography imaging. In 1 case, monthly injections of bevacizumab reduced the microvascular complexity of the neovascularization, and the telangiectatic changes within the retinal microvasculature. In another case, less frequent bevacizumab therapy was associated with growth of the subretinal neovascular complex.CONCLUSION: Optical coherence tomography based microangiography imaging provided detailed, depth-resolved information about subretinal neovascularization in macular telangiectasia Type 2 eyes demonstrating superiority to fluorescein angiography imaging, and similarities to indocyanine green angiography imaging for documenting the retinal microvascular changes, the size and extent of the neovascular complex, the communications between the neovascular complex and the choroidal circulation, and the response to monthly bevacizumab therapy.

Ebola virus disease outbreaks in animals (including humans and great apes) start with sporadic host switches from unknown reservoir species. The factors leading to such spillover events are little explored. Filoviridae viruses have a wide range of natural hosts and are unstable once outside hosts. Spillover events, which involve the physical transfer of viral particles across species, could therefore be directly promoted by conditions of host ecology and environment. In this report, we outline a proof of concept that temporal fluctuations of a set of ecological and environmental variables describing the dynamics of the host ecosystem are able to predict such events of Ebola virus spillover to humans and animals. We compiled a data set of climate and plant phenology variables and Ebola virus disease spillovers in humans and animals. We identified critical biotic and abiotic conditions for spillovers via multiple regression and neural network-based time series regression. Phenology variables proved to be overall better predictors than climate variables. African phenology variables are not yet available as a comprehensive online resource. Given the likely importance of phenology for forecasting the likelihood of future Ebola spillover events, our results highlight the need for cost-effective transect surveys to supply phenology data for predictive modelling efforts.

The ease with which a particular DNA segment adopts the left-handed Z-conformation depends largely on the sequence and on the degree of negative supercoiling to which it is subjected. We describe a computer program (Z-hunt) that is designed to search long sequences of naturally occurring DNA and retrieve those nucleotide combinations of up to 24 bp in length which show a strong propensity for Z-DNA formation. Incorporated into Z-hunt is a statistical mechanical model based on empirically determined energetic parameters for the B to Z transition accumulated to date. The Z-forming potential of a sequence is assessed by ranking its behavior as a function of negative superhelicity relative to the behavior of similar sized randomly generated nucleotide sequences assembled from over 80,000 combinations. The program makes it possible to compare directly the Z-forming potential of sequences with different base compositions and different sequence lengths. Using Z-hunt, we have analyzed the DNA sequences of the bacteriophage phi X174, plasmid pBR322, the animal virus SV40 and the replicative form of the eukaryotic adenovirus-2. The results are compared with those previously obtained by others from experiments designed to locate Z-DNA forming regions in these sequences using probes which show specificity for the left-handed DNA conformation.

OBJECTIVE:  To develop a prediction model to estimate the chances of a live birth over multiple complete cycles of in vitro fertilisation (IVF) based on a couple's specific characteristics and treatment information.DESIGN:  Population based cohort study.SETTING:  All licensed IVF clinics in the UK. National data from the Human Fertilisation and Embryology Authority register.PARTICIPANTS:  All 253 417 women who started IVF (including intracytoplasmic sperm injection) treatment in the UK from 1999 to 2008 using their own eggs and partner's sperm.MAIN OUTCOME MEASURE:  Two clinical prediction models were developed to estimate the individualised cumulative chance of a first live birth over a maximum of six complete cycles of IVF-one model using information available before starting treatment and the other based on additional information collected during the first IVF attempt. A complete cycle is defined as all fresh and frozen-thawed embryo transfers arising from one episode of ovarian stimulation.RESULTS:  After exclusions, 113 873 women with 184 269 complete cycles were included, of whom 33 154 (29.1%) had a live birth after their first complete cycle and 48 925 (43.0%) after six complete cycles. Key pretreatment predictors of live birth were the woman's age (31 v 37 years; adjusted odds ratio 1.66, 95% confidence interval 1.62 to 1.71) and duration of infertility (3 v 6 years; 1.09, 1.08 to 1.10). Post-treatment predictors included number of eggs collected (13 v 5 eggs; 1.29, 1.27 to 1.32), cryopreservation of embryos (1.91, 1.86 to 1.96), the woman's age (1.53, 1.49 to 1.58), and stage of embryos transferred (eg, double blastocyst v double cleavage; 1.79, 1.67 to 1.91). Pretreatment, a 30 year old woman with two years of unexplained primary infertility has a 46% chance of having a live birth from the first complete cycle of IVF and a 79% chance over three complete cycles. If she then has five eggs collected in her first complete cycle followed by a single cleavage stage embryo transfer (with no embryos left for freezing) her chances change to 28% and 56%, respectively.CONCLUSIONS:  This study provides an individualised estimate of a couple's cumulative chances of having a baby over a complete package of IVF both before treatment and after the first fresh embryo transfer. This novel resource may help couples plan their treatment and prepare emotionally and financially for their IVF journey.

We describe a patient undergoing long-term hemodialysis, in whom severe chondrolysis of the hip joint developed. The chondrolysis evolved in the absence of synovial inflammation and articular chondrocalcinosis. Biochemical studies of articular cartilage retained at surgery revealed deposition of exclusively small proteoglycans in the matrix. This may have been an important factor leading to the rapid chondrolysis in this patient.

A multi-institutional study was undertaken to define the predictive power for mortality of the Rapid Acute Physiology Score (RAPS) in a large and diverse group of transported patients. RAPS is a truncated version of the Acute Physiology and Chronic Health Evaluation (APACHE II) score that uses definitions and weighting consistent with APACHE II, but is modified to provide a consistent score just before transport, just after transport, and to use the most deranged (worst) physiologic values during the initial 4 h after arrival at the receiving hospital. During an 8-month period, 1,927 patients transported by six helicopter emergency medical service programs were studied. Over 97% (1,881) of the patients had RAPS obtained before and after transport to the receiving hospital and 92.6% (1,785) had APACHE II scoring completed after hospital admission. Receiver operating curves demonstrate similar predictive power for RAPS and APACHE II (both based on the most deranged physiologic values during the initial 24 h after admission). Before- and after-transport RAPS were also highly predictive of mortality. RAPS appears to be a reliable and highly predictive measure of patient severity/physiologic stability before and after transport to critical care.

Myofibroblasts, the primary cells associated with corneal stromal haze (opacity), can be derived from both cornea-derived and bone marrow-derived precursor cells. In the present study, the role of TGFâ or PDGF blockage on bone marrow-derived myofibroblast development was investigated using a green fluorescent protein (GFP) chimeric bone marrow mouse model and plasmid vectors that blocked TGFâ or PDGF signaling. At the peak of corneal haze one month after irregular phototherapeutic keratectomy the central stroma had significantly less alpha-smooth muscle actin (á-SMA)-positive cells derived from GFP+ bone marrow-derived cells or GFP- keratocyte/corneal fibroblast-derived cells when corneas were treated with the TGFâ blocking vector pGFPC1.TGFRBKDEL or the PDGF blocking vector pCMV.PDGFRB.23KDEL compared with the corresponding empty vector treated or untreated control groups. In individual animals, 30-60% of myofibroblasts were derived from bone marrow-derived precursor cells and 40-70% of myofibroblasts were derived from keratocyte-derived precursor cells. TGFâ and PDGF regulate corneal myofibroblast development from bone marrow-derived precursor cells and keratocyte/corneal fibroblast-derived precursor cells.

Stated and measured patient heights and weights were compared, and the clinical importance of any differences was determined. A total of 112 health-clinic patients were interviewed for height and weight determinations. They were divided into four groups: men 21-35 years old; men 65 years and older; women 21-35 years old; and women 65 years and older. The stated and the actual heights and weights were analyzed for significant differences. Calculations of body surface area (BSA) and basal energy expenditure (BEE) were used to determine the clinical impact of any discrepancies. Patients in all groups tended to overestimate their height, but only the estimates of men differed significantly from the measured values. Differences between stated and measured heights for older women showed statistical differences from younger men and women but not from older men. All groups except young men overestimated their weight. Older men showed the greatest tendency towards overestimation of weight. In elderly men, the calculations of BSA and BEE were significantly different (p less than 0.002) when stated versus measured values were used. These differences were not considered clinically important. Overall, patients in all groups were well aware of their heights and weights.

Visuospatial stimuli are normally perceived from the global structure to local details. A right-brain stroke often disrupts this perceptual organization, resulting in piecemeal encoding and thus poor visuospatial memory. Using a randomized controlled design, the present study examined whether promoting the global-to-local encoding improves retrieval accuracy in right-brain-damaged stroke survivors with visuospatial memory deficits. Eleven participants received a single session of the Global Processing Training (global-to-local encoding) or the Rote Repetition Training (no encoding strategy) to learn the Rey-Osterrieth Complex Figure. The result demonstrated that the Global Processing Training significantly improved visuospatial memory deficits after a right-brain stroke. On the other hand, rote practice without a step-by-step guidance limited the degree of memory improvement. The treatment effect was observed both immediately after the training procedure and 24 h post-training. Overall, the present findings are consistent with the long-standing principle in cognitive rehabilitation that an effective treatment is based on specific training aimed at improving specific neurocognitive deficits. Importantly, visuospatial memory deficits after a right-brain stroke may improve with treatments that promote global processing at encoding.

One of the fundamental issues in the study of animal cognition concerns categorization. Although domestic dogs (Canis familiaris) are on the brink to become one of the model animals in animal psychology, their categorization abilities are unknown. This is probably largely due to the absence of an adequate method for testing dogs' ability to discriminate between large sets of pictures in the absence of human cueing. Here we present a computer-automated touch-screen testing procedure, which enabled us to test visual discrimination in dogs while social cueing was ruled out. Using a simultaneous discrimination procedure, we first trained dogs (N = 4) to differentiate between a set of dog pictures (N = 40) and an equally large set of landscape pictures. All subjects learned to discriminate between the two sets and showed successful transfer to novel pictures. Interestingly, presentation of pictures providing contradictive information (novel dog pictures mounted on familiar landscape pictures) did not disrupt performance, which suggests that the dogs made use of a category-based response rule with classification being coupled to category-relevant features (of the dog) rather than to item-specific features (of the background). We conclude that dogs are able to classify photographs of natural stimuli by means of a perceptual response rule using a newly established touch-screen procedure.

Influences of dietary patterns on musculoskeletal health are poorly understood in middle-aged women. This cross-sectional analysis from a cohort of 347 women (aged 36-57 years) aimed to examine associations between dietary patterns and musculoskeletal health outcomes in middle-aged women. Diet was measured by the Cancer Council of Victoria FFQ. Total body bone mineral content (TB BMC), femoral neck and lumbar spine bone density (dual-energy X-ray absorptiometry), lower limbs muscle strength (LMS) and balance tests (timed up and go test, step test, functional reach test (FRT) and lateral reach test) were also measured. Exploratory factor analysis was used to identify dietary patterns and scores for each pattern generated using factor loadings with absolute values ?0·20. Associations between food pattern scores and musculoskeletal outcomes were assessed using multivariable linear regression. Three dietary patterns were identified: 'Healthy' (high consumption of a plant-based diet - vegetables, legumes, fruit, tomatoes, nuts, snacks, garlic, whole grains and low intake of high-fat dairy products), 'high protein, high fat' (red meats, poultry, processed meats, potatoes, cruciferous and dark-yellow vegetables, fish, chips, spirits and high-fat dairy products) and 'Processed foods' (high intakes of meat pies, hamburgers, beer, sweets, fruit juice, processed meats, snacks, spirits, pizza and low intake of cruciferous vegetables). After adjustment for confounders, Healthy pattern was positively associated with LMS, whereas Processed foods pattern was inversely associated with TB BMC and FRT. The associations were not significant after accounting for multiple comparisons. There were no associations with any other outcomes. These results suggest that maintaining a healthy diet could contribute to bone acquisition, muscle strength and balance in adult life. However, while they provide some support for further investigating dietary strategies for prevention of age-related loss of muscle and deterioration in balance, the exploratory nature of the analyses means that confirmation in longitudinal studies and/or trials with pre-specified hypotheses is needed.

BACKGROUND: There have been conflicting reports about pregnancy outcome in the hypertensive disorders of pregnancy. The present study was undertaken to examine outcomes using a population database.AIMS: To examine for differences in a range of pregnancy outcomes between three different groups of hypertensive women and normotensive women in South Australia.METHODS: Nine pregnancy outcomes were compared for 70,386 singleton pregnancies in the South Australian perinatal data collection in 1998-2001, consisting of 639 women with pre-existing hypertension, 5356 women with pregnancy hypertension, 448 women with superimposed pre-eclampsia and 63 943 normotensive women. Means for the four groups were calculated for birthweight, gestational age, the baby's and mother's length of stay. The groups were also compared for perinatal deaths with an earlier period, 1991-1997.RESULTS: While all three hypertensive groups had high incidences of induction of labour and emergency Caesarean, only pre-existing hypertension and superimposed pre-eclampsia were significantly associated with elective Caesarean section. All hypertensive groups had increased risks for low birthweight and preterm birth and special and neonatal intensive care. Uncomplicated pre-existing hypertension was not associated with small for gestational age infants, but with preterm delivery between 32 and 36 weeks' gestation. Superimposed pre-eclampsia had the worst prognosis for perinatal and maternal morbidity. While pregnancy hypertension held the intermediate position, it was not associated with an increase in perinatal mortality. The perinatal mortality rate for women with hypertensive disorders in 1998-2001 was significantly lower than that of an earlier period and equivalent to that for normotensive women.CONCLUSIONS: Superimposed pre-eclampsia occurs in approximately 40% of pregnancies of women with pre-existing hypertension and has the most severe outcomes. The hypertensive disorders are associated with high levels of morbidity and intervention, but the high perinatal mortality associated with these disorders has fallen significantly.

A method of identification and quantitative determination of amitriptyline and cocaine at trace levels in biological fluids is described. After the extraction of both drugs from the biological material in an alkaline medium, and posterior purification and concentration of the extract, one proceeds to unequivocal identification using the combined capillary GC/MS system with the Selected Ion Monitoring (SIM) technique. Quantitative determination is carried out by GC with a N-P detector. The precision of the method and limits of sensitivity are presented.

A lab-scale study on the application of supported liquid membranes (SLM) has been conducted for recovery and selective removal of Malachite Green dye from wastewater. Naturally occurring non-toxic vegetable oils have been used as membrane liquids. Polyvinylidene fluoride (PVDF) films have been used as supports for the liquid membrane. Various parameters affecting the dye permeation such as initial dye concentration, pH, stripping acid concentration, oil viscosity and membrane stability have been investigated. The highest flux value (1.65 ? 10-5 mg/cm2/sec) was obtained with a sunflower oil supported membrane at pH 11 in the feed and 0.25 M HCl in the stripping solution. The membrane showed good stability under optimum conditions and maximum transport was achieved in 8 h of permeation time.

A basic protein, BpH2, with an apparent molecular mass of 18 kDa was purified from Bordetella pertussis, and the corresponding gene, bph2, was cloned. Sequence analysis revealed some homology to the H1 class of eukaryotic histones and to AlgP protein of Pseudomonas aeruginosa. BpH2 binds both single- and double-stranded DNA in a nonspecific manner. Deletion of the corresponding gene in B. pertussis generated a BpH2 null mutant with an altered growth rate in which the expression of two virulence factors, adenylate cyclase-hemolysin (CyaA) and filamentous hemagglutinin (FhaB), was reduced. It is suggested that BpH2 may exhibit specific regulatory functions through its interaction with chromosomal DNA.

PURPOSE: Transobturator slings have higher rates of de novo neurologic symptoms than retropubic slings, most commonly related to the thigh. Cases refractory to conservative management may require removal of the thigh portion of the sling. In this series we prospectively examine the effect of thigh dissection with mesh removal on refractory thigh pain.MATERIALS AND METHODS: All thigh dissections for refractory neurologic symptoms after transobturator sling placement were followed prospectively from October 2012 to October 2015. Patients were assessed preoperatively, with a pain score using a visual analog scale, and postoperatively with a global response assessment.RESULTS: A total of 12 thigh dissections were performed from October 2012 to October 2015 in 8 patients. Mean (±SD) time from original mesh placement to presentation was 2.7 (±1.5) years. Average preoperative pain score was 7.9 (±1.7) out of 10, with pain in the thigh in all patients. Seven cases involved unilateral thigh dissection and 1 had concomitant bilateral thigh dissection. Five patients underwent concurrent transvaginal excision. On postoperative evaluation the average global response rating was 1.6, with 1 defined as very much better and 2 defined as much better. Of the 8 patients 3 went on to have the contralateral side done with an average global response rating of 1.3 (±0.6). One patient underwent further treatment for stress urinary incontinence with placement of a retropubic mid urethral sling.CONCLUSIONS: Our prospective series supports the use of thigh dissection in patients with refractory neurologic symptoms after transobturator sling placement. The procedure can be performed safely with positive outcomes for the patient.

Cardiopulmonary bypass (CPB) is known to induce several pathogenic responses in cardiovascular surgery. To explore leukocyte activation during PCB, we investigated superoxide anion (O2-) production by granulocytes in 6 patients undergoing aortocoronary bypass surgery. O2- production was determined with chemiluminescence amplified by a cypridina luciferin analogue. Granulocytes collected from the blood in the arterial site of the CPB circuit were stimulated by phorbol myristate acetate, n-formyl-methionyl-leucyl-phenylalanine, and opsonized zymosan. All the stimulators failed to disclose a significant difference between the magnitude of chemiluminescence during and after CPB. However, significant complement activation was detected, and the plasma level of granulocyte elastase increased gradually during and after CPB. This discrepancy between the unchanged O2- production by stimulated granulocytes and the increase in inflammatory mediators including granulocyte elastase may be due to sequestration of activated granulocytes in extravascular tissues. Namely, it was highly likely that activated granulocytes responsible for the increased plasma elastase level were sequestered and remained outside the blood circulation.

During one academic year, three patients were referred to Parasitology Laboratory from Dermatology Outpatients Clinics in King Abdulaziz University Hospitals. They were diagnosed as Sowda (chronic hyperactive form of onchocerciasis volvulus). The patients came from Asir Region in the Southern of the Kingdom. The lesion was characterized by a sever papule dermatitis localized to the lower limbs, with marked skin darkening. There was extensive follicular hyperplasia of the regional lymph nodes in two cases only. The skin snips taken from the three patients were positive microfilariae. On the other hand, the urine sample of one patient was positive. Six months after the onset of treatment by the clinicians in the Specialized Hospital, skin snips and urine samples were negative.

Strategies are needed for human immunodeficiency virus type 1 vaccine development that improves the neutralizing antibody response against primary isolates of the virus. Here we examined recombinant DNA priming followed by subunit protein boosting as a strategy to generate neutralizing antibodies. Both plasmid-based and recombinant protein envelope (Env) glycoprotein immunogens were derived from a primary viral isolate, JR-FL. Serum from rabbits immunized with either gp120 or gp140 DNA vaccines delivered by gene gun inoculation followed by recombinant gp120 protein boosting was capable of neutralizing JR-FL. Neither the DNA vaccines alone nor the gp120 protein alone generated a detectable neutralizing antibody response against this virus. Neutralizing antibody responses using gp120 DNA and gp140 DNA for priming were similar. The results suggest that Env DNA priming followed by gp120 protein boosting provides an advantage over either approach alone for generating a detectable neutralizing antibody response against primary isolates that are not easily neutralized.

Age-related muscle atrophy or sarcopenia results in progressive loss of muscle function and satellite cells in aging muscle are increasingly refractory to activation that could mitigate atrophy. We know that nitric oxide release triggered by mechanical stretch of skeletal muscle, initiates satellite cell activation in vitro in single fiber, single cell and whole-muscle cultures, and in vivo in animals. This study examined muscle cell activation using tritiated-thymidine incorporation into the DNA of muscle cells in cultured muscles from female mice between 6 weeks and 18 months-of-age. Experiments examined age-related changes in activation by mechanical stretch and/or NO treatments (with the substrate of nitric oxide synthase (l-arginine), a nitric oxide donor (isosorbide dinitrate) and/or nitric oxide synthase inhibition). Activation without stretch was highest at 8 months. Stretching muscles by 10% more than doubled activation in muscles at 6 weeks of age and only a 20% stretch similarly activated cells in cultured 6-month-old muscles. Only treatment with ISDN in combination with a 20% stretch activated cell proliferation in muscles from 8-month-old mice. A nitric-oxide donor drug rescued muscle satellite cells in adult, 8-month-old mice from being refractory to mechanical stretch, apparently by overcoming an ineffective release of nitric oxide during stretch. Results suggest that treatment with nitric oxide has the potential to enhance the effectiveness of exercise in preventing the onset of age-related muscle atrophy in adult muscle.

Cells within connective tissues routinely experience a wide range of non-uniform mechanical loads that regulate many cell behaviors. In this study, we developed an experimental system to produce complex strain patterns for the study of strain magnitude, anisotropy, and gradient effects on cells in culture. A standard equibiaxial cell stretching system was modified by affixing glass coverslips (5, 10, or 15 mm diameter) to the center of 35 mm diameter flexible-bottomed culture wells. Ring inserts were utilized to limit applied strain to different levels in each individual well at a given vacuum pressure thus enabling parallel experiments at different strain levels. Deformation fields were measured using high-density mapping for up to 6% applied strain. The addition of the rigid inclusion creates strong circumferential and radial strain gradients, with a continuous range of stretch anisotropy ranging from strip biaxial to equibiaxial strain and radial strains up to 24% near the inclusion. Dermal fibroblasts seeded within our 2D system (5 mm inclusions; 2% applied strain for 2 days at 0.2 Hz) demonstrated the characteristic orientation perpendicular to the direction of principal strain. Dermal fibroblasts seeded within fibrin gels (5 mm inclusions; 6% applied strain for 8 days at 0.2 Hz) oriented themselves similarly and compacted their surrounding matrix to an increasing extent with local strain magnitude. This study verifies how inhomogeneous strain fields can be produced in a tunable and simply constructed system and demonstrates the potential utility for studying gradients with a continuous spectrum of strain magnitudes and anisotropies.

UNLABELLED: Polycyclic aromatic hydrocarbons (PAH) are a common environmental contaminant originating from both anthropogenic and natural sources. Mycobacterium species are highly adapted to utilizing a variety of PAH. Silver nanoparticles (AgNP) are an emerging contaminant that possess bactericidal properties, interferes with the bacterial membrane and alters function. Mycobacterium sp. strain RJGII-135 provided a model bacterium to assess changes in carbon metabolism by focusing on PAH degradation, which is dependent upon passive uptake of hydrophobic molecules into the cell membrane. A mixture of 18 PAH served as a complex mixture of carbon sources for assessing carbon metabolism. At environmentally relevant PAH concentrations, RJGII-135 degraded two-, three-, and four-ring PAH within 72 h, but preferentially attacked phenanthrene and fluorene. Total cell growth and PAH degradation were successively reduced when exposed to 0·05-0·5 mg 1(-1) AgNP. However, 0·05 mg l(-1) AgNP inhibited degradation of naphthalene, acenaphthylene and acenaphthalene. RJGII-135 retained the ability to degrade the methylated naphthalenes regardless of AgNP concentration suggesting that proteins involved in dihydrodiol formation were inhibited. The reduced PAH metabolism of RJGII-135 when exposed to sublethal concentrations of AgNP provides evidence that nanoparticle pollution could alter carbon cycling in soils, sediment and aquatic environments.SIGNIFICANCE AND IMPACT OF THE STUDY: Silver nanoparticle (AgNP) pollution threatens bacterial-mediated processes due to their antibacterial properties. With the widespread commercial use of AgNP, continued environmental release is inevitable and we are just beginning to understand the potential environmental ramifications of nanoparticle pollution. This study examined AgNP inhibition of carbon metabolism through the polycyclic aromatic hydrocarbon degradation by Mycobacterium species RJGII-135. Sublethal doses altered PAH metabolism, which is dependent upon cell membrane properties and intracellular proteins. The changed carbon metabolism when exposed to sublethal doses of AgNP suggests broad impacts of this pollution on bacterial carbon cycling in diverse environments.