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There has been a considerable research on the process analytical technology (PAT) and real-time monitoring based on NIR, but the model development is still an important issue and persons in charge have difficulty in building good models. In this study, to realize efficient NIR-based real-time monitoring of ingredient concentration and establish a model development method, we investigated the effect of a calibration set, spectral preprocessing, wavelengths, and other factors on the prediction error through pilot and commercial scale blending experiments. The results confirmed that the small prediction error was realized by a calibration set, including dynamic measurement spectra acquired with the target blender. In addition, the results demonstrated that locally weighted partial least squares (LW-PLS) achieved the smaller prediction error than conventional PLS. The present study has also clarified that spectral preprocessing methods and wavelengths selected to build a model affect the prediction error of ingredient concentration interactively. A wide wavelength range should be selected when the spectral preprocessing does not lessen the effect of baseline variation, while a narrow wavelength range should be selected when it strongly decreases the effect.

Chitosan (CS)/heparin (HEP) polyelectrolyte complex (PEC) was covalently immobilized onto the surface of polyacrylonitrile (PAN) membrane. The effect of surface modification on the protein adsorption and platelet adhesion, metabolites permeation and anticoagulation activity of the resulting membrane was investigated. Surface characterization such as water contact angle, and X-ray photoelectron spectroscope were performed. The immobilization of PEC caused the water contact angle to reduce, thereby indicating the increase in the hydrophilicity. Protein adsorption, platelet adhesion, and thrombus formation were all reduced by the immobilization of HEP. Anticoagulant activity was evaluated with activated partial thrombin time (APTT), prothrombin time (PT), fibrinogen time, and thrombin time (TT). The results revealed that PEC-immobilizing membrane can improve antithrombogenicity of PAN membrane. In addition, the PEC-immobilized membranes can suppress the proliferation of Pseudomonas aeruginosa. In vitro cytotoxicity test showed leachable substance released was below cytotoxic level. The pure water permeability results show little variation due to PEC-immobilization. Thus PEC-immobilization can endow the PAN membrane hemocompatibility and antibacterial activity while retaining the original permeability.

Nanoscale copper ferrite was prepared by co-precipitation method, while citrate acid assisted method was used as reference. Microwave-induced degradation of crystal violet was performed with synthesized copper ferrite, and the behavior of copper ferrite in this process was studied by X-ray photoelectron spectroscopy, SEM/EDS and vector network analyzer. Microwave radiation could greatly enhance the activity of copper ferrite in organic oxidation. The variant of copper and iron on the surface and in the inner core of copper ferrite was studied here. Copper ferrite presents relatively low dielectric loss. Meanwhile, microwave radiation makes a faster degradation than conventional heating process, indicating an indispensable non-thermal effect of microwave with copper ferrite in the process. Microwave induced holes could be responsible for the efficient degradation. The effect of annealing on crystallization and degradation process was considered here, and the intermediates and products were studied by GC-MS and LC-MS to provide a comprehensively evaluation of degradation.

OBJECTIVE: To investigate the relationship between the SMAS and the facial nerve divisions in the cheek area.METHOD: We dissected 12 cadaver heads(24 sides).RESULTS: 1. SMAS distributed over the middle face. It became thinner as it extended forward and there was a small aperture lateral to the mouth. The branches of facial nerve lay directly beneath the parotidomassetric fascia after emerging from the parotid gland. 2. The frontal branch penetrated the deep fascia to the SMAS at about 0.5 cm below the zygomatic arch. 3. Some buccal branches went through the cheek fat pad while the others lay on its surface directly under the thin SMAS. 4. There was constantly a zygomatic ramus went into the upper one third of the zygomaticus. It innervated the lower and lateral orbicularis oculi muscle in 9 of 24 sides (37.5%) of the cadaver heads, zygomaticus major and minor and orbicularis oculi muscle in 8 of 24 sides (33.3%), and the zygomaticus major and minor in 7 of 24 sides (29.2%).CONCLUSION: During facelifting, wide dissection of the SMAS should be done directly above the parotidomassetric fascia and 0.5 cm below the zygomatic arch. While approaching the middle face, the dissection should be limited to the lower two third of the zygomaticus, followed by elevating the zygomatic fat. The authors dissect the nasolabial fold through the lower eyelid incision, then the dissection should go downwards, under the orbicularis oculi muscle, to the nasolabial area. In a clinical situation, care must be taken not to damage the facial nerve trunk, and dissection of the upper one third of the zygomaticus should be avoided.

Female noninbred Sprague-Dawley rats were exposed to single doses of 0.28, 0.56, and 0.85 gray (Gy = 1 J/kg or 100 rads) of X-rays or 0.001, 0.004, 0.016, and 0.064 Gy of 430-keV neutrons at 62 +/- 1 days of age and were then observed over the rest of their lives for the appearance of mammary neoplasia. As mammary neoplasms were detected, they were removed and given a classification of adenocarcinoma(s) (AC) or fibroadenoma(s) (FA) after microscopic study. All irradiated groups exhibited an increased incidence of mammary neoplasia. The tumor rate increased steeply with age of the animals, and the effect of the irradiation could be adequately described as a forward shift in time of the spontaneous incidence. The cumulative prevalence was derived from first neoplasms only, and a formalism was presented that makes it possible to derive the integral tumor rate from all neoplasms in all animals. Mortality-corrected cumulative prevalences and integral tumor rates as a function of age were given for the different doses and separately for FA and AC. The mammary FA response and the total mammary neoplastic response (including both FA and AC) were approximately proportional to the absorbed dose of X-rays or the square root of the neutron dose. The relative biological effectiveness (RBE) of the neutrons increased with decreasing dose and reached values exceeding 100 at a neutron dose of 1 mGy; the single dose of 1 mGy of neutrons produced a significant increase of the tumor rate that corresponded to a foward shift or roughly 35 days of the spontaneous incidence. The AC, taken separately, were subject to considerable statistical uncertainties due to their small numbers. However, their RBE-dose dependence was consistent with that for the FA and, even at the highest dose studied, the RBE value exceeded 10. The nonrandom development of multiple FA within individual animals appeared to be the result of differences in susceptibility to radiation. However, mammary FA and AC within individual animals were not statistically correlated.

The rapid development of the small interfering ribonucleic acid (siRNA)-induced inhibition of the gene expression at the RNA level offers to research groups a new strategy for the understanding of gene functions. The siRNA approach is close to antisense oligonucleotide technology and takes advantage of the progress of chemically synthesized oligoribonucleotides. This approach for the mammalian cells was described by Elbashir et al. at the beginning of 2001, and in this chapter we describe methods for the design of siRNA molecules, solutions for efficiently transfecting cells, and methods for analyzing the inhibition of targeted genes. Methods for in vivo approach are also proposed.

Although nuclear type 2C protein phosphatase (PP2Cä) has been demonstrated to be pro-oncogenic with an important role in tumorigenesis, the underlying mechanisms that link aberrant PP2Cä levels with cancer development remain elusive. Here, we found that aberrant PP2Cä activity decreases p53 acetylation and its transcriptional activity and suppresses doxorubicin-induced cell apoptosis. Mechanistically, we show that BRCA1 facilitates p300-mediated p53 acetylation by complexing with these two proteins and that S1423/1524 phosphorylation is indispensable for this regulatory process. PP2Cä, via dephosphorylation of ATM, suppresses DNA damage-induced BRCA1 phosphorylation, leading to inhibition of p300-mediated p53 acetylation. Furthermore, PP2Cä levels correlate with histological grade and are inversely associated with BRCA1 phosphorylation and p53 acetylation in breast cancer specimens. C23, our newly developed PP2Cä inhibitor, promotes the anticancer effect of doxorubicin in MCF-7 xenograft-bearing nude mice. Together, our data indicate that PP2Cä impairs p53 acetylation and DNA damage response by compromising BRCA1 function.

OBJECTIVE: The principal objective of this investigation was to identify novel cytokine associations with BMI and type 2 diabetes (T2D).METHODS: Cytokines were profiled from African American women with obesity who donated plasma to the Komen Tissue Bank. Multiplex bead arrays of analytes were used to quantify 88 cytokines and chemokines in association with clinical diagnoses of metabolic health. Regression models were generated after elimination of outliers.RESULTS: Among women with obesity, T2D was associated with breast adipocyte hypertrophy and with six plasma analytes, including four chemokines (chemokine [C-C motif] ligand 2, chemokine [C-C motif] ligand 16, chemokine [C-X-C motif] ligand 1, and chemokine [C-X-C motif] ligand 16) and two growth factors (interleukin 2 and epidermal growth factor). In addition, three analytes were associated with obesity independently of diabetes: interleukin 4, soluble CD40 ligand, and chemokine (C-C motif) ligand 3.CONCLUSIONS: Profiling of inflammatory cytokines combined with measures of BMI may produce a more personalized risk assessment for obesity-associated disease in African American women.

We report five cases of primary synovial sarcomas arising in the parapharyngeal space. The patients were all men with a median age of 35 years (range 22 to 41 years). The tumors were non-encapsulated solid masses ranging from 2.0 to 6.6 cm in size. Histologically, three cases were biphasic subtype, and the other two cases were monophasic subtype. Immunohistochemically, the tumor cells were strongly positive for bcl-2 and CD99, partly positive for CK and EMA, and negative for CD117, CD34, SMA and desmin in all five cases. S-100 protein was detected in one case. The presence of an SYT-SSX1 and/or SYT-SSX2 gene fusion resulting from t(X;18) was demonstrated from paraffin blocks by reverse transcriptase polymerase chain reaction in five cases. All five patients received tumor radical excision and postoperative radiotherapy, and two patients with pulmonary metastasis received additional chemotherapy. Follow-up data revealed that two patients with tumor size <5 cm were alive without disease for 54 and 57 months, one patient with tumor size <5 cm was alive with pulmonary metastasis for 78 months, and two patients with tumor size >5 cm died of disease 26 and 37 months after the diagnosis, respectively. Primary parapharyngeal synovial sarcoma is a rare variant that occurs more frequently in males than females. Accurate diagnosis depends on morphologic and immunohistochemical examination and proper molecular analysis. The prognosis is relatively good in those patients whose tumor size is less than 5 cm.

OBJECTIVE: To evaluate the concordance of the Modified Morisky Scale (MMS) with a pharmacist assessment of medication adherence during a medication review.METHODS: This retrospective study examined the electronic medical records (EMRs) of patients ?18 years who received a medication review by a pharmacist from October 2008 to September 2009 at a homeless behavioral health clinic. In addition to the 6-item MMS, adherence was assessed using the first 4 items of the MMS, which comprise the original Morisky Scale. A final pharmacist assessment of adherence based upon the medication review was documented in the EMR. The McNemar test was used to assess the agreement between the MMS (6 and 4 items) and the pharmacist assessment of medication adherence.RESULTS: A total of 288 patients were eligible for the study, which included 449 medication reviews. Nonadherence was identified in 61.7% and 49.7% of medication reviews using the 6 and 4 items of the MMS. The pharmacist assessment determined nonadherence in 23.8% of medication reviews. There were significant differences between the pharmacist adherence assessment and the 6 (P < .0001) and 4 (P < .0001) items of the MMS.CONCLUSION: A combination of methods including self-report and pharmacist assessment may provide the greatest insight into adherence.

(113)Sn (115.09 d) is the parent nuclide of the (113)Sn/(113m)In generator system. (113m)In (99.476 min) is used in diagnostic nuclear medicine and as an Auger-electron emitter is a candidate for internal radiotherapy. Excitation functions of the (nat)In(d,x) (113 mg)Sn, (116 m)In, (ind115m)In, (114m)In, (ind113m)In, (cum111)In, (115g)Cd,(111m)Cd reactions were measured up to 40 MeV for the first time. The experimental results were compared with the curves calculated with the ALICE-D and EMPIRE-D theoretical model codes and curves given in the EAF-2007 and TENDL-2009 databases. Thick target yields, impurity levels and specific activities for the optimal energy range were deduced and compared with the same parameters of other charged particle production routes of (113)Sn.

Deer farming is on its increase in Denmark. Based on experiences from other countries, lungworm infection is expected to cause severe problems in farmed deer. Therefore, in the present paper, which is the first one to deal with pathogens in Danish deer farms, the faecal larval excretion in red deer is examined.

Aim: This study aims to evaluate the effect of two bioflavonoids (epigallocatechin-3-gallate [EGCG] and catechin) and a protein inhibitor (chlorhexidine [CHX]) on the immediate and delayed microtensile bond strength of self-etch and total-etch adhesive systems to sound dentin.Materials and Methods: The occlusal surfaces of 96 mandibular human third molar teeth specimens were ground after removal of the excess tissues, to expose the middle dentin. The dentin specimens were randomly allocated into four groups, each consisting of 24 teeth (n = 24) according to the application of the enzyme inhibitor. The adhesive system used in this study was Adper easy bond, a self-etch adhesive system, and Adper Single Bond 2, a total-etch adhesive system. Microtensile bond strength testing was conducted using thermocycler 2000, Heto-Holten A/S.Results: All the three enzyme inhibitors increase the bond strength values of the resin-dentin interphase when used during dentin bonding. The EGCG enzyme inhibitor has shown the highest immediate bond strength to dentin when used with both the adhesive systems.

An extradural spinal tumor was diagnosed in a 12-year-old Labrador retriever that was presented with a one-week history of paraparesis. Myelography indicated a deviation of the spinal cord to the right side at the level of the second lumbar (L2) vertebra. The difference in length measuring the left and right sides of the L2 vertebra suggested a fracture of the vertebral body. Severe bone remodeling and an extradural mass were seen on computed tomography (CT). Clinical, radiographical, and histological findings are described and considered homologous to extradural angiolipomas described in the human literature.

Regulated intramembrane proteolysis (RIP) is a mechanism of transmembrane signal transduction that functions through intramembrane proteolysis of substrates. We previously reported that the RIP metalloprotease Rv2869c (Rip1) is a determinant of Mycobacterium tuberculosis (Mtb) cell envelope composition and virulence, but the substrates of Rip1 were undefined. Here we show that Rip1 cleaves three transmembrane anti-sigma factors: anti-SigK, anti-SigL and anti-SigM, negative regulators of Sigma K, L and M. We show that transcriptional activation of katG in response to phenanthroline requires activation of SigK and SigL by Rip1 cleavage of anti-SigK and anti-SigL. We also demonstrate a Rip1-dependent pathway that activates the genes for the mycolic acid biosynthetic enzyme KasA and the resuscitation promoting factor RpfC, but represses the bacterioferritin encoding gene bfrB. Regulation of these three genes by Rip1 is not reproduced by deletion of Sigma K, L or M, either indicating a requirement for multiple Rip1 substrates or additional arms of the Rip1 pathway. These results identify a branched proteolytic signal transduction system in which a single intramembrane protease cleaves three anti-sigma factor substrates to control multiple downstream pathways involved in lipid biosynthesis and defence against oxidative stress.

The scholarly literature over the past decade has chronicled a growing problem in the forensic technique colloquially called criminal profiling. The basis of this conundrum appears to originate from a concept referred to as "offender homology," which presumes an inherent uniformity among offenders that is believed to underpin the analytic process incumbent to criminal profiling. Studies thus far conducted have apparently struggled to find evidence of offender homology, and based upon these findings arguments have been promulgated that various approaches to criminal profiling imputably labeled as "trait-based" are therefore not viable. Indirectly contradicting these arguments, however, have been studies testing profiler accuracy that have found evidence of individuals who appear to use trait-based methods but can nonetheless proficiently predict the characteristics of unknown offenders. Against this backdrop, the present article examines a number of tenets and disjunctions that appear to have arisen from research into offender homology and imputed to the practices of so-called trait-based profiling. The notion of whether trait-based profiling is, in fact, representative of profiling methods is examined and an integrative hypothesis proposed that attempts to resolve the quandary between offender homology and profiler accuracy.

The role of the structural organization of intercorneocyte lipids in the barrier function of human stratum corneum was evaluated by treatment with heat and sodium lauryl sulfate. Measurement of transepidermal water loss in treated samples was used to quantify variations in stratum corneum permeability. Thermodynamic transition of lamellar lipids and their degree of organization were evaluated by differential scanning calorimetry and small-angle X-ray diffraction, respectively. Progressively preheating stratum corneum samples from 75 degrees C to 90 degrees C increased stratum corneum permeability to water vapor, while the fusion temperature of lamellar lipids and the intensity of the X-ray diffraction peaks of the polar lipids decreased. Sodium lauryl sulfate induced similar variations of these three parameters. These results support the hypothesis that, in addition to the chemical nature of intercorneocyte lipids, their structural arrangement and thermodynamic properties play an important role in the barrier function of the stratum corneum to water vapor.

A contaminated drinking water distribution network can be responsible for major outbreaks of infections. In this study, two chemical decontaminants, peracetic acid (PAA) and chlorine, were used to test how a laboratory-scale pipeline system can be cleaned after simultaneous contamination with human adenovirus 40 (AdV40) and Escherichia coli. In addition, the effect of the decontaminants on biofilms was followed as heterotrophic plate counts (HPC) and total cell counts (TCC). Real-time quantitative polymerase chain reaction (qPCR) was used to determine AdV40 and plate counting was used to enumerate E. coli. PAA and chlorine proved to be effective decontaminants since they decreased the levels of AdV40 and E. coli to below method detection limits in both water and biofilms. However, without decontamination, AdV40 remained present in the pipelines for up to 4 days. In contrast, the concentration of cultivable E. coli decreased rapidly in the control pipelines, implying that E. coli may be an inadequate indicator for the presence of viral pathogens. Biofilms responded to the decontaminants by decreased HPCs while TCC remained stable. This indicates that the mechanism of pipeline decontamination by chlorine and PAA is inactivation rather than physical removal of microbes.

Giant occipital encephaloceles rarely contain large amounts of neural tissue that cannot be replaced in the abnormally small calvarium. Resection of neural elements is therefore often necessary in order to accomplish a closure. A technique is described wherein an extracranial compartment is prepared utilizing fine tantalum mesh to enclose the neural contents. The mesh is attached to the periphery of the skull defect providing a rigid extracranial compartment for the encephalocele. As intracranial pressure increases, the calvarium is forced to expand. The tantalum mesh is gradually imbricated into the calvarium by daily digital compression. If ventriculomegaly occurs, an interval ventriculoperitoneal shunt is placed. The encephalocele repair is reopened and the tantalum is surgically imbricated at that time. This allows for a satisfactory cosmetic result with preservation of all neural elements.

JC virus (JCV) is a human neurotropic polyomavirus whose replication in the central nervous system induces the fatal demyelinating disease, progressive multifocal leukoencephalopathy (PML). JCV particles have been detected primarily in oligodendrocytes and astrocytes of the brains of patients with PML and in the laboratory its propagation is limited to primary cultures of human fetal glial cells. In this short communication, the development of a new cell culture system is described through the fusion of primary human fetal astrocytes with the human glioblastoma cell line, U-87MG. The new hybrid cell line obtained from this fusion has the capacity to support efficiently expression of JCV and replication of viral DNA in vitro up to 16 passages. This cell line can serve as a reliable culture system to study the biology of JCV host-cell interaction, determine the mechanisms involved in cell type specific replication of JCV, and provide a convenient cell culture system for high throughput screening of anti-viral agents.

This work reports the construction of Escherichia coli in-frame deletion strains of tmk, which encodes thymidylate kinase, Tmk. The tmk gene is located at the third position of a putative five-gene operon at 24.9 min on the E. coli chromosome, which comprises the genes pabC, yceG, tmk, holB, and ycfH. To avoid potential polar effects on downstream genes of the operon, as well as recombination with plasmid-encoded tmk, the tmk gene was replaced by the kanamycin resistance gene kka1, encoding amino glycoside 3'-phosphotransferase kanamycin kinase. The kanamycin resistance gene is expressed under the control of the natural promoter(s) of the putative operon. The E. coli tmk gene is essential under any conditions tested. To show functional complementation in bacteria, the E. coli tmk gene was replaced by thymidylate kinases of bacteriophage T4 gp1, E. coli tmk, Saccharomyces cerevisiae cdc8, or the Homo sapiens homologue, dTYMK. Growth of these transgenic E. coli strains is completely dependent on thymidylate kinase activities of various origin expressed from plasmids. The substitution constructs show no polar effects on the downstream genes holB and ycfH with respect to cell viability. The presented transgenic bacteria could be of interest for testing of thymidylate kinase-specific phosphorylation of nucleoside analogues that are used in therapies against cancer and infectious diseases.

We evaluate the influence of demographic, socioeconomic, and maternal variables on the nutritional status of adolescents aged 11 years. We conducted a prospective cohort study including 4,452 adolescents born in Pelotas, Southern Brazil, in 1993, accounting for 87.5% of the original cohort. Nutritional status was evaluated based on World Health Organization criteria. Subjects were classified according to nutritional status into thin, normal, overweight and obese. Independent variables analyzed included skin color, socioeconomic status, maternal schooling, and maternal body mass index (BMI). Analyses were stratified by sex, and multivariable regression was performed using the multinomial logistic approach. Overall, 7% of adolescents were classified as thin, 11.6% as overweight, and 11.6% as obese. Among boys, thinness was inversely associated with maternal schooling and maternal BMI. Among girls, thinness was directly associated with maternal BMI. Overweight and obesity were directly associated with socioeconomic status and maternal BMI, the former showing the strongest association with nutritional status among adolescents.

Paroxysmal non-reentrant supraventricular tachycardia due to double ventricular response through antegrade dual atrioventricular nodal pathways by a single atrial excitation has been reported in limited adult cases but not in pediatric patients with structurally normal hearts or with congenital heart defects. We report the case of a 5-year-old boy with non-reentrant double-ventricular response (DVR) supraventricular tachycardia (SVT) after repair of ventricular septal defect. To the best of our knowledge, this is the first pediatric report about an electrophysiologic study and successful selective radiofrequency (RF) catheter ablation for the slow pathway leading to tachyarrhythmia that is difficult to manage medically. In conclusion, non-reentrant DVR SVT is a rare form of tachycardia that should be considered in the differential diagnosis of SVT in children after repair of congenital heart diseases. It is amenable to mapping and RF catheter ablation.

BACKGROUND AND OBJECTIVES: Solid tumors evade the host immunologic responses they initiate by unknown mechanisms. The authors investigated patterns of cytokine content in human colon carcinomas, colon cancer cell lines in vitro, and nude mouse xenografts from those lines in order to clarify those mechanisms.METHODS: Epithelial tumor cell lines were developed from specimens of human colon adenocarcinoma. Aliquots of these cells were then xenografted into female heterozygous BALB/c nu/+ immunologically deficient mice and serially passaged. Original tumors, cell lines, and resultant xenografts were then analyzed for histology/cytology and for levels of TGF-beta and TNF-alpha by enzyme linked immunoassay.RESULTS: Cytokine levels were elevated beyond baseline mucosal levels in original tumors and xenograft mouse tumors but not detectable in extracts from epithelial cultures.CONCLUSIONS: While the precise source of cytokine production remains unclear, these data suggest tumor/host interactions not found in pure epithelial cancer cells in culture.

This case report concerns a 53-year old woman suffering from recurrent spastic pain and a painful "resistance" in the left lower bowel for the last 30 years. Earlier clinical investigations including endoscopy and laparoscopy did not yield any results. In a recent investigation, only sonography showed wall thickening and an echo-poor wall pattern of the sigmoid colon indicating this to be the site of painful resistance. Resection of the sigmoid colon was performed. Histologically a slight hypogangliosis of the colon and muscular hypertrophy were detected (as the only pathological signs). The patient was free from symptoms since operation. This case report proves that ultrasound may yield pointers (or confirm the diagnosis) in unclear abdominal diseases.

This case control study was carried out in the Paediatric wards of Mymensingh Medical College Hospital for a period of one year from April 2002 to March 2003 to determine the sensitivity, specificity and predictive values of Aldehyde test in the diagnosis of Kala-azar. A total of seventy five febrile cases of Kala-azar from Paediatric wards were enrolled in the study and Seventy five controls having splenomegaly with or without fever were also included from the same source. Aldehyde test was done in both cases and controls. Diagnosis of Kala-azar was confirmed by demonstration of Leish-man-Don-o-van body (LD) in bone marrow or splenic aspirates. Out of 75 parasitologically proven cases of Kala-azar, AT was positive in 56 cases. The sensitivity irrespective of duration of illness was 74.6%. We found sensitivity of AT increases with the duration of illness where AT was sensitive in 34.7% cases having fever for less than 3 months, 90.90% with fever for 3 months to less than 6 months and 100% with fever for 6 months or more in duration. Specificity of AT was calculated as 96% with positive and negative predictive values of 94.9% and 79.1% respectively. So AT is a very sensitive and specific test with high positive and negative predictive values. Considering the cost, availability, simplicity, sensitivity, and specificity we would recommend the Aldehyde test as an important diagnostic tool for field diagnosis of Kala-azar especially after three months of febrile illness.

OBJECTIVE: High frequency oscillations (HFOs; > 80 Hz), especially fast ripples (FRs, 250-500 Hz), are novel biomarkers for epileptogenic tissue. The pathophysiology suggests enhanced functional connectivity within FR generating tissue. Our aim was to determine the relation between brain areas showing FRs and 'baseline' functional connectivity within EEG networks, especially in the high frequency bands.METHODS: We marked FRs, ripples (80-250 Hz) and spikes in the electrocorticogram of 14 patients with refractory temporal lobe epilepsy. We assessed 'baseline' functional connectivity in epochs free of epileptiform events within these recordings, using the phase lag index. We computed the Eigenvector Centrality (EC) per channel in the FR and gamma band network. We compared EC between channels that did or did not show events at other moments in time.RESULTS: FR-band EC was higher in channels with than without spikes. Gamma-band EC was lower in channels with ripples and FRs.CONCLUSIONS: We confirmed previous findings of functional isolation in the gamma-band and found a first proof of functional integration in the FR-band network of channels covering presumed epileptogenic tissue.SIGNIFICANCE: 'Baseline' high-frequency network parameters might help intra-operative recognition of epileptogenic tissue without the need for waiting for events. These findings can increase our understanding of the 'architecture' of epileptogenic networks and help unravel the pathophysiology of HFOs.

BACKGROUND: In this study, 30-year longitudinal data from the Christchurch Health and Development Study (CHDS) were used to examine the associations between childhood exposure to sexual abuse and intimate relationship outcomes at age 30. In addition, a broad range of early childhood and family confounding factors were tested, and the role of intervening factors from adolescence was explored.METHOD: The investigation analyzed data from a birth cohort of over 900 New Zealand adults studied to the age of 30. At ages 18 and 21 cohort members reported on any exposure to sexual abuse prior to age 16. This information, along with prospective data gathered in childhood and adolescence, was used to predict partnership outcomes at age 30.RESULTS: After adjustment for early childhood and family factors, exposure to more severe forms of childhood sexual abuse (CSA) was associated with earlier and more frequent cohabitation, higher rates of perpetrated interpartner violence (IPV), and early parenthood, lower relationship satisfaction and investment. Several factors from adolescence partially or fully mediated these associations, notably a history of early consensual sexual intercourse, higher number of sexual partnerships, substance abuse problems, and self-esteem. After adjustment for intervening factors, exposure to CSA remained significantly associated with IPV.CONCLUSIONS: The findings support a causal chain process, whereby early childhood and family factors place some individuals at risk for CSA. The extent of CSA exposure is related to adolescent risk taking, which in turn leads to early and more frequent cohabitation, risk of IPV, and lower relationship satisfaction and investment.

Youth with gender dysphoria, also known as transgender youth, are increasingly presenting to multidisciplinary clinics within academic pediatric centers across the United States. Gender-affirming pharmacological interventions for adolescents with gender dysphoria may be used to promote positive psychological well-being and mental health outcomes. Interventions range from completely reversible to partially irreversible, based on the age and sexual maturity of the adolescent. For each intervention, dilemmas and controversies exist regarding age at treatment initiation, treatment duration, safety, and cost. Pharmacists' awareness of these considerations and interventions is important when providing evidence-based gender-affirming care to this underserved population.

Biological membranes composed of lipids and proteins are in contact with electrolytes like aqueous NaCl solutions. Based on molecular dynamics studies it is widely believed that Na(+) ions specifically bind to 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) membranes, whereas Cl(-) ions stay in solution. Here, we present a careful comparison of recent data from electrophoresis and isothermal titration calorimetry experiments as well as molecular dynamics simulations suggesting that in fact both ions show very similar affinities. The corresponding binding constants are 0.44(±0.05) M(-1) for Na(+) and 0.40(±0.04) M(-1) for Cl(-) ions. This is highlighted by our observation that a widely used simulation setup showing asymmetric affinities of Na(+) and Cl(-) for POPC bilayers overestimates the effect of NaCl on the electrophoretic mobility of a POPC membrane by an order of magnitude. Implications for previous simulation results on the effect of NaCl on polarization of interfacial water, transmembrane potentials, and mechanisms for ion transport through bilayers are discussed. Our findings suggest that a range of published simulations results on the interaction of NaCl with phosphocholine bilayers have to be reconsidered and revised and that force field refinements are necessary for reliable simulation studies of membranes at physiological conditions on a molecular level.

The diffusional and osmotic water permeability of collecting ducts in isolated papillae of rats' kidneys were measured in papillae taken from normal and lithium pretreated rats. The diffusional water permeability of collecting ducts in papillae from normal rats in the absence of ADH was 4.1 +/- 0.2 (S.E.M.) (n = 18) muM s-1 increasing to 7.2 +/- 0.6 mum s-1 with ADH. Values obtained with lithium (10 mM) in the medium, perfusate or both and in papillae taken from lithium pretreated rats did not differ significantly from the above. The cyclic AMP content of the papillae taken from normal rats was 83 +/- 6 pm mg protein in the absence of ADH and increased to 196 +/- 12 (n = 13) with 500 mu units ml-1 ADH. Lithium 10 mM in the medium did not alter this response. Papillae from lithium pretreated rats had a similar basal level of cyclic AMP but the increment in a lithium (10 mM) medium after ADH was significantly less. These results indicate that the impaired water handling of lithium treated rats is probably not due to a failure of the membrane to increase its permeability to water after ADH. Though lithium does alter the production of cyclic AMP this is not believed to be important regarding any alteration in water permeability. We believe it is probable that lithium interferes with sodium chloride transport at some more proximal nephron segment thereby producing the syndrome of polyuria.

Limb blood flow is widely used as an indicator of the human vascular properties. There are only few non-invasive methods for its measurement such as venous occlusion plethysmography. However, several authors have questioned its validity. The problems appear to be related to the process of venous occlusion. We developed two methods to measure forearm blood flow by plethysmography without venous occlusion in combination with Doppler velocimetry (without imaging). Method 1: the gradient of a tangent drawn on the latter part of the down stroke of the plethysmographic volume pulse is an approximation of venous blood flow in the absence of diastolic blood flow. At equilibrium, it equals the average arterial flow in a cardiac cycle. The Doppler velocity waveform recorded simultaneously allows improvement of this approximation when there is diastolic blood flow. Method 2: the volume pulse detected by a plethysmograph calibrated in absolute volume is used to calibrate the velocity waveform recorded simultaneously to produce an approximation of arterial volumetric flow waveform. Bland-Altman analysis shows both methods have good correlation and agreement with venous occlusion plethysmography at rest. Method 1: mean difference (blood flow measured by venous occlusion minus calculated flow) = 0.10 ml/pulse (+/-0.18), limits of agreement = -0.41 and 0.61 ml/pulse. Method 2: mean difference = -0.041 ml/pulse (+/-0.15), limits of agreement = -0.45 and 0.37 ml/pulse. During hyperaemia, venous occlusion plethysmography grossly underestimated relative to the new methods. The new methods are not dependent on venous occlusion and produce consistent results with or without hyperaemia.

PURPOSE: The purpose of this longitudinal whitening study was to determine the stability, post-treatment side effects, and patient satisfaction at 90 months post treatment after 6 months of active treatment of tetracycline-stained teeth with 10% carbamide peroxide.MATERIALS AND METHODS: Fifteen of 21 participants enrolled in the study (71%) were contacted and asked to participate in a survey concerning their whitening experience. Participants were asked whether there had been any change in the shade of their teeth after treatment and if they had experienced any side effects that they believed were treatment related. Eight of the 15 participated in a clinical examination.RESULTS: Nine participants (60%) reported no obvious shade change or only a slight darkening not noticed by others. None reported darkening back to the original shade; however, four had re-treated their teeth. Examiners were in agreement with the participants' perception of shade change upon comparing pretreatment and post-treatment photographs and Vita shade (Vita Zahnfabrik D-79713, Bad Sackingen, Germany) values. The degree of improvement over the pretreatment shade was significant for the 90-month post-treatment shade (p < .01). All respondents (n = 15) denied having to have a crown or root canal or tooth sensitivity that they believed was treatment related.CLINICAL SIGNIFICANCE: The results of this study of nightguard vital bleaching indicate that tetracycline-stained teeth can be whitened successfully using extended treatment time and that shade stability may last at least 90 months post treatment (range 84-100 mo). Patients participating in this study were over-whelmingly positive about the procedure in terms of shade retention and lack of post-treatment side effects.

A series of experiments has been carried out to characterize 58-kDa human neutrophil collagenase (HNC) and compare it with human fibroblast collagenase (HFC). N-Terminal sequencing of latent and spontaneously activated HNC shows that it is a distinct collagenase that is homologous to HFC and other members of the matrix metalloproteinase gene family. Activation occurs autolytically by hydrolysis of an M-L bond at a locus homologous to the Q80-F81-V82-L83 autolytic activation site of HFC. This releases a 16-residue propeptide believed to contain the "cysteine switch" residue required for latency. Polyclonal antibody raised against HNC cross-reacts with HFC but with none of the other major human matrix metalloproteinases examined. Treatment of HNC with endoglycosidase F or N-glycosidase F indicates that it is glycosylated at multiple sites. The deglycosylated latent and spontaneously activated enzymes have molecular weights of approximately 44K and 42K, respectively. Differences in the carbohydrate processing of HFC and HNC may determine why HFC is a secreted protein while HNC is stored in intracellular granules. The kinetic parameters kcat and KM for the hydrolysis of the interstitial collagen types I, II, and III in solution by both collagenases have been determined. The strong preferences of HNC for type I collagen and of HFC for type III collagen found in earlier studies have been confirmed. The preference of HNC for type I over type III collagen is almost abolished when fibrillar collagens are used as substrates, but the preference for HFC for type III over type I collagen is only partially decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

The aim of the study was to evaluate, from a technical and economic standpoint, the enzymatic processes involved in the production of fuel ethanol from softwood. Two base case configurations, one based on simultaneous saccharification and fermentation (SSF) and one based on separate hydrolysis and fermentation (SHF), were evaluated and compared. The process conditions selected were based mainly on laboratory data, and the processes were simulated by use of Aspen plus. The capital costs were estimated using the Icarus Process Evaluator. The ethanol production costs for the SSF and SHF base cases were 4.81 and 5.32 SEK/L or 0.57 and 0.63 USD/L (1 USD = 8.5SEK), respectively. The main reason for SSF being lower was that the capital cost was lower and the overall ethanol yield was higher. A major drawback of the SSF process is the problem with recirculation of yeast following the SSF step. Major economic improvements in both SSF and SHF could be achieved by increasing the income from the solid fuel coproduct. This is done by lowering the energy consumption in the process through running the enzymatic hydrolysis or the SSF step at a higher substrate concentration and by recycling the process streams. Running SSF with use of 8% rather than 5% nonsoluble solid material would result in a 19% decrease in production cost. If after distillation 60% of the stillage stream was recycled back to the SSF step, the production cost would be reduced by 14%. The cumulative effect of these various improvements was found to result in a production cost of 3.58 SEK/L (0.42 USD/L) for the SSF process.

In a medium without oxygen in the presence of nitrates, E. coli transforms p-chloranilin (p-CA) to yield a more hydrophilic compound which cannot be extracted with an organic solvent from water. The conditions for consecutive transformation of p-nitro-chlorobenzene (p-NCB) and p-CA have been determined: the reaction p-NCB leads to p-CA is inhibited by nitrates, p-CA transformation occurs in the presence of nitrates in the medium and depends on their concentration.

In order to investigate the role played by extracellular calcium mobilization in activating human airway contraction, we studied the effects of A23187, a calcium ionophore, in human isolated bronchial spiral strips. In this preparation, ionophore induced a concentration dependent contraction from 10(-7) M to 10(-5) M which resulted from a direct effect on smooth muscle cells and was not a consequence of mediator release. Ionophore-induced contraction was dependent upon an entry of extracellular calcium which did not occur through the verapamil sensitive voltage dependent channel. Maximal ionophore contraction was 97 +/- 11% (n = 5) of the maximal histamine contraction but only 46 +/- 11% (n = 5) of the maximal carbachol contraction. However, when extracellular calcium concentration was doubled to 5 mM before addition of ionophore, the significant difference in amplitude between carbachol and ionophore maximal contraction was abolished. At physiological calcium concentrations addition of carbachol or histamine to the plateau of the ionophore maximal contraction produced a significant increase in the tension. Verapamil blocked the increase in ionophore tension produced only by histamine. These results suggest that (i) calcium mobilization from the extracellular source alone can produce contraction comparable in magnitude to that induced by histamine or carbachol. (ii) Extracellular calcium mobilization through different pathways has a cumulative effect on human airway contraction.

AIM: The aim of this paper was to investigate the value of Global Registry of Acute Coronary Events (GRACE) and thrombolysis in myocardial infarction (TIMI) risk scores for risk stratification and prognosis in female patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS).METHODS: Non-elderly (<65 years) and elderly (?65 years) female patients with NSTE-ACS (totally 869 cases) were enrolled in this study. The patients were further divided into low, intermediate and high-risk groups according to their GRACE and TIMI scores. Patients were followed up for 1 year to record the mortality and incidence of major adverse cardiac events (MACE). Differences in mortality and MACE incidence between the two scoring systems were compared by the area under the ROC curve.RESULTS: The area under ROC curve (AUC) corresponding to the mortality and MACE incidence in any period by the GRACE scoring system was significantly larger than the TIMI scoring system in the elderly patients at 1 year of follow-up (AUC of mortality, 0.79 vs. 0.68; AUC of MACE, 0.78 vs. 0.72; P<0.05). Mortality and MACE incidence increased in parallel with the scores. Risk ratio values of Cox regression analysis based on GRACE and TIMI scores were greater than 1 (P<0.001).CONCLUSION: Both GRACE and TIMI were adoptable in clinical risk stratification and prognosis of female patients with NSTE-ACS at different age groups. GRACE showed better accuracy than the TIMI scores.

DO 710, a benzamide derivative previously shown to display a dopamine antagonistic potency superior to that of sulpiride, was 3H-labeled. Its use as radioligand was assessed in membrane binding and autoradiographic studies. The compound displayed relatively high affinity (Kd 2 nM) and pronounced selectivity for dopamine receptors (distinct from D-1 receptors) as well as low non-specific binding particularly evidenced in autoradiographic experiments. Hence [3H](-)-DO 710 displays distinct technical advantages over commonly used dopaminergic radioligands.

Transesophageal echocardiography (TEE) is a semi-invasive diagnostic tool which allows a unique intraoperative visualization of cardiac chambers and valves. It is mainly used for intraoperative monitoring during cardiac surgery and in cardiopathic patients undergoing major non cardiac surgical procedures. TEE gives a beat-to-beat assessment of cardiac morphology and function, it is less invasive and more readily performed than pulmonary artery catheterization, and it allows an etiological diagnosis of hemodynamic problems. Based on TEE data, the anesthesiologist is able to modify in real time vasoactive therapy and fluid management. TEE data concern: 1) preload: left ventricular endodiastolic area is measured and this is considered an index of volemia; 2) systolic function: the circumferential shortening fraction, which correlates with LV ejection fraction, is measured; 3) onset of ischemia: ischemia is detected as a regional modification of normal kinetics; 4) causes of hemodynamic instability; 5) assessment of sovrahepatic anastomoses during liver transplantation.

Progressive childhood encephalopathy is an etiologically heterogeneous condition characterized by progressive central nervous system dysfunction in association with a broad range of morbidity and mortality. The causes of encephalopathy can be either non-genetic or genetic. Identifying the genetic causes and dissecting the underlying mechanisms are critical to understanding brain development and improving treatments. Here, we report that variants in TRAPPC12 result in progressive childhood encephalopathy. Three individuals from two unrelated families have either a homozygous deleterious variant (c.145delG [p.Glu49Argfs?14]) or compound-heterozygous variants (c.360dupC [p.Glu121Argfs?7] and c.1880C>T [p. Ala627Val]). The clinical phenotypes of the three individuals are strikingly similar: severe disability, microcephaly, hearing loss, spasticity, and characteristic brain imaging findings. Fibroblasts derived from all three individuals showed a fragmented Golgi that could be rescued by expression of wild-type TRAPPC12. Protein transport from the endoplasmic reticulum to and through the Golgi was delayed. TRAPPC12 is a member of the TRAPP protein complex, which functions in membrane trafficking. Variants in several other genes encoding members of the TRAPP complex have been associated with overlapping clinical presentations, indicating shared and distinct functions for each complex member. Detailed understanding of the TRAPP-opathies will illuminate the role of membrane protein transport in human disease.

BACKGROUND: The hybridizing field crickets, Gryllus firmus and Gryllus pennsylvanicus have several barriers that prevent gene flow between species. The behavioral pre-zygotic mating barrier, where males court conspecifics more intensely than heterospecifics, is important because by acting earlier in the life cycle it has the potential to prevent a larger fraction of hybridization. The mechanism behind such male mate preference is unknown. Here we investigate if the female cuticular hydrocarbon (CHC) profile could be the signal behind male courtship.RESULTS: While males of the two species display nearly identical CHC profiles, females have different, albeit overlapping profiles and some females (between 15 and 45%) of both species display a male-like profile distinct from profiles of typical females. We classified CHC females profile into three categories: G. firmus-like (F; including mainly G. firmus females), G. pennsylvanicus-like (P; including mainly G. pennsylvanicus females), and male-like (ML; including females of both species). Gryllus firmus males courted ML and F females more often and faster than they courted P females (p < 0.05). Gryllus pennsylvanicus males were slower to court than G. firmus males, but courted ML females more often (p < 0.05) than their own conspecific P females (no difference between P and F). Both males courted heterospecific ML females more often than other heterospecific females (p < 0.05, significant only for G. firmus males).CONCLUSIONS: Our results suggest that male mate preference is at least partially informed by female CHC profile and that ML females elicit high courtship behavior in both species. Since ML females exist in both species and are preferred over other heterospecific females, it is likely that this female type is responsible for most hybrid offspring production.

We compared the FXG™: RESP (Asp +) real-time PCR assay (Myconostica Ltd) with two microscopic staining methods (direct immunofluorescence [IFA] and calcofluor white) for the detection of Pneumocystis jirovecii in 411 respiratory specimens submitted for P. jirovecii examination. We considered the specimen to be microscopically positive if the organism could be visualized through the use of either IFA or calcofluor white. A second, published real-time PCR assay targeting the cdc2 gene of P. jirovecii was used to adjudicate those specimens that were microscopically negative but Myconostica PCR positive. The Myconostica PCR positive samples were deemed to be true positives if they were concordant with microscopically positive results or if they were positive by the second PCR assay. As a result, the Myconostica PCR assay was found to be more sensitive than the two microscopy methods in detecting P. jirovecii (10.5% true positivity rate by PCR, 8.0% by immunofluorescence, and 7.1% by calcofluor white). The Myconostica PCR assay showed 93.5% sensitivity, 95.1% specificity, 70.5% positive predictive value, and 99.1% negative predictive value. Its high negative predictive value suggests a role of the Myconostica PCR assay in ruling out Pneumocystis pneumonia.

The University of Tartu provides a quality control service to the majority of diagnostic X-ray departments in Estonia. Its methodology has been adopted from the IEC and other relevant standards. Recently the Testing Centre of the University of Tartu was accredited on this methodology by ISO/IEC 17025. Besides the implementation of the quality management system, participation in interlaboratory comparison (ILC) was one of the prerequisites for the accreditation. Tests for estimating reproducibility of tube voltage and dose rate, accuracy of the voltage and accuracy of exposure time were carried out on a diagnostic X-ray unit in the Radiation and Nuclear Safety Authority in Helsinki. The measurement performance was judged by calculating deviation E(n) normalised with respect to the stated uncertainties. E(n) values for all tests were less than unity and by the common ILC criteria the testing performance could be considered as acceptable.

OBJECTIVE: Evaluations of point of care tests (PCT) are often hampered by a lack of appropriate gold standards. This study aimed to compare the results of a Bayesian statistical analysis and a maximum likelihood method to evaluate the performance of a PCT for Helicobacter pylori in primary care.METHODS: The Helisal Rapid Blood Test (Cortecs Diagnostics) was performed in 311 patients from 6 primary care centers, and a concurrent venous sample was taken for 2 enzyme-linked immunosorbent assays (ELISA) performed at the laboratory, blind to the PCT result. The Bayesian analysis was conducted using Markov Chain Monte Carlo methods (WinBUGS). The performance characteristics of the PCT and the 2 ELISA tests were estimated together with 95% credible intervals (95% CIs).RESULTS: The estimate of prevalence of H. pylori in this population was 64% (95% CI, 59% to 70%), the sensitivity and specificity of the PCT were 89% (84% to 94%) and 84% (77% to 91%), respectively (likelihood ratios positive 5.6, negative 0.13). The equivalent maximum likelihood results were prevalence, 65%; sensitivity, 90%; and specificity, 83%.CONCLUSIONS: The Helisal Rapid Blood Test performed as well as laboratory-based ELISA tests in this cohort of patients. The Bayesian analysis and the maximum likelihood method gave similar results, the Bayesian method also simultaneously estimating 95% CIs.

The maize NCS6 mitochondrial mutation is a partial deletion of the cytochrome oxidase subunit 2 gene (cox2) that survives heteroplasmically in the plant. Mutant mitochondria segregate from normal mitochondria during somatic development giving rise to defective sectors on the plants, including areas of kernel abortion on the ears. Embryos from NCS6 kernels can be rescued by tissue culture. Slowly growing Type II callus derived from one of these embryos has been shown by PCR analysis to be homoplasmic for the mutation, carrying only the defective mitochondrial cox2 gene. Most of the rescued embryos were heteroplasmic for normal and mutant genes and heteroplasmy was maintained in the callus cultures. However, when suspension cultures were initiated from heteroplasmic calli, normal cells were shown to have a selective advantage. When the homoplasmic cox2 mutant callus cultures were placed on regeneration medium, plantlets did not regenerate. Heteroplasmic calli were capable of regeneration under the same conditions. These studies suggest that the functioning of mitochondrial cytochrome oxidase is not essential for growth as callus, but is required for the differentiation and development of plants.

Quantum dots (QD) have unique electronic and optical properties promoting biotechnological advances. However, our understanding of the toxicological structure-activity relationships remains limited. This study aimed to determine the biological impact of varying nanomaterial surface chemistry by assessing the interaction of QD with either a negative (carboxyl), neutral (hexadecylamine; HDA) or positive (amine) polymer coating with human lymphoblastoid TK6 cells. Following QD physico-chemical characterisation, cellular uptake was quantified by optical and electron microscopy. Cytotoxicity was evaluated and genotoxicity was characterised using the micronucleus assay (gross chromosomal damage) and the HPRT forward mutation assay (point mutagenicity). Cellular damage mechanisms were also explored, focusing on oxidative stress and mitochondrial damage. Cell uptake, cytotoxicity and genotoxicity were found to be dependent on QD surface chemistry. Carboxyl-QD demonstrated the smallest agglomerate size and greatest cellular uptake, which correlated with a dose dependent increase in cytotoxicity and genotoxicity. Amine-QD induced minimal cellular damage, while HDA-QD promoted substantial induction of cell death and genotoxicity. However, HDA-QD were not internalised by the cells and the damage they caused was most likely due to free cadmium release caused by QD dissolution. Oxidative stress and induced mitochondrial reactive oxygen species were only partially associated with cytotoxicity and genotoxicity induced by the QD, hence were not the only mechanisms of importance. Colloidal stability, nanoparticle (NP) surface chemistry, cellular uptake levels and the intrinsic characteristics of the NPs are therefore critical parameters impacting genotoxicity induced by QD.

The present investigation was undertaken for the study of the comparative neurohistological observations of pancreatic-Artery (blood vessel) in Gallus domesticus (white leghorn) and Suncus murinus (Indian musk shrew) by cholinesterase technique. In Gallus, the innervation of arteries (blood vessel) was by a good number of non-myelinated nerevs, which formed the periarterial plexus in participation with the postganglionic fibres at one end and the fibres of the nerve cells of the other end. In Suncus, the periarterial and AChE-positive ganglia were arranged in chain-like fashion on the periphery of the artery. Periarterial plexus was formed by tortuous, myelinated nerves and the nerve fibres of the ganglia.

Glechoma hederacea (GH) is an herb widely used herb medicine for the treatment of a variety of pathologies. In this study, the effect of GH on interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS)-induced production of nitric oxide (NO), interleukin (IL)-12p70, IL-12p40, tumor necrosis factor-alpha (TNF-alpha), and IL-6 were examined using mouse peritoneal macrophages. GH inhibits IFN-gamma/LPS-induced NO in a dose-dependent manner. The decrease in NO synthesis was reflected as a decreased amount of inducible NO synthase protein. We also found that GH inhibits pro-inflammatory cytokine, IL-12p70, and TNF-alpha production. However, GH increased IFN-gamma/LPS-induced IL-12p40 production. GH doesn't affect the IL-6 production. These findings mean that GH can be used in controlling macrophages mediated inflammation related disease.

Research into the effectiveness of epilepsy specialist nursing needs to take into account a number of factors, which have not been adequately addressed in previous studies. Nursing outcome measures are different to medical ones and it is inappropriate to confuse these. Specialist nurses affect the whole culture of a service, and their impact on service quality may go beyond that of their individual patient contacts. Thus randomized studies within a service that already has specialist nurses may not give valid results. Some service users will benefit more from direct contact with a specialist nurse than others, and people who give informed consent to take part in randomized controlled trials might not be representative of those who would benefit most from specialist nurse access. The stampede for level one evidence risks failing to address the issues properly by overvaluing research process (form) against its appropriateness (content), yet there remain great opportunities for good quality research in this area.

Transient ischemic attacks are not only the consequence of cerebral atherosclerosis. A woman of 48 years had transient ischemic attacks because of a meningeom narrowing the internal carotid artery. A steal syndrome in tumor vessels of a glioblastoma must be presumed in a man of 67 showing initial hemisyndrome with first transient, later on remaining palsy.

Development of the rat optic nerve is studied electron microscopically. By marked bionecrosis, many neuroepithelial cells of the fissure portion of the optic stalk are eliminated immediately following optic cup formation. A small number of the surviving neuroepithelial cells forms the tubular optic stalk. The wall cells of the stalk elongate and proliferate to become a cluster of cells at the retrobulbar region. These cells differentiate into glia cells, astrocytes first and oligodendroglia cells second. Axons invade into the intercellular spaces of the elongating stalk cells which are differentiating into astrocytes. The invading axons are found first in the space at the basal portion of the stalk cells, or the peripheral zone of the optic nerve. Myelination occurs in the later stage of development. The fine processes of the oligodendroglia cells which surround groups of axons, eliminate the cytoplasm, and become the first myelin membrane.

The regulation of intracellular pools of Ca2+ was investigated in an interleukin-3 (IL-3)-dependent hematopoietic cell line 32D that undergoes programmed cell death ("apoptosis") when deprived of lymphokine. Comparisons were made with 32D cells that had been stably transfected with a bcl-2 expression plasmid that encodes a 26-kDa intracellular integral-membrane protein known to abrogate apoptosis resulting from IL-3 withdrawal. Removal of IL-3 from cultures of 32D cells or control-transfected 32D-NEO cells for 1-2 days led to cell cycle arrest and oligonucleosomal DNA fragmentation and was associated with lower cytosolic free Ca2+ concentrations ([Ca2+]i), as measured by Indo-1 fluorescence of viable cells in Ca(2+)-containing media. In bcl-2-expressing 32D-BCL2 cells, IL-3 withdrawal also resulted in cessation of proliferation, but [Ca2+]i levels were not decreased and DNA fragmentation was markedly suppressed. Nonmitochondrial stores of Ca2+ were also significantly diminished in IL-3-deprived 32D-NEO but not in 32D-BCL2 cells, based on measurements of Ca2+ release into the cytosol following exposure of cells to thapsigargin (an inhibitor of endoplasmic reticulum Ca(2+)-ATPases) under Ca(2+)-free conditions. In contrast, estimates of mitochondrial Ca2+ stores using an uncoupler of oxidative phosphorylation 1799 (2,6-dihydroxy-1,1,1,7,7,7-he xafluoro-2,6-bis(trifluoromethyl)heptan-4-one[bis(he xafluoroacetonyl)]acetone) suggested that IL-3 deprivation leads to an increase in this intracellular pool of Ca2+ in 32D-NEO but not in 32D-BCL2 cells. Re-addition of IL-3 to factor-deprived 32D-NEO cells reversed the changes in thapsigargin- and 1799-releasable Ca2+ pools and rescued many of the cells from death. Measurements of total cellular Ca2+ revealed no difference in 32D-NEO cells before and after IL-3 withdrawal, suggesting that the observed alterations in mitochondrial and nonmitochondrial Ca2+ pools result from intracellular repartitioning of Ca2+. Treatment of IL-3-deprived 32D-NEO cells with Ca2+ ionophores blocked DNA fragmentation and prolonged cell survival, whereas addition of Ca2+ chelators to IL-3-stimulated 32D cells resulted in oligonucleosomal DNA fragmentation and cell death, suggesting that diminutions in the concentrations of Ca2+ in cytosol, endoplasmic reticulum, or other intracellular compartments either directly or indirectly regulate apoptosis in these lymphokine-dependent hematopoietic cells.

Currently, there are only a handful of synthetic S = 2 oxoiron(IV) complexes. These serve as models for the high-spin (S = 2) oxoiron(IV) species that have been postulated, and confirmed in several cases, as key intermediates in the catalytic cycles of a variety of nonheme oxygen activating enzymes. The trigonal bipyramidal complex [Fe(IV)(O)(TMG(3)tren)](2+) (1) was both the first S = 2 oxoiron(IV) model complex to be generated in high yield and the first to be crystallographically characterized. In this study, we demonstrate that the TMG(3)tren ligand is also capable of supporting a tricationic cyanoiron(IV) unit, [Fe(IV)(CN)(TMG(3)tren)](3+) (4). This complex was generated by electrolytic oxidation of the high-spin (S = 2) iron(II) complex [Fe(II)(CN)(TMG(3)tren)](+) (2), via the S = 5/2 complex [Fe(III)(CN)(TMG(3)tren)](2+) (3), the progress of which was conveniently monitored by using UV-vis spectroscopy to follow the growth of bathochromically shifting ligand-to-metal charge transfer (LMCT) bands. A combination of X-ray absorption spectroscopy (XAS), M?ssbauer and NMR spectroscopies was used to establish that 4 has a S = 0 iron(IV) center. Consistent with its diamagnetic iron(IV) ground state, extended X-ray absorption fine structure (EXAFS) analysis of 4 indicated a significant contraction of the iron-donor atom bond lengths, relative to those of the crystallographically characterized complexes 2 and 3. Notably, 4 has an Fe(IV/III) reduction potential of ?1.4 V vs Fc(+/o), the highest value yet observed for a monoiron complex. The relatively high stability of 4 (t(1/2) in CD(3)CN solution containing 0.1 M KPF(6) at 25 °C ? 15 min), as reflected by its high-yield accumulation via slow bulk electrolysis and amenability to (13)C NMR at -40 °C, highlights the ability of the sterically protecting, highly basic peralkylguanidyl donors of the TMG(3)tren ligand to support highly charged high-valent complexes.

One-dimensional (1D) helical organic nanostructures were synthesized by a modified vapor-solid (VS) process, called the vaporization-condensation-recrystallization (VCR) process. The conventional solution-phase synthetic methods generally mediate self-assemblies of repeating unit molecules. To provide enough intermolecular interaction forces among the unit molecules, such strategy requires specific designs and syntheses of complex unit molecules as they possess numerous functional groups including phenyl rings, hydroxyl groups, long aliphatic chains, etc. On the contrary, we found that small and simple organic molecules, for example, m-ABA, could be self-assembled by the VCR process, resulting in 1D helical organic nanostructures. When m-aminobenzoic acid (m-ABA) powders were vaporized and transported to be condensed on a cooler region, the condensates were recrystallized into 1D helical nanobelts. Each step of the VCR process was confirmed from control experiments performed by varying reaction times, substrate types, and reaction temperatures. Powder XRD data, SAED analysis, and theoretical calculations revealed that dimers of m-ABA molecules have repeating units, and the growth axis of m-ABA nanohelices is [100].

BACKGROUND: In the early phase of viral encephalitis, conventional MRI may appear normal. Diffusion-weighted imaging (DWI) is a sensitive tool for detecting early changes in cellular function in the central nervous system.PURPOSE: To investigate the usefulness of DWI in the diagnosis of enterovirus 71 (EV71) encephalitis, and to determine whether DWI is superior to conventional MR sequences.MATERIAL AND METHODS: MRI scans in 26 patients were retrospectively evaluated for distribution of lesions on T1-weighted images (T1WI), T2-weighted images (T2WI), fluid-attenuated inversion recovery (FLAIR), and DWI. Contrast-to-noise ratios (CNRs) were calculated for all regions on each sequence and differences in the four MRI sequences were assessed using CNRs. Apparent diffusion coefficient (ADC) values were measured for all regions to look for true restriction of diffusion.RESULTS: Fifteen out of 26 cases showed positive findings on MR imaging. The brain stem was involved in 11 patients, cortex and subcortical white matter in four patients. DWI was more sensitive in detecting the abnormalities (89.7%) compared to T2WI (48.7%), FLAIR (41.0%), and T1WI (35.9%), and the positive ratio of DWI was significantly higher compared to other sequences. Furthermore, no significant difference was found between T2WI and FLAIR (P = 0.649). The corresponding mean CNRs were 8.73 ± 2.57, 83.59 ± 29.28, 24.22 ± 6.22, and 132.27 ± 78.32 on T1WI, T2WI, FLAIR, and DWI, respectively. The absolute values of CNRs of lesions on DWI were significantly greater than those on other sequences.CONCLUSION: DWI appears to be more sensitive in detecting EV71 encephalitis than conventional MRI sequences. This capability may improve the accuracy in diagnosing EV71 encephalitis, especially at the early stage.

The present study investigates antimutagenic and anticytotoxic effect of polyvitamin complex Polijen in laboratory mice. Mutation in mice was induced by pesticide - copper oxychloride 3Cu(OH)2 CuCl2 , which is characterizes by the mutagenic and cytotoxic effect. Introduction of copper oxychloride (dosage 1/2, 1/5, 1/10 LD50) per oral to animals induces strong increase (p<0,001) of frequency of chromosomal aberrations (multiple fragments, lyses), genomic mutations (triploidy, tetraploidy), pathological mitosis (hollow metaphase, K-mitosis, adhesion of chromosomes) and destruction of interphase nucleuses (hollow nucleus). Experiments showed that administration of polyvitamin complex Polijen decreased 2, 5 times mutagenic and cytotoxic effect of pesticide-copper oxychloride.

Sources of background and background variation in a BEGe type HPGe detector located in a surface laboratory were identified. Different strategies for background reduction were applied. A cosmic veto was installed, and optimised using a digital acquisition system in list-mode with time-stamped data. This resulted in the reduction of total background by a factor of 1.4. Thermal and fast neutron fluxes were also calculated. The radon induced background component and its variation were significantly reduced.

The MET protein is involved in the malignant progression of different tumors. This study aimed to analyze the relationship of MET expression with tumor phenotype and clinical outcome in bladder cancer and the role of gene amplification for MET overexpression. A bladder cancer tissue microarray containing 686 bladder cancers was analyzed by immunohistochemistry and by fluorescence in situ hybridization. MET immunostaining was seen in normal urothelium and was recorded in 459 of 560 analyzable urothelial carcinomas (82.0%). Low MET staining was associated with a more unfavorable tumor phenotype. MET staining was seen in 89.8% of 266 pTa, 81.1% of 132 pT1, and 69.4% of 160 pT2-4 cancers (P < 0.0001). MET staining was detectable in 92.4% of 66 grade 1, 85.6% of 257 grade 2, and 75.1% of 237 grade 3 cancers (P = 0.001). MET expression status was not associated with overall or tumor-specific survival in muscle-invasive cancers (pT2-4), tumor progression in pT1 cancers, or recurrences in pTa tumors. Only four of the analyzed tumors (0.8%) showed amplification of the MET gene. We conclude that MET is not overexpressed in urothelial cancer but rather downregulated in a fraction of cancers. Accordingly, rare amplification of the genomic area including the MET gene was not associated with MET protein overexpression.

The zeta chain is required in the TCR complex to guarantee its surface expression and function. However, an understanding of the interaction(s) between the zeta chain and the other proteins in the TCR/CD3 has not yet been achieved. In this report, we attempt to assign a functional role to the short extracellular (EC) domain of the zeta chain by studying its unique positive charge, a lysine at position 9, because of its interesting location to the interchain disulphide bond of the zeta chain homodimer. We show that amino acid exchanges of lysine 9 to glycine, serine, cysteine or asparagine generate TCR complexes which are clearly defective in antigenic signalling. Interestingly, the non-conservative point mutations were segregating TCR complex signalling pathways. However, lysine 9 is not critical for TCR complex surface expression unless the positively charged lysine is exchanged for the negatively charged amino acid aspartic acid. The zeta chain mutant bearing a lysine to cysteine exchange is the sole mutant to be inefficiently co-precipitated with the TCR/CD3 complex suggesting a loose interaction of the zeta chain within the TCR complex.

The purpose of this article is to describe a service learning opportunity where interprofessional teams of students worked together to address patients' social determinants of health through home visits. This article describes this process, known as "hotspotting," and presents the development of this project, including collaboration with a local home health agency, recruiting of students, and weekly team meetings for debriefing. Evaluation data, barriers with implementation, and next steps for sustainability are also discussed.

BACKGROUND: The prostatic epithelium consists principally of basal epithelial cells, luminal epithelial cells, and neuroendocrine cells. Several studies support the concept that among basal cells, a subpopulation of stem cells resides which is capable of giving rise to other stem cells, basal epithelial cells, and also luminal epithelial cells and neuroendocrine cells. Other investigators suggest that luminal epithelial cells can also regenerate prostatic epithelium. Availability of pure populations of basal and luminal epithelial cells will aid in studies on defining the cellular pathways of differentiation during normal and pathological conditions. This study was designed to isolate and characterize pure populations of basal and luminal epithelial cells from adult rat ventral prostates.METHODS: Sequential enzymatic digestion and differential plating permitted the separation of glandular epithelial cells from stromal cells. The glandular epithelial cells were subjected to the STAPUT technique.RESULTS: Two types of cell populations, a large single-cell population and a small single-cell population, were obtained and characterized as basal and luminal epithelial cells by immunostaining for cytokeratin 5 and cytokeratin 8, respectively.CONCLUSIONS: Our results indicate that purified populations of prostatic basal and luminal epithelial cells can be isolated by the STAPUT technique.

Impedance spectroscopy has been proposed as a method of monitoring mucosal injury due to hypoperfusion and ischemia in the critically ill. The present paper presents an algorithm developed to calculate the characteristic electrical values that best describe human gastric impedance measurements and simplify the information obtained with this method. An impedance spectroscopy probe and nasogastric tube (ISP/NGT) was placed into the stomach of healthy volunteers, cardiovascular surgery and critically ill patients, and a database with 16199 spectra was obtained. The gastric spectrum forms two semi circles in the complex domain, divided into low frequency (F < 10 kHz) and high frequency (F > 10 kHz). A fitting algorithm was developed based on the Cole model, and central characteristic parameters were calculated. The parameters were validated using the normalized mean squared error and 0.66% of the spectra were discarded. From the experimental data obtained in humans, the greatest changes observed as the gastric mucosa becomes ischemic occur at low frequencies, which are specific and sensitive to tissue damage, and vary with the degree of hypoperfusion.

Clones possessing inserts of brain myosin II have been obtained by screening a rat brain cDNA expression library with a polyclonal antibody, raised against myosin II from the mouse neuroblastoma cell line, Neuro-2A. A partial sequence comprising the 3' coding and non-coding regions of the myosin message has been determined which is markedly different from other myosin sequences. The derived amino-acid sequence comprises the C-terminal 90 amino acids: VSS(PO4)LKNKLRRGDLPFVVTRRLVRKGTLELS(PO4)DDDDESKASLINETQPPQCLDQQ LDQQ LDQLFNWPVNAGCVCGWGVEQTQGEEAVHKCRT(CO2H). This sequence encompasses regions homologous to both the casein kinase II and protein kinase C heavy-chain phosphorylation sites. The non-helical "tail-piece" is considerably longer (an additional 39 amino acid residues) than found in other myosins. Northern blot analysis demonstrates this myosin II message to be unique to cerebral cortex, with no expression in all other non-cortical brain regions and peripheral tissues tested. Our results suggest functional diversity for myosin II isozymes within the brain.

On the basis of 110 prostatic osteoses that were histologically proven, constantly painful and demonstrated by X-ray, treated by early estrogenotherapy using very high doses, backed up by a high-dose maintenance estrogenotherapy, the authors study the clinical, radiological, histological and biological profile of this metastatic cancer, as well as the response to treatment. The median actuarial survival time of the patients studied is 18.5 months. No statistically significant prognostic correlation was found. Only patients who are clinically estrogen-sensitive, are suffering from bone metastases without a combined visceral conditions, and have a normal initial rate of alcaline phosphates, tend to have a better prognosis (median actuarial survival 31 months versus 18.5 months for the overall population).

Aim: Novel bifunctional VEGF-A neutralizing therapies are being developed for the treatment of retinal vascular diseases such as age-related macular degeneration and diabetic retinopathy. In developing new therapeutic drugs, only small aqueous humor sample volumes are available for analyzing several parameters. Highly sensitive detection methods must be applied in analyzing VEGF-A levels in ocular fluids in order to demonstrate VEGF-A suppression following drug administration. Experimental: A highly sensitive immunoassay for VEGF-A was developed on the single molecule array (Simoa) platform, and validated before being used for the analysis of clinical aqueous humor samples from patients treated with anti-VEGF-A therapeutics. Results: This highly sensitive immunoassay allows the detection of baseline VEGF-A levels and suppression effects after drug administration, even in sample volumes as low as 12 ìl. Conclusion: The Simoa VEGF-A assay is a valuable tool for the reliable monitoring of VEGF-A suppression after intravitreal administration of anti-VEGF-A drugs.

A comparative study of cytotoxicity and antiherpes activity of acycloguanosine (Acg) of the Soviet and American manufacture and a Soviet preparation of phosphonoacetic acid (PAA) for herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) was carried out in primary and continuous cell cultures. The Acg preparation was shown not to be inferior in maximal tolerated concentration, minimal inhibiting concentration, and chemotherapeutic index (CTI) to American drug. Zovirax (Zvr), in relation to both herpes simplex virus types in primary and continuous cell lines. The CTI of Acg and Zvr was 25-30-fold higher than that of PAA for HSV-1 (Vero cells) and 80-fold higher in chick embryo fibroblast cultures (CEF), and 25-fold higher for HSV-2 in CEF.

We tested the ability of lewis (LEW; RT-1(1)) recipients to reject DA (RT-1av1) cardiac allografts following the selective elimination of alpha/beta T cells with the mouse monoclonal antibody R73. One group of adult rats (6 weeks old) received 1000 microg R73 i.p. on days 2 and 1 before transplantation, and 100 microg R73 every third day after transplantation up to day 18. Prolonged cardiac graft survival was noted (30, 30, 32, 51, 62, 108, > 500, > 500, > 500 days). Untreated controls (n = 10) rejected their grafts within 7 +/- 1 days. R73 therapy induced a dramatic decrease in alpha/beta T cells from 69% before treatment to 5% within the first 5 days, followed by an increase to 64% by day 8. The T cell increase was paralleled by the appearance of anti-mouse antibody. A second group of adult rats (10 weeks old) received the same treatment. These "older" recipients rejected their grafts within 20 +/- 5 days. Chronic R73 therapy from birth until the day of transplantation (100 microg R73 i.p. twice a week) resulted in graft survival of 37 +/- 9 days in eight animals. Two rats had a graft survival of more than 200 days. When chronic R73 therapy was continued to day 70 after transplantation, DA hearts were accepted well in all animals for more than 100 days. Alpha/beta T cells were virtually absent throughout the whole time of treatment. Antibodies against R73 were not detected. We concluded that selective elimination of alpha/beta T cells has a strong effect on allograft survival.

Applying manganese(IV)- or iron(III)-(hydr)oxides to remove pharmaceuticals from water could be attractive, due to the capacity of these metal oxides to remove pharmaceuticals and be regenerated. As pharmaceutical removal under anaerobic conditions is foreseen, Mn(IV) or Fe(III) regeneration under anaerobic conditions, or with minimum oxygen dosage, is preferred. In this study, batch experiments are performed to investigate (1) Mn(IV) and Fe(III) regeneration from Mn(II) and Fe(II); (2) the pharmaceutical removal during biological Mn(IV) and Fe(III) regeneration; and (3) anaerobic abiotic pharmaceutical removal with different Mn(IV) or Fe(III) species. Results show that biological re-oxidation of reduced Mn(II) to Mn(IV) occurs under oxygen-limiting conditions. Biological re-oxidation of Fe(II) to Fe(III) is obtained with nitrate under anaerobic conditions. Both bio-regenerated Mn(IV)-oxides and Fe(III)-hydroxides are amorphous. The pharmaceutical removal is insignificant by Mn(II)- or Fe(II)-oxidizing bacteria during regeneration. Finally, pharmaceutical removal is investigated with various Mn(IV) and Fe(III) sources. Anaerobic abiotic removal using Mn(IV) produced from drinking water treatment plants results in 23% metoprolol and 44% propranolol removal, similar to chemically synthesized Mn(IV). In contrast, Fe(III) from drinking water treatment plants outperformed chemically or biologically synthesized Fe(III); Fe (III) from drinking water treatment can remove 31-43% of propranolol via anaerobic abiotic process. In addition, one of the Fe(III)-based sorbents tested, FerroSorp®RW, can also remove propranolol (20-25%). Biological regeneration of Mn(IV) and Fe(III) from the reduced species Mn(II) and Fe(II) could be more effective in terms of cost and treatment efficiency.

PURPOSE: To describe the clinical and imaging findings of ureteropelvic junction (UPJ) injuries caused by blunt trauma.MATERIALS AND METHODS: In two children (aged 10 and 16 years) and eight adults (aged 23-82 years) with UPJ injuries, findings at computed tomography (CT) (n = 10), excretory urography (n = 6), and retrograde pyelography (n = 8) were retrospectively reviewed to identify the location and extent of contrast material extravasation. Clinical and follow-up data were correlated with radiologic findings.RESULTS: CT and urography played complementary roles in diagnosis. UPJ avulsion, defined as complete transection of the ureter with no filling of the ipsilateral ureter below the level of the UPJ, was diagnosed in four patients. UPJ laceration, defined as contrast material extravasation from the UPJ with contrast material in the ipsilateral ureter distal to the point of injury, was diagnosed in six patients. Medial perirenal contrast extravasation was seen in all 10 patients but failed to help differentiate UPJ avulsion from laceration. A distinctive pattern of contrast material extravasation at CT termed "circumrenal urinoma" was present in five patients and was found to be specific for UPJ injury.CONCLUSION: Medial perinephric contrast material extravasation was highly suggestive of UPJ injury. Demonstration of ureteral filling differentiated UPJ laceration from avulsion.

This study was designed to evaluate the effects of roxithromycin (RXM), a newly synthesized macrolide antibiotic on allergic responses in mice. RXM was orally administered into BALB/c mice once a day for 42 days in a single dose of 5 mg/kg body weight. Spleen cells (Sp C) collected from mice on day 7, 14, 28 and 42 post-RXM administration showed higher blastic activity of lymphocytes than those from control. The activity peaked on the 7th day, then gradually decreased, and returned to the control level by the 42nd day. Production of cytokines, IL-2 and IL-5, by Sp C in response to concanavalin A stimulation was also examined in the course of RXM administration. The capacity of Sp C to produce IL-2 was enhanced by oral administration of RXM for 28 days. However, a long-term (for 42 days) administration inhibited it. On the other hand, the capacity of of Sp C to produce IL-5 was strongly inhibited by oral administration of RXM; the titer of IL-5 was similar to that obtained in cultures of Sp C from control mice. These results strongly suggest that oral administration of RXM inhibits the function of Th2-type helper T lymphocytes and that a long-term administration of RXM may be beneficial in asthma and allergy.

The majority of computer tomography stereotactic biopsy lesions enhance after administration of intravenous contrast, whereas patients with nonenhancing lesions are often followed conservatively or undergo craniotomies. There are few studies showing the effectiveness of stereotactic biopsies of nonenhancing cerebral lesions. Stereotactic biopsies were performed on 19 patients with lesions that did not enhance on CT after intravenous contrast. Pathological diagnoses were made in 90% (17/19) of patients. Four HIV-positive patients had progressive multifocal leukoencephalopathy, 11 patients had gliomas (4 astrocytomas, 6 anaplastic astrocytomas, and 1 ganglioma), 1 had multiple sclerosis, and 1 had herpes encephalitis. In 2 patients multiple biopsies revealed only gliosis. There was no morbidity or mortality. Stereotactic biopsies for nonenhancing brain lesions have a high diagnostic yield and can favorably alter the treatment course.

BACKGROUND: The evidence for a potential benefit of antioxidant vitamins and folic acid in cardiovascular disease (CVD) prevention is derived from laboratory, clinical, and observational epidemiological studies but remains inconclusive. Large-scale randomized trials with clinical end points are necessary to minimize confounding and provide unbiased estimates of the balance of benefits and risks, yet data from such trials are scarce, especially among women.METHODS: The Women's Antioxidant Cardiovascular Study (WACS) is a randomized, double-blind, placebo-controlled trial testing whether antioxidant vitamins and a folic acid/vitamin B(6)/vitamin B(12) combination prevent future cardiovascular events among women with preexisting CVD or >or=3 CVD risk factors. This paper describes the design of the trial and baseline characteristics of participants, evaluates the success of randomization, and addresses the generalizability of future findings.RESULTS: In a factorial design, 8171 U.S. female health professionals aged >or=40 years were randomized to vitamin E, vitamin C, beta-carotene, or placebos. Of these women, 5442 were also subsequently randomized to folic acid/vitamin B(6)/vitamin B(12) or placebo. The randomization was successful, as evidenced by similar distributions of baseline demographic, health, and behavioral characteristics across treatment groups. The clinical profile of participants was similar to that observed in another large trial of women with CVD.CONCLUSIONS: The similar distribution of known potential confounders across treatment groups provides reassurance that unmeasured or unknown potential confounders are also equally distributed. Although a definitive conclusion regarding generalizability requires additional trials in diverse populations, there is little biological basis for supposing that the benefit-risk balance differs in other high-risk women.

Alcohol and other drug abuse are frequently treated in a group therapy setting. If participants are allowed to enroll in therapy on a rolling basis, irregular patterns of participant overlap can induce complex correlations of participant outcomes. Previous work has accounted for common session attendance by modeling random effects for each therapy session, which map to participant outcomes via a multiple membership construction when modeling normally distributed outcome measures. We build on this earlier work by extending the models to semicontinuous outcomes, or outcomes that are a mixture of continuous and discrete distributions. This results in multivariate session effects, for which we allow temporal dependencies of various orders. We illustrate our methods using data from a group-based intervention to treat substance abuse and depression, focusing on the outcome of average number of drinks per day. Alcohol and other drug abuse are frequently treated in a group therapy setting. If 2 clients attend the some of the same sessions, we might expect that-on average-their posttreatment outcomes would be more similar than if they had not attended any sessions together. Hence, if participants are allowed to enroll in therapy on a rolling basis, irregular patterns of session attendance can induce complex relationships between participant outcomes. Statistical methods have been developed previously to account for rolling admission group therapy when the outcomes are normally distributed. In the case of alcohol and other drug use interventions, however, a substantial fraction of participants often report zero use after treatment. We extend previous work to build models that accommodate semicontinuous outcomes, which are a mixture of continuous and discrete distributions, for such situations. We find that modern Bayesian statistical methods and software allow users to efficiently estimate nonstandard models such as these. We illustrate our methods using data from a group-based intervention to treat substance abuse and depression, focusing on the outcome of average number of drinks per day. We find that the intervention is associated with a drop in the probability of any drinking, but find no evidence of a change in the amount of drinking, conditional on some drinking. (PsycINFO Database Record

BACKGROUND: Excluding nicotine and caffeine dependence, almost 50% of individuals with schizophrenia also meet the criteria for substance abuse or dependence. Comorbid drug abuse presents complications to the effective treatment of these patients because they have increased psychotic symptoms and poorer treatment compliance.CASE REPORT: This report describes thecase of a young man with schizophrenia and comorbid alcohol and cocaine abuse who was successfully treated with quetiapine. The patient was previously treated with olanzapine and developed priapism, which required emergency medical treatment.CONCLUSIONS: The possible utility of atypical antipsychotics in the treatment of patients with schizophrenia and comorbid substance abuse needs to be confirmed in clinical trials.

Chemotherapy is a predominant strategy to treat cancer and is often associated with toxicities like severe diarrhea that puts patients at additional risk and can hinder treatment strategies. Lian et al. recently explored the immune-mediated mechanisms of Irinotecan-induced diarrhea in colorectal cancer and found that double-stranded DNA in small vesicles can launch inflammation pathways in immune cells through the cytosolic DNA sensor AIM2.

A prospective study of postoperative wounds was carried out in West Dorset to determine the incidence of infection, describe the time distribution of presentation before and after discharge from hospital and identify possible contributory factors. There were 702 consecutive patients admitted to the study (600 in-patients and 102 day cases). Fifty one became infected (47 in-patients and 4 day cases), corresponding to an overall infection rate of 7.3%. Over 50% of infections presented during the first week after operation, and almost 90% were diagnosed within 2 weeks of surgery Twenty-eight (55%) wounds that became infected presented after hospital discharge. Of 23 specific aetiological variables studied, four (age, preoperative stay, shaving and the surgeon) were shown to have a statistically significant association with the development of wound infection. A strong association between the individual surgeon and the development of a wound infection was demonstrated and this supports the need for routine surgical audit.

We examine the spatial resolution and variance properties of PET images reconstructed using maximum a posteriori (MAP) or penalized-likelihood methods. Resolution is characterized by the contrast recovery coefficient (CRC) of the local impulse response. Simplified approximate expressions are derived for the local impulse response CRC's and variances for each voxel. Using these results we propose a practical scheme for selecting spatially variant smoothing parameters to optimize lesion detectability through maximization of the local CRC-to-noise ratio in the reconstructed image.

Heregulin beta1 (HRG), a combinatorial ligand for human growth factor receptors 3 and 4, is a regulatory polypeptide that promotes the differentiation of mammary epithelial cells into secretory lobuloalveoli. Emerging evidence suggests that the processes of secretory pathways, such as biogenesis and trafficking of vesicles in neurons and adipose cells, are regulated by the Rab family of low-molecular-weight GTPases. In this study, we identified Rab3A as a gene product induced by HRG. Full-length Rab3A was cloned from a mammary gland cDNA library. We demonstrated that HRG stimulation of human breast cancer cells and normal breast epithelial cells induces the expression of Rab3A protein and mRNA in a cycloheximide-independent manner. HRG-mediated induction of Rab3A expression was blocked by an inhibitor of phosphatidylinositol 3-kinase but not by inhibitors of mitogen-activated protein kinases p38(MAPK) and p42/44(MAPK). Human breast epithelial cells also express other components of regulated vesicular traffic, such as rabphilin 3A, Doc2, and syntaxin. Rab3A was predominantly localized in the cytosol, and HRG stimulation of the epithelial cells also raised the level of membrane-bound Rab3A. HRG treatment induced a profound alteration in the cell morphology in which cells displayed neuron-like membrane extensions that contained Rab3A-coated, vesicle-like structures. In addition, HRG also promoted the secretion of cellular proteins from the mammary epithelial cells. The ability of HRG to modify exocytosis was verified by using a growth hormone transient-transfection system. Analysis of mouse mammary gland development revealed the expression of Rab3A in mammary epithelial cells. Furthermore, expression of the HRG transgene in Harderian tumors in mice also enhanced the expression of Rab3A. These observations provide new evidence of the existence of a Rab3A pathway in mammary epithelial cells and suggest that it may play a role in vesicle trafficking and secretion of proteins from epithelial cells in response to stimulation by the HRG expressed within the mammary mesenchyma.

Cholesterol and triglyceride levels have been analyzed in the forensic setting and their values correlated with atherosclerotic lesions found at autopsy and histology. Nevertheless, the results of these investigations have provided diverging information on postmortem molecule stability and postmortem measurement reliability. The aim of this study was to determine triglycerides, total cholesterol, low-density and high-density lipoprotein cholesterol, apolipoprotein B100, and apolipoprotein A-I in antemortem and postmortem serum samples in a series of cases (N = 10, including cardiac and noncardiac deaths) that underwent forensic investigations and had both samples available, measure the same molecules in postmortem serum from femoral blood and pericardial and pleural fluids (N = 39, including cardiac and noncardiac deaths), and evaluate whether different levels of these molecules could be observed in cases characterized by different degrees of coronary artery atherosclerosis (N = 39, including cardiac and noncardiac deaths). Preliminary results indicated that total cholesterol and low-density and high-density lipoprotein cholesterol levels in postmortem serum samples tended to be lower than those in antemortem specimens, whereas triglyceride levels in postmortem serum samples tended to be higher than those in antemortem samples. No relationship could be found between postmortem serum and pericardial fluid levels or between postmortem serum and pleural fluid levels of all tested biomarkers. Lastly, cases characterized by severe coronary artery atherosclerosis revealed higher postmortem serum levels of total cholesterol and apolipoprotein B. Globally considered, these data confirm that femoral blood postmortem serum levels of cholesterol and apolipoproteins may be considered suitable to estimate their antemortem values in forensic cases characterized by coronary artery atherosclerosis.

DET1 is a pleiotropic regulator of Arabidopsis development and controls the expression of many light-regulated genes. To gain a better understanding of the mechanism by which DET1 controls transcription from light-regulated promoters, we identified elements in the chlorophyll a/b-binding protein 2 (CAB2) promoter that are required for DET1-mediated expression. Using a series of reporter constructs in which the luciferase gene is controlled by CAB2 promoter fragments, we defined two DET1-responsive elements in the CAB2 promoter that are essential for proper CAB2 transcription. A 40-bp DET1 dark-response element (DtRE) is required for both dark and root-specific repression of CAB2, whereas the known CAB upstream factor-1 element is required for DET1 activation-associated effects in the light and repression in the roots. HY5, a factor that binds CAB upstream factor-1, is also required for DET1 effects in the light. DtRE binds two distinct activities in Arabidopsis seedling extracts: a novel activity with binding site CAAAACGC that we have named CAB2 DET1-associated factor 1 plus an activity that is likely to be the myb transcription factor Circadian Clock-Associated 1. Both activities are altered in dark-grown det1 extracts as compared with wild type, correlating a change in extractable DNA binding activity with a major change in CAB2 expression. We conclude that DET1 represses the CAB2 promoter in the dark by regulating the binding of two factors, CAB2 DET1-associated factor 1 and Circadian Clock-Associated 1, to the DtRE.

To investigate possible relationships between genetic alterations and hormonal deregulation during breast cancer development and/or progression, we examined 616 primary breast cancers for loss of heterozygosity (LOH) at chromosomal regions 16q24, 17p13.3 and 17q21, and for amplifications of the ERBB2 and c-MYC loci. A comparison of oestrogen receptor (ER) and progesterone receptor (PgR) status in tumour cells with data concerning these genetic alterations revealed that LOH at 17q21 was significantly correlated with absence of oestrogen receptors (ER) (P < 0.0003) or progesterone receptors (PgR) (P < 0.0001), and with the absence of both (P < 0.0001). Similarly, a significant association was observed between amplification of ERBB2 and the absence of either ER or PgR. LOH at 17p13.3 was associated with the absence of PgR (P < 0.01). These data suggest a possible relationship between specific genetic changes on chromosome 17 and hormonal deregulation in the progression of breast cancer.

BACKGROUND: Some patients with nonischemic left ventricular (LV) systolic failure recover to have normal LV systolic function. However, few studies on the rates of recovery and recurrence have been reported, and no definitive indicators that can predict the recurrence of LV dysfunction in recovered idiopathic dilated cardiomyopathy (IDCMP) patients have been determined. It was hypothesized that patients who recovered from nonischemic LV dysfunction have a substantial risk for recurrent heart failure.METHODS: Forty-two patients (32 men) with IDCMP (mean [+/- SD] age 56.9+/-8.7 years) who recovered from systolic heart failure (LV ejection fraction [LVEF] of 26.5+/-6.9% at initial presentation) to a near-normal state (LVEF of 40% or greater, and a 10% increase or greater in absolute value) were monitored for recurrence of LV systolic dysfunction. Patients with significant coronary artery disease were excluded. Patients were monitored for 41.0+/-26.3 months after recovery (LVEF 53.4+/-7.6%) from LV dysfunction.RESULTS: LV systolic dysfunction reappeared (LVEF 27.5+/-8.1%) during the follow-up period in eight of 42 patients (19.0%). No significant difference between the groups with or without recurrent heart failure was observed in the baseline clinical and echocardiographic characteristics. However, more patients in the recurred IDCMP group than those in the group that maintained the recovery state had discontinued antiheart failure medication (62.5% versus 5.9%, P<0.05).CONCLUSIONS: LV dysfunction recurs in some patients with reversible IDCMP. The recurrence was significantly correlated with the discontinuation of antiheart failure drugs. The results suggest that continuous medical therapy may be mandatory in patients who recover from LV systolic dysfunction.

AIMS: To assess the effects of brinzolamide and dorzolamide on ocular haemodynamics and retinal oxygen saturation in patients with primary open-angle glaucoma (OAG).METHODS: Fifteen patients with OAG were evaluated in a randomised, cross-over, double-blind study. They were treated with either brinzolamide or dorzolamide for 3 months and then crossed-over after a 4-week washout period. They were given timolol during a 4-week run-in period and during washout. The following were performed after run-in, after washout and after each treatment period: adverse events check, measurement of visual acuity, contrast sensitivity, blood pressure, heart rate, and intraocular pressure, and fundus examination. Ocular blood flow was assessed using confocal scanning laser Doppler flowmetry (HRF) and colour Doppler imaging (CDI). Retinal oxygenation levels were determined using a non-invasive measurement of haemoglobin oxygen saturation by digital photographic fundus oximetry.RESULTS: Both brinzolamide and dorzolamide reduced the number of zero-flow pixels in the retina as measured by HRF, suggesting an increase in retinal blood flow (-6.86 and -0.452 respectively) with brinzolamide treatment resulting in fewer zero-flow pixels than dorzolamide (-6.41) (p = 0.024). Both brinzolamide and dorzolamide increased oxygen saturation in the retina as measured by photographic retinal oximetry in the superior (0.82 (p = 0.002) and 0.87 (p = 0.005)) and inferior (0.88 (p = 0.035) and 0.82 (p = 0.002)) retinal veins. No significant changes were found in CDI measurements of the retrobulbar blood supply during either treatment.CONCLUSION: This pilot study suggests that brinzolamide and dorzolamide may increase retinal oxygen saturation in patients with OAG.

The glucose transporter type 4 (glut4) is critical for metabolic homeostasis. Insulin regulates glut4 by modulating its expression on the cell surface. This regulation is mainly achieved by targeting the endocytic recycling of glut4. We identify general receptor for 3-phosphoinositides 1 (Grp1) as a guanine nucleotide exchange factor for ADP-ribosylation factor 6 (ARF6) that promotes glut4 vesicle formation. Grp1 also promotes the later steps of glut4 recycling through ARF6. Insulin signaling regulates Grp1 through phosphorylation by Akt. We also find that mutations that mimic constitutive phosphorylation of Grp1 can bypass upstream insulin signaling to induce glut4 recycling. Thus, we have uncovered a major mechanism by which insulin regulates glut4 recycling. Our findings also reveal the complexity by which a single small GTPase in vesicular transport can coordinate its multiple steps to accomplish a round of transport.

The clinical benefit of adding FMS-like tyrosine kinase-3 (FLT3)-directed small molecule therapy to standard first-line treatment of acute myeloid leukemia (AML) has not yet been established. As part of the UK AML15 and AML17 trials, patients with previously untreated AML and confirmed FLT3-activating mutations, mostly younger than 60 years, were randomly assigned either to receive oral lestaurtinib (CEP701) or not after each of 4 cycles of induction and consolidation chemotherapy. Lestaurtinib was commenced 2 days after completing chemotherapy and administered in cycles of up to 28 days. The trials ran consecutively. Primary endpoints were overall survival in AML15 and relapse-free survival in AML17; outcome data were meta-analyzed. Five hundred patients were randomly assigned between lestaurtinib and control: 74% had FLT3-internal tandem duplication mutations, 23% FLT3-tyrosine kinase domain point mutations, and 2% both types. No significant differences were seen in either 5-year overall survival (lestaurtinib 46% vs control 45%; hazard ratio, 0.90; 95% CI 0.70-1.15; P = .3) or 5-year relapse-free survival (40% vs 36%; hazard ratio, 0.88; 95% CI 0.69-1.12; P = .3). Exploratory subgroup analysis suggested survival benefit with lestaurtinib in patients receiving concomitant azole antifungal prophylaxis and gemtuzumab ozogamicin with the first course of chemotherapy. Correlative studies included analysis of in vivo FLT3 inhibition by plasma inhibitory activity assay and indicated improved overall survival and significantly reduced rates of relapse in lestaurtinib-treated patients who achieved sustained greater than 85% FLT3 inhibition. In conclusion, combining lestaurtinib with intensive chemotherapy proved feasible in younger patients with newly diagnosed FLT3-mutated AML, but yielded no overall clinical benefit. The improved clinical outcomes seen in patients achieving sustained FLT3 inhibition encourage continued evaluation of FLT3-directed therapy alongside front-line AML treatment. The UK AML15 and AML17 trials are registered at www.isrctn.com/ISRCTN17161961 and www.isrctn.com/ISRCTN55675535 respectively.

The current study investigated concurrent relations between emotional and social functioning in youth with anxiety disorders using a multi-reporter (i.e., children, parents, teachers) assessment strategy. Ninety youth (M age = 8.98 years, SD = 1.68) with a primary diagnosis of generalized anxiety disorder, social phobia, and/or separation anxiety disorder, and a parent participated. Regression analyses indicated that positive affect and emotion regulation coping were related to adaptive measures of social functioning, whereas positive affect, negative affect, reluctance to share emotional experiences with peers, and lability/negativity were related to maladaptive measures of social functioning in the expected directions. For youth high in lability/negativity and low in emotion regulation coping, the relationship between diagnostic severity and social problems was exacerbated. This research contributes to our understanding of the interplay of social and emotional variables and suggests that efforts to facilitate child emotional functioning may improve social functioning for anxious youth, or vice versa.

CXC chemokine receptor 4 (CXCR4) is involved in multiple physiological and pathological processes, notably as a coreceptor for human immunodeficiency virus (HIV) cell entry. Its broad expression pattern and vital biological importance make CXCR4 a troublesome drug target, as disruption of the interaction with its endogenous ligand, CXC chemokine ligand 12 (CXCL12), has severe consequences. In fact, only one CXCR4 drug, the bicyclam antagonist and HIV entry inhibitor AMD3100 (Plerixafor/Mozobil), has been approved for clinical use, however only for stem cell mobilization-a consequence of CXCR4 antagonism. Here, we report the engineering of an efficacy switch mutation in CXCR4-F292A7.43 in the middle of transmembrane helix 7-that converted the antagonists AMD3100 and AMD11070 into partial agonists. As agonists on F292A CXCR4, AMD3100 and AMD11070 were less disruptive to CXCR4 signaling while they remained efficient inhibitors of HIV fusion. This demonstrates that small molecule CXCR4 agonists can have a therapeutic potential as HIV entry inhibitors.

High-quality single-crystal and polycrystalline chemical-vapor-deposition diamond detectors with platinum contacts have been tested at the white-beam X28C beamline at the National Synchrotron Light Source under high-flux conditions. The voltage dependence of these devices has been measured under both DC and pulsed-bias conditions, establishing the presence or absence of photoconductive gain in each device. Linear response consistent with the theoretically determined ionization energy has been achieved over eleven orders of magnitude when combined with previous low-flux studies. Temporal measurements with single-crystal diamond detectors have resolved the nanosecond-scale pulse structures of both the NSLS and the APS. Prototype single-crystal quadrant detectors have provided the ability to simultaneously resolve the X-ray beam position and obtain a quantitative measurement of the flux.

Crowding conditions of larvae may have a significant impact on commercial production efficiency of some insects, such as Tenebrio molitor L. (Coleoptera: Tenebrionidae). Although larval densities are known to affect developmental time and growth in T. molitor, no reports were found on the effects of crowding on food utilization. The effect of larval density on food utilization efficiency of T. molitor larvae was studied by measuring efficiency of ingested food conversion (ECI), efficiency of digested food conversion (EDC), and mg of larval weight gain per gram of food consumed (LWGpFC) at increasing larval densities (12, 24, 36, 48, 50, 62, 74, and 96 larvae per dm(2)) over four consecutive 3-wk periods. Individual larval weight gain and food consumption were negatively impacted by larval density. Similarly, ECI, ECD, and LWGpFC were negatively impacted by larval density. Larval ageing, measured as four consecutive 3-wk periods, significantly and independently impacted ECI, ECD, and LWGpFC in a negative way. General linear model analysis showed that age had a higher impact than density on food utilization parameters of T. molitor larvae. Larval growth was determined to be responsible for the age effects, as measurements of larval mass density (in grams of larvae per dm(2)) had a significant impact on food utilization parameters across ages and density treatments (in number of larvae per dm(2)). The importance of mass versus numbers per unit of area as measurements of larval density and the implications of negative effects of density on food utilization for insect biomass production are discussed.

A dean at a private school of nursing implemented a leadership development program for early- to mid-career nursing faculty consisting of one 4-hour evening session per academic quarter for 7 quarters. Eight faculty members who had expressed interest in assuming a leadership role or been recommended by their supervisors as having strong leadership potential were invited to join. Program topics included leadership pathways, legal issues, budgeting and governance, diversity, the political arena, human resources, and student issues. Interviews with participants revealed 6 themes: the support a peer cohort provided, a desire for real-life application, a lack of previous exposure to related content or experiences, new perceptions of themselves as academic nurse leaders, the value of the program as preparation for academic nursing leadership roles, and broad program applicability.

Novel measures of coding based on interspike intervals were used to characterize the responses of supraoptic cells to osmotic stimulation. Infusion of hypertonic NaCl in vivo increased the firing rate of continuous (putative oxytocin) cells (Wilcoxon z= 3.84, P= 0.001) and phasic (putative vasopressin) cells (z= 2.14, P= 0.032). The irregularity of activity, quantified by the log interval entropy, was decreased for continuous (Student's t= 3.06, P= 0.003) but not phasic cells (t= 1.34, P= 0.181). For continuous cells, the increase in frequency and decrease in entropy was significantly greater (t= 2.61, P= 0.036 and t= 3.06, P= 0.007, respectively) than for phasic cells. Spike patterning, quantified using the mutual information between intervals, was decreased for phasic (z=-2.64, P= 0.008) but not continuous cells (z=-1.14, P= 0.256). Although continuous cells showed similar osmotic responses to mannitol infusion, phasic cells showed differences: spike frequency decreased (z=-3.70, P < 0.001) and entropy increased (t=-3.41, P < 0.001). Considering both cell types together, osmotic stimulation in vitro using 40 mm NaCl had little effect on firing rate (z=-0.319, P= 0.750), but increased both entropy (t= 2.75, P= 0.010) and mutual information (z=-2.73, P= 0.006) in contrast to the decreases (t= 2.92, P= 0.004 and z=-2.40, P= 0.017) seen in vivo. Responses to less severe osmotic stimulation with NaCl or mannitol were not significant. Potassium-induced depolarization in vitro increased firing rate (r= 0.195, P= 0.034), but the correlation with decreased entropy was not significant (r=-0.097, P= 0.412). Intracellular recordings showed a small depolarization and decrease in input resistance during osmotic stimulation with NaCl or mannitol, and membrane depolarization following addition of potassium. Differences in responses of oxytocin and vasopressin cells in vivo, suggest differences in the balance between the synaptic and membrane properties involved in coding their osmotic responses. The osmotic responses in vivo constrasted with those seen in vitro, which suggests that, in vivo, they depend on extrinsic circuitry. Differences in responses to osmolality and direct depolarization in vitro indicate that the mechanism of osmoresponsiveness within a physiological range is unlikely to be fully explained by depolarization.

Tracings of serial histological sections from 4 human embryos at different Carnegie stages were used to create 3-dimensional (3D) computer models of the developing heart. The models were constructed using commercially available software developed for graphic design and the production of computer generated virtual reality environments. They are available as interactive objects which can be downloaded via the World Wide Web. This simple method of 3D reconstruction offers significant advantages for understanding important events in morphological sciences.

This study reports results of a bilateral intracarotid amytal test in 73 epileptic patients with medically intractable focal seizures. No right-handers but 50% of left-handers have a right dominance for speech in this particular population. Lateralization of cerebral speech functions, as well as manual preference, are dependent on the neurological disease and can shift conjointly or independently. We study the relationships of those shifts to different variables related to the cerebral pathology: age at onset and lateralization of epilepsy, extensive brain damage, neurological deficit.

Africa's economy is growing faster than any other continent and it has been estimated that the middle class in Africa now exceeds 350 million people. This has meant a parallel increase in the importation of consumer goods and in the implementation of communication and information technologies (ICT), but also in the generation of large quantities of e-waste. However, inadequate infrastructure development remains a major constraint to the continent's economic growth and these highly toxic residues are not always adequately managed. Few studies have been conducted to date assessing the possible association between socioeconomic development factors, including e-waste generation, and blood levels of inorganic elements in African population. To disclose the role of geographical, anthropogenic, and socioeconomic development determinants on the blood levels of Ag, Al, As, Be, Cd, Co, Cr, Hg, Ni, Pb, Sb, and V -all of them frequently found in e-waste-, an immigrant population-based study was made including a total of 245 subjects from 16 countries recently arrived to the Canary Islands (Spain). Women presented higher levels of blood elements than men, and Northern Africans (Moroccans) were the most contaminated. People from low-income countries exhibited significantly lower blood levels of inorganic elements than those from middle-income countries. We found a significant association between the use of motor vehicles and the implementation of information and communication technologies (ICT) and the level of contamination. Immigrants from the countries with a high volume of imports of second-hand electronic equipment, telephone and internet use had higher levels of inorganic elements. In general terms, the higher level of economic development the higher the blood levels of inorganic pollutants, suggesting that the economic development of Africa, in parallel to e-waste generation and the existence of informal recycling sites, have directly affected the level of contamination of the population of the continent.

An operatively removed apocrine carcinoma of the breast from a 62-year-old Japanese lady has been observed by the ABC method, using the monoclonal antibody 115D8. The cancer cells and metaplastic epithelia exhibited similar ultrastructural findings (an apical snout, apocrine granules, etc.) as the apocrine sweat gland cells, although no evidence of apocrine secretion could be detected. The immunohistochemical testing, using monoclonal antibody, 115D8, showed an apical, linear, dot-like, staining in the supranuclear regions on the apocrine sweat gland cells and on the apocrine metaplastic cells of the mammary gland. Similar stainability also was observed in the well-differentiated area of the apocrine carcinoma, while a heterogeneity in staining, such as unstained cells and diffuse cytoplasmic-stained cells were found in the poorly-differentiated areas. These abnormal staining patterns indicate the malignant changes of the apocrine cells.

Interpersonal and Social Rhythm Therapy (IPSRT) delays bipolar disorder (BP) recurrence in adults by stabilizing daily routines and sleep/wake cycles. Because adolescence is a key developmental stage for illness onset and altered social and sleep patterns, this period may prove optimal for intervention with adolescents at-risk for BP. We describe a treatment development trial of IPSRT for adolescents at-risk for BP by virtue of a positive family history. Adolescents with a first-degree relative with BP were evaluated for Axis I psychopathology via semistructured interview, and relatives' BP diagnoses were confirmed via record review. IPSRT consisted of 12 sessions delivered over 6 months. Outcome variables including sleep, mood symptoms, and functioning were assessed via clinician interview and self-/parent-report at pretreatment, 3 months, and posttreatment (6 months). Thirteen adolescents attended at least one IPSRT session. Half of the sample denied Axis I psychopathology at intake; the remainder met criteria for a range of internalizing and externalizing disorders. Families reported high satisfaction with IPSRT, yet, on average, participants attended about half of scheduled sessions. Missed sessions were primarily associated with parental BP illness severity. Data indicate significant change in select sleep/circadian patterns (i.e., less weekend sleeping in and oversleeping) with treatment. Preliminary data suggest the IPSRT focus on stabilizing daily rhythms and interpersonal relationships may be beneficial for adolescents at-risk for BP. Controlled trials with longitudinal follow-up are needed to examine whether early intervention for at-risk youth helps prevent or delay disorder.

In this article, the authors discuss their experiences of two separate research projects involving interviews with both partners in care relationships that pushed the ethics of research methods along unfamiliar routes. The desire to understand the relationship from both sides was seen to outweigh the perils of accessing both stories but only when the ethical and procedural elements had been sufficiently worked through. It is those ethical and procedural elements that they share in this article, which is offered as a provocative nudge toward a continued critical appraisal of ethical standards within qualitative research and begins with the authors' reflection on their processes for such research through the examination of a fictionalized vignette.

With Sophora japonica at the flowering stage as the object, the effect of nitrogen, phosphorus and potassium fertilizers on the yield composition factors, yield and quality of Flos Sophorae Immaturus (FSI) was studied. The results indicated that in early spring, nitrogen, phosphorus and potassium fertilizer on the amplification rate of S. japonica, FSI yield composition, yield and quality were different significantly, middle to high nitrogen (1.5-2.0 kg/plant) significantly increased the level of panicled clusters, raceme and flower bud number and yield. Phosphorus (1.5-2.0 kg/plant) could significantly increase the total buds of flower number and yield, potassium showed no significant increase in yield and yield components. Comprehensively considering yield and quality of FSI, nitrogen 1.5-2.0 kg/plant, phosphorus 1.5-2.0 kg/plant and potassium 0.6-0.9 kg/plant are appropriate.

INTRODUCTION: Decompressive craniectomy(DC)with craniotomy for acute epidural hematoma(AEDH)removal is controversial. Here, we summarized two difficult AEDH cases where DC was performed. CASE 1:A 26-year-old man sustained a head injury in a bicycle accident, with a Japan Coma Scale(JCS)score of 200, right pupil mydriasis, and a left decerebrate posture on admission. Computed tomography(CT)revealed right AEDH with a midline shift. Craniotomy was performed without DC. Postoperatively, his consciousness level and anisocoria improved(JCS score, 30). Furthermore, no cerebral infarction was observed on CT at 9 h after surgery;however, at 48 h after surgery, a cerebral infarction with a mild midline shift was evident in the right hemisphere. His consciousness level deteriorated(JCS score, 100), and we initiated glyceol infusion. Worsening of the midline shift was apparent on CT 100 h after surgery;thus, DC was immediately performed. CASE 2:A 15-year-old boy was injured in a fall. On admission, his JCS score was 10. Immediately afterward, he showed neurological deterioration(JCS score, 200), right pupil mydriasis, and a left decorticate posture. CT revealed right AEDH with a midline shift;thus, craniotomy was performed with DC. On hospitalization day 10, he had orthostatic headache and a JCS score of 1. CT revealed paradoxical midline shift to the opposite side of craniotomy, and syndrome of the trephined was considered. He was placed in the Trendelenburg position until cranioplasty was performed on hospitalization day 18.CONCLUSION: Patients with AEDH presenting severe consciousness issues should undergo hematoma removal. Although DC is controversial, surgeons should administer intensive and prompt treatment according to the circumstance and should consider DC for appropriate AEDH cases.