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BACKGROUND: Exercise training is a non-pharmacological strategy for treatment of heart failure. Exercise training improves functional capacity and quality of life in patients. Moreover, exercise training reduces muscle sympathetic nerve activity (MSNA) and peripheral vasoconstriction. However, most of these studies have been conducted in middle-aged patients. Thus, the effects of exercise training in older patients are much less understood. The present study was undertaken to investigate whether exercise training improves functional capacity, muscular sympathetic activation and muscular blood flow in older heart failure patients, as it does in middle-aged heart failure patients.DESIGN: Fifty-two consecutive outpatients with heart failure from the database of the Unit of Cardiovascular Rehabilitation and Physiology Exercise were divided by age (middle-aged, defined as 45-59 years, and older, defined as 60-75 years) and exercise status (trained and untrained).METHODS: MSNA was recorded directly from the peroneal nerve using the microneurography technique. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. Functional capacity was evaluated by cardiopulmonary exercise test.RESULTS: Exercise training significantly and similarly increased FBF and peak VO(2) in middle-aged and older heart failure patients. In addition, exercise training significantly and similarly reduced MSNA and forearm vascular resistance in these patients. No significant changes were found in untrained patients.CONCLUSION: Exercise training improves neurovascular control and functional capacity in heart failure patients regardless of age.

Two strains (Gsoil 492(T) and Gsoil 643(T)) isolated in Pocheon Province, South Korea, from soil used for ginseng cultivation were characterized using a polyphasic approach. Both isolates comprised Gram-negative, aerobic, non-motile, rod-shaped bacteria. They had similar chemotaxonomic characteristics, e.g. containing MK-7 as the major quinone, having a DNA G+C content in the range 42.5-43.3 mol% and possessing iso-C(15 : 0) and iso-C(17 : 0) 3-OH as the major fatty acids. A phylogenetic analysis based on 16S rRNA gene sequences indicated that the two isolates formed a tight cluster with several uncultured bacterial clones and with the established genera Terrimonas, Niastella and Chitinophaga in the phylum Bacteroidetes but were clearly separate from these genera. The levels of 16S rRNA gene sequence similarity between the isolates and type strains of related genera ranged from 87.5 to 92.4 %. Furthermore, the results of physiological and biochemical tests allowed phenotypic differentiation of the isolates from phylogenetically closely related species with validly published names. The level of 16S rRNA gene sequence similarity between the two strains was 99.5 %, whereas the DNA-DNA relatedness value was 44 %, indicating that they represent separate species. On the basis of the polyphasic evidence, a novel genus, Flavisolibacter gen. nov., and two novel species, Flavisolibacter ginsengiterrae sp. nov. (type strain Gsoil 492(T)=KCTC 12656(T)=DSM 18136(T)) and Flavisolibacter ginsengisoli sp. nov. (type strain Gsoil 643(T)=KCTC 12657(T)=DSM 18119(T)), are proposed. Flavisolibacter ginsengiterrae is the type species of the genus.

UNLABELLED: Self-ligating brackets engage the wire by means of a slide mechanism. Forces that have to be applied to open and close the sliding mechanism of brackets are still unknown.OBJECTIVE: The aim of this study was to measure and compare the opening and closure forces of different self-ligating brackets.MATERIAL AND METHODS: Three different stainless steel self-ligating brackets (Carriere LX, Ortho Organizers; F1000, Leone; Damon Q, Ormco) were tested. For each different bracket, 20 maxillary right central incisors and 20 mandibular right central incisors were used. Opening and closure forces were measured using an Instron Universal Testing Machine. Statistical analysis was performed and ANOVA and Tukey tests were carried out.RESULTS: Opening forces were registered between 1.1 N and 5.6 N, whereas closure forces were recorded between 1.57 N and 4.87 N. Significant differences were detected among the different brackets and between the two prescriptions tested.CONCLUSION: The knowledge of different opening and closure forces of self-ligating brackets can help the orthodontist in the clinical management of these devices.

PURPOSE: This study was performed to reveal the relationship of nursing students' personality traits and entrepreneurship tendency with career adaptability.METHOD: This descriptive and correlational study's sample consisted of the junior and senior students in the nursing faculty of a state university in Istanbul (n = 265). The data was collected using the Student Information Questionnaire, Career Adapt-Abilities Scale, Ten Item Personality Inventory, and Scale of University Students Entrepreneurship. Descriptive tests and Pearson's correlation analysis were used for data analysis. Multiple linear regression analysis was used to determine the variables that affect the career adaptability of nursing students.RESULTS: The mean points on the personality inventory sub-dimensions of nursing students were highest in conscientiousness (5.72, SD 1.29) and lowest in emotional stability (4.46, SD 1.33). The mean on the Scale of University Students Entrepreneurship was 135.2 (SD 19.50) and on the Career Adapt-Abilities Scale was 78.7 (SD 9.05). The significant relationship between the personality traits, entrepreneurship tendency, and career adaptability scores of the students was weak and moderate. The regression model used to determine the variables that affect the career adaptability of nursing students was significant. Of the variables in the model, entrepreneurship tendency and being a fourth-year student significantly influenced the total score on career adaptability.CONCLUSION: The results showed a correlation between personality traits and career adaptability. In addition, there is a positive correlation between entrepreneurship tendency and career adaptability. The students with high entrepreneurship tendencies have better career adaptability. The results suggest that nursing education should improve entrepreneurial and intrapreneurial traits by considering the personality traits of students in order to ensure their adaptation to the nursing profession.

Background: The Oswestry Disability Index (ODI) is among the most widely used patient reported outcome measures for the assessment of spinal conditions. Traditionally, the ODI has been administered in outpatient clinics on a face-to-face basis, which can be expensive and time consuming. Furthermore, the percentage of patients lost to clinical follow-up is high, particularly after 2-5 years. Thus, telephonic administration of the ODI, if valid, could be a convenient way of capturing patient outcomes and increasing follow-up rates. The objective of this study was to validate telephonic administration of the ODI compared to face-to-face administration.Methods: A convenience sample of individuals with and without back pain in an academic medical center were recruited for this study. Face-to-face administration of the ODI was completed and retested 24 hours later via phone. Test-retest reliability was determined by calculating the intraclass correlation coefficient.Results: 22 individuals completed the ODI questionnaire face-to-face, then via telephone 24 hours later. There was a mean 2% (± 3) intra-rater ODI score difference (range: 0% to 12%). The intraclass correlation coefficient overall was 0.98 (95% CI: 0.96, 0.99, p<0.001) with a range of 0.95 to 1.0, revealing near-perfect test-retest reliability.Conclusions: Administration of the ODI questionnaire over the phone has excellent test-retest reliability when compared to face-to-face administration. Telephone administration is a convenient and reliable option for obtaining follow-up outcomes data.Clinical Relevance: Telephonic administration of the ODI is scientifically valid, and should be an accepted method of data collection for state-level and national-level outcomes projects.

Although experiments show a positive association between vascular plant and arbuscular mycorrhizal fungal (AMF) species richness, evidence from natural ecosystems is scarce. Furthermore, there is little knowledge about how AMF richness varies with belowground plant richness and biomass. We examined relationships among AMF richness, above- and belowground plant richness, and plant root and shoot biomass in a native North American grassland. Root-colonizing AMF richness and belowground plant richness were detected from the same bulk root samples by 454-sequencing of the AMF SSU rRNA and plant trnL genes. In total we detected 63 AMF taxa. Plant richness was 1.5 times greater belowground than aboveground. AMF richness was significantly positively correlated with plant species richness, and more strongly with below- than aboveground plant richness. Belowground plant richness was positively correlated with belowground plant biomass and total plant biomass, whereas aboveground plant richness was positively correlated only with belowground plant biomass. By contrast, AMF richness was negatively correlated with belowground and total plant biomass. Our results indicate that AMF richness and plant belowground richness are more strongly related with each other and with plant community biomass than with the plant aboveground richness measures that have been almost exclusively considered to date.

We examined whether relational perceptions (social involvement, relational value, interaction experience) differ depending on interaction acceptance goals (establish, maintain, or repair). Results indicated that relational perceptions were more positive in the maintain condition compared to the establish condition, which in turn was more positive than the repair condition. The data also supported a moderated mediation model: the indirect effects of social involvement and relational value on the relationship between acceptance goals and participant's interaction experience were contingent on self-esteem. These findings identify boundary conditions that influence the impact of acceptance goals on how much people experience an interaction positively. The findings provide an integrated framework outlining the potential relationship between acceptance goals, relational perceptions, interaction experience, and self-esteem.

Presents an obituary for Karl H. Pribram, who died on January 19, 2015. Karl had a very successful and extensive 70-year career in neuroscience research. He was a prolific researcher and writer, publishing approximately 150 data papers, almost 300 theoretical papers, and 19 books. His work is recognized through many awards and titles, including a Doctorate in Psychology from the University of Montreal in 1992, a Doctorate in Philosophy from the University of Bremen (1996), and a lifetime achievement award from the International Neural Network Society. His professional interactions extended beyond the traditional boundaries of science into the arts and humanities. His work in these integrative areas resulted in his becoming the first recipient of the Baclav Havel Prize for integrating science with the humanities and arts.

Genistein is one of the major isoflavones in soy products. It has been reported that genistein has apoptotic effects on certain hematological malignancies. However, so far there have been no completely comparative studies of the effect of genistein on malignant hematological diseases, especially multiple myeloma. We investigated genistein's inhibitory effect on the growth of acute lymphoblastic leukemia (RS4;11 and CEM), lymphoma (Toledo and GA10) and multiple myeloma (OPM-2 and U266) cell lines in vitro. We observed that genistein dose- and time-dependently inhibited proliferation of these cells. The cell line sensitivity to genistein treatment based on the 50% inhibitory concentration (IC(50)) values in decreasing order of toxicity was found to be as follows: RS4;11 (4.89 ± 4.28 ìM) > GA10 (13.08 ± 3.49 ìM) > Toledo (16.94 ± 3.89 ìM) > CEM (17.31 ± 0.72 ìM) > OPM-2 (46.76 ± 2.26 ìM) > U266 (128.82 ± 1.90 ìM). The mechanism of growth inhibition was through induction of apoptosis and cell cycle arrest. The concomitant altered expression of apoptosis pathway proteins and cell cycle modulators (caspases 9, 3, 7, PARP [poly(ADP-ribose) polymerase], cIAP1 [inhibitor of apoptosis protein 1], Bcl-2 and cyclin B1) were observed by Western blot and real-time polymerase chain reaction (PCR) analyses. In addition, some malignancy-related embryologic pathway proteins, e.g. Notch1 and Gli1, were modulated by genistein treatment in sensitive cell lines.

The ego of a psychosomatic patient enters the relations with the external world in a very archaic way. In new traumatic situations such a personality structure possesses a very poor repertoire of adaptation mechanisms. Owing to the lack of intrapsychic elaboration of the trauma, the conflict is solved in an "interpersonal" way. The authors emphasize the importance of interpersonal conflict as an actual necessity of maintaining the connection with reality. Such a response in the development corresponds to the fixation or regression to the conflict with the object from the subphase of practising. Unpleasure, because of the early forbidding of pleasurable activities by the object, is experienced as actual, thus the object becomes a hindrance in itself. The increased hostility is being discharged through the interpersonal conflict with the object. The quality of the actual object (the therapist) affects the development of the conflict, i.e. it either allows a more successful reparation of the patient's personality structure or brings about a deeper regression.

OBJECTIVE: Status epilepticus is an under diagnosed entity in Pakistan. It is a potentially reversible condition but has a high mortality, if it is not recognized and managed on time. The purpose of this study was to determine the clinical profile and the relationship of mortality of status epilepticus with its known risk factors.METHODS: This was a retrospective study. Medical records of all the patients admitted in the last five years (1998-2002) with a diagnosis of status epilepticus (ICDcode 345.30, 345.31) were reviewed. Data was recorded on a Performa and analyzed by using the statistical programme SPSS, chi square and Fischer exact test.RESULTS: The total number of patients were twenty-four. Sixteen patients were males (66.7%). Mean age was fifty-eight months and mean duration of hospital stay 5.5 days (range 2 to 22days). Eight patients were diagnosed to have epilepsy. Four (16.7%) had a previous history of status epilepticus. Three patients presented with status epilepticus for the first time without any previous history of seizures. Ten patients required midazolam infusion (41.7%) and out of these 3 (12.5%) were also given thiopentone infusion to control the seizures. Nine patients were shifted to the ICU for ventilation and control of seizures. Mortality in our study was 25%. Risk factors for mortality included age less than or equal to one year, abnormal MRI, type of the status epilepticus and the total duration of status epilepticus. No significant relationship was found with any of the known risk factorsCONCLUSION: Status epilepticus is a neurological emergency. A very high mortality was seen in our study. No risk factors were identified for this high mortality.

The Breast Adjuvant Chemotherapy Study of the Anti-Cancer Council of Victoria was set up to encourage the cooperation of clinicians from many centres who are involved in the management of early node-positive breast cancer in Victoria. Data sheets were completed by participants, and an analysis was made of the first 100 registered patients to determine the reliability of clinical assessment related to pathological findings and to study the extent of axillary node clearance. Although all subjects were histologically node positive, 47 had no palpable axillary lymph nodes, and in only 38 were nodes considered to be clinically involved. Correlation between clinical and pathological measurements of breast tumour size was significantly better (86%) with tumours over 5 cm in extent than with tumours of 5 cm or less (70%). Total mastectomy with total axillary clearance was the most common operative procedure performed. The pectoralis major was preserved in 97 and the pectoralis minor was divided or removed in 71 cases as part of the axillary clearance. In a subgroup (33) the location of involved nodes in the axilla was studied, and of these seven (21%) were found to have involved upper axillary nodes in the absence of lower axillary nodal involvement, emphasizing the inadequacy of axillary sampling in determining nodal status.

We investigated the expression of reticulocalbin-1 (RCN1) and its prognostic significance in non-small cell lung cancer (NSCLC). RCN1 expression was evaluated by immunohistochemical analysis with tissue microarrays in NSCLC tissues and matched adjacent noncancerous tissues. Furthermore, quantitative polymerase chain reaction and Western blot were also used to examine the expression of RCN1. Moreover, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, clone formation, and transwell assays were used to measure cell proliferation, migration, and invasion. Lastly, we used the Kaplan-Meier method and log-rank test to compare overall survival rates between the RCN1-high expression group and the RCN1-low expression group. In this study, immunohistochemistry by tissue microarray at RCN1 expression was significantly up-regulated in NSCLC tissues compared with adjacent noncancerous tissues. We further confirmed the up-regulation of RCN1 by quantitative polymerase chain reaction and Western blot assay. RCN1 expression level was closely related to lymph node metastasis (P < .001) and TNM stage (P = .012). Kaplan-Meier analysis showed that high RCN1 expression was remarkably associated with poor prognosis with NSCLC patients. A suppression of cell proliferation, migration, and invasion was obtained in A549 cells treated with RCN1 small interfering RNA. Our data indicate that RCN1 expression may have an vital role at promoting the occurrence of NSCLC, and it may be a vital molecular marker in the diagnosis and prognosis of NSCLC patients.

Carcinoma-associated fibroblasts (CAFs) play a pivotal role in promoting the growth, invasion and metastasis of tumor cells. However, to date little is known about the oncogenic mechanisms of CAFs. This study aimed to identify the microenvironmental factors involved in tumor development and progression directed by CAFs in liver metastases. Tissue samples collected from 20 patients with colorectal liver metastases were used in this study. Histological and morphological characterization of the samples was performed using hybridization and immunohistological assays. The mRNA expression of á-smooth muscle actin (á-SMA) was measured by northern blotting. The expression of plasminogen activator inhibitor type 1 (PAI-1) was measured by enzyme-linked immunosorbent assay (ELISA). As a result, co-expression of Thy-1 (CD90) and á-SMA was identified in CAFs, while normal liver samples were negative for á-SMA and Thy-1. Compared with epidermal growth factor (EGF) and tumor necrosis factor (TNF) incubation, the expression of á-SMA increased significantly following transforming growth factor-1 (TGF-1) incubation (P<0.05), while platelet-derived growth factor (PDGF) caused a significant suppression of á-SMA expression (P<0.05). PAI-1 expression was significantly lower in unstimulated fibroblasts compared to TGF-1-treated fibroblasts (P<0.01). The levels of PAI-1 transcription were significantly higher in CAFs from the patient samples compared with the healthy controls. Taken together, our findings suggest that CAFs may be important in migration, matrix degradation, invasion and angiogenesis of tumors, and TGF-1 may promote the activation of PAI-1 transcription in CAFs.

A twenty-six year old lady presented herself with multiple erythmatous, scaly, well-defined, hypo-esthetic plaques over bilateral soles, face and left leg. Histopathology revealed features consistent with borderline tuberculoid leprosy.

Presenilins (PSs) are involved in processing several proteins such as the amyloid precursor protein (APP), as well as in pathways for cell death and survival. We previously showed that some familial Alzheimer's disease PS mutations cause increased basal and acetylcholine muscarinic receptor-stimulated phospholipase C (PLC) activity which was gamma-secretase dependent. To further evaluate the dependence of PLC on PSs we measured PLC activity and the activation of variant protein kinase C (PKC) isoforms in mouse embryonic fibroblasts (MEFs) lacking either PS1, PS2, or both. PLC activity and PKCalpha and PKCgamma activations were significantly lower in PS1 and PS2 double knockout MEFs after PLC stimulation. Protein levels of PKCalpha and PKCgamma were lower in PS1 and PS2 double knockout MEFs. In contrast, PKCdelta levels were significantly elevated in PS1 and PS2 double knockout as well as in PS1 knockout MEFs. Also, PKCdelta levels were lowered after transfection of PS1 into PS1 knockout or PS double knockout MEFs. Using APP knockout MEFs we showed that the expression of PKCalpha, but not the other PKC isoforms is partially dependent on APP and can be regulated by APP intracellular domain (AICD). These results show that PLC and PKC activations are modulated by PS and also that PSs differentially regulate the expression of PKC isoforms by both APP/AICD-dependent and independent mechanisms.

To estimate the extent of the third carpal bone (C3) visible for evaluation in the dorsoproximal-dorsodistal oblique projection of the distal row of carpal bones, 13 forelimbs collected at post mortem from 7 horses were examined radiographically. The limbs were frozen with the carpal joints flexed then radiographed using fixed beam-cassette angles of 15 degrees to 45 degrees, at 5 degree intervals. The influence of beam-cassette angle on; the depth of the proximal articular surface examined, the radiographic appearance of C3 and the assessment of subchondral sclerosis was evaluated. Beam-cassette angles of 25 degrees to 40 degrees produced subjectively acceptable radiographs and did not appear to influence assessments of sclerosis. The mean depth of the examined proximal articular surface of the C3 increased significantly with each 5 degree increase in beam-cassette angle up to 40 degrees. The use of beam-cassette angles >35 degrees is recommended for the DPr-DDiO projection.

OBJECTIVE: This paper proposes the unification of entrance exams to medical residency programs (MRP) in Brazil. Problems related to MRP and its interface with public health problems in Brazil are highlighted and how this proposal are able to help solving these problems.METHODS: The proposal is to create a database to be applied in MRP unified exams. Some advantages of using the Item Response Theory (IRT) in this database are highlighted.RESULTS: The MRP entrance exams are developed and applied decentralized where each school is responsible for its examination. These exams quality are questionable. Reviews about items quality, validity and reliability of appliances are not common disclosed.CONCLUSION: Evaluation is important in every education system bringing on required changes and control of teaching and learning. The proposal of MRP entrance exams unification, besides offering high quality exams to institutions participants, could be as an extra source to rate medical school and cause improvements, provide studies with a database and allow a regional mobility.

Cochlear efferent innervation originates in two different groups of neurons located in the superior olivary complex. A first group of olivocochlear neurons (lateral efferent neurons) lies in the lateral superior olive. They send axons to the organ of Corti, where they synapse with radial afferent dendrites of primary auditory neurons, postsynaptic to the inner hair cells. The second group of neurons (medial efferent neurons) is found in medial subnuclei of the superior olivary complex and sends axons to synapse with outer hair cells. Subpopulations of both medial and lateral olivocochlear neurons probably use gamma-aminobutyric acid (GABA) as a neurotransmitter. We have used an immunoperoxidase technique to detect GABA-like immunoreactivity (GABA-LI) in postnatal maturing rat cochleas. The GABA-LI appeared in the inner hair cell region by P3 (P1 = birth) and reached a mature appearance by P15-P16. In the outer hair cell region, GABA-like immunoreactive fibers and terminals could not be identified until P9 and they were only found in the apical end of the cochlea. There was a dual gradient of maturation of GABA-LI in the cochlea. The GABA-LI appeared first at the cochlear base and then extended towards the apex. It also appeared earlier (about a week) in the inner hair cell region than in the outer hair cell region. This dual gradient of maturation is in close agreement with previous data concerning the maturation of the cochlea.

PURPOSE: To report our results in the treatment with radiation therapy of 25 patients affected by B-cell lymphoma with initial cutaneous presentation.MATERIALS AND METHODS: From October 1978 to June 1997, we have treated 25 patients with cutaneous B-cell lymphoma (CBCL) by cutaneous irradiation. There were 17 males and eight females, aged from 23 to 89 years (median age 50 years). The mean follow-up time for the series was 3.9 years (range from 0.2 to 15 years) from the completion of radiation therapy. All patients were staged as follows: in group 1, single lesion; group 2, multiple lesions; group 3, disseminated lesions. There were six (24%) patients in group 1, 15 (60%) patients in group 2, and four (16%) in group 3. There were nine patients with head and neck lesions, 11 patients with trunk lesions, and five patients with leg lesions. Thirteen patients (52%) had previously received chemotherapy for CBCL. Extended field irradiation was used to treat six patients (24%). Localized field irradiation (LFI) was performed for the other 19 patients (76%).RESULTS: The overall survival rate at 5 years was 73%. The complete response (CR) to the treatment for our series was 92%. The length of complete remission ranged from 2 to 180 months. There were three patients (8%) who obtained partial response (PR). Disease-free survival (DFS) at 1 year was 91% and at 5 years was 75%. Radiotherapy was generally well tolerated.CONCLUSIONS: Localized field irradiation is an effective treatment for some localized forms of primary cutaneous B-cell lymphoma and can obtain prolonged remissions. The patients with wide-spread skin involvement are usually candidates for extended field irradiation and/or chemotherapy. For the advanced stages of cutaneous B-cell lymphoma, where the chemotherapy is the treatment of choice, some good palliation can be achieved using local field irradiation.

The immunomodulatory properties of NIM-76 have been described in this paper. Pre-treatment of rats with a single i.p. injection of NIM-76 resulted in an increase in polymorphonuclear (PMN) leukocytes with a concomitant decrease in lymphocyte counts. The immunomodulatory activity of NIM-76 was found to be concentration-dependent. At 120 mg/kg body weight, there was an enhanced macrophage activity and lymphocyte proliferation response, while the humoral component of immunity was unaffected. At higher concentrations of NIM-76 (300 mg/kg body weight), there was a stimulation of mitogen-induced lymphocyte proliferation, while macrophage activity remained unaffected. However, a fall in primary and secondary antibody titres was observed. The study indicates that NIM-76 acts through cell-mediated mechanisms by activating macrophages and lymphocytes.

BACKGROUND: Alefacept blocks T-cell activation and induces apoptosis of memory T cells. It improves psoriasis vulgaris and may induce prolonged remissions. Experience with alefacept in palmar plantar pustulosis (PPP) is limited.OBJECTIVE: The objective of the study was to observe the effectiveness and safety of alefacept in the treatment of PPP.METHODS: Alefacept was administered weekly for 16 weeks by intramuscular (IM) injection of 15 mg to 15 patients with moderate to very severe PPP. Patients were followed for an additional 12 weeks.RESULTS: Four weeks after 16 weeks of treatment, there was a 49.6% reduction in the Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) and a 38.6% and a 64.5% reduction in total and fresh pustules, respectively. Eight weeks after dosing, 53.3% achieved PPPASI 50, 26.7% achieved PPPASI 75, and one patient was clear. The mean percent reduction in total pustules and fresh pustules was 46.1% and 61.2%, respectively; 73% had no pain, 53% had no itching, and 80% had no functional impairment. The palms responded better than the soles.CONCLUSIONS: This pilot showed that 16 weeks of once-weekly alefacept 15 mg IM was safe, led to improvement in PPP in all 15 treated patients, and induced a remission in one patient. Larger double-blind studies are warranted.

The heterotrimeric Sec61p complex is a major component of the protein-conducting channel of the endoplasmic reticulum (ER) membrane, associating with either ribosomes or the Sec62/63 complex to perform co- and posttranslational transport, respectively. We show by electron microscopy that purified mammalian and yeast Sec61p complexes in detergent form cylindrical oligomers with a diameter of approximately 85 A and a central pore of approximately 20 A. Each oligomer contains 3-4 heterotrimers. Similar ring structures are seen in reconstituted proteoliposomes and native membranes. Oligomer formation by the reconstituted Sec61p complex is stimulated by its association with ribosomes or the Sec62/63p complex. We propose that these cylindrical oligomers represent protein-conducting channels of the ER, formed by ligands specific for co- and posttranslational transport.

We examined the stabilization of anthocyanins with flavones from the practical and theoretical perspective. The influence of addition of skullcap flavones, heating to 50 °C, and 12 day storage time (in the presence and absence of light) on the stability of anthocyanins in honeysuckle concentrates was investigated experimentally. Theoretical study was conducted with molecular dynamics methods in a model system, preceded by simulated annealing and thermalization. By the methods of the computer simulation of the copigmentation process we determined the sites responsible for the stabilization of a cyanidin quinoidal base-baicalin complex. We revealed both direct and water-mediated hydrogen bondings that keep the lamellar stacking structure of these molecules in the bounded form in water medium. The stacking occurs also due to hydrophobic interactions of the rings of both molecules. The experimental part of the study confirmed the effectiveness of anthocyanins stabilization in a concentrate of honeysuckle with the use of skullcap flavones.

Nociceptin/orphanin FQ and nocistatin are two neuropeptides with opposing effects on spinal neurotransmission and nociception. Nociceptin/orphanin FQ selectively suppresses excitatory glutamatergic neurotransmission, while nocistatin selectively interferes with glycinergic and gamma-aminobutyric acid (GABA)-ergic transmission. Here, we performed whole-cell patch-clamp recordings from superficial rat spinal cord dorsal horn neurons to investigate the role of the opioid receptor-like (ORL)1 receptor for modulatory actions of these peptides. The partial ORL1 receptor antagonist [phe1psi(CH(2)-NH)Gly(2)]nociceptin-(1-13)NH(2) competitively reversed the effects of nociceptin/orphanin FQ on excitatory neurotransmission (estimated pA(2) 6.43), but left the suppression of inhibitory synaptic transmission by nocistatin unaffected. These results indicate that the inhibitory action of nociceptin/orphanin FQ on glutamatergic transmission is mediated via ORL1 receptors, while nocistatin acts via a different so far unidentified receptor.

This ongoing study investigates the neural correlates of ankle dorsi-plantar flexion in active, passive, and proprioceptive tasks. Specifically, we investigated two proprioceptive matching tasks that required a simple combination of active and passive ankle movements: (1) a memory-based ipsilateral matching task and (2) a contralateral concurrent matching task. As expected, during the passive tasks, subjects recruited the same brain areas involved in the correspondent active movements (primary motor cortex (M1), premotor cortex (PM) supplementary motor cortex (SMA) and primary somatosensory cortex (S1)), but the activations were lower. Instead, in both the proprioceptive matching tasks, subjects recruited more motor and sensory-motor areas of the brain and the activations were greater.

The present case study examined an adolescent boy who initially was evaluated at our clinic and was found to meet DSM-III-R criteria for autistic disorder. After placement in a residential school using Daily Life Therapy for autistic disorder, the subject reported being physically abused by a staff member. Additional psychiatric evaluation revealed post-traumatic stress disorder (PTSD) including symbolic anxiety and repetition of the trauma. The diagnosis of PTSD should be considered in children with autistic disorder and other severe developmental disorders who have experienced physical and sexual abuse. Furthermore, parents, professionals, educators, and child care workers struggle with emotional reactions to children with severe developmental disorders and may have difficulty accepting the reality of the child rather than the fantasy of the "wished-for child." The disappointment of this fantasy and the equating of the child's weaknesses as one's own may lead to personal devaluation and increase the risk of abusive behavior.

Pepsin chromatography was studied on peptide ligand sorbents, differing in the length of the polypeptide chains, ionogenic groups and the nature of hydrophobic side groups. Pepsin sorption was found to be dependent of a specific interaction of the substrate analogs with the enzyme and ionic interactions with the matrix and ionogenic groups of the ligand. Non-specific hydrophobic interactions of the enzyme and the ligand have little effect on the sorption. Efficient methods for the isolation of pepsin and separation of the mixture of bovine chymosin and pepsin are described.

Yarrowia lipolytica SEC62 cDNA was cloned by functional complementation of a thermo-sensitive sec62 Saccharomyces cerevisiae mutant strain. The Y. lipolytica SEC62 promoter region was amplified by the inverse polymerase chain reaction (PCR). The cDNA codes for a 396 amino-acid protein with two potential trans-membrane domains. Y. lipolytica Sec62p behaves as an integral membrane protein as shown by Western blotting. Y. lipolytica SEC62 cDNA is able to complement a S. cerevisiae sec62 null mutant strain confirming functional conservation, although only 53.6% amino-acid similarity is observed between Y. lipolytica and S. cerevisiae Sec62.

The investigation of the effect of oxidized lipoproteins on platelet activity is important for the understanding of the plague formation under atherosclerosis. In the present work, we examined the influence of low density lipoproteins (LDL) on ADP-induced platelet aggregation in the platelet rich plasma. In was demonstrated that mixing of plasma and LDL was accompanied by the decrease of ADP-induced aggregation parameters as compared to control (mixing with buffer). After 1 h incubation, platelet ADP-aggregation in the sample containing oxidized LDL (oxLDL) exceeded the ADP-aggregation in the control sample. The dependence of the aggregation parameters on the incubation time and on the degree of LDL oxidation were obtained. No difference in the cholesterol and phospholipid content was observed between cells incubated with buffer, native or oxidized LDL. Therefore, the possible oxLDL-induced accumulation of cholesterol in platelet membranes is excluded as a reason for the increased cell aggregation.

OBJECTIVE: To evaluate the impact of xerostomia on the quality of life (QOL) of people living with HIV/AIDS (PLWHA) from Brazil.STUDY DESIGN: A cross-sectional study was performed on 195 PLWHA. Xerostomia was detected by asking a question about the sensation of having "dry mouth," and Oral Health Impact Profile 14 (OHIP-14) was used to measure the impact of xerostomia on QOL. Time of diagnosis of HIV/AIDS was assessed.RESULTS: A total of 78 (40.0%) subjects presented with xerostomia. Xerostomia was associated with female gender, low amount of saliva perceived (p ? .01), difficulty in swallowing food (p ? .05), and showed to have a negative impact on QOL as measured by OHIP-14 (p ? .01).CONCLUSION: Xerostomia was frequent and showed to have a negative impact on the QOL of PLWHA.

MOTIVATION: Regulatory RNAs often unfold their action via RNA-RNA interaction. Transcriptional gene silencing by means of siRNAs and miRNA as well as snoRNA directed RNA editing rely on this mechanism. Additionally ncRNA regulation in bacteria is mainly based upon RNA duplex formation. Finding putative target sites for newly discovered ncRNAs is a lengthy task as tools for cofolding RNA molecules like RNAcofold and RNAup are too slow for genome-wide search. Tools like RNAhybrid that neglects intramolecular interactions have runtimes proportional to O(m x n), albeit with a large prefactor. Still in many cases the need for even faster methods exists.RESULTS: We present a new program, RNAplex, especially designed to quickly find possible hybridization sites for a query RNA in large RNA databases. RNAplex uses a slightly different energy model which reduces the computational time by a factor 10-27 compared to RNAhybrid. In addition a length penalty allows to focus the target search on short highly stable interactions.AVAILABILITY: RNAplex can be downloaded at http://www.tbi.univie.ac.at/~htafer/SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

The effect of epidermal growth factor on the levels of cytosolic phospholipase A2 mRNA and protein in cultured rat endometrial stromal cells isolated from uteri sensitized for the decidual cell reaction was examined. Treatment with epidermal growth factor increased the steady-state cytosolic phospholipase A2 mRNA and protein levels as demonstrated by Northern and Western blot analyses, respectively. Immunocytochemical analysis demonstrated an increase of cytosolic phospholipase A2 protein in most cells, as opposed to a small subpopulation of cells in culture. These results show that epidermal growth factor causes an increase in steady-state cytosolic phospholipase A2 mRNA and protein levels in rat endometrial stromal cells from uteri sensitized for the decidual cell reaction. Epidermal growth factor receptor ligands may regulate cytosolic phospholipase A2 and thus prostaglandin production in the endometrial stromal cells during implantation.

OBJECTIVE: Although a remarkable proportion of adolescents suffering from adjustment disorder (AD) are suicidal, few studies have documented the characteristics of suicidal AD patients. We examined background, psychopathology and treatment-related factors among suicidal adolescent AD outpatients.METHOD: Data on 302 consecutively referred psychiatric outpatient adolescents, aged 12-22 years, were collected. DSM-III-R diagnoses were assigned at the end of treatment based on all available data. Of the patients 89 received a diagnosis of AD, 25% of whom showed suicide attempts, suicidal threats or ideation.RESULTS: Compared with non-suicidal AD patients, suicidal AD patients were characterized by previous psychiatric treatment (OR = 6.1), poor psychosocial functioning at treatment entry (OR = 16.2), suicide as a stressor (OR = 33.3), dysphoric mood (OR = 6.9) and psychomotor restlessness (OR = 3.7).CONCLUSIONS: Common risk factors for suicidality in major psychiatric disorders characterized suicidal AD patients. Psychiatric assessment of AD patients should include careful monitoring of both symptomatology and exposure to suicide of significant others.

The contribution of the maculo-ocular reflex to gaze stability was studied in 10 pigmented rabbits by rolling the animals at various angles of sagittal inclination of the rotation and/or longitudinal animal axes. At low frequencies (0.005-0.01 Hz) of sinusoidal stimulation the vestibulo-ocular reflex (VOR) was due to macular activation, while at intermediate and high frequencies it was mainly due to ampullar activation. The following results were obtained: 1) maculo-ocular reflex gain decreased as a function of the cosine of the angle between the rotation axis and the earth's horizontal plane. No change in gain was observed when longitudinal animal axis alone was inclined. 2) At 0 degrees of rotation axis and with the animal's longitudinal axis inclination also set at 0 degrees, the maculo-ocular reflex was oriented about 20 degrees forward and upward with respect to the earth's vertical axis. This orientation remained constant with sagittal inclinations of the rotation and/or longitudinal animal axes ranging from approximately 5 degrees upward to 30 degrees downward. When the longitudinal animal axis was inclined beyond these limits, the eye trajectory tended to follow the axis inclination. In the upside down position, the maculo-ocular reflex was anticompensatory, oblique and fixed with respect to orbital coordinates. 3) Ampullo-ocular reflex gain did not change with inclinations of the rotation and/or longitudinal animal axes. The ocular responses were consistently oriented to the stimulus plane. At intermediate frequencies the eye movement trajectory was elliptic because of directional differences between the ampullo- and maculo-ocular reflexes.(ABSTRACT TRUNCATED AT 250 WORDS)

In the United States, the population aged 65 and older is rapidly growing, and this group uses more healthcare resources and has unique healthcare needs that do not exist in younger populations. However, it was reported that older adults are excluded or underrepresented in clinical trials for several diseases. We examined phase III clinical trials funded by the National Institutes of Health found in www.clinicaltrials.gov from 1965 to 2015 that addressed top causes for hospitalization and/or disability-adjusted life years in older adults: congestive heart failure (n = 45), cardiac dysrhythmias (n = 24), coronary atherosclerosis (n = 106), heart attack (n = 76), stroke (n = 113), chronic obstructive pulmonary disease (n = 14), pneumonia (n = 48), lung cancer (n = 117), prostate cancer (n = 65), and osteoarthritis (n = 15). We then analyzed the representation of older adults in these studies. We found that 33% of studies had arbitrary upper age limits, and 67% of studies reported mean and/or median ages that skewed younger than expected for the disease or condition of interest. Beyond explicit exclusion by age, older adults were often implicitly excluded based on various comorbid conditions such as polypharmacy/concomitant medication (37%) or cardiac issues (30%). We conclude that outcomes of these trials may not be fully generalizable to the general population of older adults. J Am Geriatr Soc 67:218-222, 2019.

We have determined the NMR structure of a ligand-binding domain of the granulocyte colony-stimulating factor (G-CSF) receptor, containing the highly conserved WSxWS motif. The domain consists of seven beta-strands with the fibronectin type III-like topology seen in several cytokine receptors. Comparisons between the spectra of the 15N-labelled domain with and without G-CSF indicate that the major ligand-recognition site is on the FG loop just upstream of the WSxWS sequence, and not on the BC loop which is mainly used in the growth hormone system. The WSxWS residues are suggested to contribute to ligand-recognition and to the protein architecture of the G-CSF receptor.

The key to designing optical mesocaptors is to construct a chromogenic receptor, namely, diphenylcarbazide (DPC), as a nanoscale platform scavenger with different functional characteristics, such as density, accessibility, and intrinsic mobility. Engineering of optical captors allows facile and reliable signaling in continuous monitoring modes, and enables simple and high-speed removal of toxic chromium (VI) ions. Mesoporous aluminosilica monoliths, with unique morphologies, active surface sites, and physical properties, enhance sensing/removal characteristics in terms of sensitivity, selectivity, and response time. The systematic design of optical mesocaptor is based on a densely patterned selective binding site (DPC) in engineered mesocylinder carriers that have multidirectional pores and microsized particle-like monoliths to control the adsorption/detection assays of Cr(VI) ions. Synthetic mesocaptor can be used for visual removal of Cr(VI) ions even at low concentration levels of 10(-10)M (i.e., 0.07 ppb) with rapid response time in minutes. Moreover, these new classes of design-made hybrid mesocaptor exhibit long-term signaling stability and recognition functionalities that provided extraordinary sensitivity, selectivity, reusability, and fast kinetic detection and quantification of various deleterious metal ions in the environment.

Laser projection based on phase modulation promises several advantages over amplitude modulation. We examine and compare the merits of two phase modulation techniques; phase-only computer generated holography and generalized phase contrast, for the application of dynamic laser image projection. We adopt information theory as a guiding framework and analyze information-relevant metrics such as space-bandwidth product, output display resolution, efficiency, speckle noise, computational load and device requirements. The analysis takes into account the perspective of potential end-users.

1. Procedures are described for the isolation of seven distinct cyanogen bromide fragments in high yield from human serum transferrin. 2. Cyanogen bromide-cleaved transferrin is separated into three fragments (CN-A, CN-B and CN-C) by gel filtration with Sephadex G-100. 3. Four peptides are obtained from CN-A (the largest fragment) after reduction and carboxamidomethylation, by gel filtration in acidic solvents. Two peptides are similarly obtained from fragment CN-B, whereas fragment CN-C is a single cystine-free peptide. 4. The molecular weights of the seven peptides, as determined by polyacrylamide-gel electrophoresis in the presence of sodium dodecyl sulphate, by sedimentation-equilibrium ultracentrifugation and by sequence studies, range from 3100 to 27000. Together they account for a molecular weight of 76200 for transferrin. 5. The two largest fragments contain the carbohydrate attachment sites of the protein, and the smallest fragment is derived from the N-terminus. 6. The amino acid compositions and N-terminal groups of the fragments are reported and the results compared with those of previous investigations.

At present, there are no efficacious vaccines or effective drugs against leishmaniasis; therefore new and innovative control methods are urgently required. One way to achieve this important goal is through using reverse genetic engineering to evaluate important enzymes, proteins and macromolecules. One of the most important enzymes for Glycosylphosphatidylinositol (GPI) biosynthetic pathways is GlcNAc-PI-de-N-acetylase (GPI12). The molecular constructs were cloned in Escherichia coli strain Top 10 and confirmed by molecular methods and were transfected by electroporation into Leishmania major. We demonstrated that two alleles of the GPI12 gene in L. major were successfully removed and enabling the generation of a null mutant, which supports the idea that GPI12 is not an essential gene for the growth and survival of Leishmania and the homozygous knockouts of Leishmania are able to survive. We were able to produce a mutant parasite that caused no damaged to the host. Further investigations are essential to check the safety profile in laboratory animals.

OBJECTIVE: This study investigated whether the functional abnormalities in prefrontal systems observed in adult bipolar disorder are manifested in adolescents with this illness.METHOD: Ten adolescents with bipolar disorder and 10 healthy comparison subjects participated in a color-naming Stroop task during event-related functional magnetic resonance imaging.RESULTS: Signal increases in the left putamen and thalamus were significantly greater in the bipolar disorder group than in the healthy group. Age correlated positively with signal increases in the bilateral rostroventral prefrontal cortex and the striatum in the healthy group but not in the bipolar disorder group. In the bipolar disorder subjects, depressive symptoms correlated positively with signal increases in the ventral striatum.CONCLUSIONS: These findings suggest the presence of dysfunction in the subcortical portions of the frontostriatal circuits in adolescents with bipolar disorder. The absence of the prefrontal abnormalities that were observed previously in adults and the absence of the age-related increases in prefrontal activity observed in normal comparison subjects suggest that a developmental disturbance in prefrontal function may emerge in bipolar disorder over the course of adolescence.

Interleukin-6 (IL-6) is multipotent cytokine that acts in a network of factors directing the inflammatory reaction of purulent bacterial meningitis (PBM). However, little is known about the role of IL-6 in aseptic or "viral" meningitis (AM). IL-6 was assayed by RIA in cerebrospinal fluid (CSF) and serum samples obtained from patients with AM (n = 65), PBM (n = 8), and lymphocytic bacterial meningitis (LBM, n = 11). Of patients with AM, 89% had detectable IL-6 in CSF, with high IL-6 titers (median, 2160 pg/mL; 95% confidence interval [CI], 1320-2540 pg/mL) compared with 100% in patients with PBM (median, 6575 pg/mL; 95% CI, 450-32,000 pg/mL) and 90.9% in patients with LBM (median, 875 pg/mL; 95% CI, 150-2180 pg/mL). There was a highly symmetrical correlation between IL-6 and the percentage of polymorphonuclear cells in CSF of patients with PBM (r = .97, P = .01) and AM (r = .49, P = .002). In conclusion, this study shows evidence that IL-6 is released into the meningeal space in aseptic meningitis and is correlated with the local acute inflammatory response.

Patients with myotonic dystrophy frequently suffer from excess daytime sleepiness, which can be a significant cause of disability. Previous studies have indicated that this excess daytime sleepiness is only occasionally due to obstructive sleep apnoea and may be principally of central nervous system origin. Modafinil has been successfully used to treat narcolepsy, a central disorder causing excess daytime sleepiness. We have investigated the use of this drug in myotonic dystrophy patients with excess daytime sleepiness. Patients were recruited from a clinic population on the basis of screening with the Epworth Sleepiness Scale. Patients scoring 10 and above were invited to participate in a randomized double-blind crossover trial of modafinil versus placebo, with four weeks in each arm of the study separated by a 2-week washout period. Patients were assessed by polysomnography at baseline. The primary outcome measures were change in both the Epworth Sleepiness Scale and a modified Maintenance of Wakefulness Test, which were measured at the start of each arm of the trial and in week 3 of each intervention period. In agreement with previous smaller studies, sleepiness is not correlated with CTG expansion size. Treatment with modafinil showed a non-significant reduction in median Epworth Sleepiness Scale. However, the median Maintenance of Wakefulness Test score was prolonged by treatment (31.7-40 min, P=0.006). There were no significant adverse cardiac effects of the drug in this group of patients (resting 12 lead and 24 h ECG monitoring). Selected patients with myotonic dystrophy and excess daytime sleepiness may benefit from modafinil. In this patient group the Epworth Sleepiness Scale may not be the most reliable measure of sleepiness. Despite the potential for cardiac disease in these patients, the drug was well tolerated with no adverse effects.

PURPOSE: To investigate the association of quantitative magnetic resonance imaging (qMRI) parameters with arthroscopic grading of cartilage degeneration. Arthroscopy of the knee is considered to be the gold standard of osteoarthritis diagnostics; however, it is operator-dependent and limited to the evaluation of the articular surface. qMRI provides information on the quality of articular cartilage and its changes even at early stages of a disease.METHODS: qMRI techniques included T 1 relaxation time, T 2 relaxation time, and delayed gadolinium-enhanced MRI of cartilage mapping at 3 T in ten patients. Due to a lack of generally accepted semiquantitative scoring systems for evaluating severity of cartilage degeneration during arthroscopy, the International Cartilage Repair Society (ICRS) classification system was used to grade the severity of cartilage lesions. qMRI parameters were statistically compared to arthroscopic grading conducted with the ICRS classification system.RESULTS: qMRI parameters were not linearly related to arthroscopic grading. Spearman's correlation coefficients between qMRI and arthroscopic grading were not significant. The relative differences in qMRI parameters of superficial and deep cartilage varied with degeneration, suggesting different macromolecular alterations in different cartilage zones.CONCLUSIONS: Results suggest that loss of cartilage and the quality of remaining tissue in the lesion site may not be directly associated with each other. The severity of cartilage degeneration may not be revealed solely by diagnostic arthroscopy, and thus, qMRI can have a role in the investigation of cartilage degeneration.

OBJECTIVES: Small clinical trials reported that repetitive sessions of tDCS could improve naming abilities in post-stroke aphasia. However, systematic meta-analyses found no effect, but all of these analyses pooled data from both single and repetitive sessions at the group level. The aim of this paper was to perform a meta-analysis based on individual patient data to explore the effects of repetitive tDCS sessions on naming in post-stroke aphasia and in prespecified subgroups.METHODS: We searched for published sham-controlled trials using the keywords "aphasia OR language" AND "transcranial direct current stimulation OR tDCS" AND "stroke". We computed an active and sham improvement ratio by dividing the difference between naming scores after and before the active or sham sessions, respectively, by the total number of picture items. Because of heterogeneity (I2 = 66%, p: 0.002), we used random-effects models to estimate the standardized mean difference (SMD) for the naming outcome. We then analyzed subgroups according to number of sessions, polarity, side/location of the active electrode, post-stroke delay, aphasia severity and comprehension disorders.RESULTS: Seven eligible studies were identified, including 68 chronic stroke patients. tDCS was beneficial on naming ability (35% ±34% in the active vs. 25% ±37% in the sham condition). An SMD of 0.8 (95% CI: 0.27-1.33) was found for the naming outcome. Additionally, there was a dose-dependent effect (5 vs. >5 sessions). We also demonstrated a prevalence of anodal vs. cathodal condition and left vs. right targeting electrode. Finally, repetitive sessions were beneficial regardless of the severity of aphasia, comprehension disorders or post-stroke delay.CONCLUSION: Repetitive sessions of tDCS are likely to be valuable in enhancing naming accuracy in post-stroke aphasia.

Alterations in total body sodium (TBSodium) that covered the range from moderate deficit to large surplus were induced by 10 experimental protocols in 66 dogs to study whether large amounts of Na+ are stored in an osmotically inactive form during Na+ retention. Changes in TBSodium, total body potassium (TBPotassium), and total body water (TBWater) were determined by 4-day balance studies. A rather close correlation was found between individual changes in TBSodium and those in TBWater (r2 = 0.83). Changes in TBSodium were often accompanied by changes in TBPotassium. Taking changes of both TBSodium and TBPotassium into account, the correlation with TBWater changes became very close (r2 = 0.93). The sum of changes in TBSodium and TBPotassium was accompanied by osmotically adequate TBWater changes, and plasma osmolality remained unchanged. Calculations reveal that even moderate TBSodium changes often included substantial Na+/K+ exchanges between extracellular and cellular space. The results support the theory that osmocontrol effectively adjusts TBWater to the body's present content of the major cations, Na+ and K+, and do not support the notion that, during Na+ retention, large portions of Na+ are stored in an osmotically inactive form. Furthermore, the finding that TBSodium changes are often accompanied by TBPotassium changes and also include Na+/K+ redistributions between fluid compartments suggests that cells may serve as readily available Na+ store. This Na+ storage, however, is osmotically active, since osmotical equilibration is achieved by opposite redistribution of K+.

We show that a two-step process, involving spontaneous self-assembly of lipids and apolipoproteins and surface patterning, produces single, supported lipid bilayers over two discrete and independently adjustable length scales. Specifically, an aqueous phase incubation of DMPC vesicles with purified apolipoprotein A-I results in the reconstitution of high density lipoprotein (rHDL), wherein nanoscale clusters of single lipid bilayers are corralled by the protein. Adsorption of these discoidal particles to clean hydrophilic glass (or silicon) followed by direct exposure to a spatial pattern of short-wavelength UV radiation directly produces microscopic patterns of nanostructured bilayers. Alternatively, simple incubation of aqueous phase rHDL with a chemically patterned hydrophilic/hydrophobic surface produces a novel compositional pattern, caused by an increased affinity for adsorption onto hydrophilic regions relative to the surrounding hydrophobic regions. Further, by simple chemical denaturation of the boundary protein, nanoscale compartmentalization can be selectively erased, thus producing patterns of laterally fluid, lipid bilayers structured solely at the mesoscopic length scale. Since these aqueous phase microarrays of nanostructured lipid bilayers allow for membrane proteins to be embedded within single nanoscale bilayer compartments, they present a viable means of generating high-density membrane protein arrays. Such a system would permit in-depth elucidation of membrane protein structure-function relationships and the consequences of membrane compartmentalization on lipid dynamics.

Simultaneous thrombosis of multiple epicardial coronary arteries is an uncommon clinical finding in ST-segment elevation myocardial infarction (STEMI). We describe a 44 year-old male present with STEMI who was found to have simultaneously occluded two epicardial arteries. There is many clinical states that can lead to multiple thrombosis i.e. essential trombocytosis, hiperhomocysteinaemia, depletion of antitrombin III, cocaine abuse etc. In this particular case L-arginin supplementation and association with thrombosis or atherosclerosis progression is discussed.

Background: Birth measures of twins are potentially influenced by sex of co-twin.Aim: To analyse the association between sex of co-twin and birth weight, length and ponderal index in twin infants from Yucatan, Mexico.Subjects and methods: A total of 2057 twin pairs born during 2008-2017 were analysed. Female-female (F-F), male-male (M-M) and male-female (M-F) twin pair types were defined. Multiple linear regression models were used to analyse the association of (1) being female from M-F pairs and birth measures among overall female infants (M-F and F-F), and (2) being male from M-F pairs and birth measures among overall male infants (M-F and M-M). The length of gestation and mothers' age and level of education were used as covariates.Results: Models showed that being male from M-F pairs was associated with increases of 81 g in birth weight and 0.61 cm in length, compared to males from M-M pairs, and being female from opposite-sex pairs was associated with increases of 0.36 cm in length, compared to females from same-sex pairs.Conclusions: Males from M-F pairs show greater birth size than males from same-sex pairs, which supports the hypothesis that birth measures of twins are influenced by sex of the co-twin.

INTRODUCTION: Giant juvenile breast fibroadenoma can cause deformity and should be excised. Cosmesis is an important consideration in young patients.PATIENT CONCERNS: The patient was admitted to our hospital for a mass of 6 ? 6 cm in her left breast.DIAGNOSE: A giant juvenile fibroadenoma.INTERVENTIONS: With the help of Mammotome, we translated the larger mass to smaller one and removed it via a small circumareolar incision with no residual tumor.OUTCOMES: There was no recurrence of disease after 2 years.CONCLUSION: Mammotome-combined resection is a new approach that can be used to excise giant fibroadenomas with a minimal incision, and provides a favorable contour to the breast.

BACKGROUND AND METHODS: Curcumin has extraordinary anticancer properties but has limited use due to its insolubility in water and instability, which leads to low systemic bioavailability. We have developed a novel nanoparticulate formulation of curcumin encapsulated in stearic acid-g-chitosan oligosaccharide (CSO-SA) polymeric micelles to overcome these hurdles.RESULTS: The synthesized CSO-SA copolymer was able to self-assemble to form nanoscale micelles in aqueous medium. The mean diameter of the curcumin-loaded CSO-SA micelles was 114.7 nm and their mean surface potential was 18.5 mV. Curcumin-loaded CSO-SA micelles showed excellent internalization ability that increased curcumin accumulation in cancer cells. Curcumin-loaded CSO-SA micelles also had potent antiproliferative effects on primary colorectal cancer cells in vitro, resulting in about 6-fold greater inhibition compared with cells treated with a solution containing an equivalent concentration of free curcumin. Intravenous administration of curcumin-loaded CSO-SA micelles marginally suppressed tumor growth but did not increase cytotoxicity to mice, as confirmed by no change in body weight. Most importantly, curcumin-loaded CSO-SA micelles were effective for inhibiting subpopulations of CD44(+)/CD24(+) cells (putative colorectal cancer stem cell markers) both in vitro and in vivo.CONCLUSION: The present study identifies an effective and safe means of using curcumin-loaded CSO-SA micelles for cancer therapy.

AIMS: Success of opening single (SOS)-comedy is a prospective multicenter study to compare the improvement in the decrease of myocardial viability by percutaneous coronary intervention (PCI) with that by optimal medical therapy (OMT) alone in patients with chronic total occlusion (CTO) of a single coronary artery.METHODS AND RESULTS: The risks and the benefits of both options (PCI and OMT) were listed in a CTO decision aid (DA). Eligible participants detected by invasive coronary angiography (ICA) or coronary computed tomography angiography (CCTA) were divided into PCI or OMT groups according to patients' choice after shared-decision making process with DA. Participants will undergo positron emission tomography/computed tomography (PET/CT), cardiac magnetic resonance (CMR) and transthoracic echocardiography (TTE), and proceed to ICA and revascularization if possible. Blinded core laboratory interpretation will be performed for ICA, CCTA, PET/CT, CMR, and TTE. All participants will be followed up for 12 months. The primary endpoint is the improvement to the decrease of myocardial viability from baseline assessed with the use of PET/CT after 12-month follow-up.CONCLUSIONS: All of the patients are appropriately consented before enrolling in this study, which has been approved by the Ethics Committee. Results of SOS-COMEDY will be helpful to develop a strategy for single CTO patients.

OBJECTIVE: To assess the effectiveness and safety of oxcarbazepine (OXC) in bipolar disorder (BD) and related conditions.METHODS: We reviewed medical records of patients given OXC treatment between March 2003 and March 2005 at the University of British Columbia Hospital. Response to treatment was assessed retrospectively using the Clinical Global Impression of Severity (CGI-S), and the Clinical Global Impression of Improvement (CGI-I) scales.RESULTS: OXC was prescribed to 15 patients with bipolar I (n = 12), bipolar II (n = 2) and schizoaffective (n = 1) disorder who presented with depression (n = 9), mania (n = 3), hypomania (n = 1), or mixed state (n = 2). Six patients had Axis II diagnoses and 10 patients had a family history of mood disorders. Psychiatric co-morbidity was found in four patients. The mean daily dose of OXC was 775 +/- 556.11 mg/day and the mean duration of follow-up was 31.60 +/- 41.51 weeks. The OXC add-on led to a significant reduction in symptoms as indicated by reduction in CGI-S scores at 1 and 2 months. Nine of 12 patients at 1 month and seven of 14 at 1 or 2 months were much or very much improved on CGI-I scale. One patient (7%) developed hyponatremia. Six patients (40%) experienced no side effects and three patients (20%) stopped the medication because of side effects.CONCLUSION: OXC was effective and well-tolerated in refractory BD and schizoaffective disorder. These preliminary data are promising but controlled studies are needed to confirm its efficacy in refractory BD.

An extract of porcine brain acetone powder incubated with thyrotropin-releasing hormone (TRH; pGlu-His-ProNH2) produces acid TRH (pGlu-His-Pro), histidine, and prolineamide. Fractionation of the brain extract by DEAE-cellulose chromatography produces three protein fractions which metabolize TRH. The activity of these fractions was characterized using TRH with a 3H-label on the histidine or proline as well as [His-3H]His-ProNH2. Fraction I contains pyroglutamate aminopeptidase and Fraction II contains TRH deamidase. Fraction III was found to contain a previously unrecognized enzyme which cleaves His-ProNH2 to histidine and proline. The histidylprolineamide imidopeptidase has been characterized. A competition study using a variety of compounds containing histidine or proline suggests that the best substrates for the imidopeptidase contain a free alpha-amino group on histidine and a blocked carboxyl group on proline, as is found in His-ProNH2. A survey of a variety of polypeptide hormones indicates that many of them inhibit the imidopeptidase activity. A kinetic study of the inhibition of the enzyme by adrenocorticotropic hormone (1-24) shows that the inhibition by polypeptide hormones is noncompetitive. We hypothesize that pituitary hormones may stimulate the production of (cyclo)-His-Pro by inhibiting alternate routes of TRH metabolism.

Montelukast, a cysteinyl leukotriene type 1 receptor antagonist, exhibits secondary anti-inflammatory properties when used at higher concentrations. Low-molecular-weight heparin (LMWH) evokes pronounced anti-inflammatory effects by interrupting leukocyte adhesion and migration. We hypothesized that inhalable particles containing montelukast plus LMWH release both drugs in a sustained fashion and protect the lungs against allergen-induced inflammation. Large porous particles of montelukast and LMWH were prepared using a double-emulsion-solvent-evaporation method. Montelukast was first encapsulated in copolymer-based particles using polyethylenimine as a porosigen; the resulting particles were then coated with LMWH. The particles were evaluated for physicochemical properties, respirability, and release profiles. The anti-inflammatory effect of the optimized formulation was studied in ovalbumin-sensitized asthmatic Sprague Dawley rats. The optimized large porous particles had a diameter of 10.3 ± 0.7 ìm, exhibited numerous surface indentations and pores, showed acceptable drug entrapment efficiency (66.8% ± 0.4% for montelukast; 91.7% ± 0.8% adsorption efficiency for LMWH), demonstrated biphasic release patterns, and escaped the uptake by the rat alveolar macrophages. The number of infiltrating inflammatory cells in asthmatic rat lungs, treated with dual-drug particles, was >74% fewer than in untreated asthmatic rat lungs. Similarly, the airway walls of asthmatic animals treated with dual-drug particles were 3-fold thinner than those of untreated asthmatic animals (p < 0.001). The optimized formulation protects lungs against methacholine-induced airway hyper-reactivity. Overall, this study demonstrates the feasibility of loading 2 drugs, montelukast and LMWH, into an inhalable particulate system and establishes that this novel combination therapy produces sustained drug release and elicits a robust anti-inflammatory response in the lungs.

Integumentary wounds in mammalian fetuses heal without scar; this scarless wound healing is intrinsic to fetal tissues and is notable for absence of the contraction seen in postnatal (adult) wounds. The precise molecular signals determining the scarless phenotype remain unclear. We have previously reported that the eta subunit of the chaperonin containing T-complex polypeptide (CCT-eta) is specifically reduced in healing fetal wounds in a rabbit model. In this study, we examine the role of CCT-eta in fibroblast motility and contractility, properties essential to wound healing and scar formation. We demonstrate that CCT-eta (but not CCT-beta) is underexpressed in fetal fibroblasts compared to adult fibroblasts. An in vitro wound healing assay demonstrated that adult fibroblasts showed increased cell migration in response to epidermal growth factor (EGF) and platelet derived growth factor (PDGF) stimulation, whereas fetal fibroblasts were unresponsive. Downregulation of CCT-eta in adult fibroblasts with short inhibitory RNA (siRNA) reduced cellular motility, both basal and growth factor-induced; in contrast, siRNA against CCT-beta had no such effect. Adult fibroblasts were more inherently contractile than fetal fibroblasts by cellular traction force microscopy; this contractility was increased by treatment with EGF and PDGF. CCT-eta siRNA inhibited the PDGF-induction of adult fibroblast contractility, whereas CCT-beta siRNA had no such effect. In each of these instances, the effect of downregulating CCT-eta was to modulate the behavior of adult fibroblasts so as to more closely approximate the characteristics of fetal fibroblasts. We next examined the effect of CCT-eta modulation on alpha-smooth muscle actin (alpha-SMA) expression, a gene product well known to play a critical role in adult wound healing. Fetal fibroblasts were found to constitutively express less alpha-SMA than adult cells. Reduction of CCT-eta with siRNA had minimal effect on cellular beta-actin but markedly decreased alpha-SMA; in contrast, reduction of CCT-beta had minimal effect on either actin isoform. Direct inhibition of alpha-SMA with siRNA reduced both basal and growth factor-induced fibroblast motility. These results indicate that CCT-eta is a specific regulator of fibroblast motility and contractility and may be a key determinant of the scarless wound healing phenotype by means of its specific regulation of alpha-SMA expression.

QT interval prolongation is an important marker for the development of cardiac arrhythmias (CAs). Optimal methods to estimate QT/QTc intervals in patients with ventricular pacing (VP) and its correlation with CA have not been widely investigated. We aimed to validate the currently available formulas for QT determination during VP and to compare their abilities in predicting the occurrence of CA (atrial fibrillation [AF] and malignant ventricular arrhythmias [VAs] in patients with advanced heart failure and cardiac resynchronization therapy). Consecutive patients with advanced heart failure who underwent cardiac resynchronization therapy implantation between August 2001 and April 2015 were included in a retrospective study. Four proposed formulas for QT correction in VP rhythms were evaluated. One hundred eighty patients were enrolled. During 44 months of follow-up, 43 patients (37.7%) developed AF and 16 patients (8.9%) developed VA. There was no correlation between corrected QT increments and AF risk with any of the formulas for paced rhythms. Regarding VA, higher corrected QT values measured with Massachusetts' formula (QTcM) were found to have a higher risk of event (p = 0.036) (Beta = 1.012 [1.001 to 1.023]). Each 1 ms increase in QTc increased the probability of experiencing VA by 12‰. QTcM >444 was found to be a strong predictor of VA. In conclusion, there are significant differences in mean QTc interval measured by the currently advised formulas. QTc interval was not associated with AF in any of the formulas. Only the QTcM formula showed a significant stepwise increase in the risk of experiencing malignant VA.

While research has steadily begun to explore thoughts and beliefs linked with helplessness and despair in schizophrenia, it is less clearly understood how to account phenomenologically for the related experience of being unable to commit to action in the midst of grave discomfort. To explore this issue, the current paper presents an analysis of the experience of volitional paralysis of two persons over the course of long-term integrative psychotherapy. In particular, we explore the experience of the inability to commit to action and the consequences of the gradual recovery of a sense that one is capable of action. Results suggest that in both cases inaction was tethered to a sense of self as insufficiently centered to survive action. In particular, we suggest both men appeared initially unable to commit to action because such a commitment threatened them with forces both felt would undo the tenuous conversations that comprised their identities. Finally, as a sense of self as capable of action emerged, both men began to experience themselves as relatively more complex human beings and to sustain more complex conversation within themselves and between themselves and others. Implications for psychotherapy and rehabilitation are discussed.

BACKGROUND: Sirtuin 1 (SIRT1), a histone/protein deacetylase, has been implicated in aging, metabolism, and stress resistance. SIRT1 regulates endothelial nitric oxide (NO) synthase, restores NO availability, and is involved in different aspects of cardiovascular disease. The aim of this study was to evaluate any abnormalities with regard to SIRT1 protein level in the blood, SIRT1 activity, and impaired endothelial function in patients with obstructive sleep apnea syndrome (OSAS). We also investigated whether or not OSAS patients who received nasal continuous positive airway pressure (CPAP) treatment showed improvements in the levels of SIRT1.METHODS: Thirty-five patients with moderately severe to severe OSAS who requested nasal CPAP treatment and 20 healthy controls were prospectively enrolled. The SIRT1 protein levels in blood and its activity, and the serum levels of nitric oxide derivative (NO x ) were assessed. All subjects participated in sleep studies, which were repeated 3 months after nasal CPAP treatment in the patients with OSAS.RESULTS: In the patients with OSAS, the level of SIRT1 in the blood, its activity, and that of NO x was lower than those of normal subjects before nasal CPAP treatment. After nasal CPAP treatment, the level of SIRT1 in the blood and its activity increased from 0.55 ± 0.32 pg/ìg of total protein and 3085.53 ± 1071.57 arbitrary fluorescence units (AFUs)/ìg of total protein to 1.13 ± 0.43 pg/ìg of total protein and 5344.65 ± 1579.71 AFUs/ìg of total protein. The serum levels of NO x in the patients with OSAS increased from 16.36 ± 5.78 to 25.94 ± 5.17 µM.CONCLUSIONS: Successful treatment for OSAS with nasal CPAP can restore blood levels of the SIRT1 protein and its activity and serum levels of NO x .

Whereas beta-2-microglobulin (beta2M) has mainly been used as a prognostic factor in patients with lymphoproliferative disorders, some studies have reported the value of beta2M in myeloproliferative disorders (MPD). In order to investigate a potential role in the pathogenesis of MPD and to find a possible value as indicators in monitoring the course of the disease, we measured beta2M, TNF-alpha, IL-1alpha, IL-1beta, IL-2, sIL-2R, IL-6 and IL-10 in 55 patients with MPD, at diagnosis and during the course of the disease. In progressive disease and particularly when transformation to acute leukemia occurred, high levels of beta2M, IL-2 and sIL-2R were found in all patients; the elevation was progressive, which suggests a potential prognostic usefulness in the individual patient.

PURPOSE: To investigate how speech-language pathologists (SLPs) report involving parents in intervention for phonology-based speech sound disorders (SSDs), and to describe the home practice that they recommend. Further aims were to describe the training SLPs report providing to parents, to explore SLPs' beliefs and motivations for involving parents in intervention, and to determine whether SLPs' characteristics are associated with their self-reported practice.METHOD: An online survey of 288 SLPs working with SSD in Australia was conducted.RESULT: The majority of SLPs (96.4%) reported involving parents in intervention, most commonly in providing home practice. On average, these tasks were recommended to be completed five times per week for 10 min. SLPs reported training parents using a range of training methods, most commonly providing opportunities for parents to observe the SLP conduct the intervention. SLPs' place of work and years of experience were associated with how they involved and trained parents in intervention. Most (95.8%) SLPs agreed or strongly agreed that family involvement is essential for intervention to be effective.CONCLUSION: Parent involvement and home practice appear to be intricately linked within intervention for phonology-based SSDs in Australia. More high-quality research is needed to understand how to best involve parents within clinical practice.

Background Coronary artery calcium is important in cardiovascular risk stratification, but this knowledge is based on studies with a significant selection bias. This study aims to evaluate the external validity of a screening programme including coronary artery calcium examination, and the association between coronary artery calcium and cardiovascular events. Design Multi-centre population based study. Methods Randomly selected middle-aged men and women ( N = 1751) free of cardiovascular disease were invited to the examination during 2009-2010. Participation rate in the examination was 70%. Participants ( n = 1227) and non-participants ( n = 524) were compared regarding: cardiovascular medical treatment, Charlson comorbidity index and socioeconomic status (evaluated by cohabitation, gross income and education). Study endpoints were cardiovascular events and mortality. Results Non-participants had a significant higher comorbidity ( p = 0.003) and a lower socioeconomic status ( p < 0.0001), while cardiovascular medical treatment was alike. Over a median follow-up time of 6.5 years the cardiovascular event and mortality rates were equal (6.7% vs. 6.4%, p = 0.80 and 0.4% vs. 0.5%, p = 0.76, respectively). Adjusted hazard ratio was 0.90 (95% confidence interval (CI) 0.63-1.37). Among participants, the extent of coronary artery calcium was significantly associated with increased risk of cardiovascular events (hazard ratio 1.92, 95% CI 1.03-3.54, hazard ratio 3.66, 95% CI 1.82-7.32, hazard ratio 6.51, 95% CI 3.17-13.36 for coronary artery calcium scores 1-99, 100-399, ?400 AU, respectively). Conclusions Non-participants had a higher comorbidity index and a lower socioeconomic status, but the cardiovascular event and mortality rates were equal to those of participants. Thus, a screening programme including a coronary artery calcium examination had a high external validity regarding cardiovascular risk, but also a significant social imbalance.

Stem cell divisions are either asymmetric-in which one daughter cell remains a stem cell and one does not-or symmetric, in which both daughter cells adopt the same fate, either stem or non-stem. Recent studies show that in many tissues operating under homeostatic conditions stem cell division patterns are strongly biased toward the symmetric outcome, raising the question of whether symmetry confers some benefit. Here, we show that symmetry, via extinction of damaged stem-cell clones, reduces the lifetime risk of accumulating phenotypically silent heritable damage (mutations or aberrant epigenetic changes) in individual stem cells. This effect is greatest in rapidly cycling tissues subject to accelerating rates of damage accumulation over time, a scenario that describes the progression of many cancers. A decrease in the rate of cellular damage accumulation may be an important factor favoring symmetric patterns of stem cell division.

In the gammaproteobacteria, the FeoA, FeoB, and FeoC proteins constitute the Feo system, which mediates ferrous iron [Fe(II)] import. Of these Feo proteins, FeoB is an inner membrane Fe(II) transporter that is aided by the small protein FeoA. However, the role of another small protein, FeoC, has remained unknown. Here we report that the FeoC protein is necessary for FeoB protein-mediated Fe(II) uptake in Salmonella experiencing low levels of oxygen and iron. The FeoC protein was found to directly bind to the FeoB transporter, leading to high cellular levels of FeoB. Depletion of the FtsH protease enabled high levels of FeoB in the absence of FeoC, suggesting that the FeoC protein protects the FeoB transporter from FtsH-mediated proteolysis. Our present study provides a singular example of bacteria that can control expression of iron uptake systems posttranslationally by employing a small iron transporter-binding protein.

Two fungal cyclooligomer depsipeptide synthetases(CODSs), BbBEAS (352 kDa) and BbBSLS (348 kDa) from Beauveria bassiana ATCC7159, were reconstituted in Saccharomyces cerevisiae BJ5464-NpgA, leading to the production of the corresponding anticancer natural products, beauvericins and bassianolide, respectively. The titers of beauvericins (33.8 ± 1.4 mg/l) and bassianolide (21.7± 0.1 mg/l) in the engineered S. cerevisiae BJ5464-NpgA strains were comparable to those in the native producer B. bassiana. Feeding D-hydroxyisovaleric acid (D-Hiv) and the corresponding L-amino acid precursors improved the production of beauvericins and bassianolide. However, the high price of D-Hiv limits its application in large-scale production of these cyclooligomer depsipeptides. Alternatively, we engineered another enzyme, ketoisovalerate reductase (KIVR) from B. bassiana, into S. cerevisiae BJ5464-NpgA for enhanced in situ synthesis of this expensive substrate. Co-expression of BbBEAS and KIVR in the yeast led to significant improvement of the production of beauvericins.The total titer of beauvericin and its congeners (beauvericins A-C) was increased to 61.7 ± 3.0 mg/l and reached 2.6-fold of that in the native producer B. bassiana ATCC7159. Supplement of L-Val at 10 mM improved the supply of ketoisovalerate, the substrate of KIVR, which consequently further increased the total titer of beauvericins to 105.8 ± 2.1 mg/l. Using this yeast system,we functionally characterized an unknown CODS from Fusarium venenatum NRRL 26139 as a beauvericin synthetase, which was named as FvBEAS. Our work thus provides a useful approach for functional reconstitution and engineering of fungal CODSs for efficient production of this family of anticancer molecules.

BACKGROUND: Inborn errors of metabolism are on the differential for patients presenting with a cyclic vomiting syndrome phenotype. Classes of disorders to consider include: mitochondrial disorders, fatty acid oxidation disorders, urea cycle defects, organic acidurias, and acute intermittent porphyria.AIM: This article reviews the metabolic differential diagnosis and approach to screening for inborn errors in children and adults presenting with a cyclic or recurrent vomiting phenotype.CONCLUSION: Cyclic vomiting syndrome is thought to be an episodic syndrome that may be associated with migraine. It is a diagnosis of exclusion. Inborn errors of metabolism should be considered in the patient presenting with a recurrent vomiting phenotype. Mitochondrial dysfunction may play a role in cyclic vomiting syndrome, and true mitochondrial disorders can present with a true cyclic vomiting phenotype.

OBJECTIVE: To investigate the antitumor effects of intrasplenically transplanted interleukin-18 (IL-18) gene-modified hepatocytes on murine implanted liver carcinoma.METHODS: Embryonic murine hepatocyte cell line (BNL-CL2) was transfected with a recombinant adenovirus encoding IL-18 and used as delivery cells for IL-18 gene transfer. Two cell lines, BNL-LacZ and BNL-CL2, were used as controls. One week after intrasplenic injection of C26 cells (colon carcinoma line), tumor-bearing syngeneic mice underwent the intrasplenic transplantation of IL-18 gene-modified hepatocyte cell line and were divided into treatment group (BNL IL-18) and control groups (BNL-LacZ and BNL-CL2). Two weeks later, the serum levels of IL-18, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) in the implanted liver carcinoma-bearing mice were assayed, the cytotoxicity of murine splenic cytotoxic T-lymphocytes (CTLs) was measured, and the morphology of the hepatic tumors was studied to evaluate the antitumor effects of the approach.RESULTS: In the treatment group, the serum levels of IL-18, IFN-gamma, TNF-alpha and NO increased significantly. The splenic CTL activity increased markedly (P < 0.01), accompanied by a substantial decrease in tumor volume and the percentage of tumor area and prolonged survival of liver carcinomo-being mice.CONCLUSIONS: In vivo IL-18 expression by ex vivo manipulated cells with IL-18 recombinant adenovirus is able to exert potent antitumor effects by inducing a predominantly T-cell-helper type 1 (Th1) immune response. Intrasplenic transplantation of adenovirus-mediated IL-18 gene-modified hepatocytes could be used as a targeting treatment for implanted liver carcinoma.

The recidivism rate for violent injuries in the United States has been reported as high as 45 per cent. Based on a retrospective review, the 5-year recidivism rate at the Indiana University/Wishard Trauma Center is 31 per cent, and the 1-year recidivism rate is 8.7 per cent. Individuals who have been admitted with a violent injury are screened by one of the Prescription for Hope (RxH) support specialists (SS). If the individual consents to participate, the SS conducts an in-depth assessment of risk factors. The SS and participant identify personal goals and develop a tailored service plan, which is outlined in a formalized agreement. In the first year of the RxH program (June 1, 2009, to May 31, 2010), 64 patients were enrolled. The most-often referred community services are in the category of social integration (84%). The SS have a 99 per cent success rate in getting clients to initiate services; 82 per cent have completed the services and 12 per cent are still using the services. As of the time of this writing, 34 subjects have been in RxH for at least 1 year. One patient returned to the trauma center in September 2010 with a repeat violent injury; this represents a 2.9 per cent 1-year recidivism rate. In the first 12 months of our program we did not have any participants return with a violent injury (0% recidivism), and we have only had one patient return to date. We conclude that the RxH SS model may play a significant role in decreasing the recidivism of violent injuries.

Vitamin K1 levels were measured by high performance liquid chromatography in cord blood (n = 33) and at the age of 97-120 h after administration of 2 mg of vitamin K1 orally (n = 88) or 1 mg of vitamin K1 by im injection (n = 88). Vitamin K1 levels were less than 0.05 micrograms/l in cord blood. The mean (range), SEM, mode and median values (micrograms/l) for the infants given oral vitamin K1 were 17.99 (1-56), 1.25, 8 and 15.5 and those for the infants given im vitamin K1 15.83 (2-57), 1.01, 11 and 14, respectively. The t-test showed no significant difference in the mean values (p = 0.09) in the infants given oral or im vitamin K.

In the past, the training of health information professionals (HIPs) has focussed almost exclusively on technical matters, the concerns of software developers and purveyors have essentially centred on security and functionality, and health care providers have mainly worried about costs and efficiency. This paper outlines some ethical threats that are ignored by such a purely technical focus and argues that because of the increasing globalization of health care delivery through e-Health, and because of the international threats to confidentiality posed by legislation such as the US Patriot Act, the health informatics community should pursue a project of global certification for HIPs that includes information ethics as an integral component. It also argues that a corresponding certification process for health care institutions and software developers should be initiated.

With steroid therapy, it is commonly considered that prognosis is good in giant cell arteritis. However serious or even fatal complications may occur. Here we report the case of a patient who developed fatal giant cell arteritis with severe stenosis of both vertebral arteries and right carotid siphon. Several similar cases have been reported in the literature. Initially diagnosis may be difficult because neurological manifestations are intermittent and classical signs of giant cell arteritis may be lacking. In such condition the reason of poor outcome is unknown and therapy remains empiric.

PURPOSE: Arterial spin-labeling (ASL) perfusion MRI, a noninvasive method of assessing cerebral blood flow, is becoming a diagnostic tool of epilepsy. This study was undertaken to evaluate the diagnostic validity of ASL in patients with status epilepticus (SE) in a periictal state.METHOD: Twenty cases with SE were studied. Patients were imaged at a 3T MRI including ASL and diffusion-weighted imaging (DWI), and were also examined using electroencephalography (EEG). The abnormal findings of ASL were compared with those obtained from DWI and EEG.RESULT: Focal hyperperfusion was found in the cortical territory of 13 cases (65%). In 10 of those 13 cases, the ASL hyperperfusion region corresponded to DWI high intensity and EEG abnormality. Two cases showed hyperperfusion corresponding to EEG abnormalities in ASL despite the absence of high intensity in DWI. The remaining single case showed hyperperfusion in ASL despite the absence of high intensity in DWI and EEG abnormalities. Hyperperfusion in the subcortical territory was observed in the ipsilateral thalamus in three cases and in the contralateral cerebellum in one case.CONCLUSION: Our results suggest that ASL is a useful tool to diagnose status epilepticus and localization of the epilepsy focus.

OBJECTIVE: To evaluate the safety, tolerability, immunogenicity, and viral shedding profiles of a recombinant, live, attenuated human parainfluenza virus type 3 (HPIV3) vaccine, rHPIV3cp45, in healthy HPIV3-seronegative infants 6 to <12 months of age.METHODS: In this double-blind, multicenter study, subjects were randomized 2:1 to receive a 10(5)TCID(50) dose of rHPIV3cp45 (n=20) or placebo (n=10) at enrollment and at 2 and 4 months after the first dose. Blood for evaluation of antibody to HPIV3 was collected at baseline and approximately 1 month after each dose. Solicited adverse events (SEs) and unsolicited adverse events (AEs) were collected on days 0-28 after each dose. Nasal wash samples for vaccine virus shedding were collected 3 times after each dose (7-10, 12-18, and 28-34 days post dose) and at unscheduled illness visits. Subjects were followed for 180 days after the last dose.RESULTS: Vaccine virus was shed by 85% of vaccine recipients after dose 1, by 1 subject after dose 2, and was not shed by any subject after dose 3. The highest titer of shed virus was detected on day 7 after dose 1. The attenuation phenotype and the genotype of the vaccine virus were stable in shed virus. Seroresponse (? 4-fold rise in HPIV3 antibody from baseline) occurred in 61% of subjects after dose 1 and in 77% after dose 3. Either seroresponse or shedding occurred in 95% of vaccine subjects. Adverse events were similar in vaccine and placebo recipients.CONCLUSION: The safety, shedding, and immunogenicity profiles of rHPIV3cp45 in HPIV3-seronegative infants 6 to <12 months of age support further development of this vaccine.

PURPOSE: The purpose of this study was to identify the effects of hand acupuncture therapy on sleep quality by means of a sleep questionnaire, polysomnography and a cerebral blood flow test in 30-59 year old adults.METHODS: The study was a sham controlled design. Twenty-two adults were assigned to the pellet stimulating group (11) or sham group (11). The pellet stimulating group received hand acupuncture therapy using New Seoam Press Pellets number 1 for 4 weeks. On the other hand, the sham group used the same Adhesive tape in terms of shape, size and quality as New Seoam Press Pellets number 1 for 4 weeks. A Transcranial Doppler Ultrasonography and Carotid Duplex Ultrasonography examination were used for evaluating cerebral blood flow. Data was analyzed using the SPSS 12.0 version program with chi(2)-test, Fisher's exact test and Mann Whitney U-test.RESULTS: In the pellet stimulating group, subjective sleep quality significantly improved more than that of the sham group. Among the sleep indices of the polysomnography, total sleep time and sleep latency of the sham group significantly improved. The cerebral blood flow test didn't show any differences.CONCLUSION: These results suggest that hand acupuncture therapy is effective for subjective sleep improvement only, not polysomnographical sleep indices and cerebral blood flow.

16 patients developed locking of the M.P. joint of the thumb as the result of a hyperextension injury. Four were successfully treated by manipulation under an intra-articular injection of a local anaesthetic, while the remaining twelve required open reduction. All were examined 4 to 48 months after treatment (average 12 months). The torn palmar plate and the accessory collateral ligament, which acted as a constrictive band, were trapped on the prominence of the radial condyle of the metacarpal. Four of the twelve surgically-treated patients had a deformity which we believe was congential: a transverse groove over the radial condyle of the metacarpal. No patients had a recurrence of the locked joint.

BACKGROUND: The Internet serves as an important resource for adult cancer patients, but little is known about Internet use among adolescent and young adults (AYA) with cancer. The aims of this study were to describe (1) cancer-specific websites which AYA with cancer visit and (2) Internet features desired by AYA on cancer-specific websites and how many current AYA cancer websites contain these features.PROCEDURE: Individual phone interviews were conducted with a convenience sample of 16 AYA with cancer from across North America in June 2005. Content analysis of these interviews were coded and validated for desired website features. Current AYA cancer websites were identified on the Internet and the features on these sites were compared to the features desired by our sample.RESULTS: Favorite websites visited by AYA with cancer (cancer-related and unrelated) were identified along with current Internet use. Twenty-one distinct cancer website features desired by AYA with cancer were described. Twenty-seven unique AYA cancer websites were found on the Internet during May-June 2006. Each site contained 7.7 (SD = 2.7) of the 21 features identified by participants as desirable, but the highest ranked features did not occur in the majority of these websites.CONCLUSIONS: AYA with cancer indicate that they prefer to visit cancer websites that contain cancer-related information, provide the ability to chat with AYA with cancer, and offer some type of game. Although many websites exist for AYA with cancer, few individual sites contain the web features identified as most desired by AYA with cancer.

Chronic blockade of the renin angiotensin system became possible when orally active inhibitors of angiotensin converting enzyme, the enzyme which catalyzes the transformation of angiotensin I into angiotensin II, were synthetized. Two compounds, captopril and enalapril, have been investigated in clinical studies. The decrease of the pressor response to exogenous angiotensin I and of the circulating levels of angiotensin II following administration of these inhibitors has been demonstrated to be directly related to the degree of suppression of plasma angiotensin converting enzyme activity. These inhibitors have been shown to normalize blood pressure alone in some hypertensive patients whereas in many others, satisfactory blood pressure control can be achieved only after the addition of a diuretic. Captopril and enalapril also markedly improve cardiac function of patients with chronic congestive heart failure. Chronic blockade of the renin angiotensin system has therefore provided an interesting new approach to the treatment of clinical hypertension and heart failure.

A new colimetric assay for serum monoamine oxidase and clinical findings based on this method are described. This rapid, precise procedure employs 1-[(4-aminomethylphenyl)azol]-2-naphthol as a substrate. The enzymatically generated 1-[(4-formyl phenyl)azo]-2-naphthol is extracted into cyclohexane to form a colored solution whose absorbance is determined at 500 nm. The method proved to be extremely simple, and the results obtained correlated well with those given by the standard method of McEwen.

Behavioural studies indicate that cannabinoid receptors are implicated in cocaine addiction. The synaptic underpinning of cocaine-cannabinoid receptor interaction is however, obscure. We have studied electrophysiologically the sensitivity of cannabinoid receptors modulating synaptic transmission in the striatum of rats exposed to cocaine. One-day treatment with cocaine did not modify the synaptic response to HU210, a cannabinoid CB1 receptor agonist. Seven days cocaine-treatment, conversely, caused conditioned place preference, and sensitized striatal GABAergic synapses to the presynaptic effect of cannabinoid CB1 receptor stimulation. The cannabinoid receptor-induced modulation of glutamate transmission was unaltered by cocaine. Furthermore, the effects of chronic cocaine on cannabinoid-mediated regulation of striatal GABA synapses were attenuated one week after the discontinuation of cocaine, and absent two weeks later, indicating the progressive reversibility of the adaptations of cannabinoid system during abstinence of drug consumption. Our data support the concept that modulation of cannabinoid receptors might be useful against drug abuse.

Duodenal perforation may occur at the time of insertion of a biliary endoprosthesis or following endoscopic manipulation of such a stent. The possibility of perforation as a late sequela of stent migration, after percutaneous placement of an endoprosthesis, however, has not been emphasized. In the authors' experience with a 12-F soft-stent endoprosthesis, duodenal perforation occurred in four of 50 patients following initially satisfactory stent placement. One intraperitoneal perforation necessitated immediate surgical intervention. The three retroperitoneal perforations were treated conservatively.

Whether species can respond evolutionarily to current climate change is crucial for the persistence of many species. Yet, very few studies have examined genetic responses to climate change in manipulated experiments carried out in natural field conditions. We examined the evolutionary response to climate change in a common annelid worm using a controlled replicated experiment where climatic conditions were manipulated in a natural setting. Analyzing the transcribed genome of 15 local populations, we found that about 12% of the genetic polymorphisms exhibit differences in allele frequencies associated to changes in soil temperature and soil moisture. This shows an evolutionary response to realistic climate change happening over short-time scale, and calls for incorporating evolution into models predicting future response of species to climate change. It also shows that designed climate change experiments coupled with genome sequencing offer great potential to test for the occurrence (or lack) of an evolutionary response.

We introduce a new extension of image correlation spectroscopy (ICS) and image cross-correlation spectroscopy (ICCS) that relies on complete analysis of both the temporal and spatial correlation lags for intensity fluctuations from a laser-scanning microscopy image series. This new approach allows measurement of both diffusion coefficients and velocity vectors (magnitude and direction) for fluorescently labeled membrane proteins in living cells through monitoring of the time evolution of the full space-time correlation function. By using filtering in Fourier space to remove frequencies associated with immobile components, we are able to measure the protein transport even in the presence of a large fraction (>90%) of immobile species. We present the background theory, computer simulations, and analysis of measurements on fluorescent microspheres to demonstrate proof of principle, capabilities, and limitations of the method. We demonstrate mapping of flow vectors for mixed samples containing fluorescent microspheres with different emission wavelengths using space time image cross-correlation. We also present results from two-photon laser-scanning microscopy studies of alpha-actinin/enhanced green fluorescent protein fusion constructs at the basal membrane of living CHO cells. Using space-time image correlation spectroscopy (STICS), we are able to measure protein fluxes with magnitudes of mum/min from retracting lamellar regions and protrusions for adherent cells. We also demonstrate the measurement of correlated directed flows (magnitudes of mum/min) and diffusion of interacting alpha5 integrin/enhanced cyan fluorescent protein and alpha-actinin/enhanced yellow fluorescent protein within living CHO cells. The STICS method permits us to generate complete transport maps of proteins within subregions of the basal membrane even if the protein concentration is too high to perform single particle tracking measurements.

Several multiple, large-scale, genetic studies on autoimmune-disease-associated SNPs have been reported recently: peptidylarginine deiminase type 4 (PADI4) in rheumatoid arthritis (RA); solute carrier family 22 members 4 and 5 (SLC22A4 and 5) in RA and Crohn's disease (CD); programmed cell death 1 (PDCD1) in systemic lupus erythematosus (SLE), type 1 diabetes mellitus (T1D), and RA; and protein tyrosine phosphatase nonreceptor type 22 (PTPN22) in T1D, RA, and SLE. Because these reports on association were not always evaluated in multiple ethnic groups and because ethnic difference in allele frequency of the variants has been also reported, we investigated allele frequencies of nine SNPs in four autoimmune-disease-associated loci in Caucasian, African-descent, and Japanese populations. Although SNPs in PADI4 had similar allele frequency among three groups [maximal difference 11%; (P >0.05)], the other three loci revealed statistically significant allele frequency differences (maximal difference 39% (P <0.00001), 13% (P <0.00001), and 8% (P <0.00001) in SLC22A4, PDCD1, and PTPN22, respectively). Of note, three SNPs in the three loci that had allele frequency more than 8% in the Caucasian population were either not polymorphic at all or extremely rare in the Japanese population. Our data suggest that ethnic variations of polymorphisms should be evaluated in detail, and differences should be incorporated into investigations of susceptibility variants for common diseases.

Clinical antimicrobial susceptibility breakpoints are used to predict the clinical outcome of antimicrobial treatment. In contrast, microbiologic breakpoints are used to identify isolates that may be categorized as susceptible when applying clinical breakpoints but harbor resistance mechanisms that result in their reduced susceptibility to the agent being tested. Currently, the National Committee for Clinical Laboratory Standards (NCCLS) guidelines utilize clinical breakpoints to characterize the activity of the fluoroquinolones against Streptococcus pneumoniae. To determine whether levofloxacin breakpoints can identify isolates that harbor recognized resistance mechanisms, we examined 115 S. pneumoniae isolates with a levofloxacin MIC of >2 mg/mL for first-step parC mutations. A total of 48 (59%) of 82 isolates with a levofloxacin MIC of 2 mg/mL, a level considered susceptible by NCCLS criteria, had a first-step mutation in parC. Whether surveillance programs that use levofloxacin data can effectively detect emerging resistance and whether fluoroquinolones can effectively treat infections caused by such isolates should be evaluated.

Laser excitation of aqueous solutions of fenofibric acid (FA) at pH 7.4 show the formation of two reaction intermediates, the triplet state and the hydrated electron. The former is longer lived in water than in acetonitrile; its anionic form decays irreversibly by decarboxylation to give a carbanion that protonates before or after rearrangement. Several spectroscopic and quenching studies suggest that in aqueous media the triplet state of FA has a pi,pi* character, in comparison with an n,pi* character in organic media. Further, the known chemistry of the triplet, including decarboxylation and hydrogen abstraction, occurs predominantly from the n,pi* state, and as a consequence, activation energies are higher when the lowest triplet has a pi,pi* character. Photoionization is more important in aqueous than in organic media and involves a biphotonic process. Hydrated electrons are trapped by FA, leading to the corresponding ketyl radical after protonation.

The Turing instability in the reaction-diffusion system is a widely recognized mechanism of the morphogen gradient self-organization during the embryonic development. One of the essential conditions for such self-organization is sharp difference in the diffusion rates of the reacting substances (morphogens). In classical models this condition is satisfied only for significantly different values of diffusion coefficients which cannot hold for morphogens of similar molecular size. One of the most realistic explanations of the difference in diffusion rate is the difference between adsorption of morphogens to the extracellular matrix (ECM). Basing on this assumption we develop a novel mathematical model and demonstrate its effectiveness in describing several well-known examples of biological patterning. Our model consisting of three reaction-diffusion equations has the Turing-type instability and includes two elements with equal diffusivity and immobile binding sites as the third reaction substance. The model is an extension of the classical Gierer-Meinhardt two-components model and can be reduced to it under certain conditions. Incorporation of ECM in the model system allows us to validate the model for available experimental parameters. According to our model introduction of binding sites gradient, which is frequently observed in embryonic tissues, allows one to generate more types of different spatial patterns than can be obtained with two-components models. Thus, besides providing an essential condition for the Turing instability for the system of morphogen with close values of the diffusion coefficients, the morphogen adsorption on ECM may be important as a factor that increases the variability of self-organizing structures.

The renowned medieval Persian physician Rhazes was an early proponent of experimental medicine. Rhazes made fundamental and enduring contributions to medicine and to other scientific fields. He wrote over 200 scientific books, more than half of which concerned medicine. He was well versed in Persian, Greek, and Indian medical knowledge, and made numerous contributions to the medical field through his own observations and discoveries. He was also a pioneer in the field of neurosurgery and, as he was predominantly a pediatrician, he dealt with the subject of hydrocephalus. A large part of his medical tome, al-Hawi, deals with head-related disorders including the hydrocephalus. Although he did not introduce novel concepts of hydrocephalus and its management, by combining the different approaches of experienced scholars he endeavored to improve treatment and knowledge of this problematic disease.

Cytochrome b-561 in chromaffin granules interacts with antimycin and its alpha-peak shifts 1 nm towards red. When chromaffin granules were treated with Triton X-100 antimycin no effect was observed. Cytochrome b-561 is located in the plasma membrane isolated from the chromaffin cells. The plasma membrane b-561 does not seem to interact with antimycin. A number of NADH or NADPH (acceptor) oxidoreductase activity has been observed in isolated plasma membrane providing clues to the origin of plasma membrane dehydrogenase. The possible role of cytochrome b-561 in secretory granules other than its accredited energy conserving electron transport property is projected.

BACKGROUND:  A randomized controlled trial of screening, brief intervention, and referral to treatment (SBIRT) among at-risk (based on average number of drinks per week and drinks per drinking day) and dependent drinkers was conducted in an emergency department (ED) among 446 patients 18 and older in Sosnowiec, Poland.METHODS: Patients were recruited over a 23-week period (4:00 pm to 12:00 midnight) and randomized to 1 of 3 conditions: screened-only (n = 147), assessed (n = 152), and intervention (n = 147). Patients in the assessed and intervention conditions were blindly reassessed via a telephone interview at 3 months, and all 3 groups were assessed at 12 months (screened-only = 92, assessed = 99, and intervention = 87).RESULTS: No difference was found across the 3 conditions in at-risk drinking at 12 months, as the primary outcome variable, or in decrease in the number of drinks per drinking day, with all 3 groups showing a significant reduction in both. Significant declines between baseline and 12 months in secondary outcomes of the RAPS4, number of drinking days per week, and the maximum number of drinks on an occasion were seen only for the intervention condition, and in negative consequences for both the assessment and intervention conditions.CONCLUSIONS: Data suggest that improvements in drinking outcomes found in the assessment condition were not because of assessment reactivity, with both the screened and intervention conditions demonstrating greater (although nonsignificant) improvement than the assessed condition. Only those in the intervention condition showed significant improvement in all outcome variables from baseline to 12-month follow-up. Although group by time interaction effects were not found to be significant, these findings suggest that declines in drinking measures for those receiving a brief intervention can be maintained at long-term follow-up.

UNLABELLED: In 2004, according to socio- demographic criteria and to the improvement in the welfare quality, we incorporated to the portfolio of services of our section a work tool that meant a novel technology; the "telemedicine". The Objective has been to asses the utility of telemedicine in the follow- up of the renal patients, bringing the consultation of nephrology closer to the patient's home as well as the relationship between two welfare levels.MATERIAL AND METHOD: Retrospective and descriptive study of the patients with renal pathology treated in the consultation of telenephrology at our hospital in a period of time of 27 months (November 2004-January 2007). Such study is carried out in primary care centers of our sanitary area (4 centers). The general practician (G.P) starts up the system by elaborating a document of derivation to the consultation of "telenephrology". All this information is included in a computerized data base that arrives via "Intranet" at the Hospital. From the consultation of Telenephrology the question is answered in real- time and through a system of videoconference.RESULTS: A total of 105 first consultations have been made. 52 men and 53 women between 18 and 94 years of age. The diagnoses made in the consultation of Telenephrology have been: HTA (essential and secondary): 90 (85.7%). IRC: 61 (58%). Diabetic Nefropathy: 17 (16%). Renal Polycystic: 3 (2.8%). Urinary Lithiasis: 2 (1.9%). Congenital malformations: 1 (0.95%). Obstructive Nefropathy: 1 (0.95%). Chronic Glomerulonephritis: 6 (5.7%). Urinary infection: 1 (0.95%). Absence of renal pathology: 5 (4.8%). Some of the diagnoses coincide in several patients. The causes of the IRC have been Nephroangioesclerosis: 33. Diabetic Nefropathy: 14. Not drafted: 8. Disease to glomerular: 2. Urinary Lithiasis: 2. Renal Polycystic: 1. Ischemic Nephropathy: 1. 82 out of the 90 patients with HTA had essential arterial hypertension and 8 suffered from secondary HTA. The causes of this were: 5 HTA of parenquimatous renal origin. 2 vasculorrenal HTA and one with a primary hyperaldosteronism. The associated factors of risk to the observed HTA have been: Dyslipemia: 29. Diabetes m?llitus: 29. Hyperuricemia: 11. Obesity: 12.CONCLUSION: The telecare in nephrology is possible promoting also the approach between two welfare levels, without a decrease in the quality of assistance. That way, we can get a lower number of hospital visits and, subsequently, a saving in sanitary transport as well as in hospital consultations.

The effect of DHEA administration on the age-associated decline in immunity against influenza vaccine was studied. Increased humoral response was observed in 16- and 24-month-old mice immunized by live A/PR/8/34 (H1N1) influenza virus following DHEA treatment (a single injection adjacent to immunization). Furthermore, DHEA-treated mice demonstrated increased resistance to postvaccination intranasal challenge with live influenza virus. Thus, DHEA treatment overcomes the age-related defect in the immunity of old mice against influenza.

The effects of dietary protein and fat on renal function-related blood and urine parameters, such as albumin, urinary protein,and inflammatory cytokines were investigated in adriamycin- (ADR) induced nephrotic syndrome rats. ADR (2 mg/kg BW) was injected i.p. weekly for six weeks to develop nephrotic syndrome; thereafter rats were fed low-protein/high-fat (LPHF) or high-protein/low-fat (HPLF) diets for five weeks. Renal function-related blood and urine parameters were measured before and after dietary intervention. Serum levels of albumin, TG, and creatinine were significantly higher in the LPHF group than in the HPLF group. Serum levels of albumin were low and urinary protein excretion protein was high in HPLF group. BUN and UUN levels were higher in the HPLF group than in the LPHF. Urinary excretion of creatinine was significantly higher in the HPLF group than in the LPHF group. Serum inflammatory cytokine levels did not differ between the two groups, however the levels of IL-6, TNF-á, and IL-13 in splenocyte supernatants were significantly higher in the LPHF group than in the HPLF group. We confirmed that protein and fat contents in diet affect renal function-related blood and urine parameters and splenocyte inflammatory cytokine levels in ADR-induced nephrotic syndrome rats.

The long-term effects of the R-irradiation of D. melanogaster at the 1-hour egg stage with the dosages of 0.25, 0.50, 0.75, 1.0, 2.0 and 4.0 Gy were investigated. DNA samples were isolated from whole 5-6-days adult males. The aliquots of DNA were digested by S1-nuclease. Preimaginal stage lethality increased with irradiation dose increasing. At the same time, decrease in imaginal LS (life span) was observed after irradiation with the greatest dose (4 Gy) only. Moreover, hormesis by LS has revealed: in males irradiation with 0.25, 0.75 and 1 Gy increased the mean LS, and with 0.25 and 0.5 Gy caused the maximum LS; in females exposures with 0.25, 0.75 and 2 Gy increased the maximum LS. The densitometric assay of DNA electrophoregrams showed decrease by 39.2% of the part of high-molecular-weight DNA in control as a result of S1-nuclease action. Samples of DNA from the irradiated flies were more stable to enzyme action. The higher stability of DNA originated from the irradiated flies could be the result of reparation system activation. Ultrastructural changes induced at the egg stage by irradiation at the dose of 0.75 Gy testify the increased transcriptional activity of the brain cells.

BACKGROUND AND AIM: Our aim was to assess adequacy and diagnostic accuracy of endoscopic ultrasound-fine needle aspiration (EUS-FNA) specimens with or without rapid on-site evaluation (ROSE) from pancreatic, upper gastrointestinal tract (UGIT) and adjacent masses.METHOD: A retrospective cohort study based on patients' files who underwent EUS-FNA in Galilee Medical Center in a 4 years period. Number of needle passes, repeated EUS and ROSE effect on tissue adequacy and diagnostic accuracy were reported.RESULTS: One-hundred sixty-one patients were included. Ninety-three patients (57.7%) underwent EUS-FNA without ROSE (group A) compared to 68 patients (42.3%) with ROSE (group B). The most common location was in the pancreas (55% in group A vs 81% in group B). Addition of ROSE yielded a significantly higher specimen adequacy (65% in group A vs 92.6% in group B (Chi-Square < 0.0001, OR 6.72, 95% CI 2.45-18.38). The matching rate (accuracy) between ROSE diagnosis and final histopathological diagnosis was noticed in 61 out of 68 patients (89.7%, 95% CI 0.7993-0.9576). The Kappa coefficient correlations of matching rate between ROSE and final histopathological diagnosis of all lesion and in pancreatic lesions were 0.7558, (95% CI 0.625-0.887) and 0.7814, (95% CI 0.639-0.924), respectively.CONCLUSIONS: EUS-FNA with ROSE significantly improve specimen adequacy and was associated with high diagnostic accuracy.

Sex chromosomes in mammals are about 300 million years old and typically have a highly degenerated Y chromosome. The sex chromosomes in the dioecious plant Silene latifolia in contrast, represent an early stage of evolution in which functional X-Y gene pairs are still frequent. In this study, we characterize a novel tandem repeat called TRAYC, which has accumulated on the Y chromosome in S. latifolia. Its presence demonstrates that processes of satellite accumulation are at work even in this early stage of sex chromosome evolution. The presence of TRAYC in other species of the Elisanthe section suggests that this repeat had spread after the sex chromosomes evolved but before speciation within this section. TRAYC possesses a palindromic character and a strong potential to form secondary structures, which could play a role in satellite evolution. TRAYC accumulation is most prominent near the centromere of the Y chromosome. We propose a role for the centromere as a starting point for the cessation of recombination between the X and Y chromosomes.

BACKGROUND: This study aimed to evaluate the vitamin D status in an adult population across latitudinal gradient and to investigate its possible associations with certain cardiometabolic risk factors.METHODS: A total of 1406 healthy subjects aged 19-60 years were randomly selected from six regions of Iran across latitudinal gradient from 29° N to 37.5° N. Anthropometric and biochemical assessments were performed. The combination of high body mass index (>25 kg/m2), low high-density lipoprotein cholesterol (< 40 mg/dl in males and < 50 mg/dl in females) and high triglycerides (> 150 mg/dl) was defined as cardiometabolic risk factors.RESULTS: The mean concentration of serum 25-hydroxycalciferol (25(OH)D) was 26.8±17.7 nmol/l. There were no significant differences in the mean serum 25(OH)D levels among different latitudes. Undesirable vitamin D status (deficiency and insufficiency) was found in 90.7% of the subjects. After adjustment for age and gender, the association between weight status and serum 25(OH)D was significant ( p< 0.04, odds ratio:1.49; confidence interval: 1.01-2.19). The prevalence of cardiometabolic risk factors among the subjects with serum 25(OH)D less than 27.5 nmol/l was significantly higher than those with serum calcidiol concentrations above 27.5 nmol/l (13.3% vs. 10.0%, p = 0.033).CONCLUSION: Undesirable vitamin D status is highly prevalent among Iranian adults of both sexes irrespective of latitude and even in sunny regions. The occurrence of cardiometabolic risk factors was significantly higher in those subjects with circulating calcidiol concentrations below 27.5 nmol/l.

CONCLUSIONS: The statistically significant correlations between vestibular evoked myogenic potential (VEMP) parameters and age may be due to hair cell loss of the otolith organ and/or to degenerative changes of the vestibular neural pathway. These findings indicate that age should be taken into account when interpreting VEMP results. It is also important to determine a standard method for performing VEMP and a universal index for comparison among laboratories.OBJECTIVES: VEMP, which measures the surface electric potential from the cervical muscle evoked by sufficiently loud sounds, is a useful tool to evaluate vestibule-colic reflex function. We have assayed the effect of age on VEMP results.SUBJECTS AND METHODS: After excluding subjects with a previous history of dizziness, middle ear pathology, or other inner ear symptoms, a total of 97 healthy volunteers (194 ears) were included. All VEMP parameters were analyzed to find differences related to side and gender, as well as the relationship between age and each VEMP parameter.RESULTS: Age was correlated with all VEMP parameters. Latency of p13, n23 showed a negative correlation and amplitude of p13-n23 showed a positive correlation with age. Differences between the right and left sides were not significant.

Intrinsic disorder is common in nature and has been studied to play important biological roles in bacterial effectors. However, disorder in oomycete RxLR effectors has not been investigated previously and the roles are unknown. Our results of PONDR VL-XT disorder analysis showed that predicted oomycete RxLR effectors were significantly more disordered than other effectors and secretome. The distribution of disorder content presented preference that RxLR-dEER regions were enriched in disordered residues, suggesting potential role of disorder in effector translocation. In contrast, the disorder content was depleted in the C-terminal regions, especially for W/Y/L motifs. We also found that around 42 % of putative RxLR proteins were predicted to contain at least one á-helix-forming molecular recognition feature (á-MoRF), and most á-MoRFs were located in the C-terminal regions. Furthermore, both of the disorder mutants of PsAvh18 and PcAvh207 lost the cell death-inducing activity, indicating the potential important role of disordered structure in RxLR effector function. Overall, these results demonstrate that intrinsic disorder is a common characteristic of oomycete RxLR proteins, and we postulate that such structure feature may be important for effector translocation or function. This study extends our understanding of RxLR effectors in protein structures, and opens up new directions to explore novel mechanisms of oomycete RxLR effectors.

Small cell transformation is a rare but well recognised mechanism of acquired resistance to EGFR-TKI therapy in EGFR-mutated NSCLC, but optimal drug therapy thereof is unknown. Nivolumab has demonstrated activity in relapsed de novo small cell lung cancer in early phase trials. Here, we report a case of transformed EGFR-mutant SCLC treated with nivolumab with no benefit.