Identification of two distinct regions within the adenovirus minimal origin of replication that are required for adenovirus type 4 DNA replication in vitro.
The adenovirus type 4 origins of replication are located at each end of the linear, protein-linked viral DNA molecule and consist of the terminal 18 bp of the viral genome. The sequence of the first 8 bp of the viral genome varies among different adenovirus serotypes, but the sequence from bp 9 to 18 is conserved in all human serotypes, suggesting that it may be of critical importance to origin function. Using an in vitro system in which purified fractions or crude extracts of adenovirus type 4-infected HeLa cells can support initiation and elongation on linearized plasmid templates containing cloned origin sequences, we examined the effect of single base changes in positions 9 to 18 of the adenovirus origin on DNA replication in vitro. Changes in positions 12 to 16 have little effect, whereas alterations at positions 9, 10, 11, 17, and 18 all reduce the efficiency of initiation of DNA replication by between 50 and 90%. Our results show that the region from bp 9 to 18 contains two sets of bases essential for DNA replication which are separated by 5 bp in which single base changes can be accommodated. The likely role of the region from bp 9 to 18 as containing the recognition sequence for a DNA-protein interaction essential for viral DNA replication is discussed.


Short-term meditation increases network efficiency of the anterior cingulate cortex.
Previous studies have found that short-term integrative body-mind training (IBMT) has positive effects on the brain structure and function in the anterior cingulate cortex. Here, we determined whether 11 h of IBMT alters topological properties of the anterior cingulate cortex in brain functional networks. We applied network analysis to resting-state functional connectivity between 90 cortical and subcortical regions before and after IBMT and relaxation training. The results demonstrated a significant increase in the network efficiency and connectivity of the anterior cingulate cortex after IBMT, but not after relaxation training. These findings indicated that the change in network topology might occur by altering the brain or psychological state. IBMT might be an intervention tool for improvement of self-regulation.


Adverse changes in mood and cognitive performance of house officers after night duty.
The effects of long hours of work by junior doctors are the subject of growing concern. Experimental investigations of the effects of night duty on young doctors are few and have given inconclusive results. To measure the effects of long hours of work and reduced sleep on cognitive performance and mood 20 house officers (14 men and six women; mean age 25, range 24-35) were examined for 35 minutes in one session towards the end of a normal working day and in a second session at the same time after working for up to 31 continuous hours with reduced sleep. The order of the sessions was counterbalanced across the subjects. Each session comprised a series of cognitive tests: choice reaction time, vigilance reaction time, and haptic sorting tests and completion of a profile of mood states and a general questionnaire. After night duty there was a significant slowing in cognitive processing together with a decline in reaction times in the vigilance test. Loss of sleep contributed only to increased variability in the choice reaction time. Significant deleterious changes in mood after night duty occurred in all the mood scales after night duty. Continuous working may adversely affect the cognitive function and mood to the detriment of the welfare of doctors and their patients.


Prevalence of bovine subclinical endometritis 4h after insemination and its effects on first service conception rate.
The objective of this study was to investigate the prevalence of subclinical endometritis 4h after AI and its effect on first service conception rate (FSCR) in dairy cows. A total of 201 Holstein-Friesian cows with no signs of clinical endometritis were examined 4h after first AI for signs of subclinical endometritis. Endometrial samples were collected from the uterus using the cytobrush technique. The proportion of polymorphonuclear cells (PMN) in the cytological sample was used to characterize an inflammation of the endometrium. Cows were categorized into three groups according to the proportion of PMN in the sample. Cows with 0% PMN (n=115) were assigned to group Zero, cows with >0-15% PMN (n=59) to group Medium, and cows with >15% PMN (n=27) to group High. Pregnancy diagnosis was performed between days 38-44 after AI by palpation of the uterus and its contents per rectum. The FSCR was significantly higher in group Medium than in groups Zero and High (57.6% vs. 39.1% and 29.6%). Statistical analysis revealed an interaction between parity and PMN group. Primiparous cows were at higher risk of being classified into group Medium than multiparous cows (OR=2.27, P=0.01). Primiparous cows in group Zero had lower odds of pregnancy after first AI than primiparous cows in group Medium (OR=0.3, P=0.02). A comparison with cows that were not examined for subclinical endometritis showed that the collection of endometrial samples itself had no effect on FSCR.


Health systems' responses to the roll-out of antiretroviral therapy (ART) in India: a comparison of two HIV high-prevalence settings.
The government of India launched the free anti-retroviral therapy (ART) initiative in 2004 and the programme has since scaled up expansion in a phased manner. Programme authorities acknowledge problems in scale-up, yet discussions have been restricted to operational constraints, with little consideration for how local health system responses to HIV/AIDS influence the delivery of ART. This paper draws on the perspectives of key informants and people living with HIV (PLHIV) to compare delivery of ART in two ART centres in the States of Maharashtra and Andhra Pradesh at two distinct points of time. In 2005, data were collected through key informant interviews (KIIs) using interview guides and a survey of PLHIV using a semi-structured interview schedule. Differences were observed in the functioning and resources of the two centres, indicating different levels of preparedness which in turn influenced PLHIV's pathways in accessing ART. We examine these differences in the light of programme leadership, ownership and the roles of public, private and non-governmental organisation actors in HIV care. KIIs conducted during a follow-up visit in 2009 focused on changes in ART delivery. Many operational problems had been resolved; however, new challenges were emerging as a result of the increased patient load. An understanding of how ART programmes evolve within local health systems has bearing on future developments of the ART programme and must include a consideration of the wider socio-political environment within which HIV programmes are embedded.


Complete Genome Sequencing and Comparative Genome Characterization of Lactobacillus johnsonii ZLJ010, a Potential Probiotic With Health-Promoting Properties.
Lactobacillus johnsonii ZLJ010 is a probiotic strain isolated from the feces of a healthy sow and has putative health-promoting properties. To determine the molecular basis underlying the probiotic potential of ZLJ010 and the genes involved in the same, complete genome sequencing and comparative genome analysis with L. johnsonii ZLJ010 were performed. The ZLJ010 genome was found to contain a single circular chromosome of 1,999,879 bp with a guanine-cytosine (GC) content of 34.91% and encoded 18 ribosomal RNA (rRNA) genes and 77 transfer RNA (tRNA) genes. From among the 1,959 protein coding sequences (CDSs), genes known to confer probiotic properties were identified, including genes related to stress adaptation, biosynthesis, metabolism, transport of amino acid, secretion, and the defense machinery. ZLJ010 lacked complete or partial biosynthetic pathways for amino acids but was predicted to compensate for this with an enhanced transport system and some unique amino acid permeases and peptidases that allow it to acquire amino acids and other precursors exogenously. The comparative genomic analysis of L. johnsonii ZLP001 and seven other available L. johnsonii strains, including L. johnsonii NCC533, FI9785, DPC6026, N6.2, BS15, UMNLJ22, and PF01, revealed 2,732 pan-genome orthologous gene clusters and 1,324 core-genome orthologous gene clusters. Phylogenomic analysis based on 1,288 single copy genes showed that ZLJ010 had a closer relationship with the BS15 from yogurt and DPC6026 from the porcine intestinal tract but was located on a relatively standalone branch. The number of clusters of unique, strain-specific genes ranged from 42 to 185. A total of 219 unique genes present in the genome of L. johnsonii ZLJ010 primarily encoded proteins that are putatively involved in replication, recombination and repair, defense mechanisms, transcription, amino acid transport and metabolism, and carbohydrate transport and metabolism. Two unique prophages were predicted in the ZLJ010 genome. The present study helps us understand the ability of L. johnsonii ZLJ010 to better adapt to the gut environment and also its probiotic functionalities.


Anatomy of proximal attachment, course, and innervation of hamstring muscles: a pictorial essay.
Hamstring injuries are very common in sports medicine. Knowing their anatomy, morphology, innervation, and function is important to provide a proper diagnosis, treatment as well as appropriate prevention strategies. In this pictorial essay, based on anatomical dissection, the detailed anatomy of muscle-tendon complex is reviewed, including their proximal attachment, muscle course, and innervation. To illustrate hamstrings' role in the rotational control of the tibia, the essay also includes the analysis of their biomechanical function.Level of evidence V (expert opinion based on laboratory study).


Method of Measuring Diffuse RMS Granularity.
The rms granularity values normally produced by an optical scanner are in terms of semispecular instrument density. It is shown that these semispecular values can be converted to a diffuse density basis by dividing by a quantity q that is defined as the ratio of the instrument density of the sample to the diffuse density. The q factor has been measured by two methods, one of which is convenient for use in the routine measurement of diffuse granularity with existing equipment. It has been found that, except at very low density levels, the q of a given material varies only slightly as the diffuse density changes. It does, however, increase significantly as the numerical aperture of the optical system decreases. When a range of samples is measured, maximum values of q occur at moderate values of sample granularity.


Functional and prognostic relevance of the homeobox protein MSX2 in malignant melanoma.
The homeobox containing transcription factor MSX2 is a key regulator of embryonic development and has been implicated to have a role in breast and pancreatic cancer. Using a selection of two- and three-dimensional in vitro assays and tissue microarrays (TMAs), the clinical and functional relevance of MSX2 in malignant melanoma was explored. A doxycyline-inducible over-expression system was applied to study the relevance of MSX2 in vitro. For TMA construction, tumour material from 218 melanoma patients was used. Ectopic expression of MSX2 resulted in the induction of apoptosis and reduced the invasive capacity of melanoma cells in three-dimensional culture. MSX2 over-expression was shown to affect several signalling pathways associated with cell invasion and survival. Downregulation of N-Cadherin, induction of p21 and inhibition of both BCL2 and Survivin were observed. Cytoplasmic MSX2 expression was found to correlate significantly with increased recurrence-free survival (P=0.008). Nuclear expression of MSX2 did not result in significant survival correlations, suggesting that the beneficial effect of MSX2 may be independent of its DNA binding activity. MSX2 may be an important regulator of melanoma cell invasion and survival. Cytoplasmic expression of the protein was identified as biomarker for good prognosis in malignant melanoma patients.


Dynamics of protein folding: probing the kinetic network of folding-unfolding transitions with experiment and theory.
The problem of spontaneous folding of amino acid chains into highly organized, biologically functional three-dimensional protein structures continues to challenge the modern science. Understanding how proteins fold requires characterization of the underlying energy landscapes as well as the dynamics of the polypeptide chains in all stages of the folding process. In recent years, important advances toward these goals have been achieved owing to the rapidly growing interdisciplinary interest and significant progress in both experimental techniques and theoretical methods. Improvements in the experimental time resolution led to determination of the timescales of the important elementary events in folding, such as formation of secondary structure and tertiary contacts. Sensitive single molecule methods made possible probing the distributions of the unfolded and folded states and following the folding reaction of individual protein molecules. Discovery of proteins that fold in microseconds opened the possibility of atomic-level theoretical simulations of folding and their direct comparisons with experimental data, as well as of direct experimental observation of the barrier-less folding transition. The ultra-fast folding also brought new questions, concerning the intrinsic limits of the folding rates and experimental signatures of barrier-less "downhill" folding. These problems will require novel approaches for even more detailed experimental investigations of the folding dynamics as well as for the analysis of the folding kinetic data. For theoretical simulations of folding, a main challenge is how to extract the relevant information from overwhelmingly detailed atomistic trajectories. New theoretical methods have been devised to allow a systematic approach towards a quantitative analysis of the kinetic network of folding-unfolding transitions between various configuration states of a protein, revealing the transition states and the associated folding pathways at multiple levels, from atomistic to coarse-grained representations. This article is part of a Special Issue entitled: Protein Dynamics: Experimental and Computational Approaches.


Genomes of the parapoxviruses ORF virus and bovine papular stomatitis virus.
Bovine papular stomatitis virus (BPSV) and orf virus (ORFV), members of the genus Parapoxvirus of the Poxviridae, are etiologic agents of worldwide diseases affecting cattle and small ruminants, respectively. Here we report the genomic sequences and comparative analysis of BPSV strain BV-AR02 and ORFV strains OV-SA00, isolated from a goat, and OV-IA82, isolated from a sheep. Parapoxvirus (PPV) BV-AR02, OV-SA00, and OV-IA82 genomes range in size from 134 to 139 kbp, with an average nucleotide composition of 64% G+C. BPSV and ORFV genomes contain 131 and 130 putative genes, respectively, and share colinearity over 127 genes, 88 of which are conserved in all characterized chordopoxviruses. BPSV and ORFV contain 15 and 16 open reading frames (ORFs), respectively, which lack similarity to other poxvirus or cellular proteins. All genes with putative roles in pathogenesis, including a vascular endothelial growth factor (VEGF)-like gene, are present in both viruses; however, BPSV contains two extra ankyrin repeat genes absent in ORFV. Interspecies sequence variability is observed in all functional classes of genes but is highest in putative virulence/host range genes, including genes unique to PPV. At the amino acid level, OV-SA00 is 94% identical to OV-IA82 and 71% identical to BV-AR02. Notably, ORFV 006/132, 103, 109, 110, and 116 genes (VEGF, homologues of vaccinia virus A26L, A33R, and A34R, and a novel PPV ORF) show an unusual degree of intraspecies variability. These genomic differences are consistent with the classification of BPSV and ORFV as two PPV species. Compared to other mammalian chordopoxviruses, PPV shares unique genomic features with molluscum contagiosum virus, including a G+C-rich nucleotide composition, three orthologous genes, and a paucity of nucleotide metabolism genes. Together, these data provide a comparative view of PPV genomics.


Interrater agreement statistics with skewed data: evaluation of alternatives to Cohen's kappa.
In this study, we aimed to evaluate interrater agreement statistics (IRAS) for use in research on low base rate clinical diagnoses or observed behaviors. Establishing and reporting sufficient interrater agreement is essential in such studies. Yet the most commonly applied agreement statistic, Cohen's κ, has a well known sensitivity to base rates that results in a substantial penalization of interrater agreement when behaviors or diagnoses are very uncommon, a prevalent and frustrating concern in such studies. We performed Monte Carlo simulations to evaluate the performance of 5 of κ's alternatives (Van Eerdewegh's V, Yule's Y, Holley and Guilford's G, Scott's π, and Gwet's AC₁), alongside κ itself. The simulations investigated the robustness of these IRAS to conditions that are common in clinical research, with varying levels of behavior or diagnosis base rate, rater bias, observed interrater agreement, and sample size. When the base rate was 0.5, each IRAS provided similar estimates, particularly with unbiased raters. G was the least sensitive of the IRAS to base rates. The results encourage the use of the G statistic for its consistent performance across the simulation conditions. We recommend separately reporting the rates of agreement on the presence and absence of a behavior or diagnosis alongside G as an index of chance corrected overall agreement.


Purification of heat-labile enterotoxin from four Escherichia coli strains by affinity immunoadsorbent: evidence for similar subunit structure.
A single-step method for the purification of heat-labile enterotoxin of Escherichia coli is described. The method involves an affinity immunoadsorbent made with antiserum to cholera toxin. Crude toxin preparations of three human and one porcine enterotoxinogenic strains of E. coli were purified on this immunoadsorbent, and the elution products suggest that the toxin molecule is composed of subunits. One kind of subunit shared by these four strains showed similar mobility of sodium dodecyl sulfate-polyacrylamide gel electrophoresis, close antigenic relationship, and an antigen in common with cholera enterotoxin.


NOD1 Participates in the Innate Immune Response Triggered by Hepatitis C Virus Polymerase.
Hepatitis C virus (HCV) triggers innate immunity signaling in the infected cell. Replication of the viral genome is dispensable for this phenotype, and we along with others have recently shown that NS5B, the viral RNA-dependent RNA polymerase, synthesizes double-stranded RNA (dsRNA) from cellular templates, thus eliciting an inflammatory response, notably via activation of type I interferon and lymphotoxin β. Here, we investigated intracellular signal transduction pathways involved in this process. Using HepaRG cells, a model that largely recapitulates the in vivo complexities of the innate immunity receptor signaling, we have confirmed that NS5B triggered increased expression of the canonical pattern recognition receptors (PRRs) specific for dsRNA, namely, RIG-I, MDA5, and Toll-like receptor 3 (TLR3). Unexpectedly, intracellular dsRNA also led to accumulation of NOD1, a receptor classically involved in recognition of bacterial peptidoglycans. NOD1 activation, confirmed by analysis of its downstream targets, was likely due to its interaction with dsRNA and was independent of RIG-I and mitochondrial antiviral signaling protein (MAVS/IPS-1/Cardif/VISA) signaling. It is likely to have a functional significance in the cellular response in the context of HCV infection since interference with the NOD1 pathway severely reduced the inflammatory response elicited by NS5B. In this study, we show that NOD1, a PRR that normally senses bacterial peptidoglycans, is activated by HCV viral polymerase, probably through an interaction with dsRNA, suggesting that NOD1 acts as an RNA ligand recognition receptor. In consequence, interference with NOD1-mediated signaling significantly weakens the inflammatory response to dsRNA. These results add a new level of complexity to the understanding of the cross talk between different classes of pattern recognition receptors and may be related to certain complications of chronic hepatitis C virus infection.


Early effects of iodine deficiency on radial glial cells of the hippocampus of the rat fetus. A model of neurological cretinism.
The most severe brain damage associated with thyroid dysfunction during development is observed in neurological cretins from areas with marked iodine deficiency. The damage is irreversible by birth and related to maternal hypothyroxinemia before mid gestation. However, direct evidence of this etiopathogenic mechanism is lacking. Rats were fed diets with a very low iodine content (LID), or LID supplemented with KI. Other rats were fed the breeding diet with a normal iodine content plus a goitrogen, methimazole (MMI). The concentrations of -thyroxine (T4) and 3,5,3'triiodo--thyronine (T3) were determined in the brain of 21-d-old fetuses. The proportion of radial glial cell fibers expressing nestin and glial fibrillary acidic protein was determined in the CA1 region of the hippocampus. T4 and T3 were decreased in the brain of the LID and MMI fetuses, as compared to their respective controls. The number of immature glial cell fibers, expressing nestin, was not affected, but the proportion of mature glial cell fibers, expressing glial fibrillary acidic protein, was significantly decreased by both LID and MMI treatment of the dams. These results show impaired maturation of cells involved in neuronal migration in the hippocampus, a region known to be affected in cretinism, at a stage of development equivalent to mid gestation in humans. The impairment is related to fetal cerebral thyroid hormone deficiency during a period of development when maternal thyroxinemia is believed to play an important role.


Data from a pre-publication independent replication initiative examining ten moral judgement effects.
We present the data from a crowdsourced project seeking to replicate findings in independent laboratories before (rather than after) they are published. In this Pre-Publication Independent Replication (PPIR) initiative, 25 research groups attempted to replicate 10 moral judgment effects from a single laboratory's research pipeline of unpublished findings. The 10 effects were investigated using online/lab surveys containing psychological manipulations (vignettes) followed by questionnaires. Results revealed a mix of reliable, unreliable, and culturally moderated findings. Unlike any previous replication project, this dataset includes the data from not only the replications but also from the original studies, creating a unique corpus that researchers can use to better understand reproducibility and irreproducibility in science.


Genetic evidence for transmembrane acetylation by lysosomes.
Acetyl-CoA:alpha-glucosaminide N-acetyltransferase is a lysosomal-membrane enzyme deficient in a genetic disorder, Sanfilippo disease type C. The enzyme catalyzes the transfer of an acetyl group from cytoplasmic acetyl-coenzyme A (acetyl-CoA) to terminal alpha-glucosamine residues of heparan sulfate within the organelle. Previous kinetic experiments indicated that the enzyme carries out a transmembrane acetylation via a ping-pong mechanism; the reaction can therefore be dissected into two half reactions--acetylation of the enzyme, and transfer of the acetyl group to glucosamine. Cells derived from patients were found to differ in their ability to perform each half reaction. Five cell lines (derived from three families) were able to catalyze acetylation of the lysosomal membrane and to carry out acetyl-CoA/CoA exchange, whereas a sixth cell line was devoid of this activity.


Göteborg Metoprolol Trial: effects on arrhythmias.
During the initial hospitalization, ventricular fibrillation (VF) developed in 6 metoprolol-treated patients (0.9%) vs 17 placebo-treated patients (2.4%) after inclusion in the study (p = 0.035). There were 6 episodes of VF in the metoprolol group compared with 41 episodes in the placebo group (p less than 0.001). During the same period, 14 metoprolol-treated patients had treated ventricular tachycardia vs 26 placebo-treated patients (p = 0.076). Similar favorable results were found when the incidence of severe ventricular arrhythmias during the first rehospitalization within the 3-month double-blind treatment period was analyzed.


Termination control of electronic phases in oxide thin films and interfaces: LaAlO3/SrTiO3(001).
A wealth of intriguing properties emerge in the seemingly simple system composed of the band insulators LaAlO(3) and SrTiO(3) such as a two-dimensional electron gas, superconductivity and magnetism. In this paper, we review the current insight obtained from first principles calculations on the mechanisms governing the behaviour of thin LaAlO(3) films on SrTiO(3)(001). In particular, we explore the strong dependence of the electronic properties on the surface and interface termination, the finite film thickness, lattice polarization and defects. A further aspect that is addressed is how the electronic behaviour and functionality can be tuned by an SrTiO(3) capping layer, adsorbates and metallic contacts. Lastly, we discuss recent reports on the coexistence of magnetism and superconductivity in this system for what they might imply about the electronic structure of this system.


Giant bullous lung disease: evaluation, selection, techniques, and outcomes.
Patient selection remains one of the most important aspects of successful surgery for bullous disease. Operation is indicated for patients who have incapacitating dyspnea with large bullae that fill more than 30% of the hemithorax and result in the compression of healthy adjacent lung tissue. Operation is also indicated for patients who have complications related to bullous disease such as infection or pneumothorax. Patients who have bullous disease in the presence of diffuse lung disease (emphysematous or nonemphysematous) should be evaluated on an individual basis and surgery should be performed on patients in whom even a small increase in pulmonary function might be of major benefit. Smoking cessation and outpatient pulmonary rehabilitation are required of all patients preoperatively. Patients should undergo PFTs including lung volumes by whole body plethysmography, spirometry, diffusion capacity, and arterial blood gas. CT remains the most important preoperative evaluation because it is useful assessing the extent of bullous disease and the quality of the surrounding lung tissue. The authors favor a minimally invasive technique through VATS whenever possible because it might allow for a quicker recovery and might be associated with less pain than is seen following thoracotomy. Modified Monaldi-type drainage procedures are also effective, especially in high-risk patients who cannot tolerate excisional procedures. Special care must be taken to avoid sacrifice of any potentially functional lung tissue. Lobectomies should be avoided whenever possible. The best results are seen in limited resections of large bullae that spare all surrounding functional pulmonary parenchyma. Postoperative complications are minimized through aggressive tracheobronchial toilet and vigorous chest physiotherapy. Adequate pain control in maintained throughout the postoperative period, initially by way of epidural infusion of morphine or fentanyl and later through oral opioids. Early ambulation and pulmonary rehabilitation also help minimize complications.


Novel APC-like properties of human NK cells directly regulate T cell activation.
Initiation of the adaptive immune response is dependent on the priming of naive T cells by APCs. Proteomic analysis of unactivated and activated human NK cell membrane-enriched fractions demonstrated that activated NK cells can efficiently stimulate T cells, since they upregulate MHC class II molecules and multiple ligands for TCR costimulatory molecules. Furthermore, by manipulating antigen administration, we show that NK cells possess multiple independent unique pathways for antigen uptake. These results highlight NK cell-mediated cytotoxicity and specific ligand recognition by cell surface-activating receptors on NK cells as unique mechanisms for antigen capturing and presentation. In addition, we analyzed the T cell-activating potential of human NK cells derived from different clinical conditions, such as inflamed tonsils and noninfected and CMV-infected uterine decidual samples, and from transporter-associated processing antigen 2-deficient patients. This in vivo analysis revealed that proinflammatory, but not immune-suppressive, microenvironmental requirements can selectively dictate upregulation of T cell-activating molecules on NK cells. Taken together, these observations offer new and unexpected insights into the direct interactions between NK and T cells and suggest novel APC-like activating functions for human NK cells.


Effect of Cashew Nut on Lipid Profile: A Systematic Review and Meta-Analysis.
Nuts are one of the dietary components which appear to have beneficial effects on cardiovascular disease biomarkers. Studies demonstrate beneficial effects of cash-ews on serum lipids concentration, but results in the literature remain inconclusive. We conducted a review to examine the effects of cashew nut supplementation on serum lipid profile. Two reviewers independently searched PubMed, Web of Science, Cochrane Library, Scopus, and EMBASE electronic databases from inception until June 2019 without language limitation. Random- and fixed-effects models were used to calculate 95% confidence intervals (CI) for studies. Six randomized clinical trials comprising 531 participants were included in this systematic review. Three studies were included in the meta-analysis model. There were no significant changes for total cholesterol (TC) (standardized mean difference [SMD]: -0.02, 95% CI: -0.32, 0.28), triglycerides (TG) (SMD: -0.01, 95% CI: -0.22, 0.20), high-density lipoprotein (HDL) cholesterol (SMD: 0.09, 95% CI: -0.16, 0.34), or low-density lipoprotein (LDL) cholesterol (SMD: -0.18, 95% CI: -0.75, 0.39). The results of this analysis demonstrate that treatment with cashew nut supplementation alone did not significantly change serum levels of LDL, HDL, TC, or TG.


Video-assisted thoracoscopic surgery versus open thymectomy for thymoma: a systematic review.
Video-assisted thoracoscopic surgery (VATS) thymectomy is an increasingly utilized alternative to traditional open approaches for the resection of thymomas. Recent studies have suggested comparable survival and oncological efficacy as well as reduced perioperative morbidity when using the VATS approach. This current systematic review thus aimed to critically evaluate existing evidence for the efficacy and safety of VATS versus open (transsternal or transthoracic) thymectomy for thymomas. Six electronic databases were searched from their date of inception to April 2015. Relevant studies were identified using specific eligibility criteria and data were extracted and analyzed based on predefined primary and secondary endpoints. Fourteen comparative observational studies with a total of 1,061 patients were obtained for qualitative assessment, data extraction and analysis. Five-year overall survival and 10-year recurrence-free survival was similar or higher in patients undergoing VATS compared to open thymectomy. On average, the VATS group also demonstrated reduced intraoperative blood loss (131.8 vs. 340.5 mL), shorter hospital stays (7.0 vs. 9.8 days), and lower rates of postoperative pneumonia (1.9% vs. 4.1%). The mean rate of conversion from VATS to open thymectomy was relatively low (3.1%), while 30-day mortality remained low in both the VATS and open groups (0 vs. 0.3%). The current evidence suggests that VATS thymectomy for thymoma has at least equal if not superior oncological efficacy and survival outcomes, as well as reduced perioperative complications, compared to open surgery. Further adequately powered studies and future randomized trials are required to confirm these findings.


Population Pharmacokinetic Analysis of Piperacillin/Tazobactam in Korean Patients with Acute Infections.
For more effective and safer usage of antibiotics, the dosing strategy should be individualized based on the patients' characteristics, including race. The aim of this study was to investigate the population pharmacokinetic (PK) profiles of piperacillin and tazobactam in Korean patients with acute infections. At least four consecutive 2/0.25 g or 4/0.5 g doses of piperacillin/tazobactam (TZP) were intravenously infused over 1 h every 8 h for patients with creatinine clearance (CL(cr)) ≤50 ml/min or CL(cr) >50 mL/min, respectively. Blood samples from 33 patients at a steady-state were taken pre-dose and at 0 min, 30 min, and 4-6 h after the fourth infusion. The population PK analysis was conducted using a non-linear mixed-effects method. A likelihood ratio test was used to select significant covariates, with significance levels of P < 0.05 for selection and P < 0.01 for elimination. Both piperacillin PK and tazobactam PK were well described by a two-compartment model with first-order elimination. Creatinine clearance and body weight, as covariates on clearance (CL) and volume of central compartment (V1), were selected among the covariates possibly affecting PK parameters of both drugs. CL was defined as CL = 2.9 + 4.03 × CL(cr) /47 for piperacillin and CL = 1.76 + 4.81 × CL(cr) /47 for tazobactam. V1 was defined as V1 = 19.5 × weight/60 for piperacillin and V1 = 22.6 × weight/60 for tazobactam. The PK profiles of TZP at a steady-state in Korean patients with acute infections were well described by a two-compartment model with first-order elimination. Both piperacillin and tazobactam clearances were significantly influenced by creatinine clearance.


Gender norms in South Africa: implications for HIV and pregnancy prevention among African and Indian women students at a South African tertiary institution.
In post-Apartheid South Africa, women are constitutionally guaranteed protections and freedoms that were previously unknown to them. These freedoms may have positive implications for women's ability to negotiate sexual protection with partners and hence prevent unintended pregnancy and decrease their risk of HIV. Among tertiary institution students, who are a relatively 'privileged' group, there is little information on gender norms that might shape responses to HIV-prevention programmes. To elicit gender norms regarding women's and men's roles, condom and contraceptive use, sexual communication and sexual pleasure, we conducted 10 semi-structured focus group discussions with African and Indian female tertiary institution students in order to understand how norms might be used to buttress HIV- and pregnancy-prevention. Participants reported dramatic changes in the structure of gender norms and relations with the formal recognition of women's rights in the post-Apartheid context. These generational shifts in norms are supported by other research in South Africa. At the same time, women recognized the co-existence of traditional constructions of gender that operate to constrain women's freedom. The perceived changes that have taken place provide an entry point for intervention, particularly for reinforcing emerging gender norms that promote women's protection against unintended pregnancy and HIV/STIs.


Extending primary care: potential learning from Italy.
Health systems across Europe are under increasing pressure to shift care outside hospitals and into community settings. The emphasis is on providing high-quality, coordinated care for a growing population of older patients and those with long-term conditions. Extended primary care is regarded as the key means of achieving such a shift. We report learning following exploratory visits to two sites in Italy, each providing an example of a primary care organisation with extended general practices, community health and local resource utilisation responsibilities. We draw out three areas of potential interest--shifting care from hospital to community settings, facilitating localism and enabling stable leadership--all of which appear to provide a means for local clinicians, managers and their communities to commission care according to local needs. We conclude by recommending that primary care researchers consider undertaking further work in Italy, building on this exploratory work and more systematically exploring the effects of such programmes.


Sop-GPU: accelerating biomolecular simulations in the centisecond timescale using graphics processors.
Theoretical exploration of fundamental biological processes involving the forced unraveling of multimeric proteins, the sliding motion in protein fibers and the mechanical deformation of biomolecular assemblies under physiological force loads is challenging even for distributed computing systems. Using a C(α)-based coarse-grained self organized polymer (SOP) model, we implemented the Langevin simulations of proteins on graphics processing units (SOP-GPU program). We assessed the computational performance of an end-to-end application of the program, where all the steps of the algorithm are running on a GPU, by profiling the simulation time and memory usage for a number of test systems. The ∼90-fold computational speedup on a GPU, compared with an optimized central processing unit program, enabled us to follow the dynamics in the centisecond timescale, and to obtain the force-extension profiles using experimental pulling speeds (v(f) = 1-10 μm/s) employed in atomic force microscopy and in optical tweezers-based dynamic force spectroscopy. We found that the mechanical molecular response critically depends on the conditions of force application and that the kinetics and pathways for unfolding change drastically even upon a modest 10-fold increase in v(f). This implies that, to resolve accurately the free energy landscape and to relate the results of single-molecule experiments in vitro and in silico, molecular simulations should be carried out under the experimentally relevant force loads. This can be accomplished in reasonable wall-clock time for biomolecules of size as large as 10(5) residues using the SOP-GPU package.


Measuring breathing patterns and respiratory movements with the respiratory movement measuring instrument.
The respiratory movement measuring instrument (RMMI) is a laser-based non-invasive technique to measure breathing patterns and respiratory movements (RMs). Little knowledge is known about the ability of the RMMI to measure breathing patterns and the correlation between RMs and breathing volumes. One aim was to investigate whether the RMMI could discriminate between normal versus abdominal versus high costal breathing patterns in different body positions. A second aim was to determine the correlation between RMs and breathing volumes in different body positions. Twenty adult, healthy subjects (10 women) were included in the study. The RMMI was used to study the above-mentioned breathing patterns in supine, sitting and standing positions. A subgroup of 12 subjects (6 women) simultaneously performed measurements of breathing volumes while RMs were recorded. The RMMI was able to discriminate between different breathing patterns in different body positions (P<0·001). The upper thoracic contribution to RMs in the sitting position was 47% for natural breathing, 32% for abdominal breathing and 64% for high costal breathing; similar results were found in the supine and standing positions. A strong correlation was observed between RMs as measured by the RMMI and different breathing volumes in all three body positions (Spearman's rho 0·86-1·00). The RMMI can be used to measure and analyse different breathing patterns in different body positions, and the correlation between measured RMs and breathing volumes is strong.


Effect of Stretching on Thoracolumbar Fascia Injury and Movement Restriction in a Porcine Model.
Stretching of fascia is an important component of manual and movement therapies. We previously showed that in pigs, a unilateral thoracolumbar fascia injury combined with movement restriction (hobble) produced contralateral loss of fascia mobility (shear strain during passive trunk flexion measured with ultrasound) similar to findings in human subjects with chronic low back pain. We now tested whether such abnormalities could be reversed by removing the hobble with or without daily stretching for 1 mo. Thirty pigs were randomized to control, injury, or injury + hobble for 8 wks. The hobble restricted hip extension ipsilateral to the injury. At week 8, the injury + hobble group was subdivided into continued hobble, removed hobble, and removed hobble + stretching (passively extending the hip for 10 min daily). Removing hobbles restored normal gait speed but did not restore fascia mobility. Daily passive stretching was not superior to removing hobbles, as there was no significant improvement in fascia mobility with either treatment group (removed hobble or stretching). Reduced fascia mobility in response to injury and movement restriction worsens over time and persists even when movement is restored. Reversing fascia abnormalities may require either longer than 1 mo or a different treatment "dose" or modality.


Carbohydrate restricted recovery from long term endurance exercise does not affect gene responses involved in mitochondrial biogenesis in highly trained athletes.
The aim was to determine if the metabolic adaptations, particularly PGC-1α and downstream metabolic genes were affected by restricting CHO following an endurance exercise bout in trained endurance athletes. A second aim was to compare baseline expression level of these genes to untrained. Elite endurance athletes (VO2max 66 ± 2 mL·kg(-1)·min(-1), n = 15) completed 4 h cycling at ~56% VO2max. During the first 4 h recovery subjects were provided with either CHO or only H2O and thereafter both groups received CHO. Muscle biopsies were collected before, after, and 4 and 24 h after exercise. Also, resting biopsies were collected from untrained subjects (n = 8). Exercise decreased glycogen by 67.7 ± 4.0% (from 699 ± 26.1 to 239 ± 29.5 mmol·kg(-1)·dw(-1)) with no difference between groups. Whereas 4 h of recovery with CHO partly replenished glycogen, the H2O group remained at post exercise level; nevertheless, the gene expression was not different between groups. Glycogen and most gene expression levels returned to baseline by 24 h in both CHO and H2O. Baseline mRNA expression of NRF-1, COX-IV, GLUT4 and PPAR-α gene targets were higher in trained compared to untrained. Additionally, the proportion of type I muscle fibers positively correlated with baseline mRNA for PGC-1α, TFAM, NRF-1, COX-IV, PPAR-α, and GLUT4 for both trained and untrained. CHO restriction during recovery from glycogen depleting exercise does not improve the mRNA response of markers of mitochondrial biogenesis. Further, baseline gene expression of key metabolic pathways is higher in trained than untrained.


The voltage-gated proton channel Hv1/VSOP inhibits neutrophil granule release.
Neutrophil granule exocytosis is crucial for host defense and inflammation. Neutrophils contain 4 types of granules, the exocytotic release of which is differentially regulated. This exocytosis is known to be driven by diverse mediators, including calcium and nucleotides, but the precise molecular mechanism remains largely unknown. We show in the present study that voltage-gated proton (Hv) channels are necessary for the proper release of azurophilic granules in neutrophils. On activation of NADPH oxidase by PMA and IgG, neutrophils derived from Hvcn1 gene knockout mouse exhibited greater secretion of MPO and elastase than WT cells. In contrast, release of LTF enriched in specific granules was not enhanced in these cells. The excess release of azurophilic granules in Hv1/VSOP-deficient neutrophils was suppressed by inhibiting NADPH oxidase activity and, in part, by valinomycin, a potassium ionophore. In addition, Hv1/VSOP-deficient mice exhibited more severe lung inflammation after intranasal Candida albicans infection than WT mice. These findings suggest that the Hv channel acts to specifically dampen the release of azurophilic granules through, in part, the suppression of increased positive charges at the plasma membrane accompanied by the activation of NADPH oxidase in neutrophils.


Preservation of endothelial cells in excised rat carotid arteries. Effects of transmural pressure and segment length.
When arteries are excised, they collapse and shorten spontaneously, which can result in damage to the endothelium. To determine if an intact endothelial cell layer could be preserved in excised vessels, we isolated and cannulated rat carotid artery segments (in situ length, Lis, 10-20 mm) at both ends while maintaining both transmural pressure (70 mm Hg) and Lis, while either transmural pressure or Lis, or after allowing vessel collapse and shortening (n = 4 vessels per treatment). After each treatment, vessel segments were perfused with fixative and stained with AgNO3 to visualize endothelial cells. The amount of endothelial cell loss was quantified using stereological analysis of video microscopic images of the luminal surface. Results demonstrated that maintenance of both Lis and transmural pressure minimized endothelial cell denudation (1.6 +/- 0.9%); permitting the vessel to collapse and shorten resulted in the greatest loss of endothelial cells (59.4 +/- 13.2%); and maintenance of either pressure or Lis resulted in intermediate endothelial cell loss (13-30%). We conclude that the spontaneous collapse and shortening that normally accompany the excision of arterial segments result in substantial endothelial cell loss, which can be virtually eliminated with the maintenance of transmural pressure and vessel segment length. These findings have implications for surgical and experimental procedures requiring intact endothelium.


Managing expectations of antibiotics for upper respiratory tract infections: a qualitative study.
Communication experts have suggested that it is good practice to ask patients' directly whether they expect to receive antibiotics as part of asking about the triad of ideas, concerns, and expectations for health care. Our aim was to explore the views and experiences of family physicians about using this strategy with their patients, focusing the interview on the problem of eliciting expectations of antibiotics as a possible treatment for upper respiratory tract infections. We conducted a qualitative study using semistructured interviews with 20 family physicians in South Wales, United Kingdom, and performing thematic analysis. Family physicians assumed most patients or parents wanted antibiotics, as well as wanting to be "checked out" to make sure the illness was "nothing serious." Physicians said they did not ask direct questions about expectations, as that might lead to confrontation. They preferred to elicit expectations for antibiotics in an indirect manner, before performing a physical examination. The majority described reporting their findings of the examination as a "running commentary" so as to influence expectations and help avoid generating resistance to a soon-to-be-made-explicit plan not to prescribe antibiotics. The physicians used the running commentary to preserve and enhance the physician-patient relationship. Real-world family physicians use indirect methods to explore expectations for treatment and, on the basis of their physical examination, build an argument for reassuring the patient or parent. In contrast to proposed models in the communication literature, interventions to promote appropriate antibiotic prescribing might include a focus on training in communication skills that (1) integrates these indirect methods as part of building collaborative physician-patient relationships and (2) uses the running commentary of examination findings to facilitate participation in clinical decisions.


Transitional adherence and persistence in the use of aldosterone antagonist therapy in patients with heart failure.
Aldosterone antagonist therapy is recommended for selected patients with heart failure and reduced ejection fraction. Adherence to therapy in the transition from hospital to home is not well understood. We identified patients with heart failure and reduced ejection fraction who were ≥65 years old, eligible for aldosterone antagonist therapy, and discharged home from hospitals in the Get With the Guidelines-Heart Failure registry between January 1, 2005, and December 31, 2008. We used Medicare prescription drug event data to measure adherence. Main outcome measures were prescription at discharge, outpatient prescription claim within 90 days, discontinuation, and adherence as measured with the medication possession ratio. We used the cumulative incidence function to estimate rates of initiation and discontinuation. Among 2,086 eligible patients, 561 (26.9%) were prescribed an aldosterone antagonist at discharge. Within 90 days, 78.6% of eligible patients with a discharge prescription filled a prescription for the therapy, compared with 13.0% of eligible patients without a discharge prescription (P < .001). The median medication possession ratio was 0.63 over 1 year of follow-up. Among 634 patients who filled a prescription within 90 days of discharge, 7.9% discontinued therapy within 1 year. Most eligible patients were not prescribed aldosterone antagonist therapy at discharge from a heart failure hospitalization. Eligible patients without a discharge prescription seldom initiated therapy as outpatients. Most patients who were prescribed an aldosterone antagonist at discharge filled the prescription within 90 days and remained on therapy.


Utility of right ventricular free wall speckle-tracking strain for evaluation of right ventricular performance in patients with pulmonary hypertension.
The objectives of this study were to test the utility of right ventricular (RV) speckle-tracking strain as an assessment tool for RV function in patients with pulmonary hypertension (PH) compared with conventional echocardiographic parameters and to investigate the relationship of the findings obtained with RV speckle-tracking strain with the hemodynamic parameters of RV performance. Forty-five prospective consecutive patients with PH were studied. RV free wall longitudinal speckle-tracking strain (RV-free) and RV septal wall longitudinal speckle-tracking strain (RV-septal) were calculated by averaging each of three regional peak systolic strains along the entire right ventricle. The conventional echocardiographic parameters-RV fractional area change, RV myocardial performance index, tricuspid annular plane systolic excursion, and tricuspid annular peak systolic velocity-were also studied. For comparison, 22 age-matched volunteers with normal ejection fractions were studied. RV-free in patients with PH was significantly lower than that in normal controls, but RV-septal in the two groups was similar. Importantly, multivariate analysis revealed that RV-free was an independent echocardiographic predictor of hemodynamic RV performance items, including mean pulmonary artery pressure (β = -0.844, P = .001) and pulmonary vascular resistance (β = -0.045, P < .001). RV-free was also correlated with RV ejection fraction and RV end-systolic volume measured by cardiac magnetic resonance imaging and with 6-min walking distance (r = 0.60, r = 0.56, and r = 0.49, respectively, P < .05). Furthermore, the improvement in RV-free 5 ± 3 months after adding medical treatment was significantly correlated with that in 6-min walking distance (r = 0.68, P < .0001). RV-free has the potential to allow for noninvasive follow-up of patients with PH.


Weakly-supervised High-resolution Segmentation of Mammography Images for Breast Cancer Diagnosis.
In the last few years, deep learning classifiers have shown promising results in image-based medical diagnosis. However, interpreting the outputs of these models remains a challenge. In cancer diagnosis, interpretability can be achieved by localizing the region of the input image responsible for the output, i.e. the location of a lesion. Alternatively, segmentation or detection models can be trained with pixel-wise annotations indicating the locations of malignant lesions. Unfortunately, acquiring such labels is labor-intensive and requires medical expertise. To overcome this difficulty, weakly-supervised localization can be utilized. These methods allow neural network classifiers to output saliency maps highlighting the regions of the input most relevant to the classification task (e.g. malignant lesions in mammograms) using only image-level labels (e.g. whether the patient has cancer or not) during training. When applied to high-resolution images, existing methods produce low-resolution saliency maps. This is problematic in applications in which suspicious lesions are small in relation to the image size. In this work, we introduce a novel neural network architecture to perform weakly-supervised segmentation of high-resolution images. The proposed model selects regions of interest via coarse-level localization, and then performs fine-grained segmentation of those regions. We apply this model to breast cancer diagnosis with screening mammography, and validate it on a large clinically-realistic dataset. Measured by Dice similarity score, our approach outperforms existing methods by a large margin in terms of localization performance of benign and malignant lesions, relatively improving the performance by 39.6% and 20.0%, respectively. Code and the weights of some of the models are available at https://github.com/nyukat/GLAM.


Large mode area fibers with asymmetric bend compensation.
Fibers with asymmetrical bend compensation offer to completely remove the tradeoff between mode area and single-modedness, with potentially huge impact on high-power amplification. These fibers would be difficult to fabricate, but are the only fundamental-mode strategy that can remove the bend-distortion limitations on mode-area scaling. Here, we show that even imperfect fibers can achieve essentially complete HOM suppression for areas of 2000 square microns or larger. Ultimate performance limits due to finite cladding size and fabrication imperfections are calculated.


Murine Lyme arthritis development mediated by p38 mitogen-activated protein kinase activity.
Borrelia burgdorferi, the Lyme disease agent, causes joint inflammation in an experimental murine model. Inflammation occurs, in part, due to the ability of B. burgdorferi to induce the production of proinflammatory cytokines and a strong CD4(+) T helper type 1 response. The mechanisms by which spirochetes induce these responses are not completely known, although transcription factors, such as NF-kappa B in phagocytic cells, initiate the proinflammatory cytokine burst. We show here that the mitogen-activated protein (MAP) kinase of 38 kDa (p38 MAP kinase) is involved in the proinflammatory cytokine production elicited by B. burgdorferi Ags in phagocytic cells and the development of murine Lyme arthritis. B. burgdorferi Ags activated p38 MAP kinase in vitro, and the use of a specific inhibitor repressed the spirochete-induced production of TNF-alpha. The infection of mice that are deficient for a specific upstream activator of the kinase, MAP kinase kinase 3, resulted in diminished proinflammatory cytokine production and the development of arthritis, without compromising the ability of CD4(+) T cells to respond to borrelial Ags or the production of specific Abs. Overall, these data indicated that the p38 MAP kinase pathway plays an important role in B. burgdorferi-elicited inflammation and point to potential new therapeutic approaches to the treatment of inflammation induced by the spirochete.


The bacterial microflora of fish.
The results of numerous studies indicate that fish possess bacterial populations on or in their skin, gills, digestive tract, and light-emitting organs. In addition, the internal organs (kidney, liver, and spleen) of healthy fish may contain bacteria, but there is debate on whether or not muscle is actually sterile. The numbers and taxonomic composition of the bacterial populations often reflect those of the surrounding water. The role of the bacteria includes the ability to degrade complex molecules (therefore exercising a potential benefit in nutrition), to produce vitamins and polymers, and to be responsible for the emission of light by the light-emitting organs of deep-sea fish. Taxa, including Pseudomonas, may contribute to spoilage by the production of histamines in fish tissue.


Systemic vascular resistance: an unreliable index of left ventricular afterload.
Systemic vascular resistance (SVR) is a frequently used clinical index of left ventricular afterload. However, SVR may not adequately assess left ventricular afterload (i.e., ventricular internal fiber load during systole) since it reflects only peripheral vasomotor tone. In contrast, left ventricular end-systolic wall stress (sigma es) reflects the combined effects of peripheral loading conditions and left ventricular chamber pressure, dimension, and wall thickness. To determine the relationship between SVR and sigma es, left ventricular afterload and contractility were pharmacologically altered in eight dogs instrumented with central aortic microtip and Swan-Ganz thermodilution catheters. Left ventricular wall thicknesses and dimensions were measured from two-dimensionally targeted M mode echocardiograms. Aortic, right atrial, and left ventricular end-systolic pressures as well as cardiac output were recorded. SVR and sigma es were determined under control conditions as well as during infusions of nitroprusside, methoxamine, dobutamine, and norepinephrine. Control data acquired before each drug infusion were similar. When compared with baseline values, SVR underestimated the magnitude of change in left ventricular sigma es by 22% when afterload alone was decreased (nitroprusside), 54% when afterload alone was increased (methoxamine), and 50% when afterload was decreased and contractility was augmented (dobutamine). Most importantly, when afterload was minimally decreased in association with augmented contractility (norepinephrine), SVR increased by 21% while sigma es fell by 9%. Thus, discordant changes in left ventricular afterload (i.e., sigma es) and SVR can occur during pharmacologic interventions. SVR is an unreliable index of left ventricular afterload, reflecting only peripheral arteriolar tone rather than left ventricular systolic wall force. This emphasizes the fact that a true measure of left ventricular afterload must consider the interaction of factors internal and external to the myocardium.


Optical and Physical Probing of Thermal Processes in Semiconductor and Plasmonic Nanocrystals.
This article reviews thermal properties of semiconductor and emergent plasmonic nanomaterials, focusing on mechanisms through which hot carriers and phonons are produced and dissipated as well as the related impacts on optoelectronic properties. Elevated equilibrium temperatures, of particular relevance for implementation of nanomaterials in devices, affect absorptive and radiative transitions as well as emission efficiency that can present reversible and irreversible changes with temperature. In noble metal or doped semiconductor/insulator nanomaterials, hot carriers and lattice heating can substantially influence localized surface plasmon resonances and yield large ultrafast changes in transmission or strongly oscillatory coherences. Transient optical and diffraction characterizations enable nonequilibrium investigations of phonon dynamics and cooling such as lattice expansion and crystal phase stability. Timescales of nanoparticle thermalization with surroundings and transport of heat within films of such materials are also discussed.


Anticoagulant effects of heparin in neonatal plasma.
Available data on the anticoagulant effects of heparin in neonatal plasma are scarce and conflicting: relative to adult plasma, neonatal plasma has been reported to show both resistance as well as sensitivity to heparin. We explored this apparent paradox by comparing how well heparin accelerated inhibition of exogenous thrombin and prevented thrombin generation in defibrinated neonatal and adult plasmas. Using amidolytic assays, we determined the effects of heparin on 1) the neutralization of exogenous human alpha-thrombin and on 2) the formation of endogenous thrombin activity after contact activation and recalcification. Neonatal plasma proved resistant to heparin (0.05 U/mL) during inhibition of added thrombin (15 NIH U/mL). Inhibition of thrombin in heparinized neonatal plasma became as efficient as in adult plasma only after raising the AT III activity to normal adult values. However, de novo generation of thrombin activity was very susceptible to inhibition by heparin, even in neonatal plasmas with physiologically low AT III levels. Peak thrombin activity generated in neonatal plasma in the absence of heparin was 50% or less of peak adult activity, and this already reduced ability of neonatal plasma to generate thrombin activity upon prothrombin activation was further decreased by heparin (0.05-0.2 U/mL). We conclude that due to the neonatal AT III deficiency, added thrombin is inactivated less effectively by heparin in neonatal than in normal adult plasma. Yet, the generation of thrombin activity is impaired in neonatal plasma and easily suppressed by heparin. We speculate that newborn infants may be resistant to heparin therapy during overt thrombotic disease, when neutralization of abnormal thrombin activity is the therapeutic goal.(ABSTRACT TRUNCATED AT 250 WORDS)


Social representation of hearing aids: cross-cultural study in India, Iran, Portugal, and the United Kingdom.
The current study was aimed at understanding the social representation of hearing aids in India, Iran, Portugal, and the United Kingdom. We also compared these results to explore the cross-cultural differences and similarities among these countries. The study involved a cross-sectional design, and the data were collected from four different countries using the snowball sampling method. Data were analyzed using a content analysis to identify the most-similar categories of responses reported, a co-occurrences analysis to see which of these categories are reported commonly, and a chi-square analysis to study if there was any association between positive, neutral, and negative connotations among participants in different countries. The current study revealed four different social representations of hearing aids from India, Iran, Portugal, and the United Kingdom, and also a global index. The study results provide very useful insights into how hearing aids are represented in the society. These findings may have important implications for public education and also for manufacturers from the viewpoint of designing and marketing hearing aids in different countries.


Mechanical strain induces involution-associated events in mammary epithelial cells.
Shortly after weaning, a complex multi-step process that leads to massive epithelial apoptosis is triggered by tissue local factors in the mouse mammary gland. Several reports have demonstrated the relevance of mechanical stress to induce adaptive responses in different cell types. Interestingly, these signaling pathways also participate in mammary gland involution. Then, it has been suggested that cell stretching caused by milk accumulation after weaning might be the first stimulus that initiates the complete remodeling of the mammary gland. However, no previous report has demonstrated the impact of mechanical stress on mammary cell physiology. To address this issue, we have designed a new practical device that allowed us to evaluate the effects of radial stretching on mammary epithelial cells in culture. We have designed and built a new device to analyze the biological consequences of applying mechanical stress to cells cultured on flexible silicone membranes. Subsequently, a geometrical model that predicted the percentage of radial strain applied to the elastic substrate was developed. By microscopic image analysis, the adjustment of these calculations to the actual strain exerted on the attached cells was verified. The studies described herein were all performed in the HC11 non-tumorigenic mammary epithelial cell line, which was originated from a pregnant BALB/c mouse. In these cells, as previously observed in other tissue types, mechanical stress induced ERK1/2 phosphorylation and c-Fos mRNA and protein expression. In addition, we found that mammary cell stretching triggered involution associated cellular events as Leukemia Inhibitory Factor (LIF) expression induction, STAT3 activation and AKT phosphorylation inhibition. Here, we show for the first time, that mechanical strain is able to induce weaning-associated events in cultured mammary epithelial cells. These results were obtained using a new practical and affordable device specifically designed for such a purpose. We believe that our results indicate the relevance of mechanical stress among the early post-lactation events that lead to mammary gland involution.


Impaired hippocampal long-term potentiation and failure of learning in β1,4-N-acetylgalactosaminyltransferase gene transgenic mice.
Gangliosides (sialic acid-containing glycosphingolipids) play important roles in many physiological functions, including synaptic plasticity in the hippocampus, which is considered as a cellular mechanism of learning and memory. In the present study, three types of synaptic plasticity, long-term potentiation (LTP), long-term depression (LTD) and reversal of LTP (depotentiation, DP), in the field excitatory post-synaptic potential in CA1 hippocampal neurons and learning behavior were examined in β1,4-N-acetylgalactosaminyltransferase (β1,4 GalNAc-T; GM2/GD2 synthase) gene transgenic (TG) mice, which showed a marked decrease in b-pathway gangliosides (GQ1b, GT1b and GD1b) in the brain and isolated hippocampus compared with wild-type (WT) mice. The magnitude of the LTP induced by tetanus (100 pulses at 100 Hz) in TG mice was significantly smaller than that in control WT mice, whereas there was no difference in the magnitude of the LTD induced by three short trains of low-frequency stimulation (LFS) (200 pulses at 1 Hz) at 20 min intervals between the two groups of mice. The reduction in the LTP produced by delivering three trains of LFS (200 pulses at 1 Hz, 20 min intervals) was significantly greater in the TG mice than in the WT mice. Learning was impaired in the four-pellet taking test (4PTT) in TG mice, with no significant difference in daily activity or activity during the 4PTT between TG and WT mice. These results suggest that the overexpression of β1,4 GalNAc-T resulted in altered synaptic plasticity of LTP and DP in hippocampal CA1 neurons and learning in the 4PTT, and this is attributable to the shift from b-pathway gangliosides to a-pathway gangliosides.


Exploring the gap between knowledge and behavior: a qualitative study of clinician action following an educational intervention.
Many medical education interventions improve clinicians' knowledge but fail to change behavior. The authors exposed this knowledge-behavior gap through standardized clinical interactions, thus allowing in-depth exploration of the contributing factors. A typical evidence-based educational intervention in one clinical domain (early signs of autism) was administered to family medicine residents at the University of Toronto in 2001-02, and change in knowledge was assessed through a multiple-choice test. Six to eight weeks later, participants' relevant knowledge was documented, and their clinical behavior was observed during four interactions with standardized patients. Factors producing a knowledge-behavior discrepancy were then explored using semistructured interviews, which were audiotaped, transcribed, and analyzed using grounded theory methods. Half of participants demonstrated varying degrees of knowledge-behavior gap. Eight main rationalizations (relationships, patient agenda, knowledge deficit, clinical style, means to an end, ideals, autism stigma, and systems barriers) were used to justify choices of clinical behavior, and the same rationalizations were used to justify opposite choices of behavior. Two conditions that promote clinical action based on knowledge (level of certainty and sense of urgency) were identified. The knowledge-behavior gap was exposed and factors reported to influence clinicians' decisions about whether to implement new knowledge were elicited. That identical rationalizations were used to justify opposite behaviors implies these factors may not be behavioral determinants. Sense of urgency and level of certainty promote clinical action based on knowledge; focusing on these may increase the impact of education on practice.


Diet Quality Is Associated with Physical Performance and Special Forces Selection.
This study determined associations between diet quality measured by the Healthy Eating Index (HEI)-2015, physical performance, and successful selection following a U.S. Army Special Forces Assessment and Selection course characterized by arduous cognitive and physical demands. The HEI-2015 scores were calculated from usual diet assessed with a Block food frequency questionnaire among 782 soldiers attending Special Forces Assessment and Selection. Differences in HEI-2015 scores according to demographics and physical performance were determined with analysis of variance. Differences in likelihood of selection according to HEI-2015 scores were determined with logistic regression. Models were adjusted for potential confounders: age, education, body mass index (BMI), duration and type of resistance training, and smoking. The HEI-2015 total score was higher among older soldiers (≥25 yr), those with more education (≥some college), higher body mass index (≥25), longer duration of resistance training (≥400 min·wk), those that reported use of free weights, suspension training, Olympic lifting, and nonsmokers (P < 0.05). The HEI-2015 total score was higher among those with higher Army Physical Fitness Test (APFT) total scores, APFT sit-up score, APFT run score, and faster loaded road march times (P < 0.05). Those with higher HEI-2015 total scores were 75% (quartile 3 vs quartile 1: odds ratio, 1.75; 95% confidence interval, 1.09-2.81) and 65% (quartile 4 vs quartile 1: odds ratio, 1.65, 95% confidence interval, 1.03-2.65) more likely to be selected. Higher scores for total vegetables, greens and beans, seafood and plant protein, and refined grains, but lower sodium scores (indicating more sodium consumed), were associated with better physical performance (P < 0.05). Dietary patterns that conform to federal dietary guidelines (except sodium) are associated with physical performance and Special Forces selection.


Towards indirect potable reuse in South East Queensland.
Faced with limited water supply options in the longer term and the worst drought on record in the short term, the Queensland Government is constructing the Western Corridor Recycled Water Project which will supply up to 182 ML/day of purified recycled water for industrial and potable purposes. The project is one of a suite of capital works projects in progress which in the longer term will supply up to 10% of the region's potable water supply.


The relationship of age, race, and ethnicity with survival in dialysis patients.
Reports on the racial and ethnic differences in dialysis patient survival rates have been inconsistent. The literature suggests that these survival differences may be modified by age as well as categorizing white race as inclusive of Hispanic ethnicity. The goal of this study was to better understand these associations by examining survival among US dialysis patients by age, ethnicity, and race. Between 1995 and 2009, 1,282,201 incident dialysis patients ages 18 years or older were identified in the United States Renal Data System. Dialysis survival was compared among non-Hispanic blacks, non-Hispanic whites, and Hispanics overall and stratified by seven age groups. The median duration of follow-up was 22.3 months. Compared with non-Hispanic whites, a lower mortality risk was seen in Hispanics in all age groups. Consequently, when Hispanic patients were excluded from the white race, the mortality rates in white race all increased. Using non-Hispanic whites as the reference, a significantly lower mortality risk for non-Hispanic blacks was consistently observed in all age groups above 30 years (unadjusted hazard ratios ranged from 0.70 to 0.87; all P<0.001). In the 18- to 30-years age group, there remained an increased mortality risk in blacks versus non-Hispanic whites after adjustment for case mix (adjusted hazard ratio=1.19, 95% confidence interval=1.13-1.25). The mortality risk was lowest in Hispanics, intermediate in non-Hispanic blacks, and highest in non-Hispanic whites. This pattern generally holds in all age groups except for the 18- to 30-years group, where the adjusted mortality rate for non-Hispanic blacks exceeds the adjusted mortality rate of non-Hispanic whites.


Neighbourhood environment and the incidence of depressive symptoms among middle-aged African Americans.
To investigate the association between attributes of subject location and incidence of clinically relevant levels of depressive symptoms (CRLDS), and to investigate whether an association remained after adjusting for individual-level factors using data from the population-based African American Health Study. An 11-item depression scale (Center for Epidemiologic Studies Depression scale) was obtained at baseline and 3 years later through in-home evaluations. Census tract and block group deprivation indices were obtained from the 2000 census. The external appearance of the block where the subject lived was rated during sample enumeration, and the interior and exterior of the subject's dwelling were observed during the initial in-home interview. Of 998 subjects at baseline, 21.1% had CRLDS. Although 12.7% of the 672 people without CRLDS at baseline developed them by the 3-year follow-up, univariate and propensity-adjusted analyses revealed no association between the subject's location and the incidence of CRLDS. Sensitivity analyses confirmed the robustness of the findings. Despite other studies showing independent effects of neighbourhood characteristics on the prevalence of CRLDS, attributes of subject location are not independent contributors to the incidence of CRLDS in middle-aged urban African Americans.


Effects of clustered epitopes in multivalent ligand-receptor interactions.
Many biological ligands are composed of clustered binding epitopes. However, the effects of clustered epitopes on the affinity of ligand-receptor interactions in many cases are not well understood. Clustered carbohydrate epitopes are present in naturally occurring multivalent carbohydrates and glycoproteins, which are receptors on the surface of cells. Recent studies have provided evidence that the enhanced affinities of lectins, which are carbohydrate binding proteins, for multivalent carbohydrates and glycoproteins are due to internal diffusion of lectin molecules from epitope to epitope in these multivalent ligands before dissociation. Indeed, binding of lectins to mucins, which are large linear glycoproteins, appears to be similar to the internal diffusion mechanism(s) of protein ligands binding to DNA, which have been termed the "bind and slide" or "bind and hop" mechanisms. The observed increasing negative cooperativity and gradient of decreasing microaffinity constants of a lectin binding to multivalent carbohydrates and glycoproteins result in an initial fraction of lectin molecules that bind with very high affinity and dynamic motion. These findings have important implications for the mechanisms of binding of lectins to mucins, and for other ligand-biopolymer interactions and clustered ligand-receptor systems in general.


Caveolin-1 is a critical determinant of autophagy, metabolic switching, and oxidative stress in vascular endothelium.
Caveolin-1 is a scaffolding/regulatory protein that interacts with diverse signaling molecules. Caveolin-1(null) mice have marked metabolic abnormalities, yet the underlying molecular mechanisms are incompletely understood. We found the redox stress plasma biomarker plasma 8-isoprostane was elevated in caveolin-1(null) mice, and discovered that siRNA-mediated caveolin-1 knockdown in endothelial cells promoted significant increases in intracellular H₂O₂. Mitochondrial ROS production was increased in endothelial cells after caveolin-1 knockdown; 2-deoxy-D-glucose attenuated this increase, implicating caveolin-1 in control of glycolytic pathways. We performed unbiased metabolomic characterizations of endothelial cell lysates following caveolin-1 knockdown, and discovered strikingly increased levels (up to 30-fold) of cellular dipeptides, consistent with autophagy activation. Metabolomic analyses revealed that caveolin-1 knockdown led to a decrease in glycolytic intermediates, accompanied by an increase in fatty acids, suggesting a metabolic switch. Taken together, these results establish that caveolin-1 plays a central role in regulation of oxidative stress, metabolic switching, and autophagy in the endothelium, and may represent a critical target in cardiovascular diseases.


H2O2-Depleting and O2-Generating Selenium Nanoparticles for Fluorescence Imaging and Photodynamic Treatment of Proinflammatory-Activated Macrophages.
Macrophages have a pivotal role in chronic inflammatory diseases (CIDs), so imaging and controlling activated macrophage is critical for detecting and reducing chronic inflammation. In this study, photodynamic selenium nanoparticles (SeNPs) with photosensitive and macrophage-targeting bilayers were developed. The first layer of the photosensitive macromolecule was composed of a conjugate of a photosensitizer (rose bengal, RB) and a thiolated chitosan (chitosan-glutathione), resulting in a plasmonic coupling-induced red shift and broadening of RB absorption bands with increased absorption intensity. Electron paramagnetic resonance (EPR) and diphenylanthracene (DPA) quenching studies revealed that the SeNPs that were coated with the photosensitive layer were more effective than RB alone in producing singlet oxygen (1O2) under photoirradiation. The second layer of the activated macrophage-targetable macromolecule was synthesized by conjugation of hyaluronic acid with folic acid using an ethylenediamine linker. Proinflammatory-activated macrophages rapidly internalized the SeNPs that were covered with the targeting ligand, exhibiting a much stronger fluorescence signal of the SeNPs than did the nonactivated macrophages. Since proinflammatory-activated macrophage was known to generate a substantial amount of H2O2 while the inflamed site generally caused inflammation-associated tissue hypoxia, the SeNPs were further modified with O2 self-sufficient function for photodynamic therapy. Catalase was immobilized on the SeNPs by the formation of disulfide bonds. Intracellular reduction of disulfide bonds induced the subsequent release of catalase, which catalyzed the decomposition of H2O2. The H2O2-depleting and O2-generating photodynamic SeNPs efficiently killed activated macrophages and quenched the intracellular H2O2 and NO that are associated with inflammation. The SeNPs may have potential as a theranostic nanomaterial to image and control the activation of macrophages.


Antischistosomal Properties of Hederacolchiside A1 Isolated from Pulsatilla chinensis.
Background: Schistosomiasis is a major neglected disease for which the current control strategy involves mass treatment with praziquantel, the only available drug. Hence, there is an urgent need to develop new antischistosomal compounds. Methods: The antischistosomal activity of hederacolchiside A1 (HSA) were determined by total or female worm burden reductions in mice harboring Schistosoma japonicum or S. mansoni. Pathology parameters were detected on HSA against 1-day-old S. japonicum-harboring mice. Moreover, we confirmed the antischistosomal effect of HSA on newly transformed schistosomula (NTS) of S. japonicum in vitro. Results: HSA, a natural product isolated from Pulsatilla chinensis (Bunge) Regel, was initially corroborated to possess promising antischistosomal properties. We demonstrated that HSA had high activity against S. japonicum and S. mansoni less in 11 days old parasites harbored in mice. The antischistosomal effect was even more than the currently used drugs, praziquantel, and artesunate. Furthermore, HSA could ameliorate the pathology parameters in mice harboring 1-day-old juvenile S. japonicum. We also confirmed that HSA-mediated antischistosomal activity is partly due to the morphological changes in the tegument system when NTS are exposed to HSA. Conclusions: HSA may have great potential to be an antischistosomal agent for further research.


Contrasting plant diversification histories within the Andean biodiversity hotspot.
The Andes are the most species-rich global biodiversity hotspot. Most research and conservation attention in the Andes has focused on biomes such as rain forest, cloud forest, and páramo, where much plant species diversity is the hypothesized result of rapid speciation associated with the recent Andean orogeny. In contrast to these mesic biomes, we present evidence for a different, older diversification history in seasonally dry tropical forests (SDTF) occupying rain-shadowed inter-Andean valleys. High DNA sequence divergence in Cyathostegia mathewsii, a shrub endemic to inter-Andean SDTF, indicates isolation for at least 5 million years of populations separated by only ca. 600 km of high cordillera in Peru. In conjunction with fossil evidence indicating the presence of SDTF in the Andes in the late Miocene, our data suggest that the disjunct small valley pockets of inter-Andean SDTF have persisted over millions of years. These forests are rich in endemic species but massively impacted, and merit better representation in future plans for science and conservation in Andean countries.


Long term effects of community-based STI screening and mass media HIV prevention messages on sexual risk behaviors of African American adolescents.
We examined the long-term effects of two interventions designed to reduce sexual risk behavior among African American adolescents. African American adolescents (N = 1383, ages 14-17) were recruited from community-based organizations over a period of 16 months in two northeastern and two southeastern mid-sized U.S. cities with high rates of sexually transmitted infection (STI). Participants were screened for three STIs (gonorrhea, chlamydia, and trichomoniasis) and completed an audio computer-assisted attitude, intention, and behavior self-interview. Youth who tested positive for an STI (8.3%) received treatment and risk reduction counseling. In addition, television and radio HIV-prevention messages were delivered during the recruitment period and 18 months of follow-up in one randomly selected city in each region. Analyses determined effects of the media program for those receiving a positive versus negative STI test result on number of sexual partners and occurrence of unprotected sex. Adolescents who tested STI-positive reduced their number of vaginal sex partners and the probability of unprotected sex over the first 6 months. However, in the absence of the mass media program, adolescents returned to their previously high levels of sexual risk behavior after 6 months. Adolescents who tested STI-positive and received the mass media program showed more stable reductions in unprotected sex. Community-based STI treatment and counseling can achieve significant, but short-lived reductions in sexual risk behavior among STI-positive youth. A culturally sensitive mass media program has the potential to achieve more stable reductions in sexual risk behavior and can help to optimize the effects of community-based STI screening.


First-trimester ultrasound dating of twin pregnancy: are singleton charts reliable?
The aim of this study was to assess the performance of validated singleton crown-rump length (CRL) formulae in dating twin pregnancies at 11-14 weeks of gestation. Retrospective cohort study. Fetal medicine unit of a London teaching hospital. Three hundred and eighty-four pregnancies with known dates of conception. Retrospective analysis of 266 singletons and 118 twin pregnancies conceived by in vitro fertilisation (IVF), with a known date of conception. The gestation calculated from the date of conception was compared with the expected gestation from fetal size using a number of different CRL formulae. Difference in gestational age computed from fetal size (CRL) of the bigger and smaller fetus in twin pregnancies and singleton pregnancies using three formulae. Two of the three studied CRL formulae systematically underestimated the mean gestational age and size of singleton IVF pregnancies (Robinson formula: gestation = 1.4 days, size = 2.7 mm). Twin CRL measurements straddled those of singletons, regardless of the CRL formula used (Robinson formula: larger twin gestation = 2.4 days, size = 4.7 mm; smaller twin gestation = 0.8 days, size = 1.7 mm). These underestimates in gestation and size for IVF singleton and twin pregnancies are well within the known limits of accuracy of first = trimester ultrasound measurements, and are of limited clinical significance. Currently available CRL charts underestimate both the age and size of IVF singleton pregnancies by a clinically insignificant amount. This difference is similar for twin pregnancies, suggesting that singleton CRL charts can be used to date twin pregnancies accurately.


Which interventions increase hearing protection behaviors during noisy recreational activities? A systematic review.
Hearing loss and tinnitus are global concerns that can be reduced through hearing protection behaviors (e.g., earplug use). Little is known about the effectiveness of interventions to increase hearing protection use in recreational domains. For the first time we review systematically the effectiveness of such interventions. Systematic searches of nine databases, as well as grey literature and hand-searching, were conducted. Any study design was included if it assessed quantitatively a purposeful attempt to increase hearing protection in recreational settings. Studies were excluded if they assessed noise exposure from occupational sources and headphones/earphones, as these have been reviewed elsewhere. PROSPERO protocol: CRD42018098573. Eight studies were retrieved following the screening of 1908 articles. Two pretest-posttest studies detected a small to medium effect (d ≥ 0·3 ≤ 0·5), one a small effect (d ~ =0·2) and two no real effect. Three posttest experimental studies detected small to medium effects (d ≥ 0·3 ≤ 0·5). Studies were rated as "poor quality" and 17 out of a possible 93 behavior change techniques were coded, with the majority targeting the intervention function 'education'. Hearing loss and tinnitus due to recreational noise exposure are major public health concerns yet very few studies have examined preventive interventions. The present systematic review sets the agenda for the future development and testing of evidence-based interventions designed to prevent future hearing loss and tinnitus caused by noise in recreational settings, by recommending systematic approaches to intervention design, and implementation of intervention functions beyond education, such as incentivization, enablement and modeling.


Influence of smartphone Wi-Fi signals on adipose-derived stem cells.
The use of smartphones is expanding rapidly around the world, thus raising the concern of possible harmful effects of radiofrequency generated by smartphones. We hypothesized that Wi-Fi signals from smartphones may have harmful influence on adipose-derived stem cells (ASCs). An in vitro study was performed to assess the influence of Wi-Fi signals from smartphones. The ASCs were incubated under a smartphone connected to a Wi-Fi network, which was uploading files at a speed of 4.8 Mbps for 10 hours a day, for a total of 5 days. We constructed 2 kinds of control cells, one grown in 37°C and the other grown in 39°C. After 5 days of Wi-Fi exposure from the smartphone, the cells underwent cell proliferation assay, apoptosis assay, and flow cytometry analysis. Three growth factors, vascular endothelial growth factor, hepatocyte growth factor, and transforming growth factor-β, were measured from ASC-conditioned media. Cell proliferation rate was higher in Wi-Fi-exposed cells and 39°C control cells compared with 37°C control cells. Apoptosis assay, flow cytometry analysis, and growth factor concentrations showed no remarkable differences among the 3 groups. We could not find any harmful effects of Wi-Fi electromagnetic signals from smartphones. The increased proliferation of ASCs under the smartphone, however, might be attributable to the thermal effect.


Transcanal Endoscopic Ear Surgery for Excision of a Facial Nerve Venous Malformation With Interposition Nerve Grafting: A Case Report.
To illustrate a novel approach for the surgical management of a venous malformation of the facial nerve, including interposition nerve grafting, via an exclusively transcanal endoscopic ear surgery (TEES) approach. Thirty nine-year-old woman with a preoperative House-Brackmann (HB) grade IV facial paresis secondary to a facial nerve tumor. Surgical excision and interposition nerve graft via a transcanal endoscopic approach. Completeness of resection, approach morbidities, and facial nerve outcome. The TEES approach provided wide exposure of the facial nerve from the geniculate ganglion through the mastoid segment. This visualization facilitated gross total tumor resection, incus interposition ossicular reconstruction, and placement of an interposition nerve graft. The nerve graft was positioned in the fallopian canal and was secured at both ends with surgicel. The patient had no postoperative complications. At 11-month follow-up her facial function had returned to HB grade IV. This is the first report of resecting a venous malformation of the facial nerve with concomitant interposition nerve graft reconstruction via an exclusively endoscopic approach. This report adds to the growing body of evidence that TEES can manage diverse middle ear and lateral skull base pathology. Additional studies are needed to fully elucidate the risk-benefit profile of this technique.


A comparison between connective tissue grafts combined with either double pedicle grafts or coronally positioned pedicle grafts: A clinical study.
Various surgical techniques have been proposed for treating gingival recession. This randomized clinical study compared the effectiveness of using a sub-epithelial connective tissue graft (SCTG) combined with an overlying double pedical graft (DPG) or a coronally positioned flap (CPF) in the treatment of isolated gingival recession. A total of 20, healthy, non-smoking subjects with single Miller's Class I or Class II recession defects were selected. The defects, at least 3.0 mm deep, were randomly assigned to the test (DPG + SCTG) or control group (CPF + SCTG). Gingival recession (REC), probing pocket depth (PPD), clinical attachment level (CAL), width of keratinized gingival tissue (WKG), plaque index and papillary bleeding index were assessed at baseline and 6 months post-operatively. Recession depth was significantly reduced 6 months post-operatively (P < 0.05) for both groups. Mean root coverage was 88% and 84% in the test and control groups, respectively. There were no significant differences between the two groups in REC, PPD, CAL, or WKG at baseline. However, at 6 months post-operatively, there were statistically significant changes in REC, CAL and WKG in favor of the test group (P < 0.05) from the baseline, but the comparison between the two was not statistically significant. The percentage of teeth with complete root coverage was greater in the test group when compared to the control group, but the results were not statistically significant. The results indicate that both surgical approaches are effective in addressing root coverage. Furthermore, when an increase in keratinized tissue width is a desired outcome, both the treatment modalities have shown comparable outcomes.


Novel organization and divergent dockerin specificities in the cellulosome system of Ruminococcus flavefaciens.
The DNA sequence coding for putative cellulosomal scaffolding protein ScaA from the rumen cellulolytic anaerobe Ruminococcus flavefaciens 17 was completed. The mature protein exhibits a calculated molecular mass of 90,198 Da and comprises three cohesin domains, a C-terminal dockerin, and a unique N-terminal X domain of unknown function. A novel feature of ScaA is the absence of an identifiable cellulose-binding module. Nevertheless, native ScaA was detected among proteins that attach to cellulose and appeared as a glycosylated band migrating at around 130 kDa. The ScaA dockerin was previously shown to interact with the cohesin-containing putative surface-anchoring protein ScaB. Here, six of the seven cohesins from ScaB were overexpressed as histidine-tagged products in E. coli; despite their considerable sequence differences, each ScaB cohesin specifically recognized the native 130-kDa ScaA protein. The binding specificities of dockerins found in R. flavefaciens plant cell wall-degrading enzymes were examined next. The dockerin sequences of the enzymes EndA, EndB, XynB, and XynD are all closely related but differ from those of XynE and CesA. A recombinant ScaA cohesin bound selectively to dockerin-containing fragments of EndB, but not to those of XynE or CesA. Furthermore, dockerin-containing EndB and XynB, but not XynE or CesA, constructs bound specifically to native ScaA. XynE- and CesA-derived probes did however bind a number of alternative R. flavefaciens bands, including an approximately 110-kDa supernatant protein expressed selectively in cultures grown on xylan. Our findings indicate that in addition to the ScaA dockerin-ScaB cohesin interaction, at least two distinct dockerin-binding specificities are involved in the novel organization of plant cell wall-degrading enzymes in this species and suggest that different scaffoldins and perhaps multiple enzyme complexes may exist in R. flavefaciens.


Changes in adiponectin receptor expression in muscle and adipose tissue of type 2 diabetic patients during rosiglitazone therapy.
Adiponectin is important in the regulation of insulin sensitivity in man. Its receptors, adipoR1 and R2, have recently been identified, but their expression in adipose tissue and their regulation in response to insulin sensitisation of diabetic patients have never been assessed. We therefore explored the regulation of adipoR1/R2 and adiponectin expression in adipose tissue and skeletal muscle, and of adiponectin plasma concentrations in response to insulin sensitisation by rosiglitazone. Patients with type 2 diabetes were studied in a double-blind, placebo-controlled crossover study, using in vivo arteriovenous techniques of measuring adipose tissue and muscle blood flow, combined with measurement of adipose tissue and skeletal muscle gene expression. Rosiglitazone treatment increased adiponectin concentrations by 69%. Skeletal muscle adipoR1 expression was down-regulated from 109.0 (70.1-165.7) (median [interquartile range]) to 82.8 (63.6-89.3) relative units (p=0.04), but adipose tissue adipoR1 expression was up-regulated from 5.3 (4.4-9.4) to 11.2 (4.8-15.3) relative units (p=0.02) by rosiglitazone. In contrast to adipoR1 expression, adipoR2 expression was not altered by rosiglitazone in either of the tissues. The increase in adipose tissue adipoR1 expression with rosiglitazone was associated with increased postprandial triglyceride clearance (r=0.67, p=0.05), and increased fasting fatty acid output (r=0.78, p=0.01) measured in subcutaneous adipose tissue. AdipoR1 expression is up-regulated in adipose tissue but down-regulated in skeletal muscle by rosiglitazone. These data suggest that adipoR1 plays a role in mediating the effects of adiponectin in specific tissues in relation to insulin sensitisation.


PRevalence of Abuse and Intimate Partner Violence Surgical Evaluation (P.R.A.I.S.E.): rationale and design of a multi-center cross-sectional study.
Intimate partner violence (IPV) is described by the American Medical Association as "a pattern of coercive behaviors that may include repeated battering and injury, psychological abuse, sexual assault, progressive social isolation, deprivation, and intimidation." The long-term consequences of IPV include health risks, posttraumatic stress disorder, depression, and staggering economic costs for health care of victims. Intimate partner violence is often underreported among women who seek medical attention. The current study seeks to address the issue of possible underreporting of IPV in orthopaedic fracture clinics by establishing prevalence rates of IPV among women seeking treatment for musculoskeletal injuries. We propose a cross-sectional multicenter study wherein 3,600 women will complete a self-reported written questionnaire across clinical sites in North America, Europe, and Australia. Recruitment of participants will take place at orthopaedic fracture clinics at each clinical site. The questionnaire will contain a validated set of questions used to screen for IPV, as well as questions that pertain to the participant's demographic, injury characteristics, and experiences with health care utilization. Female patients presenting to the orthopaedic fracture clinics will complete two validated self-reported written questionnaires (Woman Abuse Screening Tool (WAST) and the Partner Violence Screen (PVS)) to determine the prevalence of IPV in the past 12 months and in their lifetime. The two questionnaires were designed for rapid assessment of IPV status in emergency departments, family practice, and women's health clinics that we believe are similar to our intended setting of an orthopaedic clinic. If the prevalence of IPV among women attending orthopaedic clinics is greater than the current perceptions of orthopaedic surgeons, this study will serve to advocate for the continued education of medical professionals to better recognize probable IPV cases and offer existing services to enhance the care of these patients.