A Systematic Review of Longitudinal Risk and Protective Factors and Correlates for Posttraumatic Stress and Its Natural History in Forcibly Displaced Children.
Posttraumatic stress (PTS) results in significant distress or functional impairment. Prevalence studies report higher rates of PTS in forcibly displaced children (FDC). Current evidence deriving mainly from cross-sectional studies is unable to make causal attributions. Given rising rates of forcible displacement reported by the United Nations High Commissioner for Refugees (UNHCR) in 2014, there is increasing need to determine the best policies and practice for engaging mental health needs of FDC. This systematic review identifies (1) longitudinal risk and protective factors and correlates for PTS and (2) its natural history in FDC, contributing to research identifying vulnerable subgroups and malleable factors for PTS and understanding its natural history. No meta-analysis was conducted due to heterogeneity; results were analyzed through narrative synthesis. Eleven longitudinal studies were identified. All but one were prospective cohort designs. They identified prevalence rates between 20% and 48.7% at baseline, 10% and 48.3% at 1 year ( k = 7), 18% and 48% at 2-3 years ( k = 2), 8% and 38% at 6 years ( k = 2), and 35% at 12 years using nine measurement methods in seven independent samples. Evidence from multiple associations supported the following risk factors: exposure to traumatic stressors or other stress, older age, and prior psychopathology. Evidence predominantly supported the stability of PTS with some decline. While results should be interpreted with caution given small or unrepresentative samples, they suggest regular mental health screenings should be conducted for FDC, who are a vulnerable subgroup with variable onset and remission. Risk associations with prior psychopathology also suggest that screening upon arrival may be advisable for early intervention and prevention.


The relative diffusive transport rate of SrI2 in water changes over the nanometer length scale as measured by coherent quasielastic neutron scattering.
X-ray and neutron scattering have been used to provide insight into the structures of ionic solutions for over a century, but the probes have covered distances shorter than 8 Å. For the non-hydrolyzing salt SrI2 in aqueous solution, a locally ordered lattice of ions exists that scatters slow neutrons coherently down to at least 0.1 mol L(-1) concentration, where the measured average distance between scatterers is over 18 Å. To investigate the motions of these scatterers, coherent quasielastic neutron scattering (CQENS) data on D2O solutions with SrI2 at 1, 0.8, 0.6, and 0.4 mol L(-1) concentrations was obtained to provide an experimental measure of the diffusive transport rate for the motion between pairs of ions relative to each other. Because CQENS measures the motion of one ion relative to another, the frame of reference is centered on an ion, which is unique among all diffusion measurement methods. We call the measured quantity the pairwise diffusive transport rate Dp. In addition to this ion centered frame of reference, the diffusive transport rate can be measured as a function of the momentum transfer q, where q = (4π/λ)sin θ with a scattering angle of 2θ. Since q is related to the interion distance (d = 2π/q), for the experimental range 0.2 Å(-1)≤q≤ 1.0 Å(-1), Dp is, then, measured over interion distances from 40 Å to ≈6 Å. We find the measured diffusional transport rates increase with increasing distance between scatterers over the entire range covered and interpret this behavior to be caused by dynamic coupling among the ions. Within the model of Fickian diffusion, at the longer interionic distances Dp is greater than the Nernst-Hartley value for an infinitely dilute solution. For these nm-distance diffusional transport rates to conform with the lower, macroscopically measured diffusion coefficients, we propose that local, coordinated counter motion of at least pairs of ions is part of the transport process.


T lymphocytes in the intestinal epithelium and lamina propria of mice.
Mesenteric lymphoblasts have a predilection to localize selectively in the murine small intestine within 24 hr after adoptive transfer. In this report, we quantify the localization and intraintestinal distribution of radiolabelled mesenteric lymph node (MLN) T and B blasts in relation to the in situ distribution of intestinal T and B cells which were detected immunohistochemically. Our results show that, within 24 hr after transfer, MLN T blasts localized predominantly in the intestinal epithelium and villus lamina propria, whereas B blasts were found mostly in the basal lamina propria of the gut. In the epithelium and villus lamina propria, 100% and 68%, respectively, of labelled were of thymic origin; this cell type comprised 54% of labelled cells in the basal lamina propria. This pattern of localization was the reverse of the distribution of T lymphocytes and B-cell derived plasmacytes residing in the intestinal wall. These results suggest that MLN T lymphocytes may be a component of common mucosal immunological system and may be integrated with peripheral immunity according to the immunological needs of the host.


Is large loop excision of the transformation zone (LLETZ) more accurate than colposcopically directed punch biopsy in the diagnosis of cervical intraepithelial neoplasia?
In 100 women with suspected cervical intraepithelial neoplasia (CIN) attending the colposcopy clinic the histological diagnoses made from excision biopsies taken by large loop excision of the transformation zone (LLETZ) were compared with those from colposcopically directed punch biopsies taken concurrently. One unsuspected microinvasive tumour was found and the diagnosis made by LLETZ was significantly worse than that made by punch biopsy in 24 cases (24%: 95% CI 15.6 to 32.4%). LLETZ improves the accuracy of diagnosis of CIN.


Superoxide Dismutase as an Intervention for Radiation Therapy-Associated Toxicities: Review and Profile of Avasopasem Manganese as a Treatment Option for Radiation-Induced Mucositis.
Toxicities associated with radiation therapy are common, symptomatically devastating, and costly. The best chance to effectively mitigate radiation-associated normal tissue side effects are interventions aimed at disrupting the biological cascade, which is the basis for toxicity development, while simultaneously not reducing the beneficial impact of radiation on tumor. Oxidative stress is a key initiator of radiation-associated normal tissue injury as physiologic antioxidant mechanisms are overwhelmed by the accumulation of effects produced by fractionated treatment regimens. And fundamental to this is the generation of superoxide, which is normally removed by superoxide dismutases (SODs). Attempts to supplement the activity of endogenous SOD to prevent radiation-induced normal tissue injury have included the administration of bovine-derived SOD and increasing SOD production using gene transfer, neither of which has resulted in a clinically acceptable therapy. A third approach has been to develop synthetic small molecule dismutase mimetics. This approach has led to the creation and development of avasopasem manganese, a unique and specific dismutase mimetic that, in clinical trials, has shown promising potential to reduce the incidence, severity and duration of severe oral mucositis amongst patients being treated with concomitant chemoradiation for cancers of the head and neck. Further, avasopasem and related analogues have demonstrated mechanism-related antitumor synergy in combination with high dose per fraction radiotherapy, an observation that is also being tested in clinical trials. An ongoing Phase 3 trial seeks to confirm avasopasem manganese as an effective intervention for severe oral mucositis associated with chemoradiation in head and neck cancer patients.


Mechanisms in endocrinology: vitamin D as a potential contributor in endocrine health and disease.
It has been suggested that vitamin D may play a role in the pathogenesis of several endocrine diseases, such as hyperparathyroidism, type 1 diabetes (T1DM), type 2 diabetes (T2DM), autoimmune thyroid diseases, Addison's disease and polycystic ovary syndrome (PCOS). In this review, we debate the role of vitamin D in the pathogenesis of endocrine diseases. Narrative overview of the literature synthesizing the current evidence retrieved from searches of computerized databases, hand searches and authoritative texts. Evidence from basic science supports a role for vitamin D in many endocrine conditions. In humans, inverse relationships have been reported not only between blood 25-hydroxyvitamin D and parathyroid hormone concentrations but also with risk of T1DM, T2DM, and PCOS. There is less evidence for an association with Addison's disease or autoimmune thyroid disease. Vitamin D supplementation may have a role for prevention of T2DM, but the available evidence is not consistent. Although observational studies support a potential role of vitamin D in endocrine disease, high quality evidence from clinical trials does not exist to establish a place for vitamin D supplementation in optimizing endocrine health. Ongoing randomized controlled trials are expected to provide insights into the efficacy and safety of vitamin D in the management of endocrine disease.


Genome Architecture Mediates Transcriptional Control of Human Myogenic Reprogramming.
Genome architecture has emerged as a critical element of transcriptional regulation, although its role in the control of cell identity is not well understood. Here we use transcription factor (TF)-mediated reprogramming to examine the interplay between genome architecture and transcriptional programs that transition cells into the myogenic identity. We recently developed new methods for evaluating the topological features of genome architecture based on network centrality. Through integrated analysis of these features of genome architecture and transcriptome dynamics during myogenic reprogramming of human fibroblasts we find that significant architectural reorganization precedes activation of a myogenic transcriptional program. This interplay sets the stage for a critical transition observed at several genomic scales reflecting definitive adoption of the myogenic phenotype. Subsequently, TFs within the myogenic transcriptional program participate in entrainment of biological rhythms. These findings reveal a role for topological features of genome architecture in the initiation of transcriptional programs during TF-mediated human cellular reprogramming.


Beyond mean-field theories with zero-range effective interactions: a way to handle the ultraviolet divergence.
Zero-range effective interactions are commonly used in nuclear physics and in other domains to describe many-body systems within the mean-field model. If they are used within a beyond-mean-field framework, contributions to the total energy that display an ultraviolet divergence are found. We propose a general strategy to regularize this divergence and we illustrate it in the case of the second-order corrections to the equation of state (EOS) of uniform symmetric matter. By setting a momentum cutoff Λ, we show that for every (physically meaningful) value of Λ it is possible to determine a new interaction such that the EOS with the second-order corrections reproduces the empirical EOS, with a fit of the same quality as that obtained at the mean-field level.


Stem cells in dermatology.
Preclinical and clinical research have shown that stem cell therapy could be a promising therapeutic option for many diseases in which current medical treatments do not achieve satisfying results or cure. This article describes stem cells sources and their therapeutic applications in dermatology today.


Applied nasal anatomy & embryology.
The embryology & anatomy of the nose as it is applied to rhinoplasty is surveyed so that the surgeon in training can develop a basis from which to review the literature. This review demonstrates the need for the consolidation and clarification of the nomenclature associated with the complex anatomy of the nasal pyramid.


Roles of nucleic acid substrates and cofactors in the vhs protein activity of pseudorabies virus.
Pseudorabies virus (PrV) belongs to the α-herpesvirinae of which human simplex virus (HSV) is the prototype virus. One of the hallmarks of HSV infection is shutoff of protein synthesis that is mediated by various viral proteins including vhs (virion host shutoff), which is encoded by the UL41 gene. However, the function of PrV vhs is poorly understood. Due to the low sequence similarity (39.3%) between the HSV and PrV UL41 proteins, vhs might not share the same biochemistry characteristics. The purpose of this study was to characterize the nuclease activity of the PrV vhs protein with respect to substrate specificity, its requirements in terms of cofactors, and the protein regions, as well as key amino acids, which contribute to vhs activity. Our results indicated that, similar to HSV vhs, PrV vhs is able to degrade ssRNA and mRNA. However, PrV vhs also targeted rRNA for degradation, which is novel compared to the HSV-1 vhs. Activity assays indicated that Mg(2+) alone enhances RNA degradation mediated by PrV vhs, while K(+) and ATP are not sufficient to induce activity. Finally, we demonstrated that each of the four highly conserved functional boxes of PrV vhs contributes to RNA degradation and that, in particular, residues 152, 169, 171, 172, 173 343, 345, 352 and 356, which are conserved among α-herpesviruses, are key amino acids needed for PrV vhs ribonuclease activity.


Tight glycemic control in critical care--the leading role of insulin sensitivity and patient variability: a review and model-based analysis.
Tight glycemic control (TGC) has emerged as a major research focus in critical care due to its potential to simultaneously reduce both mortality and costs. However, repeating initial successful TGC trials that reduced mortality and other outcomes has proven difficult with more failures than successes. Hence, there has been growing debate over the necessity of TGC, its goals, the risk of severe hypoglycemia, and target cohorts. This paper provides a review of TGC via new analyses of data from several clinical trials, including SPRINT, Glucontrol and a recent NICU study. It thus provides both a review of the problem and major background factors driving it, as well as a novel model-based analysis designed to examine these dynamics from a new perspective. Using these clinical results and analysis, the goal is to develop new insights that shed greater light on the leading factors that make TGC difficult and inconsistent, as well as the requirements they thus impose on the design and implementation of TGC protocols. A model-based analysis of insulin sensitivity using data from three different critical care units, comprising over 75,000h of clinical data, is used to analyse variability in metabolic dynamics using a clinically validated model-based insulin sensitivity metric (S(I)). Variation in S(I) provides a new interpretation and explanation for the variable results seen (across cohorts and studies) in applying TGC. In particular, significant intra- and inter-patient variability in insulin resistance (1/S(I)) is seen be a major confounder that makes TGC difficult over diverse cohorts, yielding variable results over many published studies and protocols. Further factors that exacerbate this variability in glycemic outcome are found to include measurement frequency and whether a protocol is blind to carbohydrate administration.


Spermidine requirement for cell proliferation in eukaryotic cells: structural specificity and quantitation.
Six structural homologs of spermidine and five of its precursor, putrescine, were studied for their ability to prevent cytostasis of cultured L1210 leukemia cells induced by alpha-difluoromethylornithine (DFMO), a specific inhibitor of putrescine biosynthesis. High-performance liquid chromatography and competition studies with spermidine indicated that the homologs, which vary in the length of the carbon chain separating the amines, penetrated the cells. The structural specificity of the spermidine carrier was defined. Three of the six spermidine homologs supported cell growth during a 48-hour incubation in the presence of DFMO, indicating that a two-carbon extension of spermidine structure was tolerated for biological function. Two of the five putrescine homologs supported growth after being converted by the cells to their respective spermidine homologs. The central nitrogen of spermidine appears to be essential for function since diamines of chain length comparable to that of spermidine did not prevent DFMO cytostasis. No more than 15 percent of the spermidine normally present in L1210 cells was required for cell proliferation in the presence of DFMO.


Graphene-based nanopore approaches for DNA sequencing: A literature review.
DNA (deoxyribonucleic acid) is the blueprint of life as it encodes all genetic information. In genetic disorder such as gene fusion, copy number variation (CNV) and single nucleotide polymorphism, DNA sequencing is used as the gold standard for successful diagnosis. Researchers have been conducting rigorous studies to achieve genome sequence at low cost while maintaining high accuracy and high throughput, as such sequencer devices have been developed which led to the evolvement of this technology. These devices are categorized into first, second, and third DNA sequencing generations. One successful endeavor for DNA sequencing is nanopore sequencing. This specific method is considered desirable due to its ability to achieve DNA sequencing while maintaining the required standards such as low cost, high accuracy, long read length, and high throughput. On the other hand, non-nanopore sequencing techniques require extensive preparation as well as complex algorithms, and are restricted by high cost, small throughput, and small read lengths. In this review, the concepts, history, advances, challenges, applications, and potentials of nanopore sequencing are discussed including techniques and materials used for nanopore production and DNA translocation speed control. Additionally, in light of the importance of the nanopore material configuration and fabrication, graphene which is a common and effective material will be discussed in the context of nanopore fabrication techniques. Finally, this review will shed light on some nanopore-related investigations in the area of molecular biology.


Hepatoprotective effect of flavonoids from Cirsium japonicum DC on hepatotoxicity in comparison with silymarin.
Cirsium japonicum DC is a perennial plant that is widely distributed throughout China. Flavonoids are the major active constituents of C. japonicum, which has been reported to possess many bioactivities. This study was designed to investigate the protective effects of flavonoids from C. japonicum against liver injury using carbon tetrachloride (CCl4)-induced hepatocyte injury, with silymarin as a positive control. Silymarin is a mixture of flavonoids from Silybum marianum, a traditional European food plant with clear hepatoprotective effects. The results indicated that the pretreatment with C. japonicum flavonoids could significantly reverse CCl4-induced L02 cell viability decrease similarly to silymarin. Analysis of flavonoids of C. japonicum and silymarin by HPLC showed that these two mixtures may contain one common component, which may be the major active ingredient responsible for their hepatoprotective effects. It is concluded that C. japonicum could be developed into functional foods with hepatoprotective efficacy, similarly to S. marianum.


Periodic Density Functional Theory Calculations of Uranyl Tetrachloride Compounds Engaged in Uranyl-Cation and Uranyl-Hydrogen Interactions: Electronic Structure, Vibrational, and Thermodynamic Analyses.
Solid-state uranyl hybrid structures are often formed through unique intermolecular interactions occurring between a molecular uranyl anion and a charge-balancing cation. In this work, solid-state structures of the uranyl tetrachloride anion engaged in uranyl-cation and uranyl-hydrogen interactions were studied using density functional theory (DFT). As most first-principles methods used for systems of this type focus primarily on the molecular structure, we present an extensive benchmarking study to understand the methods needed to accurately model the geometric properties of these systems. From there, the electronic and vibrational structures of the compounds were investigated through projected density of states and phonon analysis and compared to the experiment. Lastly, we present a DFT + thermodynamics approach to calculate the formation enthalpies (ΔHf) of these systems to directly relate to experimental values. Through this methodology, we were able to accurately capture trends observed in experimental results and saw good quantitative agreement in predicted ΔHf compared to the value calculated through referencing each structure to its standard state. Overall, results from this work will be used for future combined experimental and computational studies on both uranyl and neptunyl hybrid structures to delineate how varying intermolecular interaction strengths relates to the overall values of ΔHf.


Kinetic characterization and gene expression of adenosine deaminase in intact trophozoites of Trichomonas vaginalis.
Trichomonas vaginalis is a parasite that resides in the human urogenital tract and causes trichomonosis, the most prevalent nonviral sexually transmitted disease. Nucleoside triphosphate diphosphohydrolase (NTPDase), which hydrolyzes extracellular di- and triphosphate nucleotides, and ecto-5'-nucleotidase, which hydrolyzes AMP, have been characterized in T. vaginalis. The aim of this study was to characterize the adenosine deaminase (ADA) activity in intact trophozoites of T. vaginalis. A strong inhibition in adenosine deamination was observed in the presence of calcium and magnesium, which was prevented by EDTA. The apparent K(M) value for adenosine was 1.13 ± 0.07mM. The calculated V(max) was 2.61 ± 0.054 nmol NH(3) min(-1) mg(-1) protein. Adenosine deamination was inhibited in the presence of erythro-9-(2-hydroxy-3-nonyl)adenine. Semi-quantitative reverse transcriptase-PCR experiments were performed and both ADA-related genes ada(125) and ada(231) mRNA were expressed, although ada(231) in higher quantity when compared with the ada(125) : α-tubulin ratio. Furthermore, a phylogenetic analysis showed that the T. vaginalis sequences formed a clade with Entamoeba histolytica and Dictyostelium discoideum sequences, and it strongly suggests homologous functions in the T. vaginalis genome. The presence of ADA activity in T. vaginalis may be important to modulate the adenosine/inosine levels during infection and, consequently, to maintain the anti-inflammatory properties through different nucleoside-signalling mechanisms.


Prosocial behaviour emerges independent of reciprocity in cottontop tamarins.
The cooperative breeding hypothesis posits that cooperatively breeding species are motivated to act prosocially, that is, to behave in ways that provide benefits to others, and that cooperative breeding has played a central role in the evolution of human prosociality. However, investigations of prosocial behaviour in cooperative breeders have produced varying results and the mechanisms contributing to this variation are unknown. We investigated whether reciprocity would facilitate prosocial behaviour among cottontop tamarins, a cooperatively breeding primate species likely to engage in reciprocal altruism, by comparing the number of food rewards transferred to partners who had either immediately previously provided or denied rewards to the subject. Subjects were also tested in a non-social control condition. Overall, results indicated that reciprocity increased food transfers. However, temporal analyses revealed that when the tamarins' behaviour was evaluated in relation to the non-social control, results were best explained by (i) an initial depression in the transfer of rewards to partners who recently denied rewards, and (ii) a prosocial effect that emerged late in sessions independent of reciprocity. These results support the cooperative breeding hypothesis, but suggest a minimal role for positive reciprocity, and emphasize the importance of investigating proximate temporal mechanisms underlying prosocial behaviour.


Musculoskeletal Geometry, Muscle Architecture and Functional Specialisations of the Mouse Hindlimb.
Mice are one of the most commonly used laboratory animals, with an extensive array of disease models in existence, including for many neuromuscular diseases. The hindlimb is of particular interest due to several close muscle analogues/homologues to humans and other species. A detailed anatomical study describing the adult morphology is lacking, however. This study describes in detail the musculoskeletal geometry and skeletal muscle architecture of the mouse hindlimb and pelvis, determining the extent to which the muscles are adapted for their function, as inferred from their architecture. Using I2KI enhanced microCT scanning and digital segmentation, it was possible to identify 39 distinct muscles of the hindlimb and pelvis belonging to nine functional groups. The architecture of each of these muscles was determined through microdissections, revealing strong architectural specialisations between the functional groups. The hip extensors and hip adductors showed significantly stronger adaptations towards high contraction velocities and joint control relative to the distal functional groups, which exhibited larger physiological cross sectional areas and longer tendons, adaptations for high force output and elastic energy savings. These results suggest that a proximo-distal gradient in muscle architecture exists in the mouse hindlimb. Such a gradient has been purported to function in aiding locomotor stability and efficiency. The data presented here will be especially valuable to any research with a focus on the architecture or gross anatomy of the mouse hindlimb and pelvis musculature, but also of use to anyone interested in the functional significance of muscle design in relation to quadrupedal locomotion.


Detection of respiratory viruses and the associated chemokine responses in serious acute respiratory illness.
A specific diagnosis of a lower respiratory viral infection is often difficult despite frequent clinical suspicion. This low diagnostic yield may be improved by use of sensitive detection methods and biomarkers. The prevalence, clinical predictors and inflammatory mediator profile of respiratory viral infection in serious acute respiratory illness were investigated. Sequential bronchoalveolar lavage (BAL) fluids from all patients hospitalised with acute respiratory illness over 12 months (n=283) were tested for the presence of 17 respiratory viruses by multiplex PCR assay and for newly discovered respiratory viruses (bocavirus, WU and KI polyomaviruses) by single-target PCR. BAL samples also underwent conventional testing (direct immunoflorescence and viral culture) for respiratory virus at the clinician's discretion. 27 inflammatory mediators were measured in a subset of the patients (n=64) using a multiplex immunoassay. 39 respiratory viruses were detected in 37 (13.1% of total) patients by molecular testing, including rhinovirus (n=13), influenza virus (n=8), respiratory syncytial virus (n=6), human metapneumovirus (n=3), coronavirus NL63 (n=2), parainfluenza virus (n=2), adenovirus (n=1) and newly discovered viruses (n=4). Molecular methods were 3.8-fold more sensitive than conventional methods. Clinical characteristics alone were insufficient to separate patients with and without respiratory virus. The presence of respiratory virus was associated with increased levels of interferon gamma-inducible protein 10 (IP-10) (p<0.001) and eotaxin-1 (p=0.017) in BAL. Respiratory viruses can be found in patients with serious acute respiratory illness by use of PCR assays more frequently than previously appreciated. IP-10 may be a useful biomarker for respiratory viral infection.


Membrane protein turnover by the m-AAA protease in mitochondria depends on the transmembrane domains of its subunits.
AAA proteases are membrane-bound ATP-dependent proteases that are present in eubacteria, mitochondria and chloroplasts and that can degrade membrane proteins. Recent evidence suggests dislocation of membrane-embedded substrates for proteolysis to occur in a hydrophilic environment; however, next to nothing is known about the mechanism of this process. Here, we have analysed the role of the membrane-spanning domains of Yta10 and Yta12, which are conserved subunits of the hetero-oligomeric m-AAA protease in the mitochondria of Saccharomyces cerevisiae. We demonstrate that the m-AAA protease retains proteolytic activity after deletion of the transmembrane segments of either Yta10 or Yta12. Although the mutant m-AAA protease is still capable of processing cytochrome c peroxidase and degrading a peripheral membrane protein, proteolysis of integral membrane proteins is impaired. We therefore propose that transmembrane segments of m-AAA protease subunits have a direct role in the dislocation of membrane-embedded substrates.


[Effects of genistein on bone mineralization in ovariectomized rats].
To investigate the effects of genistein on bone mineralization in ovariectomized rats. Forty-seven Wistar rats were randomly allocated into six groups: sham-operated (sham), ovariectomized (ovx), ovariectomized supplied with diethyl stilbestrol (E, 20 microg x kg bw(-1) x d(-1)) or genistein (25, 50, 100 mg x kg bw(-1) x d(-1)). After the rats had been fed for three months, analysis of the bone mineral density, parameters related to mineralization, bone content of Ca, P, Mg, Mn and Zn and serum concentration of parathyroid calcitonin and estrogen was performed. Bone mineral density, bone Ca, P, Zn and Mg content and serum estrogen concentration in ovariectomized rats were significantly decreased, but mean osteoid width increased, mineralization lag time and osteoid maturation period prolonged compared with sham animals. After three months supplementation to ovariectomized rats, bone Ca, P and Mg content increased, mean osteoid width decreased, mineralization lag time and osteoid maturation period shortened compared with ovariectomized animals. Genistein promotes bone mineralization by increasing bone Ca, P, Mg and adjusting serum calcitonin to prevent osteoporosis.


Fusion mechanism of the myoblasts in the myotome of the chick embryo.
We have studied the fusion process of myoblasts in the mytome corresponding to H.H. stages 22, 23 and 24 from calcitonin-treated chick embryos and their untreated controls. The micrograph images of this process were studied to detect the ultrastructural changes in myoblast morphology that could be associated with the known hormonal and biochemical changes that take place in preparation of fusion. Once actin and myosin myofilament differentiation and sarcomerogenesis had begun, the myotome myoblasts fused in bundles of 10-14 myoblasts, and the following was observed during this process: plasmatic membrane interdigitation and invagination; the appearance of cytoplasmic flaps covering other myoblasts and fading at the point of contact; plasmatic membranes that fade and disintegrate; membrane rupturing; double closed lamina; small ringed lamina; large disperse vesicles; small vesicles (liposomes), and semi-dense amorphous material. Seven stages were established: 1--Membrane rupture; 2--Double closed and elongated lamina; 3--Small ringed lamina aligned lengthwise; 4--Large dispersed vesicles; 5--Imprecise boundaries with amorphous material in diffuse areas; 6--Cytoplasm fusion; and 7--Prefunctional syncitium. Answers to the questions: "how", "when", "where", "why" and "for what purpose" the fusion of myoblasts takes place are suggested.


Reproducibility of an oral cancer and precancer detection program using a primary health care model in Sri Lanka.
A pilot feasibility study utilizing primary health care workers (PHCW) in the early detection of oral cancer and precancer was reported in 1984. The present study was to assess the reproducibility of this model in a different geographic area using existing Government Health Services. In order to improve the compliance of individual referrals following detection (54% in the previous study) a simultaneous health education program was mounted. Of 72,867 villagers aged 20 years and over who were allocated for screening, 57,124 (78%) were examined during 1 year by 36 PHCWs. Oral lesions were detected in 3559 (6.2%). Of these, 2193 (62%) complied by presenting for a reexamination at the hospital. Twenty new cancers and 1716 subjects with oral precancerous lesions were confirmed. While the population screening coverage achieved was higher than in the feasibility study, compliance was marginally improved. Noteworthy, however, was the detection of 20 new cancers as compared to 4 in the feasibility study. This primary health care model for cancer detection appears to be organizationally feasible for a developing country.


Delivering the English smoking treatment services.
This paper describes how smoking treatment services in England were delivered beyond the initial set-up phase and explores key factors affecting their development. Services were expected to treat smokers in line with the evidence-base and were issued with government guidance regarding the type of interventions that should be offered. One factor complicating this was the issue of service funding. Funding was initially issued for a 3-year period and although this was extended on two occasions, these extensions were both announced close to the end of funding periods. To critically assess key elements in the delivery of the English cessation services, including the nature of treatments offered and the impact of short-term funding on staffing. A national postal survey of smoking cessation coordinators in April 2002. Semi-structured interviews with 50 smoking cessation staff in two health regions in autumn 2001, followed by further interviews with 28 staff in the same areas in the autumn of 2002. Treatment was delivered in a wide range of venues, ranging from primary care to local authority-owned premises such as town halls and libraries. Most services offered both one-to-one and group support, although interviewees reported an increase in demand for one-to-one support from clients. Pharmacotherapies were used widely; by 2002, 99% of coordinators reported that their advisers recommended nicotine replacement therapy (NRT) to clients, and 95% bupropion. However, prior to April 2001 bupropion was available on prescription, but NRT was not and this variable access to pharmacotherapies posed problems for services. Coordinators reported that the short-term nature of funding made recruiting and retaining staff difficult and interviews revealed that they believed a longer period of protected funding was required for services to demonstrate their effectiveness. As English smoking treatment services developed, lessons were learned that could inform the development of services in other health systems. First, early guidance from government can encourage services to adhere to evidence-based treatment. Secondly, treatment needs to be accessible to smokers and thus there must be a flexible approach to implementation at local level. Thirdly, the availability of nicotine addiction and behavioural therapies should be coordinated to minimize barriers and maximize uptake. Finally, fixed-term funding can exacerbate staff recruitment and retention difficulties and countries establishing treatment services need to consider carefully the initial funding period that is required for stable services to become established within their health systems.


Therapeutic and diagnostic colonoscopy in nonobstructive colonic dilatation.
Cecal perforation has been well established as a consequence of mechanical obstruction of the distal colon and has been estimated to occur in 1.5% to 7% of patients with colon obstruction. Perforation of the cecum also occurs in cases of nonobstructive colonic dilatation (NCD). Although the incidence is unknown, the mortality rate is nearly 50%. Over an eight-year period, 44 patients (mean age 59 years) underwent 52 colonoscopic examinations for presumed NCD. Twelve patients (27%) developed NCD while convalescing from a recent operation and 29 patients (66%) had major systemic disorders that preceded the development of NCD. Medical treatment for an average of 2.6 days was uniformly unsuccessful. Mean cecal diameter prior to colonoscopy was 12.8 cm (range 9.5 to 17 cm). Based on radiographic or clinical criteria, 38 patients (86%) were successfully decompressed on the initial colonoscopic examination; mean cecal diameter decreased to 8.7 cm (p less than 0.01). Perforation of the cecum during colonsocopy occurred in one patient (2%) who survived. Fourteen patients died; six deaths were attributed solely to the patient's who underwent operation. In summary, colonoscopy is a safe and effective therapeutic and diagnostic tool in cases of massive cecal dilatation. It should be considered before cecostomy in patients without radiographic evidence of pneumoperitoneum or clinical signs of peritoneal irritation.


Automated Stroke Lesion Segmentation in Rat Brain MR Images Using an Encoder-Decoder Framework.
Stroke is a leading cause of serious long-term disability and the major cause of mortality worldwide. Experimental ischemic stroke models play an important role in realizing the mechanism of cerebral ischemia and evaluating the development of pathological extent. An accurate and reliable image segmentation tool to automatically identify the stroke lesion is important in the subsequent processes. However, the intensity distribution of the infarct region in the diffusion weighted imaging (DWI) images is usually nonuniform with blurred boundaries. A deep learning-based infarct region segmentation framework is developed in this paper to address the segmentation difficulties. The proposed solution is an encoder-decoder network that includes a hybrid block model for efficient multiscale feature extraction. An in-house DWI image dataset was created to evaluate this automated stroke lesion segmentation scheme. Through massive experiments, accurate segmentation results were obtained, which outperformed many competitive methods both qualitatively and quantitatively. Our stroke lesion segmentation system is potential in providing a decent tool to facilitate preclinical stroke investigation using DWI images.Clinical Relevance- This facilitates neuroscientists the investigation of a new scoring system with less examination time and better inter-rater reliability, which helps to understand the function of specific brain areas underlying neuroimaging signatures clinically.


Estimating the effective radiation dose imparted to patients by intraoperative cone-beam computed tomography in thoracolumbar spinal surgery.
Observational. To estimate the radiation dose imparted to patients during typical thoracolumbar spinal surgical scenarios. Minimally invasive techniques continue to become more common in spine surgery. Computer-assisted navigation systems coupled with intraoperative cone-beam computed tomography (CT) represent one such method used to aid in instrumented spinal procedures. Some studies indicate that cone-beam CT technology delivers a relatively low dose of radiation to patients compared with other x-ray-based imaging modalities. The goal of this study was to estimate the radiation exposure to the patient imparted during typical posterior thoracolumbar instrumented spinal procedures, using intraoperative cone-beam CT and to place these values in the context of standard CT doses. Cone-beam CT scans were obtained using Medtronic O-arm (Medtronic, Minneapolis, MN). Thermoluminescence dosimeters were placed in a linear array on a foam-plastic thoracolumbar spine model centered above the radiation source for O-arm presets of lumbar scans for small or large patients. In-air dosimeter measurements were converted to skin surface measurements, using published conversion factors. Dose-length product was calculated from these values. Effective dose was estimated using published effective dose to dose-length product conversion factors. Calculated dosages for many full-length procedures using the small-patient setting fell within the range of published effective doses of abdominal CT scans (1-31 mSv). Calculated dosages for many full-length procedures using the large-patient setting fell within the range of published effective doses of abdominal CT scans when the number of scans did not exceed 3. We have demonstrated that single cone-beam CT scans and most full-length posterior instrumented spinal procedures using O-arm in standard mode would likely impart a radiation dose within the range of those imparted by a single standard CT scan of the abdomen. Radiation dose increases with patient size, and the radiation dose received by larger patients as a result of more than 3 O-arm scans in standard mode may exceed the dose received during standard CT of the abdomen. Understanding radiation imparted to patients by cone-beam CT is important for assessing risks and benefits of this technology, especially when spinal surgical procedures require multiple intraoperative scans.


A White Paper. Professional chaplaincy: its role and importance in healthcare.
This paper describes the role and significance of spiritual care and is the first joint statement on this subject prepared by the five largest healthcare chaplaincy organizations in North America representing over 10,000 members. As a consensus paper, it presents the perspectives of these bodies on the spiritual care they provide for the benefit of individuals, healthcare organizations and communities. Throughout this paper, the word spirituality is inclusive of religion; spiritual care includes pastoral care. Spiritual caregivers in healthcare institutions are often known as chaplains although they may have different designations in some settings, i.e. spiritual care providers. The paper contains four sections. 1. The Meaning and Practice of Spiritual Care This first section describes spirit as a natural dimension of all persons and defines the nature of spiritual care. With the basic premise that attention to spirituality is intrinsic to healthcare, the paper establishes their relationship and outlines the various environments in which it is provided. 2. Who Provides Spiritual Care? Professional chaplains provide spiritual care and this section describes their education, skills and certification. 3. The Functions and Activities of Professional Chaplains This section delineates the typical activities of professional chaplains within healthcare settings, focusing on their care of persons and their participation in healthcare teams. 4. The Benefits of Spiritual Care Provided by Professional Chaplains The materials here describe how professional chaplains benefit healthcare patients and their families, staff members, employing organizations, and communities.


Scratching the Surface: Bacterial Cell Envelopes at the Nanoscale.
The bacterial cell envelope is essential for viability, the environmental gatekeeper and first line of defense against external stresses. For most bacteria, the envelope biosynthesis is also the site of action of some of the most important groups of antibiotics. It is a complex, often multicomponent structure, able to withstand the internally generated turgor pressure. Thus, elucidating the architecture and dynamics of the cell envelope is important, to unravel not only the complexities of cell morphology and maintenance of integrity but also how interventions such as antibiotics lead to death. To address these questions requires the capacity to visualize the cell envelope in situ via high-spatial resolution approaches. In recent years, atomic force microscopy (AFM) has brought novel molecular insights into the assembly, dynamics, and functions of bacterial cell envelopes. The ultrafine resolution and physical sensitivity of the technique have revealed a wealth of ultrastructural features that are invisible to traditional optical microscopy techniques or imperceptible in their true physiological state by electron microscopy. Here, we discuss recent progress in our use of AFM imaging for understanding the architecture and dynamics of the bacterial envelope. We survey recent studies that demonstrate the power of the technique to observe isolated membranes and live cells at (sub)nanometer resolution and under physiological conditions and to track in vitro structural dynamics in response to growth or to drugs.


Effect of water on the composition of partial melts of greenstone and amphibolite.
Closed-system partial melts of hydrated, metamorphosed arc basalts and andesites (greenstones and amphibolites), where only water structurally bound in metamorphic minerals is available for melting (dehydration melting), are generally water-undersaturated, coexist with plagioclase-rich, anhydrous restites, and have compositions like island arc tonalites. In contrast, water-saturated melting at water pressures of 3 kilobars yields strongly peraluminous, low iron melts that coexist with an amphibolebearing, plagioclase-poor restite. These melt compositions are unlike those of most natural silicic rocks. Thus, dehydration melting over a range of pressures in the crust of island arcs is a plausible mechanism for the petrogenesis of islands arc tonalite, whereas water-saturated melting at pressure of 3 kilobars and above is not.


Topological origin of equatorial waves.
Topology sheds new light on the emergence of unidirectional edge waves in a variety of physical systems, from condensed matter to artificial lattices. Waves observed in geophysical flows are also robust to perturbations, which suggests a role for topology. We show a topological origin for two well-known equatorially trapped waves, the Kelvin and Yanai modes, owing to the breaking of time-reversal symmetry by Earth's rotation. The nontrivial structure of the bulk Poincaré wave modes encoded through the first Chern number of value 2 guarantees the existence of these waves. This invariant demonstrates that ocean and atmospheric waves share fundamental properties with topological insulators and that topology plays an unexpected role in Earth's climate system.


[Study of temperature-sensitive mutations in the virilis group of Drosophila. 4. Phenogenetics of a temperature-sensitive mutation affecting the development of imaginal discs in Drosophila virilis Sturt].
The phenogenetics of a new temperature-sensitive mutation diskless-ts (dl-ts, 2nd chromosome) has been studied in D. virilis. The rearing of larvae from the 1st instar at the temperature 31 degrees resulted in the complete or partial arrest of the development of imaginal discs and, consequently, the death of larvae prior to the pupation, at the prepupa stage. The change of temperature from 25 to 31 degrees during the second half of development in the 3rd instar affects the differentiation of imaginal discs. Some organs differentiate completely or partially (eyes, wings, legs) whereas the rest do not develop at all. The sensitive period embraces the whole larval development till the beginning of pupation.


A combined assay of cell viability and in vitro cytotoxicity with a highly water-soluble tetrazolium salt, neutral red and crystal violet.
Cell viability and in vitro cytotoxicity assay methods were developed using a combination of dyes, 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1), neutral red (NR) and crystal violet (CV), with HeLa cells as a bioindicatior. As WST-1 produces a highly water soluble and non-cytotoxic formazan dye, ti allows each assay to be carried out in one culture dish. The combined cell viability assay using WST-1, NR and CV gave an absorbance that correlated linearly with the number of cells over the range 1000 to 50,000 cells/well. The combined assay was applied to the evaluation of IC50 values for sodium dodecyl sulfate as a model toxicant, which yielded similar values to those obtained with each assay independently.


Macular translocation surgery with 360-degree peripheral retinectomy following ocular photodynamic therapy of choroidal neovascularization.
To determine the visual outcomes of eyes that underwent macular translocation surgery with 360 degrees peripheral retinectomy and silicone oil tamponade (MTS360) following ocular photodynamic therapy (OPT) with verteporfin for subfoveal choroidal neovascularization (CNV) associated with age-related macular degeneration (ARMD). Observational case series. A retrospective review of patients who underwent MTS360 with silicone oil tamponade from August 5, 1998 through December 1, 2002. Patients who had at least one episode of OPT with verteporfin before surgery were identified. The number of OPT session, best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity, complications (including postoperative CNV, retinal detachment [RD]), the presence or absence of cystoid macular edema (CME) by optical coherence tomography (OCT) were recorded. Eight eyes of eight patients were identified that fulfilled the inclusion criteria. All eyes had at least one episode of OPT (mean, 1.5 treatments). All of these patients at the time of MTS360 demonstrated continued visual loss following the most recent OPT session. The mean preoperative visual acuity was 56 letters. Four of the eight eyes demonstrated CME by OCT on preoperative examination. There were no significant postoperative complications other than one eye that had a successful repair of an RD. At 3 months, the mean visual acuity was 54 letters. At last follow-up (mean, 10 months), the mean visual acuity was 61 letters (P =.5). The final mean visual acuity change for the patients who had only one prior OPT (five eyes) was +10 letters. The mean final visual acuity change for the patients who had multiple OPT sessions (three eyes) was -1 letter. Three of the four eyes that had preoperative CME continued to demonstrate CME at last follow-up. Two eyes that had concurrent cataract extraction surgery with MTS360 did not develop CME. No eyes developed a recurrent CNV during the postoperative period. MTS360 with silicone oil tamponade for CNV associated with ARMD appears to be a viable option for patients who are continuing to lose vision in their better seeing eye following OPT with verteporfin. MTS360 appears to be effective in stabilizing vision, especially in patients who had previously undergone only one OPT session. Further studies are indicated to evaluate the efficacy of MTS360 in this current era of OPT.


Strain and defect engineering on phase transition of monolayer black phosphorene.
The phase transition of monolayer black phosphorene (MBP, α-P) to β-P and γ-P is explored by density functional theory (DFT) calculations and molecular dynamics (MD) simulations using reactive force fields. It is found that MBP can convert to a mixed phase of β-P and γ-P under biaxial strain, while the Stone-Wales defect (SW-2) in MBP can serve as an excellent 'phase transition catalyzer', significantly decreasing the critical strain for phase transition and increasing the homogeneity of the phase transition. The biaxial strain state (i.e. the strain components in the armchair and zigzag direction) and loading mode (i.e. the proportional and staged loading) have significant effects on the phase transition of MBP. In general, the phase transition of MBP is driven by the tension strain in the armchair direction, but large tension or compression strain in the zigzag direction can also promote the phase transition. Besides, MBP has a larger fracture strain under staged loading, generating a more uniform phase transition structure. The effects of curvature and SW-2 defect concentration on the phase transition of MBP are also studied, which shows an easier phase transition for a larger curvature and higher SW-2 defect concentration. The systematic results presented herein provide useful insights for designing and tuning the structure of MBP through phase transition facilitated by strain and defect engineering.


How the assembly and protection of the bacterial cell envelope depend on cysteine residues.
The cell envelope of Gram-negative bacteria is a multilayered structure essential for bacterial viability; the peptidoglycan cell wall provides shape and osmotic protection to the cell, and the outer membrane serves as a permeability barrier against noxious compounds in the external environment. Assembling the envelope properly and maintaining its integrity are matters of life and death for bacteria. Our understanding of the mechanisms of envelope assembly and maintenance has increased tremendously over the past two decades. Here, we review the major achievements made during this time, giving central stage to the amino acid cysteine, one of the least abundant amino acid residues in proteins, whose unique chemical and physical properties often critically support biological processes. First, we review how cysteines contribute to envelope homeostasis by forming stabilizing disulfides in crucial bacterial assembly factors (LptD, BamA, and FtsN) and stress sensors (RcsF and NlpE). Second, we highlight the emerging role of enzymes that use cysteine residues to catalyze reactions that are necessary for proper envelope assembly, and we also explain how these enzymes are protected from oxidative inactivation. Finally, we suggest future areas of investigation, including a discussion of how cysteine residues could contribute to envelope homeostasis by functioning as redox switches. By highlighting the redox pathways that are active in the envelope of Escherichia coli, we provide a timely overview of the assembly of a cellular compartment that is the hallmark of Gram-negative bacteria.


Double-blind cluster randomised controlled trial of wheat flour chapatti fortified with micronutrients on the status of vitamin A and iron in school-aged children in rural Bangladesh.
Food fortification is a cost-effective and sustainable strategy to prevent or correct micronutrient deficiencies. A double-blind cluster (bari) randomised controlled trial was conducted in a rural community in Bangladesh to evaluate the impact of consumption of chapatti made of micronutrient-fortified wheat flour for 6 months by school-aged children on their vitamin A, haemoglobin and iron status. A total of 43 baris (group of households) were randomly selected. The baris were randomly assigned to either intervention or control group. The intervention group received wheat flour fortified with added micronutrients (including 66 mg hydrogen-reduced elemental iron and 3030 μg retinol equivalent as retinyl palmitate per kilogram of flour), while the control group received wheat flour without added micronutrients. A total of 352 children were enrolled in the trial, 203 in the intervention group and 149 in the control group. Analyses were carried out on children who completed the study (191 in the intervention group and 143 in the control group). Micronutrient-fortified wheat flour chapatti significantly increased serum retinol concentration at 6 months by 0.12 μmol L(-1) [95% confidence interval (CI): 0.06, 0.19; P < 0.01]. The odds of vitamin A deficiency was significantly lower for children in the intervention group at 3 months [odds ratio (OR) = 0.26; 95% confidence interval (CI): 0.07, 0.89; P < 0.05] and 6 months (OR = 0.21; 95% CI: 0.06, 0.68; P < 0.01). No demonstrable effect of fortified chapatti consumption on iron status, haemoglobin levels or anaemia was observed. Consumption of fortified chapattis demonstrated a significant improvement in the vitamin A status, but not in iron, haemoglobin or anaemia status.


Sex differences in affective response to opioid withdrawal during adolescence.
Drug withdrawal is suggested to play a role in precipitating mood disorders in individuals with familial predisposition. Age-related differences in affective responses to withdrawal might explain the increased risk of mental illnesses when drug use begins during adolescence. Recently we observed that, in contrast to adult male mice, adolescent males exhibited a decrease in immobility in the forced swim test on the third day of withdrawal, as compared with controls. Thus, the present study examined forced swim test behaviors of adolescent female mice during opioid withdrawal. Similar to the male study, adolescent female mice were injected with two morphine regimens which differed in dosage. Three and nine days following discontinuation of morphine administration, forced swim test immobility time and locomotion were evaluated. In contrast to males, which exhibited a decrease in immobility, no significant differences in immobility were observed in female adolescents undergoing withdrawal as compared with saline-injected controls. This sex difference in forced swim test behaviors was not due to changes in overall motor activity, since differences in locomotion were not observed in either male or female adolescent mice. Thus, this study demonstrates sex differences in forced swim test behavior during opioid withdrawal. Forced swim test behaviors are classically used to evaluate mood in rodents, thus this study suggests that opioid withdrawal might affect mood differentially across sexes.


The Relationship Between Obsessive Belief Level and Cognitive Flexibility in Patients with Obsessive Compulsive Disorder.
It is known that dysfunctional beliefs are important in the onset and maintenance of symptoms of Obsessive Compulsive Disorder (OCD) according to the cognitive model of OCD. OCD patients with higher obsessive beliefs would be expected to have greater deficits in cognitive flexibility. In this study, we aimed to examine the relationship between obsessive belief levels and cognitive flexibility in OCD patients. Patients with OCD (50) and Panic Disorder (30) as a control group were evaluated and diagnosed using Structured Clinical Interview for DSM-IV Axis I Disorders. A socio-demographic data form, Beck Depression Inventory, Beck Anxiety Inventory and Wisconsin Card Sorting Test (WCST) were administered to all the patients. The Yale-Brown Obsessive Compulsive Scale and Obsessive Beliefs Questionnaire-44 (OBQ-44) were administered to the OCD group. The OCD group was divided into two subgroups as higher obsessive beliefs (OCD-H) (n=29) and lower obsessive beliefs (OCD-L) (n=21) according to a cluster analytic approach. When the subgroups were compared according to WCST; the number of completed categories was statistically significantly lower, and the numbers of total errors, perseverative errors and non-perseverative errors were significantly higher in the OCD-H group. The results of our study show that cognitive flexibility is impaired in OCD patients with higher obsessive beliefs.


Virus Prevalence and Genetic Diversity Across a Wild Bumblebee Community.
Viruses are key population regulators, but we have limited knowledge of the diversity and ecology of viruses. This is even the case in wild host populations that provide ecosystem services, where small fitness effects may have major ecological impacts in aggregate. One such group of hosts are the bumblebees, which have a major role in the pollination of food crops and have suffered population declines and range contractions in recent decades. In this study, we investigate the diversity of four recently discovered bumblebee viruses (Mayfield virus 1, Mayfield virus 2, River Liunaeg virus, and Loch Morlich virus), and two previously known viruses that infect both wild bumblebees and managed honeybees (Acute bee paralysis virus and Slow bee paralysis virus) from isolates in Scotland. We investigate the ecological and environmental factors that determine viral presence and absence. We show that the recently discovered bumblebee viruses were more genetically diverse than the viruses shared with honeybees. Coinfection is potentially important in shaping prevalence: we found a strong positive association between River Liunaeg virus and Loch Morlich virus presence after controlling for host species, location and other relevant ecological variables. We tested for a relationship between environmental variables (temperature, UV radiation, wind speed, and prevalence), but as we had few sampling sites, and thus low power for site-level analyses, we could not conclude anything regarding these variables. We also describe the relationship between the bumblebee communities at our sampling sites. This study represents a first step in the description of predictors of bumblebee infection in the wild.


Molecular diagnosis of the 5q deletion in malignant myeloid disorders.
The 5q-chromosome is found in a spectrum of malignant myeloid disorders (1). The 5q deletion is the most commonly reported deletion in the myelodysplastic syndromes (MDS) and is found in 10-l5% of patients (1). The 5q-chromosome occurs as a sole karyotypic abnormality in the distinct myelodysplastic syndrome the 5q-syndrome (2). The 5q-chromosome is also observed frequently in therapy related MDS and acute myeloid leukemia (AML) where it is typically reported together with other karyotypic abnormalities (3). The 5q deletton is interstitial and the breakpoints are variable. The breakpoints most frequently reported are 5q12-q14 (proximal) and 5q3l-q33 (distal) (4). The most commonly reported 5q deletion is the del (5)(q13q33) (5). There appears to be no difference in the pattern of 5q deletion breakpoints between MDS and AML (4, 5).


[Safe surgery checklist: analysis of the safety and communication of teams from a teaching hospital].
This study aimed to apply the WHO surgical safety checklist in the surgical specialties of a university hospital and to evaluate the opinion of the team regarding the influence of its application on the safety of the surgical process and on the interpersonal communication of the team. It is a descriptive, analytical qualitative field study conducted in the surgical center of a university hospital Data were collected by applying the checklist in a total of 30 surgeries. The researcher conducted its application in three phases, and then members of the surgical team were invited to voluntarily participate in the study, signifying their agreement to participate by signing an informed consent form and answering guiding questions. Bardin's Content Analysis Method was used to organize and analyze the data. The subjects did not notice any changes in their interpersonal communication when using the checklist; however, they gave suggestions and reported that its use provided greater safety to the procedure.


Living with idiopathic pulmonary fibrosis: an in-depth qualitative survey of European patients.
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fatal lung disease of unknown origin. Despite recent advancements, the diagnosis and management of IPF remains a distinct clinical challenge; as a result, patients often experience considerable delays in receiving an accurate diagnosis and confusion regarding prognosis and the availability of treatment options. In order to gain further insights regarding patients' perspectives on the diagnostic process, disease education, emotional well-being, and quality of life, we conducted a qualitative in-depth survey among IPF patients in Europe. Patients with a physician-confirmed IPF diagnosis were recruited to participate in an in-depth interview conducted by a trained facilitator who used a qualitative topic guide. A total of 45 patients from 5 European countries participated in the survey. The median reported time from initial presentation to confirmed diagnosis of IPF was 1.5 years (range <1 week to 12 years); in 58% of cases there was a delay of >1 year between initial presentation and a confirmed diagnosis of IPF. Additionally, 55% of patients reported consulting ≥3 physicians before receiving an IPF diagnosis. Patient satisfaction with medical care and disease education appeared to be higher among patients who were receiving care at a recognized center of excellence. Patients generally had reasonable expectations regarding the goals of therapy, with most recognizing the irreversibility of the disease and the limited prospects for achieving a cure. The most common unmet needs cited by participants were disease education resources, access to centers of excellence, and familial support programs. Our findings suggest that patients with IPF commonly experience protracted delays in receiving an accurate diagnosis and generally perceive the level of medical care as suboptimal, despite expressing reasonable expectations regarding the goals of therapy. These results support the need for further improvement in the areas of diagnosis, disease management, and patient education.


GliomaPredict: a clinically useful tool for assigning glioma patients to specific molecular subtypes.
Advances in generating genome-wide gene expression data have accelerated the development of molecular-based tumor classification systems. Tools that allow the translation of such molecular classification schemas from research into clinical applications are still missing in the emerging era of personalized medicine. We developed GliomaPredict as a computational tool that allows the fast and reliable classification of glioma patients into one of six previously published stratified subtypes based on sets of extensively validated classifiers derived from hundreds of glioma transcriptomic profiles. Our tool utilizes a principle component analysis (PCA)-based approach to generate a visual representation of the analyses, quantifies the confidence of the underlying subtype assessment and presents results as a printable PDF file. GliomaPredict tool is implemented as a plugin application for the widely-used GenePattern framework. GliomaPredict provides a user-friendly, clinically applicable novel platform for instantly assigning gene expression-based subtype in patients with gliomas thereby aiding in clinical trial design and therapeutic decision-making. Implemented as a user-friendly diagnostic tool, we expect that in time GliomaPredict, and tools like it, will become routinely used in translational/clinical research and in the clinical care of patients with gliomas.


Correlation between premeiotic DNA replication and chromatin transition at yeast recombination initiation sites.
The DNA double-strand breaks (DSBs) that initiate meiotic recombination in Saccharomyces cerevisiae are preceded first by DNA replication and then by a chromatin transition at DSB sites. This chromatin transition, detected as a quantitative increase in micrococcal nuclease (MNase) sensitivity, occurs specifically at DSB sites and not at other MNase-sensitive sites. Replication and DSB formation are directly linked: breaks do not form if replication is blocked, and delaying replication of a region also delays DSB formation in that region. We report here experiments that examine the relationship between replication, the DSB-specific chromatin transition and DSB formation. Deleting replication origins (and thus delaying replication) on the left arm of one of the two parental chromosomes III affects DSBs specifically on that replication-delayed arm and not those on the normally replicating arm. Thus, replication timing determines DSB timing in cis. Delaying replication on the left arm of chromosome III also delays the chromatin transition at DSB sites on that arm but not on the normally replicating right arm. Since the chromatin transition precedes DSB formation and requires the function of many genes necessary for DSB formation, these results suggest that initial events for DSB formation in chromatin are coupled with premeiotic DNA replication.


Hepatic fatty acid metabolism in pigs and rats: major differences in endproducts, O2 uptake, and beta-oxidation.
Models of mammalian hepatic lipid metabolism are based largely on observations made in adult rats, emphasizing ketogenesis as a primary adjunct to mitochondrial beta-oxidation. Studies using piglets have illustrated the divergent nature of intermediary metabolism in this model, wherein ketogenesis and beta-oxidation are small and acetogenesis is an important route of fuel carbon flux. To clarify potential species differences in hepatic lipid metabolism and its control, we compared O2 consumption and metabolic end products in fasted pig and rat liver homogenates treated with 1-[14C]C16:0. Carboxyl carbon accumulation in acid-soluble products (ASP) plus CO2 was threefold greater and O2 consumption was twofold greater in rats (P < 0.05). Unlike rats, pigs showed negligible carboxyl carbon accumulation in ketone bodies (3-7% of ASP), whereas acetate was a carboxyl carbon reservoir in both animals (17-31% of ASP in pigs). Malonate increased (approximately 2-fold) and antimycin/rotenone decreased (40-60%) radiolabel accumulation in acetate. These data concur with the hypotheses that comparatively low hepatic beta-oxidative flux in piglets is partially related to a smaller metabolic rate and that substantial acetogenesis occurs intramitochondrially in both pigs and rats.


Chemical composition and in vitro antibacterial activity of essential oil and methanol extract of Echinophora platyloba D.C against some of food-borne pathogenic bacteria.
Echinophora Platyloba D.C as a medicinal plant is used for preservation of foods and treatment of many diseases in different regions of Iran. The present study was undertaken to determine the chemical composition and investigation of the antibacterial effects of essential oil as well as methanol extract from aerial part of Echinophora Platyloba D.C against S. aureus, L. monocytogenes, S. Thyphimurium and E. coli. Chemical analysis using gas chromatography and mass spectrophotometry (GC/MS) showed that ocimene (26.51%), 2,3-Dimethyl-cyclohexa-1,3-diene (9.87%), alpha-pinene (7.69%) and gamma-dodecanolactone (5.66%) were dominant components of essential oil and the main constituents of methanol extract were o-Cymene (28.66%), methanol (8.50%), alpha-pinene (7.42%) and gamma-decalactone (5.20%). The essential oil showed strong antimicrobial activity against tested bacteria, whereas the methanol extract almost remained inactive against gram-negative bacteria. The most sensitive bacteria to essential oil and extract of Echinophora Platyloba D.C were L. mono-cytogenes and S. aureus. Minimum inhibitory concentration (MIC) values of essential oil against L. monocytogenes and S. aureus were 6250 and 12500 ppm, respectively. MIC of methanol extract against S. aureus and L. monocytogenes was 25000 ppm. Therefore, purifying and evaluation of antibacterial effects of the active substances of the essential oil and methanol extract of this plant for future application as antibacterial agents and food preservatives to combat pathogenic and toxigenic microorganisms is recommended.


Enzyme Digestive Activities During Ontogeny in Marosatherina ladigesi Larvae.
Marosatherina ladigesi, including native fish in South Sulawesi Indonesia, are vulnerable and must be preserved. The objective of the study was to examine known food consumption, survival, growth and the activities of digestive enzymes of M. ladigesi larvae. The larvae were obtained from natural spawning and the mixed live feed: Infusoria sp., Daphnia sp. and Artemia salina were given twice a day. Feed intake, growth, survival, activities of protease, lipase and amylase enzymes were observed in ages 3, 5, 10, 15, 20, 25, 30, 35 Days after Hatching (DAH). Data were analyzed by following a complete randomized trial design. Activities of protease, amylase and lipase enzymes have been detected since 3 DAH. The protease enzyme activity was obtained at 0.438 U mL min-1 at 35 DAH, while amylase and lipase activities fluctuated. Activities of amylase and lipase reached 0105 and 0.093 U mL-1 min-1 at 15 DAH, respectively. The activity of the enzyme increased at the same age of 10-15 DAH larvae entering a phase of flexion. It was concluded that the use of mixed live feed Infusoria sp., Daphnia sp. and A. salina contribute to enzyme protease, lipase and amylase activities during the ontogeny stages of M. ladigesi. The highest activity of protease suggests that the fish have carnivorous feeding habits. The results of this study can be used to improve the maintenance technique of M. ladigesi larvae in order to accelerate growth and improve survival as an effort to increase the production of M. ladigesi.


Molecular modeling of the non-covalent binding of the dietary tomato carotenoids lycopene and lycophyll, and selected oxidative metabolites with 5-lipoxygenase.
Numerous studies on human prostate cancer cell lines indicate a role for arachidonic acid (AA) and its oxidative metabolites in prostate cancer proliferation. The metabolism of AA by either the cyclooxygenase (COX) or the lipoxygenase (LOX) pathways generates eicosanoids involved in tumor promotion, progression, and metastasis. In particular, products of the 5-LOX pathway (including 5-HETE and 5-oxo-EET) have been implicated as potential 'survival factors' that may confer escape after androgen withdrawal therapy through fatty-acid (i.e., AA) drive. Potent natural dietary antioxidant compounds such as lycopene and lycophyll, with tissue tropism for human prostate, have been shown to be effective in ameliorating generalized oxidative stress at the DNA level. Suppressing the 5-LOX axis pharmacologically is also a promising avenue for intervention in human patients. The recently recognized direct interaction of the astaxanthin-based soft-drug Cardax to human 5-LOX with molecular modeling, and the downregulation of both 5-HETE and 5-oxo-EET in vivo in a murine peritonitis model, suggest that other important dietary carotenoids may share this enzyme regulatory feature. In the current study, the acyclic tomato carotene lycopene (in all-trans and 5-cis isomeric configurations) and its natural dihydroxy analog lycophyll (also present in tomato fruit) were subjected to molecular modeling calculations in order to investigate their predicted binding interaction(s) with human 5-LOX. Two bioactive oxidative metabolites of lycopene (4-methyl-8-oxo-2,4,6-nonatrienal and 2,7,11-trimethyl-tetradecahexaene-1,14-dial) were also investigated. A homology model of 5-LOX was constructed using 8-LOX and 15-LOX structures as templates. The model was validated by calculating the binding energy of Cardax to 5-LOX, which was demonstrated to be in good agreement with the published experimental data. Blind docking calculations were carried out in order to explore the possible binding sites of the carotenoids on 5-LOX, followed by focused docking to more accurately calculate the predicted energy of binding. Lycopene and lycophyll were predicted to bind with high affinity in the superficial cleft at the interface of the beta-barrel and the catalytic domain of 5-LOX (the 'cleavage site'). Carotenoid binding at this cleavage site provides the structural rationale by which polyenic compounds could modify the 5-LOX enzymatic function via an allosteric mechanism, or by radical scavenging in proximity to the active center. In addition, the two bioactive metabolites of lycopene were predicted to bind to the catalytic site with high affinity--therefore suggesting potential direct competitive inhibition of 5-LOX activity that should be shared by both lycopene and lycophyll after in vivo supplementation, particularly in the case of the dial metabolite.


[Crown and bridgework prostheses. A survey of the literature].
From 1975 to 1977, 20 dental journals of German, Anglo-American, French and Scandinavian origin were examined for articles concerning crowns and bridges. 286 articles specifically concerned fixed prosthetics, and certain subjects were treated more than others (metal ceramics, relation between restorations and periodontium). It was attempted to give a survey of articles that were clinically oriented, which permitted to reduce the number of articles reviewed.


Low-dose methotrexate results in the selective accumulation of aminoimidazole carboxamide ribotide in an erythroblastoid cell line.
Therapeutic and toxic response to low-dose methotrexate (MTX) in the treatment of autoimmune disease continues to be highly variable, resulting in a critical need to identify predictive biomarkers of response. Biomarker development has been hampered by an incomplete understanding of the molecular pharmacology of low-dose MTX. To address this issue, accumulation of the substrates for aminoimidazole carboxamide ribonucleotide transformylase (AICART) and thymidylate synthase (TS) was measured as markers of pharmacological activity of MTX in an erythroblastoid cell line. A 115-fold increase in the AICART substrate and anti-inflammatory mediator, 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranosyl 5'-monophosphate (ZMP), was observed following exposure to 10 nM MTX but subsequently decreased with increasing MTX concentrations, declining to baseline levels with 1000 nM MTX. In contrast, the TS substrate, 2'-deoxyuridine 5'-monophosphate disodium salt (dUMP), displayed concentration-dependent accumulation, increasing 29-, 342-, and 471-fold over baseline with 10, 100, and 1000 nM MTX, respectively. Cellular levels of dUMP correlated with levels of the parent drug (MTX-PG1; r = 0.66, P < 0.001) and its polyglutamates (MTX-PG2-6) (r = 0.81, P < 0.001), whereas cellular levels of ZMP were only moderately correlated with MTX-PG1 (r = 0.34, P < 0.01). In contrast, accumulation of ZMP at 10 nM MTX was associated with a 2.9-fold increase in the AICART inhibitor dihydrofolate (DHF), represented primarily by long-chain DHF polyglutamates. Selectivity, defined as the ratio of ZMP to dUMP, was maximal following exposure to 6 nM MTX. Characterizing the range of MTX concentrations that selectively promote ZMP accumulation while preserving pyrimidine biosynthesis may lead to optimization of low-dose MTX therapy.


Comparative efficacy and safety of interventions for preventing chemotherapy-induced oral mucositis in adult cancer patients: a systematic review and network meta-analysis.
To examine the comparative efficacy and safety of interventions for preventing chemotherapy-induced oral mucositis (OM) in adult cancer patients. We searched PubMed, Embase and the Cochrane Central systematically for the randomised control trials (RCTs) of interventions for preventing OM. Network meta-analysis (NMA) was performed to estimate risk ratios (RR) and 95% confidence intervals (CI) from both direct and indirect evidence. The primary outcome was any grade of OM. Secondary outcomes were mild-moderate OM, severe OM and adverse events, such as taste disturbance and gastrointestinal adverse events. This study was registered with PROSPERO, number CRD42016052489. A total of 29 RCTs with 2348 patients (median age, 56.1 years; 57.5% male) were included. Cryotherapy was associated with a significantly lower risk of OM than control (RR 0.51, 95% CI 0.38 to 0.68), and zinc sulphate (RR 0.47, 95% CI 0.23 to 0.97), but not significantly lower than sucralfate and palifermin. No significant differences were observed between cryotherapy and control for taste disturbance and gastrointestinal adverse events. Palifermin was associated with the highest risk of taste disturbance. This NMA suggests that cryotherapy was the most effective intervention for preventing chemotherapy-induced OM with a safety profile similar to control, but not significantly lower than sucralfate and palifermin. Large RCTs are needed to confirm these findings.


Design of potential anti-tumor PARP-1 inhibitors by QSAR and molecular modeling studies.
Poly ADP-ribose polymerase-1 (PARP-1) inhibitors have been recognized as new agents for the treatment of patients with breast cancer type 1 (BRCA1) disorders. The quantitative structure-activity relationships (QSAR) technique was used in order to achieve the required medicines for anticancer activity easier and faster. In this study, the QSAR method was developed to predict the half-maximal inhibitory concentration (IC50) of 51 1H-benzo[d]immidazole-4-carboxamide derivatives by genetic algorithm-multiple linear regression (GA-MLR) and least squares-support vector machine (LS-SVM) methods. Results in the best QSAR model represented the coefficient of leave-one-out cross-validation (Q cv 2 ) = 0.971, correlation coefficient (R2) = 0.977, Fisher parameter (F) = 259.016 and root mean square error (RMSE) = 0.095, respectively, which indicated that the LS-SVM model had a good potential to predict the pIC50 (9 - log(IC50 nM)) values compared with other modeling methods. Also, molecular docking evaluated interactions between ligands and enzyme and their free energy of binding were calculated and used as descriptors. Molecular docking and the QSAR study completed each other. The results represented that the final model can be useful to design some new inhibitors. So, the knowledge of the QSAR modeling and molecular docking was used in pIC50 prediction and 51 new compounds were developed as PARP-1 inhibitors that 9 compounds had the best-proposed values for pIC50. The maximum enhancement of the inhibitory activity of compounds was 33.394%.


A facilely controlled length, cytotoxicity, length-dependent and cell type-dependent cellular uptake of silica nanotubes and their applications in the delivery of immunostimulatory CpG oligodeoxynucleotides.
A controllable length of inorganic nanotubes as a drug delivery system is crucial to understanding internalization mechanisms and designing new biomedical applications. In this study, silica nanotubes (SiNTs) with controlled length ranging from several hundred nanometers to several micrometers were firstly fabricated via a facile and effective acid-degradation collagen template route and then functionalized with chitosan (ChSiNTs) to deliver immunostimulatory cytosine-phosphodiester-guanine oligodeoxynucleotides (CpG ODNs). It was found that the length of SiNTs could be well controlled through the adjustment of the acid-treatment temperature. Cytotoxic assessment indicated that SiNTs exhibited good biocompatibility when separately incubated with four types of cell lines: 293XL-hTLR9, A549, NIH3T3, and C2C12. The cellular uptake of SiNTs was strongly affected by their length and cell type. A decrease in the length led to an increase in the cellular uptake of SiNTs, while a significantly higher cellular uptake by C2C12 cells was observed in comparison with A549 and NIH3T3 cells. An immunochemical assay revealed that SiNTs were located in the endolysosomes after cellular internalization. ChSiNTs were positive and well complexed with negative CpG ODNs to produce a ChSiNT/CpG ODN complex (CpG-ChSiNT) via electric force. ChSiNTs were located in the endolysosomes after internalization and enhanced the cellular uptake of CpG-ODNs. CpG ODNs could be released from CpG-ChSiNTs in a sustained way and specifically recognized by the TLR9 receptor in 293XL-hTLR9 cells. The amount of interleukin-6 cytokine stimulated by CpG-ChSiNT against peripheral blood mononuclear cells was higher than that by free CpG ODNs and ChSiNTs significantly enhanced the immunostimulatory response of CpG ODNs.


Pulmonary alveolar macrophages contribute to the premetastatic niche by suppressing antitumor T cell responses in the lungs.
In contrast to tumor-associated macrophages, myeloid-derived suppressor cells, or inflammatory monocytes, functions of tissue resident macrophages, including alveolar macrophages (AM), in cancer were not well studied. Using a mouse model of breast cancer, we show that AM promote cancer metastasis to the lungs by suppressing antitumor T cells in this organ. AM accumulated in the premetastatic lungs through complement C5a receptor-mediated proliferation but not through recruitment from the circulation. AM preconditioned by breast tumors inhibited Th1 and favored generation of Th2 cells that had lower tumoricidal activity than Th1 cells. In addition, AM reduced the number and maturation of lung dendritic cells by regulating TGF-β in the lung environment. Depletion of AM reversed immunosuppression imposed by these cells and strengthened local Th1 responses, which significantly reduced lung metastatic burden. C5a receptor deficiency, which also lessens myeloid-derived suppressor cells in the premetastatic niche, synergized with the depletion of AM in preventing metastasis, leading to protection of mice from lung metastases. This study identifies AM as a new component of the premetastatic niche, which is harnessed by tumors to impose immunosuppression, and as a new target for cancer immunotherapies to eliminate or reduce metastasis. Because the lungs are the most common target for hematogenous metastasis, this research offers a plausible explanation for susceptibility of the lungs to cancer metastasis.


Three-dimensional HepaRG model as an attractive tool for toxicity testing.
The culture of HepaRG cells as three dimensional (3D) structures in the spinner-bioreactor may represent added value as a hepatic system for toxicological purposes. The use of a cost-effective commercially available bioreactor, which is compatible with high-throughput cell analysis, constitutes an attractive approach for routine use in the drug testing industry. In order to assess specific aspects of the biotransformation capacity of the bioreactor-based HepaRG system, the induction of CYP450 enzymes (i.e., CYP1A2, 2B6, 2C9, and 3A4) and the activity of the phase II enzyme, uridine diphosphate glucuronoltransferase (UGT), were tested. The long-term functionality of the system was demonstrated by 7-week stable profiles of albumin secretion, CYP3A4 induction, and UGT activities. Immunofluorescence-based staining showed formation of tissue-like arrangements including bile canaliculi-like structures and polar distribution of transporters. The use of in silico models to analyze the in vitro data related to hepatotoxic activity of acetaminophen (APAP) demonstrated the advantage of the integration of kinetic and dynamic aspects for a better understanding of the in vitro cell behavior. The bioactivation of APAP and its related cytotoxicity was assessed in a system compatible to high-throughput screening. The approach also proved to be a good strategy to reduce the time necessary to obtain fully differentiated cell cultures. In conclusion, HepaRG cells cultured in 3D spinner-bioreactors are an attractive tool for toxicological studies, showing a liver-like performance and demonstrating a practical applicability for toxicodynamic approaches.


Molecular and morphological characterization of Belondira coomansi n. sp. (Nematoda: Dorylaimida, Belondiridae) from Iran.
A new species belonging to the genus Belondira is described from natural areas in Iran. Belondira coomansi n. sp. is characterized by its general size, the dimensions and appearance of its lip region, presence of distinct labial and post-labial sclerotization, the length of the odontostyle and its inconspicuous lumen and aperture, the length of the neck and its pharyngeal expansion, the reduction of the female anterior genital branch to a simple uterine sac, a very short posterior uterus, the anterior position of the vulva, the length and shape of the caudal region with distinctly thick cuticle at its tip, the length of the spicules, and the presence of only one pair of ventromedian supplements. The new species is close to Belondira brevibulba, B. sacchari, B. tenuidens and B. thornei, and it is compared to them. Molecular characterization (D2-D3 expansion segments of the rRNA large subunit) of the new species is also provided, representing only the second species of this genus for which any DNA sequence data are available.


Monensin and FCCP inhibit the intracellular transport of alphavirus membrane glycoproteins.
Temperature-sensitive mutants of semliki forest virus (SFV) and sindbis virus (SIN) were used to study the intracellular transport of virus membrane glycoproteins in infected chicken embryo fibroblasts. When antisera against purified glycoproteins and (125)I- labeled protein A from staphylococcus aureus were used only small amounts of virus glycoproteins were detected at the surface of SFV ts-1 and SIN Ts-10 infected cells incubated at the restrictive temperature (39 degrees C). When the mutant-infected cells were shifted to the permissive temperature (28 degrees C), in the presence of cycloheximide, increasing amounts of virus glycoproteins appeared at the cell surface from 20 to 80 min after the shift. Both monensin (10muM) and carbonylcyanide-p- trifluoromethoxyphenylhydrazone (FCCP; 10-20 muM) inhibited the appearance of virus membrane glycoproteins at the cell surface. Vinblastine sulfate (10 mug/ml) inhibited the transport by approximately 50 percent, whereas cytochalasin B (1 mug/ml) had only a marginal effect. Intracellular distribution of virus glycoproteins in the mutant-infected cells was visualized in double-fluorescence studies using lectins as markers for endoplasmic reticulum and Golgi apparatus. At 39 degrees C, the virus membrane glycoproteins were located at the endoplasmic reticulum, whereas after shift to 28 degrees C, a bright juxtanuclear reticular fluorescence was seen in the location of the Golgi apparatus. In the presence of monensin, the virus glycoproteins could migrate to the Golgi apparatus, although transport to the cell surface did not take place. When the shift was carried out in the presence of FCCP, negligible fluorescence was seen in the Golgi apparatus and the glycoproteins apparently remained in the rough endoplasmic reticulum. A rapid inhibition in the accumulation of virus glycoproteins at the cell surface was obtained when FCCP was added during the active transport period, whereas with monensin there was a delay of approximately 10 min. These results suggest a similar intracellular pathway in the maturation of both plasma membrane and secretory glycoproteins.


Competitive Memory Training (COMET) for low self-esteem in patients with personality disorders: a randomized effectiveness study.
Self-esteem is a major concern in the treatment of patients with personality disorders in general. In patients with borderline personality disorder, low self-esteem is associated with factors contributing to suicidal and self-injurious behaviour. At the moment there are no well-proven interventions that specifically target low self-esteem. Recently, a new approach, Competitive Memory Training or COMET, aimed at the enhancement of retrieving beneficial information from memory, appeared to be successful in addressing low self-esteem in different patient populations. To assess whether COMET for low self-esteem is also an effective intervention for patients with personality disorders. 91 patients with personality disorders who were already in therapy in a regular mental health institution were randomly assigned to either 7 group sessions of COMET in addition to their regular therapy or to 7 weeks of ongoing regular therapy. These latter patients received COMET after their "7 weeks waiting period for COMET". All patients that completed COMET were contacted 3 months later to assess whether the effects of COMET had remained stable. Compared to the patients who received regular therapy only, patients in the COMET + regular therapy condition improved significantly and with large effect sizes on indices of self-esteem and depression. Significant differential improvements on measures of autonomy and social optimism were also in favour of COMET, but had small to intermediate effect sizes. The therapeutic effects of COMET remained stable after 3 months on three out of the four outcome measures. COMET for low self-esteem seems to be an efficacious trans-diagnostic approach that can rather easily be implemented in the treatment of patients with personality disorders.


New Respiratory Inductive Plethysmography (RIP) Method for Evaluating Ventilatory Adaptation during Mild Physical Activities.
The pneumotachometer is currently the most accepted device to measure tidal breathing, however, it requires the use of a mouthpiece and thus alteration of spontaneous ventilation is implied. Respiratory inductive plethysmography (RIP), which includes two belts, one thoracic and one abdominal, is able to determine spontaneous tidal breathing without the use of a facemask or mouthpiece, however, there are a number of as yet unresolved issues. In this study we aimed to describe and validate a new RIP method, relying on a combination of thoracic RIP and nasal pressure signals taking into account that exercise-induced body movements can easily contaminate RIP thoracic signals by generating tissue motion artifacts. A custom-made time domain algorithm that relies on the elimination of low amplitude artifacts was applied to the raw thoracic RIP signal. Determining this tidal ventilation allowed comparisons between the RIP signal and simultaneously-recorded airflow signals from a calibrated pneumotachometer (PT). We assessed 206 comparisons from 30 volunteers who were asked to breathe spontaneously at rest and during walking on the spot. Comparisons between RIP signals processed by our algorithm and PT showed highly significant correlations for tidal volume (Vt), inspiratory (Ti) and expiratory times (Te). Moreover, bias calculated using the Bland and Altman method were reasonably low for Vt and Ti (0.04 L and 0.02 s, respectively), and acceptable for Te (<0.1 s) and the intercept from regression relationships (0.01 L, 0.06 s, 0.17 s respectively). The Ti/Ttot and Vt/Ti ratios obtained with the two methods were also statistically correlated. We conclude that our methodology (filtering by our algorithm and calibrating with our calibration procedure) for thoracic RIP renders this technique sufficiently accurate to evaluate tidal ventilation variation at rest and during mild to moderate physical activity.


Burden and Associated Factors of Virological Failure Among People Living with HIV in Sub-Saharan Africa: A Systematic Review and Meta-Analysis.
United Nations program on HIV/AIDS 90-90-90 ambitious goal recommends 90% of people living with HIV and taking antiretroviral therapy should achieve viral suppression by 2020. However, virological failure is still a global public health problem, especially in sub-Saharan African countries. Thus, this systematic review and meta-analysis aimed at estimating the burden of virological failure and its associated factors among peoples living with HIV in sub-Saharan Africa. We searched Google Scholar, PubMed, Cochrane Library, and Scopus for studies that reported virologic failure and its associated factors. I-squared statistics and Egger's statistical test were used to detect heterogeneity and publication bias respectively. The pooled prevalence of virological failure was estimated using the DerSimonian-Laird random-effects model. Sensitivity analysis was done to check the presence of outlier results included in the studies. The estimated pooled prevalence of virological failure was 1.7.25%. Lower Adherence to ART drugs,longer ART duration, lower CD4 count,and being co-infected with TB were significantly associated with the pooled estimate of virological failure.Virological failure was found to be high in sub-Saharan Africa. Adherence, duration of ART, CD4 + count, and TB co-infection were the significant factors associated with the pooled estimate of virological failure. Therefore, to achieve the 90-90-90 target and sustainable development goal 3 policymakers should design mechanisms to improve ART adherence, and early detecting and prevent opportunistic infections such as TB.


A change in ionization of the NADP(H)-binding component (dIII) of proton-translocating transhydrogenase regulates both hydride transfer and nucleotide release.
Transhydrogenase couples the transfer of hydride-ion equivalents between NAD(H) and NADP(H) to proton translocation across a membrane. The enzyme has three components: dI binds NAD(H), dIII binds NADP(H) and dII spans the membrane. Coupling between transhydrogenation and proton translocation involves changes in the binding of NADP(H). Mixtures of isolated dI and dIII from Rhodospirillum rubrum transhydrogenase catalyse a rapid, single-turnover burst of hydride transfer between bound nucleotides; subsequent turnover is limited by NADP(H) release. Stopped-flow experiments showed that the rate of the hydride transfer step is decreased at low pH. Single Trp residues were introduced into dIII by site-directed mutagenesis. Two mutants with similar catalytic properties to those of the wild-type protein were selected for a study of nucleotide release. The way in which Trp fluorescence was affected by nucleotide occupancy of dIII was different in the two mutants, and hence two different procedures for determining the rate of nucleotide release were developed. The apparent first-order rate constants for NADP(+) release and NADPH release from isolated dIII increased dramatically at low pH. It is concluded that a single ionisable group in dIII controls both the rate of hydride transfer and the rate of nucleotide release. The properties of the protonated and unprotonated forms of dIII are consistent with those expected of intermediates in the NADP(H)-binding-change mechanism. The ionisable group might be a component of the proton-translocation pathway in the complete enzyme.


Modulation of the urokinase-type plasminogen activator receptor by the beta6 integrin subunit.
Over-expression of components of the urokinase system is well documented in cancer and is thought to enable tumour cells to migrate and invade. Changes in integrin expression are also a common feature of tumours and have been linked to changes in protease activity. It has been shown that the alphavbeta6 integrin is neo-expressed in a number of epithelial carcinomas and in wound healing situations. We therefore investigated whether alphavbeta6 is able to modulate a key regulator of proteolysis, the urokinase receptor. We report that epithelial cells expressing full-length alphavbeta6 exhibit decreased urokinase receptor expression and function. Furthermore, this novel modulation requires the C-terminal 11 amino acids of the cytoplasmic tail of the beta6 integrin subunit. Cells expressing alphavbeta3, however, did not affect urokinase receptor expression. De novo expression of beta6 by melanoma cells and beta3 by epithelial cells did not influence urokinase receptor expression or function, suggesting that modulation of urokinase system is both integrin subunit and cell-specific.