Topical vitamin A treatment of recalcitrant common warts.
Common warts (verruca vulgaris) are benign epithelial proliferations associated with human papillomavirus (HPV) infection. Salicylic acid and cryotherapy are the most frequent treatments for common warts, but can be painful and cause scarring, and have high failure and recrudescence rates. Topical vitamin A has been shown to be a successful treatment of common warts in prior informal studies. The subject is a healthy, physically-active 30 old female with a 9 year history of common warts on the back of the right hand. The warts resisted treatment with salicylic acid, apple cider vinegar and an over-the-counter blend of essential oils marketed for the treatment of warts. Daily topical application of natural vitamin A derived from fish liver oil (25,000 IU) led to replacement of all the warts with normal skin. Most of the smaller warts had been replaced by 70 days. A large wart on the middle knuckle required 6 months of vitamin A treatment to resolve completely. Retinoids should be further investigated in controlled studies to determine their effectiveness in treating common warts and the broad range of other benign and cancerous lesions induced by HPVs.


A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients. Prophylaxis in Medical Patients with Enoxaparin Study Group.
The efficacy and safety of thromboprophylaxis in patients with acute medical illnesses who may be at risk for venous thromboembolism have not been determined in adequately designed trials. In a double-blind study, we randomly assigned 1102 hospitalized patients older than 40 years to receive 40 mg of enoxaparin, 20 mg of enoxaparin, or placebo subcutaneously once daily for 6 to 14 days. Most patients were not in an intensive care unit. The primary outcome was venous thromboembolism between days 1 and 14, defined as deep-vein thrombosis detected by bilateral venography (or duplex ultrasonography) between days 6 and 14 (or earlier if clinically indicated) or documented pulmonary embolism. The duration of follow-up was three months. The primary outcome could be assessed in 866 patients. The incidence of venous thromboembolism was significantly lower in the group that received 40 mg of enoxaparin (5.5 percent [16 of 291 patients]) than in the group that received placebo (14.9 percent [43 of 288 patients]) (relative risk, 0.37; 97.6 percent confidence interval, 0.22 to 0.63; P< 0.001). The benefit observed with 40 mg of enoxaparin was maintained at three months. There was no significant difference in the incidence of venous thromboembolism between the group that received 20 mg of enoxaparin (43 of 287 patients [15.0 percent]) and the placebo group. The incidence of adverse effects did not differ significantly between the placebo group and either enoxaparin group. By day 110, 50 patients had died in the placebo group (13.9 percent), 51 had died in the 20-mg group (14.7 percent), and 41 had died in the 40-mg group (11.4 percent); the differences were not significant. Prophylactic treatment with 40 mg of enoxaparin subcutaneously per day safely and effectively reduces the risk of venous thromboembolism in patients with acute medical illnesses.


A mitochondrial retroplasmid integrates into mitochondrial DNA by a novel mechanism involving the synthesis of a hybrid cDNA and homologous recombination.
The Mauriceville and Varkud mitochondrial plasmids of Neurospora spp. are closely related, small circular DNAs that propagate via an RNA intermediate and reverse transcription. Although the plasmids ordinarily replicate autonomously, they can also integrate into mitochondrial DNA (mtDNA), yielding defective mtDNAs that in some cases cause senescence. To investigate the integration mechanism, we analyzed four cases in which the Varkud plasmid integrated into the mitochondrial small rRNA gene, three in wild-type subcultures and one in a senescent mutant. Our analysis suggests that the integrations occurred by the plasmid reverse transcriptase template switching between the plasmid transcript and internal sequences in the mitochondrial small rRNA to yield hybrid cDNAs that circularized and recombined homologously with the mtDNA. The integrated plasmid sequences are transcribed, presumably from the mitochondrial small rRNA promoters, resulting in hybrid RNAs containing the 5' segment of the mitochondrial small rRNA linked head-to-tail to the full-length plasmid transcript. Analysis of additional senescent mutants revealed three cases in which the plasmid used the same mechanism to integrate at other locations in the mtDNA. In these cases, circular variant plasmids that had incorporated a mitochondrial tRNA or tRNA-like sequence by template switching integrated by homologous recombination at the site of the corresponding tRNA or tRNA-like sequence in mtDNA. This simple integration mechanism involving template switching to generate a hybrid cDNA that integrates homologously could have been used by primitive retroelements prior to the acquisition of a specialized integration machinery.


Functional and topological analysis of yeast acyl-CoA:diacylglycerol acyltransferase 2, an endoplasmic reticulum enzyme essential for triacylglycerol biosynthesis.
Acyl-CoA:diacylglycerol acyltransferase (EC 188.8.131.52) is a membrane protein present mainly in the endoplasmic reticulum. It catalyzes the final and committed step in the biosynthesis of triacylglycerol, which is the principal repository of fatty acids for energy utilization and membrane formation. Two distinct family members of acyl-CoA:diacylglycerol acyltransferase, known as DGAT1 and DGAT2, have been characterized in different organisms, including mammals, fungi, and plants. In this study, we characterized the functional role and topological orientation of signature motifs in yeast (Saccharomyces cerevisiae) DGAT2 using mutagenesis in conjunction with chemical modification. Our data provide evidence that both the N and C termini are oriented toward the cytosol and have different catalytic roles. A highly conserved motif, (129)YFP(131), and a hydrophilic segment exclusive to yeast DGAT2 reside in a long endoplasmic reticulum luminal loop following the first transmembrane domain and play an essential role in enzyme catalysis. In addition, the strongly conserved His(195) within the motif HPHG, which may play a role in the active site of DGAT2, is likely embedded in the membrane. These results indicate some similarities to the topology model of murine DGAT2 but also reveal striking differences suggesting that the topological organization of DGAT2 is not ubiquitously conserved.


Identification of pathogenic fungi with an optoelectronic nose.
Human fungal infections have gained recent notoriety following contamination of pharmaceuticals in the compounding process. Such invasive infections are a more serious global problem, especially for immunocompromised patients. While superficial fungal infections are common and generally curable, invasive fungal infections are often life-threatening and much harder to diagnose and treat. Despite the increasing awareness of the situation's severity, currently available fungal diagnostic methods cannot always meet diagnostic needs, especially for invasive fungal infections. Volatile organic compounds produced by fungi provide an alternative diagnostic approach for identification of fungal strains. We report here an optoelectronic nose based on a disposable colorimetric sensor array capable of rapid differentiation and identification of pathogenic fungi based on their metabolic profiles of emitted volatiles. The sensor arrays were tested with 12 human pathogenic fungal strains grown on standard agar medium. Array responses were monitored with an ordinary flatbed scanner. All fungal strains gave unique composite responses within 3 hours and were correctly clustered using hierarchical cluster analysis. A standard jackknifed linear discriminant analysis gave a classification accuracy of 94% for 155 trials. Tensor discriminant analysis, which takes better advantage of the high dimensionality of the sensor array data, gave a classification accuracy of 98.1%. The sensor array is also able to observe metabolic changes in growth patterns upon the addition of fungicides, and this provides a facile screening tool for determining fungicide efficacy for various fungal strains in real time.


Low-temperature electrospun silk scaffold for in vitro mucosal modeling.
Electrospinning is often used to create scaffolding as a biomimetic of the extracellular matrix of tissues. A frequent limitation of this technique for three-dimensional tissue modeling is poor cell infiltration throughout the void volume of scaffolds. Here, we generated low-temperature electrospun silk scaffolds and compared these with conventional electrospun silk scaffolds in terms of mechanical properties, void volume, cell infiltration, cell viability, and potential to support mucosal models under three-dimensional culture conditions. Low-temperature electrospun silk scaffolds supported fibroblast attachment and infiltration throughout the volume of the scaffolds, while conventional electrospun scaffolds exhibited limited cell infiltration with fibroblasts attaching exclusively to the seeding surface of the scaffolds. The porosity of low-temperature electrospun scaffolds was 93% compared with 88% of conventional electrospun silk scaffolds. Uniaxial tensile testing showed a 3.5-fold reduction in strength of low-temperature electrospun silk compared with the conventional in terms of peak stress and modulus but no significant change in strain at break. Mucosal modeling with fibroblast-keratinocyte or fibroblast-carcinoma cocultures showed similar results, with cell infiltration occurring only in low-temperature electrospun scaffolds. Cell viability was confirmed using live/dead staining after 21 days in culture. Furthermore, low-temperature electrospun silk scaffolds were able to support keratinocyte differentiation, as judged by involucrin immunoreactivity. The low-temperature electrospun silk scaffold that we have developed eliminates the limitation of electrospun silk scaffolds in terms of cell infiltration and, therefore, can potentially be used for a wide range of tissue engineering purposes ranging from in vitro tissue modeling to in vivo tissue regeneration purposes.


Development of the larval anterior neurogenic domains of Terebratalia transversa (Brachiopoda) provides insights into the diversification of larval apical organs and the spiralian nervous system.
Larval features such as the apical organ, apical ciliary tuft, and ciliated bands often complicate the evaluation of hypotheses regarding the origin of the adult bilaterian nervous system. Understanding how neurogenic domains form within the bilaterian head and larval apical organ requires expression data from animals that exhibit aspects of both centralized and diffuse nervous systems at different life history stages. Here, we describe the expression of eight neural-related genes during the larval development of the brachiopod, Terebratalia transversa. Radially symmetric gastrulae broadly express Tt-Six3/6 and Tt-hbn in the animal cap ectoderm. Tt-NK2.1 and Tt-otp are restricted to a central subset of these cells, and Tt-fez and Tt-FoxQ2 expression domains are already asymmetric at this stage. As gastrulation proceeds, the spatial expression of these genes is split between two anterior ectodermal domains, a more dorsal region comprised of Tt-Six3/6, Tt-fez, Tt-FoxQ2, and Tt-otp expression domains, and an anterior ventral domain demarcated by Tt-hbn and Tt-NK2.1 expression. More posteriorly, the latter domains are bordered by Tt-FoxG expression in the region of the transverse ciliated band. Tt-synaptotagmin 1 is expressed throughout the anterior neural ectoderm. All genes are expressed late into larval development. The basiepithelial larval nervous system includes three neurogenic domains comprised of the more dorsal apical organ and a ventral cell cluster in the apical lobe as well as a mid-ventral band of neurons in the mantle lobe. Tt-otp is the only gene expressed in numerous flask-shaped cells of the apical organ and in a subset of neurons in the mantle lobe. Our expression data for Tt-Six3/6, Tt-FoxQ2, and Tt-otp confirm some aspects of bilaterian-wide conservation of spatial partitioning within anterior neurogenic domains and also suggest a common origin for central otp-positive cell types within the larval apical organs of spiralians. However, the field of sensory neurons within the larval apical organ of Terebratalia is broader and composed of more cells relative to those of other spiralian larvae. These cellular differences are mirrored in the broader spatial and temporal expression patterns of Tt-FoxQ2 and Tt-otp. Corresponding differences in the expression of Tt-hbn, Tt-NK2.1, and Tt-FoxG are also observed relative to their respective domains within the cerebral ganglia of spiralians. Based on these data we argue that the anterior region of the bilaterian stem species included Six3/6, NK2.1, otp, hbn, fez, and FoxQ2 expression domains that were subsequently modified within larval and adult neural tissues of protostome and deuterostome animals.


mRNA localisation gets more complex.
Recent advances in techniques for visualising mRNA movement in living cells have led to rapid progress in understanding the mechanism of mRNA localisation in the cytoplasm. There is an emerging consensus that in many cases the mRNA signals that determine intracellular destination are more complex and difficult to define than was first anticipated. Furthermore, the transacting factors that interpret the mRNA signals are numerous and their combinations change during the life of an mRNA, perhaps allowing the selection of many sub-destinations in the cell. Lastly, an emerging theme over the past few years is that many proteins that determine the destinations of mRNAs are recruited on nascent transcripts in the nucleus. They often function in many different processes in the biogenesis of mRNA and probably act in concert to provide specificity.


Real-time measurements of spatial velocity distribution with a laser Doppler imaging system.
A new laser Doppler imaging system with a TV camera has been constructed, which brightly displays 1-D velocity distribution on a monitor. Some characteristics of this system have been experimentally investigated from measurements of simple velocity distribution on a constantly rotating ground glass disk. From an adaptation to fluid flow, it has been shown that the measurements of spatial velocity distribution can be achieved in real time.


Sexual Competition Among Male Blue Crab, Callinectes sapidus.
Experiments and field data on blue crab, Callinectes sapidus, from mid-Chesapeake Bay between 1991 and 1994 were used to test whether large males have advantages over small males in accessing females and in sperm competition. In the field, large males were paired more often, especially with large, more fecund females. However, the variance in the relationship between male and female size in mating pairs was high, suggesting that mating with large females may not be the primary determinant of male reproductive success. Large males had proportionately longer chelipeds, which may provide an advantage in aggressive interactions for females or in struggles to control females. Previous work indicates that sperm competition may occur in blue crabs and that ejaculate size may influence a male's ability to compete during sperm competition. Large males stored more seminal fluid and spermatophores and passed a larger volume of ejaculate to each mate than did small males. Ejaculate volume averaged 47% of a male's stored supply. However, ejaculate volume increased with the duration of copulation but decreased with successive matings, such that males needed about 15 days between matings to pass similar-sized ejaculates to successive mates. Pre-copulatory mate guarding may serve as a time to replenish ejaculate contents, and thus its duration also influences a male's performance in sperm competition.


Deletions and insertions within an amino-terminal domain of pp60v-src inactivate transformation and modulate membrane stability.
We previously showed (V. W. Raymond and J. T. Parsons, Virology 160:400-410, 1987) that variants of the Prague A strain of Rous sarcoma virus containing large deletions impinging on a region of the src gene encoding amino acid residues 143 to 169 were defective for transformation of chicken cells in culture. Here we report that introduction of small (tri-and tetrapeptide) deletions into a region of pp60v-src containing amino acid residues 155 to 175 was found to inactivate transformation. In addition, insertion of four, but not one, amino acid residues at position 161 also inhibited transformation. Biochemical analysis of the src proteins encoded by individual transformation-defective variants revealed that the structural alterations introduced into this domain had only marginal effects upon src tyrosine-specific protein kinase activity. However, the src proteins encoded by defective variants exhibited a significantly shorter half-life within the cell, although these proteins efficiently and rapidly associated with cellular membranes. Our results suggest that the structural domain encompassing residues 155 to 177 may influence the stability of pp60src in the cellular membrane, possibly via the interaction of src with a cellular membrane component(s) or substrate(s).


Identification, Functional Characterization, and Regulon Prediction of the Zinc Uptake Regulator (zur) of Bacillus anthracis - An Insight Into the Zinc Homeostasis of the Pathogen.
Zinc has an abounding occurrence in the prokaryotes and plays paramount roles including catalytic, structural, and regulatory. Zinc uptake regulator (Zur), a Fur family transcriptional regulator, is connoted in maintaining zinc homeostasis in the pathogenic bacteria by binding to zinc and regulating the genes involved in zinc uptake and mobilization. Zinc homeostasis has been marginally scrutinized in Bacillus anthracis, the top-rated bio-terror agent, with no decipherment of the role of Zur. Of the three Fur family regulators in B. anthracis, BAS4181 is annotated as a zinc-specific transcriptional regulator. This annotation was further substantiated by our stringent computational and experimental analyses. The residues critical for zinc and DNA binding were delineated by homology modeling and sequence/structure analysis. ba zur existed as a part of a three-gene operon. Purified BaZur prodigiously existed in the dimeric form, indicated by size exclusion chromatography and blue native-polyacrylamide gel electrophoresis (PAGE). Computational and manual strategies were employed to decipher the putative regulon of ba zur, comprising of 11 genes, controlled by six promoters, each harboring at least one Zur box. The DNA binding capability of the purified BaZur to the upstream regions of the ba zur operon, yciC, rpmG, znuA, and genes encoding a GTPase cobalamine synthesis protein and a permease was ascertained by electrophoretic mobility shift assays. The regulon genes, implicated in zinc uptake and mobilization, were mostly negatively regulated by BaZur. The ba zur expression was downregulated upon exposure of cells to an excess of zinc. Conversely, it exhibited a marked upregulation under N, N, N', N'-Tetrakis (2-pyridylmethyl) ethylenediamine (TPEN) mediated zinc-depleted environment, adding credence to its negative autoregulation. Moreover, an increase in the transcript levels of the regulon genes znuA, rpmG, and yciC upon exposure of cells to TPEN connoted their role in combating hypo-zincemic conditions by bringing about zinc uptake and mobilization. Thus, this study functionally characterizes Zur of B. anthracis and elucidates its role in maintaining zinc homeostasis.


Kidney Exchange Program Reporting Standards: Evidence-Based Consensus From Europe.
Background: Kidney Exchange Programs can play an important role to increase access to the life saving and most cost-effective treatment for End Stage Renal Disease. The rise of national KEPs in Europe brings a need for standardized performance reporting to facilitate the development of an international evidence base on program practices. Methods: We systematically searched and reviewed the literature to extract kidney exchange program performance measures. Reported measures were initially categorized as structure, process, and outcome measures. Expert feedback was used to redefine categories and extend the set of measures to be considered. Using the Delphi method and a panel of 10 experts, the resulting measures were subsequently classified as mandatory (Base set), optional (Extended set), or deleted. Results: Out of the initial 1,668 articles identified by systematic literature search, 21 European publications on kidney exchange programs were included to collect performance measures, accompanied by three national program reports. The final measurement categories were Context, Population, Enrollment, Matching, Transplantation, and Outcomes. The set of performance measures resulting from the literature review was modified and classified as mandatory or optional. The resulting Base set and Extended set form the kidney exchange program reporting standard. Conclusions: The evidence-based and consensus-based kidney exchange program reporting standard can harmonize practical and scientific reporting on kidney exchange programs, thus facilitating the advancement of national programs. In addition, the kidney exchange program reporting standard can promote and align cross-national programs.


[EDNOS is an eating disorder of clinical relevance, on a par with anorexia and bulimia nervosa].
The category 'eating disorder 'not otherwise specified'' (EDNOS) in DSM-IV is restricted to eating disorders of clinical severity that do not completely fulfil the criteria for anorexia and bulimia nervosa. The EDNOS category is, by definition, often regarded as a a residual category and in principle designed to incorporate a small group of patients with atypical characteristics. Health insurance companies argue that the treatment of patients diagnosed with EDNOS should not be treated in mental health institutions and therefore should not get their treatment costs reimbursed by the insurance companies. The most important argument of the insurance companies is that patients in the EDNOS category do not display serious psychiatric symptoms. The aim of this paper is to show that EDNOS is an eating disorder category of clinical relevance. The article provides a critical overview of literature on EDNOS which studies the prevalence, severity and course of the disorder. We also discuss to what extent the fifth version of dsm solves the problems relating to this residual category. We reviewed the literature. The classification given in DSM-IV is not an accurate reflection of clinical reality. Half of the patients presenting with an eating disorder and seeking treatment do meet the criteria for EDNOS. The duration and the severity of eating disorder psychopathology, the presence of comorbidity, the mortality, and the use of the mental health care services by individuals with an eating disorder appear to be very similar in EDNOS patients and in patients with anorexia and bulimia nervosa. Eating disorder classifications can be regarded as snapshots taken throughout the course of an illness. Over of the years patients can be afflicted with various subtypes of an eating disorder. DSM-5 places fewer patients in the EDNOS category that did DSM-IV. In the latest version of dsm, namely DSM-5, the number of patients with an eating disorder classified as EDNOS has declined. There appears to be sufficient scientific evidence for EDNOS to be considered as an eating-disorder category of clinical severity, comparable to anorexia and bulimia nervosa. In our view, patients classified as having EDNOS should be offered regular treatment in mental health institutions.


The 'secrets' of the long livers in Mediterranean islands: the MEDIS study.
The aim of the present work was to evaluate various socio-demographic, clinical, lifestyle and psychological characteristics of elderly (> 65 years) and very elderly (> 90 years) individuals without known cardiovascular disease. During 2005-7, 1190 elderly (aged > 65) men and women (from Cyprus, Mitilini, Samothraki, Cephalonia, Crete, Lemnos, Corfu and Zakynthos) were randomly enrolled. Socio-demographic, clinical, psychological and lifestyle factors were assessed using standard questionnaires and procedures. From all islands, the proportion of males aged 65-80, 80-90 and > 90 years was 71.8, 24.8 and 3.4%, respectively. The proportion of women, for the same age categories, was 80.4, 17.9 and 1.7%, respectively. Walking and other activities significantly declined with age (P < 0.001); however, nearly one in five participants over the age of 90 years remained physically active. Current smoking significantly declined in males as age increased (P < 0.001). All participants above the age of 90 years reported sleeping at noon. The proportion of participants living alone differs significantly (P < 0.001) across the three age groups. However, considerably more women live alone (men vs. women living alone: aged 65-80 years 12 vs. 37%; 80-90 years 16 vs. 55%; > 90 years 52 vs. 55%). Dietary characteristics of The Mediterranean Islands Study (MEDIS) sample display a favourable adherence to dietary recommendations (Mediterranean diet). A favourable adherence to the Mediterranean diet, mid-day naps and smoking cessation with an increase in age was characteristic of our elderly population. Future research should further evaluate whether the aforementioned characteristics are associated with longevity beyond the average life expectancy.


Ancient DNA from giant extinct lemurs confirms single origin of Malagasy primates.
The living Malagasy lemurs constitute a spectacular radiation of >50 species that are believed to have evolved from a common ancestor that colonized Madagascar in the early Tertiary period. Yet, at least 15 additional Malagasy primate species, some of which were relative giants, succumbed to extinction within the past 2,000 years. Their existence in Madagascar is recorded predominantly in its Holocene subfossil record. To rigorously test the hypothesis that all endemic Malagasy primates constitute a monophyletic group and to determine the evolutionary relationships among living and extinct taxa, we have conducted an ancient DNA analysis of subfossil species. A total of nine subfossil individuals from the extinct genera Palaeopropithecus and Megaladapis yielded amplifiable DNA. Phylogenetic analysis of cytochrome b sequences derived from these subfossils corroborates the monophyly of endemic Malagasy primates. Our results support the close relationship of sloth lemurs to living indriids, as has been hypothesized on morphological grounds. In contrast, Megaladapis does not show a sister-group relationship with the living genus Lepilemur. Thus, the classification of the latter in the family Megaladapidae is misleading. By correlating the geographic location of subfossil specimens with relative amplification success, we reconfirm the global trend of increased success rates of ancient DNA recovery from nontropical localities.


Early warning score predicts acute mortality in stroke patients.
Clinical deterioration and death among patients with acute stroke are often preceded by detrimental changes in physiological parameters. Systematic and effective tools to identify patients at risk of deterioration early enough to intervene are therefore needed. The aim of the study was to investigate whether the aggregate weighted track and trigger system early warning score (EWS) can be used as a simple observational tool to identify patients at risk and predict mortality in a population of patients with acute stroke. Patients admitted with acute stroke at the Copenhagen University Hospital, Nordsjaellands Hospital, Denmark, from May to September 2012 were enrolled in a retrospective cohort study (n = 274). Vital signs were measured immediately after admission and consistently during the hospitalization period. Based on the vital signs, a single composite EWS was calculated. Death within 30 days was used as outcome. Area under the receiver operating characteristics curve (AUROC) and a Kaplan-Meier curve were computed to examine the prognostic validity of EWS. A total of 24 patients (8.8%) died within 30 days. The prognostic performance was high for both the EWS at admission (AUROC 0.856; 95% CI 0.760-0.951; P-value < 0.001) and the maximal EWS measured (AUROC 0.949; 95% CI 0.919-0.980; P-value < 0.001). Mortality rates were lowest for admission EWS 0-1 (2%) and highest for admission EWS ≥ 5 (63%). Early warning score is a simple and valid tool for identifying patients at risk of dying after acute stroke. Readily available physiological parameters are converted to a single score, which can guide both nurses and physicians in clinical decision making and resource allocation.


Attitudes toward psychopharmacology among hospitalized patients from diverse ethno-cultural backgrounds.
Biological factors influencing individual response to drugs are being extensively studied in psychiatry. Strikingly, there are few studies addressing social and cultural differences in attitudes toward psychotropic medications. The objective of this study was to investigate ethno-culturally determined beliefs, expectations and attitudes toward medication among a sample of hospitalized psychiatric patients. An ad hoc questionnaire was designed to assess patients' expectations, attitudes and prejudice toward medication. The study included 100 adult patients hospitalized in Geneva, Switzerland. Patients were in majority male (63%), originated from Switzerland (54%) and spoke the local language fluently (93%). They took on the average 3 different psychotropic drugs. Sixty-eight percent of patients expected side effects and 60% were ready to stop medication because of them. Thirty percent of patients expected negative personal changes with treatment and 34% thought that their mental disorder could have been treated without drugs. Thirty six percent of the sample used alternative or complementary medicines. 35% of immigrant patients believed that medication had different effects on them than on local patients. When compared with Swiss patients, they more often reported that significant others had an opinion about medication (p = 0.041) and more frequently valued information provided by other patients about treatment (p = 0.010). Patients' attitudes toward medication should be investigated in clinical practice, as specific expectations and prejudice exist. Targeted interventions, especially for immigrant patients, might improve adherence.


Development and validation of a new predictive model for breast cancer survival in New Zealand and comparison to the Nottingham prognostic index.
The only available predictive models for the outcome of breast cancer patients in New Zealand (NZ) are based on data in other countries. We aimed to develop and validate a predictive model using NZ data for this population, and compare its performance to a widely used overseas model, the Nottingham Prognostic Index (NPI). We developed a model to predict 10-year breast cancer-specific survival, using data collected prospectively in the largest population-based regional breast cancer registry in NZ (Auckland, 9182 patients), and assessed its performance in this data set (internal validation) and in an independent NZ population-based series of 2625 patients in Waikato (external validation). The data included all women with primary invasive breast cancer diagnosed from 1 June 2000 to 30 June 2014, with follow up to death or Dec 31, 2014. We used multivariate Cox proportional hazards regression to assess predictors and to calculate predicted 10-year breast cancer mortality, and therefore survival, probability for each patient. We assessed observed survival by the Kaplan Meier method. We assessed discrimination by the C statistic, and calibration by comparing predicted and observed survival rates for patients in 10 groups ordered by predicted 10-year survival. We compared this NZ model with the Nottingham Prognostic Index (NPI) in this validation data set. Discrimination was good: C statistics were 0.84 for internal validity and 0.83 for an independent external validity. For calibration, for both internal and external validity the predicted 10-year survival probabilities in all groups of patients, ordered by predicted survival, were within the 95% confidence intervals (CI) of the observed Kaplan-Meier survival probabilities. The NZ model showed good discrimination even within the prognostic groups defined by the NPI. These results for the New Zealand model show good internal and external validity, transportability, and potential clinical value of the model, and its clear superiority over the NPI. Further research is needed to assess other potential predictors, to assess the model's performance in specific subgroups of patients, and to compare it to other models, which have been developed in other countries and have not yet been tested in NZ.


Kinetic studies on phosphorus sorption by selected soil amendments for septic tank effluent renovation.
A systematic kinetic study of phosphorus (P) sorption by various materials in the soil infiltration system of septic tanks was undertaken by following the time course of P sorption by sorbents in contact with various P solutions over periods up to 360 days. Uptake of P seemed to consist of two distinct stages. Initial uptake was very rapid and this phase was completed in 4 days or less. A slower removal stage followed for some materials over many months. Phosphorus sorption during the fast reaction stage appeared to be associated with the soluble Ca content of the materials. The fast reaction of calcareous materials accounted for the bulk (>70%) of the total P removed. Merribrook loamy sand exhibited the highest proportion of P sorption during the slow phase. It should be noted, however, that for solution P concentrations in the range found in typical effluents (approximately 20 mg L(-1)) the fast reaction phase seemed to be responsible for virtually all P removed. None of the six kinetic formulae examined possessed the sophistication and detail needed to portray accurately the time course of P sorption for all the sorbents investigated. The Elovich equation and the kinetic modification of the Freundlich isotherm expression appeared to provide a reasonable fit of the experimental data.


Neuropathological responses to chronic NMDA in rats are worsened by dietary n-3 PUFA deprivation but are not ameliorated by fish oil supplementation.
Dietary long-chain n-3 polyunsaturated fatty acid (PUFA) supplementation may be beneficial for chronic brain illnesses, but the issue is not agreed on. We examined effects of dietary n-3 PUFA deprivation or supplementation, compared with an n-3 PUFA adequate diet (containing alpha-linolenic acid [18:3 n-3] but not docosahexaenoic acid [DHA, 22:6n-3]), on brain markers of lipid metabolism and excitotoxicity, in rats treated chronically with NMDA or saline. Male rats after weaning were maintained on one of three diets for 15 weeks. After 12 weeks, each diet group was injected i.p. daily with saline (1 ml/kg) or a subconvulsive dose of NMDA (25 mg/kg) for 3 additional weeks. Then, brain fatty acid concentrations and various markers of excitotoxicity and fatty acid metabolism were measured. Compared to the diet-adequate group, brain DHA concentration was reduced, while n-6 docosapentaenoic acid (DPA, 22:5n-6) concentration was increased in the n-3 deficient group; arachidonic acid (AA, 20:4n-6) concentration was unchanged. These concentrations were unaffected by fish oil supplementation. Chronic NMDA increased brain cPLA2 activity in each of the three groups, but n-3 PUFA deprivation or fish oil did not change cPLA2 activity or protein compared with the adequate group. sPLA2 expression was unchanged in the three conditions, whereas iPLA2 expression was reduced by deprivation but not changed by supplementation. BDNF protein was reduced by NMDA in N-3 PUFA deficient rats, but protein levels of IL-1β, NGF, and GFAP did not differ between groups. N-3 PUFA deprivation significantly worsened several pathological NMDA-induced changes produced in diet adequate rats, whereas n-3 PUFA supplementation did not affect NMDA induced changes. Supplementation may not be critical for this measured neuropathology once the diet has an adequate n-3 PUFA content.


Post-transplant lymphoproliferative disease after liver transplantation.
We have read the article "Post-transplant lymphoproliferative disease in liver transplant recipients" with great interest. This article reports a series of liver transplant recipients with post-transplant lymphoproliferative disease (PTLD). The effect on patient survival and the potential benefit of rituximab-based therapy are highlighted. Rituximab is a chimeric antibody against the CD20 surface marker. This marker is found in most PTLD of a B cell origin. A recent study from our center also highlighted the role of rituximab in PTLD therapy (3). The overall response rate of patients treated with rituximab was 66% in both series. In our series, this included heart, kidney and liver transplant recipients. Rituximab-based therapy was also associated with an increased overall survival. Rituximab should be considered as part of the first-line therapy in patients with PTLD when CD20 expression is present.


Efficacy and safety of a newly developed polylactic acid microsphere as an injectable bulking agent for penile augmentation: 18-months follow-up.
Polylactic acid (PLA) fillers are widely used for cosmetic volume augmentation. But, no study has evaluated the use of PLA filler in penile augmentation (PA No. 4). We evaluated the efficacy and safety of a newly developed PLA filler for PA during a 18-month follow-up period. A total of 23 healthy adult men were prospectively enrolled between June and November 2012. Penile girth was measured at proximal-, mid- and distal-shaft at baseline, 3, 6, 12 and 18 months following injection. Subjects' satisfaction was assessed with visual analogue scale (VAS). Adverse events (AEs) were also reported. Mean injected volume was 20 ml. The circumference of proximal-, mid-, and distal-shaft increased by a mean of 2.2±0.2, 2.7±1.0 and 2.7±1.0 cm at 3 months, respectively (each P<0.001). No significant differences were noted in girth circumference between 3 and 18 months post-injection (each P>0.05). VAS score increased from 51.6±14.7 at baseline to 64.8±19.3 and 74.3±14.6 at 3 and 6 months, respectively (each P<0.05). Six cases of mild, transient treatment-emergent AEs were reported in 5 subjects. Serious AEs were not reported. In conclusion, penile injection of a newly developed PLA filler led to significant penile augmentative effects for up to 18 months and was well tolerated without serious AEs.


Hydrogen-rich saline prevents bone loss in diabetic rats induced by streptozotocin.
As an antioxidant molecule, hydrogen has been received much more attention and reported to be used as the treatment strategy for various diseases. In this study, we hypothesize that systemic delivery of hydrogen saline water may improve the reservation of bone tissue in the tibias and femurs of osteoporotic rats caused by diabetes mellitus (DM), which is characterized by increased levels of oxidative stress and overproducing reactive oxygen species (ROS). The animals were divided into three groups of 12 animals and lavaged with normal saline (normal control and DM), or hydrogen saline water (DM + HRS). General status, blood glucose level, tibial and femoral mechanical strength, and micro-CT scans of the proximal tibia were recorded and analyzed. After 12 weeks, the glucose level was significantly decreased in the DM + HRS group compared with that of the DM group. Micro-CT scans showed that bone volume/total volume, connectivity density, trabecular thickness, and trabecular number were significantly increased compared with the DM group. Mechanical results of energy, stiffness and elastic modulus in the DM + HRS group were significantly higher than in the other groups for the tibia and femur. The results indicate that the systemic delivery of hydrogen saline water, which is safe and well tolerated, preserves bone volume and decreases fracture risks in streptozotocin-induced diabetic status rats, whose bone structure or inherent material properties of bone tissues are changed.


Phylogeographic Assessment Reveals Geographic Sources of HIV-1 Dissemination Among Men Who Have Sex With Men in Kenya.
HIV-1 transmission dynamics involving men who have sex with men (MSM) in Africa are not well understood. We investigated the rates of HIV-1 transmission between MSM across three regions in Kenya: Coast, Nairobi, and Nyanza. We analyzed 372 HIV-1 partial pol sequences sampled during 2006-2019 from MSM in Coast (N = 178, 47.9%), Nairobi (N = 137, 36.8%), and Nyanza (N = 57, 15.3%) provinces in Kenya. Maximum-likelihood (ML) phylogenetics and Bayesian inference were used to determine HIV-1 clusters, evolutionary dynamics, and virus migration rates between geographic regions. HIV-1 sub-subtype A1 (72.0%) was most common followed by subtype D (11.0%), unique recombinant forms (8.9%), subtype C (5.9%), CRF 21A2D (0.8%), subtype G (0.8%), CRF 16A2D (0.3%), and subtype B (0.3%). Forty-six clusters (size range 2-20 sequences) were found-half (50.0%) of which had evidence of extensive HIV-1 mixing among different provinces. Data revealed an exponential increase in infections among MSM during the early-to-mid 2000s and stable or decreasing transmission dynamics in recent years (2017-2019). Phylogeographic inference showed significant (Bayes factor, BF > 3) HIV-1 dissemination from Coast to Nairobi and Nyanza provinces, and from Nairobi to Nyanza province. Strengthening HIV-1 prevention programs to MSM in geographic locations with higher HIV-1 prevalence among MSM (such as Coast and Nairobi) may reduce HIV-1 incidence among MSM in Kenya.


Development of an integrated rehabilitation pathway for individuals recovering from COVID-19 in the community.
COVID-19 is a multisystem illness that has considerable long-term physical, psychological, cognitive, social and vocational sequelae in survivors. Given the scale of this burden and lockdown measures in most countries, there is a need for an integrated rehabilitation pathway using a tele-medicine approach to screen and manage these sequelae in a systematic and efficient way. A multidisciplinary team of professionals in the UK developed a comprehensive pragmatic telephone screening tool, the COVID-19 Yorkshire Rehabilitation Screen (C19-YRS), and an integrated rehabilitation pathway, which spans the acute hospital trust, community trust and primary care service within the National Health Service (NHS) service model. The C19-YRS telephone screening tool, developed previously, was used to screen symptoms and grade their severity. Referral criteria thresholds were applied to the output of C19-YRS to inform the decision-making process in the rehabilitation pathway. A dedicated multidisciplinary COVID-19 rehabilitation team is the core troubleshooting forum for managing complex cases with needs spanning multiple domains of the health condition. The authors recommend that health services dealing with the COVID-19 pandemic adopt a comprehensive telephone screening system and an integrated rehabilitation pathway to manage the large number of survivors in a timely and effective manner and to enable the provision of targeted interventions.


The mechanistic basis for the induction of hepatic steatosis by xenobiotics.
Hepatic steatosis is the histological observation of numerous lipid inclusions due to an excess accumulation of triacylglycerols. They are a concern with new therapeutic candidates because they signify altered lipid metabolism that can progress to more serious liver toxicity. This article is based on an article search using the PubMed database from 1987 to 2011 and confirms associations for several previously marketed drugs with four basic hepatocellular mechanisms. The article also describes how these mechanisms are controlled by master regulators of lipid metabolism, which include gene transcription factors, nuclear receptors, hormonal signaling, energy sensing proteins, endoplasmic reticulum stress signaling and certain key metabolic intermediates. Drug-induced hepatic steatosis is typically not detectable by conventional means other than invasive histological examinations. By understanding the basic mechanisms, key regulators and energy signaling systems of the liver, the investigator is better equipped to avoid xenobiotics with steatogenic potential in the drug discovery or early development process. There are now a number of methods for detecting this potential, specifically gene expression or metabolomic profiling and pathway analysis or mechanism-based in vitro systems.


NCAM: a surface marker for human small cell lung cancer cells.
Immunocytochemical and immunochemical techniques were used to study the expression of the neural cell adhesion molecule (NCAM) by human lung cancer cell lines. Intense surface staining for NCAM was found at light and electron microscopic levels on small cell lung cancer cells. The NCAM polypeptide of Mr 140,000 (NCAM 140) was detected by immunoblotting in all of 7 small cell lung cancer cell lines examined and in one out of two of the closely related large cell cancer cell lines: it was not detected in cell lines obtained from one patient with a mesothelioma, in two cases of adenocarcinoma, nor in two cases of squamous cell cancer. In contrast, neuron-specific enolase was found by immunoblotting in all the lung cancer cell lines tested and synaptophysin in all but the adenocarcinoma cell lines. These antigens were localized intracellularly. The specific expression of NCAM 140 by human small and large cell lung carcinomas suggests its potential as a diagnostic marker.


The nuclear receptor DHR3 modulates dS6 kinase-dependent growth in Drosophila.
S6 kinases (S6Ks) act to integrate nutrient and insulin signaling pathways and, as such, function as positive effectors in cell growth and organismal development. However, they also have been shown to play a key role in limiting insulin signaling and in mediating the autophagic response. To identify novel regulators of S6K signaling, we have used a Drosophila-based, sensitized, gain-of-function genetic screen. Unexpectedly, one of the strongest enhancers to emerge from this screen was the nuclear receptor (NR), Drosophila hormone receptor 3 (DHR3), a critical constituent in the coordination of Drosophila metamorphosis. Here we demonstrate that DHR3, through dS6K, also acts to regulate cell-autonomous growth. Moreover, we show that the ligand-binding domain (LBD) of DHR3 is essential for mediating this response. Consistent with these findings, we have identified an endogenous DHR3 isoform that lacks the DBD. These results provide the first molecular link between the dS6K pathway, critical in controlling nutrient-dependent growth, and that of DHR3, a major mediator of ecdysone signaling, which, acting together, coordinate metamorphosis.


Preparation, characterization, and surface immobilization of native vesicles obtained by mechanical extrusion of mammalian cells.
Native vesicles or "reduced protocells" derived by mechanical extrusion concentrate selected plasma membrane components, while downsizing complexities of whole cells. We illustrate this technique, characterize the physical-chemical properties of these reduced configurations of whole cells, and demonstrate their surface immobilization and patternability. This simple detergent-free vesicularized membrane preparation should prove useful in fundamental studies of cellular membranes, and may provide a means to engineer therapeutic cells and enable high-throughput devices containing near-native, functional proteolipidic assemblies.


Complex Admixture Preceded and Followed the Extinction of Wisent in the Wild.
Retracing complex population processes that precede extreme bottlenecks may be impossible using data from living individuals. The wisent (Bison bonasus), Europe's largest terrestrial mammal, exemplifies such a population history, having gone extinct in the wild but subsequently restored by captive breeding efforts. Using low coverage genomic data from modern and historical individuals, we investigate population processes occurring before and after this extinction. Analysis of aligned genomes supports the division of wisent into two previously recognized subspecies, but almost half of the genomic alignment contradicts this population history as a result of incomplete lineage sorting and admixture. Admixture between subspecies populations occurred prior to extinction and subsequently during the captive breeding program. Admixture with the Bos cattle lineage is also widespread but results from ancient events rather than recent hybridization with domestics. Our study demonstrates the huge potential of historical genomes for both studying evolutionary histories and for guiding conservation strategies.


Art Interventions for Children With Autism Spectrum Disorder: A Scoping Review.
Autism spectrum disorder (ASD) is a neurological condition characterized by impairments in social interaction, communication, and behavior. Occupational therapy practitioners use creative arts interventions for children with ASD, but relevant evidence for these interventions is lacking. To provide occupational therapists evidence of the benefit of creative arts interventions for children with ASD by evaluating treatment efficacy and connecting the evidence with the Occupational Therapy Practice Framework: Domain and Process (4th ed.; OTPF-4). We searched peer-reviewed articles in six databases: CINAHL, Cochrane, PubMed, Ovid, PsycInfo, and Scopus. Eighteen articles published between 2000 and 2020 met Level 1b or 2b evidence criteria and were retrieved for full review; 15 were included in this scoping review. We used Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to extract data. Inclusion criteria were as follows: (1) Level 1b or 2b study; (2) quantitative data; (3) published in English; (4) population of children (ages <18 yr); (5) primary diagnosis of ASD; and (6) creative arts intervention in the forms of drawing, painting, or coloring; music; or theater. Creative arts interventions benefited children with ASD in two OTPF-4 areas (process and social interaction) pertaining to the Performance Skills domain and one OTPF-4 area (body functions) pertaining to the Client Factors domain. We found similar effects for group and individual intervention sessions, and significant improvements required multiple sessions. Our findings provide evidence for the efficacy of creative arts interventions to enhance occupation-based outcomes for children with ASD. What This Article Adds: Our findings support occupational therapy practitioners' use of creative arts interventions to improve OTPF-4-based client factors and process and social interaction skills for children with ASD.


To what extent does the Health Professions Admission Test-Ireland predict performance in early undergraduate tests of communication and clinical skills? An observational cohort study.
Internationally, tests of general mental ability are used in the selection of medical students. Examples include the Medical College Admission Test, Undergraduate Medicine and Health Sciences Admission Test and the UK Clinical Aptitude Test. The most widely used measure of their efficacy is predictive validity.A new tool, the Health Professions Admission Test- Ireland (HPAT-Ireland), was introduced in 2009. Traditionally, selection to Irish undergraduate medical schools relied on academic achievement. Since 2009, Irish and EU applicants are selected on a combination of their secondary school academic record (measured predominately by the Leaving Certificate Examination) and HPAT-Ireland score. This is the first study to report on the predictive validity of the HPAT-Ireland for early undergraduate assessments of communication and clinical skills. Students enrolled at two Irish medical schools in 2009 were followed up for two years. Data collected were gender, HPAT-Ireland total and subsection scores; Leaving Certificate Examination plus HPAT-Ireland combined score, Year 1 Objective Structured Clinical Examination (OSCE) scores (Total score, communication and clinical subtest scores), Year 1 Multiple Choice Questions and Year 2 OSCE and subset scores. We report descriptive statistics, Pearson correlation coefficients and Multiple linear regression models. Data were available for 312 students. In Year 1 none of the selection criteria were significantly related to student OSCE performance. The Leaving Certificate Examination and Leaving Certificate plus HPAT-Ireland combined scores correlated with MCQ marks.In Year 2 a series of significant correlations emerged between the HPAT-Ireland and subsections thereof with OSCE Communication Z-scores; OSCE Clinical Z-scores; and Total OSCE Z-scores. However on multiple regression only the relationship between Total OSCE Score and the Total HPAT-Ireland score remained significant; albeit the predictive power was modest. We found that none of our selection criteria strongly predict clinical and communication skills. The HPAT- Ireland appears to measures ability in domains different to those assessed by the Leaving Certificate Examination. While some significant associations did emerge in Year 2 between HPAT Ireland and total OSCE scores further evaluation is required to establish if this pattern continues during the senior years of the medical course.


Multi-class motor imagery EEG decoding for brain-computer interfaces.
Recent studies show that scalp electroencephalography (EEG) as a non-invasive interface has great potential for brain-computer interfaces (BCIs). However, one factor that has limited practical applications for EEG-based BCI so far is the difficulty to decode brain signals in a reliable and efficient way. This paper proposes a new robust processing framework for decoding of multi-class motor imagery (MI) that is based on five main processing steps. (i) Raw EEG segmentation without the need of visual artifact inspection. (ii) Considering that EEG recordings are often contaminated not just by electrooculography (EOG) but also other types of artifacts, we propose to first implement an automatic artifact correction method that combines regression analysis with independent component analysis for recovering the original source signals. (iii) The significant difference between frequency components based on event-related (de-) synchronization and sample entropy is then used to find non-contiguous discriminating rhythms. After spectral filtering using the discriminating rhythms, a channel selection algorithm is used to select only relevant channels. (iv) Feature vectors are extracted based on the inter-class diversity and time-varying dynamic characteristics of the signals. (v) Finally, a support vector machine is employed for four-class classification. We tested our proposed algorithm on experimental data that was obtained from dataset 2a of BCI competition IV (2008). The overall four-class kappa values (between 0.41 and 0.80) were comparable to other models but without requiring any artifact-contaminated trial removal. The performance showed that multi-class MI tasks can be reliably discriminated using artifact-contaminated EEG recordings from a few channels. This may be a promising avenue for online robust EEG-based BCI applications.


A sequence pattern for peptides presented to cytotoxic T lymphocytes by HLA B8 revealed by analysis of epitopes and eluted peptides.
HLA B8-restricted cytotoxic T lymphocytes (CTL) specific for influenza A virus were generated and shown to recognize the nucleoprotein (NP). The dominant epitope was mapped using recombinant vaccinia viruses that expressed fragments of the NP and then synthetic peptides based on the NP amino acid sequence. The peptide 380-393 was first identified and further refined; it was shown that the glutamic acid at position 380 was essential for recognition by CTL and that the nonamer 380-388 was the optimum peptide. Six HLA B8-positive influenza immune donors that we have tested respond to this peptide as part of their influenza-specific CTL response. The amino acid sequence of the peptide epitope was compared to six other known virus peptides known to be restricted by HLA B8 and a sequence homology was identified, which predicted nonamer and octamer epitope sequences. Probable anchor residues were identified at peptide residues 3 (lysine/arginine), 5 (lysine/arginine) and 9 (leucine/isoleucine). Support for this pattern came from sequencing peptides eluted from purified HLA B8 molecules, where lysines were predominant at positions 3 and 5. One of the predicted epitope peptides was made and shown to be recognized by specific CTL. These and the two others were shown to compete with NP 380-388 for binding to HLA B8. A model was made of the HLA B8 molecule and negatively charged pockets predicted, which could accommodate the positively charged side chains of the peptide anchor residues.


Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet.
Trials comparing the effectiveness and safety of weight-loss diets are frequently limited by short follow-up times and high dropout rates. In this 2-year trial, we randomly assigned 322 moderately obese subjects (mean age, 52 years; mean body-mass index [the weight in kilograms divided by the square of the height in meters], 31; male sex, 86%) to one of three diets: low-fat, restricted-calorie; Mediterranean, restricted-calorie; or low-carbohydrate, non-restricted-calorie. The rate of adherence to a study diet was 95.4% at 1 year and 84.6% at 2 years. The Mediterranean-diet group consumed the largest amounts of dietary fiber and had the highest ratio of monounsaturated to saturated fat (P<0.05 for all comparisons among treatment groups). The low-carbohydrate group consumed the smallest amount of carbohydrates and the largest amounts of fat, protein, and cholesterol and had the highest percentage of participants with detectable urinary ketones (P<0.05 for all comparisons among treatment groups). The mean weight loss was 2.9 kg for the low-fat group, 4.4 kg for the Mediterranean-diet group, and 4.7 kg for the low-carbohydrate group (P<0.001 for the interaction between diet group and time); among the 272 participants who completed the intervention, the mean weight losses were 3.3 kg, 4.6 kg, and 5.5 kg, respectively. The relative reduction in the ratio of total cholesterol to high-density lipoprotein cholesterol was 20% in the low-carbohydrate group and 12% in the low-fat group (P=0.01). Among the 36 subjects with diabetes, changes in fasting plasma glucose and insulin levels were more favorable among those assigned to the Mediterranean diet than among those assigned to the low-fat diet (P<0.001 for the interaction among diabetes and Mediterranean diet and time with respect to fasting glucose levels). Mediterranean and low-carbohydrate diets may be effective alternatives to low-fat diets. The more favorable effects on lipids (with the low-carbohydrate diet) and on glycemic control (with the Mediterranean diet) suggest that personal preferences and metabolic considerations might inform individualized tailoring of dietary interventions. (ClinicalTrials.gov number, NCT00160108.)


Psychometric properties of the Korean version of the job content questionnaire: data from health care workers.
To test the validity and reliability of selected scales, namely, decision latitude, psychological job demand, social support, job insecurity, and macro-level decision latitude from the Korean version of the job content questionnaire (K-JCQ), as part of a psychosocial epidemiological study among university hospital workers. K-JCQ was developed by translation and back translation complying with the JCQ usage policy, and its psychometric properties were explored among 338 workers (290 females and 48 males) in a university hospital in Korea. Internal consistency was examined using Cronbach's alpha correlation coefficients. Factorial validity was tested using exploratory factor analysis. Pearson's correlation coefficients were used for test-retest reliability among a subset of 157 workers who responded to a repeat survey. Criterion-related validity was assessed by investigating the effects of the scales on job satisfaction and self-identity through work in multiple regression models. Cronbach's alpha for all selected scales was higher than 0.6, except for job insecurity (0.53) and macro-level decision authority (0.52), indicating appropriate internal consistency. Correlation coefficients between test and retest scales of decision latitude, psychological job demand, and social support were 0.60, 0.41, and 0.35, respectively. Exploratory factor analysis found three- and four-factor models, i.e., with and without macro-level decision latitude, respectively, closely corresponding to the theoretical constructs. High levels of decision latitude and social support, and low levels of psychological job demand and job insecurity were significantly associated with high level of job satisfaction. Higher self-identity through work was positively related to decision latitude and social support. These findings suggest that K-JCQ is valid and reliable for assessing psychosocial job stress among Korean workers. Macro-level decision latitude showed a separate factorial structure and was strongly associated with task-level decision latitude.


Preliminary trial of the effect of general practice based nutritional advice.
Despite formal recommendations for dietary change to reduce the incidence of ischaemic heart disease, the acceptability and effectiveness of the proposed diets have not been well investigated in population based studies. In this preliminary investigation of nutritional advice in a well population, subjects in one group practice were randomized to receive either dietary instruction or simple follow up without instruction. The dietary recommendations were well received, and a substantial proportion of subjects reported altering their diets in accordance with them. There were modest beneficial changes in plasma lipid levels among men. Thus, using general practice as an avenue for promoting dietary change is feasible, and may be effective among men.


A spatial analysis of dietary patterns in a large representative population in the north of The Netherlands - the Lifelines cohort study.
Diet is an important modifiable risk factor for chronic diseases. In the search for effective strategies to improve dietary patterns in order to promote healthy ageing, new approaches considering contextual factors in public health medicine are warranted. The aim of this study is to examine the spatial clustering of dietary patterns in a large representative sample of adults. Dietary patterns were defined on the basis of a 111 item Food Frequency Questionnaire among n = 117,570 adults using principal components analysis. We quantified the spatial clustering of dietary pattern scores at the neighborhood level using the Global Moran's I spatial statistic, taking into consideration individual demographic and (neighborhood) socioeconomic indicators. Four dietary patterns explaining 27% of the variance in dietary data were extracted in this population and named the "bread and cookies" pattern, the "snack" pattern, the "meat and alcohol" pattern and the "vegetable, fruit and fish" pattern. Significant spatial clustering of high (hot spot) and low (cold spot) dietary pattern scores was found for all four dietary patterns irrespective of age and gender differences. Educational attainment and neighborhood income explained the global clustering to some extent, although clustering at smaller regional scales persisted. The significant region-specific hot and cold spots of the four dietary patterns illustrate the existence of regional "food cultures" and underscore the need for interventions targeted at the sub-national level in order to tackle unhealthy dietary behavior and to stimulate people to make healthy dietary choices.


Mechanisms of serotonin receptor agonist-induced activation of the hypothalamic-pituitary-adrenal axis in the rat.
A substantial body of experimental evidence indicates that serotonin (5-HT) and several synthetic 5-HT receptor agonists activate the hypothalamic-pituitary-adrenal (HPA) axis. To explore the mechanism(s) by which 5-HT or 5-HT agonists enhance the activity of the HPA axis in vitro, we examined the stimulatory effects of the 5-HT1a agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), the 5-HT1c/5-HT1b agonist m-chlorophenylpiperazine (m-CPP), and the 5-HT2/5-HT1c agonist 1-(2,5-dimethoxy-4-iodophenyl)2-amino-propane (DOI) on plasma ACTH and corticosterone secretion in the rat. To test whether 8-OH-DPAT, m-CPP, or DOI increase plasma ACTH levels by stimulating the release of endogenous CRH, catheterized conscious male Sprague-Dawley rats were pretreated with hyperimmune CRH rabbit serum (TS-6) or normal rabbit serum and subsequently challenged with a maximally stimulatory dose of the above 5-HT agonists. Pretreatment with TS-6 completely suppressed the ACTH response to m-CPP and significantly blunted the responses to 8-OH-DPAT or DOI. To examine whether the remaining ACTH response to 8-OH-DPAT or DOI was also mediated by a pituitary site of action, we administered each of these agents to pituitary stalk-transected or sham-operated rats. The ACTH responses to 8-OH-DPAT and DOI in stalk-transected rats were preserved, although significantly blunted, compared to those in sham-operated rats. This suggested that both of these 5-HT agonists may also act at the pituitary level to stimulate ACTH release in vivo. Although the ACTH responses to 8-OH-DPAT, m-CPP, and DOI were blunted after both TS-6 pretreatment and pituitary stalk transection, corticosterone responses were only slightly affected, suggesting that some of these compounds may cause corticosterone release in the rat through another mechanism. To evaluate this hypothesis, ACTH and corticosterone responses to 8-OH-DPAT, m-CPP, and DOI were examined in rats whose HPA axis had been suppressed by a single high dose injection of dexamethasone. The corticosterone responses to 8-OH-DPAT and DOI were blunted compared to those of saline-pretreated rats, but were inappropriately high compared to the ACTH responses observed in these rats. On the other hand, both ACTH and corticosterone responses to m-CPP were completely abolished by dexamethasone.(ABSTRACT TRUNCATED AT 400 WORDS)


Sphingosine-1-phosphate is a missing cofactor for the E3 ubiquitin ligase TRAF2.
Tumour-necrosis factor (TNF) receptor-associated factor 2 (TRAF2) is a key component in NF-kappaB signalling triggered by TNF-alpha. Genetic evidence indicates that TRAF2 is necessary for the polyubiquitination of receptor interacting protein 1 (RIP1) that then serves as a platform for recruitment and stimulation of IkappaB kinase, leading to activation of the transcription factor NF-kappaB. Although TRAF2 is a RING domain ubiquitin ligase, direct evidence that TRAF2 catalyses the ubiquitination of RIP1 is lacking. TRAF2 binds to sphingosine kinase 1 (SphK1), one of the isoenzymes that generates the pro-survival lipid mediator sphingosine-1-phosphate (S1P) inside cells. Here we show that SphK1 and the production of S1P is necessary for lysine-63-linked polyubiquitination of RIP1, phosphorylation of IkappaB kinase and IkappaBalpha, and IkappaBalpha degradation, leading to NF-kappaB activation. These responses were mediated by intracellular S1P independently of its cell surface G-protein-coupled receptors. S1P specifically binds to TRAF2 at the amino-terminal RING domain and stimulates its E3 ligase activity. S1P, but not dihydro-S1P, markedly increased recombinant TRAF2-catalysed lysine-63-linked, but not lysine-48-linked, polyubiquitination of RIP1 in vitro in the presence of the ubiquitin conjugating enzymes (E2) UbcH13 or UbcH5a. Our data show that TRAF2 is a novel intracellular target of S1P, and that S1P is the missing cofactor for TRAF2 E3 ubiquitin ligase activity, indicating a new paradigm for the regulation of lysine-63-linked polyubiquitination. These results also highlight the key role of SphK1 and its product S1P in TNF-alpha signalling and the canonical NF-kappaB activation pathway important in inflammatory, antiapoptotic and immune processes.


History of total knee replacement.
In the early 1970s, the condylar knee was developed independently in the United States and overseas. The concept of replacing the tibiofemoral condylar surfaces with cemented fixation, along with preservation of the cruciate ligaments, was developed and refined. To correct severe knee deformities, the condylar knee with posterior cruciate-sacrificing design was introduced, also in the early 1970s. By 1974, replacing the patellofemoral joint and either preserving or sacrificing the cruciate ligaments had become standard practice. Subsequently, condylar knee designs were improved to include modularity and noncemented fixation, with use of universal instrumentation. Today, over 19 companies in the United States distribute total knee implants of three different types: cruciate-preserving, cruciate-substituting, and TC-III. Six major companies are actively involved in designing mobile-bearing knees. Future developments, such as navigation-guided surgery, enhanced kinematics, and wear-resistant bearing surfaces with better fixation, promise a consistent evolution for the total knee replacement.


Rapid asymptomatic transmission of COVID-19 during the incubation period demonstrating strong infectivity in a cluster of youngsters aged 16-23 years outside Wuhan and characteristics of young patients with COVID-19: A prospective contact-tracing study.
The outbreak of coronavirus-disease-2019 (COVID-19) has rapidly spread to many places outside Wuhan. Previous studies on COVID-19 mostly included older hospitalized-adults. Little information on infectivity among and characteristics of youngsters with COVID-19 is available. A cluster of 22 close-contacts of a 22-year-old male (Patient-Index) including youngsters with laboratory-confirmed COVID-19 and hospitalized close-contacts testing negative for severe-acute-respiratory-syndrome-coronavirus-2 (SARS-CoV-2) in Anhui Province, China was prospectively-traced. Since January 23, 2020, we enrolled a cluster of eight youngsters with COVID-19 (median age [range], 22 [16-23] years; six males) originating from Patient-Index returning from Wuhan to Hefei on January 19. Patient-Index visited his 16-year-old female cousin in the evening on his return, and met 15 previous classmates in a get-together on January 21. He reported being totally asymptomatic and were described by all his contacts as healthy on January 19-21. His very first symptoms were itchy eyes and fever developed at noon and in the afternoon on January 22, respectively. Seven youngsters (his cousin and six classmates) became infected with COVID-19 after a-few-hour-contact with Patient-Index. None of the patients and contacts had visited Wuhan (except Patient-Index), or had any exposure to wet-markets, wild-animals, or medical-institutes within three months. For affected youngsters, the median incubation-period was 2 days (range, 1-4). The median serial-interval was 1 day (range, 0-4). Half or more of the eight COVID-19-infected youngsters had fever, cough, sputum production, nasal congestion, and fatigue on admission. All patients had mild conditions. Six patients developed pneumonia (all mild; one bilateral) on admission. As of February 20, four patients were discharged. SARS-CoV-2-infection presented strong infectivity during the incubation-period with rapid transmission in this cluster of youngsters outside Wuhan. COVID-19 developed in these youngsters had fast onset and various nonspecific atypical manifestations, and were much milder than in older patients as previously reported.


Traffic-related Air Pollution and Attention in Primary School Children: Short-term Association.
Although air pollution's short-term effects are well understood to be marked and preventable, its acute neuropsychological effects have, to our knowledge, not yet been studied. We aim to examine the association between daily variation in traffic-related air pollution and attention. We conducted a follow-up study from January 2012 to March 2013 in 2,687 school children from 265 classrooms in 39 schools in Barcelona (Catalonia, Spain). We assessed four domains of children's attention processes every 3 months over four repeated visits providing a total of 10,002 computerized tests on 177 different days using the child Attention Network test (ANT). Ambient daily levels of nitrogen dioxide (NO2) and elemental carbon (EC) in particulate matter <2.5 µm (PM2.5) filters were measured at a fixed air quality background monitoring station and in schools. Daily ambient levels of both NO2 and EC were negatively associated with all attention processes (e.g., children in the bottom quartile of daily exposure to ambient NO2 levels had a 14.8 msecond [95% confidence interval, 11.2, 18.4] faster response time than those in the top quartile, which was equivalent to a 1.1-month [0.84, 1.37] retardation in the natural developmental improvement in response speed with age). Similar findings were observed after adjusting for the average indoor (classroom) levels of pollutants. Associations for EC were similar to those for NO2 and robust to several sensitivity analyses. The short-term association of traffic-related air pollutants with fluctuations in attention adds to the evidence that air pollution may have potential harmful effects on neurodevelopment. See video abstract at, http://links.lww.com/EDE/B158.


Diversity and distribution of nuclease bacteriocins in bacterial genomes revealed using Hidden Markov Models.
Bacteria exploit an arsenal of antimicrobial peptides and proteins to compete with each other. Three main competition systems have been described: type six secretion systems (T6SS); contact dependent inhibition (CDI); and bacteriocins. Unlike T6SS and CDI systems, bacteriocins do not require contact between bacteria but are diffusible toxins released into the environment. Identified almost a century ago, our understanding of bacteriocin distribution and prevalence in bacterial populations remains poor. In the case of protein bacteriocins, this is because of high levels of sequence diversity and difficulties in distinguishing their killing domains from those of other competition systems. Here, we develop a robust bioinformatics pipeline exploiting Hidden Markov Models for the identification of nuclease bacteriocins (NBs) in bacteria of which, to-date, only a handful are known. NBs are large (>60 kDa) toxins that target nucleic acids (DNA, tRNA or rRNA) in the cytoplasm of susceptible bacteria, usually closely related to the producing organism. We identified >3000 NB genes located on plasmids or on the chromosome from 53 bacterial species distributed across different ecological niches, including human, animals, plants, and the environment. A newly identified NB predicted to be specific for Pseudomonas aeruginosa (pyocin Sn) was produced and shown to kill P. aeruginosa thereby validating our pipeline. Intriguingly, while the genes encoding the machinery needed for NB translocation across the cell envelope are widespread in Gram-negative bacteria, NBs are found exclusively in γ-proteobacteria. Similarity network analysis demonstrated that NBs fall into eight groups each with a distinct arrangement of protein domains involved in import. The only structural feature conserved across all groups was a sequence motif critical for cell-killing that is generally not found in bacteriocins targeting the periplasm, implying a specific role in translocating the nuclease to the cytoplasm. Finally, we demonstrate a significant association between nuclease colicins, NBs specific for Escherichia coli, and virulence factors, suggesting NBs play a role in infection processes, most likely by enabling pathogens to outcompete commensal bacteria.


High frequency of lambda gene activation in bone marrow pre-B cells.
The frequency of lambda light chain (L) producing cells in immunoglobulin-producing cells that have been generated in vitro from bone marrow pre-B cells was investigated. The frequency of lambda-producing cells obtained in such a culture was three- to eightfold higher than that observed in the culture of mature spleen B cells. These results suggest that the activation of lambda gene at pre-B cell stage occurs far more frequently than the frequency presumed from the percentage of lambda-bearing cells in mature B cells.


Assessing Cancer Risk Associated with Aquatic Polycyclic Aromatic Hydrocarbon Pollution Reveals Dietary Routes of Exposure and Vulnerable Populations.
Polycyclic aromatic hydrocarbon (PAH) exposure is widespread, and many PAHs are considered carcinogenic. The PAH-contaminated AWI Superfund site in Virginia provides a model for studying a complex PAH mixture and its extrapolation to cancer risk and PAH exposure in the general population. We examined cancer risk at the Superfund site due to sediment-derived PAHs and then evaluated PAH sources in the general population and potentially vulnerable subpopulations upon PAH mixture exposure. The PAH mixture was assessed for potential carcinogenicity using the US EPA's OncoLogic™ ranking tool and the US EPA list of priority PAHs. Cancer risk due to PAH exposure was calculated for Superfund site users and compared to the US EPA assessment. Human intake and health endpoints of PAHs within the mixture were extracted from USEtox® chemical fate database, while mean intake exposure was calculated for U.S. adults for select PAHs using NHANES database urinary biomarkers. Eleven PAH compounds within the mixture were of carcinogenic concern, and seven PAHs conveyed significant excess cancer risk at the Superfund site and in the general population, wherein PAH-contaminated seafood ingestion was a main contributor. Other dietary sources of PAHs derived from PAH-contaminated soil or water could also play a role in total exposure. Vulnerable populations to PAH exposure and coinciding increased cancer risk may include, in addition to smokers, children and non-Hispanic blacks, which is a public health concern.


Sea urchin coelomocytes are resistant to a variety of DNA damaging agents.
Increasing anthropogenic activities are creating environmental pressures that threaten marine ecosystems. Effective environmental health assessment requires the development of rapid, sensitive, and cost-effective tools to predict negative impacts at the individual and ecosystem levels. To this end, a number of biological assays using a variety of cells and organisms measuring different end points have been developed for biomonitoring programs. The sea urchin fertilization/development test has been useful for evaluating environmental toxicology and it has been proposed that sea urchin coelomocytes represent a novel cellular biosensor of environmental stress. In this study we investigated the sensitivity of coelomocytes from the sea urchin Lytechinus variegatus to a variety of DNA-damaging agents including ultraviolet (UV) radiation, hydrogen peroxide (H(2)O(2)), methylmethane sulfonate (MMS) and benzo[a]pyrene (BaP). LD(50) values determined for coelomocytes after 24h of exposure to these DNA damaging agents indicated a high level of resistance to all treatments. Significant increases in the formation of apurinic/apyrimidinic (AP or abasic) sites in DNA were only detected using high doses of H(2)O(2), MMS and UV radiation. Comparison of sea urchin coelomocytes with hemocytes from the gastropod mollusk Aplysia dactylomela and the decapod crustacean Panulirus argus indicated that sensitivity to different DNA damaging agents varies between species. The high level of resistance to genotoxic agents suggests that DNA damage may not be an informative end point for environmental health assessment using sea urchin coelomocytes however, natural resistance to DNA damaging agents may have implications for the occurrence of neoplastic disease in these animals.


Tritiated digoxin binding to (Na+ + K+)-activated adenosine triphosphatase: possible allosteric site.
Tritiated H(3)-digoxin specifically binds to a cardiac (Na(+) + K(+))-activated adenosine triphosphatase. In the presence of adenosine triphosphate and other nucleoside di- and triphosphates, binding is stimulated by sodium ion, the apparent rate constant being similar to that reported for phosphorus-32 incorporation from adenosine triphosphate and for the adenosine triphosphatase activity. In the presence of magnesium, manganese, inorganic phosphate, or other ions, sodium ion inhibits binding. The data support an allosteric type of sodium-potassium ion pump.


The no-touch rubber hand paradigm and mirror-touch sensation: Support for the self-other theory of mirror-touch synesthesia.
We thoroughly enjoyed Ward and Banissy's Discussion Paper on mirror-touch synesthesia. The authors contrast two theories for explaining this phenomenon-the Threshold Theory and their Self-Other Theory. Ward and Banissy note that the Self-Other Theory garners support from studies that have tested individuals with mirror-touch synesthesia using the rubber hand paradigm. In this Commentary, we provide further support for the Self-Other Theory by drawing on findings from control participants without mirror-touch synesthesia tested with two different no-touch rubber hand paradigms-one paradigm makes it easier while the other makes it more difficult to make the self-other distinction.


Germinated brown rice combined with Lactobacillus acidophilus and Bifidobacterium animalis subsp. lactis inhibits colorectal carcinogenesis in rats.
Colorectal cancer is a common cancer strongly associated with diet. Certain probiotics and prebiotics possess an inhibitory activity against colorectal cancer, while synbiotics may be more effective in preventing this cancer than either prebiotics or probiotics alone. Germinated brown rice (GBR) is considered as a candidate prebiotics with anticancer potential. However, the effect of GBR combined with probiotics on colorectal cancer is not clear. The present study investigated the preventive effect of combination of GBR and Lactobacillus acidophilus, Bifidobacterium animalis subsp. lactis, or both on colorectal carcinogenesis and the possible mechanism in rats treated with 1,2-dimethylhydrazine (DMH) and dextran sulfate sodium (DSS). DMH/DSS treatment induced preneoplastic aberrant crypt foci (ACF) and mucin-depleted foci (MDF), reduced superoxide dismutase (SOD) activity, increased anti-apoptotic Bcl-2 expression, and decreased the expression of pro-apoptotic p53, Bax, and caspase-3 in the colon. Germinated brown rice alone or combined with probiotics inhibited the formation of MDF in the middle colon, enhanced the colonic expression of p53 and Bax, and increased the ratio of Bax/Bcl-2. Combined treatment of GBR and probiotics inhibited the formation of ACF-producing sialomucin (SIM-ACF) and recovered the activity of SOD in the colon. Combination of GBR and L. acidophilus further increased caspase-3 expression and decreased Bcl-2 expression. These findings suggest that GBR combined with L. acidophilus and/or B. animalis subsp. lactis may inhibit colorectal carcinogenesis by enhancing antioxidative capacity and inducing apoptosis. This synbiotics may be a potential functional food or chemopreventive agent for controlling colorectal cancer.


Virtual-'light-sheet' single-molecule localisation microscopy enables quantitative optical sectioning for super-resolution imaging.
Single-molecule super-resolution microscopy allows imaging of fluorescently-tagged proteins in live cells with a precision well below that of the diffraction limit. Here, we demonstrate 3D sectioning with single-molecule super-resolution microscopy by making use of the fitting information that is usually discarded to reject fluorophores that emit from above or below a virtual-'light-sheet', a thin volume centred on the focal plane of the microscope. We describe an easy-to-use routine (implemented as an open-source ImageJ plug-in) to quickly analyse a calibration sample to define and use such a virtual light-sheet. In addition, the plug-in is easily usable on almost any existing 2D super-resolution instrumentation. This optical sectioning of super-resolution images is achieved by applying well-characterised width and amplitude thresholds to diffraction-limited spots that can be used to tune the thickness of the virtual light-sheet. This allows qualitative and quantitative imaging improvements: by rejecting out-of-focus fluorophores, the super-resolution image gains contrast and local features may be revealed; by retaining only fluorophores close to the focal plane, virtual-'light-sheet' single-molecule localisation microscopy improves the probability that all emitting fluorophores will be detected, fitted and quantitatively evaluated.


Vaccine Delays, Refusals, and Patient Dismissals: A Survey of Pediatricians.
Parental noncompliance with the American Academy of Pediatrics and Centers for Disease Control and Prevention immunization schedule is an increasing public health concern. We examined the frequency of requests for vaccine delays and refusals and the impact on US pediatricians' behavior. Using national American Academy of Pediatrics Periodic Surveys from 2006 and 2013, we describe pediatrician perceptions of prevalence of (1) vaccine refusals and delays, (2) parental reasons for refusals and/or delays, and (3) physician dismissals. Questions about vaccine delays were asked only in 2013. We examined the frequency, reasons for, and management of both vaccine refusals and delays by using bivariate and multivariable analyses, which were controlled for practice characteristics, demographics, and survey year. The proportion of pediatricians reporting parental vaccine refusals increased from 74.5% in 2006 to 87.0% in 2013 (P < .001). Pediatricians perceive that parents are increasingly refusing vaccinations because parents believe they are unnecessary (63.4% in 2006 vs 73.1% in 2013; P = .002). A total of 75.0% of pediatricians reported that parents delay vaccines because of concern about discomfort, and 72.5% indicated that they delay because of concern for immune system burden. In 2006, 6.1% of pediatricians reported "always" dismissing patients for continued vaccine refusal, and by 2013 that percentage increased to 11.7% (P = .004). Pediatricians reported increased vaccine refusal between 2006 and 2013. They perceive that vaccine-refusing parents increasingly believe that immunizations are unnecessary. Pediatricians continue to provide vaccine education but are also dismissing patients at higher rates.


Autonomic nervous system modulation during an archery competition in novice and experienced adolescent archers.
We assessed autonomic nervous system modulation through changes in heart rate variability during an archery competition as well as archery performance by comparing novice and experienced adolescent archers. Seven novice (age 14.0 ± 8.5 years, body mass index 22.9 ± 4.3 kg · m(-2), training experience 0.4 ± 0.3 years) and ten experienced archers (age 16.5 ± 10.3 years, body mass index 22.4 ± 3.1 kg · m(-2), training experience 4.1 ± 0.9 years) volunteered. Using beat-by-beat heart rate monitoring, heart rate variability was measured for 20 s before each arrow shot during two rounds of competition. We found that, compared with novices, experienced adolescent archers: (i) take more time per shot; (ii) have a higher low frequency band, square root of the mean of squared differences between successive R-R intervals (i.e. the time elapsing between two consecutive R waves in the electrocardiogram), and percentage of successive normal-to-normal intervals greater than 50 ms; and (iii) demonstrate an increase in parasympathetic nervous system activity compared with pre-competition values. We propose that these characteristics of experienced archers are appropriate for optimal performance during competition.


Transcriptional changes in Schistosoma mansoni during early schistosomula development and in the presence of erythrocytes.
Schistosomes cause more mortality and morbidity than any other human helminth, but control primarily relies on a single drug that kills adult worms. The newly transformed schistosomulum stage is susceptible to the immune response and is a target for vaccine development and rational drug design. To identify genes which are up-regulated during the maturation of Schistosoma mansoni schistosomula in vitro, we cultured newly transformed parasites for 3 h or 5 days with and without erythrocytes and compared their transcriptional profiles using cDNA microarrays. The most apparent changes were in the up-regulation of genes between 3 h and 5 day schistosomula involved in blood feeding, tegument and cytoskeletal development, cell adhesion, and stress responses. The most highly up-regulated genes included a tegument tetraspanin Sm-tsp-3 (1,600-fold up-regulation), a protein kinase, a novel serine protease and serine protease inhibitor, and intestinal proteases belonging to distinct mechanistic classes. The inclusion of erythrocytes in the culture medium resulted in a general but less pronounced increase in transcriptional activity, with the highest up-regulation of genes involved in iron metabolism, proteolysis, and transport of fatty acids and sugars. We have identified the genes that are up-regulated during the first 5 days of schistosomula development in vitro. Using a combination of gene silencing techniques and murine protection studies, some of these highly up-regulated transcripts can be targeted for future development of new vaccines and drugs.


Evaluation of FASTPlaqueTB to diagnose smear-negative tuberculosis in a peripheral clinic in Kenya.
To evaluate the performance and feasibility of FASTPlaqueTB in smear-negative tuberculosis (TB) suspects in a peripheral clinic after laboratory upgrading. Patients with cough > or=2 weeks, two sputum smear-negative results, no response to 1 week of amoxicillin and abnormal chest X-ray were defined as smear-negative suspects. One sputum sample was collected, decontaminated and divided into two: half was tested with FASTPlaqueTB in the clinic laboratory and the other half was cultured on Löwenstein-Jensen medium in the Kenyan Medical Research Institute. Test sensitivity and specificity were evaluated in all patients and in human immunodeficiency virus (HIV) infected patients. Feasibility was assessed by the contamination rate and the resources required to upgrade the laboratory. Of 208 patients included in the study, 56.2% were HIV-infected. Of 203 FASTPlaqueTB tests, 95 (46.8%) were contaminated, which interfered with result interpretation and led to the interruption of the study. Sensitivity and specificity were respectively 31.2% (95%CI 12.1-58.5) and 94.9% (95%CI 86.8-98.4) in all patients and 33.3% (95%CI 9.9-65.1) and 93.9% (95%CI 83.1-98.7) in HIV-infected patients. Upgrading the laboratory cost euro 20,000. FASTPlaqueTB did not perform satisfactorily in this setting. If contamination can be reduced, in addition to laboratory upgrading, its introduction in peripheral clinics would require further assessment in smear-negative and HIV co-infected patients and test adaptation for friendlier use.


Stress fermentation strategies for the production of hyperthermostable superoxide dismutase from Thermus thermophilus HB27: effects of ions.
In this study, we explored how ammonium and metal ion stresses affected the production of recombinant hyperthermostable manganese superoxide dismutase (Mn-SOD). To improve Mn-SOD production, fed-batch culture in shake flasks and bioreactor fermentation were undertaken to examine the effects of [Formula: see text] and Mn(2+) feeding. Under the optimized feeding time and concentrations of [Formula: see text] and Mn(2+), the maximal SOD activity obtained from bioreactor fermentation reached some 480 U/ml, over 4 times higher than that in batch cultivation (113 U/ml), indicating a major enhancement of the concentration of Mn-SOD in the scale-up of hyperthermostable Mn-SOD production. In contrast, when the fed-batch culture with appropriate [Formula: see text] and Mn(2+) feeding was carried out in the same 5-L stirred tank bioreactor, a maximal SOD concentration of some 450 U/ml was obtained, again indicating substantial increase in SOD activity as a result of [Formula: see text] and Mn(2+) feeding. The isoelectric point (pI) of the sample was found to be 6.2. It was highly stable at 90 °C and circular dichroism measurements indicated a high α-helical content of 70 % as well, consistent with known SOD properties. This study indicates that [Formula: see text] and Mn(2+) play important roles in Mn-SOD expression. Stress fermentation strategies established in this study are useful for large-scale efficient production of hyperthermostable Mn-SOD and may also be valuable for the scale-up of other extremozymes.


Diagnosing allergic sensitizations in the third millennium: why clinicians should know allergen molecule structures.
Diagnostic tests to detect allergic sensitization were introduced at the end of the nineteenth century but only in the late 1990s did the advent of molecular allergology revolutionize the approach to the allergic patient. Personalized Medicine, a medical procedure that separates patients into different groups with different medical decisions, practices and interventions has sanctioned this change. In fact, in the last few years molecular allergology and the observation that not every patient has the same allergic profile, even when allergic to the same allergenic source, has originated the concept "one size does not fit all". This new approach requires the identification of still unknown allergens, but also the more detailed investigation of those already known. In depth studies of the structure-function relationships in allergenic molecules can reveal the structural determinants involved in the IgE-binding. Then, the knowledge of the epitope profile of each allergen and of the environmental/experimental conditions affecting the exposure of IgE-binding epitopes can provide important contributions to the understanding of cross-reaction processes and to the improvement of diagnosis, immunotherapy and the overall patient treatment. The evolution of diagnostic systems cannot ignore these new needs in this field.


Spatiotemporal Characterization of Sclerotinia Crown Rot Epidemics in Pyrethrum.
Sclerotinia crown rot, caused by Sclerotinia minor and S. sclerotiorum, is a disease of pyrethrum in Australia that may cause substantial decline in plant density. The spatiotemporal characteristics of the disease were quantified in 14 fields during three growing seasons. Fitting the binary power law to disease incidence provided slope (b = 1.063) and intercept (ln(Ap) = 0.669) estimates significantly (P ≤ 0.0001) greater than 1 and 0, respectively, indicating spatial aggregation at the sampling unit scale that was dependent upon disease incidence. Covariate analyses indicated that application of fungicides did not significantly influence these estimates. Spatial autocorrelation and spatial analysis by distance indices indicated that spatial aggregation above the sampling unit scale was limited to 20 and 17% of transects analyzed, respectively. The range of significant aggregation was limited primarily to neighboring sampling units only. Simple temporal disease models failed to adequately describe disease progress, due to a decline in disease incidence in spring. The relationships between disease incidence at the scales of individual plants within quadrats and quadrats within a field was modeled using four predictors of sample size. The choice of the specific incidence-incidence relationship influenced the classification of disease incidence as greater than or less than 2% of plants, a provisional commercial threshold for fungicide application. Together, these studies indicated that epidemics of Sclerotinia crown rot were dominated by small-scale aggregation of disease. Larger scale patterns of diseased plants, when present, were associated with severe disease outbreaks. The spatial and temporal analyses were suggestive of disease epidemics being associated with localized primary inoculum and other factors that favor disease development at a small scale.


A Systematic Review and Meta-Analysis Comparing Pigtail Catheter and Chest Tube as the Initial Treatment for Pneumothorax.
The optimal initial treatment approach for pneumothorax remains controversial. This systemic review and meta-analysis investigated the effectiveness of small-bore pigtail catheter (PC) drainage compared with that of large-bore chest tube (LBCT) drainage as the initial treatment approach for all subtypes of pneumothorax. PubMed and Embase were systematically searched for observational studies and randomized controlled trials published up to October 9, 2017, that compared PC and LBCT as the initial treatment for pneumothorax. The investigative outcomes included success rates, recurrence rates, complication rates, drainage duration, and hospital stay. Of the 11 included studies (875 patients), the success rate was similar in the PC (79.84%) and LBCT (82.87%) groups, with a risk ratio of 0.99 (95% CI, 0.93 to 1.05; I2 = 0%). Specifically, PC drainage was associated with a significantly lower complication rate following spontaneous pneumothorax than LBCT drainage (Peto odds ratio: 0.49 [95% CI, 0.28 to 0.85]; I2 = 29%). In the spontaneous subgroup, PC drainage was associated with a significantly shorter drainage duration (mean difference, -1.51 [95% CI, -2.93 to -0.09]) and hospital stay (mean difference: -2.54 [95% CI, -3.16 to -1.92]; P < .001) than the LBCT group. Collectively, results of the meta-analysis suggest PC drainage may be considered as the initial treatment option for patients with primary or secondary spontaneous pneumothorax. Ideally, randomized controlled trials are needed to compare PC vs LBCT among different subgroups of patients with pneumothorax, which may ultimately improve clinical care and management for these patients. PROSPERO; No.: CRD42017078481; URL: https://www.crd.york.ac.uk/prospero/.