Self-tanning lotions: are they a healthy way to achieve a tan?
Self-tanning creams utilize dihydroxyacetone (DHA) as an active agent, to produce a temporary staining of the skin. DHA is a 3-carbon sugar that interacts with the protein-rich stratum corneum to produce melanoidins, which are brown chromophores. Lower concentrations of DHA produce lighter skin-staining, while higher concentrations produce darker skin-staining, resulting in the simulation of a tan for persons of all skin types. DHA is well tolerated, for both internal ingestion and topical application, with the exception of infrequent allergic reaction in some patients. However, self-tanning creams only offer a sun protection factor (SPF) of 3 to 4, with protection at the low end of the visible spectrum and limited ultraviolet A protection. In addition, this SPF is only present for several hours after application of the product, and does not last for the duration of the tan. Self-tanning creams are a method of safely simulating the appearance of a tan without photoprotection. However, other sun protection will be required.


Induction of cytotoxic T cell precursors in vivo. Role of T helper cells.
Strain AS rats respond with two populations of cytotoxic T lymphocytes to stimulation in vitro by the major histocompatibility complex (MHC)-incompatible strain HL rat tumor (HL-A2T2). One is specific for MHC alloantigens present on both HL-A2T2 and normal HL targets, the other is tumor specific. The activation of these killer cells requires helper T lymphocytes. The tumor-specific helper cells depend on syngeneic radioresistant accessory cells to present the tumor antigens in an immunogenic form. The appropriate helper-accessory cell interaction results in the production of soluble factors which then induce the maturation of precursor cells into effective killer cells. Studies with a procedure for inducing negative selection of T cells in vivo showed that short-term exposure to HL-A2T2 tumor induced selection only for TH but not cytotoxic T lymphocyte precursors (CTLp). Simultaneous injection of supernatants from concanavalin A-activated spleen cell cultures, however, did produce selection of CTLp. These and other findings suggest that under normal circumstances in vivo, both signals (recognition of antigen and acceptance of maturation factors) are provided in the vicinity of an antigen presenting macrophage-like accessory cell.


Excellent dispersion of MWCNTs in PEO polymer achieved through a simple and potentially cost-effective evaporation casting.
A simple, reliable and potentially cost-effective composite film casting procedure is presented using the evaporation of solvent (water) from a dilute mixture of multiwalled carbon nanotubes (MWCNTs) and polyethylene oxide (PEO) polymer. It is found that the fabrication method develops excellent dispersion of MWCNTs in PEO confirmed by morphology observations, final crystallinity of polymer (amorphous) and a lower percolation threshold (closer to theoretical value) as well as higher electrical conductivity. A film thickness prediction model is derived based upon the fact that final film thickness is mainly dependent upon the dimensions of the casting mold and the loading of the MWCNTs and polymer. This simple model provides important insight that the material loss and the actual density of the base polymer are critical factors making the current casting method truly cost effective and controlling final thickness.


An empirical survey on biobanking of human genetic material and data in six EU countries.
Biobanks correspond to different situations: research and technological development, medical diagnosis or therapeutic activities. Their status is not clearly defined. We aimed to investigate human biobanking in Europe, particularly in relation to organisational, economic and ethical issues in various national contexts. Data from a survey in six EU countries (France, Germany, the Netherlands, Portugal, Spain and the UK) were collected as part of a European Research Project examining human and non-human biobanking (EUROGENBANK, coordinated by Professor JC Galloux). A total of 147 institutions concerned with biobanking of human samples and data were investigated by questionnaires and interviews. Most institutions surveyed belong to the public or private non-profit-making sectors, which have a key role in biobanking. This activity is increasing in all countries because few samples are discarded and genetic research is proliferating. Collections vary in size, many being small and only a few very large. Their purpose is often research, or research and healthcare, mostly in the context of disease studies. A specific budget is very rarely allocated to biobanking and costs are not often evaluated. Samples are usually provided free of charge and gifts and exchanges are the common rule. Good practice guidelines are generally followed and quality controls are performed but quality procedures are not always clearly explained. Associated data are usually computerised (identified or identifiable samples). Biobankers generally favour centralisation of data rather than of samples. Legal and ethical harmonisation within Europe is considered likely to facilitate international collaboration. We propose a series of recommendations and suggestions arising from the EUROGENBANK project.


Mifepristone inhibits extracellular matrix formation in uterine leiomyoma.
To characterize the efficacy of mifepristone treatment on extracellular matrix (ECM) production in leiomyomas. Laboratory study. University research laboratory. None. Treatment of human immortalized two-dimensional (2D) and three-dimensional (3D) leiomyoma and myometrial cells with mifepristone and the progestin promegestone (R5020). Expression of COL1A1, fibronectin, versican variant V0, and dermatopontin in treated leiomyoma cells by Western blot analysis and confirmatory immunohistochemistry staining of treated 3D cultures. Treatment with progestin stimulated production of COL1A1, fibronectin, versican, and dermatopontin. Mifepristone treatment inhibited protein production of these genes, most notably with versican expression. Combination treatment with both the agonist and antagonist further inhibited protein expression of these genes. Immunohistochemistry performed on 3D cultures demonstrated generalized inhibition of ECM protein concentration. Our study demonstrated that the progesterone agonist R5020 directly stimulated extracellular matrix components COL1A1, fibronectin, versican, and dermatopontin production in human leiomyoma cells. Progesterone antagonist mifepristone decreased protein production of these genes to levels comparable with untreated leiomyoma cells.


Generation of antigenic diversity in Plasmodium falciparum by structured rearrangement of Var genes during mitosis.
The most polymorphic gene family in P. falciparum is the ∼60 var genes distributed across parasite chromosomes, both in the subtelomeres and in internal regions. They encode hypervariable surface proteins known as P. falciparum erythrocyte membrane protein 1 (PfEMP1) that are critical for pathogenesis and immune evasion in Plasmodium falciparum. How var gene sequence diversity is generated is not currently completely understood. To address this, we constructed large clone trees and performed whole genome sequence analysis to study the generation of novel var gene sequences in asexually replicating parasites. While single nucleotide polymorphisms (SNPs) were scattered across the genome, structural variants (deletions, duplications, translocations) were focused in and around var genes, with considerable variation in frequency between strains. Analysis of more than 100 recombination events involving var exon 1 revealed that the average nucleotide sequence identity of two recombining exons was only 63% (range: 52.7-72.4%) yet the crossovers were error-free and occurred in such a way that the resulting sequence was in frame and domain architecture was preserved. Var exon 1, which encodes the immunologically exposed part of the protein, recombined in up to 0.2% of infected erythrocytes in vitro per life cycle. The high rate of var exon 1 recombination indicates that millions of new antigenic structures could potentially be generated each day in a single infected individual. We propose a model whereby var gene sequence polymorphism is mainly generated during the asexual part of the life cycle.


ISL-1 is induced in stomach mesenchyme in the presence of pancreatic epithelia.
beta-Cell replacement offers a potential cure for type 1 diabetes mellitus in children. We have previously shown that stomach mesenchyme (SM) is competent to derive islet tissue by mesenchymal-to-epithelial transition (iMET). The aim of this study was to further characterize the developmental fate of this SM in the presence of pancreatic epithelia (PE) in SM/PE recombinants. The homeobox ISL-1 was examined in these recombinants because this gene is restricted to the dorsal pancreatic mesenchyme and endocrine cells in early pancreatic development. Chick-quail recombinants of SM + PE (n = 15) and whole stomach controls (n = 8) were cultured for 7 days. In addition, organ blocks were examined after normal development at days 4 to 10 (n = 4 for each stage). Tissues were analyzed using immunochemistry against quail-specific antigen and ISL-1. Thirteen of 15 SM + PE recombinants expressed the ISL-1 protein in cells from SM origin. Nine of 15 of these recombinants showed iMET and coexpression of insulin, and ISL-1 was recorded. Pancreatic epithelium is able to reprogram SM to a more caudal pancreatic fate when cocultured. Islet tissue by mesenchymal-to-epithelial transition observed in recombinants showed coexpression of insulin and ISL-1. These experiments are important to identify the molecular mechanisms behind iMET for potential therapeutic use for treating children with diabetes.


Metal and redox selectivity of protoporphyrin binding to the heme chaperone CcmE.
The interaction of heme with the heme chaperone CcmE is central to our understanding of cytochrome c maturation, a complex post-translational process involving at least eight proteins in many Gram-negative bacteria and plant mitochondria. We have shown previously that Escherichia coli CcmE can interact with heme non-covalently in vitro, before forming a novel covalent histidine-heme bond, in a redox-sensitive manner. The function of CcmE is to bind heme in the periplasm before transferring it to apocytochromes c. In the absence of structural information on the complex of CcmE and heme, we have further characterized it by examining the binding of the soluble domain of CcmE (CcmE') to protoporphyrins containing metals other than Fe, namely Zn-, Sn-, Co- and Mn-protoporphyrin (PPIX). CcmE' demonstrated no affinity for the Zn- or Sn-containing protoporphyrins and low affinity for Mn(ii)-PPIX. High-affinity, reversible binding was, however, observed for Co(iii)-PPIX, which was highly sensitive to oxidation state as demonstrated by release of the ligand from the chaperone on reduction; no binding to Co(ii)-PPIX was observed. The non-covalent complex of CcmE' and Co(iii)-PPIX was characterized by non-denaturing mass spectrometry. The implications of these observations for the in vivo function of CcmE are discussed.


What Is the Role of Dietary Inflammation in Severe Mental Illness? A Review of Observational and Experimental Findings.
Severe mental illnesses (SMI), including major depressive disorder, bipolar disorder, and schizophrenia, are associated with increased inflammation. Given diet's role in modulating inflammatory processes, excessive calorie-dense, nutrient-deficient processed food intake may contribute toward the heightened inflammation observed in SMI. This review assesses the evidence from observational and experimental studies to investigate how diet may affect physical and mental health outcomes in SMI through inflammation-related pathways. Cross-sectional studies indicate that individuals with SMI, particularly schizophrenia, consume more pro-inflammatory foods and fewer anti-inflammatory nutrients than the general population. Cohort studies indicate that high levels of dietary inflammation are associated with increased risk of developing depression, but there is currently a lack of evidence for schizophrenia or bipolar disorder. Randomized controlled trials show that dietary interventions improve symptoms of depression, but none have tested the extent to which these benefits are due to changes in inflammation. This review summarizes evidence on dietary inflammation in SMI, explores the directionality of these links, and discusses the potential use of targeted nutritional interventions for improving psychological well-being and physical health outcomes in SMI. Establishing the extent to which diet explains elevated levels of inflammatory markers observed in SMI is a priority for future research.


A New Root-Knot Nematode Parasitizing Sea Rocket from Spanish Mediterranean Coastal Dunes: Meloidogyne dunensis n. sp. (Nematoda: Meloidogynidae).
High infection rates of European sea rocket feeder roots by an unknown root-knot nematode were found in a coastal dune soil at Cullera (Valencia) in central eastern Spain. Morphometry, esterase and malate dehydrogenase electrophoretic phenotypes and phylogenetic trees demonstrated that this nematode species differs clearly from other previously described root-knot nematodes. Studies of host-parasite relationships showed a typical susceptible reaction in naturally infected European sea rocket plants and in artificially inoculated tomato (cv. Roma) and chickpea (cv. UC 27) plants. The species is herein described and illustrated and named as Meloidogyne dunensis n. sp. The new root-knot nematode can be distinguished from other Meloidogyne spp. by: (i) perineal pattern rounded-oval, formed of numerous fine dorsal and ventral cuticle striae and ridges, lateral fields clearly visible; (ii) female excretory pore at the level of stylet knobs, EP/ST ratio 1.6; (iii) second-stage juveniles with hemizonid located 1 to 2 annuli anteriorly to excretory pore and long, narrow, tapering tail; and (iv) males with lateral fields composed of four incisures anteriorly and posteriorly, while six distinct incisures are observed for large part at mid-body. Phylogenetic trees derived from distance and maximum parsimony analyses based on 18S, ITS1-5.8S-ITS2 and D2-D3 of 28S rDNA showed that M. dunensis n. sp. can be differentiated from all described root-knot nematode species, and it is clearly separated from other species with resemblance in morphology, such as M. duytsi, M. maritima, M. mayaguensis and M. minor.


New CO-CO interaction potential tested by rovibrational calculations.
A four-dimensional potential energy surface (PES) for the CO dimer consisting of rigid molecules has been calculated, using a scheme that combines density functional theory to describe the monomers and symmetry adapted perturbation theory for the interaction energy (DFT-SAPT). The potential is fitted in terms of analytic functions, and the fitted potential is used to compute the lowest rovibrational states of the dimer. The quality of the PES is comparable to that of a previously published surface, which was calculated with the coupled cluster single double and perturbative triples [CCSD(T)] method. It is shown that a weighted average of the DFT-SAPT and the CCSD(T) potential gives results that are in very good agreement with experimental data, for both ((12)CO)(2) and ((13)CO)(2). The relative weight was determined by adjusting the energy gap between the origins of the lowest two stacks of rotational levels of ((12)CO)(2) to the measured value.


Steps in the morphogenesis of a polarized epithelium. II. Disassembly and assembly of plasma membrane domains during reversal of epithelial cell polarity in multicellular epithelial (MDCK) cysts.
A fundamental aspect in the morphogenesis of a polarized epithelium is the formation of structurally and functionally distinct apical and basal-lateral domains of the plasma membrane. The formation of these membrane domains involves the accumulation of domain-specific proteins and removal of incorrectly localized proteins. The mechanisms involved in these processes are not well understood. We have approached this problem by detailed analysis of the distribution and fate of proteins specific for different membrane domains during reversal of epithelial polarity. In the preceding paper we showed that MDCK cells form multicellular cysts comprising a closed monolayer of polarized cells. The orientation of cell polarity depends upon whether cysts are formed in suspension culture or in a collagen gel. Here, we show that, when fully developed cysts formed in suspension culture are placed in a collagen gel, polarity is rapidly reversed without cell dissociation. We show that during the process of polarity reversal, plasma membrane domains are disassembled by uptake of proteins into cytoplasmic vesicles, followed by protein degradation that probably occurs in lysosomes. The disassembly and assembly of the apical and the basal-lateral membrane domains occur in a sequential order with different kinetics. Our results provide further insights into the establishment of protein specificity of plasma membrane domains in polarized cells.


Muscle relaxation: evidence for an intrafibrillar restoring force in vertebrate striated muscle.
Observations of contracting muscle fibrils in cultured cells indicate that the force which restores the resting length of the sarcomere comes from the contractile elements themselves and not from external elasticity, as is now generally accepted. In light of biochemical studies on the contraction-relaxation cycle, it is postulated that the elongating force is one of internal elasticity in the sarcomere, which arises during contraction from the distortion of bonds between filaments and/or structural proteins. This mechanism of restoration may serve to establish optimal sarcomere length for production of maximum contractile force, and in cardiac muscle this mechanism may be a factor in ventricular filling.


Bevacizumab with erlotinib as first-line therapy in Asian patients with advanced hepatocellular carcinoma: a multicenter phase II study.
The bevacizumab/erlotinib combination was reported with high clinical activity for advanced hepatocellular carcinoma (HCC) by a phase II study conducted in the USA. This multicenter study across several Asian countries was to evaluate the safety and efficacy of the combination in this population. Patients with histology-proven HCC, advanced disease and Child-Pugh class A liver function received bevacizumab 5 mg/kg intravenously every 2 weeks and erlotinib 150 mg/day orally as first-line therapy. The primary end point was progression-free survival at 16 weeks (PFS-16W). The expression of epidermal growth factor receptor (EGFR), phospho-AKT and vascular endothelial growth factor, the microvessel density and the EGFR gene copy number in HCC tissues were correlated with treatment efficacy. Fifty-one patients were enrolled. The PFS-16W was 35.3% (95% CI 22.4-49.9), the median PFS was 2.9 months (95% CI, 1.3-4.4) and the median overall survival was 10.7 months (95% CI, 6.2-15.2). Grade 3/4 toxicities were uncommon, including rash, acne (10% each), diarrhea (6%) and gastrointestinal bleeding (4%). None of the evaluated biomarkers correlated with disease control or PFS. Bevacizumab plus erlotinib showed good tolerability and modest activity in this Asian cohort. Further studies are warranted to identify the predictive biomarkers of this combination.


Modulating effects of humic acids on genotoxicity induced by water disinfectants in Cyprinus carpio.
The use of chlorinated disinfectants during drinking-water production has been shown to generate halogenated compounds as a result of interactions of humic acids with chlorine. Such chlorinated by-products have been shown to induce genotoxic effects and consumption of chlorinated drinking-water has been correlated with increased risk for cancer induction in human populations. The aim of this work was to test the potential genotoxic effects on circulating erythrocytes of the fish Cyprinus carpio exposed in vivo to well-waters disinfected with sodium hypochlorite (NaClO), chlorine dioxide (ClO2) or peracetic acid (CH3COO2H, PAA), in the absence or presence of standard humic acids (HA). The effects were measured by use of the micronucleus (MN) and the single-cell gel electrophoresis (Comet) assays at different sampling times after a 3-day exposure period. The exposure to chlorine disinfectants without the addition of HA produced a clear toxic effect. Significant cytogenetic damage (i.e. MN induction) was detected in fish populations exposed to both NaClO and ClO2 with humic acids. In the Comet assay, a significant decrease of DNA migration was observed in erythrocytes of specimens after exposure to NaClO-disinfected water without HA. No effects were observed in any other experimental condition.


Distinct regulation of autophagic activity by Atg14L and Rubicon associated with Beclin 1-phosphatidylinositol-3-kinase complex.
Beclin 1, a mammalian autophagy protein that has been implicated in development, tumour suppression, neurodegeneration and cell death, exists in a complex with Vps34, the class III phosphatidylinositol-3-kinase (PI(3)K) that mediates multiple vesicle-trafficking processes including endocytosis and autophagy. However, the precise role of the Beclin 1-Vps34 complex in autophagy regulation remains to be elucidated. Combining mouse genetics and biochemistry, we have identified a large in vivo Beclin 1 complex containing the known proteins Vps34, p150/Vps15 and UVRAG, as well as two newly identified proteins, Atg14L (yeast Atg14-like) and Rubicon (RUN domain and cysteine-rich domain containing, Beclin 1-interacting protein). Characterization of the new proteins revealed that Atg14L enhances Vps34 lipid kinase activity and upregulates autophagy, whereas Rubicon reduces Vps34 activity and downregulates autophagy. We show that Beclin 1 and Atg14L synergistically promote the formation of double-membraned organelles that are associated with Atg5 and Atg12, whereas forced expression of Rubicon results in aberrant late endosomal/lysosomal structures and impaired autophagosome maturation. We hypothesize that by forming distinct protein complexes, Beclin 1 and its binding proteins orchestrate the precise function of the class III PI(3)K in regulating autophagy at multiple steps.


Serum creatine phosphokinase as predictor of intermediate syndrome in organophosphorus poisoning.
Organophosphorus (OP) compounds are commonly used pesticides. In OP poisoning, intermediate syndrome (IMS) manifests between the end of the acute cholinergic crisis and delayed neuropathy. Respiratory paralysis in IMS, if identified early can reduce the need for ventilator support, morbidity, and mortality. Serum creatine phosphokinase (CPK) is elevated in IMS. The objectives of our study were to measure serum CPK level, correlate CPK levels with severity of poisoning and estimate atropine dose used. A prospective, observational study was conducted for 1-year. Patients diagnosed with OP poisoning were included. Demographic characteristics, type of poison, time since poisoning, Peradeniya Organophosphorus Poisoning (POP) score, serum pseudocholinesterase, CPK levels, atropine dose, and outcome of treatment were documented. Seventy-five patients were recruited of which 57% and 43% were males and females, respectively, with a mean age of 31.48 ± 11.76 years. The most common OP compound was chlorpyriphos followed by triazophos and methylparathion. The time required to reach hospital was 181.26 ± 89.53 min. About 73.3% and 26.7% of patients had mild and moderate poisoning, respectively, as per POP scale. Pseudocholinesterase level was 364 (205-2168) IU. The amount of atropine used was 190.66 ± 78.83 mg. Serial serum CPK values were 279.72 ± 350.21 IU, 389.78 ± 376.33 IU and 163.13 ± 155.15 IU at admission, 48 h, and 96 h after admission, respectively. A weak positive correlation between serum CPK levels and severity of poisoning (r = 0.352) was observed. All patients recovered completely within 10.69 ± 5.57 days. Three patients developed IMS, and their serial CPK levels were 1837.33 ± 243.19 IU/L, 1935 ± 97.41 IU/L, and 714.66 ± 394.82 IU/L; and recovered in 17 ± 5.6 days. Increased serum CPK levels at 48 h after poisoning was observed in all the patients, but three patients had more than 1500 IU/L, who manifested with IMS. Early diagnosis of IMS by serial estimation of CPK may help in timely intervention and reduce further life-threatening complications.


Heterologous expression and secretion of an antifungal Bacillus subtilis chitosanase (CSNV26) in Escherichia coli.
The aims of the study were the production improvement, the purification, the characterization and the activity investigation of chitosanase CSNV26 of Bacillus subtilis (V26). The gene csnV26 encoding for this protein was amplified and cloned in the pBAD vector then expressed in Escherichia coli (Top10). The SDS-PAGE and zymogram analysis of the recombinant protein showed that it has two active forms sized 27 and 31 kDa, corresponding to the protein with and without signal peptide. This protein has the particularity of being secreted by Top10-pBAD-csnV26 with a high yield of 6.2 g/l. The HPLC purification of CSNV26 from supernatant confirmed the presence of the two sizes. The investigation of the CSNV26 thermostability showed that the pure protein is highly stable keeping 68 % of its activity after 30-min treatment at 100 °C, contrarily to the protein present within the supernatant of E. coli and B. subtilis (V26). The molecular dynamics study of the predicted structure of protein in both forms showed that the presence of the peptide signal in the form of 31 kDa gave it a remarkable thermal stability. The antifungal activity of CSNV26 was evidenced on Rhizopus nigricans and Rhizopus oryzae. Indeed, it has provoked an alteration and embrittlement of their hyphae with onset of protoplast.


A hierarchical word-merging algorithm with class separability measure.
In image recognition with the bag-of-features model, a small-sized visual codebook is usually preferred to obtain a low-dimensional histogram representation and high computational efficiency. Such a visual codebook has to be discriminative enough to achieve excellent recognition performance. To create a compact and discriminative codebook, in this paper we propose to merge the visual words in a large-sized initial codebook by maximally preserving class separability. We first show that this results in a difficult optimization problem. To deal with this situation, we devise a suboptimal but very efficient hierarchical word-merging algorithm, which optimally merges two words at each level of the hierarchy. By exploiting the characteristics of the class separability measure and designing a novel indexing structure, the proposed algorithm can hierarchically merge 10,000 visual words down to two words in merely 90 seconds. Also, to show the properties of the proposed algorithm and reveal its advantages, we conduct detailed theoretical analysis to compare it with another hierarchical word-merging algorithm that maximally preserves mutual information, obtaining interesting findings. Experimental studies are conducted to verify the effectiveness of the proposed algorithm on multiple benchmark data sets. As shown, it can efficiently produce more compact and discriminative codebooks than the state-of-the-art hierarchical word-merging algorithms, especially when the size of the codebook is significantly reduced.


Efficacy and Acceptability of Interventions for Attenuated Positive Psychotic Symptoms in Individuals at Clinical High Risk of Psychosis: A Network Meta-Analysis.
Background: Attenuated positive psychotic symptoms represent the defining features of the clinical high-risk for psychosis (CHR-P) criteria. The effectiveness of each available treatment for reducing attenuated positive psychotic symptoms remains undetermined. This network meta-analysis (NMA) investigates the consistency and magnitude of the effects of treatments on attenuated positive psychotic symptoms in CHR-P individuals, weighting the findings for acceptability. Methods: Web of Science (MEDLINE), PsycInfo, CENTRAL and unpublished/gray literature were searched up to July 18, 2017. Randomized controlled trials in CHR-P individuals, comparing at least two interventions and reporting on attenuated positive psychotic symptoms at follow-up were included, following PRISMA guidelines. The primary outcome (efficacy) was level of attenuated positive psychotic symptoms at 6 and 12 months; effect sizes reported as standardized mean difference (SMD) and 95% CIs in mean follow-up scores between two compared interventions. The secondary outcome was treatment acceptability [reported as odds ratio (OR)]. NMAs were conducted for both primary and secondary outcomes. Treatments were cluster-ranked by surface under the cumulative ranking curve values for efficacy and acceptability. Assessments of biases, assumptions, sensitivity analyses and complementary pairwise meta-analyses for the primary outcome were also conducted. Results: Overall, 1,707 patients from 14 studies (57% male, mean age = 20) were included, representing the largest evidence synthesis of the effect of preventive treatments on attenuated positive psychotic symptoms to date. In the NMA for efficacy, ziprasidone + Needs-Based Intervention (NBI) was found to be superior to NBI (SMD = -1.10, 95% CI -2.04 to -0.15), Cognitive Behavioral Therapy-French and Morrison protocol (CBT-F) + NBI (SMD = -1.03, 95% CI -2.05 to -0.01), and risperidone + CBT-F + NBI (SMD = -1.18, 95% CI -2.29 to -0.07) at 6 months. However, these findings did not survive sensitivity analyses. For acceptability, aripiprazole + NBI was significantly more acceptable than olanzapine + NBI (OR = 3.73; 95% CI 1.01 to 13.81) at 12 months only. No further significant NMA effects were observed at 6 or 12 months. The results were not affected by inconsistency or evident small-study effects, but only two studies had an overall low risk of bias. Conclusion: On the basis of the current literature, there is no robust evidence to favor any specific intervention for improving attenuated positive psychotic symptoms in CHR-P individuals.


Non-Precious Electrodes for Practical Alkaline Water Electrolysis.
Water electrolysis is a promising approach to hydrogen production from renewable energy sources. Alkaline water electrolyzers allow using non-noble and low-cost materials. An analysis of common assumptions and experimental conditions (low concentrations, low temperature, low current densities, and short-term experiments) found in the literature is reported. The steps to estimate the reaction overpotentials for hydrogen and oxygen reactions are reported and discussed. The results of some of the most investigated electrocatalysts, namely from the iron group elements (iron, nickel, and cobalt) and chromium are reported. Past findings and recent progress in the development of efficient anode and cathode materials appropriate for large-scale water electrolysis are presented. The experimental work is done involving the direct-current electrolysis of highly concentrated potassium hydroxide solutions at temperatures between 30 and 100 °C, which are closer to industrial applications than what is usually found in literature. Stable cell components and a good performance was achieved using Raney nickel as a cathode and stainless steel 316L as an anode by means of a monopolar cell at 75 °C, which ran for one month at 300 mA cm-2. Finally, the proposed catalysts showed a total kinetic overpotential of about 550 mV at 75 °C and 1 A cm-2.


Sacral fractures following stand-alone L5-S1 anterior lumbar interbody fusion for isthmic spondylolisthesis.
Recent studies have demonstrated excellent results in treating isthmic spondylolisthesis via an anterior lumbar interbody fusion (ALIF). The authors describe 3 patients with isthmic spondylolisthesis at L5-S1 who experienced sacral fractures after insertion of a unique, stand-alone anterior interbody fixation device. Three consecutive patients at a single institution were treated for Grade I spondylolisthesis at L5-S1 via a standalone ALIF with insertion of a novel biomechanical interbody device. This device is made of polyetheretherketone and has an integrated system for internal fixation into the vertebral bodies. In each patient a bone morphogenetic protein-soaked sponge was placed for the fusion. The indications for treatment in each patient were back and radicular pain that had been unsuccessfully treated with conservative measures. All 3 patients had reduction of their spondylolisthesis and resolution of their unilateral radiculopathies immediately postoperatively. Within 1 month of surgery, all 3 patients had failure of the device and recurrence of their symptoms. In each case the failure was due to fracture of the anterior portion of the S-1 body. Each patient underwent reduction and pedicle screw fixation at L5-S1. In all cases, there was successful reduction in their recurrent spondylolisthesis and resolution of their radiculopathies. Treatment of Grade I isthmic spondylolisthesis at L5-S1 with stand-alone ALIF and fixation can lead to sacral fracture from high stress loads at that level in the spine, and consideration should be made either for supplemental pedicle screw fixation or a completely posterior approach.


The prevalence of multiple sclerosis in the world: an update.
The systematic study of multiple sclerosis (MS) in populations, started in 1929 by Sydney Allison, now consists of over 400 publications dealing with the prevalence of MS throughout the world. However, any attempt to redefine the pattern of geographical differences in MS frequency remains as difficult as ever. The comparison of prevalence studies carried out in different areas and times is made difficult by the variability in surveyed population sizes, age structures, ethnic origins and composition, and the difficult quantification of numerators, especially regarding the recognition of benign and very early cases. Additionally, complete case ascertainment depends on access to medical care, local medical expertise, number of neurologists, accessibility and availability of new diagnostic procedures, the degree of public awareness about MS, and the investigators' zeal and resources. Critical examination of the more recent data on MS prevalence leads to some revisions of previously held concepts, the most interesting of which is the appreciation of the greater influence of genetic factors on disease acquisition. The rarity of MS among Samis, Turkmen, Uzbeks, Kazakhs, Kyrgyzis, native Siberians, North and South Amerindians, Chinese, Japanese, African blacks and New Zealand Maoris, as well as the high risk among Sardinians, Parsis and Palestinians, clearly indicate that the different susceptibilities of distinct racial and ethnic groups are an important determinant of the uneven geographic distribution of the disease. The updated distribution of MS in Europe, showing many exceptions to the previously described north-south gradient, requires more explanation than simply a prevalence-latitude relationship. Prevalence data imply that racial and ethnic differences are important in influencing the worldwide distribution of MS and that its geography must be interpreted in terms of the probable discontinuous distribution of genetic susceptibility alleles, which can however be modified by environment. Because the environmental and genetic determinants of geographic gradients are by no means mutually exclusive, the race versus place controversy is, to some extent, a useless and sterile debate.


Intermediate-spin state of a 3d ion in the octahedral environment and generalization of the Tanabe-Sugano diagrams.
Electronic spectra of 3d(n) transition ions in an octahedral ligand surrounding have been studied using the modified crystal field approach (MCFA), which includes a relativistic spin-orbital interaction. A new variable parameter, the effective nuclear charge Z(eff) of a metal ion that allows accounting implicitly the covalence degree of a metal-ligand bond, has been introduced. Energy diagrams similar to the Tanabe-Sugano ones have been calculated. To study the spin state evolution of the metal ion in an arbitrary distorted octahedral complex, a spin state diagram approach has been proposed. The intermediate-spin (IS) state problem for 3d(4), 3d(5), and 3d(6) metal ions has been considered and conditions for the IS state realization have been formulated. The regions of the mixed high-, intermediate-, and low-spin states have been found. The possibility of coexistence of the different spin states of 3d ions in the octahedral complexes has been considered using crystallography data for the YBaCo(2)O(5.5) layered cobaltite.


Subunits of the alkaline phosphatase of Bacillus licheniformis: chemical, physicochemical, and dissociation studies.
The alkaline phosphatase (orthophosphoric monoester phosphydrolase, EC 220.127.116.11) of Bacillus licheniformis MC14 was studied in an attempt to determine the number of subunits contained in the 120,000-molecular-weight native enzyme. Two moles of arginine was liberated per mole of native enzyme by carboxypeptidases A and B in the presence of sodium dodecyl sulfate. The effect on the native enzyme of progressively lowering the solvent buffer pH was monitored by determining the molecular weight by sedimentation equilibrium analysis, the sedimentation coefficient, the frictional coefficient, and the percent alpha-helix content of the enzyme. The alkaline phosphatase dissociates into two subunits around pH 4. At pH 2.8 a further decrease in S value, but no change in molecular weight, is observed, indicating a change in conformation. The frictional coefficients and percent alpha-helix content agree with this interpretation. A subunit molecular weight of 59,000 was calculated from sodium dodecyl sulfate gels.


Hemiarthroplasties after hip fractures in Norway and Sweden: a collaboration between the Norwegian and Swedish national registries.
National registration of hemiarthroplasties after hip fractures has been established in both Norway and Sweden. We aimed to investigate differences in demographics, choice of implant selection, surgical approaches, and reoperations between the Norwegian Hip Fracture Register (NHFR) and the Swedish Hip Arthroplasty Register (SHAR). As part of the Nordic Arthroplasty Register Association (NARA) project a common hemiarthroplasty dataset has been established. 36,989 primary hemiarthroplasties (HAs) for acute hip fractures reported to NHFR (n = 12,761) and SHAR (n = 24,228) for the period 2005-2010 were included. Cemented prostheses were used in 78% of the operations in Norway and in 95% of the patients in Sweden. In Norway HAs almost exclusively had bipolar design (98%), whereas in Sweden HAs with unipolar design were used in 42% of the cases. Monoblock (non-modular) prostheses were uncommon, but still more frequently used in Sweden than in Norway (6.9% and 2.1% respectively). The lateral approach was more common in Norway (83%) than in Sweden (52%), where the posterior approach was used in 42% of the cases. The five-year survival of all HAs was 95.5% (95% CI: 94.8-96.2) in Norway and 94.8% (95% CI: 94.4-95.3) in Sweden. We concluded that surprisingly large differences between the two countries in demographics, implant design, and surgical technique had been revealed. This common dataset enables further investigations of the impact of these differences on revision rates and mortality.


Public health for the hunter-gatherer in us all.
In evolutionary terms, the transformations which humans have engendered in social, ecological and built environments are increasingly out of step with their biological makeup. We briefly review the evidence on health-relevant practices and status of our Paleolithic ancestors and contrast these with current food, transportation, work and governance systems with their associated impacts on human health. As public health and planning practitioners engaged in the EcoHealth Ontario Collaborative, we argue for recognition of our hunter-gatherer nature to promote joint efforts in building sustainable and equitable community infrastructures, both built and green. Although such efforts are underway at multiple jurisdictional levels across Canada, the pace is frustratingly slow for the burden of endemic chronic diseases and global environmental change which humans face. Reminding reluctant stakeholders of the hunter-gatherers in us all could bring about deeper reflection on the urgent work in redirecting community planning.


Characterization of functional oligosaccharide mimics of the Shigella flexneri serotype 2a O-antigen: implications for the development of a chemically defined glycoconjugate vaccine.
Protection against reinfection with noncapsulated Gram-negative bacteria, such as Shigella, an enteroinvasive bacterium responsible for bacillary dysentery, is mainly achieved by Abs specific for the O-Ag, the polysaccharide part of the LPS, the major bacterial surface Ag. The use of chemically defined glycoconjugates encompassing oligosaccharides mimicking the protective determinants carried by the O-Ag, thus expected to induce an efficient anti-LPS Ab response, has been considered an alternative to detoxified LPS-protein conjugate vaccines. The aim of this study was to identify such functional oligosaccharide mimics of the S. flexneri serotype 2a O-Ag. Using protective murine mAbs specific for S. flexneri serotype 2a and synthetic oligosaccharides designed to analyze the contribution of each sugar residue of the branched pentasaccharide repeating unit of the O-Ag, we demonstrated that the O-Ag exhibited an immunodominant serotype-specific determinant. We also showed that elongating the oligosaccharide sequence improved Ab recognition. From these antigenicity data, selected synthetic oligosaccharides were assessed for their potential to mimic the O-Ag by analyzing their immunogenicity in mice when coupled to tetanus toxoid via single point attachment. Our results demonstrated that induction of an efficient serotype 2a-specific anti-O-Ag Ab response was dependent on the length of the oligosaccharide sequence. A pentadecasaccharide representing three biological repeating units was identified as a potential candidate for further development of a chemically defined glycoconjugate vaccine against S. flexneri 2a infection.


Effects of education and experience on nurses' value of ulcer prevention.
Few studies have focused on the value that nurses place on pressure ulcer prevention, even though values are a key determinant of a person's behaviour and actions. Previous studies have reported that the value that a nurse places on pressure ulcer prevention is linked to the skin care that they deliver. This article describes a study that was undertaken to determine the value that nurses place on pressure ulcer prevention, which also identified how this value is formed. The participants in this study (n=16), were recruited from non-acute adult medical wards of 14 hospitals in one NHS trust, and a university. Data was gathered via semi-structured interviews and interpreted through Straussian grounded theory. The findings of this study show how the participants underwent a transition from placing a low to a high value on pressure ulcer prevention and how this affected patient care. The key point in this transition appears to be an encounter with a patient with a high grade pressure ulcer, which caused the nurses to reappraise their values. Looking after patients with pressure ulcers seems to increase the value that a nurse places on pressure ulcer prevention. The education that nurses receive on pressure ulcer prevention only appears to alter their values when they have some experience of looking after patients with pressure ulcers.


Tumor endothelial inflammation predicts clinical outcome in diverse human cancers.
Vascular endothelial cells contribute to the pathogenesis of numerous human diseases by actively regulating the stromal inflammatory response; however, little is known regarding the role of endothelial inflammation in the growth of human tumors and its influence on the prognosis of human cancers. Using an experimental model of tumor necrosis factor-alpha (TNF-α)-mediated inflammation, we characterized inflammatory gene expression in immunopurified tumor-associated endothelial cells. These genes formed the basis of a multivariate molecular predictor of overall survival that was trained and validated in four types of human cancer. We report that expression of experimentally derived tumor endothelial genes distinguished pathologic tissue specimens from normal controls in several human diseases associated with chronic inflammation. We trained these genes in human cancer datasets and defined a six-gene inflammatory signature that predicted significantly reduced overall survival in breast cancer, colon cancer, lung cancer, and glioma. This endothelial-derived signature predicted outcome independently of, but cooperatively with, standard clinical and pathological prognostic factors. Consistent with these findings, conditioned culture media from human endothelial cells stimulated by pro-inflammatory cytokines accelerated the growth of human colon and breast tumors in immunodeficient mice as compared with conditioned media from untreated endothelial cells. This study provides the first prognostic cancer gene signature derived from an experimental model of tumor-associated endothelial inflammation. These findings support the notion that activation of inflammatory pathways in non-malignant tumor-infiltrating endothelial cells contributes to tumor growth and progression in multiple human cancers. Importantly, these results identify endothelial-derived factors that could serve as potential targets for therapy in diverse human cancers.


Biodegradation of carbon nanohorns in macrophage cells.
With the rapid developments in the medical applications of carbon nanomaterials such as carbon nanohorns (CNHs), carbon nanotubes, and graphene based nanomaterials, understanding the long-term fate, health impact, excretion, and degradation of these materials has become crucial. Herein, the in vitro biodegradation of CNHs was determined using a non-cellular enzymatic oxidation method and two types of macrophage cell lines. Approximately 60% of the CNHs was degraded within 24 h in a phosphate buffer solution containing myeloperoxidase. Furthermore, approximately 30% of the CNHs was degraded by both RAW 264.7 and THP-1 macrophage cells within 9 days. Inflammation markers such as pro-inflammatory cytokines interleukin 6 and tumor necrosis factor α were not induced by exposure to CNHs. However, reactive oxygen species were generated by the macrophage cells after uptake of CNHs, suggesting that these species were actively involved in the degradation of the nanomaterials rather than in an inflammatory pathway induction.


Change of conformation of the DNA-binding domain of p53 is the only key element for binding of and interference with p73.
Xenopus p53 has biological and biochemical properties similar to those of human p53, except for optimal temperature. The frog protein is fully active at 30 degrees C and inactive at 37 degrees C, leading to a temperature-sensitive behavior similar to that of the human mutant p53Ala(143) and the murine mutant p53Val(135). Using hybrid proteins between human and Xenopus expressed from artificial p53 minigenes, we have been able to demonstrate that change of conformation of the DNA-binding domain is the major determinant of this heat sensitivity. It has been reported that some human tumor-derived p53 mutants can engage in a physical association with p73, thus inhibiting its transactivating properties. The mechanism of this association remains to be elucidated. The nature of the mutant p53 that can engage in this association also remains controversial. Using the unique opportunity of the temperature sensitivity of Xenopus p53, we demonstrate that binding of and interference with p73 require a change of conformation in the p53 protein. This interaction occurs through the DNA-binding domain of p53 only when it is in a denatured state. These results reinforce the notion that mutant p53 with a conformational change can act as a down-regulator of the p73 pathway in human cancer and could confer a selective advantage to the tumor.


Assessing the accuracy of quantitative molecular microbial profiling.
The application of high-throughput sequencing in profiling microbial communities is providing an unprecedented ability to investigate microbiomes. Such studies typically apply one of two methods: amplicon sequencing using PCR to target a conserved orthologous sequence (typically the 16S ribosomal RNA gene) or whole (meta)genome sequencing (WGS). Both methods have been used to catalog the microbial taxa present in a sample and quantify their respective abundances. However, a comparison of the inherent precision or bias of the different sequencing approaches has not been performed. We previously developed a metagenomic control material (MCM) to investigate error when performing different sequencing strategies. Amplicon sequencing using four different primer strategies and two 16S rRNA regions was examined (Roche 454 Junior) and compared to WGS (Illumina HiSeq). All sequencing methods generally performed comparably and in good agreement with organism specific digital PCR (dPCR); WGS notably demonstrated very high precision. Where discrepancies between relative abundances occurred they tended to differ by less than twofold. Our findings suggest that when alternative sequencing approaches are used for microbial molecular profiling they can perform with good reproducibility, but care should be taken when comparing small differences between distinct methods. This work provides a foundation for future work comparing relative differences between samples and the impact of extraction methods. We also highlight the value of control materials when conducting microbial profiling studies to benchmark methods and set appropriate thresholds.


Predictive Value of Age-Bilirubin-International Normalized Ratio-Creatinine Score in Short-Term Survival of Acute-on-Chronic Hepatitis B Liver Failure.
The age-bilirubin-international normalized ratio-creatinine (ABIC) score, which is a predictive model commonly used for alcoholic hepatitis, has not yet been studied in acute-on-chronic hepatitis B liver failure (HBV-ACLF). We aimed to investigate the predictive value of the ABIC score in patients with HBV-ACLF. This retrospective study involved 398 patients diagnosed with HBV-ACLF, who were divided into a training cohort of 305 patients and a validation cohort of 93 patients. Univariate and multivariate Cox regression models were used to determine risk factors for mortality. Area under the receiver operating characteristic curve (AUC) was calculated to estimate and compare the predictive values of different prognostic scores. The ABIC score was significantly higher in the death group of the training cohort than in its survival group. Independent risk factors for mortality identified by multivariate Cox analysis included blood urea nitrogen, ABIC score, and Chronic Liver Failure Consortium Organ Failure (CLIF-C OF) score. For predicting 1- and 3-month mortality, AUC was higher for the ABIC score than for the Model for End-stage Liver Diseases (MELD) score (0.732 vs. 0.653, P < 0.05, 0.695 vs. 0.619, P < 0.05, respectively), CLIF-C OF score (0.693, P=0.353, 0.656, P=0.341, respectively), and Child-Pugh score (0.675, P=0.189, 0.656, P=0.300, Respectively). Patients with ABIC score > 9.44 had reduced 1- and 3-month survival rates. ABIC score is superior to MELD score in predicting short-term survival in HBV-ACLF patients. ABIC score > 9.44 predicts high short-term mortality risk in HBV-ACLF patients.


Nonlinear photoacoustic microscopy via a loss modulation technique: from detection to imaging.
In order to achieve high-resolution deep-tissue imaging, multi-photon fluorescence microscopy and photoacoustic tomography had been proposed in the past two decades. However, combining the advantages of these two imaging systems to achieve optical-spatial resolution with an ultrasonic-penetration depth is still a field with challenges. In this paper, we investigate the detection of the two-photon photoacoustic ultrasound, and first demonstrate background-free two-photon photoacoustic imaging in a phantom sample. To generate the background-free two-photon photoacoustic signals, we used a high-repetition rate femtosecond laser to induce narrowband excitation. Combining a loss modulation technique, we successfully created a beating on the light intensity, which not only provides pure sinusoidal modulation, but also ensures the spectrum sensitivity and frequency selectivity. By using the lock-in detection, the power dependency experiment validates our methodology to frequency-select the source of the nonlinearity. This ensures our capability of measuring the background-free two-photon photoacoustic waves by detecting the 2nd order beating signal directly. Furthermore, by mixing the nanoparticles and fluorescence dyes as contrast agents, the two-photon photoacoustic signal was found to be enhanced and detected. In the end, we demonstrate subsurface two-photon photoacoustic bio-imaging based on the optical scanning mechanism inside phantom samples.


Increased gene copy numbers at chromosome 20q are frequent in both squamous cell carcinomas and adenocarcinomas of the cervix.
Genome-wide microarray-based comparative genomic hybridization (array CGH) was used to identify common chromosomal alterations involved in cervical carcinogenesis as a first step towards the discovery of novel biomarkers. The genomic profiles of nine squamous cell carcinomas (SCCs) and seven adenocarcinomas (AdCAs), as well as four human papillomavirus (HPV)-immortalized keratinocyte cell lines, were assessed. On a genome-wide scale, SCCs showed significantly more gains than AdCAs. More specifically, there was a striking and highly significant difference between the two histological types for gain at 3q12.1-28, which was predominantly observed in SCC. Other frequent alterations included gains of 1q21.1-31.1 and 20q11.21-13.33, and losses of 11q22.3-25 and 13q14.3-21.33. Subsequent FISH analysis for hTR, located at 3q26, confirmed the presence of 3q gain in SCCs and HPV-immortalized cell lines. Fine mapping of chromosome 20q using multiplex ligation-dependent probe amplification (MLPA) showed copy number increases for a number of genes located at 20q11-q12, including DNMT3B and TOP1. For DNMT3B, this correlated with elevated mRNA expression in 79% of cases. In conclusion, the assessment of frequent genomic alterations resulted in the identification of potential novel biomarkers, which may ultimately enable a better risk stratification of high-risk (hr)-HPV-positive women.


Abundantly Present miRNAs in Milk-Derived Extracellular Vesicles Are Conserved Between Mammals.
Mammalian milk is not only a source of nutrition for the newborn, but also contains various components that regulate further development. For instance, milk is an abundant source of microRNAs (miRNAs), which are evolutionary conserved small non-coding RNAs that are involved in post-transcriptional regulation of target mRNA. MiRNAs present in milk can occur in extracellular vesicles (EVs), which are nanosized membrane vesicles released by many cell types as a means of intercellular communication. The membrane of EVs protects enclosed miRNAs from degradation and harbors molecules that allow specific targeting to recipient cells. Although several studies have investigated the miRNA content in milk EVs from individual species, little is known about the evolutionary conserved nature of EV-associated miRNAs among different species. In this study, we profiled the miRNA content of purified EVs from human and porcine milk. These data were compared to published studies on EVs from human, cow, porcine, and panda milk to assess the overlap in the top 20 most abundant miRNAs. Interestingly, several abundant miRNAs were shared between species (e.g., let-7 family members let-7a, let-7b, let-7f, and miR-148a). Moreover, these miRNAs have been implicated in immune-related functions and regulation of cell growth and signal transduction. The conservation of these miRNA among species, not only in their sequence homology, but also in their incorporation in milk EVs of several species, suggests that they are evolutionarily selected to regulate cell function in the newborn.


Can greenhouse gases in breath be used to genetically improve feed efficiency of dairy cows?
There is considerable interest in improving feed utilization of dairy cattle while limiting losses to the environment (i.e., greenhouse gases, GHG). To breed for feed-efficient or climate-friendly cattle, it is first necessary to obtain accurate estimates of genetic parameters and correlations of feed intake, greenhouse gases, and production traits. Reducing dry matter take (DMI) requirements while maintaining production has high economic value to farmers, but DMI is costly to record and thus limited to small research or nucleus herds. Conversely, enteric methane (CH4) currently has no economic value, is also costly to record, and is limited to small experimental trials. However, breath gas concentrations of methane (CH4c) and carbon dioxide (CO2c) are relatively cheap to measure at high throughput under commercial conditions by installing sniffers in automated milking stations. The objective of this study was to assess the genetic correlations between DMI, body weight (BW), fat- and protein-corrected milk yield (FPCM), and GHG-related traits: CH4c and CO2c from Denmark (DNK) and the Netherlands (NLD). A second objective was to assess the genetic potential for improving feed efficiency and the added benefits of using CH4c and CO2c as indicators. Feed intake data were available on 703 primiparous cows in DNK and 524 in NLD; CH4c and CO2c records were available on 434 primiparous cows in DNK and 656 in NLD. The GHG-related traits were heritable (e.g., CH4c h2: DNK = 0.26, NLD = 0.15) but were differentially genetically correlated with DMI and feed efficiency in both magnitude and sign, depending on the population and the definition of feed efficiency. Across feed efficiency traits and DMI, having bulls with 100 daughters with FPCM, BW, and GHG traits resulted in sufficiently high accuracy to almost negate the need for DMI records. Despite differences in genetic correlation structure, the relatively cheap GHG-related traits showed considerable potential for improving the accuracy of breeding values of highly valuable feed intake and feed efficiency traits.


Space Analysis of School Violence in the Educational Setting of Peru, 2019.
Schools are increasingly experiencing physical, psychological, and sexual violence, which impacts students' academic achievement and physical and emotional health. Our objective was to identify regional prevalence rates, average prevalence by aggressor type, and provincial spatial conglomerates with higher rates for each type of school violence reported in educational settings in Peru during 2019. An analysis was made of 12,132 cases reported through Peru's Specialized School Violence System (SíseVe). The Moran indices were calculated using provincial prevalence rates to identify conglomerates with high prevalence. In the coast region, the Department of Tacna reported the highest prevalence rates for physical (99.7) and psychological (107); the Department of Amazonas, which is in the jungle, reported the highest prevalence rate for sexual violence (74.6), with teachers in public schools accounting for the majority of sexual assaults against students (56%). Sexual violence predominated in the jungle zone, with a significant percentage of teachers participating in violence with sexual connotations. Physical and psychological violence prevailed in the coastal region.


A Critical Review of Extraction and Identification Methods of Microplastics in Wastewater and Drinking Water.
This critical review analyzes methodologies used to collect, quantify, and characterize microplastics in both wastewater and drinking water. Researchers used different techniques at all stages, from collection to characterization, for quantifying microplastics in urban water systems. This represents a barrier to comprehensively assess the current loads of microplastic and to compare the results obtained by such assessments. The compiled studies address microplastic contamination using four types of sample collection techniques, four methods for processing samples, and four techniques for characterizing microplastics. This results in significant discrepancies in each of the following: (1) reported concentrations in both wastewater effluents and drinking water, (2) microplastic characteristics (i.e., size, color, shape, and composition), and (3) quality control and assurance procedures. Finally, this review qualitatively evaluated the reports by the completeness of their data based on a ranking system using five criteria: sample collection, sample processing, quality control, identification technique, and results. The results of this ranking system clarify disparities between the studies.


Role of hyperbaric oxygen therapy in severe head injury in children.
A brain injury results in a temporary or permanent impairment of cognitive, emotional, and/or physical function. Predicting the outcome of pediatric brain injury is difficult. Prognostic instruments are not precise enough to reliably predict individual patient's mortality and long-term functional status. The purpose of this article is to provide a guide to the strengths and limitations of the use of hyperbaric oxygen therapy (HBOT) in treating pediatric patients with severe brain injury. We studied total 56 patients of head injury. Out of them 28 received HBOT. Only cases with severe head injury [Glasgow Coma Scale (GCS) < 8] with no other associated injury were included in the study group. After an initial period of resuscitation and conservative management (10-12 days), all were subjected to three sessions of HBOT at 1-week interval. This study group was compared with a control group of similar severity of head injury (GCS < 8). The study and control groups were compared in terms of duration of hospitalization, GCS, disability reduction,and social behavior. Patients who received HBOT were significantly better than the control group on all the parameters with decreased hospital stay, better GCS, and drastic reduction in disability. In children with traumatic brain injury, the addition of HBOT significantly improved outcome and quality of life and reduced the risk of complications.


A cerebellar mechanism for learning prior distributions of time intervals.
Knowledge about the statistical regularities of the world is essential for cognitive and sensorimotor function. In the domain of timing, prior statistics are crucial for optimal prediction, adaptation and planning. Where and how the nervous system encodes temporal statistics is, however, not known. Based on physiological and anatomical evidence for cerebellar learning, we develop a computational model that demonstrates how the cerebellum could learn prior distributions of time intervals and support Bayesian temporal estimation. The model shows that salient features observed in human Bayesian time interval estimates can be readily captured by learning in the cerebellar cortex and circuit level computations in the cerebellar deep nuclei. We test human behavior in two cerebellar timing tasks and find prior-dependent biases in timing that are consistent with the predictions of the cerebellar model.


Yeast biogeography and the effects of species recognition approaches: the case study of widespread basidiomycetous species from birch forests in Russia.
Understanding diversity and distribution patterns of fungi, including yeasts, ultimately depends on accuracy of species recognition. However, different approaches to yeast species recognition often result in different entities or operational taxonomic units. We studied the effects of using different yeast species recognition approaches, namely morphological species recognition (MSR) and phylogenetic species recognition (PSR), on the distribution patterns of widespread basidiomycetous yeasts. Hence, we have revised a collection of yeast fungi isolated from spatially remote birch forests in the Moscow Region and Western Siberia with molecular typing and identification tools. PCR fingerprinting and rDNA sequencing analyses of strains of nine species previously identified on the basis of morphological and physiological tests (MSR) yielded 21 phylogenetic species (PSR), including three currently undescribed taxa. The number of distinct phylogenetic species comprised within a single morphospecies ranged from one to seven. A total of ten species were found in both regions, whereas the distribution of 11 yeasts was restricted to a single region only. Both geographical region and type of substrate (plant or soil) influence yeast distribution. Cryptococcus wieringae, C. victoriae, C. magnus, and Leucosporidium scottii were frequently found on plant substrates, whereas C. terricola and C. podzolicus were associated to soil substrates. Occurrence of C. magnus, C. albidus and Sporobolomyces roseus was found to depend on the geographical region. Microsatellite-PCR fingerprinting, MSP-PCR, applied to studying yeast intraspecific variability revealed three different types of distribution: (a) variability that depends on geographical factors (Curvibasidium cygneicollum, C. podzolicus, C. victoriae), (b) genetic identity irrespectively of the region of isolation (Rhodotorula pinicola, C. terricola), and (c) high degree of genetic variability that did not correlate with region of sampling (C. albidus and C. magnus).


Mediterranean dietary pattern is associated with improved cardiac autonomic function among middle-aged men: a twin study.
Reduced heart rate variability (HRV), a measure of cardiac autonomic dysfunction, is a risk factor for coronary artery disease. Diet can influence HRV, but this association may be confounded by genetic and environmental factors. We administered the Willett Food Frequency Questionnaire to 276 middle-aged male twins. We derived a score measuring the extent to which an individual's diet conformed to the Mediterranean diet following a published algorithm. The higher the score, the greater the similarity to the Mediterranean diet. All twins underwent 24-hour ambulatory ECG recording. Time and frequency domain measures of HRV were calculated. Mixed-effects regression was used to partition the association into between- and within-twin pair differences. After adjusting for energy intake, other nutritional factors, shared genes, and common environment, a 1-unit higher score was significantly associated with 3.9% to 13% higher time and frequency domain HRV parameters. Further controlling for known cardiovascular risk factors and use of fish oil supplements and medications did not substantially change the estimates. The Mediterranean dietary pattern is associated with higher HRV.


Assembled coronavirus from complementation of two defective interfering RNAs.
In the presence of an RNA- temperature-sensitive (ts) mutant helper virus, two coronavirus mouse hepatitis virus (MHV) defective interfering (DI) RNAs complemented each other, resulting in the assembly of MHV particles; we used this ability to complement as a means to study coronavirus assembly. One of the two DI RNAs was DIssA, a naturally occurring self-replicating DI RNA encoding N protein and the gene 1 proteins that encode RNA polymerase function; DIssA supports the replication and transcription of other non-self-replicating DI RNAs. The other DI was a genetically engineered DI RNA that encoded sM and M proteins. Coinfection of these two DIs at the nonpermissive temperature for the ts helper virus resulted in replication and transcription of both DI RNAs but not in synthesis of the helper virus RNAs. MHV particles containing DI RNAs, N protein, and M protein, all of which were exclusively derived from the two DI RNAs, were released from the coinfected cells; the amount of sM protein was below the limits of detection. Analyses of DI RNAs with mutations in the two envelope protein genes demonstrated that M and sM proteins appeared to be required for assembly and release of MHV particles that contained DI RNAs and N protein, while S protein was not required for assembly and release of MHV particles.


No DDRama at chromosome ends: TRF2 takes centre stage.
Telomeres are nucleoprotein structures capping the natural termini of eukaryotic linear chromosomes. Telomeres possess an inherent ability to circumvent the activation of a full-blown DNA damage response (DDR), and hence fusion reactions, by limiting inappropriate double-strand break (DSB) repair and processing activities at eukaryotic chromosome ends. A telomere-specific protein complex, termed shelterin, has a crucial function in safeguarding and securing telomere integrity. Within this complex, TRF2 has emerged as the key player, dictating different states of telomere protection during the replicative lifespan of a cell. How TRF2 prevents activation of DSB repair activities at functional telomeres has now been extensively investigated. In this review we aim at exploring the complex and multi-faceted mechanisms underlying the TRF2-mediated protection of eukaryotic chromosome ends.


Is Aeromonas hydrophila the dominant motile Aeromonas species that causes disease outbreaks in aquaculture production in the Zhejiang Province of China?
The significance of Aeromonas hydrophila in association with disease outbreaks in aquaculture production in the Zhejiang province of China was investigated. Bacteriological examination of moribund fish and crabs resulted in 95 bacterial isolates: 88 bacterial isolates from fish and 7 isolates from crabs. PCR and traditional biochemical methods were used for identification of A. hydrophila. Out of 69 motile aeromonads, 35 isolates were identified as A. hydrophila by biochemical tests. However, 6 of those were not identified as A. hydrophila by a species specific PCR method. Serotyping revealed 2 dominant serotypes (O9 and O97) among A. hydrophila isolates. The data presented show that approximately 42% of the motile aeromonads isolated from disease outbreaks among various fish species were A. hydrophila. It is noteworthy that A. hydrophila accounted for more than 50% of the isolated aeromonands isolated from crucian carp Carassius carassius and Wuchang bream Megalobrama amblycephala with haemorrhagic septicaemia. Although this species was the most frequently isolated organism from internal organs of diseased fish and crabs in the present study, other motile Aeromonas spp. were also found. The PCR assay was useful in preventing misidentification of A. hydrophila, which may occur when only phenotypic tests are employed.


Reciprocal Regulation of Substance P and IL-12/IL-23 and the Associated Cytokines, IFNγ/IL-17: A Perspective on the Relevance of This Interaction to Multiple Sclerosis.
The neuropeptide substance P (SP) exhibits cytokine-like properties and exerts different effects in autoimmune inflammation. Various immune cells express SP and its neurokinin-1 receptor (NK1R) isoforms. A role for SP has been demonstrated in a number of autoimmune conditions, including multiple sclerosis (MS). In this work, we studied the role of SP and NK1R in human immune cells with a focus on their relationship with IL-12/IL-23 family cytokines and the associated IFN-γ/IL-17. (1) To determine the role of SP mediated effects on induction of various inflammatory cytokines in peripheral blood mononuclear cells (PBMC); (2) to investigate the expression of SP and its receptor in T cells and the effects of stimulation with IL-12 and IL-23. Quantitative real-time PCR, flow cytometry, ELISA, promoter studies on PBMC and primary T cells from healthy volunteers, and Jurkat cell line. Treatment with SP significantly increased the expression of IL-12/IL-23 subunit p40, IL-23 p19 and IL-12 p35 mRNA in human PBMC. Expression of NK1R and SP in T cells was upregulated by IL-23 but a trend was observed with IL-12. The IL-23 effect likely involves IL-17 production that additionally mediates IL-23 effects. Mutual interactions exist with SP enhancing the cytokines IL-23 and IL-12, and SP and NK1R expression being differentially but potentially synergistically regulated by these cytokines. These findings suggest a proinflammatory role for SP in autoimmune inflammation. We propose a model whereby immunocyte derived SP stimulates Th1 and Th17 autoreactive cells migrating to the central nervous system (CNS), enhances their crossing the blood brain barrier and perpetuates inflammation in the CNS by being released from damaged nerves and activating both resident glia and infiltrating immune cells. SP may be a therapeutic target in MS.


Learning to discriminate through long-term changes of dynamical synaptic transmission.
Short-term synaptic plasticity is modulated by long-term synaptic changes. There is, however, no general agreement on the computational role of this interaction. Here, we derive a learning rule for the release probability and the maximal synaptic conductance in a circuit model with combined recurrent and feedforward connections that allows learning to discriminate among natural inputs. Short-term synaptic plasticity thereby provides a nonlinear expansion of the input space of a linear classifier, whereas the random recurrent network serves to decorrelate the expanded input space. Computer simulations reveal that the twofold increase in the number of input dimensions through short-term synaptic plasticity improves the performance of a standard perceptron up to 100%. The distributions of release probabilities and maximal synaptic conductances at the capacity limit strongly depend on the balance between excitation and inhibition. The model also suggests a new computational interpretation of spikes evoked by stimuli outside the classical receptive field. These neuronal activities may reflect decorrelation of the expanded stimulus space by intracortical synaptic connections.


Preparation of nuclear matrices from cultured cells: subfractionation of nuclei in situ.
Analyses of the different structural systems of the nucleus and the proteins associated with them pose many problems. Because these systems are largely overlapping, in situ localization studies that preserve the in vivo location of proteins and cellular structures often are not satisfactory. In contrast, biochemical cell fractionation may provide artifactual results due to cross-contamination of extracts and structures. To overcome these problems, we have developed a method that combines biochemical cell fractionation and in situ localization and leads to the preparation of a residual cellular skeleton (nuclear matrix and cytoskeletal elements) from cultured cells. This method's main feature is that cell fractionation is performed in situ. Therefore, structures not solubilized in a particular extraction step remain attached to the substrate and retain their morphology. Before and after each extraction step they can be analyzed for the presence and location of the protein under study by using immunological or cytochemical techniques. Thereby the in vivo origin of a protein solubilized in a particular extraction step is determined. The solubilized protein then may be further characterized biochemically. In addition, to allow analyses of proteins associated with the residual cellular skeleton, we have developed conditions for its solubilization that do not interfere with enzymatic and immunological studies.


Functional dissociation of brain rhythms in social coordination.
The goal of this research was to investigate sub-band modulations in the mu domain in dyads performing different social coordination tasks. Dyads of subjects performed rhythmic finger movement under three different task conditions: intrinsic - maintain self-produced movement while ignoring their partner's movement; in-phase - synchronize with partner; and anti-phase - maintain syncopation with partner. Movement profiles of the dyads were used to estimate a synchronization index (SI) to verify differences in coordination according to each task. EEG was recorded during task performance and at baseline (partner's actions hidden from view). Log power ratios of mu band activity (active against baseline) were used to assess the relative levels of synchronization/de-synchronization in both the upper and lower mu bands. Results confirm a functional dissociation of lower (8-10 Hz) and upper (10-12 Hz) mu bands in social coordination tasks. Lower mu band activity was independent of specific modulations across tasks and hemispheric preferences. Upper mu band activity was sensitive to coordination tasks and exhibited marked differences between the hemispheres. Accentuated de-synchronization of right relative to left hemisphere in the anti-phase task appeared related to the greater demand of perceptual-motor discrimination. Left hemisphere de-synchronization in both in-phase and anti-phase coordination was interpreted in terms of successful production of imitation. Right hemisphere synchronization in the intrinsic task was interpreted as inhibition of an imitative response tendency. Functional dissociation of lower and upper mu band and hemispheric preferences exists in real-time social coordination. This research attests to the merit of analyzing sub-band activity in the alpha-mu domain in order to identify neural correlates of social coordination. Such 'neuromarkers' may be relevant for brain disorders such as apraxia and autism.


Serum concentrations of insulin-like growth factors (IGFs), IGF binding proteins 1 and 3 and growth hormone binding protein in obese women and the effects of growth hormone administration: a double-blind, placebo-controlled study.
Obesity is associated with suppressed growth hormone (GH) concentrations but relatively little is known about insulin-like growth factors(IGFs) and binding proteins for GH and IGFs (GHBP and IGFBPs) and the modulatory effect of GH administration. In a double-blind, crossover design we studied the impact of 5 weeks of placebo or GH administration (0.03 mg.kg-1 body wt.day-1) in nine obese women (mean +/- SEM: age 30.4 +/- 2.4 years; body mass index 37.0 +/- 2.8 kg/m2) on IGF-I, IGF-II, IGFBP-1 and -3 and GHBP. Serum IGF-I (microgram/l) levels were subnormal and increased significantly following GH (117 +/- 16 (placebo) vs 434 +/- 33 (GH) vs 198 +/- 15 (control (p < 0.01)). By contrast, serum IGF-II (microgram/l) levels were in the normal range and remained unchanged (608 +/- 20 (placebo) vs 647 +/- 40 (GH) (NS)). Serum IGFBP-3 was in the normal range and increased significantly during GH treatment, although relatively less than IGF-I, such that the molar ratio between IGF-I and IGFBP-3 increased with GH treatment, whereas the ratio between IGF-I + IGF-II and IGFBP-3 remained unchanged. Serum IGFBP-1 was low in the placebo situation but became further and almost completely suppressed during GH treatment. During a 2-h hyperinsulinemic, euglycemic glucose clamp, IGFBP-1 decreased in the placebo study and remained suppressed during GH. Serum GHBP (nmol/l) levels were elevated substantially compared to non-obese controls (p < 0.001) and did not change during GH treatment (2.37 +/- 0.36 (placebo) vs 2.21 +/- 0.25 (GH) vs 0.80 +/- 0.19 (control)).(ABSTRACT TRUNCATED AT 250 WORDS)


Immigrants' utilization of specialist mental healthcare according to age, country of origin, and migration history: a nation-wide register study in Norway.
As the immigrant population rises in Norway, it becomes ever more important to consider the responsiveness of health services to the specific needs of these immigrants. It has been questioned whether access to mental healthcare is adequate among all groups of immigrants. This study aims to examine the use of specialist mental healthcare services among ethnic Norwegians and specific immigrants groups. Register data were used from the Norwegian Patient Registry and Statistics Norway. The sample (age 0-59) consisted of 3.3 million ethnic Norwegians and 200,000 immigrants from 11 countries. Poisson regression models were applied to examine variations in the use of specialist mental healthcare during 2008-2011 according to country of origin, age group, reason for immigration, and length of stay. Immigrant children and adolescents had overall significantly lower use of specialist mental healthcare than ethnic Norwegians of the same age. A distinct exception was the high utilization rate among children and youth from Iran. Among adult immigrants, utilization rates were generally lower than among ethnic Norwegians, particularly those from Poland, Somalia, Sri Lanka, and Vietnam. Adult immigrants from Iraq and Iran, however, had high utilization rates. Refugees had high utilization rates of specialist mental healthcare, while labour immigrants had low use. Utilization rates of specialist mental healthcare are lower among immigrants than Norwegians. Immigrants from Poland, Somalia, Sri Lanka, and Vietnam, had generally quite low rates, while immigrants from Iran had high utilization rates. The findings suggest that specialist mental healthcare in Norway is underutilized among considerable parts of the immigrant population.


Modulation of ovomucoid-specific oral tolerance in mice fed plant extracts containing lectins.
We investigated the effect of feeding extracts of four different legumes (red kidney bean (Phaseolus vulgaris), peanut (Arachis hypogaea), soyabean (Glycine max) and pea (Pisum sativum) on the specific immune response against a food protein. Mice were fed ovomucoid and the specific immune response was evaluated. Ovomucoid fed alone resulted in oral tolerance induction measured as both a reduced ovomucoid-specific spleen cell proliferation and antibody response. Feeding kidney-bean extract prevented induction of oral tolerance to ovomucoid measured as spleen cell proliferation in vitro. Pure kidney-bean lectin also prevented oral tolerance induction, suggesting that lectin in the kidney-bean extract caused inhibition of oral tolerance. Parenteral administration (intravenous and intraperitoneal) of pure kidney-bean lectin had no significant influence on oral tolerance induction. Soyabean extract also influenced the immune response against ovomucoid; however, this was not as pronounced as for kidney bean and was only significant (P<0.001) for the antibody response. No effect was observed when pea extract was fed and peanut extract had a non-significant effect on induction of oral tolerance and on the general immune response. Plasma antibodies against kidney-bean lectin, but not against the three other legume lectins, were detected. Our current findings show that other dietary components can influence the specific immune response against food proteins. Various dietary components may thus contribute to the onset of adverse immunological responses.


The global epidemiology and burden of opioid dependence: results from the global burden of disease 2010 study.
To estimate the prevalence and burden of disease attributable to opioid dependence globally, regionally and at country level. Multiple search strategies: (i) peer-reviewed literature searches; (ii) systematic searches of online databases; (iii) internet searches; (iv) consultation and feedback from experts. Culling and data extraction followed protocols. DisMod-MR, the latest version of the generic disease modelling system, a Bayesian meta-regression tool, imputed prevalence by age, year and sex for 187 countries and 21 regions. Disability weight for opioid dependence was estimated through population surveys and multiplied by prevalence data to calculate the years of life lived with disability (YLDs). Opioid dependence premature mortality was computed as years of life lost (YLLs) and summed with YLDs to calculate disability-adjusted life years (DALYs). There were 15.5 million opioid-dependent people globally in 2010 [0.22%, 95% uncertainty interval (UI) = 0.20-0.25%]. Age-standardized prevalence was higher in males (0.30%, 95% UI = 0.27-0.35%) than females (0.14%, 95% UI = 0.12-0.16%), and peaked at 25-29 years. Prevalence was higher than the global pooled prevalence in Australasia (0.46%, 95% UI = 0.41-0.53%), western Europe (0.35%, 95% UI = 0.32-0.39) and North America (0.30%, 95% UI = 0.25-0.36). Opioid dependence was estimated to account for 9.2 million DALYs globally (0.37% of global DALYs) in 2010, a 73% increase on DALYs estimated in 1990. Regions with the highest opioid dependence DALY rates were North America (292.1 per 100,000), eastern Europe (288.4 per 100,000), Australasia (278.6 per 100,000) and southern sub-Saharan Africa (263.5 per 100,000). The contribution of YLLs to opioid dependence burden was particularly high in North America, eastern Europe and southern sub-Saharan Africa. Opioid dependence is a substantial contributor to the global disease burden; its contribution to premature mortality (relative to prevalence) varies geographically, with North America, eastern Europe and southern sub-Saharan Africa most strongly affected.


Characterization of RNA binding protein RBP-P reveals a possible role in rice glutelin gene expression and RNA localization.
RNA binding proteins (RBPs) play an important role in mRNA metabolism including synthesis, maturation, transport, localization, and stability. In developing rice seeds, RNAs that code for the major storage proteins are transported to specific domains of the cortical endoplasmic reticulum (ER) by a regulated mechanism requiring RNA cis-localization elements, or zipcodes. Putative trans-acting RBPs that recognize prolamine RNA zipcodes required for restricted localization to protein body-ER have previously been identified. Here, we describe the identification of RBP-P using a Northwestern blot approach as an RBP that recognizes and binds to glutelin zipcode RNA, which is required for proper RNA localization to cisternal-ER. RBP-P protein expression coincides with that of glutelin during seed maturation and is localized to both the nucleus and cytosol. RNA-immunoprecipitation and subsequent RT-PCR analysis further demonstrated that RBP-P interacts with glutelin RNAs. In vitro RNA-protein UV-crosslinking assays showed that recombinant RBP-P binds strongly to glutelin mRNA, and in particular, 3' UTR and zipcode RNA. RBP-P also exhibited strong binding activity to a glutelin intron sequence, suggesting that RBP-P might participate in mRNA splicing. Overall, these results support a multifunctional role for RBP-P in glutelin mRNA metabolism, perhaps in nuclear pre-mRNA splicing and cytosolic localization to the cisternal-ER.


Telomere length in blood cells is related to the chronicity, severity, and recurrence rate of schizophrenia.
Telomere shortening is strongly associated with higher mortality rates and has been shown in a number of age-related diseases, such as cardiovascular disorders, diabetes mellitus, Alzheimer's disease, and psychiatric disorders. Oxidative stress is known to induce DNA breaks and genome instability. Telomeric DNA rich in guanosine is particularly sensitive to such oxidative damages. Psychosis is associated with a disequilibrium between free radical production and antioxidative defense. Although telomere attrition has been demonstrated in schizophrenia, no relationship has been reported between telomere length and severity of schizophrenia. The aim of the present study was to identify differences in telomere length in peripheral blood cells between patients with chronic schizophrenia (C-SCZ) and early schizophrenia (E-SCZ) and to identify any relationship between telomere length and disease chronicity and severity. Relative average telomere lengths were determined using qPCR assay in patients with E-SCZ (n=42) and C-SCZ (n=44) hospitalized due to schizophrenia exacerbation. E-SCZ was diagnosed when less than 2 years had passed since the beginning of psychotic symptoms. The severity of symptoms was assessed using appropriate scales. The severity of schizophrenia symptoms, as well as the number of psychotic episodes and hospital admissions, correlated significantly with telomere length in univariate analyses. Regression analysis revealed that a model incorporating study group (E-SCZ or C-ECZ), sex, and age, as well as the combined number of documented psychotic episodes and hospital admissions, can significantly predict the length of telomeres in patients with schizophrenia, with over 50% of variance in telomere length explained by the model (adjusted R (2)=0.512). The results of the current study indicate that the recurrence of psychotic symptoms as well as their intensity and chronicity may be correlated with telomere attrition, which is well known to contribute to the development of premature senescence and age-related diseases.


Monitoring of Vital Signs with Flexible and Wearable Medical Devices.
Advances in wireless technologies, low-power electronics, the internet of things, and in the domain of connected health are driving innovations in wearable medical devices at a tremendous pace. Wearable sensor systems composed of flexible and stretchable materials have the potential to better interface to the human skin, whereas silicon-based electronics are extremely efficient in sensor data processing and transmission. Therefore, flexible and stretchable sensors combined with low-power silicon-based electronics are a viable and efficient approach for medical monitoring. Flexible medical devices designed for monitoring human vital signs, such as body temperature, heart rate, respiration rate, blood pressure, pulse oxygenation, and blood glucose have applications in both fitness monitoring and medical diagnostics. As a review of the latest development in flexible and wearable human vitals sensors, the essential components required for vitals sensors are outlined and discussed here, including the reported sensor systems, sensing mechanisms, sensor fabrication, power, and data processing requirements.


Smartphone Apps for Measuring Human Health and Climate Change Co-Benefits: A Comparison and Quality Rating of Available Apps.
Climate change and the burden of noncommunicable diseases are major global challenges. Opportunities exist to investigate health and climate change co-benefits through a shift from motorized to active transport (walking and cycling) and a shift in dietary patterns away from a globalized diet to reduced consumption of meat and energy dense foods. Given the ubiquitous use and proliferation of smartphone apps, an opportunity exists to use this technology to capture individual travel and dietary behavior and the associated impact on the environment and health. The objective of the study is to identify, describe the features, and rate the quality of existing smartphone apps which capture personal travel and dietary behavior and simultaneously estimate the carbon cost and potential health consequences of these actions. The Google Play and Apple App Stores were searched between October 19 and November 6, 2015, and a secondary Google search using the apps filter was conducted between August 8 and September 18, 2016. Eligible apps were required to estimate the carbon cost of personal behaviors with the potential to include features to maximize health outcomes. The quality of included apps was assessed by 2 researchers using the Mobile Application Rating Scale (MARS). Out of 7213 results, 40 apps were identified and rated. Multiple travel-related apps were identified, however no apps solely focused on the carbon impact or health consequences of dietary behavior. None of the rated apps provided sufficient information on the health consequences of travel and dietary behavior. Some apps included features to maximize participant engagement and encourage behavior change towards reduced greenhouse gas emissions. Most apps were rated as acceptable quality as determined by the MARS; 1 was of poor quality and 10 apps were of good quality. Interrater reliability of the 2 evaluators was excellent (ICC=0.94, 95% CI 0.87-0.97). Existing apps capturing travel and dietary behavior and the associated health and environmental impact are of mixed quality. Most apps do not include all desirable features or provide sufficient health information. Further research is needed to determine the potential of smartphone apps to evoke behavior change resulting in climate change and health co-benefits.


The consequences of polyandry for population viability, extinction risk and conservation.
Polyandry, by elevating sexual conflict and selecting for reduced male care relative to monandry, may exacerbate the cost of sex and thereby seriously impact population fitness. On the other hand, polyandry has a number of possible population-level benefits over monandry, such as increased sexual selection leading to faster adaptation and a reduced mutation load. Here, we review existing information on how female fitness evolves under polyandry and how this influences population dynamics. In balance, it is far from clear whether polyandry has a net positive or negative effect on female fitness, but we also stress that its effects on individuals may not have visible demographic consequences. In populations that produce many more offspring than can possibly survive and breed, offspring gained or lost as a result of polyandry may not affect population size. Such ecological 'masking' of changes in population fitness could hide a response that only manifests under adverse environmental conditions (e.g. anthropogenic change). Surprisingly few studies have attempted to link mating system variation to population dynamics, and in general we urge researchers to consider the ecological consequences of evolutionary processes.


Molecular hydrogen alleviates nephrotoxicity induced by an anti-cancer drug cisplatin without compromising anti-tumor activity in mice.
Cisplatin is a widely used anti-cancer drug in the treatment of a wide range of tumors; however, its application is limited by nephrotoxicity, which is affected by oxidative stress. We have reported that molecular hydrogen (H(2)) acts as an efficient antioxidant (Ohsawa et al. in Nat Med 13:688-694, 2007). Here we show that hydrogen efficiently mitigates the side effects of cisplatin by reducing oxidative stress. Mice were administered cisplatin followed by inhaling hydrogen gas (1% H(2) in air). Furthermore, instead of inhaling hydrogen gas, we examined whether drinking water containing hydrogen (hydrogen water; 0.8 mM H(2) in water) is applicable by examining oxidative stress, mortality, and body-weight loss. Nephrotoxicity was assessed by morphological changes, serum creatinine and blood urea nitrogen (BUN) levels. Inhalation of hydrogen gas improved mortality and body-weight loss caused by cisplatin, and alleviated nephrotoxicity. Hydrogen was detected in blood when hydrogen water was placed in the stomach of a rat. Consuming hydrogen water ad libitum also reduced oxidative stress, mortality, and body-weight loss induced by cisplatin in mice. Hydrogen water improved metamorphosis accompanying decreased apoptosis in the kidney, and nephrotoxicity as assessed by serum creatinine and BUN levels. Despite its protective effects against cisplatin-induced toxicity, hydrogen did not impair anti-tumor activity of cisplatin against cancer cell lines in vitro and tumor-bearing mice in vivo. Hydrogen has potential for improving the quality of life of patients during chemotherapy by efficiently mitigating the side effects of cisplatin.


Immune responses to methamphetamine by active immunization with peptide-based, molecular adjuvant-containing vaccines.
Vaccines to methamphetamine (meth) were designed by covalently attaching a meth hapten (METH) to peptide constructs that contained a conformationally biased, response-selective molecular adjuvant, YSFKPMPLaR (EP54). Rats immunized with EP54-containing meth vaccines generated serum antibody titers to authentic meth, an immune outcome that altered meth self-administration. Immunization increased meth self-administration suggesting pharmacokinetic antagonism. The ability of immune sera to bind a METH-modified target protein dramatically decreased during and shortly after the meth self-administration assay, suggesting effective sequestration of free meth. However, the binding ability of immune sera to the METH-modified target protein was recovered 34 days after meth-free clearance time.


An outbreak of Salmonella Typhimurium traced back to salami, Denmark, April to June 2010.
Between April and June 2010, a small national outbreak of Salmonella Typhimurium with a particular multilocus variable-number tandem repeat analysis (MLVA) type was identified in Denmark through laboratory-based surveillance. The outbreak involved twenty cases, primarily living within the greater Copenhagen area. Half of the cases were children aged ten years or younger and 12 were male; three cases were hospitalised.A matched case-control study showed a strong link between illness and eating a particular salami product containing pork and venison, matched odds ratio(mOR):150, confidence interval (CI): 19–1,600. The salami had been produced in Germany. Microbiological confirmation in food samples was sought but not obtained. Danish consumers were notified that they should return or dispose of any packages from the suspected salami batch. Because the salami product had potentially been sold in other European countries, the European Centre for Disease Prevention and Control urgent enquiry and Rapid Alert System for Food and Feed systems were used to highlight the possibility of outbreaks in these countries. Case-control studies area strong tool in some outbreak investigations and evidence from such studies may give sufficient information to recall a food product.