Nuclear quantum tunnelling and carrier delocalization effects to bridge the gap between hopping and bandlike behaviors in organic semiconductors.
The experimental carrier mobility value of organic semiconductors has been increasing rapidly in recent years to well exceed the theoretical limit based on the hopping model calculated using the semi-classical Marcus theory, calling for better understanding and evaluation of carrier mobility. On the other hand, bandlike transport behavior has been observed for some ultra-pure and closely-packed organic single crystals. In this work, we identify the roles of quantum nuclear tunnelling and the charge delocalization effects, leading to a comprehensive computational approach to assess the carrier mobility of organic semiconductors. We present the first-principles evaluated mobility results for some representative organic transport materials at four levels ranging from semiclassical hopping to quantum nuclear enabled hopping and to quantum wavepacket diffusion, and eventually to complete bandlike descriptions. We provide a comprehensive tool to assess the carrier mobility in organic semiconductors based on such improved understanding.


[Probability distribution of Orthezia praelonga Douglas (Hemiptera: Sternorrhyncha: Ortheziidae) in citrus].
The probability distribution of the orthezia scale, Orthezia praelonga Douglas, was studied in plots of commercial orange orchards (Citrus sinensis L., var. "Pêra Rio"), with 5, 9 and 15 years of age, during one year. The survey of presence or absence of the pest in the plants was carried through twenty samplings in the total area of each plot visually inspecting each plant. The dispersion indexes used were: variance/mean relationship (I), index of Morisita (Id), coefficient of Green (Cx) and k exponent of negative binomial distribution for each sampling. The negative binomial distribution was more representative of the frequency distribution data of this scale in citrus, since the variance was superior to the average in all samplings. The analysis of the aggregation index showed that the majority of the samplings presented aggregate distribution for the scales.


[Long-term results of surgery and preoperative hypoxyradiotherapy for colorectal cancer].
Combined treatment for colorectal cancer involving preoperative hypooxyradiotherapy was used to boost targeted irradiation of tumor cells. End results were significantly improved due to the decrease in the number of distant metastases even in cases of poor prognosis because of lymph node involvement.


Progesterone receptor-B regulation of insulin-like growth factor-stimulated cell migration in breast cancer cells via insulin receptor substrate-2.
Progesterone action contributes to the signaling of many growth factor pathways relevant to breast cancer tumor biology, including the insulin-like growth factor (IGF) system. Previous work has shown that insulin receptor substrate-2 (IRS-2) but not IRS-1 levels were regulated by progestin in progesterone receptor-B (PR-B) isoform expressing MCF-7 cells (C4-12 PR-B). Furthermore, type 1 IGF receptor (IGF1R) signaling via IRS-2 correlated with the increased cell migration observed in a number of breast cancer cell lines. Consequently, in this study, we examined whether the elevation of IRS-2 protein induced by progestin was sufficient to promote IGF-I-stimulated cell motility. Treatment of C4-12 PR-B cells with progestin shifted the balance of phosphorylation from IRS-1 to IRS-2 in response to IGF-I. This shift in IRS-2 activation was associated with enhanced migration in C4-12 PR-B cells pretreated with progestin, but had no effect on cell proliferation or survival. Treatment of C4-12 PR-B cells with RU486, an antiprogestin, inhibited IGF-induced cell migration. Attenuation of IRS-2 expression using small interfering RNA resulted in decreased IGF-stimulated motility. In addition, IRS-2 knockdown resulted in an abrogation of PKB/Akt phosphorylation but not mitogen-activated protein kinase. Consequently, LY294002, a phosphoinositide-3-kinase inhibitor, abolished IGF-induced cell motility in progestin-treated C4-12 PR-B cells. These data show a role for the PR in functionally promoting growth factor signaling, showing that levels of IRS proteins can determine IGF-mediated biology, PR-B signaling regulates IRS-2 expression, and that IRS-2 can mediate IGF-induced cell migration via phosphoinositide-3-kinase in breast cancer cells.


Closed-Loop Acoustic Stimulation During Sleep in Children With Epilepsy: A Hypothesis-Driven Novel Approach to Interact With Spike-Wave Activity and Pilot Data Assessing Feasibility.
Slow waves, the electroencephalographic (EEG) hallmark of deep sleep, can be systematically manipulated by acoustic stimulation: stimulation time-locked to the down phase of slow waves reduces, whereas stimulation time-locked to the up phase increases slow waves. Spike-waves during sleep seem to be related to slow waves, raising the question of whether spike-waves can be systematically influenced by such acoustic stimulation. In five pediatric patients, all-night EEG was recorded, combined with real-time slow wave detection. Throughout the night, acoustic stimulation was performed in a 3 × 5-min-block design (no stimulation-stimulation-no stimulation). Tones were applied time-locked either to the up or to the down phase of the detected slow waves in an alternating pattern. All patients tolerated the acoustic stimulation during sleep well. They showed high sleep quality and no signs of clinical or non-convulsive electrographic seizures. Our preliminary analysis shows no systematic effect of acoustic stimulation on spike-wave activity. Moreover, with our stimulation approach tones were distributed over a rather broad phase-range during the DOWN or UP stimulation and showed inter-individual differences in their distribution. In this study, we applied for the first time an acoustic closed-loop slow wave stimulation tool for a non-invasive manipulation of spike-wave activity. Thus, our pilot data show that closed-loop acoustic stimulation is feasible and well tolerated in children with spike wave activity during sleep. Improved precision in phase targeting and personalized stimulation parameters in a larger sample of subjects might be needed to show systematic effects.


Efficacy of single-dose ceftriaxone in experimental otitis media induced by penicillin- and cephalosporin-resistant Streptococcus pneumoniae.
We used a gerbil model of otitis media to assess the efficacy of single-dose ceftriaxone against three Streptococcus pneumoniae strains highly resistant to penicillin (MICs, 4 to 8 micrograms/ml) and with various susceptibilities to ceftriaxone (MICs, 0.5, 4, and 8 micrograms/ml). Middle ear infection was induced by bilateral transbullar challenge with 10(7) bacteria per ear. Antibiotic treatment was administered subcutaneously at 2 h postinfection. Infection status was checked 2 days later by counting the bacteria in middle ear and cerebrospinal fluid samples. With the cefriaxone-susceptible strain (MIC, 0.5 microgram/ml), we tested doses of 5 to 100 mg/kg of body weight. With a dose of 50 mg/kg, treatment outcome was equivalent to that with amoxicillin, which was used as a reference (25 mg/kg, two injections); no bacteria were recovered from 82% of the middle ear samples, and the rate of cerebrospinal fluid culture positivity was significantly reduced to 6%, relative to 59% for the untreated controls. Similar efficacy was obtained with a dose of 100 mg/kg against the two ceftriaxone-resistant strains. Pharmacokinetic study indicates that the values of the parameters in plasma after the administration of a dose of 100 mg/kg (peak level of total drug, 268 +/- 33 micrograms/ml; elimination half-life, 0.8 h; area under concentration-time curve, 488 micrograms.h.ml-1) were still suboptimal compared with the values of the parameters measured in pediatric patients after intravenous or intramuscular administration of a dose of 50 mg/kg. Our results indicate the efficacy of ceftriaxone against experimental cephalosporin-resistant pneumococcal otitis and provide a basis for the clinical use of single-dose ceftriaxone against pneumococcal otitis media.


Factors Associated with Returning At-Home Specimen Collection Kits for HIV Testing among Internet-Using Men Who Have Sex with Men.
In the United States, men who have sex with men (MSM) are known to disproportionately have HIV. The authors sought to describe the acceptability of providing at-home dried blood spot specimen collection kits for HIV testing among MSM. Between August 2010 and December 2010, the authors recruited Internet-using, HIV-negative or -unknown MSM to participate in a 12-month study of behavioral risks. Eligible participants were mailed an at-home HIV test. Of the 896 men who were sent a test kit, 735 (82%) returned the kit. Returning a test kit was significantly associated with race (P = .002), highest level of education (P = .012), and annual income (P = .026). The adjusted odds of black, non-Hispanic men returning a test kit were about half of the odds of white, non-Hispanic men returning a test kit (adjusted odds ratios: 0.49; 95% confidence intervals: 0.31-0.78). Men who have sex with men are willing to provide biological specimens as part of an Internet-based HIV prevention study.


An antigenic analysis using monoclonal antibodies of influenza A (H3N2) viruses isolated from an epidemic in a semi-closed community.
Seventy-eight influenza A (H3N2) viruses isolated from a single epidemic in a semi-closed community involving 203 clinical cases were characterized using a panel of monoclonal antibodies to virus haemagglutinin (HA). Thirty groups of antigenically distinguishable viruses were detected but the majority (41%) of the viruses belonged to two serological groupings, designated 11 and 17. Viruses in serological group 11 were present throughout the outbreak. The greatest diversity of antigenic variants occurred at the time of the epidemic peak. Antigenic differences among the HAs of the viruses were also detected using polyclonal human and animal antisera. The electrophoretic mobility of virus-induced structural and non-structural polypeptides and of the RNA of viruses of representative serological groups was similar or identical, suggesting that new introductions of viruses did not occur during the progress of the epidemic. The evolution of influenza A (H3N2) epidemics even in small communities appears to be complex, although a contribution to the observed antigenic microheterogeneity of the HA by spontaneous variants arising in the laboratory cannot be excluded.


Two-Faced: Roles of JNK Signalling During Tumourigenesis in the Drosophila Model.
The highly conserved c-Jun N-terminal Kinase (JNK) signalling pathway has many functions, regulating a diversity of processes: from cell movement during embryogenesis to the stress response of cells after environmental insults. Studies modelling cancer using the vinegar fly, Drosophila melanogaster, have identified both pro- and anti-tumourigenic roles for JNK signalling, depending on context. As a tumour suppressor, JNK signalling commonly is activated by conserved Tumour Necrosis Factor (TNF) signalling, which promotes the caspase-mediated death of tumourigenic cells. JNK pathway activation can also occur via actin cytoskeleton alterations, and after cellular damage inflicted by reactive oxygen species (ROS). Additionally, JNK signalling frequently acts in concert with Salvador-Warts-Hippo (SWH) signalling - either upstream of or parallel to this potent growth-suppressing pathway. As a tumour promoter, JNK signalling is co-opted by cells expressing activated Ras-MAPK signalling (among other pathways), and used to drive cell morphological changes, induce invasive behaviours, block differentiation, and enable persistent cell proliferation. Furthermore, JNK is capable of non-autonomous influences within tumour microenvironments by effecting the transcription of various cell growth- and proliferation-promoting molecules. In this review, we discuss these aspects of JNK signalling in Drosophila tumourigenesis models, and highlight recent publications that have expanded our knowledge of this important and versatile pathway.


Agreement of infrared temporal artery thermometry with other thermometry methods in adults: systematic review.
To critically review and synthesise the evidence on the agreement of temporal artery thermometry with invasive and noninvasive thermometry methods in hospitalised adults. Noninvasive thermometry methods aim at combining patient comfort and ease of use with satisfactory accuracy of temperature measurements. Infrared temporal artery thermometry is based on the detection of heat radiated from this artery in the forehead and temporal region. Systematic literature review. A literature search was conducted in Pubmed, CINAHL, Cochrane Library, Web of Science and Embase. Data were extracted from twenty method-comparison studies published between 2002-2015. Methodological quality of selected studies was evaluated. Temperature measurements of temporal artery were compared with pulmonary artery, urinary bladder, oesophageal or nasopharyngeal ones in eight studies for the whole temperature range. Accuracy and precision of temporal artery thermometry exceeded recommended levels of 0·3°C in three and six studies respectively. Likewise, in nine studies that compared temporal artery temperature measurements with oral and ear-based ones, satisfactory agreement and variability was reported in five and none of them respectively. With regard to fever and hypothermia, although specificity of temporal artery thermometers for detecting these disorders was satisfactory, their sensitivity was low. Existing evidence does not support that temporal artery thermometry can replace common invasive and noninvasive thermometry methods in adult patients. Health care professionals are recommended to avoid the use of infrared temporal artery temporal artery thermometry in adults, or be cautious about the accuracy and precision of its readings, until improved devices are developed.


A critical component of meiotic drive in Neurospora is located near a chromosome rearrangement.
Neurospora fungi harbor a group of meiotic drive elements known as Spore killers (Sk). Spore killer-2 (Sk-2) and Spore killer-3 (Sk-3) are two Sk elements that map to a region of suppressed recombination. Although this recombination block is limited to crosses between Sk and Sk-sensitive (Sk(S)) strains, its existence has hindered Sk characterization. Here we report the circumvention of this obstacle by combining a classical genetic screen with next-generation sequencing technology and three-point crossing assays. This approach has allowed us to identify a novel locus called rfk-1, mutation of which disrupts spore killing by Sk-2. We have mapped rfk-1 to a 45-kb region near the right border of the Sk-2 element, a location that also harbors an 11-kb insertion (Sk-2(INS1)) and part of a >220-kb inversion (Sk-2(INV1)). These are the first two chromosome rearrangements to be formally identified in a Neurospora Sk element, providing evidence that they are at least partially responsible for Sk-based recombination suppression. Additionally, the proximity of these chromosome rearrangements to rfk-1 (a critical component of the spore-killing mechanism) suggests that they have played a key role in the evolution of meiotic drive in Neurospora.


Endodontic and orthodontic treatment of fused maxillary central incisors: a case report.
The purpose of this case report was to describe combined endodontic and orthodontic treatment of a patient who had permanent maxillary central incisors fused with supernumerary teeth. A severe esthetic problem and crowding in the maxillary arch were present clinically. Radiographic examination demonstrated two separate crowns, roots and pulpal canals on each side. The therapy was initiated with endodontic treatment. Six months after the completion of endodontic therapy, mesio-distal trimming was performed and the defects were restored with anterior resin composites in order to re-establish the esthetics. Orthodontic treatment was performed for the alignment of the upper arch. Follow-up at 4 years demonstrated that the teeth were asymptomatic and neither root nor alveolar bone resorption was found. In conclusion, instead of extracting the supernumerary teeth, the anomaly was treated successfully in a conservative way.


Genome Sequence of Halomonas sp. Strain MCTG39a, a Hydrocarbon-Degrading and Exopolymeric Substance-Producing Bacterium.
Halomonas sp. strain MCTG39a was isolated from coastal sea surface water based on its ability to utilize n-hexadecane. During growth in marine medium the strain produces an amphiphilic exopolymeric substance (EPS) amended with glucose, which emulsifies a variety of oil hydrocarbon substrates. Here, we present the genome sequence of this strain, which is 4,979,193 bp with 4,614 genes and an average G+C content of 55.0%.


Pharmacological GLI2 inhibition prevents myofibroblast cell-cycle progression and reduces kidney fibrosis.
Chronic kidney disease is characterized by interstitial fibrosis and proliferation of scar-secreting myofibroblasts, ultimately leading to end-stage renal disease. The hedgehog (Hh) pathway transcriptional effectors GLI1 and GLI2 are expressed in myofibroblast progenitors; however, the role of these effectors during fibrogenesis is poorly understood. Here, we demonstrated that GLI2, but not GLI1, drives myofibroblast cell-cycle progression in cultured mesenchymal stem cell-like progenitors. In animals exposed to unilateral ureteral obstruction, Hh pathway suppression by expression of the GLI3 repressor in GLI1+ myofibroblast progenitors limited kidney fibrosis. Myofibroblast-specific deletion of Gli2, but not Gli1, also limited kidney fibrosis, and induction of myofibroblast-specific cell-cycle arrest mediated this inhibition. Pharmacologic targeting of this pathway with darinaparsin, an arsenical in clinical trials, reduced fibrosis through reduction of GLI2 protein levels and subsequent cell-cycle arrest in myofibroblasts. GLI2 overexpression rescued the cell-cycle effect of darinaparsin in vitro. While darinaparsin ameliorated fibrosis in WT and Gli1-KO mice, it was not effective in conditional Gli2-KO mice, supporting GLI2 as a direct darinaparsin target. The GLI inhibitor GANT61 also reduced fibrosis in mice. Finally, GLI1 and GLI2 were upregulated in the kidneys of patients with high-grade fibrosis. Together, these data indicate that GLI inhibition has potential as a therapeutic strategy to limit myofibroblast proliferation in kidney fibrosis.


Support of cultured hepatocytes by a laminin-rich gel. Evidence for a functionally significant subendothelial matrix in normal rat liver.
The subendothelial space of normal rat liver contains the constituent proteins of a basal lamina, as judged by immunohistochemical study of tissue sections. However, it is unknown whether these proteins constitute a complex with effects on hepatocellular function. We have examined this question, using normal rat hepatocytes cultured on substrata of matrix proteins as a model of the interaction between cells and basal lamina in vivo. In cultures on a type I collagen substratum, albumin secretion decreased progressively after 2 d. By contrast, when cells were cultured on a laminin-rich gel matrix, albumin secretion was stable for at least 3 wk; other functions and ultrastructural morphology were similarly maintained. None of the individual matrix proteins effectively substituted for the gel matrix, suggesting that full support of hepatocellular function requires a complex of matrix proteins. We speculate that a cause of hepatocellular dysfunction in acute inflammation is disruption of this matrix and alteration of its interaction with the hepatocyte plasma membrane.


[Prospective trends in pathologo-anatomic research].
New approaches and possibilities of studying such categories in general pathology as morphogenesis, pathogenesis and nozology are considered. The study of morphogenesis is shown to be the most perspective in the analysis of functioning of the systems responsible for the specialized function of a given structure; cell regulatory systems (cell cooperations); antagonistic functions at different structural levels. Pathogenesis, as a category of general pathology, can be studied most efficiently by the pathologist when investigating the responsiveness (cell defence systems, neuro-endocrine and local cell regulation, heredity). A role of the pathologist determining nozology is most efficient in the search of etiological, pathogenetic and organospecific (for tumours) markers. The prospects and methodological significance of such investigations are pointed out.


Antiproliferative mechanisms of a transcription factor decoy targeting signal transducer and activator of transcription (STAT) 3: the role of STAT1.
We previously developed a transcription factor decoy targeting signal transducer and activator of transcription 3 (STAT3) and reported antitumor activity in both in vitro and in vivo models of squamous cell carcinoma of the head and neck (SCCHN). Based on the known existence of STAT1-STAT3 heterodimers, the high sequence homology between STAT1 and STAT3, as well as expression of both STAT1 and STAT3 in SCCHN, we examined whether the STAT3 decoy interferes with STAT1 signaling. SCCHN cell lines with different STAT1 expression levels (but similar STAT3 levels) were used. Both cell lines were sensitive to the growth-inhibitory effects of the STAT3 decoy compared with a mutant control decoy. Intact STAT1 signaling was demonstrated by interferon-gamma (IFN-gamma)-mediated induction of STAT1 phosphorylation (Tyr701) and interferon-regulatory factor-1 (IRF-1) expression. Treatment with the STAT3 decoy (but not a mutant control decoy) resulted in inhibition of IRF-1 protein expression in both cell lines, indicating specific inhibition of STAT1 signaling by the STAT3 decoy. Because STAT1 is a potential tumor suppressor, we also investigated whether STAT1 signaling mitigated the therapeutic efficacy of the STAT3 decoy. In both PCI-15B and UM-22B cells, STAT1 siRNA treatment resulted in decreased STAT1 expression, without altering the antitumor activity of the STAT3 decoy. Likewise, the antitumor effects of the STAT3 decoy were not altered by STAT1 activation upon IFN-gamma treatment. These results suggest that the therapeutic mechanisms of STAT3 blockade using a transcription factor decoy are independent of STAT1 activation.


Multi-stage genome-wide association study identifies new susceptibility locus for testicular germ cell tumour on chromosome 3q25.
Recent genome-wide association studies (GWAS) and subsequent meta-analyses have identified over 25 SNPs at 18 loci, together accounting for >15% of the genetic susceptibility to testicular germ cell tumour (TGCT). To identify further common SNPs associated with TGCT, here we report a three-stage experiment, involving 4098 cases and 18 972 controls. Stage 1 comprised previously published GWAS analysis of 307 291 SNPs in 986 cases and 4946 controls. In Stage 2, we used previously published customised Illumina iSelect genotyping array (iCOGs) data across 694 SNPs in 1064 cases and 10 082 controls. Here, we report new genotyping of eight SNPs showing some evidence of association in combined analysis of Stage 1 and Stage 2 in an additional 2048 cases of TGCT and 3944 controls (Stage 3). Through fixed-effects meta-analysis across three stages, we identified a novel locus at 3q25.31 (rs1510272) demonstrating association with TGCT [per-allele odds ratio (OR) = 1.16, 95% confidence interval (CI) = 1.06-1.27; P = 1.2 × 10(-9)].


Guidelines for clinical care: anti-infective agents for intra-abdominal infection. A Surgical Infection Society policy statement.
Several antibiotics have been marketed for therapeutic use in intra-abdominal infection. Often, these agents do not provide a sufficient spectrum activity against both facultative and obligate anaerobic gram-negative organisms, or have certain toxic effects that would not otherwise support their use. Guidelines have been developed for selection of antibiotic therapy for intra-abdominal infections and are presented as a statement of the Surgical Infection Society endorsed by the Executive Council. These guidelines are restricted to infections derived from the gastrointestinal tract and deal with those microorganisms commonly seen in such infections. The recommendations are based on in vitro activity against enteric bacteria, experience in animal models, and documented efficacy in clinical trials. Other concerns regarding pharmacokinetics, mechanisms of action, microbial resistance, and safety were also used in the formation of these guidelines. For community-acquired infections of mild to moderate severity, single-agent therapy with cefoxitin, cefotetan, or cefmetazole or ticarcillin-clavulanic acid is recommended. For more severe infections, single-agent therapy with carbapenems (imipenem/cilastatin) or combination therapy with either a third-generation cephalosporin, a monobactam (aztreonam), or an aminoglycoside plus clindamycin or metronidazole is recommended. Regimens with little or no activity against facultative gram-negative rods or anaerobic gram-negative rods are not considered acceptable.


The extending network of FOXO transcriptional target genes.
The evolutionarily conserved Forkhead box O (FOXO) family of transcription factors regulates multiple transcriptional targets involved in various cellular processes, including proliferation, stress resistance, apoptosis, and metabolism. Target gene regulation appears to be controlled in a cell-type-specific manner due to association of FOXO isoforms with specific cofactors. Many of the cellular processes modulated by FOXO are themselves deregulated in tumorigenesis, and deletion of Foxo genes has demonstrated that these transcription factors function as tumor suppressors. Our understanding of the regulation of FOXO activity, and defining specific transcriptional targets, may provide clues to the molecular mechanisms controlling cell fate decisions. In this review we describe the functional consequences of FOXO activation based on our current knowledge of transcriptional targets.


TACE plus percutaneous chemotherapy-lipiodol treatment of unresectable pedunculated hepatocellular carcinoma.
Pedunculated hepatocellular carcinoma (P-HCC) is rare type of HCC. The study aimed to evaluate the clinical features and outcomes of unresectable P-HCC treated with transcatheter arterial chemoembolization (TACE) and percutaneous chemotherapeutic agents lipiodol emulsion (CALE) injection. The clinical features and outcomes of 25 patients with unresectable P-HCC treated with TACE plus percutaneous CALE injection were retrospectively reviewed, and factors associated with outcomes were analyzed. Comparison with nonpedunculated unresectable HCC was also performed. Patients underwent a median of 4 TACE sessions and received a median of 2 percutaneous CALE injections. The 1-, 2-, 3-, and 5-year actuarial survival rates were 78.9%, 52.6%, 42.1%, and 12.0%, respectively, for patients with P-HCC, and median survival was 27 months (95% confidence interval, 22.6-43.2 months). Patients with P-HCC had better overall survival than those with nonpedunculated HCC (NP-HCC) (P = .002). Vascular invasion and abdominal lymph node metastasis were poor prognostic factors for overall survival in patients with P-HCC. TACE plus percutaneous CALE injection is a safe and effective treatment for unresectable P-HCC. Patients with unresectable P-HCC might have better overall survival than those with NP-HCC after TACE plus percutaneous CALE injection. However, their prognosis remains poor.


[A spectrophotometric method of determining oxyhemoglobin in blood].
A simple method for measuring the relative content of human blood oxyhemoglobin is suggested, not involving the use of toxic reagents. The calculation is made from a newly derived third-degree polynomial reflecting the ratio of the optic densities of whole nonstabilized blood hemoglobin aqueous solution in the 560-580 and 535-560 nm bands.


Rational Design of Photoelectrodes with Rapid Charge Transport for Photoelectrochemical Applications.
Photoelectrode materials are the heart of photoelectrochemical (PEC) cells, which hold great promise to address global energy and environmental issues by converting solar energy into electricity or chemical fuels. In recent decades, significant research efforts have been devoted to the design and construction of photoelectrodes for the efficient generation and utilization of charge carriers to boost PEC performance. Herein, insights from a literature study on the relationship between the architecture and charge dynamics of photoelectrodes are presented. After briefly introducing the fundamental theories of charge dynamics in nanostructured photoelectrodes, the development of photoelectrode design in 1D polycrystalline nanotube arrays, 1D single-crystalline nanowire arrays, and hierarchical and mesoporous nanowire arrays is reviewed with a focus on the interplay between architecture and charge transport properties. For each design, commonly used synthetic approaches and the corresponding charge transport properties are discussed. Subsequently, the applications of these photoelectrodes in PEC systems are summarized. In conclusion, future challenges in the rational design of photoelectrode architecture are presented. The basic relationships between the architectures and charge dynamics of photoelectrode materials discussed here are expected to provide pertinent guidance and a reference for future advanced material design targeting improved light energy conversion systems.


Induction of Protective Immune Responses Against Schistosomiasis haematobium in Hamsters and Mice Using Cysteine Peptidase-Based Vaccine.
One of the major lessons we learned from the radiation-attenuated cercariae vaccine studies is that protective immunity against schistosomiasis is dependent on the induction of T helper (Th)1-/Th2-related immune responses. Since most schistosome larval and adult-worm-derived molecules used for vaccination uniformly induce a polarized Th1 response, it was essential to include a type 2 immune response-inducing molecule, such as cysteine peptidases, in the vaccine formula. Here, we demonstrate that a single subcutaneous injection of Syrian hamsters with 200 μg active papain, 1 h before percutaneous exposure to 150 cercariae of Schistosoma haematobium, led to highly significant (P < 0.005) reduction of >50% in worm burden and worm egg counts in intestine. Immunization of hamsters with 20 μg recombinant glyceraldehyde 3-phosphate dehydrogenase (rSG3PDH) and 20 μg 2-cys peroxiredoxin-derived peptide in a multiple antigen peptide construct (PRX MAP) together with papain (20 μg/hamster), as adjuvant led to considerable (64%) protection against challenge S. haematobium infection, similar to the levels reported with irradiated cercariae. Cysteine peptidases-based vaccination was also effective in protecting outbred mice against a percutaneous challenge infection with S. haematobium cercariae. In two experiments, a mixture of Schistosoma mansoni cathepsin B1 (SmCB1) and Fasciola hepatica cathepsin L1 (FhCL1) led to highly significant (P < 0.005) reduction of 70% in challenge S. haematobium worm burden and 60% reduction in liver egg counts. Mice vaccinated with SmCB1/FhCL1/rSG3PDH mixture and challenged with S. haematobium cercariae 3 weeks after the second immunization displayed highly significant (P < 0.005) reduction of 72% in challenge worm burden and no eggs in liver of 8-10 mice/group, as compared to unimmunized mice, associated with production of a mixture of type 1- and type 2-related cytokines and antibody responses.


Alcohol as a gastric disinfectant? The complex relationship between alcohol consumption and current Helicobacter pylori infection.
Alcoholic beverages have antimicrobial effects against Helicobacter pylori in vitro. To elucidate the relation between alcohol consumption and current infection with H. pylori in vivo, we carried out a pooled analysis of three recent studies from Southern Germany, comprising 1410 adults age 15 to 69. Detailed information on consumption of various alcoholic beverages was collected through standardized questionnaires. Helicobacter pylori infection was measured by 15C-urea breath test. Overall, prevalence of current H. pylori infection was lower among subjects who consumed alcohol (34.9%) than among nondrinkers (38.0%). The adjusted odds ratio was 0.79, with a 95% confidence interval of 0.58-1.08. Furthermore, alcohol consumption showed a strong inverse relation to the result of the 13C-urea breath test, a semiquantitative measure of the bacterial load, among infected subjects. The inverse association between alcohol consumption and H. pylori infection was not monotonic, however. Odds of infection were lowest at moderate levels of alcohol consumption and increased at higher levels of alcohol consumption, regardless of the type of alcoholic beverages consumed. These results support the hypothesis that moderate alcohol consumption may favor suppression and eventual elimination of H. pylori infection. At higher levels of alcohol consumption, the antimicrobial effects of alcoholic beverages may be opposed by adverse systemic effects of drinking, such as adverse effects on the immune defense.


Angiogenic and Immune-Related Biomarkers and Outcomes Following Axitinib/Pembrolizumab Treatment in Patients with Advanced Renal Cell Carcinoma.
Combined axitinib/pembrolizumab is approved for advanced renal cell carcinoma (aRCC). This exploratory analysis examined associations between angiogenic and immune-related biomarkers and outcomes following axitinib/pembrolizumab treatment. Prospectively defined retrospective correlative exploratory analyses tested biospecimens from 52 treatment-naïve patients receiving axitinib and pembrolizumab (starting doses 5 mg twice daily and 2 mg/kg respectively, every 3 weeks). Tumor tissue, serum, and whole blood samples were collected at baseline, at cycle 2 day 1 (C2D1), and end of treatment (EOT) for blood-based samples. Clinical outcomes were objective response rate (ORR) and progression-free survival (PFS). Higher baseline tumor levels of CD8 showed a trend toward longer PFS (HR 0.4; P = 0.091). Higher baseline serum levels of CXCL10 (P = 0.0197) and CEACAM1 (P = 0.085) showed a trend toward better ORR and longer PFS, respectively. Patients for whom IL6 was not detected at baseline had longer PFS versus patients for whom it was detected (HR 0.4; P = 0.028). At C2D1 and/or EOT, mainly immune-related biomarkers showed any association with better outcomes. The genes CA9 (P = 0.084), HIF1A (P = 0.064), and IFNG (P = 0.073) showed trending associations with ORR, and AKT3 (P = 0.0145), DDX58 (P = 0.0726), GZMA (P = 0.0666), LCN2 (NGAL; P = 0.0267), and PTPN11 (P = 0.0287) with PFS. With combined axitinib/pembrolizumab treatment in patients with aRCC, mostly immune-related biomarkers are associated with better treatment outcomes. This exploratory analysis has identified some candidate biomarkers to consider in future prospective testing.


The Maryland Acute Stroke Emergency Medical Services Routing Pilot: Expediting Access to Thrombectomy for Stroke.
Background: Mechanical thrombectomy (MT) is the standard of care for acute ischemic stroke caused by large vessel occlusion, but is not available at all stroke centers. Transfers between hospitals lead to treatment delays. Transport directly to a facility capable of MT based on a prehospital stroke severity scale score has been recommended, if transportation time is less than 30 min. Aims: We hypothesized that an Emergency Medical Services (EMS) routing algorithm for stroke, using the Los Angeles Motor Scale (LAMS) in the field, would improve time from last known well to MT, without causing patients to miss the IV Thrombolysis (IVT) window. Methods: An EMS algorithm in the Baltimore metro area using the LAMS was implemented. Patients suspected of having an acute stroke were assessed by EMS using the LAMS. Patients scoring 4 or higher and within 20 h from last known well, were transported directly to a Thrombectomy Center, if transport could be completed within 30 min. The algorithm was evaluated retrospectively with prospectively collected data at the Thrombectomy Centers. The primary outcome variables were proportion of patients with suspected stroke rerouted by EMS, proportion of rerouted ischemic stroke patients receiving MT, time to treatment, and whether the IVT window was missed. Results: A total of 303 patients were rerouted out of 2459 suspected stroke patients over a period of 6 months. Of diverted patients, 47% had acute ischemic stroke. Of these, 48% received an acute stroke treatment: 16.8% IVT, 17.5% MT, and 14% MT+IVT. Thrombectomy occurred 119 min earlier in diverted patients compared to patients transferred from other hospitals (P = 0.006). 55.3% of diverted patients undergoing MT and 38.2% of patients transferred from hospital to hospital were independent at 90 days (modified Rankin score 0-2) (P = 0.148). No patient missed the time window for IVT due to the extra travel time. Conclusions: In this retrospective analysis of prospectively acquired data, implementation of a pre-hospital clinical screening score to detect patients with suspected acute ischemic stroke due to large vessel occlusion was feasible. Rerouting patients directly to a Thrombectomy Center, based on the EMS algorithm, led to a shorter time to thrombectomy.


Resolving the prevalence of somatic transposition in Drosophila.
Somatic transposition in mammals and insects could increase cellular diversity and neural mobilization has been implicated in age-dependent decline. To understand the impact of transposition in somatic cells it is essential to reliably measure the frequency and map locations of new insertions. Here we identified thousands of putative somatic transposon insertions in neurons from individual Drosophila melanogaster using whole-genome sequencing. However, the number of de novo insertions did not correlate with transposon expression or fly age. Analysing our data with exons as 'immobile genetic elements' revealed a similar frequency of unexpected exon translocations. A new sequencing strategy that recovers transposon: chromosome junction information revealed most putative de novo transposon and exon insertions likely result from unavoidable chimeric artefacts. Reanalysis of other published data suggests similar artefacts are often mistaken for genuine somatic transposition. We conclude that somatic transposition is less prevalent in Drosophila than previously envisaged.


Clinical features and outcome of familial chronic lymphocytic leukemia.
The prognostic impact of the presence of a familial trait was analyzed in 1449 patient with chronic lymphocytic leukemia (CLL). A family history of hematologic malignancy (HM) was identified in 181 cases (12.5%) and recorded more frequently among female than male patients (HM: p < 0.05; CLL: p < 0.05). The relative was affected by CLL in 89 cases (6%). Familial and sporadic cases showed non-statistically different proportions of advanced stages (10.8 vs 7.1%) and patients requiring therapy (55 vs 60%) and a similar survival probability at 10 years (67 vs 66%). These data suggest that in CLL the presence of a familial trait does not imply an adverse prognosis.


[Body composition analysis in ballet dancers].
The aim of this study was to evaluate and compare the nutritional status and body composition in female ballet dancers and a group of non-athletic female controls. The study group consisted of 30 female ballet dancers, aged 17.4 +/- 2.01, whereas the control group included 30 non-athletic female examinees, aged 18.00 years on average. Height and weight were measured and body mass index (BMI) was calculated in all subjects. Body composition was estimated using the bioelectrical impedance method. Body composition analysis of ballet dancers revealed significantly lower values of body fat mass compared to the control group (18.85 +/- 4.50% vs. 23.41 +/- 4.34). Most examinees in both groups were of normal weight. 50% of ballet dancers and 23.33% of examinees in the control group were underweight, while overweight subjects were registered only in the control group. Most underweight ballet dancers had lower body fat mass, whereas majority of underweight examinees in the control group presented with normal body fat mass. Normal-weight obesity was established in 40.91% candidates in the control and 6.67% in the study group. Ballet dancers had significantly lower values of body mass and BMI, compared to the study group. In order to prevent very serious complications caused by changes in size and proportion of some body compartments, it is necessary to carry out assessment of body composition more often in high-risk groups, such as the study group of ballet dancers.


Prostate cancer-specific survival following salvage radiotherapy vs observation in men with biochemical recurrence after radical prostatectomy.
Biochemical disease recurrence after radical prostatectomy often prompts salvage radiotherapy, but no studies to date have had sufficient numbers of patients or follow-up to determine whether radiotherapy improves survival, and if so, the subgroup of men most likely to benefit. To quantify the relative improvement in prostate cancer-specific survival of salvage radiotherapy vs no therapy after biochemical recurrence following prostatectomy, and to identify subgroups for whom salvage treatment is most beneficial. Retrospective analysis of a cohort of 635 US men undergoing prostatectomy from 1982-2004, followed up through December 28, 2007, who experienced biochemical and/or local recurrence and received no salvage treatment (n = 397), salvage radiotherapy alone (n = 160), or salvage radiotherapy combined with hormonal therapy (n = 78). Prostate cancer-specific survival defined from time of recurrence until death from disease. With a median follow-up of 6 years after recurrence and 9 years after prostatectomy, 116 men (18%) died from prostate cancer, including 89 (22%) who received no salvage treatment, 18 (11%) who received salvage radiotherapy alone, and 9 (12%) who received salvage radiotherapy and hormonal therapy. Salvage radiotherapy alone was associated with a significant 3-fold increase in prostate cancer-specific survival relative to those who received no salvage treatment (hazard ratio [HR], 0.32 [95% confidence interval {CI}, 0.19-0.54]; P<.001). Addition of hormonal therapy to salvage radiotherapy was not associated with any additional increase in prostate cancer-specific survival (HR, 0.34 [95% CI, 0.17-0.69]; P = .003). The increase in prostate cancer-specific survival associated with salvage radiotherapy was limited to men with a prostate-specific antigen doubling time of less than 6 months and remained after adjustment for pathological stage and other established prognostic factors. Salvage radiotherapy initiated more than 2 years after recurrence provided no significant increase in prostate cancer-specific survival. Men whose prostate-specific antigen level never became undetectable after salvage radiotherapy did not experience a significant increase in prostate cancer-specific survival. Salvage radiotherapy also was associated with a significant increase in overall survival. Salvage radiotherapy administered within 2 years of biochemical recurrence was associated with a significant increase in prostate cancer-specific survival among men with a prostate-specific antigen doubling time of less than 6 months, independent of other prognostic features such as pathological stage or Gleason score. These preliminary findings should be validated in other settings, and ultimately, in a randomized controlled trial.


[Two cases of acute freon poisoning].
Freon is widely used in daily life, which is usually absorbed through the respiratory tract and causes clinical manifestations mainly in the cardiovascular system and neurological damage. Now, we analyze the clinical data, diagnosis, treatment and prognosis of two cases of freon poisoning in Affiliated Dongyang People's Hospital of Wenzhou Medical University to improve the clinicians' understanding of freon poisoning and to avoid missed diagnosis and misdiagnosis.


[Congenital long QT syndrome. Mid-term prognosis].
Twenty-five cases of the congenital, idiopathic long QT syndrome, occasionally diagnosed at birth and persisting after the 4th day of life, were analysed retrospectively to determine the medium-term prognosis and to identify risk factors. The age of the patients varied: 13 neonates including 10 of less than 5 days of age, and 12 children 1 to 12 years old. Eleven patients belonged to families with long QT syndromes. The recruitment also varied: syncope or near syncope (9 cases), bradycardias or tachyarrhythmias (9 cases) or by systematic familial enquiry (7 cases). The corrected QT interval (QTc) was greater than 0.44 s in all patients, and 17 patients had conduction (atrioventricular or intraventricular) defects and/or ventricular arrhythmias (tachycardia, torsades de pointe or fibrillation). All except two older children were prescribed betablocker therapy and in 6 cases of resistant arrhythmias a pacemaker was implanted. There were 6 deaths: 4 deaths occurred in neonates who had the longest QT intervals (greater than 0.65 s) complicated by conduction defects and tachyarrhythmias. The other 2 fatalities were in older children who both died during syncope. The 19 survivors were followed up for 3 months to 16 years: 4 children with the shortest QTc values (0.44 to 0.48 s) have completely recovered; 2 neonates treated for 9 months and then weaned off therapy without any complications and 2 older children who were not treated. The other 15 cases are all under treatment but do well and have had no syncopal episodes during follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)


Transfusion of red blood cells in patients with traumatic brain injuries admitted to Canadian trauma health centres: a multicentre cohort study.
Optimisation of healthcare practices in patients sustaining a traumatic brain injury is of major concern given the high incidence of death and long-term disabilities. Considering the brain's susceptibility to ischaemia, strategies to optimise oxygenation to brain are needed. While red blood cell (RBC) transfusion is one such strategy, specific RBC strategies are debated. We aimed to evaluate RBC transfusion frequency, determinants of transfusions and associated clinical outcomes. We conducted a retrospective multicentre cohort study using data from the National Trauma Registry of Canada. Patients admitted with moderate or severe traumatic brain injury to participating hospitals between April 2005 and March 2013 were eligible. Patient information on blood products, comorbidities, interventions and complications from the Discharge Abstract Database were linked to the National Trauma Registry data. Relative weights analyses evaluated the contribution of each determinant. We conducted multivariate robust Poisson regression to evaluate the association between potential determinants, mortality, complications, hospital-to-home discharge and RBC transfusion. We also used proportional hazard models to evaluate length of stay for time to discharge from ICU and hospital. Among the 7062 patients with traumatic brain injury, 1991 patients received at least one RBC transfusion during their hospital stay. Female sex, anaemia, coagulopathy, sepsis, bleeding, hypovolemic shock, other comorbid illnesses, serious extracerebral trauma injuries were all significantly associated with RBC transfusion. Serious extracerebral injuries altogether explained 61% of the observed variation in RBC transfusion. Mortality (risk ratio (RR) 1.23 (95% CI 1.13 to 1.33)), trauma complications (RR 1.38 (95% CI 1.32 to 1.44)) and discharge elsewhere than home (RR 1.88 (95% CI 1.75 to 2.04)) were increased in patients who received RBC transfusion. Discharge from ICU and hospital were also delayed in transfused patients. RBC transfusion is common in patients with traumatic brain injury and associated with unfavourable outcomes. Trauma severity is an important determinant of RBC transfusion. Prospective studies are needed to further evaluate optimal transfusion strategies in traumatic brain injury.


Pancreatic undifferentiated carcinoma with osteoclast-like giant cells is genetically similar to, but clinically distinct from, conventional ductal adenocarcinoma.
Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells (UCOGC) is currently considered a morphologically and clinically distinct variant of pancreatic ductal adenocarcinoma (PDAC). In this study, we report clinical and pathological features of a series of 22 UCOGCs, including the whole exome sequencing of eight UCOGCs. We observed that 60% of the UCOGCs contained a well-defined epithelial component and that patients with pure UCOGC had a significantly better prognosis than did those with an UCOGC with an associated epithelial neoplasm. The genetic alterations in UCOGC are strikingly similar to those known to drive conventional PDAC, including activating mutations in the oncogene KRAS and inactivating mutations in the tumor suppressor genes CDKN2A, TP53, and SMAD4. These results further support the classification of UCOGC as a PDAC variant and suggest that somatic mutations are not the determinants of the unique phenotype of UCOGC. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Transforming Growth Factor-β and the Renin-Angiotensin System in Syndromic Thoracic Aortic Aneurysms: Implications for Treatment.
Thoracic aortic aneurysms (TAAs) are permanent pathological dilatations of the thoracic aorta, which can lead to life-threatening complications, such as aortic dissection and rupture. TAAs frequently occur in a syndromic form in individuals with an underlying genetic predisposition, such as Marfan syndrome (MFS) and Loeys-Dietz syndrome (LDS). Increasing evidence supports an important role for transforming growth factor-β (TGF-β) and the renin-angiotensin system (RAS) in TAA pathology. Eventually, most patients with syndromic TAAs require surgical intervention, as the ability of present medical treatment to attenuate aneurysm growth is limited. Therefore, more effective medical treatment options are urgently needed. Numerous clinical trials investigated the therapeutic potential of angiotensin receptor blockers (ARBs) and β-blockers in patients suffering from syndromic TAAs. This review highlights the contribution of TGF-β signaling, RAS, and impaired mechanosensing abilities of aortic VSMCs in TAA formation. Furthermore, it critically discusses the most recent clinical evidence regarding the possible therapeutic benefit of ARBs and β-blockers in syndromic TAA patients and provides future research perspectives and therapeutic implications.


A role for IL-33-activated ILC2s in eosinophilic vasculitis.
Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare but serious disease with poorly understood mechanisms. Here, we report that patients with EGPA have elevated levels of TSLP, IL-25, and soluble ST2, which are well-characterized cytokine "alarmins" that activate or modulate type 2 innate lymphoid cells (ILC2s). Patients with active EGPA have a concurrent reduction in circulating ILC2s, suggesting a role for ILC2s in the pathogenesis of this disease. To explore the mechanism of these findings in patients, we established a model of EGPA in which active vasculitis and pulmonary hemorrhage were induced by IL-33 administration in predisposed, hypereosinophilic mice. In this model, induction of pulmonary hemorrhage and vasculitis was dependent on ILC2s and signaling through IL4Rα. In the absence of IL4Rα or STAT6, IL-33-treated mice had less vascular leak and pulmonary edema, less endothelial activation, and reduced eotaxin production, cumulatively leading to a reduction of pathologic eosinophil migration into the lung parenchyma. These results offer a mouse model for use in future mechanistic studies of EGPA, and they suggest that IL-33, ILC2s, and IL4Rα signaling may be potential targets for further study and therapeutic targeting in patients with EGPA.


Modifying protein adsorption by layers of glutathione pre-adsorbed on Au(111).
Molecular interaction with metal surfaces raises fundamental questions regarding their binding tendency, their dispersion on the surface, as well as their conformation which may change their biological properties; addressing these questions, and being able to tune protein interactions, is of primary importance for the control of biointerfaces. In this study, one tripeptide, GSH (glu-cys-gly), was used to condition gold surfaces and thus influence the adsorption of bovine serum albumin (BSA). Depending on the pH value of the GSH solution, cationic, zwitterionic or anionic forms of the tripeptide could be stabilised on the surface, before interacting with BSA solutions. The amount of proteins was observed to depend both on the chemical state of the adsorbed underlying peptide and on the solvent of the protein solution, indicating an important role of electrostatic interactions upon protein adsorption. Moreover, atomic force microscopy (AFM), and synchrotron IR microscopy revealed a heterogeneous distribution of proteins on the GSH layer.


"Passion" versus "patience": the effects of valence and arousal on constructive word recognition.
Accumulating evidence suggests that emotional information is often recognised faster than neutral information. Several studies examined the effects of valence and arousal on word recognition, but yielded partially diverging results. Here, we used two alternative versions of a constructive recognition paradigm in which a target word is hidden by a visual mask that gradually disappears, to investigate whether the emotional properties of words influence their speed of recognition. Participants were instructed either to classify the incrementally appearing word as emotional or non-emotional (semantic categorisation task) or to decide whether the appearing letter string is an existing word or not (lexical decision task). Results from both tasks revealed faster recognition times for high- compared to low-arousing words, and for positive compared to negative or neutral words. These findings indicate a recognition advantage for emotionally positive and highly arousing stimuli that persists even when visual word recognition is hampered and participants are encouraged to make more active, semantic inferences to generate the meaning of the emerging word.


Mechanical Thrombectomy of COVID-19 positive acute ischemic stroke patient: a case report and call for preparedness.
The novel coronavirus (COVID-19) global pandemic is associated with an increased incidence of acute ischemic stroke (AIS) secondary to large vessel occlusion (LVO). The treatment of these patients poses unique and significant challenges to health care providers requiring changes in existing protocols. A 54-year-old COVID-19 positive patient developed sudden onset left hemiparesis secondary to an acute right middle cerebral artery occlusion (National Institutes of Health Stroke Scale (NIHSS) score = 11). Mechanical thrombectomy (MT) was performed under a new protocol specifically designed to maximize protective measures for the team involved in the care of the patient. Mechanical Thrombectomy was performed successfully under general anesthesia resulting in TICI 3 recanalization. With regards to time metrics, time from door to reperfusion was 60 mins. The 24-h NIHSS score decreased to 2. Patient was discharged after 19 days after improvement of her pulmonary status with modified Rankin Scale = 1. Patients infected by COVID-19 can develop LVO that is multifactorial in etiology. Mechanical thrombectomy in a COVID-19 confirmed patient presenting with AIS due to LVO is feasible with current mechanical thrombectomy devices. A change in stroke workflow and protocols is now necessary in order to deliver the appropriate life-saving therapy for COVID-19 positive patients while protecting medical providers.


Bioconcentration, biotransformation, and transcriptomic impact of the UV-filter 4-MBC in the manila clam Ruditapes philippinarum.
Ultraviolet filters (UV-filters) are compounds extensively used in personal care products. These compounds are produced at increasing rates and discharged into marine ecosystems in unknown quantities and with no regulation, making them emerging contaminants. Among those, the UV-filter 4-Methylbenzylidene camphor (4-MBC) is used in a variety of personal care products such as sunscreens, soaps, or lipsticks. This high consumption has resulted in its presence in various environmental matrices at in concentrations ranging from ng to μg L-1. Very little is known, however, about the possible adverse effects in exposed non-target organisms. Our study presents novel data on the bioconcentration, toxicokinetics, and molecular effects of 4-MBC in a marine bivalve species of commercial interest, Ruditapes philippinarum (Manila clam). Organisms were exposed at two different concentrations (1.34 and 10.79 μg L-1) of 4-MBC for 7 days, followed by a 3-day depuration period (clean sea waters). Bioconcentration factors (BCF) were 3562 and 2229 L kg-1 for the low and high exposure concentrations, respectively, making this pollutant bioaccumulative according to REACH criteria. Up to six 4-MBC biotransformation products (BTPs)were identified, 2 of them for the first time. Transcriptomic analysis revealed between 658 and 1310 differently expressed genes (DEGs) after 4-MBC exposure. Functional and enrichment analysis of the DEGs showed the activation of the detoxification pathway to metabolize and excrete the bioconcentrated 4-MBC, which also involved energy depletion and caused an impact on the metabolism of carbohydrates and lipids and in the oxidative phosphorylation pathways. Oxidative stress and immune response were also evidenced through the activation of cathepsins and the complement system. Such elucidation of the mode of action of a ubiquitous pollutant such as 4-MBC at the molecular level is valuable both from an environmental point of view and for the sustainable production of Manila clam, one of the most cultivated mollusk species worldwide.


Assessment of biodegradable controlled release rod systems for pain relief applications.
Control of chronic, severe pain is a difficult and important clinical problem for most patients, especially those with cancer. Although current applications are insufficient for a satisfactory solution to this problem, the rate of disease incidence is increasing worldwide, thus making the problem more apparent. Based on this fact, this study was designed with the ultimate goal of formulating a controlled release system of pain relievers, mainly opioids, for the local treatment of pain to achieve satisfactory, fast, and less side effect-related relief and to provide a better life status for chronic pain patients. Two copolymers of a biodegradable polymer poly(L-lactide-co-glycolide) (PLGA) were used to prepare an implantable rod type drug release system containing either an analgesic or anesthetic type of pain reliever. In vitro drug release kinetics of these systems were studied. It was observed that release from PLGA 85 : 15 was more zero-order than it was from PLGA 50 : 50. A zero-order release rate was obtained for codeine, hydromorphone, and bupivacaine from PLGA (85 : 15) rods. They, however, were released from PLGA (50 : 50) rods with Higuchi kinetics. The drug solubility was also influential on release rate, as shown by the zero-order morphine release from PLGA (50 : 50) rods. Scanning electron micrographs (SEMs) of the monolithic rods revealed erosion of the rods and the removal of drug crystals from the rod structure.


Trans-platinum(II)/(IV) Complexes with Acetylpyridine Ligands as Antivascular Agents in vitro: Cytotoxic and Antiangiogenic Potential.
In vitro biological studies of four trans-platinum complexes of structural formulas trans-[PtCl2(n-acetylpyridine)2] (n = 3 or 4, complex 1 or 2) and [Pt(n-acetylpyridine)2Cl4] (n = 3 or 4, complex 3 or 4) were performed in human endothelial EA.hy 926 cells, in order to evaluate and compare their cytotoxic and antiangiogenic potential. MTT results revealed that trans-Pt(II) complexes exhibited significantly lower IC50 values: 4.0±0.9 μM (1) and 2.1±0.0 μM (2), than cisplatin (27.7±1.3 μM). Combinational drug treatment with N-Acetyl-L-cysteine and L-buthioninesulfoximine strongly counteracted effect of 1 and 2, while the same treatment rather enhanced cytotoxicity of Pt(IV) analogues. ICP-MS results suggested that differential endothelial toxicity of cisplatin and trans-platinum complexes correlated to the differences in their cellular accumulation, rather than to the different affinity of DNA binding. Intracellular accumulation of complexes (ng Pt/106 cells) for 24 h treatment, decreased in order: 1>2>4>3>CDDP, while ratio of DNA binding (pg Pt/μg DNA) decreased as following: 2>1>CDDP>4>3. FACS/Annexin-V-FITC analysis, and morphological study demonstrated that the enhanced cytotoxic and apoptotic potential (18.1%) of complex 2 was related to its highest affinity to bind nuclear DNA. Pt(IV) complexes exhibited the lowest reactivity to cellular DNA and proteins. Regardless of their antiproliferative action, 1-4 at subtoxic concentrations demonstrated in vitro inhibitory effect on tubulogenesis and matrix metalloproteinases (MMPs) 2 and 9 gelatinolitic activity, while 1 and 2 additionally downregulated MMP-2 gene expression.


DNA ploidy changes in rhino mouse skin induced by all-trans retinoic acid and retinol.
In order to assess the proliferative changes induced by all-trans retinoic acid (RA) and retinol (ROL), we have carried out a study of the DNA content of basal and suprabasal keratinocytes after epicutaneous application on the rhino mouse. Skin sections were analyzed stereologically and cytophotometrically using the Feulgen technique. The diploid DNA value (2C) was obtained from hepatocyte nuclei of control animals. Whereas cells in phase G0-G1 will show a 2C content, cells during phase S and in phase G2-M will show DNA values ranging from 2C to 4C and 4C, respectively. Although epidermal thickness (ET) increased significantly in all treated animals, surface density only increased in animals treated with all-trans RA. Quantification of DNA content of basal keratinocytes showed reduction of 2C and 2C-4C populations with a commensurate increase in proportions of cells with 4C and > 4C in the animals treated with 0.025% all-trans RA and ROL. Suprabasal keratinocytes of mice treated with 0.025% all-trans showed a decrease of the 2C population and an increased proportion of cells with 4C. Whereas 0.025% all-trans RA induced an increase of both basal and suprabasal DNA indices, ROL enhanced only the basal DNA index significantly. Animals treated with 0.025% ROL showed a significant increase in the basal proliferative index (PI) while the suprabasal PI remained constant; treatment with 0.025% all-trans RA produced a significant increase of both basal and suprabasal PIs and parakeratotic hyperkeratosis probably due to incomplete differentiation.


Scavenger receptor class B, type I-mediated uptake of A1AT by pulmonary endothelial cells.
In addition to exerting a potent anti-elastase function, α-1 antitrypsin (A1AT) maintains the structural integrity of the lung by inhibiting endothelial inflammation and apoptosis. A main serpin secreted in circulation by hepatocytes, A1AT requires uptake by the endothelium to achieve vasculoprotective effects. This active uptake mechanism, which is inhibited by cigarette smoking (CS), involves primarily clathrin- but also caveola-mediated endocytosis and may require active binding to a receptor. Because circulating A1AT binds to high-density lipoprotein (HDL), we hypothesized that scavenging receptors are candidates for endothelial uptake of the serpin. Although the low-density lipoprotein (LDL) receptor-related protein 1 (LRP1) internalizes only elastase-bound A1AT, the scavenger receptor B type I (SR-BI), which binds and internalizes HDL and is modulated by CS, may be involved in A1AT uptake. Transmission electron microscopy imaging of colloidal gold-labeled A1AT confirmed A1AT endocytosis in both clathrin-coated vesicles and caveolae in endothelial cells. SR-BI immunoprecipitation identified binding to A1AT at the plasma membrane. Pretreatment of human lung microvascular endothelial cells with SR-B ligands (HDL or LDL), knockdown of SCARB1 expression, or neutralizing SR-BI antibodies significantly reduced A1AT uptake by 30-50%. Scarb1 null mice exhibited decreased A1AT lung content following systemic A1AT administration and reduced lung anti-inflammatory effects of A1AT supplementation during short-term CS exposure. In turn, A1AT supplementation increased lung SR-BI expression and modulated circulating lipoprotein levels in wild-type animals. These studies indicate that SR-BI is an important mediator of A1AT endocytosis in pulmonary endothelium and suggest a cross talk between A1AT and lipoprotein regulation of vascular functions.


Hereditary pancreatitis-associated mutation asn(21) --> ile stabilizes rat trypsinogen in vitro.
Mutations Arg(117) --> His and Asn(21) --> Ile in human trypsinogen-I have been recently associated with hereditary pancreatitis (HP). The Arg(117) --> His substitution is believed to cause pancreatitis by stabilizing trypsin against autolytic degradation, while the mechanism of action of Asn(21) --> Ile has been unknown. In an effort to understand the effect(s) of this mutation, Thr(21) in the highly homologous rat trypsinogen-II was replaced with Asn or Ile, and the recombinant zymogens and their active trypsin forms were studied. Kinetic parameters of all three trypsins were comparable, and the active enzymes suffered autolysis at similar rates, indicating that neither catalytic properties nor proteolytic stability of trypsin are influenced by mutations at position 21. When incubated at pH 8.0, 37 degrees C, pure zymogens underwent autoactivation with concomitant trypsinolytic degradation in a Ca(2+)-dependent fashion. Thus, in the presence of 5 mM Ca(2+), autoactivation and digestion of the zymogens after Arg(117) and Lys(188) were observed, while in the presence of 1 mM EDTA autoactivation and cleavage at Lys(188) were reduced, and zymogenolysis at the Arg(117) site was enhanced. Overall rates of zymogen degradation in [Asn(21)]- and [Ile(21)]trypsinogens were higher in Ca(2+) than in EDTA, while [Thr(21)]trypsinogen demonstrated inverse characteristics. Remarkably, both in the presence and absence of Ca(2+), [Ile(21)]trypsinogen exhibited significantly higher stability against autoactivation and proteolysis than zymogens with Asn(21) or Thr(21). The observations suggest that autocatalytic trypsinogen degradation may be an important defense mechanism against excessive trypsin generation in the pancreas, and trypsinogen stabilization by the Asn(21) --> Ile mutation plays a role in the pathogenesis of HP.


The influence of psychological factors on breastfeeding duration.
This paper reports on a study examining the relationship between women's psychological characteristics and breastfeeding duration, after controlling for socio-demographic factors. The literature suggests that psychological factors may influence breastfeeding behaviour, but studies are few. Existing evidence and the results of phase 1 of our study were used to construct a list of psychological factors, which were tested for their association with breastfeeding duration in the current design. Participants were postnatal inpatients in one of two regional hospitals between October and December 2005 and they completed the initial questionnaire within 14 days of giving birth (n = 375). Infant feeding method at 6 months and the timing of introduction of other food(s), where relevant, were ascertained by telephone interview. Forty-four per cent of the sample showed signs of postnatal distress in the 14 days following the birth. Breastfeeding duration was statistically significantly associated with psychological factors including dispositional optimism, breastfeeding self-efficacy, faith in breastmilk, breastfeeding expectations, anxiety, planned duration of breastfeeding and the time of the infant feeding decision. As a set, these psychological factors were more predictive of breastfeeding duration than was the set of socio-demographic characteristics. The duration of any breastfeeding was uniquely predicted by faith in breastmilk, planned breastfeeding duration and breastfeeding self-efficacy. This increased knowledge of the factors influencing breastfeeding will assist in identifying women at risk of early weaning and in constructing programmes capable of increasing the length of time for which women breastfeed.


Closing the energy gap to prevent weight gain in China.
To estimate the energy gap (i.e. degree of positive energy balance) that is causing weight gain in the population of China in order to provide a quantitative goal for how much behaviour change is required to prevent excess weight gain in the population. This is based on data collected in the China Health and Nutrition Survey. 2288 adults (20-45 years) who took part in both the 1989 and 2000 surveys were selected. from 1989 to 2000, the average weight of this population increased from 55.4 kg to 59.1 kg. The medium increasing rate was 0.33 kg year(-1). During this time, the prevalence of overweight in the population increased dramatically from 9.0% to 23.2%. By assuming that each kilogram of body weight gained represents 7700 kcal, the estimated medium energy accumulation in the sample was 7.0 kcal day(-1) and the 90th percentile was 22.5 kcal d(-1). Further, assuming that the energy derived from mixed composition diets is stored with an average efficiency of 50%, the estimated energy gap for the population was 45 kcal day(-1). This is the degree of positive energy balance that is causing weight gain in 90% of the population. The estimate suggests that the behaviour change needed to close the energy gap is small and achievable without dramatically altering current lifestyle in China. For example, reducing energy intake by just 2-3% less each day or walking an extra 10-15 minutes each day could offset weight gain in roughly 90% of the population in China. By providing an estimate of the energy gap it can be predicted that weight gain in most of the population of China could be prevented with small lifestyle changes. It is critical that these lifestyle changes be implemented in order to prevent acceleration of the obesity epidemic in China.


Mortality following the diagnosis of a vertebral compression fracture in the Medicare population.
Vertebral compression fractures in women are associated with increased mortality, but the generality of this finding, as a function of age, sex, ethnicity, and region, among the entire elderly population in the United States remains unclear. The objective of this study was to assess the survival of the Medicare population with vertebral compression fractures. We conducted a retrospective data analysis of Medicare claims generated by a 5% sample of all Medicare enrollees from 1997 through 2004. The patient sample consisted of all 97,142 individuals with a new diagnosis of vertebral compression fracture from 1997 through 2004. Controls were matched for age, sex, race, and Medicare buy-in status, with a five-to-one control-case ratio. The survival of a patient was measured from the earliest date of a new fracture until death or until the end of the study. The patients with a fracture were compared with the controls by calculation of the mortality rates, with use of Kaplan-Meier analysis and the Cox regression method. Demographic subpopulation analysis and analysis by comorbidity levels were performed as well. Medicare patients with a vertebral fracture had an overall mortality rate that was approximately twice that of the matched controls. The survival rates following a fracture diagnosis, as estimated with the Kaplan-Meier method, were 53.9%, 30.9%, and 10.5% at three, five, and seven years, respectively, which were consistently and significantly lower than the rates for the controls. The mortality risk following a fracture was greater for men than for women. The difference in mortality between the patients with a vertebral compression fracture and the controls was greatest when the patients were younger at the time of the fracture; this difference declined as the age at the time of the fracture increased. This study establishes the mortality risk associated with vertebral fractures for elderly patients of all ages and ethnicities and both sexes in the Medicare population; however, it does not imply a causal relationship. The difference in mortality between patients with a fracture and controls is higher than previously reported, even after controlling for comorbidities.


FKBP5 rs4713916: A Potential Genetic Predictor of Interindividual Different Response to Inhaled Corticosteroids in Patients with Chronic Obstructive Pulmonary Disease in a Real-Life Setting.
Background: Chronic obstructive pulmonary disease (COPD) is a common, preventable, and manageable lung disease characterized by large heterogeneity in disease presentation and grades impairment. Inhaled corticosteroids (ICS) are commonly used to manage COPD/COPD-exacerbation. The patient's response is characterized by interindividual variability without disease progression/survival modification. Objectives: We hypothesize that a therapeutic intervention may be more effective if single nucleotide polymorphisms (SNPs) are investigated. Methods: In 71 COPD patients under pulmonary rehabilitation, a small number of powerful SNPs, selected according to current literature, were analyzed; namely the glucocorticoid receptor gene NR3C1 (rs6190/rs6189/rs41423247), the glucocorticoid-induced transcript 1 gene (GLCCI1 rs37972), and the related co-chaperone FKBP5 gene (rs4713916). MDR1 rs2032582 was also evaluated. Lung function outcomes were assessed. Results: A significant association with functional outcomes, namely FEV1 (forced expiration volume/one second) and 6MWD (six-minutes walking distance), was found for rs4713916 and weakly for rs37972. The genotype rs4713916(GA) and, in a lesser extent, the genotype rs37972(TT), were more favorable than the wild-type. Conclusions: Our study supports a possible picture of pharmacogenomic control for COPD intervention. rs4713916 and, possibly, rs37972 may be useful predictors of clinical outcome. These results may help to tailor an optimal dose for individual COPD patients based on their genetic makeup.


In type 1 diabetes a subset of anti-coxsackievirus B4 antibodies recognize autoantigens and induce apoptosis of pancreatic beta cells.
Type 1 diabetes is characterized by autoimmune destruction of pancreatic beta cells. The role played by autoantibodies directed against beta cells antigens in the pathogenesis of the disease is still unclear. Coxsackievirus B infection has been linked to the onset of type 1 diabetes; however its precise role has not been elucidated yet. To clarify these issues, we screened a random peptide library with sera obtained from 58 patients with recent onset type 1 diabetes, before insulin therapy. We identified an immunodominant peptide recognized by the majority of individual patients'sera, that shares homology with Coxsackievirus B4 VP1 protein and with beta-cell specific autoantigens such as phogrin, phosphofructokinase and voltage-gated L-type calcium channels known to regulate beta cell apoptosis. Antibodies against the peptide affinity-purified from patients' sera, recognized the viral protein and autoantigens; moreover, such antibodies induced apoptosis of the beta cells upon binding the L-type calcium channels expressed on the beta cell surface, suggesting a calcium dependent mechanism. Our results provide evidence that in autoimmune diabetes a subset of anti-Coxsackievirus antibodies are able to induce apoptosis of pancreatic beta cells which is considered the most critical and final step in the development of autoimmune diabetes without which clinical manifestations do not occur.


Blood volume and cardiac index in rats after exchange transfusion with hemoglobin-based oxygen carriers.
We have measured plasma volume and cardiac index in rats after 50% isovolemic exchange transfusion with human hemoglobin cross-linked between the alpha-chains with bis(3,5-dibromosalicyl)fumarate (alpha alpha Hb) and with bovine hemoglobin modified with polyethylene glycol (PEGHb). alpha alpha Hb and PEGHb differ in colloid osmotic pressure (23.4 and 118.0 Torr, respectively), oxygen affinity (oxygen half-saturation pressure of hemoglobin = 30.0 and 10.2 Torr, respectively), viscosity (1.00 and 3.39 cP, respectively), and molecular weight (64,400 and 105,000, respectively). Plasma volume was measured by Evans blue dye dilution modified for interference by plasma hemoglobin. Blood volumes in PEGHb-treated animals were significantly elevated (74.0 +/- 3.5 ml/kg) compared with animals treated with alpha alpha Hb (49.0 +/- 1.2 ml/kg) or Ringer lactate (48.0 +/- 2.0 ml/kg) or with controls (58.2 +/- 1.9 ml/kg). Heart rate reduction after alpha alpha Hb exchange is opposite to that expected with blood volume contraction, suggesting that alpha alpha Hb may have a direct myocardial depressant action. The apparently slow elimination of PEGHb during the 2 h after its injection is a consequence of plasma volume expansion: when absolute hemoglobin (concentration x plasma volume) is compared for PEGHb and alpha alpha Hb, no difference in their elimination rates is found. These studies emphasize the need to understand blood volume regulation when the effects of cell-free hemoglobin on hemodynamic measurements are evaluated.


Biogenesis and cargo selectivity of autophagosomes.
Autophagy is a major catabolic pathway in eukaryotes, which is required for the lysosomal/vacuolar degradation of cytoplasmic proteins and organelles. Interest in the autophagy pathway has recently gained momentum largely owing to identification of multiple autophagy-related genes and recognition of its involvement in various physiological conditions. Here we review current knowledge of the molecular mechanisms regulating autophagy in mammals and yeast, specifically the biogenesis of autophagosomes and the selectivity of their cargo recruitment. We discuss the different steps of autophagy, from the signal transduction events that regulate it to the completion of this pathway by fusion with the lysosome/vacuole. We also review research on the origin of the autophagic membrane, the molecular mechanism of autophagosome formation, and the roles of two ubiquitin-like protein families and other structural elements that are essential for this process. Finally, we discuss the various modes of autophagy and highlight their functional relevance for selective degradation of specific cargos.


Lewy body Parkinson's disease in a large pedigree with 77 Parkin mutation carriers.
We report the clinical, genetic, and neuropathological findings of a seven generation-spanning pedigree with 196 individuals, 25 of whom had levodopa-responsive parkinsonism. Genetic analyses indicated Parkin mutations in 77 subjects. Among the 25 patients, 5 carried compound heterozygous mutations and met criteria for definite Parkinson's disease (PD) according to UK PD Society Brain Bank guidelines; 8 subjects carried only a heterozygous Parkin mutation. The mutational status of five deceased patients was unknown, and seven PD patients had no Parkin mutation. Survival analyses showed a significant difference in the age-at-onset distribution between patients with compound heterozygous mutations and the groups of heterozygous carriers and subjects without detectable Parkin mutations. Autopsy of a 73-year-old patient, who carried two mutant Parkin alleles (delExon7 + del1072T), showed PD-type cell loss, reactive gliosis, and alpha-synuclein-positive Lewy bodies in the substantia nigra and locus ceruleus. Surviving neurons were reactive with antibodies to the N terminus of Parkin but not the In-Between-RING ("IBR") domain, which had been deleted by both mutations. This large Parkin pedigree represents a unique opportunity to prospectively study the role of heterozygous Parkin mutations as a PD risk factor, to identify additional contributors to the expression of late-onset PD in heterozygous carriers, and to reexamine the role of Parkin in inclusion formation.


A new endoscopic classification of Chronic Esophagitis.
Based on our experience of 97 cases of chronic esophagitis diagnosed endoscopically and histologically by guided biopsies, a new macroscopial classification is suggested as follows: Type I: Erosive-ulcerative form; Type II: Granulative form;; Type III: Barrett-type ulcers; Type IV: Esophagogastric or marginal ulcerations; Type V: Stenosing form. Type I (44.2%) and Type IV (26.7%) are commonly seen. Type II (15.4%) and Type V (11.3%) are healing stages of peptic esophagitis. Type III (2.4%) is rare. The above described classification is clearly correlated with the clinical symptoms of the disease.


Emergency mental health care for chi̇ldren and adolescents outside of regular working hours: 7 years outcomes from a tertiary hospital.
This study aims to define the clinical characteristics and management strategies of children and adolescents presenting with psychiatric crises to the emergency department (ED) of a tertiary health care facility outside of working hours, and to identify predictors of multiple ED visits among them. From January 2012 to December 2018, retrospective records of patients presenting with psychiatric symptoms to the ED and examined by a child psychiatrist after 5 p.m. on weekdays and for 24 h on weekends and public holidays were analyzed. Our sample consisted of 1576 visits and 1364 patient (Female:Male=1.8:1, mean age=14.86 ± 2.72). The most common reason for visits was self-injurious thought or behaviors (SITB), and the most common diagnosis was depression. While depression was statistically more common in girls, attention deficit hyperactivity disorder, autism and/or intellectual disability (ASD/ID), psychotic disorders, and bipolar disorder were more common in boys. The forensic evaluation was the most common reason for visits among children younger than 6 years old. Of visits, 23% transferred to hospitalization. A history of mental health contact was the lowest in depression (37.5%), psychosis (34.1%), and substance use disorders (33%). Of patients, 10.8% had multiple visits. A history of mental health contacts, conduct disorder, ASD/ID, bipolar disorder, psychotic disorder, and dissociative disorder were predictors of multiple visits to ED with psychiatric reasons. Emergency mental health care outside of regular working hours can be a critical step in the diagnosis and treatment of serious psychiatric disorders in children and adolescents.


Solid-organ Transplants From Living Donors: Cumulative United States Experience on 140,156 Living Donor Transplants Over 28 Years.
Transplantation of organs from living donors helps to decrease the organ shortage and shortens waiting times. Living donor (LD) transplantation is also generally associated with better outcomes. Unfortunately, there has been no comprehensive analysis and comparison of all types of solid-organ transplantation from living donors since the inception of the United Network for Organ Sharing (UNOS). Using the UNOS/Organ Procurement and Transplantation Network (OPTN) database, all LD transplants from October 1, 1987, to December 31, 2015, were studied with univariate and multivariate analyses. A total of 140,090 organs were transplanted from LDs, accounting for 21% of all transplants in the United States. Over 95% were kidney; 4% were liver; and <1% intestine, lung, and pancreas LDs. Only LD kidney transplant patient and graft survival rates were significantly higher compared deceased donor transplants over the period of analysis. The best long-term LD transplant results were achieved in pediatric liver recipients. Significantly more women than men donated organs and significantly more men than women received solid-organ transplants. A regional disparity was observed for LD kidney as well as for LD liver transplants. Despite improvements in outcomes and increased use of nonbiologic donors, the number of LD transplants in the United States has declined. This decline was greater in children than adults and was noted for all types of organ transplants. Further efforts are needed to educate the public, health professionals, and transplant candidates on the advantages of living vs deceased donor organ transplantation. Compared with other countries, LD transplantation has yet to reach its full potential in the United States.


Mortality and morbidity of preterm neonates weighing less than 750g: A 2-year retrospective cohort study.
The rate of premature births in France is 6% and is increasing, as is the rate of extremely premature births. Morbidity and mortality rates in this population remain high despite significant medical progress. We aimed to evaluate the morbidity and mortality rate in preterm neonates weighing<750g and to evaluate their outcome at 2 years' corrected age (CA). This was a retrospective monocentric study including babies born between May 2011 and April 2013 who were preterm and weighed<750g. We evaluated mortality and morbidity in the neonatal period. At 2 years' CA, we focused on developmental quotient (DQ) with the Brunet-Lézine test, on neurosensory assessment (sleeping/behavior), and growth evaluation. Among the 107 infants included, 29 (27%) died in the neonatal period. Mean gestational age was 25.6 weeks' gestation. Female sex and higher birth weight were independent predictors of survival. A total of 61 (78.2%) infants showed extra-uterine growth retardation at 36 weeks' postmenstrual age. At 2 years' CA, 57 children were followed up; 38 were evaluated using the Brunet-Lézine test, 20 (52.6%) had a DQc<85, and none had a severe developmental delay (DQc<50). Six (10%) children had cerebral palsy and 22 of 56 (39.2%) showed language delay. Growth retardation persisted in 15 of 52 (28.8%) children. Our results confirm the acute fragility of extremely low-birth-weight babies with a high rate of morbidity and mortality. At 2 years' CA, this population still shows a considerable rate of mild difficulties, whose long-term evolution needs to be followed.


Economic recession and health inequalities in Japan: analysis with a national sample, 1986-2001.
Little is known about whether economic crises widen health inequalities. Japan experienced more than 10 years of economic recession beginning in the 1990s. The question of whether socioeconomic-based inequality in self-rated health widened after the economic crisis was examined. Repeated cross-sectional survey design. Two pooled datasets from 1986 and 1989 and from 1998 and 2001 were analysed separately, and temporal change was examined. The study took place in Japan among the working-age population (20-60 years old). The two surveys consisted of 168 801 and 150 016 people, respectively, with about an 80% response rate. The absolute percentages of people reporting poor health declined across all socioeconomic statuses following the crisis. However, after controlling for confounding factors, the odds ratio (OR) for poor self-rated health (95% confidence intervals) among middle-class non-manual workers (clerical/sales/service workers) compared with the highest class workers (managers/administrators) was 1.02 (0.92 to 1.14) before the crisis but increased to 1.14 (1.02 to 1.29) after the crisis (p for temporal change = 0.02). The association was stronger among males. The adjusted ORs among professional workers and young female homemakers also marginally increased over time. Unemployed people were twice as likely to report poor health compared with the highest class workers throughout the period. Self-rated health of people with middle to higher incomes deteriorated in relative terms following the crisis compared with that of lower income people. Self-rated health improved in absolute terms for all occupational groups even after the economic recession. However, the relative disparity increased between the top and middle occupational groups in men.


Collective forces in scalar active matter.
Large-scale collective behavior in suspensions of active particles can be understood from the balance of statistical forces emerging beyond the direct microscopic particle interactions. Here we review some aspects of the collective forces that can arise in suspensions of self-propelled active Brownian particles: wall forces under confinement, interfacial forces, and forces on immersed bodies mediated by the suspension. Even for non-aligning active particles, these forces are intimately related to a non-uniform polarization of particle orientations induced by walls and bodies, or inhomogeneous density profiles. We conclude by pointing out future directions and promising areas for the application of collective forces in synthetic active matter, as well as their role in living active matter.


[Pathoanatomic criteria for dissecting aortic aneurysm].
The authors present the basic pathoanatomic criteria for the diagnosis of dissecting aortic aneurysm on the basis of an analysis of 144 cases of this abnormality. Its mandatory signs are the inlet (of blind rupture of the wall of the aorta) and channel of its dissection. The inner surface of the dissection channel varies with the time of (rough to smooth) dissection with connective tissue bands. The optional criteria are the outlet that connects the false aortic lumen with the true one, as well as the propagation of dissection to the visceral aortic branches. When the visceral branches are involved in the process of dissection in more than half of all cases, there are no changes in the respective organs. At the same time there are ischemic changes in the organs, the vessels of which are not involved in this process. This is suggestive of complex circulatory disorders in this disease. The main mechanisms of tanatogenesis are due to the rupture of the outer sheet of a false passage, the propagation of dissection to the visceral branches or a combination of these two factors. The optimal autopsy procedure options are shown with regard to the pathoanatomic features of dissecting aortic aneurysm.


Aggregation-Induced Emission and Light-Harvesting Function of Tetraphenylethene-Based Tetracationic Dicyclophane.
Here we report one-pot synthesis of tetraphenylethene-based tetracationic dicyclophane (1) and its self-assembly behaviors with aggregation-induced emission (AIE) and light-harvesting function. Confirmed by X-ray crystal structure and high resolution transmission electron microscopy, this tetracationic dicyclophane can self-assemble into a 3D supramolecular framework to form crystalline nanospheres (2) finally, which exhibits a strong emission (ΦF = 97.7%) via AIE effect in aqueous solution. Interestingly, AIE-active 2 as a single-molecule-based fluorescent supramolecular platform can encapsulate an organic dye (e.g., Nile red) to form light-harvesting nanospheres (3) further with a large red-shift (Δλ = ∼70 nm), highly efficient energy-transfer ability (ΦET = 77.5%), and high antenna effect (14.3).


Bioaccessibility and stability of β-carotene encapsulated in plant-based emulsions: impact of emulsifier type and tannic acid.
The effect of two plant-based emulsifiers (quillaja saponin, QS and gum arabic, GA) and a polyphenol (tannic acid) on the formation, stability, digestibility, and β-carotene (BC) bioaccessibility of flaxseed oil-in-water emulsions was investigated. The gastrointestinal behavior of the emulsions was studied using a simulated gastrointestinal tract (GIT) consisting of mouth, stomach, and small intestine regions. In the absence of tannic acid, the initial extent of lipid digestion depended strongly on emulsifier type, with 45% and 76% of the free fatty acids being released after 5 min digestion for QS- and GA-emulsions, respectively. Even so, the lipid droplets were completely digested in both emulsions after 2 h incubation in the small intestine phase. Tannic acid addition (0.01% and 0.1% w/w) slowed down lipid digestion, but did not impact the final extent. The droplets in the QS-emulsions containing 0.1% tannic acid were highly flocculated in the stomach phase. Molecular docking simulations indicated that the interactions between tannic acid and the saponins were mainly driven by hydrogen bonding and hydrophobic interactions. Moreover, they showed that the interactions between tannic acid and QS were stronger at pH 2.5 than at pH 7.0, which would account for the extensive droplet flocculation observed under acidic conditions in the stomach. Emulsifier type and tannic acid addition had no significant influence on BC bioaccessibility. The GA-emulsions exhibited better stability than the QS-emulsions when stored at elevated temperatures (55 °C for 7 days). Tannic acid addition effectively inhibited temperature-induced BC degradation. These results may facilitate the design of more efficacious nutraceutical-loaded functional foods and beverages.


Does follicular dominance occur in ewes?
The process by which a single follicle is selected to ovulate while others regress is unknown in ewes. If the dominant follicle secretes substances that directly inhibit the growth of other follicles, the superovulatory response to the administration of exogenous gonadotrophins may be blunted. Administration of 1250 iu pregnant mares' serum gonadotrophin (PMSG) before or after the emergence of the dominant follicle in the follicular phase, or 1000 iu PMSG in the presence or absence of a large healthy or atretic follicle during the luteal phase did not affect the induced ovulatory response. Comparisons between the ovary with or without the dominant follicle did not reveal any differences in ovulatory response to PMSG. The in-vitro features (i.e. mitotic index, oestradiol and testosterone production) of follicles ipsilateral or contralateral to the dominant follicle during the early and late follicular phases were also similar. If the dominant follicle secretes substances detrimental to the other follicles, this could be mimicked in vitro. Co-culture of small follicles with the largest follicles in a closed system did not reduce their incorporation of 3H thymidine in granulosa cells, compared with small follicles cultured alone. These data suggest that dominance is probably not operative in sheep. The administration of 500 iu of PMSG during the midfollicular phase increased ovulation rate in Merino ewes, indicating that dominance is essentially passive in ewes and can easily be overcome by raising gonadotrophin concentration.


Chromosome 8p as a potential hub for developmental neuropsychiatric disorders: implications for schizophrenia, autism and cancer.
Defects in genetic and developmental processes are thought to contribute susceptibility to autism and schizophrenia. Presumably, owing to etiological complexity identifying susceptibility genes and abnormalities in the development has been difficult. However, the importance of genes within chromosomal 8p region for neuropsychiatric disorders and cancer is well established. There are 484 annotated genes located on 8p; many are most likely oncogenes and tumor-suppressor genes. Molecular genetics and developmental studies have identified 21 genes in this region (ADRA1A, ARHGEF10, CHRNA2, CHRNA6, CHRNB3, DKK4, DPYSL2, EGR3, FGF17, FGF20, FGFR1, FZD3, LDL, NAT2, NEF3, NRG1, PCM1, PLAT, PPP3CC, SFRP1 and VMAT1/SLC18A1) that are most likely to contribute to neuropsychiatric disorders (schizophrenia, autism, bipolar disorder and depression), neurodegenerative disorders (Parkinson's and Alzheimer's disease) and cancer. Furthermore, at least seven nonprotein-coding RNAs (microRNAs) are located at 8p. Structural variants on 8p, such as copy number variants, microdeletions or microduplications, might also contribute to autism, schizophrenia and other human diseases including cancer. In this review, we consider the current state of evidence from cytogenetic, linkage, association, gene expression and endophenotyping studies for the role of these 8p genes in neuropsychiatric disease. We also describe how a mutation in an 8p gene (Fgf17) results in a mouse with deficits in specific components of social behavior and a reduction in its dorsomedial prefrontal cortex. We finish by discussing the biological connections of 8p with respect to neuropsychiatric disorders and cancer, despite the shortcomings of this evidence.


Predicting attrition in basic military training.
This cohort study investigated whether the risk of attrition during Australian Army recruit training was predicted by the fitness, age, date of enlistment, or injury status of recruits. Subjects were 1,317 male Australian Army recruits undertaking 12 weeks of intensive training. Fitness was measured using a 20-m progressive shuttle run test (20 mSRT) in which higher scores reflected higher fitness. A total of 184 subjects failed to complete training. Two hundred seventy-six disabling lower limb training injuries were recorded; 100 were stress fractures or periostitis. Scores on the 20 mSRT ranged between 3.5 and 13.5. Multivariate survival analysis revealed a strong negative association between 20 mSRT score and risk of attrition (p < 0.001) and a positive association between sustaining a lower limb injury and risk of attrition (p < 0.001). These effects were additive. Age and enlistment date were not significantly associated with risk of attrition. Fitness and training procedures may be important, modifiable risk factors for attrition.