Misjudgments at the mandibular angle: freehand versus computer-assisted screw positioning.
Distraction osteogenesis is a well known and frequently described technique in mandibular deformities. Buried intraoral devices have numerous advantages, but success hinges on precise positioning of the implants. Although computer navigation has repeatedly been described for craniofacial applications, research on navigating the mandibular region is scarce. Navigating the device placement for a mandibular distractor could become a viable method for distraction osteogenesis because of the possibility of certainty in achieving a defined device position. A clinical situation was simulated by a mandible model mounted inside a phantom head. The screws were positioned according to a virtual plan through transoral and transbuccal approaches, with and without navigation. Without navigation, the mean deviation from the planned position was 4.9 mm (range, 0.9-10.7 mm), with a clear tendency to position the screws in the easy-to-access regions. With navigation, the mean deviation was significantly lower at 1.5 mm (range, 0.1-3.4 mm). Computer-assisted surgery can provide a high level of accuracy in the region of the mandibular angle, where precision is crucial for buried intraoral distraction devices.


Osteosarcoma of the pelvis: outcome analysis of surgical treatment.
Risk factors to explain the poor survival of patients with osteosarcoma of the pelvis are poorly understood. Therefore, we attempted to identify factors affecting survival and development of local recurrence and metastasis. We retrospectively reviewed 43 patients who had high-grade pelvic tumors and were treated surgically. Twenty lesions were chondroblastic, 10 fibroblastic, 11 osteoblastic, and one each was giant cell-rich and small cell osteosarcomas. At a median of 3.5 years (range, 0.3-21 years) postoperatively, 13 patients were alive with no evidence of disease. The overall and disease-free 5-year survival rates were 38% and 29%, respectively, at 5 years. Anatomic location, tumor size, and margin predicted survival. Fifteen patients (35%) had local recurrence. The 5-year cumulative incidence of recurrence with death as a competing risk factor was 34%. Location in the ilium and size of the tumor predicted local recurrence. Twenty-one (49%) of 43 patients had metastases develop. The cumulative incidence of metastasis with death as a competing risk factor was 48% at 5 years. Six patients who presented with metastasis had a worse survival than patients who had no evidence of metastasis at presentation (2-year survival, 33% versus 76%). If distant metastasis is diagnosed subsequent to primary treatment, aggressive therapy may be justified. Level II, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.


Evolutionary interplay between structure, energy and epistasis in the coat protein of the ϕX174 phage family.
Viral capsids are structurally constrained by interactions among the amino acids (AAs) of their constituent proteins. Therefore, epistasis is expected to evolve among physically interacting sites and to influence the rates of substitution. To study the evolution of epistasis, we focused on the major structural protein of the ϕX174 phage family by first reconstructing the ancestral protein sequences of 18 species using a Bayesian statistical framework. The inferred ancestral reconstruction differed at eight AAs, for a total of 256 possible ancestral haplotypes. For each ancestral haplotype and the extant species, we estimated, in silico, the distribution of free energies and epistasis of the capsid structure. We found that free energy has not significantly increased but epistasis has. We decomposed epistasis up to fifth order and found that higher-order epistasis sometimes compensates pairwise interactions making the free energy seem additive. The dN/dS ratio is low, suggesting strong purifying selection, and that structure is under stabilizing selection. We synthesized phages carrying ancestral haplotypes of the coat protein gene and measured their fitness experimentally. Our findings indicate that stabilizing mutations can have higher fitness, and that fitness optima do not necessarily coincide with energy minima.


Estimated maximal and current brain volume predict cognitive ability in old age.
Brain tissue deterioration is a significant contributor to lower cognitive ability in later life; however, few studies have appropriate data to establish how much influence prior brain volume and prior cognitive performance have on this association. We investigated the associations between structural brain imaging biomarkers, including an estimate of maximal brain volume, and detailed measures of cognitive ability at age 73 years in a large (N = 620), generally healthy, community-dwelling population. Cognitive ability data were available from age 11 years. We found positive associations (r) between general cognitive ability and estimated brain volume in youth (male, 0.28; females, 0.12), and in measured brain volume in later life (males, 0.27; females, 0.26). Our findings show that cognitive ability in youth is a strong predictor of estimated prior and measured current brain volume in old age but that these effects were the same for both white and gray matter. As 1 of the largest studies of associations between brain volume and cognitive ability with normal aging, this work contributes to the wider understanding of how some early-life factors influence cognitive aging.


Reversible polymorphism-aware phylogenetic models and their application to tree inference.
We present a reversible Polymorphism-Aware Phylogenetic Model (revPoMo) for species tree estimation from genome-wide data. revPoMo enables the reconstruction of large scale species trees for many within-species samples. It expands the alphabet of DNA substitution models to include polymorphic states, thereby, naturally accounting for incomplete lineage sorting. We implemented revPoMo in the maximum likelihood software IQ-TREE. A simulation study and an application to great apes data show that the runtimes of our approach and standard substitution models are comparable but that revPoMo has much better accuracy in estimating trees, divergence times and mutation rates. The advantage of revPoMo is that an increase of sample size per species improves estimations but does not increase runtime. Therefore, revPoMo is a valuable tool with several applications, from speciation dating to species tree reconstruction.


Managing chronic hepatitis B: A qualitative study exploring the perspectives of people living with chronic hepatitis B in Australia.
The implementation of a comprehensive public health response to hepatitis B in Australia is urgently required to reduce the increasing burden of hepatitis B infection on the health system and the community. A significant gap in the public health response to hepatitis B is an understanding of how people with chronic hepatitis B (CHB) respond to CHB. A qualitative study involving semi-structured interviews and focus group discussions was conducted. Interviews were held with 20 people with CHB from three states of Australia. In addition, four focus group discussions were held with a total of 40 community and health workers from culturally and linguistically diverse communities in four Australian states.People with CHB reported no formal or informal pre or post test discussion with little information about hepatitis B provided at the point of diagnosis. Knowledge deficits about hepatitis B were found among most participants. Few resources are available for people with CHB or their families to assist them in understanding the infection and promoting their health and well-being. A lack of confidence in the professional knowledge of service providers was noted throughout interviews. People with CHB need culturally and linguistically appropriate education and information, particularly at the point of diagnosis. Primary health care professionals need the knowledge, skills and motivation to provide appropriate information to people with CHB, to ensure they have the capacity to better manage their infection.


Lipid thioesters derived from acylated proteins accumulate in infantile neuronal ceroid lipofuscinosis: correction of the defect in lymphoblasts by recombinant palmitoyl-protein thioesterase.
Palmitoyl-protein thioesterase is a lysosomal long-chain fatty acyl hydrolase that removes fatty acyl groups from modified cysteine residues in proteins. Mutations in palmitoyl-protein thioesterase were recently found to cause the neurodegenerative disorder infantile neuronal ceroid lipofuscinosis, a disease characterized by accumulation of amorphous granular deposits in cortical neurons, leading to blindness, seizures, and brain death by the age of three. In the current study, we demonstrate that [35S]cysteine-labeled lipid thioesters accumulate in immortalized lymphoblasts of patients with infantile neuronal ceroid lipofuscinosis. The accumulation in cultured cells is reversed by the addition of recombinant palmitoyl-protein thioesterase that is competent for lysosomal uptake through the mannose-6-phosphate receptor. The [35S]cysteine-labeled lipids are substrates for palmitoyl-protein thioesterase in vitro, and their formation requires prior protein synthesis. These data support a role for palmitoyl-protein thioesterase in the lysosomal degradation of S-acylated proteins and define a major new pathway for the catabolism of acylated proteins in the lysosome.


Quaternary structure and biochemical properties of mycobacterial RNase E/G.
The RNase E/G family of endoribonucleases plays the central role in numerous post-transcriptional mechanisms in Escherichia coli and, presumably, in other bacteria, including human pathogens. To learn more about specific properties of RNase E/G homologues from pathogenic Gram-positive bacteria, a polypeptide comprising the catalytic domain of Mycobacterium tuberculosis RNase E/G (MycRne) was purified and characterized in vitro. In the present study, we show that affinity-purified MycRne has a propensity to form dimers and tetramers in solution and possesses an endoribonucleolytic activity, which is dependent on the 5'-phosphorylation status of RNA. Our data also indicate that the cleavage specificities of the M. tuberculosis RNase E/G homologue and its E. coli counterpart are only moderately overlapping, and reveal a number of sequence determinants within MycRne cleavage sites that differentially affect the efficiency of cleavage. Finally, we demonstrate that, similar to E. coli RNase E, MycRne is able to cleave in an intercistronic region of the putative 9S precursor of 5S rRNA, thus suggesting a common function for RNase E/G homologues in rRNA processing.


Substituted tetrahydroisoquinolines as selective antagonists for the orexin 1 receptor.
Increasing evidence implicates the orexin 1 (OX1) receptor in reward processes, suggesting OX1 antagonism could be therapeutic in drug addiction. In a program to develop an OX1 selective antagonist, we designed and synthesized a series of substituted tetrahydroisoquinolines and determined their potency in OX1 and OX2 calcium mobilization assays. Structure-activity relationship (SAR) studies revealed limited steric tolerance and a preference for electron deficiency at the 7-position. Pyridylmethyl groups were shown to be optimal for activity at the acetamide position. Computational studies resulted in a pharmacophore model and confirmed the SAR results. Compound 72 significantly attenuated the development of place preference for cocaine in rats.


Combination probes with intercalating anchors and proximal fluorophores for DNA and RNA detection.
A new class of modified oligonucleotides (combination probes) has been designed and synthesised for use in genetic analysis and RNA detection. Their chemical structure combines an intercalating anchor with a reporter fluorophore on the same thymine nucleobase. The intercalator (thiazole orange or benzothiazole orange) provides an anchor, which upon hybridisation of the probe to its target becomes fluorescent and simultaneously stabilizes the duplex. The anchor is able to communicate via FRET to a proximal reporter dye (e.g. ROX, HEX, ATTO647N, FAM) whose fluorescence signal can be monitored on a range of analytical devices. Direct excitation of the reporter dye provides an alternative signalling mechanism. In both signalling modes, fluorescence in the unhybridised probe is switched off by collisional quenching between adjacent intercalator and reporter dyes. Single nucleotide polymorphisms in DNA and RNA targets are identified by differences in the duplex melting temperature, and the use of short hybridization probes, made possible by the stabilisation provided by the intercalator, enhances mismatch discrimination. Unlike other fluorogenic probe systems, placing the fluorophore and quencher on the same nucleobase facilitates the design of short probes containing multiple modifications. The ability to detect both DNA and RNA sequences suggests applications in cellular imaging and diagnostics.


Common genetic factors among sexual orientation, gender nonconformity, and number of sex partners in female twins: implications for the evolution of homosexuality.
Homosexuality is a stable population-level trait in humans that lowers direct fitness and yet is substantially heritable, resulting in a so-called Darwinian "paradox." Evolutionary models have proposed that polymorphic genes influencing homosexuality confer a reproductive benefit to heterosexual carriers, thus offsetting the fitness costs associated with persistent homosexuality. This benefit may consist of a "sex typicality" intermediate phenotype. However, there are few empirical tests of this hypothesis using genetically informative data in humans. This study aimed to test the hypothesis that common genetic factors can explain the association between measures of sex typicality, mating success, and homosexuality in a Western (British) sample of female twins. Here, we used data from 996 female twins (498 twin pairs) comprising 242 full dizygotic pairs and 256 full monozygotic pairs (mean age 56.8) and 1,555 individuals whose co-twin did not participate. Measures of sexual orientation, sex typicality (recalled childhood gender nonconformity), and mating success (number of lifetime sexual partners) were completed. Variables were subject to multivariate variance component analysis. We found that masculine women are more likely to be nonheterosexual, report more sexual partners, and, when heterosexual, also report more sexual partners. Multivariate twin modeling showed that common genetic factors explained the relationship between sexual orientation, sex typicality, and mating success through a shared latent factor. Our findings suggest that genetic factors responsible for nonheterosexuality are shared with genetic factors responsible for the number of lifetime sexual partners via a latent sex typicality phenotype in human females. These results may have implications for evolutionary models of homosexuality but are limited by potential mediating variables (such as personality traits) and measurement issues.


Immunization with a modified vaccinia virus expressing simian immunodeficiency virus (SIV) Gag-Pol primes for an anamnestic Gag-specific cytotoxic T-lymphocyte response and is associated with reduction of viremia after SIV challenge.
The immunogenicity and protective efficacy of a modified vaccinia virus Ankara (MVA) recombinant expressing the simian immunodeficiency virus (SIV) Gag-Pol proteins (MVA-gag-pol) was explored in rhesus monkeys expressing the major histocompatibility complex (MHC) class I allele, MamuA*01. Macaques received four sequential intramuscular immunizations with the MVA-gag-pol recombinant virus or nonrecombinant MVA as a control. Gag-specific cytotoxic T-lymphocyte (CTL) responses were detected in all MVA-gag-pol-immunized macaques by both functional assays and flow cytometric analyses of CD8(+) T cells that bound a specific MHC complex class I-peptide tetramer, with levels peaking after the second immunization. Following challenge with uncloned SIVsmE660, all macaques became infected; however, viral load set points were lower in MVA-gag-pol-immunized macaques than in the MVA-immunized control macaques. MVA-gag-pol-immunized macaques exhibited a rapid and substantial anamnestic CTL response specific for the p11C, C-M Gag epitope. The level at which CTL stabilized after resolution of primary viremia correlated inversely with plasma viral load set point (P = 0.03). Most importantly, the magnitude of reduction in viremia in the vaccinees was predicted by the magnitude of the vaccine-elicited CTL response prior to SIV challenge.


Arthroscopic Central Acetabular Decompression: Clinical Outcomes at Minimum 2-Year Follow-up Using a Matched-Pair Analysis.
To assess 2-year clinical outcomes of patients who underwent hip arthroscopy for central acetabular osteophytes (CAO) treated with central acetabular decompression (CAD), and to compare these outcomes with those of a matched control group. Data were prospectively gathered for patients undergoing CAD during hip arthroscopy from February 2008 to July 2012. All patients were assessed pre- and postoperatively at 3 months, 1 year, and 2 years with modified Harris Hip Score, Non-Arthritic Hip Score, Hip Outcome Score-Activities of Daily Living, Hip Outcome Score-Sport-Specific Subscale, and visual analog scale (VAS) for pain. Patient satisfaction (0 to 10) was collected. A matched control group of patients without CAOs who did not undergo CAD was selected on a 1:3 ratio. Forty-nine hips were included in the CAD group and 147 in the control group. The mean change in patient-reported outcome (PRO) scores at 2-year follow-up in the CAD group for modified Harris Hip Score, Hip Outcome Score-Activities of Daily Living, Hip Outcome Score-Sport-Specific Subscale, Non-Arthritic Hip Score, and VAS was 11.0, 19.6, 15.2, 21.4, and -2, respectively. The mean change in PRO scores at 2-year follow-up in the control group was 17.0, 19.8, 24.0, 20.9, and -2.75, respectively. All improvements in PRO scores for both groups were statistically significant compared with the data collected preoperatively (P < .001). There was no statistically significant difference in postoperative PRO scores and VAS between the groups. Postoperative patient satisfaction at the latest follow-up was 7.14 and 7.60 for CAD and control groups, respectively. This study showed that patients with a CAO treated with CAD during hip arthroscopy had favorable outcomes at minimum 2 years postoperatively. Furthermore, the study group showed similar PRO scores and VAS to the control group. We conclude that CAD is a viable treatment option for CAO, yielding clinical improvement at short-term follow-up. Level III, prospective comparative study.


Sex differences in neuropeptide content and release from rat dental pulp.
Studies to examine sex differences in response to pain have suggested that females exhibit lower threshold responses to painful stimuli and that threshold response varies greatly at different stages of the menstrual cycle. Additional studies suggest that sex differences may be caused by societal sex roles or differences in anxiety responses by men and women. The purpose of this study was to evaluate biologically evident sex differences in male and female rats chronically treated with a systemic algogen, the nerve growth factor (NGF), by measuring neuropeptides (calcitonin gene-related peptide) content and release from isolated dental pulp. Rats were injected subcutaneously every other day with either murine NGF (1 mg/kg) or vehicle for 7 or 13 days. Isolated incisor pulp tissue was evaluated from these male and female rats (n = 96). Capsaicin-evoked neurosecretion of CGRP and tissue content were measured using a previously validated radioimmunoassay. Dental pulp from female rats at 7 days showed significantly increased capsaicin-evoked immunoreactive CGRP release (>50% increase) compared with tissue from male rats. After 13 days, this release was significantly increased only in NGF-treated female rats (3-fold increase) when compared with control females or both male groups. The CGRP content in tissue from both female groups was also significantly increased after 7 days of treatment (>3 fold), but after 13 days this content was only significantly increased in tissue from NGF-treated female rats (P = .0001). These data suggest that sex differences affect the role of NGF in the modulation of inflammation through the regulation of peripheral neuropeptide release and content.


Comparative survey on scolicidal effects of selenium and silver nanoparticles on protoscolices of hydatid cyst.
Hydatidosis is a zoonotic diseases which affects human and livestock animals. The surgical treatment of hydatid diseases in man is still the most effective approach, but spillage of protoscolices is the risk of surgery. Therefore, it is essential to develop alternative approaches. Injection of protoscolicidal agents into the cysts preoperatively is an alternative method.The aim of the present study was the determination and comparison of lethal effects of silver nanoparticles (Ag-NPs) and selenium nanoparticles (Se-NPs) on protoscolices of hydatid cyst. Livers and lungs of sheep, which was naturally infected by hydatid cyst were collected from Tabriz slaughterhouse and transferred to the parasitology laboratory. Initially, the surface of cysts was disinfected by 70% Alcohol. Then, 25 ml of each cyst fluid were aspirated by sterile syringe and transferred to Erlenmeyer flask. After 30 minutes, the supernatant was discarded and protoscolices were washed with phosphate-buffered saline and tested by 1% eosin to assess their viability. Next, the samples of protoscolices, which were over 90%, were selected and the effect of 50, 125, 250 and 500 (µg/ml) of Se-NPs and Ag-NPs in the exposure times of 10, 20, 30 and 60 min were evaluated. Data were analysed by SAS software and analyzed by Duncan's comparison test. The significant differences were considered to be p<0.0001.The difference between the scolicidal effects of Se-NPs was statistically significant for all examined concentrations and exposure times compared to the control group (p<0.0001). On the other hand, the scolicidal effect of Ag-NPs in 10 and 20 min exposer was not significant in comparison to the control group. Overall scolicidal effect of Se-NPs was higher than Ag-NPs and the difference was significant (p<0.0001).The results of the present research indicated that it is possible to use Se-NPs as an effective scolicidal treatment. It is suggested the study of employing this compound in vivo or in combination with other procedures in treating hydatid cyst in further studies.


Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer.
The previous individual patient data meta-analyses of chemotherapy in locally advanced non-small-cell lung cancer (NSCLC) showed that adding sequential or concomitant chemotherapy to radiotherapy improved survival. The NSCLC Collaborative Group performed a meta-analysis of randomized trials directly comparing concomitant versus sequential radiochemotherapy. Systematic searches for trials were undertaken, followed by central collection, checking, and reanalysis of updated individual patient data. Results from trials were combined using the stratified log-rank test to calculate pooled hazard ratios (HRs). The primary outcome was overall survival; secondary outcomes were progression-free survival, cumulative incidences of locoregional and distant progression, and acute toxicity. Of seven eligible trials, data from six trials were received (1,205 patients, 92% of all randomly assigned patients). Median follow-up was 6 years. There was a significant benefit of concomitant radiochemotherapy on overall survival (HR, 0.84; 95% CI, 0.74 to 0.95; P = .004), with an absolute benefit of 5.7% (from 18.1% to 23.8%) at 3 years and 4.5% at 5 years. For progression-free survival, the HR was 0.90 (95% CI, 0.79 to 1.01; P = .07). Concomitant treatment decreased locoregional progression (HR, 0.77; 95% CI, 0.62 to 0.95; P = .01); its effect was not different from that of sequential treatment on distant progression (HR, 1.04; 95% CI, 0.86 to 1.25; P = .69). Concomitant radiochemotherapy increased acute esophageal toxicity (grade 3-4) from 4% to 18% with a relative risk of 4.9 (95% CI, 3.1 to 7.8; P < .001). There was no significant difference regarding acute pulmonary toxicity. Concomitant radiochemotherapy, as compared with sequential radiochemotherapy, improved survival of patients with locally advanced NSCLC, primarily because of a better locoregional control, but at the cost of manageable increased acute esophageal toxicity.


Burden of medical illness in women with depression and posttraumatic stress disorder.
Depression and posttraumatic stress disorder (PTSD) are important women's health issues. Depression is known to be associated with poor physical health; however, associations between physical health and PTSD, a common comorbidity of depression, have received less attention. To examine number of medical symptoms and physical health status in women with PTSD across age strata and benchmark them against those of women with depression alone or with neither depression nor PTSD. A random sample of Veterans Health Administration enrollees received a mailed survey in 1999-2000 (response rate, 63%). The 30 865 women respondents were categorized according to whether a health care provider had ever told them that they had PTSD, depression (without PTSD), or neither. Outcomes were self-reported medical conditions and physical health status measured with the Veterans SF-36 instrument, a version of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) modified for use in veteran populations. Across age strata, women with PTSD (n = 4348) had more medical conditions and worse physical health status (physical functioning, role limitations due to physical problems, bodily pain, and energy/vitality scales from the Veterans SF-36) than women with depression alone (n = 7580) or neither (n = 18 937). In age-adjusted analyses, the Physical Component Summary score was on average 3.4 points lower in women with depression alone and 6.3 points lower in women with PTSD than in women with neither (P<.001). Posttraumatic stress disorder is associated with a greater burden of medical illness than is seen with depression alone. The presence of PTSD may account for an important component of the excess medical morbidity and functional status limitations seen in women with depression.


Sex Differences in Fish Oil and Olanzapine Effects on Gut Microbiota in Diet-Induced Obese Mice.
Children are prescribed second-generation antipsychotic (SGA) medications, such as olanzapine (OLZ) for FDA-approved and "off-label" indications. The long-term impact of early-life SGA medication exposure is unclear. Olanzapine and other SGA medications are known to cause excessive weight gain in young and adult patients, suggesting the possibility of long-term complications associated with the use of these drugs, such as obesity, diabetes, and heart disease. Further, the weight gain effects of OLZ have previously been shown to depend on the presence of gut bacteria and treatment with OLZ, which shifts gut bacteria toward an "obesogenic" profile. The purpose of the current study was to evaluate changes in gut bacteria in adult mice following early life treatment with OLZ and being fed either a high-fat diet or a high-fat diet supplemented with fish oil, which has previously been shown to counteract gut dysbiosis, weight gain, and inflammation produced by a high-fat diet. Female and male C57Bl/6J mice were fed a high fat diet without (HF) or with the supplementation of fish oil (HF-FO) and treated with OLZ from postnatal day (PND) 37-65 resulting in four groups of mice: mice fed a HF diet and treated with OLZ (HF-OLZ), mice fed a HF diet and treated with vehicle (HF), mice fed a HF-FO diet and treated with OLZ (HF-FO-OLZ), and mice fed a HF-FO diet and treated with vehicle (HF-FO). Following euthanasia at approximately 164 days of age, we determined changes in gut bacteria populations and serum LPS binding protein, an established marker of gut inflammation and dysbiosis. Our results showed that male HF-FO and HF-FO-OLZ mice had lower body weights, at sacrifice, compared to the HF group, with a comparable body weight across groups in female mice. HF-FO and HF-FO-OLZ male groups also exhibited lower serum LPS binding protein levels compared to the HF group, with no differences across groups in female mice. Gut microbiota profiles were also different among the four groups; the Bacteroidetes-to-Firmicutes (B/F) ratio had the lowest value of 0.51 in the HF group compared to 0.6 in HF-OLZ, 0.9 in HF-FO, and 1.1 in HF-FO-OLZ, with no differences in female mice. In conclusion, FO reduced dietary obesity and its associated inflammation and increased the B/F ratio in male mice but did not benefit the female mice. Although the weight lowering effects of OLZ were unexpected, FO effects persisted in the presence of olanzapine, demonstrating its potential protective effects in male subjects using antipsychotic drugs.


Using Clinical Vignettes to Evaluate VTE Protocol Adherence.
Venous thromboembolism (VTE) prophylaxis is underutilized in hospitalized medical patients. Underutilization might occur as a result of resident practice variation incurred by using a complex risk assessment tool. To examine what impact repetitive exposure to an electronic point-based VTE risk assessment tool has on resident inter-rater reliability and protocol adherence. Pre and post intervention cross-sectional cohort study. Single academic center. Convenience samples of Internal Medicine residents. Residents completed clinical vignettes before and after any exposure to an electronic risk assessment tool and reminder alert. They were asked to make three determinations using a point-based VTE risk assessment tool: risk stratification, identify contraindications, and VTE prevention strategy. Inter-rater reliability for risk assessment, contraindications, and VTE prophylaxis strategy and protocol adherence. Kappa scores for VTE risk assessment did not change, but improved for VTE plan increasing from 0.28 to 0.37. Protocol adherence improved from 71% in 2008 to 79% (P = 0.06). There was a significant decrease in under-prophylaxis (22% to 6%, P < 0.0001) but a significant increase in over-prophylaxis (7% to 16%, P = 0.001). Using clinical vignettes, we determined that daily exposure to an electronic risk assessment tool did not improve the inter-rater reliability of a point-based risk assessment tool when used by medical residents. This might be due to inexperienced providers using a complex point-based tool. Overall, adherence improved, and under-prophylaxis decreased, but over-prophylaxis increased. Clinical vignettes are a generalizable method to monitor resident prophylaxis practices and way to identify educational and process improvement opportunities. Resident; Inter-rater reliability; Venous thromboembolism; Agreement; Risk assessment score.


Legal and psychological implications in the assessment of sexual consent in the cognitively impaired population.
The question of competency to consent to sexual activity in the cognitively impaired population continues to be a difficult assessment issue. Problems center on inconsistent legal and clinical criteria, current inadequate methods of psychological assessment, and the need to promote basic human rights, while protecting people from harm. The purpose of this study was twofold. First, the problems inherent in the psychological assessment of competency to consent to sexual activity are discussed with an emphasis on problems defining consent competency. Second, the utility of a neuropsychological test battery in assisting with the assessment of the ability to consent to sexual activity was examined. Findings indicated that executive measures of neuropsychological assessment were primarily associated with competency to consent to sexual activity. It is important that these neuropsychological measures were more accurate in categorizing competent and noncompetent individuals than methods currently in use. This suggests that sexual consent assessments in the forensic arena should include neuropsychological testing and that current methods are insufficient.


Circadian Rhythm Disruption Promotes Lung Tumorigenesis.
Circadian rhythms are 24-hr oscillations that control a variety of biological processes in living systems, including two hallmarks of cancer, cell division and metabolism. Circadian rhythm disruption by shift work is associated with greater risk for cancer development and poor prognosis, suggesting a putative tumor-suppressive role for circadian rhythm homeostasis. Using a genetically engineered mouse model of lung adenocarcinoma, we have characterized the effects of circadian rhythm disruption on lung tumorigenesis. We demonstrate that both physiologic perturbation (jet lag) and genetic mutation of the central circadian clock components decreased survival and promoted lung tumor growth and progression. The core circadian genes Per2 and Bmal1 were shown to have cell-autonomous tumor-suppressive roles in transformation and lung tumor progression. Loss of the central clock components led to increased c-Myc expression, enhanced proliferation, and metabolic dysregulation. Our findings demonstrate that both systemic and somatic disruption of circadian rhythms contribute to cancer progression.


Colonization of weakened trees by mass-attacking bark beetles: no penalty for pioneers, scattered initial distributions and final regular patterns.
Bark beetles use aggregation pheromones to promote group foraging, thus increasing the chances of an individual to find a host and, when relevant, to overwhelm the defences of healthy trees. When a male beetle finds a suitable host, it releases pheromones that attract potential mates as well as other 'spying' males, which result in aggregations on the new host. To date, most studies have been concerned with the use of aggregation pheromones by bark beetles to overcome the defences of living, well-protected trees. How insects behave when facing undefended or poorly defended hosts remains largely unknown. The spatio-temporal pattern of resource colonization by the European eight-toothed spruce bark beetle, Ips typographus, was quantified when weakly defended hosts (fallen trees) were attacked. In many of the replicates, colonization began with the insects rapidly scattering over the available surface and then randomly filling the gaps until a regular distribution was established, which resulted in a constant decrease in nearest-neighbour distances to a minimum below which attacks were not initiated. The scattered distribution of the first attacks suggested that the trees were only weakly defended. A minimal theoretical distance of 2.5 cm to the earlier settlers (corresponding to a density of 3.13 attacks dm-2) was calculated, but the attack density always remained lower, between 0.4 and 1.2 holes dm-2, according to our observations.


Absorbate-induced piezochromism in a porous molecular crystal.
Atmospherically stable porous frameworks and materials are interesting for heterogeneous solid-gas applications. One motivation is the direct and selective uptake of pollutant/hazardous gases, where the material produces a measurable response in the presence of the analyte. In this report, we present a combined experimental and theoretical rationalization for the piezochromic response of a robust and porous molecular crystal built from an extensively fluorinated trispyrazole. The electronic response of the material is directly determined by analyte uptake, which provokes a subtle lattice contraction and an observable bathochromic shift in the optical absorption onset. Selectivity for fluorinated absorbates is demonstrated, and toluene is also found to crystallize within the pore. Furthermore, we demonstrate the application of electronic structure calculations to predict a physicochemical response, providing the foundations for the design of electronically tunable porous solids with the chemical properties required for development of novel gas-uptake media.


Association between C reactive protein and depression in a population of healthy adults: the Cooper Center Longitudinal Study.
The relationship between depression and inflammation is currently a topic of much interest. Previous studies have produced mixed results regarding the association between depression and high-sensitivity C reactive protein (hs-CRP). The aim of this report was to determine the association between hs-CRP and depression in a large sample of healthy adults. This is a cross-sectional study of 26,638 healthy adults seen for preventive medical examinations between December 2000 and August 2018 at the Cooper Clinic in Dallas, Texas. Multivariable logistic regression was used to evaluate the association between hs-CRP levels and depressive symptoms as measured by the 10-item Center for Epidemiologic Studies Depression Scale. Covariates included race, age, education, smoking history, alcohol use, menopausal status, body mass index (BMI), and medication use. The Hs-CRP level demonstrated a weakly positive association with depressive symptoms (OR 1.06 per mg/L, 95% CI 1.03 to 1.09 for women; OR 1.05 per mg/L, 95% CI 1.02 to 1.09 for men) that became insignificant when controlling for BMI in women (OR 1.02 per mg/L, 95% CI 0.98 to 1.05) and men (OR 1.02 per mg/L, 95% CI 0.98 to 1.05). Adjusting for antidepressant and statin use did not affect the association between hs-CRP and depressive symptoms in women (OR 0.99 per mg/L, 95% CI 0.96 to 1.03) or men (OR 1.01 per mg/L, 95% CI 0.97 to 1.05). Levels of hs-CRP were not associated with depression independent of BMI in a predominantly white, male population of higher socioeconomic status. This finding suggests that associations between hs-CRP and depression may be explained by obesity, which warrants further investigation into shared pathways between obesity and depression.


Accelerated Accumulation of Multimorbidity After Bilateral Oophorectomy: A Population-Based Cohort Study.
To study the association between bilateral oophorectomy and the rate of accumulation of multimorbidity. In this historical cohort study, the Rochester Epidemiology Project records-linkage system was used to identify all premenopausal women who underwent bilateral oophorectomy before age 50 years between January 1, 1988, and December 31, 2007, in Olmsted County, Minnesota. Each woman was randomly matched to a referent woman born in the same year (±1 year) who had not undergone bilateral oophorectomy. We studied the rate of accumulation of 18 common chronic conditions over a median of approximately 14 years of follow-up. Although women who underwent bilateral oophorectomy already had a higher multimorbidity burden at the time of oophorectomy, they also experienced an increased risk of subsequent multimorbidity. After adjustments for 18 chronic conditions present at baseline, race/ethnicity, education, body mass index, smoking, age at baseline, and calendar year at baseline, women who underwent oophorectomy before age 46 years experienced an increased risk of depression, hyperlipidemia, cardiac arrhythmias, coronary artery disease, arthritis, asthma, chronic obstructive pulmonary disease, and osteoporosis. In addition, they experienced an accelerated rate of accumulation of the 18 chronic conditions considered together (hazard ratio, 1.22; 95% CI, 1.14-1.31; P<.001). Several of these associations were reduced in women who received estrogen therapy. Bilateral oophorectomy is associated with a higher risk of multimorbidity, even after adjustment for conditions present at baseline and for several possible confounders. However, several of these associations were reduced in women who received estrogen therapy.


Structured supervised exercise training or motivational counselling during pregnancy on physical activity level and health of mother and offspring: FitMum study protocol.
A physically active lifestyle during pregnancy improves maternal and offspring health but can be difficult to follow. In Denmark, less than 40% of pregnant women meet physical activity (PA) recommendations. The FitMum study aims to explore strategies to increase PA during pregnancy among women with low PA and assess the health effects of PA. This paper presents the FitMum protocol, which evaluates the effects of structured supervised exercise training or motivational counselling supported by health technology during pregnancy on PA level and health of mother and offspring. A single-site three-arm randomised controlled trial that aims to recruit 220 healthy, pregnant women with gestational age (GA) no later than week 15 and whose PA level does not exceed one hour/week. Participants are randomised to one of three groups: structured supervised exercise training consisting of three weekly exercise sessions, motivational counselling supported by health technology or a control group receiving standard care. The interventions take place from randomisation until delivery. The primary outcome is min/week of moderate-to-vigorous intensity PA (MVPA) as determined by a commercial activity tracker, collected from randomisation until GA of 28 weeks and 0-6 days, and the secondary outcome is gestational weight gain (GWG). Additional outcomes are complementary measures of PA; clinical and psychological health parameters in participant, partner and offspring; analyses of blood, placenta and breastmilk samples; process evaluation of interventions; and personal understandings of PA. The study is approved by the Danish National Committee on Health Research Ethics (# H-18011067) and the Danish Data Protection Agency (# P-2019-512). Findings will be disseminated via peer-reviewed publications, at conferences, and to health professionals via science theatre performances. NCT03679130. This paper was written per the study protocol version 8 dated 28 August 2019.


Anxiety-like effects of SR141716-precipitated delta9-tetrahydrocannabinol withdrawal in mice in the elevated plus-maze.
Marijuana discontinuation has been recently reported to be anxiogenic in humans, which may predict relapse. Limited animal research has been carried out to model this withdrawal-associated negative affect. The current study sought to investigate the potential anxiety-like effects of cannabinoid withdrawal in mice. Male ICR mice were injected s.c. with delta9-tetrahydrocannabinol (THC) at 10mg/kg or vehicle once daily for 10 days. To precipitate withdrawal, the cannabinoid CB1 antagonist SR141716 (0.3, 1.0, or 3.0mg/kg) or vehicle was administrated i.p. 4h following the last THC or vehicle treatment. Thirty minutes later, mice were tested on the elevated plus-maze (EPM) for 5min. SR141716 did not significantly change EPM behaviors in vehicle-treated mice. In contrast, SR141716 precipitated a reduction in exploration of the open arms of EPM in mice repeatedly treated with THC vs vehicle. At 3.0mg/kg, SR141716 significantly reduced % open arm entries of the total arm entries, % open arm time of total time in arms, and the absolute time spent in open arms. No significant differences in the number of closed or total arm entries were observed, indicating that the behavioral changes were not due to altered motor activity. Collectively, the present results constitute the first evidence that cannabinoid withdrawal produces anxiety-like effects in mice. This animal model may help to identify the mechanisms that contribute to adaptations in the neuronal circuitry of the brain that are expressed as emotional symptoms of cannabinoid withdrawal.


Consumer acceptance of quality protein maize (QPM) in East Africa.
Undernutrition in sub-Saharan Africa remains problematic, and quality protein maize (QPM) can benefit populations whose diets are heavily based on maize and who are consequently at risk for inadequate intakes of quality protein. However, changes in the chemical composition of QPM may affect its sensory characteristics and, hence, acceptance. Acceptance tests were therefore conducted to evaluate QPM varieties in three East African countries using central location tests with one or two varieties in each country, using the most popular preparations: ugali (Tanzania), githeri (Kenya) and injera (Ethiopia). In total, 281 urban and rural consumers of both sexes and varying levels of education evaluated the products on standard sensory criteria: appearance, aroma, texture, taste and overall, using a Likert scale. The results show that African consumers can differentiate QPM products from their conventional counterparts, indicating that the QPM trait results in distinguishable sensory changes. Analysis by ordinal mixed regression models showed that consumers found QPM acceptable and even preferable to conventional maize. The sensory characteristics of QPM are therefore no impediment to its adoption; on the contrary, when coupled with good agronomic performance, they may help its utilization, leading to a positive impact in nutritionally vulnerable populations.


Tenacious assumptions of person-centred care? Exploring tensions and variations in practice.
In recent decades, the 'tenacious assumptions' of biomedicine regarding the neutrality and universality of its knowledge claims have been significantly challenged by the growth of new collaborative and patient-focused models of Healthcare delivery. In this article, we discuss and critically reflect upon one such alternative Healthcare model developed at the University of Gothenburg Centre for Person-Centred Care in Sweden. This centre uses three clinical routines of narrative, partnership and documentation to provide Healthcare to people recognized as unique individuals rather than patients. Person-centred care in Gothenburg and more broadly is based on the assumption that a person is independently capable of reasoning and verbal expression and willing to provide clear and genuine narratives and cooperate with Healthcare professionals. However, we argue that by emphasizing individual capabilities of reasoning and verbal expression, an unnecessarily limited conception of personhood risks being imposed on these routines. Drawing upon semi-structured interviews with researchers in three very different Gothenburg Centre for Person-Centred Care research projects - about healthy ageing in migrant communities, neurogenic communication disorders, and psychosis - we highlight that how persons are recognized as unique and capable varies significantly in practice across different Healthcare settings. Thus, we assert that person-centred care's own potentially tenacious assumptions about the attributes of personhood risk distracting attention away from the variety of creative ways that professionals and persons promisingly find for translating the ideal of person-centred care into practice.


Suppression of erythro-megakaryocytopoiesis and the induction of reversible thrombocytopenia in mice transgenic for the thymidine kinase gene targeted by the platelet glycoprotein alpha IIb promoter.
The mechanisms that regulate the commitment of a totipotent stem cell to the megakaryocytic lineage are largely unknown. Using a molecular approach to the study of megakaryocytopoiesis and platelet production, mice in which thrombocytopoiesis could be controlled were produced by targeting the expression of the herpes simplex virus thymidine kinase toxigene to megakaryocytes using the regulatory region of the gene encoding the alpha subunit of the platelet integrin alpha IIb beta 3. The programmed eradication of the megakaryocytic lineage was induced by treating transgenic mice bearing the hybrid construct (alpha IIbtk) with the antiherpetic drug ganciclovir (GCV). After 10 d of treatment, the platelet number was reduced by > 94.6%. After discontinuing GCV, the bone marrow was repopulated with megakaryocytes and the platelet count was restored within 7 d. Prolonged GCV treatment induced erythropenia in the transgenic mice. Assays of myeloid progenitor cells in vitro demonstrated that the transgene was expressed in early erythro-megakaryocytic progenitor cells. The reversibility and facility of this system provides a powerful model to determine both the critical events in megakaryocytic and erythroid lineage development and for evaluating the precise role that platelets play in the pathogenesis of a number of vascular occlusive disorders.


"Outside the Skin": The Persistence of Black-White Disparities in U.S. Early-Life Mortality.
Research on Black-White disparities in mortality emphasizes the cumulative pathways through which racism gets "under the skin" to affect health. Yet this framing is less applicable in early life, when death is primarily attributable to external causes rather than cumulative, biological processes. We use mortality data from the National Vital Statistics System Multiple Cause of Death files and population counts from the Surveillance, Epidemiology, and End Result Program to analyze 705,801 deaths among Black and White males and females, ages 15-24. We estimate age-standardized death rates and single-decrement life tables to show how all-cause and cause-specific mortality changed from 1990 to 2016 by race and sex. Despite overall declines in early-life mortality, Black-White disparities remain unchanged across several causes-especially homicide, for which mortality is nearly 20 times as high among Black as among White males. Suicide and drug-related deaths are higher among White youth during this period, yet their impact on life expectancy at birth is less than half that of homicide among Black youth. Critically, early-life disparities are driven by preventable causes of death whose impact occurs "outside the skin," reflecting racial differences in social exposures and experiences that prove harmful for both Black and White adolescents and young adults.


Are Elderly Patients With Clinically Localized Prostate Cancer Overtreated? Exploring Heterogeneity in Survival Effects.
Clinical trial evidence shows minimal survival gains and higher complication rates from radical prostatectomy (RP) versus watchful waiting (WW) for elderly men with localized prostate cancer (PCa). It is believed that these patients are overtreated. The current analyses aim to explore patient-level heterogeneity in survival effects, examine matching of patients to treatments in practice, and identify patient characteristics driving heterogenous effects, in order to present more comprehensive evidence about the concerns of overtreatment. Eleven-year all-cause and PCa-specific survival among SEER-Medicare patients diagnosed during 1996-2002 were analyzed using local instrumental variable approaches. A total of 8462 (77%) of 11,036 patients received RP. The average effects of RP over WW on 11-year overall and cancer-specific survival were 1.1 months (95%CI, -25, 28; P=0.94) and 1.7 months (95%CI, -25, 29; P=0.90) respectively; effects did not differ significantly according to age, race, grade, and stage. Fewer than 1% of patients had significant cancer-specific survival benefit from RP at the 10% level; 6% were expected to gain over 15 months from RP. However, patients with larger expected survival gains from RP were much more likely to receive RP in practice. Such positive self-selection was driven by PCa-specific survival than overall survival. Several comorbidities may play a critical role in predicting who could benefit from RP. Our analyses corroborate concerns about PCa overtreatment. A small fraction of screen-detected PCa patients derive survival benefits from RP. Prediction tools should account for patient comorbidities to accurately predict survival benefits of RP over WW.


Fenton's treatment of actual agriculture runoff water containing herbicides.
This research was to study the efficiency of the Fenton's treatment process for the removal of three herbicides, namely 2,4-dichlorophenoxy acetic acid (2,4-D), ametryn and dicamba from the sugarcane field runoff water. The treatment process was designed with the Taguchi approach by varying the four factors such as H2O2/COD (1-3.5), H2O2/Fe2+ (5-50), pH (2-5) and reaction time (30-240 min) as independent variables. Influence of these parameters on chemical oxygen demand (COD), ametryn, dicamba and 2,4-D removal efficiencies (dependent variables) were investigated by performing signal to noise ratio and other statistical analysis. The optimum conditions were found to be H2O2/COD: 2.125, H2O2/Fe2+: 27.5, pH: 3.5 and reaction time of 135 min for removal efficiencies of 100% for ametryn, 95.42% for dicamba, 88.2% for 2,4-D and with 75% of overall COD removal efficiencies. However, the percentage contribution of H2O2/COD ratio was observed to be significant among all four independent variables and were 44.16%, 67.57%, 51.85% and 50.66% for %COD, ametryn, dicamba and 2,4-D removal efficiencies, respectively. The maximum removal of herbicides was observed with the H2O2 dosage of 5.44 mM and Fe2+ dosage of 0.12 mM at pH 3.5.


Study protocol: a mixed-methods realist evaluation of the Universal Health Visiting Pathway in Scotland.
The growing political emphasis on the early years reflects the importance of these formative years of life. Health visitors in the UK are uniquely positioned to improve health outcomes for children and families and to reduce health inequalities. Recently, there has been a policy change in Scotland in an attempt to enhance the delivery of the universal health visiting service. This study aims to examine the extent to which the enhanced Universal Health Visiting Pathway is implemented and delivered across Scotland and to assess any associated impacts. A mixed-methods study incorporating four methodological components and uses realist evaluation as the overall conceptual framework. It comprises three phases (1) initial programme theory development; (2) programme theory validation and (3) programme theory refinement. The programme theory validation will use interview and focus group data of parents and health visitors, and conduct a case note review at five study sites. It also involves a national survey of parents and health visitors and routine data analysis of existing secondary data. The analyses of the ensuing qualitative and quantitative data will be carried out using a convergent mixed-methods approach to ensure continuous triangulation of multiple data. The findings of the evaluation will provide contextually relevant understanding of how the Universal Health Visiting Pathway works and evidence the impact of increased investments in health visiting in Scotland. This protocol has been approved by the School of Health in Social Science Research Ethics Committee, University of Edinburgh. Additional approvals have been granted/will be sought from the Public Benefit and Privacy Panel for health and social care in Scotland for the case note review,survey and routine data analysis elements of the evaluation. The findings will be prepared as reports to the funders and presented at conferences. It will be submitted for publication in peer-reviewed journals.


Biomechanics of thoracic short versus long fixation after 3-column injury.
Posterior screw-rod fixation for thoracic spine trauma usually involves fusion across long segments. Biomechanical data on screw-based short-segment fixation for thoracic fusion are lacking. The authors compared the effects of spanning short and long segments in the thoracic spine. Seven human spine segments (5 segments from T-2 to T-8; 2 segments from T-3 to T-9) were prepared. Pure-moment loading of 6 Nm was applied to induce flexion, extension, lateral bending, and axial rotation while 3D motion was measured optoelectronically. Normal specimens were tested, and then a wedge fracture was created on the middle vertebra after cutting the posterior ligaments. Five conditions of instrumentation were tested, as follows: Step A, 4-level fixation plus cross-link; Step B, 2-level fixation; Step C, 2-level fixation plus cross-link; Step D, 2-level fixation plus screws at fracture site (index); and Step E, 2-level fixation plus index screws plus cross-link. Long-segment fixation restricted 2-level range of motion (ROM) during extension and lateral bending significantly better than the most rigid short-segment construct. Adding index screws in short-segment constructs significantly reduced ROM during flexion, lateral bending, and axial rotation (p < 0.03). A cross-link reduced axial rotation ROM (p = 0.001), not affecting other loading directions (p > 0.4). Thoracic short-segment fixation provides significantly less stability than long-segment fixation for the injury studied. Adding a cross-link to short fixation improved stability only during axial rotation. Adding a screw at the fracture site improved short-segment stability by an average of 25%.


Multi-particle momentum correlations extracted using covariance methods on multiple-ionization of diiodomethane molecules by soft-X-ray free-electron laser pulses.
Momenta of ions from diiodomethane molecules after multiple ionization by soft-X-ray free-electron-laser pulses are measured. Correlations between the ion momenta are extracted by covariance methods formulated for the use in multiparticle momentum-resolved ion time-of-flight spectroscopy. Femtosecond dynamics of the dissociating multiply charged diiodomethane cations is discussed and interpreted by using simulations based on a classical Coulomb explosion model including charge evolution.


Aerobactin and other virulence factor genes among strains of Escherichia coli causing urosepsis: association with patient characteristics.
To assess the role of aerobactin as a virulence factor among uropathogenic Escherichia coli, we determined the prevalence, location, and phenotypic expression of aerobactin determinants among 58 E. coli strains causing bacteremic urinary tract infections. We correlated the presence of the aerobactin system with antimicrobial-agent resistance, the presence and phenotypic expression of other uropathogenic virulence factor determinants (P fimbriae, hemolysin, and type 1 fimbriae), and characteristics of patients. Colony and Southern hybridization of total and plasmid DNA with DNA probes for each virulence factor showed that aerobactin determinants were present in 78% of the strains and were plasmid associated in 21%, whereas P fimbria, hemolysin, and type 1 fimbria determinants were present in 74, 43, and 98% of the strains, respectively, and were always chromosomal. Chromosomal aerobactin, P fimbria, and hemolysin determinants occurred together on the chromosome more often in strains from patients without predisposing urological or medical conditions (P = 0.04). Strains with plasmid-encoded aerobactin lacked determinants for P fimbriae (P = 0.004) and hemolysin (P = 0.0004), were resistant to multiple antimicrobial agents (P = 0.0001), and were found only in compromised patients. Mating experiments demonstrated that some aerobactin plasmids also encoded antimicrobial-agent resistance. These findings suggest that the determinants for aerobactin, P fimbriae, and hemolysin are conserved on the chromosome of the antimicrobial-agent-susceptible uropathogenic strains of E. coli which invade noncompromised patients. In contrast, these chromosomal virulence factors are often absent from E. coli strains causing urosepsis in compromised hosts; these strains may acquire plasmid aerobactin in conjunction with antimicrobial-agent resistance genes.


The effects of sulfurous-arsenical-ferruginous thermal water nasal irrigation in wound healing after functional endoscopic sinus surgery for chronic rhinosinusitis: a prospective randomized study.
Although several publications reported the benefits of nasal irrigation in the management of chronic rhinosinusitis and in sinonasal postoperative care, the available data are poorly controlled. The aim of this prospective randomized study was to compare the effects of sulfurous-arsenical-ferruginous thermal water nasal irrigation vs isotonic sodium chloride solution nasal irrigation after functional endoscopic sinus surgery (FESS) for chronic sinonasal disease considering the histomorphological characteristics of mucosal repair after sinus surgery. Eighty patients who consecutively underwent FESS were randomly assigned (1:1) to postoperative nasal irrigation with sulfurous-arsenical-ferruginous thermal water or isotonic sodium chloride solution for 6 months. Intraoperative and postoperative (1, 3, and 6 months) mean counts of lymphocytes, neutrophils, eosinophils, plasma cells, histiocytes, and mast cells in ethmoid biopsies were blindly determined by a pathologist. Fifty-six patients underwent at least 2 postoperative biopsies. A statistically significant reduction of eosinophil count was disclosed 6 months postoperatively only after sulfurous-arsenical-ferruginous solution nasal irrigation (P = .04). After isotonic sodium chloride solution nasal irrigation, the mean eosinophil count in 6-month postoperative biopsies did not decrease. After both irrigation modalities, the mean mast cell counts in 6-month postoperative biopsies were significantly lower than in intraoperative biopsies (P < .05). Neutrophils, lymphocytes, histiocytes, and plasma cell counts were not significantly different between intraoperative vs 6-month postoperative biopsies independently from irrigation modality. Considering the important role of eosinophils in allergic response, we should suggest sulfurous-arsenical-ferruginous solution nasal irrigation in particular, which significantly reduces local eosinophil count, for allergic patients after FESS for chronic rhinosinusitis.


Transcription of a poxvirus early gene is regulated both by a short promoter element and by a transcriptional termination signal controlling transcriptional interference.
The promoter region of an early gene (38K gene) of cowpox virus has been characterized by deletion and linker scanning mutational analyses. Modified versions of this promoter region were placed into the genome of vaccinia virus, and their transcriptional efficiencies were assessed by quantifying RNAs transcribed from these sequences. These analyses showed that the sequences in the region between 33 and 4 base pairs upstream of the transcriptional start site affect the efficiency of transcription from this promoter. Linker scanning mutations in the -27 to -10 region inhibited transcription. This region contains the sequence 5'-GAAAATATATT-3', which is present in at least two other early genes in the same positions (-21 to -11) relative to the transcriptional start sites of these genes. Elements of this sequence are similarly positioned in the promoter regions of several other poxvirus genes, suggesting that this sequence represents a transcriptional control element of at least a subset of poxvirus genes. The -8 to -2 sequence (5'-TTTTTAT-3') contains a transcriptional termination signal. Mutation of this sequence had two separate effects: (i) it reduced the efficiency of transcription from the promoter by approximately 30%, and (ii) it prevented this sequence from terminating the transcription from upstream genes. When overlapping transcription from upstream genes was not prevented by a termination signal present either within the 38K promoter or upstream of the promoter, transcription from this promoter was reduced by about 30%. This indicates that transcriptional termination has a role in the regulation of viral gene expression by controlling transcriptional interference.


Prevalence and causes of functional low vision in school-age children: results from standardized population surveys in Asia, Africa, and Latin America.
Data on the prevalence and causes of functional low vision (FLV) in adults and children are lacking but are important for planning low-vision services. This study was conducted to determine the prevalence and causes of FLV among children recruited in eight population-based prevalence surveys of visual impairment and refractive error from six countries (India [2 locations]; China [2 locations]; Malaysia, Chile, Nepal, and South Africa). Using the same protocol, 4082 to 6527 children aged 5 (or 7) to 15 years were examined at each site. Uncorrected and presenting visual acuities were successfully measured with retroilluminated logMAR tumbling-E charts in 3997 to 5949 children; cycloplegic autorefraction was performed and best corrected acuities assessed. All children were examined by an ophthalmologist and a cause of visual loss assigned to eyes with uncorrected acuity < or =6/12. The prevalence of FLV was determined overall and by site; associations with gender, age, parental education and urban/rural location were assessed with logistic regression. The prevalence of FLV ranged from 0.65 to 2.75 in 1000 children, with wide confidence intervals. The overall prevalence was 1.52 in 1000 children (95% CI 1.16-1.95). FLV was significantly associated with age (odds ratio [OR] 1.13 for each year, P = 0.01), and parental education was protective (OR 0.75 for each of five levels of education, P = 0.017). Retinal lesions and amblyopia were the commonest causes. More studies are needed to determine the prevalence and causes of FLV in children so that services can be planned that promote independence, improve quality of life, and increase access to education.


Oxidative damage of rat cerebral cortex and hippocampus, and changes in antioxidative defense systems caused by hyperoxia.
In order to elucidate the oxidative damage in rat brain caused by oxidative stress, regional changes in the levels of lipid peroxidation products and antioxidative defense systems in cerebral cortex and hippocampus, and in their synapses, which modulate learning and memory functions in the brain, were studied. When rats were subjected to hyperoxia as an oxidative stress, thiobarbituric acid reactive substance (TBARS) in the regions studied increased more than in normal rats by approximately 35%. The values in oxygen-unexposed vitamin E-deficient rats were also higher than in normal rats. It was found that the TBARS contents in synaptosomes isolated from both regions were remarkably higher than in the organs. These results imply that synapses are more susceptible to oxidative stress than the organ itself. This tendency was also observed in the content of conjugated diene. In response to oxidative stress, the status of the antioxidant defense system in each region, i.e. the concentration of vitamin E, and the activities of superoxide dismutase, catalase and glutathione peroxidase, decreased remarkably. On the other hand, in oxygen-unexposed vitamin E-deficient rats, the activities of these enzymes each region tended to increase, except for catalase activity. These results suggest that in response to the oxidative stress, the antioxidant defense systems may be consumed to prevent oxidative damage, and then, may be supplied through the antioxidant network.


Specificity of the CheR2 methyltransferase in Pseudomonas aeruginosa is directed by a C-terminal pentapeptide in the McpB chemoreceptor.
Methyltransferases of the CheR family and methylesterases of the CheB family control chemoreceptor methylation, and this dynamic posttranslational modification is necessary for proper chemotaxis of bacteria. Studies with enterobacteria that contain a single CheR or CheB show that, in addition to binding at the methylation site, some chemoreceptors bind CheR or CheB through additional high-affinity sites at distinct pentapeptide sequences in the chemoreceptors. We investigated the recognition of chemoreceptors by CheR proteins in the human pathogen Pseudomonas aeruginosa PAO1. Of the four methyltransferases in PAO1, we detected an interaction only between CheR2 and the chemoreceptor methyl-accepting chemotaxis protein B (McpB), which contains the pentapeptide GWEEF at its carboxyl terminus. Furthermore, CheR2 was also the only paralog that methylated McpB in vitro, and deletion of the pentapeptide sequence abolished both the CheR2-McpB interaction and the methylation of McpB. When clustered according to protein sequence, bacterial CheR proteins form two distinct families-those that bind pentapeptide-containing chemoreceptors and those that do not. These two families are distinguished by an insertion of three amino acids in the β-subdomain of CheR. Deletion of this insertion in CheR2 prevented its interaction with and methylation of McpB. Pentapeptide-containing chemoreceptors are common to many bacteria species; thus, these short, distinct motifs may enable the specific assembly of signaling complexes that mediate different responses.


Denervation of the periosteal origin of the adductor muscles in conjunction with adductor fasciotomy in the surgical treatment of refractory groin pull.
The purpose of this study was to determine whether resection of the nerve that innervates the origin of the adductor muscle group in addition to an adductor fasciotomy will decrease pain and improve function in patients with a chronic "groin pull." The authors conducted a retrospective multicenter chart review of 12 patients presenting with refractory groin pull. In two patients, the problem was bilateral. There were eight female and four male patients. Injuries were related to sports (n=6), gynecologic procedures (n=3), and other injuries (n=3). Surgery included adductor fasciotomy plus resection of a nerve to the periosteal origin of the adductor muscles. Cadaver dissections were performed to identify the nerve's origin. In 13 of the 14 patient specimens, nerves were identified histologically: each of the five cadaver dissections demonstrated the anterior branch of the obturator nerve to be this nerve's origin. At a mean of 16.7 months after surgery, 11 of the 12 patients (92 percent) and 13 of the 14 limbs (93 percent) responded with relief of pain and improved activities of daily living. Of the 14 patients, eight had an excellent result (67 percent), three had a good result (25 percent), and one experienced a failure (7 percent). Chronic impairment related to a groin pull injury may be considered caused by a contracture of the adductor muscle group, which can be treated with fasciotomy. A branch of the obturator nerve is shown to innervate the origin of these muscles, and denervation can be performed simultaneously with fasciotomy, improving pain and function.


Incidence and survival trends for malignant pleural and peritoneal mesothelioma, Australia, 1982-2009.
Australia is known to have had one of the highest per-capita asbestos consumption rates, yet there are few contemporary reports on malignant mesothelioma trends. Data on 10 930 people with malignant pleural mesothelioma (MPM) and 640 people with malignant peritoneal mesothelioma diagnosed in Australia during 1982-2009 were analysed. Observed incidence rate trends were quantified. Incidence rates were projected up to 2030 using observed incident cases during 1982-2012. The relative per-decade change in excess mortality during 1999-2009 was estimated. During 1982-2009, acceleration in MPM age-standardised incidence rates were highest for women and those aged 75 years and above, with average annual percentage changes of +4.9 (95% CI 3.6 to 6.2) and +7.2 (95% CI 5.4 to 9.0), respectively. Age-standardised incidence rates for men with MPM aged 0-64 years decelerated rapidly during 2003-2009, an average annual percentage change of -5.1% (95% CI -7.6% to -2.5%). Overall, male age-specific MPM incidence rates in the age group of 65-74 year during 2010-2030 are projected to decline with rates projected to increase for older men and women with MPM. There was a statistically significant 16% relative reduction in the excess mortality rate (EMR) up to 5 years postdiagnosis for people diagnosed with malignant pleural and peritoneal mesothelioma combined in 2009 compared with those diagnosed in 1999, an EMR ratio of 0.84 (95% CI 0.77 to 0.92). Australia's malignant mesothelioma incidence rates appear to have reached maximum levels but with differences over time by age, gender and tumour location. Improvements over time in survival provide a glimpse of hope for this almost invariably fatal disease.


Empirical tests on regressive estimations: implications on surveys and diaries.
Using a large real-life corporate database initially consisting of 3,990 heads of households stratified on the basis of various demographic and geographic variables, and whose communication activities (long distance telephone calls, letters, cards, and visits) were surveyed and monitored, this study investigated the direction as well as magnitude of estimation errors in survey responses and diary entries. Supporting the 1994 Fiedler and Armbruster psychometric formulation and conjecture, we show that estimation errors in reports of the frequency and duration of people's own communication activities exhibit a consistent tendency to regress toward the mean. This regressive estimation is greater for those who are further away from the mean in actual behavior and is proportional to the actual deviation from the mean. Furthermore, this regressive estimation is inversely related to the average frequency across behavioral categories. An important implication of our findings is that the distribution of estimated behavioral frequencies and durations appear more concentrated in surveys than they actually are in the general population, although the general shape of the distribution is unaffected.


Mental health service use by cleanup workers in the aftermath of the Deepwater Horizon oil spill.
High rates of mental health (MH) problems have been documented among disaster relief workers. However, few workers utilize MH services, and predictors of service use among this group remain unexplored. The purpose of this study was to explore associations between predisposing, illness-related, and enabling factors from Andersen's behavioral model of treatment-seeking and patterns of service use among participants who completed at least one full day of cleanup work after the Deepwater Horizon oil spill and participated in home visits for the NIEHS GuLF STUDY (N = 8931). Workers reported on MH symptoms and whether they had used counseling or medication for MH problems since the oil spill. Hierarchical logistic regression models explored associations between predictors and counseling and medication use in the full sample, and type of use (counseling only, medication only, both) among participants who used either service. Analyses were replicated for subsamples of participants with and without symptom inventory scores suggestive of probable post-disaster mental illness. Having a pre-spill MH diagnosis, pre-spill service use, more severe post-spill MH symptoms, and healthcare coverage were positively associated with counseling and medication use in the full sample. Among participants who used either service, non-Hispanic Black race, pre-spill counseling, lower depression, and not identifying a personal doctor or healthcare provider were predictive of counseling only, whereas older age, female gender and pre-spill medication were predictive of medication only. The results were generally consistent among participants with and without probable post-disaster mental illness. The results suggest variability in which factors within Andersen's behavioral model are predictive of different patterns of service use among disaster relief workers.


Role of dietary fats in the prevention and treatment of the metabolic syndrome.
A symposium on the health significance of dietary fat in the prevention and treatment of the metabolic syndrome (MetS) was held at the 20th International Congress of Nutrition in Granada, Spain, on September 19, 2013. Four nutrition experts addressed the topics of dietary fat and obesity, effects of dietary fat quality in obesity and insulin resistance, influence of early nutrition on the later risk of MetS and the relative merits of high- or low-fat diets in counteracting MetS. Participants agreed that preventing weight gain and achieving weight loss in overweight and obese patients were key strategies for reducing MetS. Both low-fat and low-carbohydrate diets are associated with weight loss, but adherence to the diet is the most important factor in achieving success. Avoidance of high saturated fats contributes to lower health risks among obese, MetS and diabetic patients. Further, healthy maternal weight at conception and in pregnancy is more important that weight gain during pregnancy for reducing the risk of obesity in the offspring. The effects of different polyunsaturated fatty acids on MetS and weight loss require clarification.


Probing the influence of citrate-capped gold nanoparticles on an amyloidogenic protein.
Nanoparticles (NPs) are known to exhibit distinct physical and chemical properties compared with the same materials in bulk form. NPs have been repeatedly reported to interact with proteins, and this interaction can be exploited to affect processes undergone by proteins, such as fibrillogenesis. Fibrillation is common to many proteins, and in living organisms, it causes tissue-specific or systemic amyloid diseases. The nature of NPs and their surface chemistry is crucial in assessing their affinity for proteins and their effects on them. Here we present the first detailed structural characterization and molecular mechanics model of the interaction between a fibrillogenic protein, β2-microglobulin, and a NP, 5 nm hydrophilic citrate-capped gold nanoparticles. NMR measurements and simulations at multiple levels (enhanced sampling molecular dynamics, Brownian dynamics, and Poisson-Boltzmann electrostatics) explain the origin of the observed protein perturbations mostly localized at the amino-terminal region. Experiments show that the protein-NP interaction is weak in the physiological-like, conditions and do not induce protein fibrillation. Simulations reproduce these findings and reveal instead the role of the citrate in destabilizing the lower pH protonated form of β2-microglobulin. The results offer possible strategies for controlling the desired effect of NPs on the conformational changes of the proteins, which have significant roles in the fibrillation process.


New tools for automated high-resolution cryo-EM structure determination in RELION-3.
Here, we describe the third major release of RELION. CPU-based vector acceleration has been added in addition to GPU support, which provides flexibility in use of resources and avoids memory limitations. Reference-free autopicking with Laplacian-of-Gaussian filtering and execution of jobs from python allows non-interactive processing during acquisition, including 2D-classification, de novo model generation and 3D-classification. Per-particle refinement of CTF parameters and correction of estimated beam tilt provides higher resolution reconstructions when particles are at different heights in the ice, and/or coma-free alignment has not been optimal. Ewald sphere curvature correction improves resolution for large particles. We illustrate these developments with publicly available data sets: together with a Bayesian approach to beam-induced motion correction it leads to resolution improvements of 0.2-0.7 Å compared to previous RELION versions.


Neural stem cell heterogeneity through time and space in the ventricular-subventricular zone.
The origin and classification of neural stem cells (NSCs) has been a subject of intense investigation for the past two decades. Efforts to categorize NSCs based on their location, function and expression have established that these cells are a heterogeneous pool in both the embryonic and adult brain. The discovery and additional characterization of adult NSCs has introduced the possibility of using these cells as a source for neuronal and glial replacement following injury or disease. To understand how one could manipulate NSC developmental programs for therapeutic use, additional work is needed to elucidate how NSCs are programmed and how signals during development are interpreted to determine cell fate. This review describes the identification, classification and characterization of NSCs within the large neurogenic niche of the ventricular-subventricular zone (V-SVZ). A literature search was conducted using Pubmed including the keywords "ventricular-subventricular zone," "neural stem cell," "heterogeneity," "identity" and/or "single cell" to find relevant manuscripts to include within the review. A special focus was placed on more recent findings using single-cell level analyses on neural stem cells within their niche(s). This review discusses over 20 research articles detailing findings on V-SVZ NSC heterogeneity, over 25 articles describing fate determinants of NSCs, and focuses on 8 recent publications using distinct single-cell analyses of neural stem cells including flow cytometry and RNA-seq. Additionally, over 60 manuscripts highlighting the markers expressed on cells within the NSC lineage are included in a chart divided by cell type. Investigation of NSC heterogeneity and fate decisions is ongoing. Thus far, much research has been conducted in mice however, findings in human and other mammalian species are also discussed here. Implications of NSC heterogeneity established in the embryo for the properties of NSCs in the adult brain are explored, including how these cells may be redirected after injury or genetic manipulation.


Antitumor activity of IHL-305, a novel pegylated liposome containing irinotecan, in human xenograft models.
The antitumor effect of IHL-305, a novel pegylated liposome containing irinotecan, was investigated in human xenograft models. After subcutaneous transplantation of several human cancer cell lines (colorectal, non-small cell lung, small cell lung, prostate, ovarian and gastric cancer cells) to nude mice, IHL-305 or CPT-11 was administered intravenously 3 times at 4-day intervals. In all xenograft models tested, IHL-305 showed superior antitumor activity to that of CPT‑11 and a comparable tumor-growth-inhibitory effect at one-eighth or less of the dose of CPT-11, even against HT-29 colorectal and NCI-H460 non-small cell lung cancer cell lines, which show intrinsic resistance to CPT-11. A single injection or 2 injections of IHL-305 on several dosing schedules also resulted in a significant antitumor effect compared to that of vehicle control in a dose-dependent manner and showed comparable antitumor activity at about one-fifth the dose of the maximum tolerated dose of CPT-11. The analysis of the concentrations of irinotecan and SN-38, an active metabolite of CPT-11, in plasma and tumors revealed that irinotecan was maintained at high concentrations, and the prolonged presence of SN-38 in plasma and tumors in IHL-305 treated mice compared with CPT-11-treated mice. Therefore, the stronger tumor inhibitory effect of IHL-305, as compared to CPT-11, was associated with the difference in the concentration of irinotecan in plasma or tumors after each agent was administered and with the maintainance of a higher concentration of SN-38. These results indicate that IHL-305 demonstrated superior antitumor activity against a wide range of tumors at lower doses than CPT-11.


Multiscale simulations of ligand adsorption and exchange on gold nanoparticles.
We have developed a multiscale model that combines first-principles methods with atomistic and mesoscopic simulations to explore the molecular structures and packing density of the ligands present on the gold nanoparticle (AuNP) surface, as well as the adsorption/exchange reaction kinetics of cetyltrimethylammonium bromide (CTAB)/PEG-SH ligands on different facets of gold, namely, Au(111), Au(100), and Au(110). Our model predicts that on clean gold surfaces, CTAB adsorption is diffusion limited. Specifically, CTAB has the preferentially higher adsorption rate and coverage density on Au(100) and Au(110) surfaces, forming a more compact layer with respect to that on the Au(111) surface, which could result in greater growth of gold nanoparticles along the (111) direction. As opposed to CTAB adsorption, the exchange reaction between PEG-SH with CTAB shows no selectivity to different crystal faces, and the reaction process follows Langmuir diffusion kinetics. Kinetic analysis reveals that, in water, the exchange reaction is zeroth order with respect to the concentration of an incoming PEG-SH, indicative of a dissociative exchange mechanism. The observed rate constant decreases exponentially with the PEG-SH chain length, consistent with a diffusion process for the free PEG-SH in water. In particular, we show that the exchange efficiency increases as the chain rigidness and size of the incoming ligand and/or steric bulk of the initial protecting ligand shell are decreased. Our objectives are to provide a model to assess the kinetics and thermodynamics of the adsorption/exchange reaction process, and we expect that these findings will have important implications for routine surface characterization of AuNPs.


Ethics and Community Involvement in Syntheses Concerning American Indian, Alaska Native, or Native Hawaiian Health: A Systematic Review.
The objective of the research was to review reporting of ethical concerns and community involvement in peer-reviewed systematic reviews or meta-analyses concerning American Indian, Alaska Native, or Native Hawaiian (AI/AN/NH) health. Text words and indexed vocabulary terms were used to query PubMed, Embase, Cochrane Library, and the Native Health Database for systematic reviews or meta-analyses concerning AI/AN/NH health published in peer-reviewed journals, followed by a search through reference lists. Each article was abstracted by two independent reviewers; results were discussed until consensus was reached. We identified 107 papers published from 1986-2012 that were primarily about AI/AN/NH health or presented findings separately for AI/AN/NH communities. Two reported seeking indigenous reviewer feedback; none reported seeking input from tribes and communities. Approximately 7% reported on institutional review board (IRB) approval of included studies, 5% reported on tribal approval, and 4% referenced the sovereignty of AI/AN tribes. Approximately 63% used evidence from more than one AI/AN/NH population study, and 28% discussed potential benefits to communities from the synthesis research. Reporting of ethics and community involvement are not prominent. Systematic reviews and meta-analyses making community-level inferences may pose risks to communities. Future systematic reviews and meta-analyses should consider ethical and participatory dimensions of research.


Hoxa2 and Hoxb2 control dorsoventral patterns of neuronal development in the rostral hindbrain.
Little is known about how the generation of specific neuronal types at stereotypic positions within the hindbrain is linked to Hox gene-mediated patterning. Here, we show that during neurogenesis, Hox paralog group 2 genes control both anteroposterior (A-P) and dorsoventral (D-V) patterning. Hoxa2 and Hoxb2 differentially regulate, in a rhombomere-specific manner, the expression of several genes in broad D-V-restricted domains or narrower longitudinal columns of neuronal progenitors, immature neurons, and differentiating neuronal subtypes. Moreover, Hoxa2 and Hoxb2 can functionally synergize in controlling the development of ventral neuronal subtypes in rhombomere 3 (r3). Thus, in addition to their roles in A-P patterning, Hoxa2 and Hoxb2 have distinct and restricted functions along the D-V axis during neurogenesis, providing insights into how neuronal fates are assigned at stereotypic positions within the hindbrain.


Emerging investigator series: determination of biphasic core-shell droplet properties using aerosol optical tweezers.
We present a new algorithm for the analysis of whispering gallery modes (WGMs) found in the cavity enhanced Raman spectra retrieved from optically tweezed droplets. Our algorithm improves the computational scaling when analyzing core-shell droplets (i.e. phase-separated or biphasic droplets) in the aerosol optical tweezers (AOT), making it computationally practical to analyze spectra collected at a few Hz over hours-long experiments. This enables the determination of the size and refractive index of both the core and shell phases with high accuracy, at 0.5 Hz time resolution. Phase-separated core-shell droplets are common morphologies in a wide variety of biophysical, colloidal, and aerosolized chemical systems, and have recently become a major focus in understanding the atmospheric chemistry of particulate matter. Our new approach reduces the number of parameters directly searched for, decreasing computational demands. We assess the accuracy of the diameters and refractive indices retrieved from a homogeneous or core-shell droplet. We demonstrate the performance of the new algorithm using experimental data from a droplet of aqueous glycerol coated by squalane. We demonstrate that a shell formation causes adjacent WGMs to split from each other in their wavenumber position through the addition of a secondary organic aerosol shell around a NaCl(aq) droplet. Our new algorithm paves the way for more in-depth physiochemical experiments into liquid-liquid phase separation and their consequences for interfacial chemistry-a topic with growing experimental needs for understanding the dynamics and chemistry of atmospheric aerosol particles, and in biochemical systems.


Comprehensive Analysis of mRNA Expression Profiling and Identification of Potential Diagnostic Biomarkers in Coronary Artery Disease.
The aim of this study is to investigate mRNA expression profiling by RNA sequencing (RNA-seq) in patients with coronary artery disease (CAD) and validate differentially expressed genes (DEGs) as novel biomarkers for CAD. Transcriptome-wide mRNA expression analysis of peripheral blood mononuclear cells was performed in five CAD patients and five controls. Functional enrichment analyses, protein-protein interaction network construction, and hub gene selection were further conducted. Relative expression levels of hub genes were validated by quantitative reverse transcription PCR in larger cohorts. Spearman correlation test and multiple linear regression analysis were applied to examine the relationship between confounding factors with severity of coronary artery atherosclerosis. Receiver operating characteristic (ROC) curve analysis was adopted to identify potentially diagnostic biomarkers for CAD. A total of 527 upregulated and 653 downregulated mRNAs were identified as DEGs in CAD patients. The relative expression levels of beta-transducin repeat containing E3 ubiquitin protein ligase (BTRC), F-box and leucine-rich repeat protein 4 (FBXL4), ubiquitin conjugating enzyme E2 D2 (UBE2D2), and ankyrin repeat and SOCS box containing 1 (ASB1) were significantly different between two groups (all p ≤ 0.05). The severity of coronary artery atherosclerosis was negatively associated with the BTRC gene relative expression level (r = -0.323, p < 0.001) and positively with UBE2D2 (r = 0.285, p < 0.001). ROC analysis of BTRC and UBE2D2 genes showed that the areas under the curve were 0.782 (95% CI: 0.720-0.845, p < 0.001) and 0.753 (95% CI: 0.681-0.824, p < 0.001), respectively. We described the characteristics of mRNA expression in the peripheral blood of CAD patients and controls by RNA-seq. Combined with Spearman correlation analysis and ROC analyses, BTRC and UBE2D2 genes had significantly diagnostic values, which may have potential to act as novel diagnostic biomarkers and therapeutic targets for CAD.


Ectopic expression of sex peptide alters reproductive behavior of female D. melanogaster.
Sex peptide, a secreted component of the male accessory glands, has been shown to induce behavioral and physiological changes in mated Drosophila. We transformed flies with a hybrid gene containing an hsp70 promoter fused to a cDNA encoding sex peptide. Heat-induced ectopic expression of the peptide in transgenic virgin females altered their reproductive behavior, in the presence of courting males, to that observed in mated females. This demonstrates that the peptide is functional as expected. Time course studies revealed that the behavioral change appeared earlier than the stimulated ovulation. We have also introduced a modified sex peptide gene that is driven by the yp1 enhancer, conferring expression in adult females, and shown that these flies refuse mating constitutively in the presence of courting males and lay unfertilized eggs at the rate of mated females.


Genetic variation among isolates of western equine encephalomyelitis virus from California.
The mechanism for long-term maintenance of western equine encephalomyelitis (WEE) virus in California was investigated by studying genetic variation in the E2 portion of the genome of 55 strains of WEE virus isolated since 1938 from different locations in California. Four major lineages were evident: virus strains isolated from the Central Valley since 1993 and Los Angeles in 1991 formed lineage A; southern California strains isolated since 1978 and isolates from the Central Valley from 1978 to 1987 formed lineage B; northern California isolates from 1968 to 1971 formed lineage C; and early isolates from 1938 to 1961 formed a fourth lineage, D. The separation of strains from north and south of the Tehachapi and San Bernardino Mountains (i.e., the Central Valley and southern California, respectively) since 1991 indicates that there has been little recent movement of virus between the two regions and recent strains from these two locations appear to be evolving independently. However, within the Central Valley and within southern California, virus appears to circulate freely, perhaps by movement of birds or mosquito vectors. Although the current virus lineage in the Central Valley may have been introduced from an unknown source in 1991, introduction and establishment of new viral genotypes from outside California do not seem to occur regularly. It appears most likely that virus is maintained in separate geographic areas of California through local persistence in enzootic foci.


Nanowires of methylammonium lead iodide (CH3NH3PbI3) prepared by low temperature solution-mediated crystallization.
We report the synthesis of Methylammonium Lead Iodide (CH(3)NH(3)PbI(3)) nanowires by a low temperature solution processed crystallization using a simple slip-coating method. The anisotropic particle shape exhibits advantages over nanoparticles in terms of charge transport under illumination. These results provide a basis for solvent-mediated tailoring of structural properties like the crystallite size and orientation in trihalide perovskite thin films, which, once implemented into a device, may ultimately result in an enhanced charge carrier extraction.


Progress in the direct structural characterization of fibrous amphiphilic supramolecular assemblies in solution by transmission electron microscopic techniques.
The self-assembly of amphiphilic molecules into fibrous structures has been the subject of numerous studies over past decades due to various current and promising technical applications. Although very different in their head group chemistry many natural as well as synthetic amphiphilic compounds derived from carbohydrates, carbocyanine dyes, or amino acids tend to form fibrous structures by molecular self-assembly in water predominantly twisted ribbons or tubes. Often a transition between these assembly structures is observed, which is a phenomenon already theoretically approached by Wolfgang Helfrich and still focus point in current research. With the development of suitable sample preparation and electron optical imaging techniques, cryogenic transmission electron microscopy (cryo-TEM) in combination with three-dimensional (3D) reconstruction techniques has become a particular popular direct characterization technique for supramolecular assemblies in general. Here we review the recent progress in deriving precise structural information from cryo-TEM data of particularly fibrous structures preferably in three dimensions.


N-deacetylation of Sinorhizobium meliloti Nod factors increases their stability in the Medicago sativa rhizosphere and decreases their biological activity.
Nod factors excreted by rhizobia are signal molecules that consist of a chitin oligomer backbone linked with a fatty acid at the nonreducing end. Modifications of the Nod factor structures influence their stability in the rhizosphere and their biological activity. To test the function of N-acetyl groups in Nod factors, NodSm-IV(C16:2,S) from Sinorhizobium meliloti was enzymatically N-deacetylated in vitro with purified chitin deacetylase from Colletotrichum lindemuthianum. A family of partially and completely deacetylated derivatives was produced and purified. The most abundant chemical structures identified by mass spectrometry were GlcN(C16:2)-GlcNAc-GlcNH2-GlcNAc(OH)(S), GlcN(C16,2)-GlcNAc-GlcNH2-GlcNH2(OH)(S), and GlcN(C16:2)-GlcNH2-GlcNH2-GlcNH2(OH)(S). In contrast to NodSm-IV(C16:2,S), the purified N-deacetylated derivatives were stable in the rhizosphere of Medicago sativa, indicating that the N-acetyl groups make the carbohydrate moiety of Nod factors accessible for glycosyl hydrolases of the host plant. The N-deacetylated derivatives displayed only a low level of activity in inducing root hair deformation. Furthermore, the N-deacetylated molecules were not able to stimulate Nod factor degradation by M. sativa roots, a response elicited by active Nod factors. These data show that N-acetyl groups of Nod factors are required for biological activity.


Physical modalities inducing immunogenic tumor cell death for cancer immunotherapy.
The concept of immunogenic cancer cell death (ICD), as originally observed during the treatment with several chemotherapeutics or ionizing irradiation, has revolutionized the view on the development of new anticancer therapies. ICD is defined by endoplasmic reticulum (ER) stress response, reactive oxygen species (ROS) generation, emission of danger-associated molecular patterns and induction of antitumor immunity. Here we describe known and emerging cancer cell death-inducing physical modalities, such as ionizing irradiation, ultraviolet C light, Photodynamic Therapy (PDT) with Hypericin, high hydrostatic pressure (HHP) and hyperthermia (HT), which have been shown to elicit effective antitumor immunity. We discuss the evidence of ICD induced by these modalities in cancer patients together with their applicability in immunotherapeutic protocols and anticancer vaccine development.