Prevalence of context effects: testing with a straightforward question of yesterday happiness.
Although contexts effects were found in responding to general happiness, it is little known how prevalent the effects can be in other measures of subjective wellbeing. If context effects are still found for a measure of subjective wellbeing that exhibits a host of features minimizing the effects, one can conclude that the effects can be quite prevalent. We aimed to assess this possibility. We analyzed the Indonesian Family Life Survey by exploiting the random assignment of four versions of a list of 12 yesterday affects. The random assignment established causality on firmer ground. We applied ordered probit models by sex (10,162 men and 11,531 women): the dependent variable of interest was a measure of happiness, and the independent variables of interest were four affects that immediately preceded happiness. We found that when sadness immediately preceded happiness, men were 2.4% points more likely to say not at all happy and 2.5% points less likely to say very happy. The corresponding figures for women were 1.5 and 1.8% points. We, however, found no discernible context effects when boredom and anger immediately preceded happiness. Context effects were still found for a measure of subjective wellbeing even when the effects were thought to be minimal. That said, the different influence of sadness versus boredom and anger suggests that there are ways to alleviate context effects.


Healthy aging does not compromise the augmentation of cardiac function during heat stress.
During heat stress, stroke volume is maintained in young adults despite reductions in cardiac filling pressures. This is achieved by a general augmentation of cardiac function, highlighted by a left and upward shift of the Frank-Starling relation. In contrast, healthy aged adults are unable to maintain stroke volume during heat stress. We hypothesized that this would be associated with a lack of shift in the Frank-Starling relation. Frank-Starling relations were examined in 11 aged [69 ± 4 (SD) yr, 4 men/7 women] and 12 young (26 ± 5 yr, 6 men/6 women) adults during normothermic and heat stress (1.5°C increase in core temperature) conditions. During heat stress, increases in cardiac output were attenuated in aged adults (+2.5 ± 0.3 (95% CI) vs. young: +4.5 ± 0.5 l/min, P < 0.01) because of an attenuated chronotropic response (+30 ± 4 vs. young: +42 ± 5 beats/min, P < 0.01). In contrast to our hypothesis, a leftward shift of the Frank-Starling relation maintained stroke volume during heat stress in aged adults (76 ± 8 vs. normothermic: 74 ± 8 ml, P = 0.38) despite reductions in cardiac filling pressure (6.6 ± 1.0 vs. normothermic: 8.9 ± 1.1 mmHg, P < 0.01). In a subset of participants, volume loading was used to return cardiac filling pressure during heat stress to normothermic values, which resulted in a greater stroke volume for a given cardiac filling pressure in both groups. These results demonstrate that the Frank-Starling relation shifts during heat stress in healthy young and aged adults, thereby preserving stroke volume despite reductions in cardiac filling pressures.


Simple Synthesis of 1,2-Dideoxy-2-Vinyl Carbohydrates by Tin-Free Radical Reactions of Xanthates.
Vinyl-substituted carbohydrates have been synthesized from glycals derived from hexoses and pentoses. Key step is the radical reaction of xanthates in the presence of triethylborane, a non-toxic reagent. The mechanism has been investigated by isolation of various side products, which speak for a reversibility of the cyclopropylmethyl radical ring-opening. Compared to reactions with tributyltin hydride, higher regioselectivities in favor of the 2-vinyl-substituted sugars have been obtained. Yields are slightly lower with triethylborane, but all products have been isolated in analytically pure form. The new reaction is applicable to benzyl- and silyl-protected carbohydrates, which makes free sugars accessible as well. Overall, more than 15 1,2-dideoxy-2-vinyl carbohydrates have been synthesized from simple precursors in only few steps.


Repair of strand breaks in superhelical DNA of ataxia telangiectasia lymphoblastoid cells.
A number of different assay methods have been used to study repair of strand breaks in DNA after exposure of cells to ionizing radiation. Use of these methods indicates that fibroblasts from patients with ataxia telangiectasia (AT), a multiform genetic disease exhibiting high sensitivity to ionizing radiation, have a normal ability to repair strand breaks in DNA. All of these methods determine the extent of breakage of DNA and the resealing of these breaks but do not provide information on restoration of DNA configuration in the nucleus. In this report we have used a sensitive technique to investigate restoration of the 3-dimensional structure of DNA in AT lymphoblastoid cells after exposure to ionizing radiation. This technique provides a means of lysing cells using a high concentration of salt and a non-ionic detergent, giving rise to structures called nucleoids which contain nuclear RNA and DNA, are depleted in protein, and sediment in a manner characteristic of supercoiled DNA. We have shown that the degree of supercoiling is the same in control and AT lymphoblastoid cells using sedimentation in the presence of ethidium bromide. The extent of breakage after exposure of cells to gamma-radiation, and the rate of repair of these breaks are similar in both cell types. Rate of repair of strand breaks is dose dependent and the restructured rapidly sedimenting complex behaves similarly, on sucrose gradients containing ethidium bromide, to that extracted from unirradiated cells.


Molecular phylogenetics and evolution of the endemic Hawaiian genus Adenophorus (Grammitidaceae).
Recent studies of the phylogeny of several groups of native Hawaiian vascular plants have led to significant insights into the origin and evolution of important elements of the Hawaiian flora. No groups of Hawaiian pteridophytes have been subjected previously to rigorous phylogenetic analysis. We conducted a molecular phylogenetic analysis of the endemic Hawaiian fern genus Adenophorus employing DNA sequence variation from three cpDNA fragments: rbcL, atpbeta, and the trnL-trnF intergenic spacer (IGS). In the phylogenetic analyses we employed maximum parsimony and Bayesian inference. Bayesian phylogenetic inference often provided stronger support for hypothetical relationships than did nonparametric bootstrap analyses. Although phylogenetic analyses of individual DNA fragments resulted in different patterns of relationships among species and varying levels of support for various clades, a combined analysis of all three sets of sequences produced one, strongly supported phylogenetic hypothesis. The primary features of that hypothesis are: (1) Adenophorus is monophyletic; (2) subgenus Oligadenus is paraphyletic; (3) the enigmatic endemic Hawaiian species Grammitis tenella is strongly supported as the sister taxon to Adenophorus; (4) highly divided leaf blades are evolutionarily derived in the group and simple leaves are ancestral; and, (5) the biogeographical origin of the common ancestor of the Adenophorus-G. tenella clade remains unresolved, although a neotropical origin seems most likely.


Treatment and outcome of the Dutch Childhood Craniopharyngioma Cohort study: First results after centralization of care.
Childhood craniopharyngioma (cCP) has excellent survival, but quality of life may be severely hampered by hypothalamic dysfunction. We aimed to evaluate treatment and hypothalamic outcomes of a Dutch cCP cohort, and evaluate the effect of centralization of care. A retrospective cohort study was performed, including cCP patients diagnosed between 2004 and 2021. Treatment characteristics and hypothalamic outcomes were evaluated and compared before and since centralization of care in May 2018. We included 87 cCP patients. Cyst drainage/fenestration was performed in 29.9%, limited resection in 27.6%, near-total resection in 16.1%, and gross total resection (GTR) in 25.4%. Radiotherapy was given in 46.0%. After a median follow-up of 6.5 years, hypothalamic obesity (HO) was present in 24.7% and panhypopituitarism with diabetes insipidus in 71.3%. Higher body mass index (BMI) SDS at diagnosis and Muller grade II at last magnetic resonance imaging of follow-up were associated with overweight/obesity. No association was found between extensiveness of resection and overweight/obesity at last follow-up. When comparing before and after centralization of care, rates of GTR remained similar, but BMI outcomes changed; mean ΔBMI SDS 1 year after diagnosis from 1.12 (SD 1.15) to 0.81 (SD 1.24), and HO after 1 year decreased from 33.3% to 12.0% (P = .067), and after 2 years from 28.6% to 6.7% (P = NS). In our nationwide cohort, GTR was performed in a relatively low percentage of patients and extensiveness of resection was no longer associated with HO at follow-up. A trend toward improvement of BMI is observed since centralization of care, which needs further exploration.


Mechanical energy profiles of the combined ankle-foot system in normal gait: insights for prosthetic designs.
Over the last half-century, the field of prosthetic engineering has continuously evolved with much attention being dedicated to restoring the mechanical energy properties of ankle joint musculatures during gait. However, the contributions of 'distal foot structures' (e.g., foot muscles, plantar soft tissue) have been overlooked. Therefore, the purpose of this study was to quantify the total mechanical energy profiles (e.g., power, work, and work-ratio) of the natural ankle-foot system (NAFS) by combining the contributions of the ankle joint and all distal foot structures during stance in level-ground steady state walking across various speeds (0.4, 0.6, 0.8 and 1.0 statures/s). The results from eleven healthy subjects walking barefoot indicated ankle joint and distal foot structures generally performed opposing roles: the ankle joint performed net positive work that systematically increased its energy generation with faster walking speeds, while the distal foot performed net negative work that systematically increased its energy absorption with faster walking speeds. Accounting for these simultaneous effects, the combined ankle-foot system exhibited increased work-ratios with faster walking. Most notably, the work-ratio was not significantly greater than 1.0 during the normal walking speed of 0.8 statures/s. Therefore, a prosthetic design that strategically exploits passive-dynamic properties (e.g., elastic energy storage and return) has the potential to replicate the mechanical energy profiles of the NAFS during level-ground steady-state walking.


Switching of the positive feedback for RAS activation by a concerted function of SOS membrane association domains.
Son of sevenless (SOS) is a guanine nucleotide exchange factor that regulates cell behavior by activating the small GTPase RAS. Recent in vitro studies have suggested that an interaction between SOS and the GTP-bound active form of RAS generates a positive feedback loop that propagates RAS activation. However, it remains unclear how the multiple domains of SOS contribute to the regulation of the feedback loop in living cells. Here, we observed single molecules of SOS in living cells to analyze the kinetics and dynamics of SOS behavior. The results indicate that the histone fold and Grb2-binding domains of SOS concertedly produce an intermediate state of SOS on the cell surface. The fraction of the intermediated state was reduced in positive feedback mutants, suggesting that the feedback loop functions during the intermediate state. Translocation of RAF, recognizing the active form of RAS, to the cell surface was almost abolished in the positive feedback mutants. Thus, the concerted functions of multiple membrane-associating domains of SOS governed the positive feedback loop, which is crucial for cell fate decision regulated by RAS.


Flow cytometry-based assay for titrating dengue virus.
Plaque assays for titrating dengue virus (DENV) are time-consuming and not suitable for strains that do not plaque. Fluorescence-activated cell sorting (FACS) has been used to detect DENV-infected cells. Here we describe a FACS-based assay for titrating DENV. We determined that at 24 h postinfection, the number of infected cells detected by FACS represented the first round of infection and therefore could be used as a readout of the number of infectious particles in the inoculum. When the titers of different laboratory and clinical strains of DENV were compared using FACS, plaque, and endpoint dilution assays, for most strains the FACS titers were comparable to titers obtained by plaque or endpoint dilution assays. The FACS assay is an improvement over the plaque assay because the infection period is reduced from 5 to 7 days to 24 h and the assay can be used to titrate clinical isolates that frequently do not form clear plaques on cell monolayers. The novel FACS-based methods described here will facilitate laboratory studies of dengue.


[Diagnostic significance of changes in the diastolic period of the heart cycle in ischemic heart disease patients undergoing head-down tilt loading].
In 62 patients with angina pectoris of different functional classes, physical stress tolerance has been compared to changes of apexcardiographic variables in the postural test. It has been demonstrated that anginal patients have abnormal relaxation velocity and left ventricular filling. Passive volume redistribution test allows one to reveal diastolic myocardial dysfunction, severity of which is related to the degree of coronary insufficiency.


miR-124, miR-137 and miR-340 regulate colorectal cancer growth via inhibition of the Warburg effect.
Colorectal cancer represents one of the most challenging diseases. Increasing evidence indicates that aberrant expression of microRNAs (miRNAs) is related to pathogenesis of colorectal cancer. Cancer cells reprogram metabolic pathways to sustain higher proliferation rates. Whether mechanisms underlying the role of miRNA in colorectal cancer are involved in metabolic reprogramming and the mechanisms through which miRNAs alter cancer metabolism are as yet unknown. Herein, we show that miR-124, miR-137 and miR-340 are associated with poor prognosis of colorectal cancer. Expression of these miRNAs inhibits the growth of colorectal cancer cells. PKM (pyruvate kinase isozyme) alternative splicing proteins (PTB1/hnRNAPA1/hnRNAPA2), which control the inclusion of exon 9 (PKM1) or exon 10 (PKM2), are targeted by miR-124, miR-137 and miR-340. Consequently, miR-124, miR-137 and miR-340 switch PKM gene expression from PKM2 to PKM1. High ratios of PKM1/PKM2 inhibit the glycolysis rate, but elevate the glucose flux into oxidative phosphorylation. These results demonstrate that miRNAs (miR-124, miR-137 and miR-340) impair colorectal cancer growth by counteracting the Warburg effect due to regulating alternative splicing of the PKM gene.


Converting a peptide into a drug: strategies to improve stability and bioavailability.
The discovery of peptide hormones, growth factors and neuropeptides implicated in vital biological functions of our organism has increased interest in therapeutic use of short peptides. However, the development of peptides as clinically useful drugs is greatly limited by their poor metabolic stability and low bioavailability, which is due in part to their inability to readily cross membrane barriers such as the intestinal and blood-brain barriers. The aim of peptide medicinal chemistry is, therefore, to develop strategies to overcome these problems. Recent progress in chemical synthesis and design have resulted in several strategies for producing modified peptides and mimetics with lower susceptibility to proteolysis and improved bioavailability, which has increased the probability of obtaining useful drugs structurally related to parent peptides. This review describes different experimental approaches to transforming a peptide into a potential drug and provides examples of the usefulness of these strategies.


Social Development in Children With Early Cochlear Implants: Normative Comparisons and Predictive Factors, Including Bilateral Implantation.
There are mixed results regarding psychosocial development in children with cochlear implants (CIs) compared with children with normal hearing (NH), and the effect of bilateral CIs has not yet been investigated. This study aimed to investigate whether social development differed between NH children and those with early CIs, and to identify new predictors of psychosocial development in children with early CIs. The psychosocial development, cognitive and language abilities of 159 children were measured as part of a longitudinal outcomes study of children with CIs. Parental involvement was also assessed. The children in this study did not differ significantly from their peers with NH in terms of their psychosocial development, except with regard to Prosocial Behavior, with parents reporting significantly poorer development in this area. Having bilateral CIs predicted significantly fewer difficulties with psychosocial development, with earlier age at implantation increasing the effect size of the second CI for Emotional Symptoms and Peer Problems. Receptive language ability, higher parent education, later birth order, high parent involvement, and female gender predicted significantly fewer parent reports of psychosocial problems. Higher child cognitive ability and greater screen time predicted significantly greater reported psychosocial difficulties. Marginal effects modeling quantified the effects of changes in the predictive factors examined. Psychosocial development in these children with early CIs was found to be similar to that for peers with NH, with the exception of delayed Prosocial Behavior development. Having bilateral CIs predicted significantly better emotional outcomes. A number of new predictive factors were found for psychosocial development. The results of the marginal effects modeling should be shared with parents and professionals to increase their understanding of the impact of changes in predictive factors, particularly in terms of their own contribution to psychosocial outcomes for children with CIs.


A study comparing two objective methods of quantifying the production of wound exudate.
The objective assessment of chronic wound therapies for exudate management (WRAP study) tested a variety of methods that could be used to improve understanding of dressing performance in the presence of wound exudate, including measurement of the levels of exudate production. The aim of this study was to identify a valid and reliable method of measuring wound exudate production per unit area of wound surface. Two methods were tested. Method A measured the weight of exudate collected in dressings by 'before and after' weighing of all dressing materials that came into contact with wound exudate. Method B measured wound exudate collected as part of topical negative pressure (TNP) therapy. Method A: Complete data were collected on three patients (at which point the study was halted), but it was only possible to obtain accurate measurements for two of these. Exudate production was 0.10g/cm2/24 hours and 0.21g/cm2/24 hours. It was time-consuming and required special equipment. Method B: Fifteen measurements from five patients were analysed and showed a mean exudate production of 1.3g/cm2/24 hours. There are problems with both methods of exudate measurement, but measuring wound fluid collected inTNP canisters seems simpler than weighing dressings and deserves further investigation.


TGF-β1 Inhibition of ACE2 Mediated by miRNA Uncovers Novel Mechanism of SARS-CoV-2 Pathogenesis.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for COVID-19, utilizes receptor binding domain (RBD) of spike glycoprotein to interact with angiotensin (Ang)-converting enzyme 2 (ACE2). Altering ACE2 levels may affect entry of SARS-CoV-2 and recovery from COVID-19. Decreased cell surface density of ACE2 leads to increased local levels of Ang II and may contribute to mortality resulting from acute lung injury and fibrosis during COVID-19. Studies published early during the COVID-19 pandemic reported that people with cystic fibrosis (PwCF) had milder symptoms, compared to people without CF. This finding was attributed to elevated ACE2 levels and/or treatment with the high efficiency CFTR modulators. Subsequent studies did not confirm these findings reporting variable effects of CFTR gene mutations on ACE2 levels. Transforming growth factor (TGF)-β signaling is essential during SARS-CoV-2 infection and dominates the chronic immune response in severe COVID-19, leading to pulmonary fibrosis. TGF-β1 is a gene modifier associated with more severe lung disease in PwCF but its effects on the COVID-19 course in PwCF is unknown. To understand whether TGF-β1 affects ACE2 levels in the airway, we examined miRNAs and their gene targets affecting SARS-CoV-2 pathogenesis in response to TGF-β1. Small RNAseq and micro(mi)RNA profiling identified pathways uniquely affected by TGF-β1, including those associated with SARS-CoV-2 invasion, replication, and the host immune responses. TGF-β1 inhibited ACE2 expression by miR-136-3p and miR-369-5p mediated mechanism in CF and non-CF bronchial epithelial cells. ACE2 levels were higher in two bronchial epithelial cell models expressing the most common CF-causing mutation in CFTR gene F508del, compared to controls without the mutation. After TGF-β1 treatment, ACE2 protein levels were still higher in CF, compared to non-CF cells. TGF-β1 prevented the modulator-mediated rescue of F508del-CFTR function while the modulators did not prevent the TGF-β1 inhibition of ACE2 levels. Finally, TGF-β1 reduced the interaction between ACE2 and the recombinant spike RBD by lowering ACE2 levels and its binding to RBD. Our data demonstrate novel mechanism whereby TGF-β1 inhibition of ACE2 in CF and non-CF bronchial epithelial cells may modulate SARS-CoV-2 pathogenicity and COVID-19 severity. By reducing ACE2 levels, TGF-β1 may decrease entry of SARS-CoV-2 into the host cells while hindering the recovery from COVID-19 due to loss of the anti-inflammatory and regenerative effects of ACE2. The above outcomes may be modulated by other, miRNA-mediated effects exerted by TGF-β1 on the host immune responses, leading to a complex and yet incompletely understood circuitry.


Managing for change. Models and questions for group practice leaders.
The health care environment continues to be characterized by rapid change and unpredictability. Perhaps the only constant is change itself. Managing successfully in this environment demands an increasing level of sophistication. In a rapidly changing environment, the manager must provide focus and direction and at the same time stay flexible so that the organization can quickly adjust to environmental demands. This article describes models for successful change management, followed by questions for the leader in a group practice.


A narrative review of South Asian patients' experiences of cardiac rehabilitation.
To review the empirical literature relating to South Asian patients' experiences of cardiac rehabilitation. Individuals of South Asian origin (originating from India, Pakistan, Bangladesh, or Sri Lanka) have increased risk of coronary heart disease-related mortality and morbidity. Low levels of cardiac rehabilitation participation have been reported among South Asian groups in several English-speaking countries. Narrative review. Primary research evidence published in English between 1999-2010 obtained using pre-defined search criteria in electronic databases MEDLINE, CINAHL, PubMed, EMBASE, Google Scholar and PsycINFO. Eleven studies met the inclusion criteria for review. Four prominent themes were identified in the literature related to: (1) exercise; (2) culture and religion; (3) programme access and structure; (4) communication and language. The emerging themes distilled from the review encompass several factors associated with South Asian patients' experiences of cardiac rehabilitation that are commensurate with low uptake and poor adherence. However, few researchers have disaggregated their data by ethnic origin to describe what might best meet the needs of South Asian patients. Further research is needed to thoughtfully address issues of uptake of and compliance with cardiac rehabilitation by South Asian patients and to support the development of culturally sensitive and safe CR programmes. The findings from this review can help nurses to develop guidelines for the design and delivery of culturally competent South Asian cardiac rehabilitation programmes. Important considerations related to physical exercise, language and communication preferences, religious and cultural needs and programme access and structure, need to be addressed in a culturally relevant and culturally sensitive manner to enhance the uptake and efficacy of cardiac rehabilitation for South Asian individuals.


Benefits of pre-operative oral Sucrosomial® iron supplementation in cardiac surgery: influence of patient's baseline hemoglobin and gender.
The prevalence of low pre-operative hemoglobin (Hb) among cardiac surgery patients is high. As iron homeostasis is often impaired in these patients, restoration of iron availability might over-ride iron-restricted erythropoiesis. This post-hoc analysis of a previously published, large, randomized clinical trial (ClincalTrials.gov NCT03560687; n=1,000) assesses which sub-cohort of patients benefits the most from pre-operative Hb optimization with oral Sucrosomial® iron. Patients without baseline Hb (n=349) or receiving >5 red blood cell units (n=57) were excluded from the study. Data from the remaining 594 were reanalyzed according to treatment, baseline anemia (Hb <13 g/dL) or gender. Patients (pt) received a one-month course of 60 mg/day Sucrosomial® iron (Iron group, n=309) or routine care (Control group, n=285) prior to elective cardiac surgery. Main end-point variables were increase in Hb from randomization to hospital admission, transfusion requirements, and cost-effectiveness of Sucrosomial® iron administration. At hospital admission, Hb had increased 0.7 g/dL and 0.1 g/dL, for Iron and Control groups, respectively (p<0.001), with no gender-related differences, leading to a decrease in transfusion rate (30 vs 59%, respectively; p<0.001) and transfusion index (0.5 units/patient vs 1.2 units/pt, respectively; p<0.001). Sucrosomial® iron administration was well-tolerated, and yielded cost-savings of €92/pt (p<0.001), particularly in those presenting with baseline Hb <13 g/dL. This post-hoc analysis confirms pre-operative Sucrosomial® iron administration is a safe and cost-effective strategy to increase preoperative Hb and decrease transfusion requirements in elective cardiac surgery, especially in those anemic at baseline.


Genetic and environmental factors in scleroderma.
Recent epidemiologic research on scleroderma has been directed toward both genetic and environmental factors. The nature of any genetic contribution is unknown, although the major histocompatibility complex region is important in determining antibody response. Environmentally, an occupational basis in a small proportion of cases seems likely. There is no evidence to support the hypothesis that silicone gel breast implants are an important risk factor in the development of scleroderma.


[Prolonged exposure to intravesical foreign body induces a giant calculus with attendant renal dysfunction].
A 31-year-old man came to our hospital complaining of severe voiding pain. He had inserted a fishing line made of nylon into his urethra at the age of eighteen, which was unable to be taken out and had been left there for 13 years. Preoperative ultrasonogram showed severe bilateral hydronephrosis and the serum BUN and creatinine level were as high as 45.2 mg/dl and 4.8 mg/dl, respectively. A huge bladder stone was demonstrated in X-ray film, the patient was admitted and vesicolithotomy was performed. The size of the stone was 10.5 x 7.5 x 7.5 cm and the weight was 360 grams. The fishing line was found inside the stone and the length was over 3 meters. The serum BUN and creatinine level after the operation were still high as 28.4 mg/dl and 4.1 mg/dl, respectively, and they did not improve even after six months following.


Frequency and severity of carpal tunnel syndrome according to level of cervical radiculopathy: double crush syndrome?
The double crush hypothesis (DC) proposes that a proximal lesion along an axon predisposes it to injury at a more distal site along its course through impaired axoplasmic flow. The frequency and severity of carpal tunnel syndrome (CTS) according to the level of cervical radiculopathy were investigated to evaluate the hypothesis of DC. The frequency of CTS was investigated in 277 patients with C6, C7 or C8 radiculopathies and correlation between CTS and radiculopathy level was determined. We also investigated whether the degrees of abnormal sensory responses were more severe in C6, C7 radiculopathies and whether motor responses were more severe in C8 radiculopathy. Thirty-nine patients were diagnosed with CTS and concomitant cervical radiculopathy at the C6, 7, or C8 root levels. The frequency of coexisting CTS was not statistically different according to the level of radiculopathy. The electrophysiologic results revealed no significant correlation between median sensory parameters and C6, C7 cases, and no relationship was observed between median motor responses and C8 radiculopathy. The frequency and electrophysiologic data of CTS analyzed according to cervical radiculopathy level do not support a neurophysiological explanation. Based on this study, the DC hypothesis could not be supported.


Comparisons between ethnic groups in hospitalizations for respiratory syncytial virus bronchiolitis in Israel.
Ethnic disparities have been shown in respiratory syncytial virus (RSV) bronchiolitis. However, it is unclear whether such differences are related to access to care. We compared demographic and clinical characteristics of Arab and Jewish children hospitalized for RSV bronchiolitis in Israel, a country with universal health insurance. We reviewed the medical records of all children (n = 309) aged less than 24 months who were hospitalized with RSV between 2008 and 2011 in one medical center in Israel. Demographic, clinical, laboratory and radiological data were collected. The RSV antigen was identified using immunochromatography. The annual incidence of RSV hospitalization was 5.4/1000 and 6.8/1000 among Arab and Jewish children, respectively. Arab patients were significantly younger and had significantly younger parents; most lived in low socioeconomic status towns (93.7% vs. 13.3%; p<0.001) and had more siblings (median 2 vs. 1; p = 0.01) compared to Jewish patients. Disease severity did not differ between the two ethnic groups (p = 0.3). The main predictors of severe illness were having pneumonia (adjusted odds ratio [OR] 3.86; 95% confidence intervals [CI] 1.87-7.97) and history of respiratory diseases (adjusted OR 3.89; 95% CI 1.22-12.38). The incidence of hospitalizations for RSV bronchiolitis tended to be higher among Jewish than Arab children, possibly due to differences in health care utilization patterns. Differences between the Jewish and Arab patients in demographic factors likely mirror differences between the groups in the general population. Pneumonia, and not ethnicity, affected the severity of RSV bronchiolitis.


Deletion of IL-4 receptor alpha on dendritic cells renders BALB/c mice hypersusceptible to Leishmania major infection.
In BALB/c mice, susceptibility to infection with the intracellular parasite Leishmania major is driven largely by the development of T helper 2 (Th2) responses and the production of interleukin (IL)-4 and IL-13, which share a common receptor subunit, the IL-4 receptor alpha chain (IL-4Rα). While IL-4 is the main inducer of Th2 responses, paradoxically, it has been shown that exogenously administered IL-4 can promote dendritic cell (DC) IL-12 production and enhance Th1 development if given early during infection. To further investigate the relevance of biological quantities of IL-4 acting on DCs during in vivo infection, DC specific IL-4Rα deficient (CD11c(cre)IL-4Rα(-/lox)) BALB/c mice were generated by gene targeting and site-specific recombination using the cre/loxP system under control of the cd11c locus. DNA, protein, and functional characterization showed abrogated IL-4Rα expression on dendritic cells and alveolar macrophages in CD11c(cre)IL-4Rα(-/lox) mice. Following infection with L. major, CD11c(cre)IL-4Rα(-/lox) mice became hypersusceptible to disease, presenting earlier and increased footpad swelling, necrosis and parasite burdens, upregulated Th2 cytokine responses and increased type 2 antibody production as well as impaired classical activation of macrophages. Hypersusceptibility in CD11c(cre)IL-4Rα(-/lox) mice was accompanied by a striking increase in parasite burdens in peripheral organs such as the spleen, liver, and even the brain. DCs showed increased parasite loads in CD11c(cre)IL-4Rα(-/lox) mice and reduced iNOS production. IL-4Rα-deficient DCs produced reduced IL-12 but increased IL-10 due to impaired DC instruction, with increased mRNA expression of IL-23p19 and activin A, cytokines previously implicated in promoting Th2 responses. Together, these data demonstrate that abrogation of IL-4Rα signaling on DCs is severely detrimental to the host, leading to rapid disease progression, and increased survival of parasites in infected DCs due to reduced killing effector functions.


Coexistence of Graves' disease and struma ovarii: case report and literature review.
We report a rare case of Graves' disease associated with struma ovarii. A 26-year-old Japanese woman had preexisting Graves' disease and was positive for TSH receptor antibody. She had been on antithyroid medication at presentation. She noted a mass in the lower left abdomen, which was diagnosed as a left struma ovarii by radiological work-up including computed tomography, magnetic resonance imaging and scintigraphy. The surgically excised teratomatous tumor, containing cystic spaces with thyroid tissue, was histologically proved to be struma ovarii. Since thyroid function tests and TSH receptor antibody did not change after surgery, her hyperthyroidism was considered to be due to Graves' disease. Our case was diagnosed as struma ovarii before surgery using various imaging studies.


Effects of labelling on income, work and social function among hypertensive employees.
Two hundred and thirty hypertensive Canadian steelworkers were followed for 5 years after screening and referral. Data on income, absenteeism and measures of work and social function were collected on these men and on a matched group of 230 normotensive employees. In the fifth year after screening, hypertensive employees earned an average of Can. $1093 less than normotensive employees despite similar incomes in the year before screening. This adverse effect on income was observed regardless of awareness of hypertension at the time of screening or compliance with treatment. Illness-related absenteeism among hypertensives rose in the year following screening and remained elevated for 4 years after screening. Normotensive and hypertensive employees reported similar levels of physical ability and psychological well-being. These findings need verification in other settings before inclusion in cost-effectiveness analyses of the management of hypertension.


Study of fallopian tube anatomy and mechanical properties to determine pressure limits for endoscopic exploration.
Falloposcopy is the endoscopic examination of the fallopian tubes, which are challenging to access due to their deep body location, small opening from the uterus, and lumen filled with plicae. We and others have developed endoscopes that are inserted through the uterus guided by a hysteroscope into the tubal ostium. To better understand how to utilize these endoscopes either as standalone devices or in concert with everting delivery balloons, a preliminary study of anatomy and mechanical behavior was performed ex vivo on porcine and human fallopian tubes. Segments of fallopian tubes from the isthmus, ampulla and infundibulum were inflated with saline either to bursting or held at sub-burst pressures with saline or a saline-filled balloon. Formalin fixed, paraffin embedded tissue sections stained with Masson's trichrome were examined for damage to the mucosa and muscularis. Porcine fallopian tubes tolerated saline pressurization at 15 psi for 1 minute without morphological damage. Balloon inflation to 15 psi caused no apparent damage to the muscle layer or rupture of the fallopian tube, but balloon movement within the tube can denude the mucosal epithelial layer. Human fallopian tubes averaged higher burst pressure values than porcine tubes. Under pressurization, the external tube diameter expanded by minimal to moderate amounts. Human and porcine tissues were similar in histological appearance. These studies suggest that moderate pressurization is acceptable but will not appreciably expand the fallopian tube diameter. The results also indicate that pigs are a reasonable model to study damage from falloscopy as seen in human tissue.


Does farming experience matter? A comparison of farm health and safety attitudes, perceptions, and intentions of agricultural science students with and without farming experience.
This study addresses two main questions: 'How does having the experience of farming influence college students' intrinsic motivations towards farm health and safety (FHS)?' and 'Are there any differences between the motivations reported by students with and without having such experience?'. This study seeks to investigate the role of farming experience in students' cognitive factors and intentions to evaluate whether sharing experiences and stories positively shape students' cognitive factors to perform FHS behaviours. A cross-sectional online survey using a semi-structured questionnaire was assigned to a nationally representative sample of agricultural science students in Ireland (n= 430). Applying independent sample t-test and ANOVA test, multiple comparisons were made to examine if having the experience of farming affects FHS intrinsic motivations. This study illustrated students without farming experience are less likely to perceive farming as a dangerous occupation while they reported a slightly positive attitude and intention compared with their counterparts with experience of farming. Our study illustrated students with experience of farming gave a lower priority to FHS and control over safety behaviour (pessimistic approach) and they reported a slightly higher level of risk perception (optimistic perception). Having experience of farming (destructive experience - the experience of farming without having a near miss or injury or having heard of accidents, ie negative factors affecting students' motivations) may not be necessarily a positive factor as risk-taking is admitted as a norm and a part of the nature of the work. Conversely, having experience of FHS issues (constructive experience - any kind of farming experience that positively shapes students' motivations towards FHS) can positively shape attitude, perceptions, and intention. Therefore, we recommend that constructive experiences (positive affecting intrinsic motivations) should be incorporated into the FHS training of students through peer-to-peer sharing as this enhances attitudes, perceptions, and willingness of the majority of students.


Comprehensive Review on Colorectal Cancer and Transplant.
Colorectal cancer (CRC) is a common malignancy worldwide. Some studies suggest that organ recipients are at a higher risk for CRC than the general population. The underlying transplant indications and their inherent risk factors for CRC may drive the variation in incidence rates that are seen in patients receiving different allografts. Recipients with cystic fibrosis are now recognized as a population at high risk for CRC at a young age. Transplant recipients have high mortality following a CRC diagnosis, even if it is detected at an early stage. Certain types of immunosuppression have been shown to accelerate cancer transformation and may contribute to the more aggressive phenotype seen in organ recipients. Given the high incidence and progressive nature of posttransplant CRC, shorter screening intervals with a modality that can detect early-stage polyps may be essential to prevent mortality. Future research is needed to better elucidate the role of immunosuppression in carcinogenesis. This comprehensive review examines CRC risk, screening, and management specific to organ transplant candidates and recipients.


Risk factors for mental disorder development in asylum seekers and refugees resettled in Western Europe and Turkey: Participant-level analysis of two large prevention studies.
In asylum seekers and refugees, the frequency of mental disorders, such as depression, anxiety and post-traumatic stress disorder, is higher than the general population, but there is a lack of data on risk factors for the development of mental disorders in this population. This study investigated the risk factors for mental disorder development in a large group of asylum seekers and refugees resettled in high- and middle-income settings. Participant-level data from two randomized prevention studies involving asylum seekers and refugees resettled in Western European countries and in Turkey were pooled. The two studies randomized participants with psychological distress, but without a diagnosis of mental disorder, to the Self-Help Plus psychological intervention or enhanced care as usual. At baseline, exposure to potentially traumatic events was measured using the Harvard Trauma Questionnaire-part I, while psychological distress and depressive symptoms were assessed with the General Health Questionnaire and the Patient Health Questionnaire. After 3 and 6 months of follow-up, the proportion of participants who developed a mental disorder was calculated using the Mini International Neuropsychiatric Interview. A total of 1,101 participants were included in the analysis. At 3- and 6-month follow-up the observed frequency of mental disorders was 13.51% (115/851) and 24.30% (207/852), respectively, while the frequency estimates after missing data imputation were 13.95% and 23.78%, respectively. After controlling for confounders, logistic regression analysis showed that participants with a lower education level (p = .034), a shorter duration of journey (p = .057) and arriving from countries with war-related contexts (p = .017), were more at risk of developing mental disorders. Psychological distress (p = .004), depression (p = .001) and exposure to potentially traumatic events (p = .020) were predictors of mental disorder development. This study identified several risk factors for the development of mental disorders in asylum seekers and refugees, some of which may be the target of risk reduction policies. The identification of asylum seekers and refugees at increased risk of mental disorders should guide the implementation of focused preventative psychological interventions.


Bullous pemphigoid: role of complement and mechanisms for blister formation within the lamina lucida.
Bullous pemphigoid (BP), an autoimmune subepidermal blistering skin disease, demonstrates tense blisters with or without widespread erythema, blistering along the lamina lucida, immunoglobulin G and/or complement deposits at the basement membrane zone, and the presence of circulating autoantibodies against hemidesmosomal molecules. These autoantibodies usually react against 180-kDa and/or 230-kDa proteins, designated as BP180 and BP230, respectively. The precise blistering mechanisms after autoantibodies bind to antigens are not fully understood. Immune complexes are thought to initially activate the complement cascade, which may induce activation of proteases and/or cytokines and cause dermal-epidermal separation. However, why does separation run specifically within the lamina lucida in a space as narrow as 500 nm wide? This review mainly focuses on the possible mechanisms of BP-specific blistering and how separation occurs along the lamina lucida, based on existing evidence.


Structure and luminescence evolution of annealed Europium-doped silicon oxides films.
Europium (Eu)-doped silicon oxide films with Eu concentrations from 2.1 to 4.7 at. % were deposited by electron beam evaporation. The Eu related luminescence from the films was found to be sensitive to the evolution of film microstructures at different annealing temperatures. Luminescence centers in the films changed from defects of silicon oxides to 4f(6)5d-4f(7)(8S(7/2)) transition of Eu2+ after the films annealed in N2 at temperature higher than 800 °C. The evolution of luminescence centers was attributed to the formation of europium silicate (EuSiO3), which was confirmed by x-ray photoelectron spectroscopy, x-ray diffraction, time resolved photoluminescence, and transmission electron microscopy.


T-cell receptor (TCR) signaling promotes the assembly of RanBP2/RanGAP1-SUMO1/Ubc9 nuclear pore subcomplex via PKC-θ-mediated phosphorylation of RanGAP1.
The nuclear pore complex (NPC) is the sole and selective gateway for nuclear transport, and its dysfunction has been associated with many diseases. The metazoan NPC subcomplex RanBP2, which consists of RanBP2 (Nup358), RanGAP1-SUMO1, and Ubc9, regulates the assembly and function of the NPC. The roles of immune signaling in regulation of NPC remain poorly understood. Here, we show that in human and murine T cells, following T-cell receptor (TCR) stimulation, protein kinase C-θ (PKC-θ) directly phosphorylates RanGAP1 to facilitate RanBP2 subcomplex assembly and nuclear import and, thus, the nuclear translocation of AP-1 transcription factor. Mechanistically, TCR stimulation induces the translocation of activated PKC-θ to the NPC, where it interacts with and phosphorylates RanGAP1 on Ser504 and Ser506. RanGAP1 phosphorylation increases its binding affinity for Ubc9, thereby promoting sumoylation of RanGAP1 and, finally, assembly of the RanBP2 subcomplex. Our findings reveal an unexpected role of PKC-θ as a direct regulator of nuclear import and uncover a phosphorylation-dependent sumoylation of RanGAP1, delineating a novel link between TCR signaling and assembly of the RanBP2 NPC subcomplex.


The Use of Smoothelin and Other Antibodies in the Diagnosis of Uterine and Soft Tissue Smooth Muscle Tumors.
Smoothelin is a cytoplasmic protein expressed in differentiated smooth muscle cells. Immunohistochemical evaluation of smoothelin has previously been reported in gastrointestinal (GI) smooth muscle tumors, but has yet to be studied in smooth muscle tumors of uterine and other soft tissue origin. DOG1 expression is reported to be specific for GI stromal tumors; however, variable expression has been reported in leiomyosarcomas (LMS) depending on site of origin. Overexpression of p16 is common in LMS of uterine and other sites of origin, but has not been correlated with tumor grade. This study explores the differential expression of these markers, as well as caldesmon, in LMS cases to assess diagnostic utility. Using tissue microarrays and cases from Tulane Medical Center and Medical College of Wisconsin, expression of smoothelin, DOG1, caldesmon, and p16 was evaluated by immunohistochemistry in 87 cases of LMS. The cases were subdivided by location of origin into uterine (N=31) and nonuterine (N=56) with 10 of the nonuterine of GI origin, as well as by grade into low grade (N=27) and intermediate and high grade (N=60). Differential expression among different grades and locations was evaluated. The same markers were evaluated in atypical leiomyoma cases (N=4) and 1 smooth muscle tumor of uncertain malignant potential case (N=1). Smoothelin expression was also assessed in 20 benign uterine leiomyomas. Weak DOG1 expression is rare but possible in extrauterine LMS. Expression of p16 is common in both uterine and extrauterine LMS, and more frequent in higher grades. Expression of smoothelin in this study differed depending on tumor type, grade, and site of origin. All leiomyomas and most atypical leiomyomas showed cytoplasmic positivity for smoothelin, whereas only 5% of LMS had cytoplasmic expression. The study suggests smoothelin may be downregulated in the cytoplasm of malignant smooth muscle tumor cells and may serve as a supportive aid in the distinction of LMS from benign smooth muscle tumors in cases where it is difficult by morphology alone.


Screening for blunt cerebrovascular injuries: the essential role of computed tomography angiography.
The implementation of aggressive diagnostics refuted the thesis that blunt cerebrovascular injuries (BCVI) are rare events. Given the estimates from recent studies, the prevalence may be as high as 1 per 100 among blunt multiple trauma patients. The morbidity and mortality of unrecognized and untreated BCVI is exceptionally high and warrants distinct efforts to detect these injuries during the primary trauma survey. The primary goal is to detect BCVI before neurological symptoms occur, and to introduce anticoagulation or antiplatelet therapy as appropriate. Index injuries such as cervical spine fractures increase the prior probability of disease, but are not helpful in ruling BCVI out. Computed tomography angiography (CTA) may represent the screening tool of choice, although there is still limited evidence about its accuracy. Pooled data from six studies (1368 patients) published between 2002 and 2006 suggest a sensitivity of 79% and a specificity of 97% in the trauma setting. In the two largest investigations, no false negative results were observed. Further research is needed to determine the efficacy of CTA for disclosing BCVI, and to evaluate the potential benefits to patients.


Genetically unmatched human iPSC and ESC exhibit equivalent gene expression and neuronal differentiation potential.
The potential uniformity between differentiation and therapeutic potential of human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) remains debatable. We studied the gene expression profiles, pathways analysis and the ability to differentiated into neural progenitor cells (NPCs) and motor neurons (MNs) of genetically unmatched integration-free hiPSC versus hESC to highlight possible differences/similarities between them at the molecular level. We also provided the functional information of the neurons derived from the different hESCs and hiPSCs lines using the Neural Muscular Junction (NMJ) Assay. The hiPSC line was generated by transfecting human epidermal fibroblasts (HEF) with episomal DNAs expressing Oct4, Sox2, Klf4, Nanog, L-Myc and shRNA against p53. For the hESCs line, we used the NIH-approved H9 cell line. Using unsupervised clustering both hESCs and hiPSCs were clustered together implying homogeneous genetic states. The genetic profiles of hiPSCs and hESCs were clearly similar but not identical. Collectively, our data indicate close molecular similarities between genetically unmatched hESCs and hiPS in term of gene expression, and signaling pathways. Moreover, both cell types exhibited similar cholinergic motor neurons differentiation potential with marked ability of the differentiated hESCs and hiPSCs-derived MNs to induce contraction of myotubes after 4 days of co-culture.


Somatic gain-of-function mutations in BUD13 promote oncogenesis by disrupting Fbw7 function.
Somatic mutations occurring on key enzymes are extensively studied and targeted therapies are developed with clinical promises. However, context-dependent enzyme function through distinct substrates complicated targeting a given enzyme. Here, we develop an algorithm to elucidate a new class of somatic mutations occurring on enzyme-recognizing motifs that cancer may hijack to facilitate tumorigenesis. We validate BUD13-R156C and -R230Q mutations evading RSK3-mediated phosphorylation with enhanced oncogenicity in promoting colon cancer growth. Further mechanistic studies reveal BUD13 as an endogenous Fbw7 inhibitor that stabilizes Fbw7 oncogenic substrates, while cancerous BUD13-R156C or -R230Q interferes with Fbw7Cul1 complex formation. We also find this BUD13 regulation plays a critical role in responding to mTOR inhibition, which can be used to guide therapy selections. We hope our studies reveal the landscape of enzyme-recognizing motif mutations with a publicly available resource and provide novel insights for somatic mutations cancer hijacks to promote tumorigenesis with the potential for patient stratification and cancer treatment.


Divergent effects of different antihypertensive drugs on endothelium-dependent vasodilation in the human forearm.
Several studies indicated an abnormal endothelium-dependent vasodilation (EDV) in hypertensive patients, but no study has systematically investigated the effects of different pharmacologic classes of antihypertensive drugs on EDV. This study aimed to evaluate the effects of three different antihypertensive regimens [angiotensin-converting enzyme (ACE) inhibition, calcium channel blockade, and beta-blockade] on EDV when given locally in the forearm at a constant blood pressure. The increase in forearm blood flow (FBF) during local intraarterial infusions of methacholine (MCh; inducing EDV) and sodium nitroprusside (SNP; inducing endothelium-independent vasodilation, EIDV) was measured in young, normotensive subjects by venous occlusion plethysmography, before and during concomitant local intraarterial infusion of any of the antihypertensive drugs. Without changing baseline FBF, enalaprilat (n=6, 2.4 mg/h) potentiated the increase in FBF induced by MCh [from 22.6+/-2.3 (SD) to 25.4+/-2.3 ml/min/100 ml tissue at 4 microg/min; p < 0.05], but the response to SNP was unchanged. Local intraarterial verapamil infusion (n=6), at a dose individually titrated to keep baseline FBF unchanged, did not alter the response to MCh infusion, whereas the response to SNP was potentiated. A higher dose of verapamil (n=6), which increased baseline FBF, increased both EDV and EIDV significantly in parallel (p < 0.05). The local propranolol infusion (n=6, 1.2 mg/h) attenuated the FBF response to MCh significantly (from 28.9+/-5.7 to 21.5+/-3.2 ml/min/100 ml tissue at 4 microg/min; p < 0.05), whereas both baseline FBF and the response to SNP were unchanged. In conclusion, this investigation showed that commonly used antihypertensive drugs affect endothelial vasodilator function in a different ways. ACE inhibition enhanced EDV, whereas a nonselective beta-blocker attenuated EDV. The calcium channel blocker, verapamil, improved both EDV and EIDV, probably by a direct effect on the vascular smooth-muscle cells.


Ginsenoside Rh4 induces apoptosis and autophagic cell death through activation of the ROS/JNK/p53 pathway in colorectal cancer cells.
The use of ginsenosides in cancer therapy has been intensively investigated. The ginsenoside Rh4 (Rh4), a rare saponin obtained from Panax notoginseng, dissolves in water more readily than total saponins, making this compound easier to use in anti-cancer pharmaceutics. Here, we investigated the antiproliferative activity and mechanisms of Rh4 in colorectal cancer, both in vivo and in vitro. A colorectal cancer xenograft model showed that Rh4 significantly inhibited tumor growth with few side effects. CCK-8 assays, flow cytometric analysis, Western blotting and immunohistochemistry revealed that Rh4 effectively suppressed colorectal cancer cell proliferation via inducing G0/G1 phase arrest, caspase-dependent apoptosis and autophagic cell death but was not significantly cytotoxic to normal colon epithelial cells. Furthermore, apoptosis played a dominant role in Rh4-induced cell death, as the pan-caspase inhibitor Z-VAD-FMK blocked cell death to a greater extent than the autophagy inhibitor 3-methyladenine. Moreover, Rh4 increased reactive oxygen species (ROS) accumulation and subsequently activated the JNK-p53 pathway. An ROS scavenger and JNK and p53 inhibitors significantly attenuated Rh4-induced apoptosis and autophagy. Thus, the present study is the first to illustrate that Rh4 triggers apoptosis and autophagy via activating the ROS/JNK/p53 pathway in colorectal cancer cells, providing basic scientific evidence that Rh4 shows great potential as an anti-cancer agent.


Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial.
Elderly patients are often under-represented in clinical trials of metastatic colorectal cancer. We aimed to assess the efficacy and safety of bevacizumab plus capecitabine compared with capecitabine alone in elderly patients with metastatic colorectal cancer. For this open-label, randomised phase 3 trial, patients aged 70 years and older with previously untreated, unresectable, metastatic colorectal cancer, who were not deemed to be candidates for oxaliplatin-based or irinotecan-based chemotherapy regimens, were randomly assigned in a 1:1 ratio via an interactive voice-response system, stratified by performance status and geographical region. Treatment consisted of capecitabine (1000 mg/m(2) orally twice a day on days 1-14) alone or with bevacizumab (7·5 mg/kg intravenously on day 1), given every 3 weeks until disease progression, unacceptable toxic effects, or withdrawal of consent. Efficacy analyses were based on the intention-to-treat population. The primary endpoint was progression-free survival. The trial is registered with ClinicalTrials.gov, number NCT00484939. From July 9, 2007, to Dec 14, 2010, 280 patients with a median age of 76 years (range 70-87) were recruited from 40 sites across ten countries. Patients were randomly assigned to receive either bevacizumab plus capecitabine (n=140) or capecitabine only (n=140). Progression-free survival was significantly longer with bevacizumab and capecitabine than with capecitabine alone (median 9·1 months [95% CI 7·3-11·4] vs 5·1 months [4·2-6·3]; hazard ratio 0·53 [0·41-0·69]; p<0·0001). Treatment-related adverse events of grade 3 or worse occurred in 53 (40%) patients in the combination group and 30 (22%) in the capecitabine group, and treatment-related serious adverse events in 19 (14%) and 11 (8%) patients. The most common grade 3 or worse adverse events of special interest for bevacizumab or chemotherapy were hand-foot syndrome (21 [16%] vs nine [7%]), diarrhoea (nine [7%] vs nine [7%]), and venous thromboembolic events (11 [8%] vs six [4%]). Treatment-related deaths occurred in five patients in the combination group and four in the capecitabine group. The most common any-grade adverse event of special interest for bevacizumab was haemorrhage (34 [25%] vs nine [7%]). The combination of bevacizumab and capecitabine is an effective and well-tolerated regimen for elderly patients with metastatic colorectal cancer. F Hoffmann-La Roche.


Pulmonary hypertension associated with congenital heart disease: pulmonary vascular disease: the global perspective.
The incidence of congenital heart disease is approximately 8/1,000 live births and appears to be constant around the world. The currently accepted paradigm for the development of pulmonary vascular disease associated with congenital heart disease maintains that increased pulmonary blood flow and pressure trigger unfavorable vascular remodeling. Endothelial cell dysfunction, abnormal shear stress, circumferential wall stretch, and an imbalance in vasoactive mediators conspire to promote vasoconstriction, inflammation, thrombosis, cell proliferation, impaired apoptosis, and fibrosis. We estimate that worldwide 3 million children are at risk for the development of pulmonary vascular disease due to congenital heart disease. The majority of children at risk globally will have a reparable heart defect, such as an isolated atrial septal or ventricular septal defect or patent ductus arteriosus. Cardiac repair in the first 2 years of life would prevent the development of Eisenmenger syndrome, the most advanced form of pulmonary vascular disease secondary to congenital heart disease. Worldwide, only a small fraction of those at risk are offered surgical repair. Thus, access to timely medical care would eliminate the vast majority of suffering, disability, and death from Eisenmenger syndrome. Globally, pulmonary vascular disease associated with congenital heart disease may be the most preventable cause of pulmonary artery hypertension and related mortality and morbidity.


Fast query for exemplar-based image completion.
In this paper, we present a fast algorithm for filling unknown regions in an image using the strategy of exemplar-matching. Unlike the original exemplar-based method using exhaustive search, we decompose exemplars into the frequency coefficients and select fewer coefficients which are the most significant to evaluate the matching score. We have also developed a local gradient-based algorithm to fill the unknown pixels in a query image block. These two techniques bring the ability of input with varied dimensions to the fast query of similar image exemplars. The fast query is based upon a search-array data structure, and can be conducted very efficiently. Moreover, the evaluation of search-arrays runs in parallel maps well on the modern graphics hardware with graphics processing units (GPU). The functionality of the approach has been demonstrated by experimental results on real photographs.


[Surgical treatment of injuries and cicatricial strictures of the bile ducts using changeable transhepatic drainage].
Results of 62 reconstructive and restorative operations performed on 47 patients with scarry strictures and injuries of main bile ducts are analyzed. A group of 17 patients was chosen, a spare transhepatic drain being used in 18 operations. It was established that bougieurage, dilatation of the strictures and a continuous frame drainage with the stricture of hepaticocholedochus as long as 20 mm or recurrent strictures of hepaticojejunoanastomosis provided stabilization of scarring and epithelization of the stricture zone. A favorable result of the treatment is determined by the duration of the frame drainage not less than for 2 years.


BslA-stabilized emulsion droplets with designed microstructure.
Emulsions are a central component of many modern formulations in food, pharmaceuticals, agrichemicals and personal care products. The droplets in these formulations are limited to being spherical as a consequence of the interfacial tension between the dispersed phase and continuous phase. The ability to control emulsion droplet morphology and stabilize non-spherical droplets would enable the modification of emulsion properties such as stability, substrate binding, delivery rate and rheology. One way of controlling droplet microstructure is to apply an elastic film around the droplet to prevent it from relaxing into a sphere. We have previously shown that BslA, an interfacial protein produced by the bacterial genus Bacillus, forms an elastic film when exposed to an oil- or air-water interface. Here, we highlight BslA's ability to stabilize anisotropic emulsion droplets. First, we show that BslA is capable of arresting dynamic emulsification processes leading to emulsions with variable morphologies depending on the conditions and emulsification technique applied. We then show that frozen emulsion droplets can be manipulated to induce partial coalescence. The structure of the partially coalesced droplets is retained after melting, but only when there is sufficient free BslA in the continuous phase. That the fidelity of replication can be tuned by adjusting the amount of free BslA in solution suggests that freezing BslA-stabilized droplets disrupts the BslA film. Finally, we use BslA's ability to preserve emulsion droplet structural integrity throughout the melting process to design emulsion droplets with a chosen shape and size.


Strategies in the prevention and management of ventilator-associated pneumonia.
Ventilator-associated pneumonia (VAP) is a leading cause of morbidity and mortality in the intensive care unit. Prevention of VAP is possible through the use of several evidence-based strategies intended to minimize intubation, the duration of mechanical ventilation, and the risk of aspiration of oropharyngeal pathogens. Current data favor the quantitative analysis of lower respiratory tract cultures for the diagnosis of VAP, accompanied by the initiation of broad-spectrum empiric antimicrobial therapy based on patient risk factors for infection with multi-drug-resistant pathogens and data from unit-specific antibiograms. Eventual choice of antibiotic and duration of therapy are selected based on culture results and patient stability, with an emphasis on minimization of unnecessary antibiotic use.


DUSP5-mediated inhibition of smooth muscle cell proliferation suppresses pulmonary hypertension and right ventricular hypertrophy.
Pulmonary hypertension (PH) is associated with structural remodeling of pulmonary arteries (PAs) because of excessive proliferation of fibroblasts, endothelial cells, and smooth muscle cells (SMCs). The peptide hormone angiotensin II (ANG II) contributes to pulmonary vascular remodeling, in part, through its ability to trigger extracellular signal-regulated kinase (ERK1/2) activation. Here, we demonstrate that the ERK1/2 phosphatase, dual-specificity phosphatase 5 (DUSP5), functions as a negative regulator of ANG II-mediated SMC proliferation and PH. In contrast to wild-type controls, Dusp5 null mice infused with ANG II developed PH and right ventricular (RV) hypertrophy. PH in Dusp5 null mice was associated with thickening of the medial layer of small PAs, suggesting an in vivo role for DUSP5 as a negative regulator of ANG II-dependent SMC proliferation. Consistent with this, overexpression of DUSP5 blocked ANG II-mediated proliferation of cultured human pulmonary artery SMCs (hPASMCs) derived from patients with idiopathic PH or from failed donor controls. Collectively, the data support a role for DUSP5 as a feedback inhibitor of ANG II-mediated ERK signaling and PASMC proliferation and suggest that disruption of this circuit leads to adverse cardiopulmonary remodeling.NEW & NOTEWORTHY Dual-specificity phosphatases (DUSPs) serve critical roles in the regulation of mitogen-activated protein kinases, but their functions in the cardiovascular system remain poorly defined. Here, we provide evidence that DUSP5, which resides in the nucleus and specifically dephosphorylates extracellular signal-regulated kinase (ERK1/2), blocks pulmonary vascular smooth muscle cell proliferation. In response to angiotensin II infusion, mice lacking DUSP5 develop pulmonary hypertension and right ventricular cardiac hypertrophy. These findings illustrate DUSP5-mediated suppression of ERK signaling in the lungs as a protective mechanism.


A cell in hand is worth two in the embryo: recent advances in 2-cell like cell reprogramming.
Multicellular organisms develop from a single cell, the zygote. This feature is referred to as totipotency. In the mouse, only the zygote and the 2-cell stage embryo display this attribute. Cells resembling the embryonic 2-cell stage blastomeres were identified in embryonic stem (ES) cell cultures as '2-cell-like cells' (2CLCs). This discovery brought the first cellular model with the possibility to investigate some features of the totipotent embryo and the molecular mechanisms regulating totipotency in vitro. In this article, we discuss the latest advancements on the research on 2CLCs, which have uncovered an intricate reprogramming process regulated by proteins as well as metabolites and ncRNAs. These recent findings have shed light on the combinatorial regulation of 2-cell-like cell emergence and the nature of their unique attributes.


Unnecessary Frills: Communality as a Nice (But Expendable) Trait in Leaders.
Although leader role expectations appear to have become relatively more compatible with stereotypically feminine attributes like empathy, women continue to be highly underrepresented in leadership roles. We posit that one reason for this disparity is that, whereas stereotypically feminine traits are appreciated as nice "add-ons" for leaders, it is stereotypically masculine attributes that are valued as the defining qualities of the leader role, especially by men (who are often the gatekeepers to these roles). We assessed men's and women's idea of a great leader with a focus on gendered attributes in two studies using different methodologies. In Study 1, we employed a novel paradigm in which participants were asked to design their "ideal leader" to examine the potential trade-off between leadership characteristics that were more stereotypically masculine (i.e., agency) and feminine (i.e., communality). Results showed that communality was valued in leaders only after meeting the more stereotypically masculine requirements of the role (i.e., competence and assertiveness), and that men in particular preferred leaders who were more competent (vs. communal), whereas women desired leaders who kept negative stereotypically masculine traits in check (e.g., arrogance). In Study 2, we conducted an experiment to examine men's and women's beliefs about the traits that would be important to help them personally succeed in a randomly assigned leader (vs. assistant) role, allowing us to draw a causal link between roles and trait importance. We found that both men and women viewed agentic traits as more important than communal traits to be a successful leader. Together, both studies make a valuable contribution to the social psychological literature on gender stereotyping and bias against female leaders and may illuminate the continued scarcity of women at the very top of organizations, broadly construed.


Calcium-binding protein immunoreactivity characterizes the auditory system of Gekko gecko.
Geckos use vocalizations for intraspecific communication, but little is known about the organization of their central auditory system. We therefore used antibodies against the calcium-binding proteins calretinin (CR), parvalbumin (PV), and calbindin-D28k (CB) to characterize the gecko auditory system. We also examined expression of both glutamic acid decarboxlase (GAD) and synaptic vesicle protein (SV2). Western blots showed that these antibodies are specific to gecko brain. All three calcium-binding proteins were expressed in the auditory nerve, and CR immunoreactivity labeled the first-order nuclei and delineated the terminal fields associated with the ascending projections from the first-order auditory nuclei. PV expression characterized the superior olivary nuclei, whereas GAD immunoreactivity characterized many neurons in the nucleus of the lateral lemniscus and some neurons in the torus semicircularis. In the auditory midbrain, the distribution of CR, PV, and CB characterized divisions within the central nucleus of the torus semicircularis. All three calcium-binding proteins were expressed in nucleus medialis of the thalamus. These expression patterns are similar to those described for other vertebrates.


Vital tooth bleaching: the White and Brite technique.
A new system of vital and nonvital teeth bleaching is a cosmetic and conservative method of treating dentition discolored by ingested substances, trauma, or other causes. The system also allows individuals with normal range dentition to whiten their teeth to meet cosmetic demands. This article reviews the literature, examines the effects of conventional teeth bleaching techniques, presents a new method for bleaching vital and nonvital teeth, and discusses the impact of new methods on the science of teeth whitening.


Multiple Roles for Chemokines in Neutrophil Biology.
Chemokines are recognized as the most critical mediators for selective neutrophil recruitment during inflammatory conditions. Furthermore, they are considered fundamental regulators of neutrophil mobilization from the bone marrow (BM) to the bloodstream and for their homing back at the end of their life for apoptosis and clearance. However, chemokines are also important mediators of neutrophil effector functions including oxidative burst, degranulation, neutrophil extracellular trap (NET)osis, and production of inflammatory mediators. Neutrophils have been historically considered as a homogeneous population. In recent years, several maturation stages and subsets with different phenotypic profiles and effector functions were described both in physiological and pathological conditions such as infections, autoimmunity, and cancer. The aim of this review is to give an overview of the current evidence regarding the role of chemokines and chemokine receptors in neutrophil biology, including their possible role in neutrophil maturation, differentiation, and in defining emerging neutrophil subsets.


Contemporary approach to neurologic prognostication of coma after cardiac arrest.
Coma after cardiac arrest (CA) is an important cause of admission to the ICU. Prognosis of post-CA coma has significantly improved over the past decade, particularly because of aggressive postresuscitation care and the use of therapeutic targeted temperature management (TTM). TTM and sedatives used to maintain controlled cooling might delay neurologic reflexes and reduce the accuracy of clinical examination. In the early ICU phase, patients' good recovery may often be indistinguishable (based on neurologic examination alone) from patients who eventually will have a poor prognosis. Prognostication of post-CA coma, therefore, has evolved toward a multimodal approach that combines neurologic examination with EEG and evoked potentials. Blood biomarkers (eg, neuron-specific enolase [NSE] and soluble 100-β protein) are useful complements for coma prognostication; however, results vary among commercial laboratory assays, and applying one single cutoff level (eg, > 33 μg/L for NSE) for poor prognostication is not recommended. Neuroimaging, mainly diffusion MRI, is emerging as a promising tool for prognostication, but its precise role needs further study before it can be widely used. This multimodal approach might reduce false-positive rates of poor prognosis, thereby providing optimal prognostication of comatose CA survivors. The aim of this review is to summarize studies and the principal tools presently available for outcome prediction and to describe a practical approach to the multimodal prognostication of coma after CA, with a particular focus on neuromonitoring tools. We also propose an algorithm for the optimal use of such multimodal tools during the early ICU phase of post-CA coma.


The absence of specific yeast heat-shock proteins leads to abnormal aggregation and compromised autophagic clearance of mutant Huntingtin proteins.
The functionality of a protein depends on its correct folding, but newly synthesized proteins are susceptible to aberrant folding and aggregation. Heat shock proteins (HSPs) function as molecular chaperones that aid in protein folding and the degradation of misfolded proteins. Trinucleotide (CAG) repeat expansion in the Huntingtin gene (HTT) results in the expression of misfolded Huntingtin protein (Htt), which contributes to the development of Huntington's disease. We previously found that the degradation of mutated Htt with polyQ expansion (Htt103QP) depends on both ubiquitin proteasome system and autophagy. However, the role of heat shock proteins in the clearance of mutated Htt remains poorly understood. Here, we report that cytosolic Hsp70 (Ssa family), its nucleotide exchange factors (Sse1 and Fes1), and a Hsp40 co-chaperone (Ydj1) are required for inclusion body formation of Htt103QP proteins and their clearance via autophagy. Extended induction of Htt103QP-GFP leads to the formation of a single inclusion body in wild-type yeast cells, but mutant cells lacking these HSPs exhibit increased number of Htt103QP aggregates. Most notably, we detected more aggregated forms of Htt103QP in sse1Δ mutant cells using an agarose gel assay. Increased protein aggregates are also observed in these HSP mutants even in the absence Htt103QP overexpression. Importantly, these HSPs are required for autophagy-mediated Htt103QP clearance, but are less critical for proteasome-dependent degradation. These findings suggest a chaperone network that facilitates inclusion body formation of misfolded proteins and the subsequent autophagic clearance.


Absence of Borrelia burgdorferi DNA in cutaneous B-cell lymphomas from the United States.
An association between Borrelia burgdorferi and cutaneous B-cell lymphoma (CBCL) has been made in several European countries. The evidence in favor of such an association has recently been based on more definitive tests for the pathogenetic role of B. burgdorferi in CBCL, including positive cultures or polymerase chain reaction (PCR) amplification of borrelial DNA from lesional skin. However, there is only one report of B. burgdorferi in four North American cases of B-cell lymphoma. We retrieved 38 cases of primary and secondary CBCL from different geographic regions of the United States. Two separate techniques were used to detect borrelial DNA by PCR, a nested PCR method to amplify a B. burgdorferi-specific gene as well as a borrelial chromosomal Ly-1 clone amplification method. Southern blot hybridization was used for confirmation of the PCR results. No B. burgdorferi-specific DNA was detected in any of the 38 CBCL cases, whereas detectable PCR products were obtained with our positive controls. Our findings, in light of previous studies, suggest that B. burgdorferi plays a minimal role in the development or pathogenesis of CBCL in the United States. The findings also suggest that the geographic variations in the clinical manifestations of B. burgdorferi are indeed real and may be secondary to the genetic and phenotypic differences between B. burgdorferi strains present in Europe and North America.


Craniofacial contribution to residual obstructive sleep apnea after adenotonsillectomy in children: a preliminary study.
Pediatric obstructive sleep apnea (OSA) is frequently associated with adenotonsillar hypertrophy, and the fact that about 30% of affected children continue to show OSA after adenotonsillectomy (AT) suggests the presence of some other predisposing factor(s). We hypothesized that abnormal maxillofacial morphology may be a predisposing factor for residual OSA in pediatric patients. A total of 13 pediatric OSA patients (9 boys and 4 girls, age [median (interquartile range)] = 4.7 (4.0, 6.4) y, body mass index (BMI) z score = -0.3 (-0.8, 0.5)) who had undergone AT were recruited for this study. Maxillomandibular size was measured using an upright lateral cephalogram, and correlations between size and the apnea hypopnea index (AHI) values obtained before (pre AT AHI) and about 6 months after AT (post AT AHI) were analyzed. AHI decreased from 12.3 (8.9, 26.5)/h to 3.0 (1.5, 4.6)/h after AT (p < 0.05). Residual OSA was seen in 11 of the 13 patients (84.6%) and their AHI after AT was 3.1 (2.7, 4.7)/h. The mandible was smaller than the Japanese standard value, and a significant negative correlation was seen between maxillomandibular size and post AT AHI (p < 0.05). These findings suggest that the persistence of OSA after AT may be partly due to the smaller sizes of the mandible in pediatric patients. We propose that the maxillomandibular morphology should be carefully examined when a treatment plan is developed for OSA children.


Association Between Problem Gambling and Functional Disability: A Nationally Representative Study Conducted in the United Kingdom.
Problem gambling is associated with multiple detrimental health outcomes. However, to date, no study has investigated the association between problem gambling and functional disability. Therefore, the aim of this study was to investigate the association between problem gambling and functional disability in a UK nationally representative sample. Cross-sectional data from the 2007 Adult Psychiatric Morbidity Survey were analyzed. Problem gambling was assessed using a questionnaire including 10 DSM-IV criteria, whereas functional disability referred to at least 1 difficulty in 1 of 7 activities of daily living and instrumental activities of daily living. Control variables included sociodemographic factors, smoking status, alcohol dependence, drug use, the number of chronic physical conditions, depression, and anxiety disorder. The problem gambling-functional disability relationship was studied using a logistic regression model. This study included 6941 adults aged ≥16 years (51.2% women; mean [SD] age 46.3 [18.6] years). The prevalence of functional disability was significantly higher in the at-risk problem gambling/problem gambling group than in the no problem gambling group (46.2% vs 32.1%, P value < 0.001). After adjusting for control variables, both at-risk problem gambling (OR = 1.55, 95% CI = 1.03-2.35) and problem gambling (OR = 3.05, 95% CI = 1.09-8.52) were positively and significantly associated with functional disability. In this large representative sample of UK adults, problem gambling was associated with higher odds for functional disability. If confirmed with longitudinal studies, these results suggest that those suffering from problem gambling should receive targeted intervention to aid in the prevention of functional disability.


Leprosy in medieval Denmark: Exploring life histories through a multi-tissue and multi-isotopic approach.
By focusing on two Danish leprosaria (Naestved and Odense; 13th-16th c. CE) and using diet and origin as proxies, we follow a multi-isotopic approach to reconstruct life histories of patients and investigate how leprosy affected both institutionalized individuals and the medieval Danish community as a whole. We combine archaeology, historical sources, biological anthropology, isotopic analyses (δ13 C, δ15 N, δ34 S, 87 Sr/86 Sr) and radiocarbon dating, and further analyze bones with different turnover rates (ribs and long bones). The δ13 C, δ15 N and δ34 S results indicate a C3 terrestrial diet with small contributions of marine protein for leprosy patients and individuals from other medieval Danish sites. A similar diet is seen through time, between males and females, and patients with and without changes on facial bones. The isotopic comparison between ribs and long bones reveals no significant dietary change. The δ34 S and 87 Sr/86 Sr results suggest that patients were local to the regions of the leprosaria. Moreover, the radiocarbon dates show a mere 50% agreement with the arm position dating method used in Denmark. A local origin for the leprosy patients is in line with historical evidence, unlike the small dietary contribution of marine protein. Although only 10% of the analyzed individuals have rib/long bone offsets that undoubtedly show a dietary shift, the data appear to reveal a pattern for 25 individuals (out of 50), with elevated δ13 C and/or δ15 N values in the ribs compared to the long bones, which points toward a communal type of diet and reveals organizational aspects of the institution.


Comparison of Meat Quality and Muscle Fiber Characteristics between Porcine Skeletal Muscles with Different Architectures.
This study aimed to compare the similarities, physicochemical properties, and muscle fiber characteristics of porcine skeletal muscles. Fourteen types of muscles were collected from nine pig carcasses at 24 h post-mortem and classified by muscle architecture into two main groups, namely parallel and pennate. The muscles were further differentiated into three subtypes per group. These included fan-shaped, fusiform, and strap for the parallel group, and unipennate, bipennate, and multipennate for the pennate group. Parallel-fibered muscles, which were composed of larger I, IIA, IIX, and IIXB fibers and a lower density of IIA fibers, showed higher redness and yellowness values than pennate-fibered muscles (p<0.05). However, the relative fiber area was not significantly different between the parallel and pennate groups (p>0.05). In the subtypes of parallel architecture, the strap group showed lower moisture content and higher redness values than the other subtypes and had considerably higher amounts of oxidative fibers (I and IIA; 72.3%) than the fan-shaped and fusiform groups (p<0.05). In the pennate group, unipennate showed comparatively lower moisture content and higher lightness than other pennate subtypes and was composed of smaller I, IIA, and IIX fibers than the bipennate and multipennate groups (p<0.05). Finally, a different trend of muscle clustering by hierarchical cluster analysis was found between physicochemical properties and muscle fiber characteristics. These results suggest that the physicochemical properties and muscle fiber characteristics of porcine skeletal muscles are not significantly dependent on morphological properties but are rather related to the intrinsic properties of the individual muscles.


Clonal Diversity, Virulence Potential and Antimicrobial Resistance of Escherichia coli Causing Community Acquired Urinary Tract Infection in Switzerland.
Objectives: The aim of this study was to assess the clonal structure, virulence potential and antibiotic susceptibility of uropathogenic Escherichia coli (UPEC) isolates causing community acquired urinary tract infection (CAUTI) in unselected primary care patients in Switzerland. Methods: We performed multilocus sequence typing, virulence factor determination, and phenotypic and genotypic antimicrobial resistance testing on 44 non-duplicate UPEC isolates. Results: Twenty-seven different sequence types (STs) were identified. Major UPEC clones were represented by 19 (43.2%) of the isolates, including E. coli ST131, ST69 (both 13.6%), ST73 (6.8%), ST10 (4.5%), ST127, ST140, (both 2.3%). Five (11.4%) isolates belonged to ST141. Aggregate virulence factor (VF) scores were highest among isolates belonging to ST127 and ST141. Overall, 50% of the isolates were susceptible to all 12 antimicrobials tested, and all isolates remained susceptible to fosfomycin and nitrofurantoin. Resistance to sulfamethoxazole and ciprofloxacin were found in 31.8, and 15.9% of the isolates, respectively. Plasmid-mediated resistance genes were detected in ST69 and ST131 and included aac(6')-Ib-cr (2.3% of all isolates) blaCTX-M-14 and blaCTX-M-15 (9%), and mph(A) (13.6%). None of the isolates tested positive for mcr-1 or mcr-2. Conclusions: Our results show that CAUTI in Switzerland is caused by a wide variety of UPEC STs for which fosfomycin remains a good treatment option. We suggest that ST141 is an emerging clone associated with UTI in the community, and warrants closer attention. Moreover, the high rate of E. coli harboring mph(A) from patients without a history of antimicrobial therapy or hospitalization indicates that UPEC is an important reservoir for mph(A).


Morphological Comparison of Second-Stage Juveniles of Six Populations of Meloidogyne hapla by SEM.
External morphology of second-stage juveniles of six populations of Meloidogyne hapla, hclonging to two cytological races (A and B), and one population each of M. arenaria, M. incognita, and M. javanica was compared by scanning electron microscopy (SEM). Race A of M. hapla included three facultatively parthenogenetic populations with haploid chromosome numbers of 15. 16, and 17; race B consisted of three mitotically parthenogenetic populations with somalic chromosome numhers of 45, 45, and 48. The mitotically parthenogenetic populations of M. arenaria, M. incognita, and M. javanica had 54, 41-43, and 44 chromosomes, respectively. Observations were made on head structures, lateral field, excretory pore, anal opening, and tail. Head morphology, including shape and proportion of labial disc and lips, expression of labial and cephalic sensilla, and markings on head region, was distinctly different for each species. M. hapla populations of race A were distinct from each other but showed much intrapopulatiou variation in head morphology. Populations of race B were different from those of race A and were very stable and quite similar in head morphology. Considerable inter- and intrapopulatiou variation made the structure of the lateral field, excretory pore, anal opening, and tail of little value in distinguishing species or populations. The results are discussed in relation to earlier SEM observations on the genus Helerodera.


Abl interconnects oncogenic Met and p53 core pathways in cancer cells.
The simplicity of BCR-ABL 'oncogene addiction' characterizing leukemia contrasts with the complexity of solid tumors where multiple 'core pathways', including receptor tyrosine kinases (RTKs) and p53, are often altered. This discrepancy illustrates the limited success of RTK antagonists in solid tumor treatment compared with the impact of Imatinib in BCR-ABL-dependent leukemia. Here, we identified c-Abl as a signaling node interconnecting Met-RTK and p53 core pathways, and showed that its inhibition impairs Met-dependent tumorigenesis. Met ensures cell survival through a new path in which c-Abl and p38-MAPK are employed to elicit p53 phosphorylation on Ser(392) and Mdm2 upregulation. We found a clinical correlation between activated Met, phospho-p53, and Mdm2 levels in human tumors, supporting the role of this path in tumorigenesis. Our findings introduce the concept that RTK-driven tumors may be therapeutically treated by hitting signaling nodes interconnecting core pathways. Moreover, they underline the importance of evaluating the relevance of c-Abl antagonists for combined therapies, based on the tumor signaling signature.


Foster Kennedy syndrome and an optociliary vein in a patient with a falx meningioma.
We describe a 51-year-old woman with a falx meningioma causing Foster Kennedy syndrome accompanied by optociliary shunt vessels on the atrophic optic nerve. The tumor did not directly involve optic nerves or chiasm. The optociliary vessels disappeared after successful tumor removal. The patient's arteriograms, surgical findings, and postoperative course support the theory that optic atrophy in Foster Kennedy syndrome may be caused by compression of the optic nerve by adjacent brain tissue displaced by a distant intracranial mass lesion.


Optimization of mucosal responses after intramuscular immunization with integrase defective lentiviral vector.
Many infectious agents infiltrate the host at the mucosal surfaces and then spread systemically. This implies that an ideal vaccine should induce protective immune responses both at systemic and mucosal sites to counteract invasive mucosal pathogens. We evaluated the in vivo systemic and mucosal antigen-specific immune response induced in mice by intramuscular administration of an integrase defective lentiviral vector (IDLV) carrying the ovalbumin (OVA) transgene as a model antigen (IDLV-OVA), either alone or in combination with sublingual adjuvanted OVA protein. Mice immunized intramuscularly with OVA and adjuvant were compared with IDLV-OVA immunization. Mice sublingually immunized only with OVA and adjuvant were used as a positive control of mucosal responses. A single intramuscular dose of IDLV-OVA induced functional antigen-specific CD8+ T cell responses in spleen, draining and distal lymph nodes and, importantly, in the lamina propria of the large intestine. These results were similar to those obtained in a prime-boost regimen including one IDLV immunization and two mucosal boosts with adjuvanted OVA or vice versa. Remarkably, only in groups vaccinated with IDLV-OVA, either alone or in prime-boost regimens, the mucosal CD8+ T cell response persisted up to several months from immunization. Importantly, following IDLV-OVA immunization, the mucosal boost with protein greatly increased the plasma IgG response and induced mucosal antigen-specific IgA in saliva and vaginal washes. Overall, intramuscular administration of IDLV followed by protein boosts using the sublingual route induced strong, persistent and complementary systemic and mucosal immune responses, and represents an appealing prime-boost strategy for immunization including IDLV as a delivery system.


First confirmed case of nasal pythiosis in a horse in Thailand.
Pythiosis is caused by Pythium insidiosum, a fungus-like organism in the class Oomycetes. It can infect humans and a variety of animal species in tropical, subtropical and some temperate regions. Cases of animal pythiosis have occurred predominantly in horses in the skin and subcutaneous tissue at the limbs and in the ventral portion of thoracoabdominal wall - lesions in the nasal region are rarely reported. Moreover, although many human pythiosis cases have been reported in Thailand, no cases of animal pythiosis in Thailand have been reported. We report a case of pythiosis in a horse infected at the nasal cavity. Diagnosis was performed by zoospore formation by bait technique, immunohistochemical stain, immunochromatography and sequence analysis. The sequences of rDNA were 99 % and 96 to 99 % identical to GenBank isolates of Pythium insidiosum from two Thai human patients and horses from various countries, respectively. This represents the first confirmed report of nasal equine pythiosis in Thailand.


Nurse Practitioner Knowledge, Attitudes, and Beliefs When Caring for Transgender People.
Purpose: The aim of this study was to explore Nurse Practitioner (NP) knowledge, attitudes, and beliefs when working with transgender people and to inform about Practitioner education needs. Methods: A qualitative descriptive design was used to explore (NP) experiences. Focused semistructured interviews were conducted in 2016 with 11 (N=11) NPs in the northeastern United States who represent various years of experience and encounters with transgender patients. The interviews explored NP knowledge attitudes and beliefs when caring for transgender patients and described their overall experiences in rendering care in the clinical setting. The interviews were professionally transcribed and analyzed independently and jointly by two investigators using conventional content analysis. Results: Four main themes and six subthemes were identified: Main themes include personal and professional knowledge gaps, fear and uncertainty, caring with intention and pride, and creating an accepting environment. Conclusions: NPs in this study perceive gaps in their knowledge that threaten their ability to deliver quality, patient-centered care to transgender patients, despite their best intentions. These findings have implications for changes in nursing practice, education, and research needed to address vital gaps in the healthcare of transgender people.


Chemical injuries of the upper extremity.
The prompt recognition and management (Tables 8-1 and 8-2) of chemical burns of the upper extremity may prevent injury to the deep structures of the hand and may make the difference between satisfactory rehabilitation and crippling deformities. Immediate irrigation with water is the single most important treatment that can be carried out, and should be continued for at least an hour and often for several hours, depending on the severity of the injury. Precious time should not be wasted hunting for a specific neutralizing agent. Hydrofluoric acid injuries and phosphorus injuries are the two exceptions to this principle. After copious irrigation and débridement, small superficial burns may be treated without dressings or topical therapy. Large partial-thickness burns are best treated with Sulfamylon burn cream and then with with biologic dressings until healing is achieved. Full-thickness injuries of limited extent should be excised and skin-grafted to regain maximum function, and more extensive burns treated in a nonexicisional regimen.


Plants to power: bioenergy to fuel the future.
Bioenergy should play an essential part in reaching targets to replace petroleum-based transportation fuels with a viable alternative, and in reducing long-term carbon dioxide emissions, if environmental and economic sustainability are considered carefully. Here, we review different platforms, crops, and biotechnology-based improvements for sustainable bioenergy. Among the different platforms, there are two obvious advantages to using lignocellulosic biomass for ethanol production: higher net energy gain and lower production costs. However, the use of lignocellulosic ethanol as a viable alternative to petroleum-based transportation fuels largely depends on plant biotechnology breakthroughs. We examine how biotechnology, such as lignin modification, abiotic stress resistance, nutrition usage, in planta expression of cell wall digestion enzymes, biomass production, feedstock establishment, biocontainment of transgenes, metabolic engineering, and basic research, can be used to address the challenges faced by bioenergy crop production.


Growth of large-area and highly crystalline MoS2 thin layers on insulating substrates.
The two-dimensional layer of molybdenum disulfide (MoS(2)) has recently attracted much interest due to its direct-gap property and potential applications in optoelectronics and energy harvesting. However, the synthetic approach to obtain high-quality and large-area MoS(2) atomic thin layers is still rare. Here we report that the high-temperature annealing of a thermally decomposed ammonium thiomolybdate layer in the presence of sulfur can produce large-area MoS(2) thin layers with superior electrical performance on insulating substrates. Spectroscopic and microscopic results reveal that the synthesized MoS(2) sheets are highly crystalline. The electron mobility of the bottom-gate transistor devices made of the synthesized MoS(2) layer is comparable with those of the micromechanically exfoliated thin sheets from MoS(2) crystals. This synthetic approach is simple, scalable, and applicable to other transition metal dichalcogenides. Meanwhile, the obtained MoS(2) films are transferable to arbitrary substrates, providing great opportunities to make layered composites by stacking various atomically thin layers.