bluuebunny/crossref_metadata_2025 huggingface dataset:
Polygenic risk for schizophrenia and neurocognitive performance in patients with schizophrenia
Authors: Wang S.‐H. , Hsiao P.‐C. , Yeh L.‐L. , Liu C.‐M. , Liu C.‐C. , Hwang T.‐J. , Hsieh M. H. , Chien Y.‐L. , Lin Y.‐T. , Chandler S. D. , Faraone S. V. , Laird N. , Neale B. , McCarroll S. A. , Glatt S. J. , Tsuang M. T. , Hwu H.‐G. , Chen W. J.
Published: July 2017

Both neurocognitive deficits and schizophrenia are highly heritable. Genetic overlap between neurocognitive deficits and schizophrenia has been observed in both the general population and in the clinical samples. This study aimed to examine if the polygenic architecture of susceptibility to schizophrenia modified neurocognitive performance in schizophrenia patients. Schizophrenia polygenic risk scores (PRSs) were first derived from the Psychiatric Genomics Consortium (PGC) on schizophrenia, and then the scores were calculated in our independent sample of 1130 schizophrenia trios, who had PsychChip data and were part of the Schizophrenia Families from Taiwan project. Pseudocontrols generated from the nontransmitted parental alleles of the parents in these trios were compared with alleles in schizophrenia patients in assessing the replicability of PGC‐derived susceptibility variants. Schizophrenia PRS at the P‐value threshold (PT) of 0.1 explained 0.2% in the variance of disease status in this Han‐Taiwanese samples, and the score itself had a P‐value 0.05 for the association test with the disorder. Each patient underwent neurocognitive evaluation on sustained attention using the continuous performance test and executive function using the Wisconsin Card Sorting Test. We applied a structural equation model to construct the neurocognitive latent variable estimated from multiple measured indices in these 2 tests, and then tested the association between the PRS and the neurocognitive latent variable. Higher schizophrenia PRS generated at the PT of 0.1 was significantly associated with poorer neurocognitive performance with explained variance 0.5%. Our findings indicated that schizophrenia susceptibility variants modify the neurocognitive performance in schizophrenia patients.
Clinical features of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome: a study of 25 patients in Korea
Authors: Lee Jin Y. , Lee Suh‐Young , Hahm Ji E. , Ha Jae W. , Kim Chul W. , Kim Sang S.
Published: July 2017

Background

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare adverse drug reaction. This study aimed to evaluate the incidence of association with individual drugs, clinical manifestations, disease course, and outcomes of DRESS.

Methods

Using the criteria of the European Registry of Severe Cutaneous Adverse Reactions (RegiSCAR), the medical records of 25 patients diagnosed with DRESS between 2006 and 2015 were retrospectively reviewed. Demographic data, culprit drugs, latency periods, clinical and laboratory findings, and outcomes were investigated.

Results

The study group comprised 11 men (44%) and 14 women (56%) with an age range of 13–93 years (mean, 58 ± 19.86 years). The drugs most commonly implicated were carbamazepine (28%), allopurinol (16%), and antituberculosis drugs (12%). Individual latency periods ranged from 4 to 40 days (mean, 17.6 ± 9.95 days). Latency periods for anticonvulsants were significantly longer than those for other drugs (P < 0.05). However, no statistical differences were found between the RegiSCAR scores for anticonvulsants and those for other drugs. Disease severity, based on RegiSCAR score, was correlated with blood count abnormalities (P < 0.05).

Conclusions

The results of our study revealed that anticonvulsants were the leading culprit drugs for DRESS, and carbamazepine was the individual drug most commonly associated with DRESS in Korea. Further studies of the mechanisms of action of these drugs are required in order to facilitate prompt diagnosis and effective management, which can affect prognosis and clinical outcome, of DRESS.
The impact of values‐job fit and age on work‐related learning
Authors: Van Den Ouweland Loth , Van den Bossche Piet
Published: July 2017

Research shows that both individual and job‐related factors influence a worker's work‐related learning. This study combines these factors, examining the impact of fit between one's work values and job characteristics on learning. Although research indicates that fit benefits multiple work‐related outcomes, little is known about the impact of fit on learning. Moreover, life span theories indicate that values evolve throughout the lifespan. Therefore, we examined how age influences work values and thereby work‐related learning. Our self‐report questionnaire was completed by 221 workers of various ages and occupations. Our findings indicate that work values, job characteristics and their fit influence the quantity and quality of work‐related learning. Generally, a higher fit benefits learning, but misfit can also stimulate learning. Workers of different ages report an equal amount of learning, but perform different learning activities. However, this relationship is unrelated to work values. Recommendations for research and practice are discussed.
The effect of selection history on extinction risk during severe environmental change
Authors: Lachapelle J. , Colegrave N. , Bell G.
Published: July 2017

Environments rarely remain the same over time, and populations are therefore frequently at risk of going extinct when changes are significant enough to reduce fitness. Although many studies have investigated what attributes of the new environments and of the populations experiencing these changes will affect their probability of going extinct, limited work has been directed towards determining the role of population history on the probability of going extinct during severe environmental change. Here, we compare the extinction risk of populations with a history of selection in a benign environment, to populations with a history of selection in one or two stressful environments. We exposed spores and lines of the green alga Chlamydomonas reinhardtii from these three different histories to a range of severe environmental changes. We found that the extinction risk was higher for populations with a history of selection in stressful environments compared to populations with a history of selection in a benign environment. This effect was not due to differences in initial population sizes. Finally, the rates of extinction were highly repeatable within histories, indicating strong historical contingency of extinction risk. Hence, information on the selection history of a population can be used to predict their probability of going extinct during environmental change.
Ovarian apoplexy resulting from ruptured heterotopic pregnancy following intrauterine insemination
Authors: Gundabattula Sirisha Rao , Resapu Padmasree , Surampudi Kameswari , Surapaneni Tarakeswari , De Padua Michelle
Published: July 2017

Heterotopic pregnancy is on the rise with the use of assisted conception and commonly involves the fallopian tube. Ovarian heterotopic pregnancy is rare, with fewer than 40 reported cases in PubMed/Medline; cases of ovarian ectopic pregnancy after intrauterine insemination are even rarer, with only seven published reports. We report here a case of ovarian heterotopic pregnancy following intrauterine insemination; this could possibly be the first such report. Our patient presented with circulatory collapse in the first trimester and laparoscopy disclosed an ovarian pregnancy with hemoperitoneum. Following resection of the ovarian pregnancy, the intrauterine gestation continued undisturbed and the patient delivered at term. Heterotopic pregnancy and unusual ectopic locations should be considered a possibility in pregnant women with pelvic pain, particularly following fertility treatment, including ovarian stimulation and intrauterine insemination.
New knowledge and insights about the malignant transformation of endometriosis
Authors: Taniguchi Fuminori
Published: July 2017

Endometriosis may be a definitive risk factor for ovarian cancer, the most fatal gynecological cancer. The ability of endometriosis to transform into malignancy, first described by Dr. Sampson in 1925, is considered a rare occurrence, affecting approximately 1% of ovarian endometriomas.

Recently we conducted a retrospective study regarding the malignant transformation of endometriosis in Japanese women. Many studies have reported a consistent correlation between endometriosis and ovarian cancer according to histological subtypes. However, the existing epidemiological evidence linking this association is insufficient to define the role of endometriosis as a cause of ovarian cancer and to influence changes to current clinical practice. Prospective cohort studies are therefore needed to clarify this issue. Additionally, the results of many molecular studies are conflicting, and earlier studies showing the molecular aberrations involved in genomic instability and mutation that enable malignant transformation have not been replicated in later studies. Careful long‐term observation of a patient with endometrioma is required to detect possible subsequent incidence of malignant transformation. More importantly, a precise strategy should be set up for better prevention, early detection, specific diagnosis and treatment targeting molecular pathogenesis to understand the mechanisms of endometriosis‐associated ovarian cancer. Clinicians need to be aware of the increased ovarian cancer risk in women with endometriosis.
The association between dental, general, and mental health status among underserved and vulnerable populations served at health centers in the US
Authors: Nguyen Vy H. , Lin Sue C. , Cappelli David P. , Nair Suma
Published: July 2017

Objectives

Vulnerable populations in underserved communities are disproportionately at high risk for multiple medical, dental, and behavioral health conditions. This study aims to: a) examine the occurrence of acute dental needs and b) investigate the association of acute dental needs and self‐rated general and mental health status among the adult dentate health center population.

Methods

This cross‐sectional study analyzed data on adult patients (n = 5,035) from the 2014 Health Center Patient Survey, a nationally representative survey of health center patients. Multivariate logistic regression was used to assess the association of acute dental needs and a) self‐rated general health status and b) mental health status.

Results

Approximately, two thirds of adult dentate heath center patients reported having an acute dental need. After adjusting for confounding factors, not having or having had health insurance that pays for dental care, general health status of fair or poor, and ever having a mental illness were associated with higher odds of having an acute dental need.

Conclusions

The results highlight the role of health centers in addressing oral health disparities among vulnerable populations and the importance of a team‐based multidisciplinary approach to ensuring the integration and coordination of oral health services within a comprehensive primary care delivery system.
In an era of highly effective treatment, hepatitis C screening of the United States general population should be considered
Authors: Younossi Zobair , Blissett Deidre , Blissett Rob , Henry Linda , Younossi Youssef , Beckerman Rachel , Hunt Sharon
Published: July 2017

Background & Aims

Hepatitis C virus (HCV) treatment with all oral direct acting antiviral agents (DAA's) achieve sustained virologic response (SVR) rates of 98%. Re‐assessment of general US population screening for HCV is imperative. This study compared the cost‐effectiveness (CE) of three HCV screening strategies: screen all (SA), screen Birth Cohort (BCS), and screen high risks (HRS).

Methods

Using a previous designed decision‐analytic Markov model, estimations of the natural history of HCV and CE evaluation of the three HCV screening strategies over a lifetime horizon in the US population was undertaken. Based on age and risk status, 16 cohorts were modelled. Health states included: Fibrosis stages 0 to 4, decompensated cirrhosis, hepatocellular carcinoma, LT, post‐LT, and death. The probability of liver disease progression was based on the presence or absence of virus. Treatment was with approved all‐oral DAAs; 86% were assumed to be seen annually by a primary care provider; SVR rates, transition probabilities, utilities, and costs were from the literature. One‐way sensitivity analyses tested the impact of key model drivers.

Results

SA cost $272.0 billion [$135 279 per patient] and led to 12.19 QALYs per patient. BCS and HRS cost $274.5 billion ($136 568 per patient) and $284.5 billion ($141 502 per patient) with 11.65 and 11.25 QALYs per patient respectively. Compared to BCS, SA led to an additional 0.54 QALYs per patient and saved $2.59 billion; compared to HRS, SA led to 0.95 additional QALYs per patient and saved $12.5 billion.

Conclusions

Screening the entire US population and treating active viraemia was projected as cost‐saving.
Hepatitis E virus ORF 1 induces proliferative and functional T‐cell responses in patients with ongoing and resolved hepatitis E
Authors: Al‐Ayoubi Jana , Behrendt Patrick , Bremer Birgit , Suneetha Pothakamuri Venkata , Gisa Anett , Rinker Franziska , Manns Michael P. , Cornberg Markus , Wedemeyer Heiner , Kraft Anke R. M.
Published: July 2017

Background and Aims

Hepatitis E virus (HEV) is a major cause of acute viral hepatitis with >3 million symptomatic cases per year accounting for 70 000 HEV‐related deaths. HEV‐specific T‐cell responses have been investigated against structural proteins expressed by open reading frames (ORF) 2 and 3. T‐cell responses against non‐structural HEV proteins encoded by ORF1 are hardly studied. The aim of this study was to determine HEV ORF1‐specific T‐cell responses in comparison to ORF2/3 in patients exposed to HEV.

Methods

HEV‐specific CD4+ and CD8+ T‐cell responses against HEV genotype 3 were investigated in patients with acute and chronic hepatitis E as well as in HEV seropositive and seronegative individuals. HEV‐specific T‐cell responses were determined by proliferation and intracellular cytokine assay upon stimulation of PBMCs with HEV‐specific overlapping peptide pools spanning the entire HEV genome. HEV‐antigen was measured using an anti‐HEV antigen‐specific ELISA.

Results

Broad HEV ORF1‐specific T‐cell responses were detected in patients with acute, resolved and chronic hepatitis E without distinct dominant regions. The magnitude and frequency in recognition of ORF1‐specific T‐cell responses were similar compared to responses against HEV ORF2/3. Longitudinal studies of HEV‐specific T‐cell responses displayed similar behaviour against structural and non‐structural proteins. HEV‐antigen levels were inversely correlated with HEV‐specific T‐cell responses.

Conclusions

HEV‐specific T‐cell responses are detectable against the entire HEV genome including the non‐structural proteins. HEV‐specific T‐cell responses are associated with control of HEV infection. These findings have implications for the design of HEV vaccines.
Thai people living with tuberculosis and how they adhere to treatment: A grounded theory study
Authors: Choowong Jiraporn , Tillgren Per , Söderbäck Maja
Published: July 2017

Abstract

To develop a conceptual framework of adherence to treatment among Thai people living with tuberculosis, a grounded theory approach was used. A purposive sample of 20 Thai people living with tuberculosis, aged from 23 to 85 years, was interviewed. From the participants' perspective, a core category of social belonging was highlighted, with three categories of conditions connected: personal barriers, personal resilience, and social facilitation. Personal barriers encompassed fear of stigma, concealing the illness, and lack of knowledge and motivation to complete the treatment regime. Personal resilience encompassed positive thinking and self‐awareness. Social facilitation encompassed the ease of access to health services, continuity in the health service's ability to choose a directly‐observed therapy observer, and social support. This study contributes a deeper understanding of the perspective of Thai people living with tuberculosis with regards to adherence to tuberculosis treatment. It might improve how local healthcare workers provide tuberculosis care, and inspire them to tailor care to people living with tuberculosis in a local community to increase personal resilience and reduce stigma.
Characterizing a mouse model for evaluation of countermeasures against hydrogen sulfide–induced neurotoxicity and neurological sequelae
Authors: Anantharam Poojya , Whitley Elizabeth M. , Mahama Belinda , Kim Dong‐Suk , Imerman Paula M. , Shao Dahai , Langley Monica R. , Kanthasamy Arthi , Rumbeiha Wilson K.
Published: July 2017

Hydrogen sulfide (H2S) is a highly neurotoxic gas. It is the second most common cause of gas‐induced deaths. Beyond mortality, surviving victims of acute exposure may suffer long‐term neurological sequelae. There is a need to develop countermeasures against H2S poisoning. However, no translational animal model of H2S‐induced neurological sequelae exists. Here, we describe a novel mouse model of H2S‐induced neurotoxicity for translational research. In paradigm I, C57/BL6 mice were exposed to 765 ppm H2S for 40 min on day 1, followed by 15‐min daily exposures for periods ranging from 1 to 6 days. In paradigm II, mice were exposed once to 1000 ppm H2S for 60 minutes. Mice were assessed for behavioral, neurochemical, biochemical, and histopathological changes. H2S intoxication caused seizures, dyspnea, respiratory depression, knockdowns, and death. H2S‐exposed mice showed significant impairment in locomotor and coordinated motor movement activity compared with controls. Histopathology revealed neurodegenerative lesions in the collicular, thalamic, and cortical brain regions. H2S significantly increased dopamine and serotonin concentration in several brain regions and caused time‐dependent decreases in GABA and glutamate concentrations. Furthermore, H2S significantly suppressed cytochrome c oxidase activity and caused significant loss in body weight. Overall, male mice were more sensitive than females. This novel translational mouse model of H2S‐induced neurotoxicity is reliable, reproducible, and recapitulates acute H2S poisoning in humans.
Biblical language instruction by the book: Rethinking the status quaestionis
Authors: Sanders Carl E.
Published: July 2017

Grammar‐translation pedagogy is the standard for biblical language instruction. Second language acquisition scholars have argued that grammar‐translation is ineffective and not empirically justified. Moreover, evidence suggests most seminary graduates do not use biblical languages effectively in ministry. Task‐based instruction is an important alternative pedagogy which focuses on the tasks students will be using the language for and designs the curriculum around those tasks. A task‐based approach de‐emphasizes translation and memorization of forms. Instead, the emphasis from the beginning is on biblical interpretation and exposition. Available software based resources offer new possibilities for task‐based teaching, as students can identify forms and vocabulary and have access to a library of resources. A task‐based pedagogy using these tools enables students to quickly develop skills in biblical interpretation that are normally reserved for the third or fourth semester of study. Task‐based pedagogy offers great promise for effective and efficient biblical language pedagogy.
Disruption, dialogue, and swerve: Reflective structured dialogue in religious studies classrooms
Authors: DeTemple Jill , Sarrouf John
Published: July 2017

This article focuses on Reflective Structured Dialogue as a set of practices developed in the context of conflict resolution that are well suited to handling quotidian uneasiness and extraordinary moments of disruption in religious studies classrooms. After introducing Reflective Structured Dialogue's history, goals, and general practices, the authors consider its uses in classroom settings. They argue that a classroom in which teachers understand themselves as facilitators, and in which students are experienced in structured dialogue practices – including being comfortable in a state of intellectual “wobble” – is one more apt to be able to engage with, and more likely to benefit from, disruptive events.
Proteostasis and ageing: insights from long‐lived mutant mice
Authors: Sands William A. , Page Melissa M. , Selman Colin
Published: July 2017

The global increase in life expectancy is creating significant medical, social and economic challenges to current and future generations. Consequently, there is a need to identify the fundamental mechanisms underlying the ageing process. This knowledge should help develop realistic interventions capable of combatting age‐related disease, and thus improving late‐life health and vitality. While several mechanisms have been proposed as conserved lifespan determinants, the loss of proteostasis – where proteostasis is defined here as the maintenance of the proteome – appears highly relevant to both ageing and disease. Several studies have shown that multiple proteostatic mechanisms, including the endoplasmic reticulum (ER)‐induced unfolded protein response (UPR), the ubiquitin–proteasome system (UPS) and autophagy, appear indispensable for longevity in many long‐lived invertebrate mutants. Similarly, interspecific comparisons suggest that proteostasis may be an important lifespan determinant in vertebrates. Over the last 20 years a number of long‐lived mouse mutants have been described, many of which carry single‐gene mutations within the growth‐hormone, insulin/IGF‐1 or mTOR signalling pathways. However, we still do not know how these mutations act mechanistically to increase lifespan and healthspan, and accordingly whether mechanistic commonality occurs between different mutants. Recent evidence supports the premise that the successful maintenance of the proteome during ageing may be linked to the increased lifespan and healthspan of long‐lived mouse mutants.
Dust ball physics and the Schwarzschild metric
Authors: Kassner Klaus
Published: July 2017

A physics-first derivation of the Schwarzschild metric is given. Gravitation is described in terms of the effects of tidal forces (or of spacetime curvature) on the volume of a small ball of test particles (a dust ball), freely falling after all particles were at rest with respect to each other initially. Because this formulation avoids the use of tensors, neither advanced tensor calculus nor sophisticated differential geometry are needed in the calculation. The derivation is not lengthy and it has visual appeal, so it may be useful in teaching.
Determining the muon mass using a scintillator-based detector
Authors: Woo Neal , Essick John
Published: July 2017

A scintillator-based detection system, of the type employed in the popular muon-lifetime instructional lab experiment, is used to measure the muon mass. The photomultiplier pulse pairs produced by the decay of cosmic ray muons into product electrons and positrons within the scintillator are detected by a digitizing oscilloscope and the energies of the product particles are quantified by integrating the area under their associated pulses. The observed distribution of product-particle energies is then compared with Monte Carlo simulated distributions assuming different values of the muon mass mμc2, where the modeling of product-particle energy loss within the scintillator accounts for collisional and radiative effects in a detailed way. Via a least-squares comparison, it is found that the simulated distribution based on a value of mμc2=105±5 MeV most closely matches the experimental distribution.
Measurements on a guitar string as an example of a physical nonlinear driven oscillator
Authors: Carlà Marcello , Straulino Samuele
Published: July 2017

An experimental study is described to characterize the oscillation of a guitar string around resonance. A periodic force was applied to the string, generated by the electromagnetic interaction between an alternating current flowing in the string and a magnetic field. The oscillation was studied by measuring the voltage induced in the string itself, which is proportional to the velocity. Accurate quantitative data were obtained for the velocity, both modulus and phase, with a time resolution of 3 ms, corresponding to the oscillation period. The measuring instrument was a personal computer with its sound card and an electronic amplifier, both used to generate the excitation current and record the velocity signal, while performing the required frequency sweep. The study covered an excitation force range more than two and half decades wide (51 dB). The experimental results showed very good agreement with the theoretical behavior of a Duffing oscillator with nonlinear damping over about two decades.
PD-L1 on pain
Authors: Ferrarelli Leslie K.
Published: July 2017

As well as being an immunosuppressive checkpoint, the tumor-associated cell surface molecule PD-L1 suppresses pain signaling in sensory neurons.
The sensitive cells in the gut
Authors: Wong Wei
Published: July 2017

Serotonin-producing enterochromaffin cells in the gut epithelium are chemosensors for the enteric nervous system.
A Human Biofilm-Disrupting Monoclonal Antibody Potentiates Antibiotic Efficacy in Rodent Models of both Staphylococcus aureus and Acinetobacter baumannii Infections
Authors: Xiong Yan Q. , Estellés Angeles , Li L. , Abdelhady W. , Gonzales R. , Bayer Arnold S. , Tenorio Edgar , Leighton Anton , Ryser Stefan , Kauvar Lawrence M.
Published: July 2017

Many serious bacterial infections are antibiotic refractory due to biofilm formation. A key structural component of biofilm is extracellular DNA, which is stabilized by bacterial proteins, including those from the DNABII family. TRL1068 is a high-affinity human monoclonal antibody against a DNABII epitope conserved across both Gram-positive and Gram-negative bacterial species. In the present study, the efficacy of TRL1068 for the disruption of biofilm was demonstrated
in vitro
in the absence of antibiotics by scanning electron microscopy. The
in vivo
efficacy of this antibody was investigated in a well-characterized catheter-induced aortic valve infective endocarditis model in rats infected with a methicillin-resistant
Staphylococcus aureus
(MRSA) strain with the ability to form thick biofilms, obtained from the blood of a patient with persistent clinical infection. Animals were treated with vancomycin alone or in combination with TRL1068. MRSA burdens in cardiac vegetations and within intracardiac catheters, kidneys, spleen, and liver showed significant reductions in the combination arm versus vancomycin alone (
P
< 0.001). A trend toward mortality reduction was also observed (
P
= 0.09). In parallel, the
in vivo
efficacy of TRL1068 against a multidrug-resistant clinical
Acinetobacter baumannii
isolate was explored by using an established mouse model of skin and soft tissue catheter-related biofilm infection. Catheter segments infected with
A. baumannii
were implanted subcutaneously into mice; animals were treated with imipenem alone or in combination with TRL1068. The combination showed a significant reduction of catheter-adherent bacteria versus the antibiotic alone (
P
< 0.001). TRL1068 shows excellent promise as an adjunct to standard-of-care antibiotics for a broad range of difficult-to-treat bacterial infections.
Th17-Mediated Cross Protection against Pneumococcal Carriage by Vaccination with a Variable Antigen
Authors: Kuipers Kirsten , Jong Wouter S. P. , van der Gaast-de Jongh Christa E. , Houben Diane , van Opzeeland Fred , Simonetti Elles , van Selm Saskia , de Groot Ronald , Koenders Marije I. , Azarian Taj , Pupo Elder , van der Ley Peter , Langereis Jeroen D. , Zomer Aldert , Luirink Joen , de Jonge Marien I.
Published: July 2017

Serotype-specific protection against
Streptococcus pneumoniae
is an important limitation of the current polysaccharide-based vaccines. To prevent serotype replacement, reduce transmission, and limit the emergence of new variants, it is essential to induce broad protection and restrict pneumococcal colonization. In this study, we used a prototype vaccine formulation consisting of lipopolysaccharide (LPS)-detoxified outer membrane vesicles (OMVs) from
Salmonella enterica
serovar Typhimurium displaying the variable N terminus of PspA (α1α2) for intranasal vaccination, which induced strong Th17 immunity associated with a substantial reduction of pneumococcal colonization. Despite the variable nature of this protein, a common major histocompatibility complex class (MHC-II) epitope was identified, based on
in silico
prediction combined with
ex vivo
screening, and was essential for interleukin-17 A (IL-17A)-mediated cross-reactivity and associated with cross protection. Based on 1,352 PspA sequences derived from a pneumococcal carriage cohort, this OMV-based vaccine formulation containing a single α1α2 type was estimated to cover 19.1% of strains, illustrating the potential of Th17-mediated cross protection.
Bacterial Tubulins A and B Exhibit Polarized Growth, Mixed-Polarity Bundling, and Destabilization by GTP Hydrolysis
Authors: Díaz-Celis César , Risca Viviana I. , Hurtado Felipe , Polka Jessica K. , Hansen Scott D. , Maturana Daniel , Lagos Rosalba , Mullins R. Dyche , Monasterio Octavio
Published: July 2017

Bacteria of the genus
Prosthecobacter
express homologs of eukaryotic α- and β-tubulin, called BtubA and BtubB (BtubA/B), that have been observed to assemble into filaments in the presence of GTP. BtubA/B polymers are proposed to be composed
in vitro
by two to six protofilaments in contrast to that
in vivo
, where they have been reported to form 5-protofilament tubes named bacterial microtubules (bMTs). The
btubAB
genes likely entered the
Prosthecobacter
lineage via horizontal gene transfer and may be derived from an early ancestor of the modern eukaryotic microtubule (MT). Previous biochemical studies revealed that BtubA/B polymerization is reversible and that BtubA/B folding does not require chaperones. To better understand BtubA/B filament behavior and gain insight into the evolution of microtubule dynamics, we characterized
in vitro
BtubA/B assembly using a combination of polymerization kinetics assays and microscopy. Like eukaryotic microtubules, BtubA/B filaments exhibit polarized growth with different assembly rates at each end. GTP hydrolysis stimulated by BtubA/B polymerization drives a stochastic mechanism of filament disassembly that occurs via polymer breakage and/or fast continuous depolymerization. We also observed treadmilling (continuous addition and loss of subunits at opposite ends) of BtubA/B filament fragments. Unlike MTs, polymerization of BtubA/B requires KCl, which reduces the critical concentration for BtubA/B assembly and induces it to form stable mixed-orientation bundles in the absence of any additional BtubA/B-binding proteins. The complex dynamics that we observe in stabilized and unstabilized BtubA/B filaments may reflect common properties of an ancestral eukaryotic tubulin polymer.

IMPORTANCE
Microtubules are polymers within all eukaryotic cells that perform critical functions; they segregate chromosomes, organize intracellular transport, and support the flagella. These functions rely on the remarkable range of tunable dynamic behaviors of microtubules. Bacterial tubulin A and B (BtubA/B) are evolutionarily related proteins that form polymers. They are proposed to be evolved from the ancestral eukaryotic tubulin, a missing link in microtubule evolution. Using microscopy and biochemical approaches to characterize BtubA/B assembly
in vitro
, we observed that they exhibit complex and structurally polarized dynamic behavior like eukaryotic microtubules but differ in how they self-associate into bundles and how this bundling affects their stability. Our results demonstrate the diversity of mechanisms through which tubulin homologs promote filament dynamics and monomer turnover.
Human papillomavirus prevalence and genotype distribution among young women and men in Maputo city, Mozambique
Authors: Edna Omar Viegas , Orvalho Augusto , Nália Ismael , Kaliff Malin , Lillsunde-Larsson Gabriella , Ramqvist Torbjörn , Nilsson Charlotta , Falk Kerstin , Nafissa Osman , Ilesh Vindorai Jani , Andersson Sören
Published: July 2017

Objectives

Human papillomavirus (HPV) is a well-known cause of cervical cancer, the second most frequent cancer in female African populations. This study aimed at determining the prevalence of HPV infections and the genotype distribution in young adults aged 18–24, in Maputo city, Mozambique, and to assess the suitability of commercially available HPV vaccines.

Methods

This cross-sectional study was conducted between 2009 and 2011 at a youth clinic in Maputo Central Hospital. Cervical and urethral samples were obtained from 236 women and 176 men, respectively. Demographic and behavioural data were collected using structured questionnaires. HPV genotyping was performed for 35 different high, probably or possibly high-risk and low-risk HPV types using the CLART Human Papillomavirus 2.

Results

HPV prevalence was 168/412 (40.8%; 95% CI 36.0 to 45.5) and was significantly higher in women than in men (63.6%vs10.2%). HPV52 was the most frequent type found in women, followed by HPV35, −16,–53, −58,–6 and −51. In men, HPV51 ranked the highest, followed by HPV6, −11,–52, −59 and −70. HIV infection and sexual debut before 18 years of age were associated with multiple HPV infections (OR 3.03; 95% CI 1.49 to 6.25 and OR 6.03; 95% CI 1.73 to 21.02, respectively). Women had a significantly higher HPV infection prevalence than men (p<0.001). The 9-valent HPV vaccine would cover 36.8% of the high-risk genotypes circulating in women in this study, compared with 26.3% and 15.8% coverage by the bivalent and quadrivalent vaccines, respectively.

Conclusion

This study confirmed the high burden of HPV infections in young women in Maputo city, Mozambique. The HPV prevalence was associated with high-risk sexual behaviour. Sex education and sexually transmitted infection prevention interventions should be intensified in Mozambique. Only a proportion of the high-risk HPV genotypes (37%) were covered by currently available vaccines.
Factors associated with nicotine dependence during methadone maintenance treatment: findings from a multisite survey in Vietnam
Authors: Do Huyen Phuc , Nguyen Long Hoang , Thi Nguyen Nhung Phuong , Ngo Chau , Thi Nguyen Huong Lan , Le Giang Tong , Nguyen Linh Khanh , Nguyen Cuong Tat , Tran Bach Xuan , Le Huong Thi , Vu Thuc Minh Thi , Phan Huong Thu Thi , Tran Tho Dinh , Latkin Carl A , Dunne Michael P
Published: July 2017

Objectives

Smoking is associated with adverse health outcomes among drug users, including those in treatment. To date, however, there has been little evidence about smoking patterns among people receiving opioid-dependence treatment in developing countries. We examined self-reported nicotine dependence and associated factors in a large sample of opioid-dependent patients receiving methadone maintenance treatment (MMT) in northern Vietnam.

Setting

Five clinics in Hanoi (urban area) and Nam Dinh (rural area).

Participants

Patients receiving MMT in the settings during the study period.

Primary and secondary outcome measures

We collected data about smoking patterns, levels of nicotine dependence and other covariates such as socioeconomic status, health status, alcohol use and drug use. The Fagerström test was used to measure nicotine dependence (FTND). Logistic regression and Tobit regression were employed to examine relationships between the smoking rate, nicotine dependence and potentially associated variables.

Results

Among 1016 drug users undergoing MMT (98.7% male), 87.2% were current smokers. The mean FTND score was 4.5 (SD 2.4). Longer duration of MMT (OR 0.98, 95% CI 0.96 to 0.99) and being HIV-positive (OR 0.46, 95% CI 0.24 to 0.88) were associated with lower likelihood of smoking. Being employed, older age at first drug injection and having long duration of MMT were inversely related with FTND scores. Higher age and continuing drug and alcohol use were significantly associated with higher FTND scores.

Conclusion

Smoking prevalence is high among methadone maintenance drug users. Enhanced smoking cessation support should be integrated into MMT programmes in order to reduce risk factors for cigarette smoking and improve the health and well-being of people recovering from opiate dependence.
How do clinicians prepare family members for the role of surrogate decision-maker?
Authors: Cunningham Thomas V , Scheunemann Leslie P , Arnold Robert M , White Douglas
Published: July 2017

Purpose

Although surrogate decision-making (SDM) is prevalent in intensive care units (ICUs) and concerns with decision quality are well documented, little is known about how clinicians help family members understand the surrogate role. We investigated whether and how clinicians provide normative guidance to families regarding how to function as a surrogate.

Subjects and methods

We audiorecorded and transcribed 73 ICU family conferences in which clinicians anticipated discussing goals of care for incapacitated patients at high risk of death. We developed and applied a coding framework to identify normative statements by clinicians regarding what considerations should guide surrogates’ decisions, including whether clinicians explained one or more of Buchanan and Brock’s three standard principles of SDM to family members.

Results

Clinicians made at least one statement about how to perform the surrogate role in 24 (34%) conferences (mean of 0.83 statements per conference (1.77; range 0–9)). We observed three general types of normative guidance provided to surrogates, with some conferences containing more than one type of guidance: counselling about one or more standard principles of SDM (24% of conferences); counselling surrogates to make decisions centred on the patient as a person, without specifying how to accomplish that (14% of conferences); and counselling surrogates to make decisions based on the family’s values (8% of conferences).

Conclusions

Clinicians did not provide normative guidance about the surrogate role in two-thirds of family conferences for incapacitated patients at high risk for death. When they did, clinicians’ guidance was often incomplete and sometimes conflicted with standard principles of SDM. Future work is needed to understand whether providing explicit guidance on how to perform the surrogate role improves decision-making or mitigates surrogates’ psychological distress.
Which azithromycin regimen should be used for treating Mycoplasma genitalium? A meta-analysis
Authors: Horner Patrick , Ingle Suzanne M , Garrett Frederick , Blee Karla , Kong Fabian , Muir Peter , Moi Harald
Published: July 2017

Background

There is increasing evidence that azithromycin 1 g is driving the emergence of macrolide resistance in Mycoplasma genitalium worldwide. We undertook a meta-analysis of M. genitalium treatment studies using azithromycin 1 g single dose and azithromycin 500 mg on day 1 then 250 mg daily for 4 days (5-day regimen) to determine rates of treatment failure and resistance in both regimens.

Methods

The online databases PubMed and Medline were searched using terms “Mycoplasma genitalium”, “macrolide” or “azithromycin” and “resistance” up to April 2016. Studies were eligible if they: used azithromycin 1 g or 5 days, assessed patients for macrolide resistant genetic mutations prior to treatment and patients who failed were again resistance genotyped. Random effects meta-analysis was used to estimate failure and resistance rates.

Results

Eight studies were identified totalling 435 patients of whom 82 (18.9%) had received the 5-day regimen. The random effects pooled rate of treatment failure and development of macrolide antimicrobial resistance mutations with azithromycin 1 g was 13.9% (95% CI 7.7% to 20.1%) and 12.0% (7.1% to 16.9%), respectively. Of individuals treated with the 5-day regimen, with no prior doxycycline treatment, fewer (3.7%; 95% CI 0.8% to 10.3%, p=0.012) failed treatment, all of whom developed resistance (p=0.027).

Conclusion

Azithromycin 1 g is associated with high rates of treatment failure and development of macrolide resistance in M. genitalium infection with no pre-existing macrolide mutations. There is moderate but conflicting evidence that the 5-day regimen may be more effective and less likely to cause resistance.
Factor of safety of slope stability from deformation energy
Authors: Xiao Shiguo , Guo Wei Dong , Zeng Jinxiu
Published: July 2017

The factor of safety of a slope (Fs) is invariably assessed using methods underpinned by moment, force, and (or) shear strength equilibrium concerning slip surfaces. Each method inherently embeds some form of limitations, despite being popularly adopted in practice. In this paper, a new Fs is devised using the ratio of ultimate energy (eu, upon sliding) over accumulated “elastic” energy. The Fs is then reduced to a simple expression of the power to shear stress and shear strength, by taking soil as an elastic–plastic material obeying the Mohr–Coulomb failure criterion. This expression empowers significant efficacy in gaining the factor of safety (without involving energy or directions of shear stresses). The Fs values were calculated for three typical slopes concerning various mechanical properties (dilation, Poisson’s ratio, and shear modulus) and effective computational strategies. All of the Fs values (to a congruous accuracy of available methods) were obtained in less than 1% the time of conventional numerical analyses. The proposed Fs, equally applicable to limit equilibrium methods, may be utilized in practice to expedite slope design.
Investigating performance of micropiled raft in foundation of power transmission line towers in cohesive soil: experimental and numerical study
Authors: Zekavati Ali-Asghar , Khodaverdian Alireza , Jafari Mohammad-Ali , Hosseini Ahmad
Published: July 2017

This paper captures the behavior of micropiled rafts in power transmission line tower foundations in cohesive soil, concentrating on their uplift performance whether due to the tower position along the line or under wind loading conditions. In this regard, first a number of micropiles were driven into the ground of a project site at the ParehSar power plant, Gilan, Iran. Compression and uplift loading tests were conducted according to relevant standards. On the basis of the field data, a three-dimensional finite element model was developed and subsequently calibrated and verified. The behavior of micropiled rafts subjected to uplift, which is a typical type of loading in foundations of 230 kV four-circuit lattice towers, was then studied by means of this model in terms of a wide-ranging parametric study. In the sensitivity analyses, the impacts of various parameters, such as micropile spacing-to-diameter (s/d) and length-to-diameter (l/d) ratios along with undrained shear strength of the soil, on the uplift capacity of an individual micropile within and out of the group were investigated. Furthermore, interaction factors were computed based on diverse values for undrained shear strength of the soil, s/d ratio, l/d ratio, and grout–soil adhesion. From design and analysis perspectives, the finite element method (FEM) outputs revealed that the efficiency coefficient of micropiled rafts during uplift can be considered equal to one. Moreover, it was found that not only does the behavior of micropiles affect the neighboring micropiles immediately adjacent to the loaded one, but it also influences those in further rows, the result of which would be considering their significance as well.
Convergent dendrimer synthesis by olefin metathesis and studies toward glycoconjugation
Authors: Guizzardi Roberto , Vacchini Mattia , Santambrogio Carlo , Cipolla Laura
Published: July 2017

The synthesis of novel hyperbranched monodisperse linear dendrimers, based on 2,2-bis-(hydroxymethyl)-propionic acid (bis-MPA), has been achieved by convergent metathesis-mediated coupling between the alkene-terminated focal point of bis-MPA dendrons. On their surface, dendrimers present 4, 8 and 16 functional groups. Glycodendrimers exposing multiple saccharide moieties have also been obtained. To the best of our knowledge, this is the first example of the use of metathesis for focal point coupling.
Anharmonic effect of the rate constant of the reactions of CH3SCH2OO system in high-temperature combustion
Authors: Hao Yu , Pan Xinxiang , Song Liguo , Ding Yang , Xia Wenwen , Wang Shiye , Yu Hongjing , Kang Liqiang , Yao Li
Published: July 2017

The study mainly focuses on the anharmonic effect of the reactions of CH3SCH2OO system. The geometries of the reactants and the transition states are optimized with Gaussian 09. The barrier heights are calculated with the energy of the reactants and the transition states. The RRKM theory is utilized to calculate the anharmonic and harmonic rate constants of the reactions. The anharmonic effect of these reactions can be clearly demonstrated by our results. Generally speaking, in the study, for most reactions, the rate constants increase with the temperature in the canonical case and the total energy in the microcanonical case, and the anharmonic effect of these reactions is significant and should not be neglected in high-temperature combustion. In CH3SCH2OO system, CH3SCH2OO → CH2SCH2OOH → CH2S + CH2O + OH is the main reaction channel. After a series of calculations, the anharmonic effect is remarkable, especially in high-temperature combustion. By analyzing other meaningful reactions that followed that channel above, the anharmonic effect of these reactions is generally obvious enough, especially for those reactions whose barrier heights are relatively low.
Rh(III)-catalyzed oxidative ortho-C–H alkylation of 2,4-diarylquinazoline with potassium alkyltrifluoroborates
Authors: Gao Wei , Gong Chun , Yang Qin , Yuan Jianjun , Xu Linchu , Peng Yiyuan
Published: July 2017

Alkyltrifluoroborates were used for Rh(III)-catalyzed ortho-alkylation of 2,4-disubstituted quinazoline via C–H bond activation. The reaction proceeded well with a broad substrate scope, providing a direct way to access high functional quinazoline core structure derivatives in yields up to 95%.
The impact of molecular symmetry and shape on the stability of discotic liquid crystals
Authors: Voisin Emilie , Williams Vance E.
Published: July 2017

Three series of dibenzo[a,c]phenazines were prepared in an order to assess the impact of side chain position on the phase stability of columnar liquid crystals. Each series was composed of four isomeric compounds differing only in the disposition of hexyloxy and decyloxy chains around the central aromatic core, giving rise to electronically similar compounds with varying shapes and symmetries. The substitution pattern was found to have a moderate effect on the clearing transition of the liquid crystal but a larger impact on the melting temperatures. These observations suggest a viable strategy for controlling the phase range of liquid crystals via judicious choice of peripheral chain structure and location.
Can a square-mesh panel inserted in front of the cod end improve size and species selectivity in Mediterranean trawl fisheries?
Authors: Brčić Jure , Herrmann Bent , Sala Antonello
Published: July 2017

An experiment was conducted to assess the selectivity in a typical Mediterranean bottom trawl, equipped with a square-mesh panel inserted in front of the cod end, for Atlantic horse mackerel (Trachurus trachurus), European hake (Merluccius merluccius), red mullet (Mullus barbatus), poor cod (Trisopterus minutus), broadtail shortfin squid (Illex coindetii), and deep-water rose shrimp (Parapaeneus longirostris). The release efficiency of undersized individuals through the panel was low. The differences in selectivity between the gear with and without the panel were very small. The low release efficiency of the square-mesh panel was caused by the lack of fish contact with the panel as they drifted towards the cod end, since the average contact probability was estimated not to exceed 9% for any of the species investigated. A low probability of contact with the selection device was thus found to be the reason for the low efficiency of the square-mesh panel.