3-(Benzimidazolium-2-yl)propionate dihydrate

In the crystal struture of the title compound, C10H10N2O2·2H2O, the component species are linked to the water mol­ecules by N—H⋯O and O—H⋯O hydrogen bonds to form a three-dimensional network structure

Metagenomic study of the viruses of African straw-coloured fruit bats: detection of a chiropteran poxvirus and isolation of a novel adenovirus

Viral emergence as a result of zoonotic transmission constitutes a continuous public health threat. Emerging viruses such as SARS coronavirus, hantaviruses and henipaviruses have wildlife reservoirs. Characterising the viruses of candidate reservoir species in geographical hot spots for viral emergence is a sensible approach to develop tools to predict, prevent, or contain emergence events. Here, we explore the viruses of Eidolon helvum, an Old World fruit bat species widely distributed in Africa that lives in close proximity to humans. We identified a great abundance and diversity of novel herpes and papillomaviruses, described the isolation of a novel adenovirus, and detected, for the first time, sequences of a chiropteran poxvirus closely related with Molluscum contagiosum. In sum, E. helvum display a wide variety of mammalian viruses, some of them genetically similar to known human pathogens, highlighting the possibility of zoonotic transmission

Intrathecal Immunoglobulin for treatment of adult patients with tetanus: A randomized controlled 2x2 factorial trial

Despite long-standing availability of an effective vaccine, tetanus remains a significant problem in many countries. Outcome depends on access to mechanical ventilation and intensive care facilities and in settings where these are limited, mortality remains high. Administration of tetanus antitoxin by the intramuscular route is recommended treatment for tetanus, but as the tetanus toxin acts within the central nervous system, it has been suggested that intrathecal administration of antitoxin may be beneficial. Previous studies have indicated benefit, but with the exception of one small trial no blinded studies have been performed. The objective of this study is to establish whether the addition of intrathecal tetanus antitoxin reduces the need for mechanical ventilation in patients with tetanus. Secondary objectives: to determine whether the addition of intrathecal tetanus antitoxin reduces autonomic nervous system dysfunction and length of hospital/ intensive care unit stay; whether the addition of intrathecal tetanus antitoxin in the treatment of tetanus is safe and cost-effective; to provide data to inform recommendation of human rather than equine antitoxin. This study will enroll adult patients (≥16 years old) with tetanus admitted to the Hospital for Tropical Diseases, Ho Chi Minh City. The study is a 2x2 factorial blinded randomized controlled trial. Eligible patients will be randomized in a 1:1:1:1 manner to the four treatment arms (intrathecal treatment and human intramuscular treatment, intrathecal treatment and equine intramuscular treatment, sham procedure and human intramuscular treatment, sham procedure and equine intramuscular treatment). Primary outcome measure will be requirement for mechanical ventilation. Secondary outcome measures: duration of hospital/ intensive care unit stay, duration of mechanical ventilation, in-hospital and 240-day mortality and disability, new antibiotic prescription, incidence of ventilator associated pneumonia and autonomic nervous system dysfunction, total dose of benzodiazepines and pipecuronium, and incidence of adverse events. Trial registration: ClinicalTrials.gov NCT02999815 Registration date: 21 December 2016

Sample size requirements for separating out the effects of combination treatments: Randomised controlled trials of combination therapy vs. standard treatment compared to factorial designs for patients with tuberculous meningitis

<p>Abstract</p> <p>Background</p> <p>In certain diseases clinical experts may judge that the intervention with the best prospects is the addition of two treatments to the standard of care. This can either be tested with a simple randomized trial of combination versus standard treatment or with a 2 × 2 factorial design.</p> <p>Methods</p> <p>We compared the two approaches using the design of a new trial in tuberculous meningitis as an example. In that trial the combination of 2 drugs added to standard treatment is assumed to reduce the hazard of death by 30% and the sample size of the combination trial to achieve 80% power is 750 patients. We calculated the power of corresponding factorial designs with one- to sixteen-fold the sample size of the combination trial depending on the contribution of each individual drug to the combination treatment effect and the strength of an interaction between the two.</p> <p>Results</p> <p>In the absence of an interaction, an eight-fold increase in sample size for the factorial design as compared to the combination trial is required to get 80% power to jointly detect effects of both drugs if the contribution of the less potent treatment to the total effect is at least 35%. An eight-fold sample size increase also provides a power of 76% to detect a qualitative interaction at the one-sided 10% significance level if the individual effects of both drugs are equal. Factorial designs with a lower sample size have a high chance to be underpowered, to show significance of only one drug even if both are equally effective, and to miss important interactions.</p> <p>Conclusions</p> <p>Pragmatic combination trials of multiple interventions versus standard therapy are valuable in diseases with a limited patient pool if all interventions test the same treatment concept, it is considered likely that either both or none of the individual interventions are effective, and only moderate drug interactions are suspected. An adequately powered 2 × 2 factorial design to detect effects of individual drugs would require at least 8-fold the sample size of the combination trial.</p> <p>Trial registration</p> <p>Current Controlled Trials <a href="http://www.controlled-trials.com/ISRCTN61649292">ISRCTN61649292</a></p

Discovering unique tobacco use patterns among Alaska Native people

Background . Alaska Native people are disproportionately impacted by tobacco-related diseases in comparison to non-Native Alaskans. Design. We used Alaska&#x0027;s Behavioral Risk Factor Surveillance System (BRFSS) to describe tobacco use among more than 4,100 Alaska Native adults, stratified by geographic region and demographic groups. Results . Overall tobacco use was high: approximately 2 out of every 5 Alaska Native adults reported smoking cigarettes (41.2%) and 1 in 10 reported using smokeless tobacco (SLT, 12.3%). A small percentage overall (4.8%) reported using iq&#x0027;mik, an SLT variant unique to Alaska Native people. When examined by geographic region, cigarette smoking was highest in remote geographic regions; SLT use was highest in the southwest region of the state. Use of iq&#x0027;mik was primarily confined to a specific area of the state; further analysis showed that 1 in 3 women currently used iq&#x0027;mik in this region. Conclusion . Our results suggest that different types of tobacco use are epidemic among diverse Alaska Native communities. Our results also illustrate that detailed analysis within racial/ethnic groups can be useful for public health programme planning to reduce health disparities

Teachers' resilience: conceived, perceived or lived-in

[Extract] Schools in Western countries are places where work related conditions lead to teacher disaffection and attrition. To mitigate this employers and scholars advocate fostering teacher resilience. This chapter presents a critical examination of teacher resilience. Originally conceived as a personal trait, later research showed human resilience is an attribute that can be developed. Resilience is one’s ability to manage stressors and maintain adaptive functioning across all domains of life. Latterly, scholars investigated resilience in teachers, mainly through qualitative or quantitative self-report studies. This research constitutes perceived teacher resilience, because as formulated, teacher resilience is conceptually flawed, limited in scope, based on teachers’ functioning within their professional lives. We do not know what constitutes long serving teachers’ actual, lived-in resilience: what enables teachers to maintain their wellbeing and effectiveness in the classroom, reflecting human resilience as originally conceived. For an accurate profile of teacher resilience we must study those still teaching, and teachers who have exited the profession to determine why they left. Perhaps exiting the profession signals a resilient person who does accept working conditions that do not support wellbeing or teaching effectiveness. Perhaps ‘teacher resilience’ is inaccurately used in the context of teacher attrition and disaffection

Intensified treatment with high dose Rifampicin and Levofloxacin compared to standard treatment for adult patients with Tuberculous Meningitis (TBM-IT): protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Tuberculous meningitis is the most severe form of tuberculosis. Mortality for untreated tuberculous meningitis is 100%. Despite the introduction of antibiotic treatment for tuberculosis the mortality rate for tuberculous meningitis remains high; approximately 25% for HIV-negative and 67% for HIV positive patients with most deaths occurring within one month of starting therapy. The high mortality rate in tuberculous meningitis reflects the severity of the condition but also the poor antibacterial activity of current treatment regimes and relatively poor penetration of these drugs into the central nervous system. Improving the antitubercular activity in the central nervous system of current therapy may help improve outcomes. Increasing the dose of rifampicin, a key drug with known poor cerebrospinal fluid penetration may lead to higher drug levels at the site of infection and may improve survival. Of the second generation fluoroquinolones, levofloxacin may have the optimal pharmacological features including cerebrospinal fluid penetration, with a ratio of Area Under the Curve (AUC) in cerebrospinal fluid to AUC in plasma of >75% and strong bactericidal activity against <it>Mycobacterium tuberculosis</it>. We propose a randomized controlled trial to assess the efficacy of an intensified anti-tubercular treatment regimen in tuberculous meningitis patients, comparing current standard tuberculous meningitis treatment regimens with standard treatment intensified with high-dose rifampicin and additional levofloxacin.</p> <p>Methods/Design</p> <p>A randomized, double blind, placebo-controlled trial with two parallel arms, comparing standard Vietnamese national guideline treatment for tuberculous meningitis with standard treatment <it>plus </it>an increased dose of rifampicin (to 15 mg/kg/day total) and additional levofloxacin. The study will include 750 patients (375 per treatment group) including a minimum of 350 HIV-positive patients. The calculation assumes an overall mortality of 40% vs. 30% in the two arms, respectively (corresponding to a target hazard ratio of 0.7), a power of 80% and a two-sided significance level of 5%. Randomization ratio is 1:1. The primary endpoint is overall survival, i.e. time from randomization to death during a follow-up period of 9 months. Secondary endpoints are: neurological disability at 9 months, time to new neurological event or death, time to new or recurrent AIDS-defining illness or death (in HIV-positive patients only), severe adverse events, and rate of treatment interruption for adverse events.</p> <p>Discussion</p> <p>Currently very few options are available for the treatment of TBM and the mortality rate remains unacceptably high with severe disabilities seen in many of the survivors. This trial is based on the hypothesis that current anti-mycobacterial treatment schedules for TBM are not potent enough and that outcomes will be improved by increasing the CSF penetrating power of this regimen by optimising dosage and using additional drugs with better CSF penetration.</p> <p>Trial registration</p> <p>International Standard Randomised Controlled Trial Number <a href="http://www.controlled-trials.com/ISRCTN61649292">ISRCTN61649292</a></p

Three phylogenetic groups have driven the recent population expansion of Cryptococcus neoformans.

Cryptococcus neoformans (C. neoformans var. grubii) is an environmentally acquired pathogen causing 181,000 HIV-associated deaths each year. We sequenced 699 isolates, primarily C. neoformans from HIV-infected patients, from 5 countries in Asia and Africa. The phylogeny of C. neoformans reveals a recent exponential population expansion, consistent with the increase in the number of susceptible hosts. In our study population, this expansion has been driven by three sub-clades of the C. neoformans VNIa lineage; VNIa-4, VNIa-5 and VNIa-93. These three sub-clades account for 91% of clinical isolates sequenced in our study. Combining the genome data with clinical information, we find that the VNIa-93 sub-clade, the most common sub-clade in Uganda and Malawi, was associated with better outcomes than VNIa-4 and VNIa-5, which predominate in Southeast Asia. This study lays the foundation for further work investigating the dominance of VNIa-4, VNIa-5 and VNIa-93 and the association between lineage and clinical phenotype

Re-interpreting plant morphological responses to UV-B radiation

There is a need to reappraise the effects of UV-B radiation on plant morphology in light of improved mechanistic understanding of UV-B effects, particularly elucidation of the UV RESISTANCE LOCUS 8 (UVR8) photoreceptor. We review responses at cell and organismal levels, and explore their underlying regulatory mechanisms, function in UV protection and consequences for plant fitness. UV-induced morphological changes include thicker leaves, shorter petioles, shorter stems, increased axillary branching and altered root:shoot ratios. At the cellular level, UV-B morphogenesis comprises changes in cell division, elongation and/or differentiation. However, notwithstanding substantial new knowledge of molecular, cellular and organismal UV-B responses, there remains a clear gap in our understanding of the interactions between these organizational levels, and how they control plant architecture. Furthermore, despite a broad consensus that UV-B induces relatively compact architecture, we note substantial diversity in reported phenotypes. This may relate to UV-induced morphological changes being underpinned by different mechanisms at high and low UV-B doses. It remains unproven whether UV-induced morphological changes have a protective function involving shading and decreased leaf penetration of UV-B, counterbalancing trade-offs such as decreased photosynthetic light capture and plant-competitive abilities. Future research will need to disentangle seemingly contradictory interactions occurring at the threshold UV dose where regulation and stress-induced morphogenesis overlap. We review the effects of UV-B on plant morphology, using the improved mechanistic understanding of UV perception and signalling following elucidation of the UVR8 photoreceptor to reappraise published results. Despite a substantially improved understanding of molecular, cellular and organismal UV-B responses, there remains a clear gap in our knowledge of the interactions between these organisational levels, their function in UV-protection, and consequences for plant fitness and plant-plant interactions. Future research will need to disentangle the seemingly contradictory interactions and substantial diversity in reported phenotypes that occur at the threshold UV dose where regulation and stress-induced morphogenesis overlap.Peer reviewe

Impact of periodic health examination on surgical treatment for uterine fibroids in Beijing: a case-control study

<p>Abstract</p> <p>Background</p> <p>During the past 2 decades, there has been a rapid proliferation of "health examination center (HEC)" across China. The effects of their services on public's health have not been systemically investigated. This study aimed to assess the impact of periodic health examination (PHE) at HEC on surgical treatment for uterine fibroids in Beijing residents.</p> <p>Methods</p> <p>We identified 224 patients with a primary diagnosis of uterine fibroids who had surgical treatment at four Level-1 general hospitals in Beijing, from June 1, 2009 to October 20, 2009. Controls were women who did not have surgery for uterine fibroids, matched (1:1 ratio) for age (within 2 years). A standard questionnaire was used to inquire about whether participants had PHE at HEC during the previous 2 years.</p> <p>Results</p> <p>PHE at HEC within 2 years were associated with surgical treatment for uterine fibroids. Odds ratios was 4.05 (95% CI, 2.61-6.29 P < 0.001), after adjustment for marital status, whether have children, annual family income, health insurance, education level and self-rated uterine fibroids-related symptom severity.</p> <p>Conclusions</p> <p>Our study showed PHE currently provided at HEC in China were associated with significantly increased use of surgical treatment for uterine fibroids in women. Further studies are needed to assess the effects of PHE on clinical as well as on broad societal outcomes in Chinese in contemporary medical settings.</p