Effects of social disruption in elephants persist decades after culling.

BACKGROUND Multi-level fission-fusion societies, characteristic of a number of large brained mammal species including some primates, cetaceans and elephants, are among the most complex and cognitively demanding animal social systems. Many free-ranging populations of these highly social mammals already face severe human disturbance, which is set to accelerate with projected anthropogenic environmental change. Despite this, our understanding of how such disruption affects core aspects of social functioning is still very limited. RESULTS We now use novel playback experiments to assess decision-making abilities integral to operating successfully within complex societies, and provide the first systematic evidence that fundamental social skills may be significantly impaired by anthropogenic disruption. African elephants (Loxodonta africana) that had experienced separation from family members and translocation during culling operations decades previously performed poorly on systematic tests of their social knowledge, failing to distinguish between callers on the basis of social familiarity. Moreover, elephants from the disrupted population showed no evidence of discriminating between callers when age-related cues simulated individuals on an increasing scale of social dominance, in sharp contrast to the undisturbed population where this core social ability was well developed. CONCLUSIONS Key decision-making abilities that are fundamental to living in complex societies could be significantly altered in the long-term through exposure to severely disruptive events (e.g. culling and translocation). There is an assumption that wildlife responds to increasing pressure from human societies only in terms of demography, however our study demonstrates that the effects may be considerably more pervasive. These findings highlight the potential long-term negative consequences of acute social disruption in cognitively advanced species that live in close-knit kin-based societies, and alter our perspective on the health and functioning of populations that have been subjected to anthropogenic disturbance

p190RhoGAP is cell cycle regulated and affects cytokinesis

p190RhoGAP (p190), a Rho family GTPase-activating protein, regulates actin stress fiber dynamics via hydrolysis of Rho-GTP. Recent data suggest that p190 also regulates cell proliferation. To gain insights into the cellular process(es) affected by p190, we altered its levels by conditional or transient overexpression. Overexpression of p190 resulted in a multinucleated phenotype that was dependent on the GTPase-activating protein domain. Confocal immunofluorescence microscopy revealed that both endogenous and exogenous p190 localized to the newly forming and contracting cleavage furrow of dividing cells. However, overexpression of p190 resulted in abnormal positioning of the furrow specification site and unequal daughter cell partitioning, as well as faulty furrow contraction and multinucleation. Furthermore, levels of endogenous p190 protein were transiently decreased in late mitosis via an ubiquitin-mediated degradation process that required the NH2-terminal GTP-binding region of p190. These results suggest that a cell cycle–regulated reduction in endogenous p190 levels is linked to completion of cytokinesis and generation of viable cell progeny

Understanding Clinicians’ Perceived Barriers and Facilitators to Optimal Use of Acute Oxygen Therapy in Adults

Background: Supplemental oxygen is commonly administered to patients in acute care. It may cause harm when used inappropriately. Guidelines recommend prescription of acute oxygen, yet adherence is poor. We aimed to identify barriers and facilitators to practicing in accordance with the evidence-based Thoracic Society of Australia and New Zealand (TSANZ) oxygen guideline, and to determine the beliefs and attitudes relating to acute oxygen therapy. Methods: A national cross-sectional survey was conducted. The survey consisted of 3 sections: (1) introduction and participant characteristics; (2) opinion/beliefs, knowledge and actions about oxygen therapy and other drugs; and (3) barriers and facilitators to use of the TSANZ guideline. Convenience sampling was employed. A paper-based survey was distributed at the TSANZ Annual Scientific Meeting. An online survey was emailed to the TSANZ membership and to John Hunter Hospital’s clinical staff. Results: Responses were received from 133 clinicians: 52.6% nurses, 30.1% doctors, and 17.3% other clinicians. Over a third (37.7%) were unaware/unsure of the oxygen guideline’s existence. Most (79.8%) believe that oxygen is a drug and should be treated as one. Most (92.4%) stated they only administered it based on clinical need. For four hypothetical cases, there was only one where the majority of participants identified the optimal oxygen saturation. A number of barriers and facilitators were identified when asked about practicing in accordance with the TSANZ guideline. Lack of oxygen equipment, getting doctors to prescribe oxygen and oxygen being treated differently to other drugs were seen as barriers. The guideline itself and multiple clinician characteristics were considered facilitators. Conclusion: There is discordance between clinicians’ beliefs and actions regarding the administration of oxygen therapy and knowledge gaps about optimal oxygen therapy in acute care. Identified barriers and facilitators should be considered when developing evidence-based guidelines to improve dissemination and knowledge exchange

Polymorphism and selection of rpoS in pathogenic Escherichia coli

<p>Abstract</p> <p>Background</p> <p>Though RpoS is important for survival of pathogenic <it>Escherichia coli </it>in natural environments, polymorphism in the <it>rpoS </it>gene is common. However, the causes of this polymorphism and consequential physiological effects on gene expression in pathogenic strains are not fully understood.</p> <p>Results</p> <p>In this study, we found that growth on non-preferred carbon sources can efficiently select for loss of RpoS in seven of ten representative verocytotoxin-producing <it>E. coli </it>(VTEC) strains. Mutants (Suc⁺⁺) forming large colonies on succinate were isolated at a frequency of 10^-8mutants per cell plated. Strain O157:H7 EDL933 yielded mainly mutants (about 90%) that were impaired in catalase expression, suggesting the loss of RpoS function. As expected, inactivating mutations in <it>rpoS </it>sequence were identified in these mutants. Expression of two pathogenicity-related phenotypes, cell adherence and RDAR (red dry and rough) morphotype, were also attenuated, indicating positive control by RpoS. For the other Suc⁺⁺mutants (10%) that were catalase positive, no mutation in <it>rpoS </it>was detected.</p> <p>Conclusion</p> <p>The selection for loss of RpoS on poor carbon sources is also operant in most pathogenic strains, and thus is likely responsible for the occurrence of <it>rpoS </it>polymorphisms among <it>E. coli </it>isolates.</p

Stereotactic Radiofrequency Ablation for Treatment-Refractory Depression:A Systematic Review and Meta-Analysis

(1) Background: Major depressive disorder (MDD) generates a large proportion of global disease burden. Stereotactic radiofrequency ablation (SRA) may be beneficial for selected patients with its most debilitating and refractory forms, but effect size is uncertain. (2) Methods: A systematic literature review and meta-analysis on SRA for MDD was carried out. Patient-level data were extracted from articles reporting validated depression measures (Beck Depression Inventory (BDI), Montgomery–Åsberg Depression Rating Scale (MADRS)), pre- and at least six months post surgery. To accommodate different outcome measures, the standardised mean difference (SMD) between both scores was used as the principal effect size. Data were synthesised using a random-effects model. (3) Results: Five distinct studies were identified, comprising 116 patients (64 included in meta-analysis). Effect size comparing post- vs. pre-operative scores was 1.66 (CI 1.25–2.07). Anterior cingulotomy (two studies, n = 22) and anterior capsulotomy (three studies, n = 42) showed similar effect sizes: 1.51 (CI 0.82–2.20) vs. 1.74 (CI 1.23–2.26). Multiple procedures were performed in 30 of 116 (25.9%) patients. Based on patient-level data, 53% (n = 47) were responders (≥50% improvement), of which 34% reached remission (MADRS ≤ 10 or BDI ≤ 11). BDI mean improvement was 16.7 (44.0%) after a second procedure (n = 19). (4) Conclusions: The results are supportive of the benefit of SRA in selected patients with refractory MDD

Over-Expression of Leptin Receptors in Hypothalamic POMC Neurons Increases Susceptibility to Diet-Induced Obesity

Diet-induced obesity (DIO) in rodents is characterized by impaired activation of signal-transducer and activator of transcription 3 (STAT3) by leptin receptors (LepRb) within the hypothalamic arcuate nucleus. This signaling defect likely plays an important role in development of DIO. However, the neuro-chemical identity of the leptin-STAT3 resistant arcuate neurons has not been determined and the underlying mechanisms responsible for development of cellular leptin resistance remain unclear. To investigate this, we first measured arcuate gene expression of known key signaling components of the LepRb signaling pathway and tested whether specifically the critical arcuate pro-opiomelanocortin (POMC) neurons are resistant to LepRb-STAT3 signaling in mice given a high-fat-diet (HFD) compared to mice provided a low-fat control diet (LFD). We found that leptin-dependent STAT3 phosphorylation was decreased within POMC neurons of HFD mice. In addition, Leprb mRNA and suppressor of cytokine signaling 3 (Socs3) mRNA were elevated in the arcuate of HFD mice. To investigate whether increased LepRb expression per se in POMC neurons can influence development of DIO and Socs3 expression, we created mice that over-express LepRb selectively in POMC neurons (POMC-LepRb). No differences in body weight, fat mass or food intake were found between LFD POMC-LepRb mice and LFD controls. Surprisingly, body weight, fat mass and caloric intake of HFD POMC-LepRb mice was markedly higher than HFD control mice. In addition, arcuate Socs3 mRNA was increased in HFD POMC-LepRb mice compared to HFD controls. These data show that specifically POMC neurons of DIO mice are resistant to STAT3 activation by leptin, indicating that those cells might play a role in development of DIO. Furthermore, over-expression of LepRb selectively in POMC neurons increases susceptibility to the development of DIO. We propose a model where over-reactivity of the leptin-LepRb signaling system in arcuate neurons may play causal a role in development of diet-induced obesity

Evaluation of bile salt hydrolase inhibitor efficacy for modulating host bile profile and physiology using a chicken model system

Gut microbial enzymes, bile salt hydrolases (BSHs) are the gateway enzymes for bile acid (BA) modification in the gut. This activity is a promising target for developing innovative non-antibiotic growth promoters to enhance animal production and health. Compelling evidence has shown that inhibition of BSH activity should enhance weight gain by altering the BA pool, host signalling and lipid metabolism. We recently identified a panel of promising BSH inhibitors. Here, we address the potential of them as alternative, effective, non-antibiotic feed additives, for commercial application, to promote animal growth using a chicken model. In this study, the in vivo efficacy of three BSH inhibitors (caffeic acid phenethylester, riboflavin, carnosic acid) were evaluated. 7-day old chicks (10 birds/group) were either untreated or they received one of the specific BSH inhibitors (25 mg/kg body weight) via oral gavage for 17 days. The chicks in treatment groups consistently displayed higher body weight gain than the untreated chicks. Metabolomic analysis demonstrated that BSH inhibitor treatment led to significant changes in both circulating and intestinal BA signatures in support of blunted intestinal BSH activity. Consistent with this finding, liver and intestinal tissue RNA-Seq analysis showed that carnosic acid treatment significantly altered expression of genes involved in lipid and bile acid metabolism. Taken together, this study validates microbial BSH activity inhibition as an alternative target and strategy to antibiotic treatment for animal growth promotion

Hematological, biochemical, and morphological parameters as prognostic indicators for stranded common dolphins (Delphinus delphis) from Cape Cod, Massachusetts, U.S.A.

© The Author(s), 2013. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Marine Mammal Science 30 (2014): 864–887, doi:10.1111/mms.12093.The current paucity of published blood values and other clinically relevant data for short-beaked common dolphins, Delphinus delphis, hinders the ability of veterinarians and responders to make well-informed diagnoses and disposition decisions regarding live strandings of this species. This study examined hematologic, clinical chemistry, and physical parameters from 26 stranded common dolphins on Cape Cod, Massachusetts, in light of their postrelease survival data to evaluate each parameter's efficacy as a prognostic indicator. Statistically and clinically significant differences were found between failed and survived dolphins, including lower hematocrit, hemoglobin, TCO2, and bicarbonate and higher blood urea nitrogen, uric acid, and length-to-girth ratios in animals that failed. In general when compared to survivors, failed dolphins exhibited acidosis, dehydration, lower PCVs, and decreased body condition. Additionally, failed dolphins had the highest ALT, AST, CK, LDH, GGT, and lactate values. These blood values combined with necropsy findings indicate that there are likely a variety of factors affecting postrelease survival, including both preexisting illness and stranding-induced conditions such as capture myopathy. Closer evaluation of these parameters for stranded common dolphins on point of care analyzers in the field may allow stranding personnel to make better disposition decisions in the future.The John H. Prescott Marine Mammal Rescue Assistance Program provided support for stranding response efforts during this study period (Grants: NA11NMF4390078, NA11NMF4390079, NA11NMF4390093). We would like to thank the Pegasus Foundation and Barbara Birdsey for their support and funding for the IFAW Satellite Tag Program. This project would not have been possible without a summer research grant from the US Army Medical Research and Material Command through Tufts Cummings School of Veterinary Medicine (TCSVM)

Women’s experiences of receiving care for pelvic organ prolapse: a qualitative study

Background Pelvic organ prolapse is a common urogenital condition affecting 41–50% of women over the age of 40. To achieve early diagnosis and appropriate treatment, it is important that care is sensitive to and meets women’s needs, throughout their patient journey. This study explored women’s experiences of seeking diagnosis and treatment for prolapse and their needs and priorities for improving person-centred care. Methods Twenty-two women receiving prolapse care through urogynaecology services across three purposefully selected NHS UK sites took part in three focus groups and four telephone interviews. A topic guide facilitated discussions about women’s experiences of prolapse, diagnosis, treatment, follow-up, interactions with healthcare professionals, overall service delivery, and ideals for future services to meet their needs. Data were analysed thematically. Results Three themes emerged relating to women’s experiences of a) Evaluating what is normal b) Hobson’s choice of treatment decisions, and c) The trial and error of treatment and technique. Women often delayed seeking help for their symptoms due to lack of awareness, embarrassment and stigma. When presented to GPs, their symptoms were often dismissed and unaddressed until they became more severe. Women reported receiving little or no choice in treatment decisions. Choices were often influenced by health professionals’ preferences which were subtly reflected through the framing of the offer. Women’s embodied knowledge of their condition and treatment was largely unheeded, resulting in decisions that were inconsistent with women’s preferences and needs. Physiotherapy based interventions were reported as helping women regain control over their symptoms and life. A need for greater awareness of prolapse and physiotherapy interventions among women, GPs and consultants was identified alongside greater focus on prevention, early diagnosis and regular follow-up. Greater choice and involvement in treatment decision making was desired. Conclusions As prolapse treatment options expand to include more conservative choices, greater awareness and education is needed among women and professionals about these as a first line treatment and preventive measure, alongside a multi-professional team approach to treatment decision making. Women presenting with prolapse symptoms need to be listened to by the health care team, offered better information about treatment choices, and supported to make a decision that is right for them

Management of Acute COPD Exacerbations in Australia: Do we Follow the Guidelines?

Objective: We aimed to assess adherence to the Australian national guideline (COPD-X) against audited practice, and to document the outcomes of patients hospitalised with an acute exacerbation of chronic obstructive pulmonary disease (COPD) at discharge and 28 days after. Methods: A prospective clinical audit of COPD hospital admission from five tertiary care hospitals in five states of Australia was conducted. Post-discharge follow-up was conducted via telephone to assess for readmission and health status. Results: There were 207 admissions for acute exacerbation (171 patients; mean 70.2 years old; 50.3%males). Readmission rates at 28 days were 25.4%, with one (0.6%) death during admission and eight(6.1%) post-discharge within 28 days. Concordance to the COPD-X guidance was variable; 22.7% performed spirometry, 81.1% had blood gases collected when forced expiratory volume in 1 s was \u3c1 \u3eL,99.5% had chest radiography performed, 95.1% were prescribed systemic corticosteroids and 95% were prescribed antibiotic therapy. There were 89.1% given oxygen therapy and 92.6% when arterial oxygen tension was \u3c80 \u3emmHg; 65.6% were given ventilatory assistance when pH was Conclusion: When compared against clinical practice guidelines, we found important gaps in management of patients admitted with COPD throughout tertiary care centres in Australia. Strategies to improve guideline uptake are needed to optimise care