Respiratory Insufficiency Correlated Strongly with Mortality of Rodents Infected with West Nile Virus

West Nile virus (WNV) disease can be fatal for high-risk patients. Since WNV or its antigens have been identified in multiple anatomical locations of the central nervous system of persons or rodent models, one cannot know where to investigate the actual mechanism of mortality without careful studies in animal models. In this study, depressed respiratory functions measured by plethysmography correlated strongly with mortality. This respiratory distress, as well as reduced oxygen saturation, occurred beginning as early as 4 days before mortality. Affected medullary respiratory control cells may have contributed to the animals' respiratory insufficiency, because WNV antigen staining was present in neurons located in the ventrolateral medulla. Starvation or dehydration would be irrelevant in people, but could cause death in rodents due to lethargy or loss of appetite. Animal experiments were performed to exclude this possibility. Plasma ketones were increased in moribund infected hamsters, but late-stage starvation markers were not apparent. Moreover, daily subcutaneous administration of 5% dextrose in physiological saline solution did not improve survival or other disease signs. Therefore, infected hamsters did not die from starvation or dehydration. No cerebral edema was apparent in WNV- or sham-infected hamsters as determined by comparing wet-to-total weight ratios of brains, or by evaluating blood-brain-barrier permeability using Evans blue dye penetration into brains. Limited vasculitis was present in the right atrium of the heart of infected hamsters, but abnormal electrocardiograms for several days leading up to mortality did not occur. Since respiratory insufficiency was strongly correlated with mortality more than any other pathological parameter, it is the likely cause of death in rodents. These animal data and a poor prognosis for persons with respiratory insufficiency support the hypothesis that neurological lesions affecting respiratory function may be the primary cause of human WNV-induced death

Eye Movements Predict Recollective Experience

Previously encountered stimuli can bring to mind a vivid memory of the episodic context in which the stimulus was first experienced ("remembered'' stimuli), or can simply seem familiar ("known'' stimuli). Past studies suggest that more attentional resources are required to encode stimuli that are subsequently remembered than known. However, it is unclear if the attentional resources are distributed differently during encoding and recognition of remembered and known stimuli. Here, we record eye movements while participants encode photos, and later while indicating whether the photos are remembered, known or new. Eye fixations were more clustered during both encoding and recognition of remembered photos relative to known photos. Thus, recognition of photos that bring to mind a vivid memory for the episodic context in which they were experienced is associated with less distributed overt attention during encoding and recognition. The results suggest that remembering is related to encoding of a few distinct details of a photo rather than the photo as a whole. In turn, during recognition remembering may be trigged by enhanced memory for the salient details of the photos

Associations of sitting accumulation patterns with cardio-metabolic risk biomarkers in Australian adults

Backgroun

Progress and setbacks in socioeconomic inequalities in adolescent health-related behaviours in Brazil: results from three cross-sectional surveys 2009-2015.

OBJECTIVES: Despite some progress, Brazil is still one of the most unequal countries, and the extent of socioeconomic inequalities in adolescent health is unclear. We assessed trends in socioeconomic inequalities in adolescent's health-related behaviours in Brazil between 2009 and 2015. DESIGN: We used cross-sectional data from the Brazilian National Survey of School Health carried out in 2009, 2012 and 2015. SETTING: Brazilian state capitals. PARTICIPANTS: Students attending ninth grade from public and private schools in Brazilian state capitals in 2009 (60 973 students), 2012 (61 145 students) and 2015 (51 192 students). MAIN OUTCOME MEASURE: We assessed 12 health-related behaviours (irregular fruit, vegetables and bean consumption; regular soft drink consumption; irregular physical activity; alcohol, drug and tobacco use; unsafe sex; involvement in gun fights; bullying victimisation and domestic violence victimisation), under the broad domains of lifestyle risk behaviours, engagement in risky activities and exposure to violence. Socioeconomic status was assessed through an asset-based wealth index derived from principal component analysis. Absolute and relative inequalities in these health behaviours and inequalities trends were investigated. RESULTS: From 2009 to 2015, prevalence of certain harmful health-related behaviours increased, such as unsafe sex (21.5% to 33.9%), domestic violence (9.5% to 16.2%), bullying victimisation (14.2% to 21.7%) and irregular consumption of beans (37.5% to 43.7%). Other indicators decreased: alcohol use (27.1% to 23.2%), irregular physical activity (83.0% to 75.6%) and consumption of soft drinks (37.2% to 28.8%). Over the period, we found consistent evidence of decreasing health inequalities for lifestyle behaviours (fruit, bean and soft drink consumption) and alcohol use, set against increasing inequalities in violence (domestic violence, fights using guns and bullying victimisation). CONCLUSION: Socioeconomic inequality increased in the violence domain and decreased for lifestyle behaviours among Brazilian adolescents. Widening gaps in violence domain urge immediately policy measures in Brazil

DNA Suspension Arrays: Silencing Discrete Artifacts for High-Sensitivity Applications

Detection of low frequency single nucleotide polymorphisms (SNPs) has important implications in early screening for tumorgenesis, genetic disorders and pathogen drug resistance. Nucleic acid arrays are a powerful tool for genome-scale SNP analysis, but detection of low-frequency SNPs in a mixed population on an array is problematic. We demonstrate a model assay for HIV-1 drug resistance mutations, wherein ligase discrimination products are collected on a suspension array. In developing this system, we discovered that signal from multiple polymorphisms was obscured by two discrete hybridization artifacts. Specifically: 1) tethering of unligated probes on the template DNA elicited false signal and 2) unpredictable probe secondary structures impaired probe capture and suppressed legitimate signal from the array. Two sets of oligonucleotides were used to disrupt these structures; one to displace unligated reporter labels from the bead-bound species and another to occupy sequences which interfered with array hybridization. This artifact silencing system resulted in a mean 21-fold increased sensitivity for 29 minority variants of 17 codons in our model assay for mutations most commonly associated with HIV-1 drug resistance. Furthermore, since the artifacts we characterized are not unique to our system, their specific inhibition might improve the quality of data from solid-state microarrays as well as from the growing number of multiple analyte suspension arrays relying on sequence-specific nucleic acid target capture

The Cayman Crab Fly Revisited — Phylogeny and Biology of Drosophila endobranchia

BACKGROUND: The majority of all known drosophilid flies feed on microbes. The wide spread of microorganisms consequently mean that drosophilids also can be found on a broad range of substrates. One of the more peculiar types of habitat is shown by three species of flies that have colonized land crabs. In spite of their intriguing lifestyle, the crab flies have remained poorly studied. Perhaps the least investigated of the three crab flies is the Cayman Island endemic Drosophila endobranchia. Apart from its life cycle very little is known about this species, including its phylogenetic position, which has remained unresolved due to a cryptic set of characteristics. PRINCIPAL FINDINGS: Based on molecular data, corroborated by a re-analysis of the morphological make up, we have resolved the phylogenetic position of D. endobranchia and show that it somewhat surprisingly belongs to the large Neotropical repleta radiation, and should be considered as an aberrant member of the canalinea species group. Furthermore we also provide additional data on the behavior of these remarkable flies. CONCLUSION: Our findings reveal that the two Caribbean crab flies are not as distantly related as first thought, as both species are members of the derived repleta radiation. That this lineage has given rise to two species with the same odd type of breeding substrate is curious and prompts the question of what aspects of their shared ancestry has made these flies suitable for a life on (and inside) land crabs. Knowledge of the phylogenetic position of D. endobranchia will allow for comparative explorations and will aid in efforts aimed at understanding processes involved in drastic host shifts and extreme specialization

Functional cognitive disorder: dementia's blind spot

An increasing proportion of cognitive difficulties are recognized to have a functional cause, the chief clinical indicator of which is internal inconsistency. When these symptoms are impairing or distressing, and not better explained by other disorders, this can be conceptualized as a cognitive variant of functional neurological disorder, termed functional cognitive disorder (FCD). FCD is likely very common in clinical practice but may be under-diagnosed. Clinicians in many settings make liberal use of the descriptive term mild cognitive impairment (MCI) for those with cognitive difficulties not impairing enough to qualify as dementia. However, MCI is an aetiology-neutral description, which therefore includes patients with a wide range of underlying causes. Consequently, a proportion of MCI cases are due to non-neurodegenerative processes, including FCD. Indeed, significant numbers of patients diagnosed with MCI do not 'convert' to dementia. The lack of diagnostic specificity for MCI 'non-progressors' is a weakness inherent in framing MCI primarily within a deterministic neurodegenerative pathway. It is recognized that depression, anxiety and behavioural changes can represent a prodrome to neurodegeneration; empirical data are required to explore whether the same might hold for subsets of individuals with FCD. Clinicians and researchers can improve study efficacy and patient outcomes by viewing MCI as a descriptive term with a wide differential diagnosis, including potentially reversible components such as FCD. We present a preliminary definition of functional neurological disorder-cognitive subtype, explain its position in relation to other cognitive diagnoses and emerging biomarkers, highlight clinical features that can lead to positive diagnosis (as opposed to a diagnosis of exclusion), and red flags that should prompt consideration of alternative diagnoses. In the research setting, positive identifiers of FCD will enhance our recognition of individuals who are not in a neurodegenerative prodrome, while greater use of this diagnosis in clinical practice will facilitate personalised interventions

Current status of 5α-reductase inhibitors in the management of lower urinary tract symptoms and BPH

Benign prostatic hyperplasia (BPH) is a progressive disease that is commonly associated with bothersome lower urinary tract symptoms (LUTS) and might result in complications, such as acute urinary retention and BPH-related surgery. Therefore, the goals of therapy for BPH are not only to improve LUTS in terms of symptoms and urinary flow, but also to identify those patients at a risk of unfavorable disease progression and to optimize their management. This article reviews the current status of therapy with 5 alpha-reductase inhibitors (5ARIs), namely fiasteride and dutasteride, for men with LUTS and BPH. Data from key randomized controlled trials (Oxford level 1b) on the use of 5ARIs are analyzed. The efficacy of 5ARIs either as monotherapy or in combination with alpha(1)-adrenoceptor antagonists in the management of LUTS and the impact of monotherapy and combined therapy on BPH progression are discussed. Further promises, including the withdrawal of the alpha-blocker from the combined medical treatment and the potential clinical implications from the use of 5ARIs for prostate cancer chemoprevention in patients receiving 5ARIs for symptomatic BPH are highlighted. Current evidence shows that 5ARIs are effective in treating LUTS and preventing disease progression and represent a recommended option in treatment guidelines for men who have moderate to severe LUTS and enlarged prostates

Access to the next wave of biologic therapies (Abatacept and Tocilizumab) for the treatment of rheumatoid arthritis in England and Wales: Addressing treatment outside the current NICE guidance

Patients in England and Wales with rheumatoid arthritis (RA) receive treatment from the National Health Service (NHS) with therapies approved by the European Medicines Agency (EMA), under guidance from the National Institute for Health and Clinical Excellence (NICE). This document overviews the current NICE guidelines for the treatment of RA and identifies scenarios when such guidance may not represent the optimum management strategy for individual patients. Specifically, we consider the use of tocilizumab or abatacept as the most appropriate treatments for some patients. In such scenarios, it may be possible for the clinician to secure access to the required therapy through an application procedure known as an ‘individual funding request’, the process of which is described in detail here. At present, it is unclear the extent to which the proposed reform of the NHS will affect the role of NICE in providing guidance and setting standards of care. Until the full impact of the proposed changes are realized, individual funding requests will remain a valuable way of securing the optimal treatment for all patients suffering from RA

Developing agreement on never events in primary care dentistry:an international eDelphi study

Introduction: Never events (NEs) are a subset of serious patient safety incidents that should not occur if appropriate preventive measures are implemented. Although there is a consensus in medicine, there is no agreement on NEs in dentistry. Aim: To identify NEs in primary care dentistry. Method: We undertook an electronic Delphi exercise to develop an international agreement on NEs for primary care dentistry. Results: We initially identified candidate NEs through a scoping review of the literature and then analysed dentistry-related reports in a national incident reporting system. Next, we invited an international panel of 41 experts to complete two rounds of questionnaires; 32 agreed to participate (78%) and completed the first round and 29/41 (71%) members completed the second round. We provided anonymised controlled feedback between rounds and used a cut-off of 80% agreement to define consensus. Consensus was achieved for 23 out of 42 candidate NEs. These related to routine assessment, and pre-operative, intra-operative and post-operative stages of dental procedures. Discussion and conclusion: To our knowledge, this is the first international expert consensus-based approach that has identified NEs for primary care dentistry. We suggest that dental regulators consider these to support quality assessment and governance activities