Effects of community health volunteers on infectious diseases of children under five in Volta Region, Ghana: study protocol for a cluster randomized controlled trial.

BACKGROUND: In many low- and middle-income countries, community health volunteers (CHVs) are employed as a key element of the public health system in rural areas with poor accessibility. However, few studies have assessed the effectiveness of CHVs in improving child health in sub-Saharan Africa through randomized controlled trials. The present study aims to measure the impact of health promotion and case management implemented by CHVs on the health of under-5 children in Ghana. METHODS/DESIGN: This study presents the protocol of a cluster-randomized controlled trial assessing the impacts of CHVs, in which the community was used as the randomization unit. A phase-in design will be adopted, and the intervention arm will be implemented in the intervention arm during the first phase and in the control arm during the second phase. The key intervention is the deployment of CHVs, who provide health education, provide oral rehydration solutions and zinc tablets to children with diarrhea, and diagnose malaria using a thermometer and a rapid diagnostic test kit during home visits. The primary endpoints of the study are the prevalence of diarrhea and fever/malaria in children under 5 years of age, as well as the proportion of affected children receiving case management for diarrhea and malaria. The first and second rounds of household surveys to collect data will be conducted in the first phase, and the final round will be conducted during the second phase. DISCUSSION: With growing attention paid to the roles of CHVs as an essential part of the community health system in low-income countries, this study will contribute valuable information to the body of knowledge on the effects of CHVs. TRIAL REGISTRATION: ISRCTN49236178 . (June 16th, 2015)

Crisaborole Ointment, 2%, for Treatment of Patients with Mild-to-Moderate Atopic Dermatitis:Systematic Literature Review and Network Meta-Analysis

The authors would like to replace 2 small sections of the published manuscript that refer to a qualitative review of safety data for included studies (together with an associated safety table), to provide some further clarifications on these safety data and to include some quantitative updates for rates

Time-lapse imaging and cell-specific expression profiling reveal dynamic branching and molecular determinants of a multi-dendritic nociceptor in C. elegans

AbstractNociceptive neurons innervate the skin with complex dendritic arbors that respond to pain-evoking stimuli such as harsh mechanical force or extreme temperatures. Here we describe the structure and development of a model nociceptor, the PVD neuron of C. elegans, and identify transcription factors that control morphogenesis of the PVD dendritic arbor. The two PVD neuron cell bodies occupy positions on either the right (PVDR) or left (PVDL) sides of the animal in posterior–lateral locations. Imaging with a GFP reporter revealed a single axon projecting from the PVD soma to the ventral cord and an elaborate, highly branched arbor of dendritic processes that envelop the animal with a web-like array directly beneath the skin. Dendritic branches emerge in a step-wise fashion during larval development and may use an existing network of peripheral nerve cords as guideposts for key branching decisions. Time-lapse imaging revealed that branching is highly dynamic with active extension and withdrawal and that PVD branch overlap is prevented by a contact-dependent self-avoidance, a mechanism that is also employed by sensory neurons in other organisms. With the goal of identifying genes that regulate dendritic morphogenesis, we used the mRNA-tagging method to produce a gene expression profile of PVD during late larval development. This microarray experiment identified>2,000 genes that are 1.5X elevated relative to all larval cells. The enriched transcripts encode a wide range of proteins with potential roles in PVD function (e.g., DEG/ENaC and Trp channels) or development (e.g., UNC-5 and LIN-17/frizzled receptors). We used RNAi and genetic tests to screen 86 transcription factors from this list and identified eleven genes that specify PVD dendritic structure. These transcription factors appear to control discrete steps in PVD morphogenesis and may either promote or limit PVD branching at specific developmental stages. For example, time-lapse imaging revealed that MEC-3 (LIM homeodomain) is required for branch initiation in early larval development whereas EGL-44 (TEAD domain) prevents ectopic PVD branching in the adult. A comparison of PVD-enriched transcripts to a microarray profile of mammalian nociceptors revealed homologous genes with potentially shared nociceptive functions. We conclude that PVD neurons display striking structural, functional and molecular similarities to nociceptive neurons from more complex organisms and can thus provide a useful model system in which to identify evolutionarily conserved determinants of nociceptor fate

A Community-Based Survey to Assess Knowledge, Attitudes, Beliefs and Practices Regarding Herpes Zoster in an Urban Setting

Introduction: In the USA, nearly one in three people will experience herpes zoster (HZ) in their lifetime. Underserved communities may be at even higher risk due to several factors, including access to healthcare, education, and co-morbid conditions. The purpose of this study was to investigate current knowledge, attitudes, beliefs and practices (KABP) relative to HZ and HZ vaccines in a large urban city. Methods: A cross-sectional KABP survey was conducted via in-person interview among 381 participants aged ≥ 50 years in Detroit, MI, USA, from June to August 2018. Survey results were stratified into two groups [\u3c 60 and ≥ 60 years of age (YO)] for comparison. Results: Of the 381 participants, 373 reported their age (110 \u3c 60 YO and 263 ≥ 60 YO). Overall, the majority of participants reported having heard of HZ and HZ vaccines. In addition, receiving a recommendation from a healthcare provider (37.5%) followed by gaining a better understanding of HZ vaccine (36.7%) and of HZ (29.9%) were leading factors that influenced participants’ willingness to receive the vaccine. Of note, 65.5% of participants \u3c 60 YO reported the belief that HZ is preventable versus only 53.2% in those ≥ 60 YO (p = 0.001). Conclusion: Our findings underscore the need to educate patients in underserved communities about HZ as well as new HZ vaccine recommendations to improve vaccination rates and reduce the incidence of HZ and its associated sequelae

Matching-Adjusted Indirect Comparison of Crisaborole Ointment 2% vs. Topical Calcineurin Inhibitors in the Treatment of Patients with Mild-to-Moderate Atopic Dermatitis

INTRODUCTION: Crisaborole topical ointment, 2%, is a nonsteroidal, topical anti-inflammatory phosphodiesterase-4 (PDE4) inhibitor that is approved for the treatment of mild-to-moderate atopic dermatitis (AD). The objective of the current analysis was to compare the efficacy of crisaborole 2% relative to pimecrolimus 1%, tacrolimus 0.03% and tacrolimus 0.1% in patients aged ≥ 2 years with mild-to-moderate AD by comparing improvement in Investigator’s Static Global Assessment scores ( (ISGA scores of 0/1 indicating “clear or almost clear”). ISGA was selected as the primary efficacy outcome given the US Food and Drug Administration’s recommendations on the use of ISGA for assessment of global severity in AD and to align with efficacy measurements in the crisaborole registration trials. Safety endpoints could not be analyzed due to differences in outcome definitions across studies. METHODS: Efficacy of crisaborole was evaluated using individual patient data (IPD) from two pivotal phase III randomized controlled trials (RCTs), and efficacy of comparators was evaluated using published RCTs included in a previous network meta-analysis. Vehicle controls were not comparable due to differences in ingredients and population imbalance and, therefore, an unanchored matching-adjusted indirect comparison (MAIC) was used, which reweighted IPD for crisaborole to estimate absolute response in comparator populations. RESULTS: The odds of achieving an improvement in ISGA score was higher with crisaborole 2% versus pimecrolimus 1% (odds ratio [OR] 2.03; 95% confidence interval [CI] 1.45–2.85; effective sample size =  627, reduced from 1021; p value < 0.001) and for crisaborole 2% versus tacrolimus 0.03% (OR 1.50; 95% CI 1.09–2.05; effective sample size = 311, reduced from 1021; p = 0.012). CONCLUSION: The unanchored MAIC suggests that the odds of achieving an improvement in ISGA score is greater with crisaborole 2% than with pimecrolimus 1% or tacrolimus 0.03% in patients aged ≥ 2 years with mild-to-moderate AD. These results are consistent with findings from the previously published network meta-analysis, which used a different methodology for performing indirect treatment comparisons. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13555-021-00646-1

What situations trigger intense emotions in automobiles?

Driving involves a variety of events and activities that stimulate emotional experiences. The aim of this investigation was to examine automobile experiences and to identify affective themes. 245 UK-based participants were recruited using a purposive sampling strategy. One study consisted of an online questionnaire which inquired about the automotive experiences which proved most emotionally intense. The second consisted of a simulator based immersive driving experience, followed afterwards by a questionnaire which inquired about the automotive experiences which proved most emotionally intense. Questionnaire responses were clustered into themes using a content analysis method. The study identified 13 major themes and 44 sub-themes. The findings provide guidance regarding the triggers of emotional responses which designers can use to better understand and to improve automotive experiences

The isopropylation of naphthalene with propene over H-mordenite: The catalysis at the internal and external acid sites

The isopropylation of naphthalene (NP) with propene over H-Mordenite (MOR) was studied under a wide range of reaction parameters: temperature, propene pressure, period, and NP/MOR ratio. Selective formation of 2,6-diisopropylnaphthalene (2,6-DIPN) was observed at reaction conditions, such as at low reaction temperature, under high propene pressure, and/or with high NP/MOR ratio. However, the decrease in the selectivities for 2,6-DIPN was observed at reaction conditions such as at high temperature, under low propene pressure, and/or with low NP/MOR ratio. The selectivities for 2,6-DIPN in the encapsulated products were remained high and constant under all reaction conditions. These results indicate that the selective formation of 2,6-DIPN occurs through the least bulky transition state due to the exclusion of the bulky isomers by the MOR channels. The decrease in the selectivities for 2,6-DIPN are due to the isomerization of 2,6-DIPN to 2,7-DIPN at the external acid sites, directing towards thermodynamic equilibrium of DIPN isomers

Dendritic Hold and Read: A Gated Mechanism for Short Term Information Storage and Retrieval

Two contrasting theories have been proposed to explain the mechanistic basis of short term memory. One theory posits that short term memory is represented by persistent neural activity supported by reverberating feedback networks. An alternate, more recent theory posits that short term memory can be supported by feedforward networks. While feedback driven memory can be implemented by well described mechanisms of synaptic plasticity, little is known of possible molecular and cellular mechanisms that can implement feedforward driven memory. Here we report such a mechanism in which the memory trace exists in the form of glutamate-bound but Mg2+-blocked NMDA receptors on the thin terminal dendrites of CA1 pyramidal neurons. Because glutamate dissociates from subsets of NMDA receptors very slowly, excitatory synaptic transmission can leave a silent residual trace that outlasts the electrical activity by hundreds of milliseconds. Read-out of the memory trace is possible if a critical level of these bound-but-blocked receptors accumulates on a dendritic branch that will allow these quasi-stable receptors to sustain a regenerative depolarization when triggered by an independent gating signal. This process is referred to here as dendritic hold and read (DHR). Because the read-out of the input is not dependent on repetition of the input and information flows in a single-pass manner, DHR can potentially support a feedforward memory architecture

Intraoperative visualisation and treatment of salivary glands in Sjögren's syndrome by contrast-enhanced ultrasound sialendoscopy (CEUSS):protocol for a phase I single-centre, single-arm, exploratory study

INTRODUCTION: We established a promising sialendoscopic treatment for in vivo enhancement of salivation in salivary glands affected by Sjögren's syndrome (SS). In this technique, the ducts of the salivary glands are irrigated with saline and steroids. This allows for dilatation of ductal strictures and removal of debris. Unfortunately, it is not possible to assess the delivery and penetration of saline or medications in the ductal system and parenchyma. To address this problem, we will conduct contrast-enhanced ultrasound sialendoscopy (CEUSS) using sulphur hexafluoride microbubbles. To the best of our knowledge, microbubbles have never been used for the treatment of salivary glands in SS. It is, therefore, imperative to test this application for its safety and feasibility. METHODS AND ANALYSIS: A single-arm phase I study will be performed in 10 SS patients. Under local anaesthesia, ultrasound (US) guided infusion of the parotid and submandibular glands with microbubbles will be performed. Continuous US imaging will be used to visualise the glands, including the location of strictures and occlusions. Main outcomes will be the evaluation of safety and technical feasibility of the experimental treatment. Secondary outcomes will consist of determinations of unstimulated whole mouth saliva flow, stimulated whole mouth saliva flow, stimulated parotid saliva flow, clinical oral dryness, reported pain, xerostomia, disease activity, salivary cytokine profiles and clinical SS symptoms. Finally, salivary gland topographical alterations will be evaluated by US. ETHICS AND DISSEMINATION: Ethical approval for this study was obtained from the Medical Ethics Committee of the Amsterdam University Medical Centre, Amsterdam, The Netherlands (NL68283.029.19). data will be presented at national and international conferences and published in a peer-reviewed journal. The study will be implemented and reported in line with the Standard Protocol Items: Recommendations for Interventional Trials' statement. TRIAL REGISTRATION NUMBERS: The Netherlands Trial Register: NL7731, MREC Trial Register: NL68283.029.19; Pre-results