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Intestinal ischemia results in mucosal injury, including paracellular barrier loss due to disruption of tight junctions. Larazotide acetate (LA), a small peptide studied in Phase III clinical trials for treatment of celiac disease, regulates tight junctions (TJs). We hypothesized that LA would dose-dependently hasten recovery of intestinal ischemic injury via modulation of TJs. Ischemia-injured tissue from 6-8-week-old pigs was recovered in Ussing chambers for 240-minutes in the presence of LA. LA (1 μM but not 0.1 μM or 10 μM) significantly enhanced transepithelial electrical resistance (TER) above ischemic injured controls and significantly reduced serosal-to-mucosal flux LPS (P

Population-based public health data on antibiotic resistance gene carriage is poorly surveyed. Research of the human microbiome as an antibiotic resistance reservoir has primarily focused on gut associated microbial communities, but data have shown more widespread microbial colonization across organs than originally believed, with organs previously considered as sterile being colonized. Our study demonstrates the utility of postmortem microbiome sampling during routine autopsy as a method to survey antibiotic resistance carriage in a general population. Postmortem microbial sampling detected pathogens of public health concern including genes for multidrug efflux pumps, carbapenem, methicillin, vancomycin, and polymixin resistances. Results suggest that postmortem assessments of host-associated microbial communities are useful in acquiring community specific data while reducing selective-participant biases.

Infantile spasms are the defining seizures of West syndrome, a severe form of early life epilepsy with poorly-understood pathophysiology. We present a novel comparative analysis of infants with spasms versus other seizure-types and identify clinical, etiological, and molecular-genetic factors preferentially predisposing to spasms. We compared ages, clinical etiologies, and associated-genes between spasms and non-spasms groups in a multicenter cohort of 509 infants (

Carbon monoxide (CO) at low, non-toxic concentrations has been previously demonstrated to exert anti-inflammatory protection in murine models of sickle cell disease (SCD). However CO delivery by inhalation, CO-hemoglobin infusion or CO-releasing molecules presents problems for daily CO administration. Oral administration of a CO-saturated liquid avoids many of these issues and potentially provides a platform for self-administration to SCD patients. To test if orally-delivered CO could modulate SCD vaso-occlusion and inflammation, a liquid CO formulation (HBI-002) was administered by gavage (10 ml/kg) once-daily to NY1DD and Townes-SS transgenic mouse models of SCD. Baseline CO-hemoglobin (CO-Hb) levels were 1.6% and 1.8% in NY1DD and Townes-SS sickle mice and 0.6% in Townes-AS control mice. CO-Hb levels reached 5.4%, 4.7% and 3.0% within 5 minutes in NY1DD, SS and AS mice respectively after gavage with HBI-002. After ten treatments, each once-daily, hemoglobin levels rose from 5.3g/dL in vehicle-treated Townes-SS mice to 6.3g/dL in HBI-002-treated. Similarly, red blood cell (RBC) counts rose from 2.36 x 106/μL in vehicle-treated SS mice to 2.89 x 106/μL in HBI-002-treated mice. In concordance with these findings, hematocrits rose from 26.3% in vehicle-treated mice to 30.0% in HBI-002-treated mice. Reticulocyte counts were not significantly different between vehicle and HBI-002-treated SS mice implying less hemolysis and not an increase in RBC production. White blood cell counts decreased from 29.1 x 103/μL in vehicle-treated versus 20.3 x 103/μL in HBI-002-treated SS mice. Townes-SS mice treated with HBI-002 had markedly increased Nrf2 and HO-1 expression and decreased NF-κB activation compared to vehicle-treated mice. These anti-inflammatory effects were examined for the ability of HBI-002 (administered orally once-daily for up to 5 days) to inhibit vaso-occlusion induced by hypoxia-reoxygenation. In NY1DD and Townes-SS sickle mice, HBI-002 decreased microvascular stasis in a duration-dependent manner. Collectively, these findings support HBI-002 as a useful anti-inflammatory agent to treat SCD and warrants further development as a therapeutic.

Telomere length has garnered interest due to the potential role it may play as a biomarker for the cellular aging process. Telomere measurements obtained from blood-derived DNA are often used in epidemiological studies. However, the invasive nature of blood draws severely limits sample collection, particularly with children. Buccal cells are commonly sampled for DNA isolation and thus may present a non-invasive alternative for telomere measurement. Buccal and leukocyte derived DNA obtained from samples collected at the same time period were analyzed for telomere repeat mass (TRM). TRM was measured in buccal-derived DNA samples from individuals for whom previous TRM data from blood samples existed. TRM measurement was performed by qPCR and was normalized to the single copy 36B4 gene relative to a reference DNA sample (K562). Correlations between TRM from blood and buccal DNA were obtained and also between the same blood DNA samples measured in separate laboratories. Using the classical twin design, TRM heritability was estimated (N = 1892, MZ = 1044, DZ = 775). Buccal samples measured for TRM showed a significant correlation with the blood-1 (R = 0.39, p < 0.01) and blood-2 (R = 0.36, p < 0.01) samples. Sex and age effects were observed within the buccal samples as is the norm within blood-derived DNA. The buccal, blood-1, and blood-2 measurements generated heritability estimates of 23.3%, 47.6% and 22.2%, respectively. Buccal derived DNA provides a valid source for the determination of TRM, paving the way for non-invasive projects, such as longitudinal studies in children.

Airway mucociliary clearance (MCC) is an important defense mechanism against pulmonary infections and is compromised in cystic fibrosis (CF). Cl- and HCO3- epithelial transport are integral to MCC. During pulmonary infections prostaglandin E2 (PGE2) production is abundant.To determine the effect of PGE2 on airway Cl- and HCO3- secretion and MCC in normal and CF airways.We examined PGE2 stimulated MCC, Cl- and HCO3- secretion using ferret trachea, human bronchial epithelial cell cultures (CFBE41o- with wildtype CFTR (CFBE41 WT) or homozygous F508del CFTR (CFBE41 CF) and human normal bronchial submucosal gland cell line (Calu-3) in Ussing chambers with or without pH-stat.PGE2 stimulated MCC in a dose-dependent manner and was partially impaired by CFTRinh-172. PGE2-stimulated Cl- current in ferret trachea was partially inhibited by CFTRinh-172, with niflumic acid eliminating the residual current. CFBE41 WT cell monolayers produced a robust Cl- and HCO3- secretory response to PGE2, both of which were completely inhibited by CFTRinh-172. CFBE41 CF cells exhibited no response to PGE2. In Calu-3 cells, PGE2 stimulated Cl- and HCO3- secretion. Cl- secretion was partially inhibited by CFTRinh-172, with additional inhibition by niflumic acid. HCO3- secretion was completely inhibited by CFTRinh-172.PGE2 stimulates bronchotracheal MCC and this response is decreased in CF. In CF airway, PGE2-stimulated Cl- and HCO3- conductance is impaired and may contribute to decreased MCC. There remains a CFTR-independent Cl- current in submucosal glands, which if exploited, could represent a means of improving airway Cl- secretion and MCC in CF.

Sepsis remains one of the leading causes of death in burn patients who survive the initial insult of injury. Disruption of the intestinal epithelial barrier has been shown after burn injury; this can lead to the translocation of bacteria or their products (e.g., endotoxin) from the intestinal lumen to the circulation, thereby increasing the risk for sepsis in immunocompromised individuals. Since the maintenance of the epithelial barrier is largely dependent on the intestinal microbiota, we examined the diversity of the intestinal microbiome of severely burned patients and a controlled mouse model of burn injury. We show that burn injury induces a dramatic dysbiosis of the intestinal microbiome of both humans and mice and allows for similar overgrowths of Gram-negative aerobic bacteria. Furthermore, we show that the bacteria increasing in abundance have the potential to translocate to extra-intestinal sites. This study provides an insight into how the diversity of the intestinal microbiome changes after burn injury and some of the consequences these gut bacteria can have in the host.

We introduce and make publicly available a large corpus of digitized primary source human rights documents which are published annually by monitoring agencies that include Amnesty International, Human Rights Watch, the Lawyers Committee for Human Rights, and the United States Department of State. In addition to the digitized text, we also make available and describe document-term matrices, which are datasets that systematically organize the word counts from each unique document by each unique term within the corpus of human rights documents. To contextualize the importance of this corpus, we describe the development of coding procedures in the human rights community and several existing categorical indicators that have been created by human coding of the human rights documents contained in the corpus. We then discuss how the new human rights corpus and the existing human rights datasets can be used with a variety of statistical analyses and machine learning algorithms to help scholars understand how human rights practices and reporting have evolved over time. We close with a discussion of our plans for dataset maintenance, updating, and availability.

We present a complete hardware and software system for collecting and quantifying continuous measures of feeding behaviors in the fruit fly, Drosophila melanogaster. The FLIC (Fly Liquid-Food Interaction Counter) detects analog electronic signals as brief as 50 µs that occur when a fly makes physical contact with liquid food. Signal characteristics effectively distinguish between different types of behaviors, such as feeding and tasting events. The FLIC system performs as well or better than popular methods for simple assays, and it provides an unprecedented opportunity to study novel components of feeding behavior, such as time-dependent changes in food preference and individual levels of motivation and hunger. Furthermore, FLIC experiments can persist indefinitely without disturbance, and we highlight this ability by establishing a detailed picture of circadian feeding behaviors in the fly. We believe that the FLIC system will work hand-in-hand with modern molecular techniques to facilitate mechanistic studies of feeding behaviors in Drosophila using modern, high-throughput technologies.

Across the planet, high-intensity farming has transformed native vegetation into monocultures, decreasing biodiversity on a landscape scale. Yet landscape-scale changes to biodiversity and community structure often emerge from processes operating at local scales. One common process that can explain changes in biodiversity and community structure is the creation of abrupt habitat edges, which, in turn, generate edge effects. Such effects, while incredibly common, can be highly variable across space and time; however, we currently lack a general analytical framework that can adequately capture such spatio-temporal variability. We extend previous approaches for estimating edge effects to a non-linear mixed modeling framework that captures such spatio-temporal heterogeneity and apply it to understand how agricultural land-uses alter wildlife communities. We trapped small mammals along a conservation-agriculture land-use interface extending 375 m into sugarcane plantations and conservation land-uses at three sites during dry and wet seasons in Swaziland, Africa. Sugarcane plantations had significant reductions in species richness and heterogeneity, and showed an increase in community similarity, suggesting a more homogenized small mammal community. Furthermore, our modeling framework identified strong variation in edge effects on communities across sites and seasons. Using small mammals as an indicator, intensive agricultural practices appear to create high-density communities of generalist species while isolating interior species in less than 225 m. These results illustrate how agricultural land-use can reduce diversity across the landscape and that effects can be masked or magnified, depending on local conditions. Taken together, our results emphasize the need to create or retain natural habitat features in agricultural mosaics.

Brain plasticity, in relation to new adult mammalian neurons generated in the subgranular zone of the hippocampus, has been well described. However, the functional outcome of new adult olfactory neurons born in the subventricular zone of the lateral ventricles is not clearly defined, as manipulating neurogenesis through various methods has given inconsistent and conflicting results in lab mice. Several small rodent species, including Peromyscus leucopus, display seasonal (photoperiodic) brain plasticity in brain volume, hippocampal function, and hippocampus-dependent behaviors; plasticity in the olfactory system of photoperiodic rodents remains largely uninvestigated. We exposed adult male P. leucopus to long day lengths (LD) and short day lengths (SD) for 10 to 15 weeks and then examined olfactory bulb cell proliferation and survival using the thymidine analog BrdU, olfactory bulb granule cell morphology using Golgi-Cox staining, and behavioral investigation of same-sex conspecific urine. SD mice did not differ from LD counterparts in granular cell morphology of the dendrites or in dendritic spine density. Although there were no differences due to photoperiod in habituation to water odor, SD mice rapidly habituated to male urine, whereas LD mice did not. In addition, short day induced changes in olfactory behavior were associated with increased neurogenesis in the caudal plexiform and granule cell layers of the olfactory bulb, an area known to preferentially respond to water-soluble odorants. Taken together, these data demonstrate that photoperiod, without altering olfactory bulb neuronal morphology, alters olfactory bulb neurogenesis and olfactory behavior in Peromyscus leucopus.

Pivotal components of the IFN response to virus infection include the IFN receptors (IFNR), and the downstream factor signal transducer and activator of transcription 1 (Stat1). Mice deficient for Stat1 and IFNR (Stat1(-/-) and IFNαßγR(-/-) mice) lack responsiveness to IFN and exhibit high sensitivity to various pathogens. Here we examined herpes simplex virus type 1 (HSV-1) pathogenesis in Stat1(-/-) mice and in IFNαßγR(-/-) mice following corneal infection and bioluminescent imaging. Two divergent and paradoxical patterns of infection were observed. Mice with an N-terminal deletion in Stat1 (129Stat1(-/-) (N-term)) had transient infection of the liver and spleen, but succumbed to encephalitis by day 10 post-infection. In stark contrast, infection of IFNαßγR(-/-) mice was rapidly fatal, with associated viremia and fulminant infection of the liver and spleen, with infected infiltrating cells being primarily of the monocyte/macrophage lineage. To resolve the surprising difference between Stat1(-/-) and IFNαßγR(-/-) mice, we infected an additional Stat1(-/-) strain deleted in the DNA-binding domain (129Stat1(-/-) (DBD)). These 129Stat1(-/-) (DBD) mice recapitulated the lethal pattern of liver and spleen infection seen following infection of IFNαßγR(-/-) mice. This lethal pattern was also observed when 129Stat1(-/-) (N-term) mice were infected and treated with a Type I IFN-blocking antibody, and immune cells derived from 129Stat1(-/-) (N-term) mice were shown to be responsive to Type I IFN. These data therefore show significant differences in viral pathogenesis between two commonly-used Stat1(-/-) mouse strains. The data are consistent with the hypothesis that Stat1(-/-) (N-term) mice have residual Type I IFN receptor-dependent IFN responses. Complete loss of IFN signaling pathways allows viremia and rapid viral spread with a fatal infection of the liver. This study underscores the importance of careful comparisons between knockout mouse strains in viral pathogenesis, and may also be relevant to the causation of HSV hepatitis in humans, a rare but frequently fatal infection.

Introduction: Cystic fibrosis (CF) is commonly complicated by chronic rhinosinusitis (CRS). Despite highly effective management options, CRS in people with CF (PwCF+CRS) may be refractory to medical therapy, eventually requiring endoscopic sinus surgery. The impact of sinus surgery on pulmonary, quality of life (QOL), and other outcomes in PwCF+CRS in the expanding era of highly effective modulator therapy has not been fully elucidated. This study aims to determine if endoscopic sinus surgery can offer superior outcomes for PwCF+CRS when compared to continued medical treatment of CRS. Methods and analysis: This multi-institutional, observational, prospective cohort study will enroll 150 adults with PwCF+CRS across nine US CF Centers who failed initial medical therapy for CRS and elected to pursue either endoscopic sinus surgery or continue medical treatment. To determine if sinus surgery outperforms continued medical therapy in different outcomes, we will assess changes in pulmonary, CF-specific QOL, CRS-specific QOL, sleep quality, depression, headache, cognition, olfaction, productivity loss, and health utility value after treatment. The influence of highly effective modulator therapy on these outcomes will also be evaluated. This study will provide crucial insights into the impact of endoscopic sinus surgery for PwCF+CRS and aid with development of future treatment pathways and guidelines. Ethics and dissemination: This study has been approved by each institution's internal review board, and study enrollment began August 2019. Results will be disseminated in conferences and peer-reviewed journals. Trial registration: This study was registered on ClinicalTrials.gov (NCT04469439). [ABSTRACT FROM AUTHOR]

The venous system has been historically understudied despite its critical roles in blood distribution, heart function, and systemic immunity. This study dissects the microanatomy of upper arm veins at the single cell level, and how it relates to wall structure, remodeling processes, and inflammatory responses to injury. We applied single-cell RNA sequencing to 4 non-diseased human veins (3 basilic, 1 cephalic) obtained from organ donors, followed by bioinformatic and histological analyses. Unsupervised clustering of 20,006 cells revealed a complex ecosystem of endothelial cell (EC) types, smooth muscle cell (SMCs) and pericytes, various types of fibroblasts, and immune cell populations. The venous endothelium showed significant upregulation of cell adhesion genes, with arteriovenous zonation EC phenotypes highlighting the heterogeneity of vasa vasorum (VV) microvessels. Venous SMCs had atypical contractile phenotypes and showed widespread localization in the intima and media. MYH11+DESlo SMCs were transcriptionally associated with negative regulation of contraction and pro-inflammatory gene expression. MYH11+DEShi SMCs showed significant upregulation of extracellular matrix genes and pro-migratory mediators. Venous fibroblasts ranging from secretory to myofibroblastic phenotypes were 4X more abundant than SMCs and widely distributed throughout the wall. Fibroblast-derived angiopoietin-like factors were identified as versatile signaling hubs to regulate angiogenesis and SMC proliferation. An abundant monocyte/macrophage population was detected and confirmed by histology, including pro-inflammatory and homeostatic phenotypes, with cell counts positively correlated with age. Ligand-receptor interactome networks identified the venous endothelium in the main lumen and the VV as a niche for monocyte recruitment and infiltration. This study underscores the transcriptional uniqueness of venous cells and their relevance for vascular inflammation and remodeling processes. Findings from this study may be relevant for molecular investigations of upper arm veins used for vascular access creation, where single-cell analyses of cell composition and phenotypes are currently lacking. [ABSTRACT FROM AUTHOR]

Equine glandular gastric disease (EGGD) is a common disease among athletic horses that can negatively impact health and performance. The pathophysiology of this EGGD remains poorly understood. Previous studies using controlled populations of horses identified differences in the gastric glandular mucosal microbiome associated with disease. The objective of this study was to compare the gastric microbiome in horses with EGGD and those without across multiple barns and differing management practices. We hypothesized that alterations in the microbiome of the gastric glandular mucosa are associated with EGGD. A secondary objective was to perform a risk factor analysis for EGGD using the diet and management data collected. Microbial populations of biopsies from normal pyloric mucosa of horses without EGGD (control biopsies), normal pyloric mucosa of horses with EGGD (normal biopsies) and areas of glandular mucosal disruption in horses with EGGD (lesion biopsies) were compared. Lesion biopsies had a different microbial community structure than control biopsies. Control biopsies had a higher read count for the phylum Actinomycetota compared to lesion biopsies. Control biopsies also had an enrichment of the genera Staphylococcus and Lawsonella and the species Streptococcus salivarius. Lesion biopsies had an enrichment of the genera Lactobacillus and Actinobacillus and the species Lactobacillus equigenerosi. These results demonstrate differences in the gastric glandular microbiome between sites of disrupted mucosa in horses with EGGD compared to pyloric mucosa of horses without EGGD. Risk factor analysis indicated that exercise duration per week was a risk factor for EGGD.

Malaria vectors have demonstrated resistance to pyrethroid-based insecticides used in insecticide-treated nets, diminishing their effectiveness. This systematic review and meta-analysis investigated two forms of dual active-ingredient (DAI) insecticide-treated nets (ITN(s)) for malaria prevention. A comprehensive search was conducted on July 6th 2022. The databases searched included PubMed, Embase, CINAHL, amongst others. Trials were eligible if they were conducted in a region with ongoing malaria transmission. The first DAI ITN investigated were those that combined a pyrethroid with a non-pyrethroid insecticides. The second DAI ITN investigated were that combined a pyrethroid with an insect growth regulator. These interventions were compared against either a pyrethroid-only ITN, or ITNs treated with pyrethroid and piperonyl-butoxide. Assessment of risk of bias was conducted in duplicate using the Cochrane risk of bias 2 tool for cluster-randomised trials. Summary data was extracted using a custom data-extraction instrument. This was conducted by authors THB, JCS and SH. Malaria case incidence was the primary outcome and has been meta-analysed, adverse events were narratively synthesised. The review protocol is registered on PROSPERO (CRD42022333044). From 9494 records, 48 reports were screened and 13 reports for three studies were included. These studies contained data from 186 clusters and all reported a low risk of bias. Compared to pyrethroid-only ITNs, clusters that received pyrethroid-non-pyrethroid DAI ITNs were associated with 305 fewer cases per 1000-person years (from 380 fewer cases to 216 fewer cases) (IRR = 0.55, 95%CI: 0.44–0.68). However, this trend was not observed in clusters that received pyrethroid-insect growth regulator ITNs compared to pyrethroid-only ITNs (from 280 fewer cases to 135 more) (IRR = 0.90, 95%CI: 0.73–1.13). Pyrethroid-non-pyrethroid DAI ITNs demonstrated consistent reductions in malaria case incidence and other outcomes across multiple comparisons. Pyrethroid-non-pyrethroid DAI ITNs may present a novel intervention for the control of malaria.

Background: Airway mucociliary clearance (MCC) is an important defense mechanism against pulmonary infections and is compromised in cystic fibrosis (CF). Cl- and HCO3- epithelial transport are integral to MCC. During pulmonary infections prostaglandin E2 (PGE2) production is abundant. Aim: To determine the effect of PGE2 on airway Cl- and HCO3- secretion and MCC in normal and CF airways. Methods: We examined PGE2 stimulated MCC, Cl- and HCO3- secretion using ferret trachea, human bronchial epithelial cell cultures (CFBE41o- with wildtype CFTR (CFBE41 WT) or homozygous F508del CFTR (CFBE41 CF) and human normal bronchial submucosal gland cell line (Calu-3) in Ussing chambers with or without pH-stat. Results: PGE2 stimulated MCC in a dose-dependent manner and was partially impaired by CFTRinh-172. PGE2-stimulated Cl- current in ferret trachea was partially inhibited by CFTRinh-172, with niflumic acid eliminating the residual current. CFBE41 WT cell monolayers produced a robust Cl- and HCO3- secretory response to PGE2, both of which were completely inhibited by CFTRinh-172. CFBE41 CF cells exhibited no response to PGE2. In Calu-3 cells, PGE2 stimulated Cl- and HCO3- secretion. Cl- secretion was partially inhibited by CFTRinh-172, with additional inhibition by niflumic acid. HCO3- secretion was completely inhibited by CFTRinh-172. Conclusions: PGE2 stimulates bronchotracheal MCC and this response is decreased in CF. In CF airway, PGE2-stimulated Cl- and HCO3- conductance is impaired and may contribute to decreased MCC. There remains a CFTR-independent Cl- current in submucosal glands, which if exploited, could represent a means of improving airway Cl- secretion and MCC in CF. [ABSTRACT FROM AUTHOR]

The current global COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in a public health crisis with more than 168 million cases reported globally and more than 4.5 million deaths at the time of writing. In addition to the direct impact of the disease, the economic impact has been significant as public health measures to contain or reduce the spread have led to country wide lockdowns resulting in near closure of many sectors of the economy. Antibodies are a principal determinant of the humoral immune response to COVID-19 infections and may have the potential to reduce disease and spread of the virus. The development of monoclonal antibodies (mAbs) represents a therapeutic option that can be produced at large quantity and high quality. In the present study, a mAb combination mixture therapy was investigated for its capability to specifically neutralize SARS-CoV-2. We demonstrate that each of the antibodies bind the spike protein and neutralize the virus, preventing it from infecting cells in an in vitro cell-based assay, including multiple viral variants that are currently circulating in the human population. In addition, we investigated the effects of two different mutations in the Fc portion (YTE and LALA) of the antibody on Fc effector function and the ability to alleviate potential antibody-dependent enhancement of disease. These data demonstrate the potential of a combination of two mAbs that target two different epitopes on the SARS-CoV2 spike protein to provide protection against SARS-CoV-2 infection in humans while extending serum half-life and preventing antibody-dependent enhancement of disease.

We present a complete hardware and software system for collecting and quantifying continuous measures of feeding behaviors in the fruit fly, Drosophila melanogaster. The FLIC (Fly Liquid-Food Interaction Counter) detects analog electronic signals as brief as 50 µs that occur when a fly makes physical contact with liquid food. Signal characteristics effectively distinguish between different types of behaviors, such as feeding and tasting events. The FLIC system performs as well or better than popular methods for simple assays, and it provides an unprecedented opportunity to study novel components of feeding behavior, such as time-dependent changes in food preference and individual levels of motivation and hunger. Furthermore, FLIC experiments can persist indefinitely without disturbance, and we highlight this ability by establishing a detailed picture of circadian feeding behaviors in the fly. We believe that the FLIC system will work hand-in-hand with modern molecular techniques to facilitate mechanistic studies of feeding behaviors in Drosophila using modern, high-throughput technologies. [ABSTRACT FROM AUTHOR]

We present a complete hardware and software system for collecting and quantifying continuous measures of feeding behaviors in the fruit fly, Drosophila melanogaster. The FLIC (Fly Liquid-Food Interaction Counter) detects analog electronic signals as brief as 50 µs that occur when a fly makes physical contact with liquid food. Signal characteristics effectively distinguish between different types of behaviors, such as feeding and tasting events. The FLIC system performs as well or better than popular methods for simple assays, and it provides an unprecedented opportunity to study novel components of feeding behavior, such as time-dependent changes in food preference and individual levels of motivation and hunger. Furthermore, FLIC experiments can persist indefinitely without disturbance, and we highlight this ability by establishing a detailed picture of circadian feeding behaviors in the fly. We believe that the FLIC system will work hand-in-hand with modern molecular techniques to facilitate mechanistic studies of feeding behaviors in Drosophila using modern, high-throughput technologies. [ABSTRACT FROM AUTHOR]

There has been an upsurge of e-cigarette use in the United States in recent years. While e-cigarettes may contain lower levels of toxic chemicals than combusted cigarettes, they still pose serious health hazards, including increased risk for heart and respiratory disease. Despite these risks, public awareness of the health harms of e-cigarettes remains low. Thus, it is important to educate the public about the potential harms of e-cigarettes. This study took themes commonly found in antismoking messages and used them to develop messages about harms of e-cigarettes. A national sample of 2801 current smokers and nonsmokers (aged 18+ years) were randomized to view one of four e-cigarette messages (harmful effect of chemicals, uncertainty about ingredients, distrust of big tobacco, or cost of vaping) or a control message (bottled water ad). Participants' reactions to the messages and behavioral intentions were assessed immediately following the exposure. MANOVA examined effects of the messages on blocks of the outcome variables and univariate analyses estimated adjusted means for each experimental condition for each outcome. The message about harmful chemicals was perceived as the most informative and effective and elicited the highest levels of negative emotions (Ps

Pivotal components of the IFN response to virus infection include the IFN receptors (IFNR), and the downstream factor signal transducer and activator of transcription 1 (Stat1). Mice deficient for Stat1 and IFNR (Stat1-/- and IFNaßcR-/- mice) lack responsiveness to IFN and exhibit high sensitivity to various pathogens. Here we examined herpes simplex virus type 1 (HSV-1) pathogenesis in Stat1-/- mice and in IFNaßcR-/- mice following corneal infection and bioluminescent imaging. Two divergent and paradoxical patterns of infection were observed. Mice with an N-terminal deletion in Stat1 (129Stat1-/- (N-term)) had transient infection of the liver and spleen, but succumbed to encephalitis by day 10 post-infection. In stark contrast, infection of IFNaßcR-/- mice was rapidly fatal, with associated viremia and fulminant infection of the liver and spleen, with infected infiltrating cells being primarily of the monocyte/macrophage lineage. To resolve the surprising difference between Stat1-/- and IFNaßcR-/- mice, we infected an additional Stat1-/- strain deleted in the DNA-binding domain (129Stat1-/- (DBD)). These 129Stat1-/- (DBD) mice recapitulated the lethal pattern of liver and spleen infection seen following infection of IFN&agr;&bgr;&ggr;R-/- mice. This lethal pattern was also observed when 129Stat1-/- (N-term) mice were infected and treated with a Type I IFN-blocking antibody, and immune cells derived from 129Stat1-/- (N-term) mice were shown to be responsive to Type I IFN. These data therefore show significant differences in viral pathogenesis between two commonly-used Stat1-/- mouse strains. The data are consistent with the hypothesis that Stat1-/- (N-term) mice have residual Type I IFN receptor-dependent IFN responses. Complete loss of IFN signaling pathways allows viremia and rapid viral spread with a fatal infection of the liver. This study underscores the importance of careful comparisons between knockout mouse strains in viral pathogenesis, and may also be relevant to the causation of HSV hepatitis in humans, a rare but frequently fatal infection. [ABSTRACT FROM AUTHOR]

INTRODUCTION:Stigma and discrimination (SAD) related to HIV compromise access and adherence to treatment and support programs among people living with HIV (PLHIV). The ambitious goal of ending the epidemic of HIV by 2030 set by the United Nations Joint Program of HIV/AIDS (UNAIDS) will thus only be achieved if HIV-related stigma and discrimination are reduced. The objective of this review was to locate, appraise and describe international literature reporting on interventions that addressed HIV-related SAD in healthcare settings. METHODS:The databases searched were: Cumulative Index to Nursing and Allied Health (CINAHL), Excerpta Medica Database from Elsevier (EMBASE), PubMed and Psychological Information (PsycINFO) database. Two individuals independently appraised the quality of the papers using appraisal instruments from the Joanna Briggs Institute (JBI). Data were extracted from papers included in the review using the standardized data extraction tool from JBI. Quality of evidence for major outcomes was assessed using Grading of Recommendations, Assessment, Development and Evaluation (GRADE). RESULTS:We retained 14 records reporting on eight studies. Five categories of SAD reduction (information-based, skills building, structural, contact-based and biomedical interventions) were identified. Training popular opinion leaders (POLs) resulted in significantly lower mean avoidance intent scores (MD = -1.87 [95% CI -2.05 to -1.69]), mean prejudicial attitude scores (MD = -3.77 [95% CI -5.4 to -2.09]) and significantly higher scores in mean compliance to universal precaution (MD = 1.65 [95% CI 1.41 to 1.89]) when compared to usual care (moderate quality evidence). The Summary of Findings table (SOF) is shown in Table 1. CONCLUSIONS:Evidence of moderate quality indicates that training popular opinion leaders is effective in reducing avoidance intent and prejudicial attitude and improving compliance to universal precaution. Very low quality evidence indicates that professionally-assisted peer group interventions, modular interactive training, participatory self-guided assessment and intervention, contact strategy combined with information giving and empowerment are effective in reducing HIV-related stigma.Further Randomized Controlled Trials (RCTs) are needed. Future trials need to use up-to-date and validated instruments to measure stigma and discrimination.

BackgroundThe barriers to uptake of guidelines underscore the importance of going beyound the mere synthesis of evidence to tailoring the synthesized evidence into local contexts and situations. This requires in-depth exploration of local factors. This project aimed to assess contextual barriers and facilitators to the implementation of a guideline developed to reduce HIV-related stigma and discrimination (SAD) in the Ethiopian healthcare setting.MethodsA descriptive qualitative research study was conducted using a semi-structured interview guide informed by the Registered Nurses Association of Ontario (RNAO) framework. The interview was conducted among a purposive sample of seven key informants from Jimma University and Jimma Zone HIV Prevention and Control Office. The interviews were transcribed, coded and analysed using Atlas ti version 7.5 software packages.ResultsGuideline attributes, provider-related factors and organizational and practice-related were identified as factors that can potentially affect the implementation of the guideline. The presence of expert patients were identified as agents for guideline implementation, whilst regular health education programs in addition to initiatives related to service quality improvement, were identified as suitable platforms to assist with the implementation of this guideline. Study participants recommended that the guideline should be disseminated through multidisciplinary team (MDT) meetings, gate keepers such as opinion leaders and unit heads, one-to-five networks and mentorship programs, as well as training, workshops and posters. The current study also indicated that continuous monitoring, evaluation and mentorship are critical elements in the integration of the guideline into the system of the hospital.ConclusionsThis study identified that guideline implementation can make use of existing structures and pathways such as MDT meetings, service quality improvement initiatives, one-to-five networks, training and workshops. Teamwork and partnership with stakeholders should be strengthened to strengthen facilitators and tackle barriers related to the implementation of the guideline. Effective implementation of the guideline also requires establishing an implementation structure. Moreover, indicators developed to track the implementation of stigma reduction guideline should be integrated into mentorship, MDT meetings and evaluation programs of the hospital to improve performance and to assist data collection on implementation experiences.

BACKGROUND:Developing guidelines and policies is critical to address HIV-related stigma and discrimination (SAD) in healthcare settings. To this end, a multidisciplinary panel developed a guideline to reduce SAD. This project evaluated the appropriateness of implementing the guideline in the Ethiopian context. METHODS:A consensus of the expert panel was established through a modified Delphi technique which was followed by a panel meeting. Initial tentative recommendations were distributed to experts through e-mails to be evaluated using the modified guideline implementability appraisal (GLIA) v.2.0 checklist. RESULTS:In the first round of the Delphi survey, all (13) panel members evaluated the guideline. The overall score for the general domain of the modified GLIA checklist was 96.56%. The scores for individual recommendations ranged from 68.33% to 92.76%. Maximum and minimum scores were attained for measurability (97.71%) and flexibility (59.77%) domains respectively. Percentages mean score lower than 75% was obtained for flexibility and validity domains. Participants suggested that additional tools and training should be added to the guideline. In the second round of the survey, all the recommendations received endorsement with scores above 75%. Maximum and minimum scores were attained for measurability (100%) and flexibility (86.88%) domains respectively. During the panel meeting, issues of responsibility for implementing the guideline were discussed. CONCLUSION:The project evaluated implementability of a guideline developed to reduce HIV-related SAD in healthcare settings. The Delphi survey was followed by a half-day meeting that helped in further clarification of points.

BACKGROUND:This study presents a novel methodology for estimating all-age, population-based incidence rates of norovirus and other pathogens that contribute to acute gastroenteritis in the United States using an integrated healthcare delivery system as a surveillance platform. METHODS:All cases of medically attended acute gastroenteritis within the delivery system were identified from April 1, 2014 through September 30, 2016. A sample of these eligible patients were selected to participate in two phone-based surveys and to self-collect a stool sample for laboratory testing. To ascertain household transmission patterns, information on household members with acute gastroenteritis was gathered from participants, and symptomatic household members were contacted to participate in a survey and provide stool sample as well. RESULTS:54% of individuals who met enrollment criteria agreed to participate, and 76% of those individuals returned a stool sample. Among household members, 85% of eligible individuals agreed to participate, and 68% of those returned a stool sample. Participant demographics were similar to those of the eligible population, although minority racial/ethnic groups were somewhat underrepresented in the final sample. CONCLUSIONS:This study demonstrates the feasibility of conducting acute infectious disease research within an integrated health care delivery system. The surveillance, sampling, recruitment, and data collection methods described here are broadly applicable to conduct baseline and epidemiological assessments, as well as for other research requiring representative samples of stool specimens.

Transcatheter aortic valve replacement (TAVR) reduces left ventricular (LV) afterload and improves prognosis in aortic stenosis (AS) patients. However, LV afterload consists of both valvular and arterial loads, and the benefits of TAVR may be attenuated if the arterial load dominates. We proposed a new hemodynamic index, the Relative Valve Load (RVL), a ratio of mean gradient (MG) and valvuloarterial impedance (Zva), to describe the relative contribution of the valvular load to the global LV load, and examined whether RVL predicted patient outcome following TAVR.A total of 258 patients with symptomatic severe AS (indexed aortic valve area (AVA)0.75cm2, %SWL≤25% and Zva>5mmHg/ml/m2 despite equivalent or better sensitivity. In multivariable Cox analysis, RVL≤7.95ml/m2 was an independent predictor of all cause mortality (HR 3.2, CI 1.8-5.9; p