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BACKGROUND: The Sightline ColonoSight (CS) colonoscopy system presents 3 technologic advances: (1) disposable components protect the reusable parts from contact with colonic contents, eliminating the need for disinfection between procedures, (2) an air-pressure-powered engine assists in colonoscope advancement, (3) light emitting diode (LED) illumination eliminates the need for fiber optics and an external light source. OBJECTIVES: To study the operation, performance, and safety of the Sightline CS colonoscopy system. DESIGN: The system was tested during colonoscopy in animals and in human pilot studies. An in vitro dye diffusion test, and bacterial cultures (obtained after using the colonoscope in animals and humans) were performed to ascertain the protective integrity of the disposable components. SETTING: Animal centers, hospitals in Israel and Italy, and office endoscopy centers in the United States. PATIENTS: Thirty-three volunteers and 145 patients who required a colonoscopy for various indications. INTERVENTIONS: Colonoscopy, polypectomy, biopsy, and coagulation. MAIN OUTCOME MEASURES: Complications, system function, cecal intubation, and colonoscopy time. RESULTS: The Sightline CS system performed well during a colonoscopy in 19 animals and 178 patients, without complications. Dye studies and bacterial cultures showed no transfer of dye molecules or bacterial organisms across the protective, disposable components. LIMITATIONS: This is an observational pilot study, with no comparative group. CONCLUSIONS: The new Sightline CS colonoscopy system performed well. The disposable components eliminated the need for disinfection of the colonoscope between procedures. Advancement of the colonoscope in the colon was helped by self propulsion of the instrument affected by an air-pressure-powered engine. LED illumination eliminated the need for fiber optics and an external light source. [ABSTRACT FROM AUTHOR]

BACKGROUND: Increased demand for screening colonoscopy necessitates improved efficiency in endoscopy units, especially more efficient use of existing resources. The purpose of this study was to assess the efficiency of the endoscopy unit of a large tertiary care teaching hospital. OBJECTIVE: To assess the efficiency of the endoscopy unit in a large tertiary care teaching hospital. DESIGN: Prospective study from May 16 to September 5, 2003. SETTING: Endoscopy unit of a 650-bed acute care teaching hospital. PATIENTS: Inpatient and outpatient procedures. MAIN OUTCOME MEASUREMENTS: Time elapsed between endoscopic procedures; the duration of the procedures; procedure delays (>15 minutes between procedures) and the reasons for them. RESULTS: The research assistant observed 675 endoscopic procedures done for 625 patients (207 inpatients [33%]). The most common procedure was colonoscopy (42.1%), followed by EGD (36.0%). Overall, procedures for 193 (30.9%) of the 625 patients were delayed (>15 minutes between procedures), 70.5% (136/193) because the physician was not available to start the procedure. The time elapsed between procedures was longer than 30 minutes for 47 of the 193 delayed procedures (24.4%). The duration of procedures was prolonged for about 22% (130/593) of procedures. CONCLUSIONS: Physician unavailability contributed to considerable delays in endoscopic procedures. Strategies to reduce procedure delays could have a favorable impact on the volume of procedures performed in the unit, thereby improving the use of existing resources. We encourage other groups to assess the efficiency of their hospital-based endoscopy units. [ABSTRACT FROM AUTHOR]

Access to online research databases and full text e-journals is a core element of academic library Web sites. This case study describes one such site that implemented a data-driven integrated interface for its online research collection. The project raises several issues that should be considered by libraries engaged in developing these applications. This article also addresses next steps that would enhance access to a library's online research collection. [ABSTRACT FROM AUTHOR]

Background: Family dynamics play an important role in determining the glycemic outcomes of type 1 diabetes (T1D) in children. The time interval immediately following T1D diagnosis is particularly stressful for families, and interventions to support families in adjusting their family practices to support adjustment to and management of T1D in the months following diagnosis may improve glycemic outcomes. Self-guided digital interventions offer a sustainable model for interventions to support caregivers in learning evidence-based family management skills for adjustment to and management of T1D., Objective: We hypothesized that a self-guided, web-based, family skills management program (addressing caregiver social support as well as family problem-solving, communication, and supportive behavior change strategies) initiated at the time of T1D diagnosis would improve glycemic outcomes in children with T1D. In this study, we report on the feasibility and acceptability of this program., Methods: We prospectively evaluated a sample of 37 children newly diagnosed with T1D recruited from a pediatric endocrinology clinic. Parent participants were asked to complete web-based modules addressing social support, family problem-solving, communication, and supportive behavior change strategies. Module completion was analyzed for percentage completion, patterns of completion, and differences in completion rates by coparenting status. Qualitative open-ended feedback was collected at the completion of each module., Results: A total of 31 (84%) of the 37 participants initiated the web-based program. Of those 31 participants, 25 (81%) completed some content and 15 (48%) completed all 5 modules. Completion rates were higher when coparenting partners engaged in the intervention together (P=.04). Of the 18 participants given a choice about the spacing of content delivery, 15 (83%) chose to have all sessions delivered at once and 3 (17%) chose to space sessions out at 2-week intervals. Qualitative feedback supported the acceptability of the program for delivery soon after T1D diagnosis. Families reported on positive benefits, including requesting future access to the program and describing helpful changes in personal or family processes for managing T1D., Conclusions: In this study, we found that a self-guided digital family support intervention initiated at the time of a child's T1D diagnosis was largely feasible and acceptable. Overall, rates of participation and module completion were similar to or higher than other self-guided digital prevention interventions for mental and physical health outcomes. Self-guided digital programs addressing family management skills may help prevent challenges common with T1D management and can decrease cost, increase access, and add flexibility compared to traditional interventions., Trial Registration: ClinicalTrials.gov NCT03720912; https://clinicaltrials.gov/study/NCT03720912., (©Amy Hughes Lansing, Laura B Cohen, Nicole S Glaser, Lindsey A Loomba. Originally published in JMIR Formative Research (https://formative.jmir.org), 21.10.2024.)

Background: Shared medical appointments (SMAs) in heart failure (HF) are medical visits where several patients with HF meet with multidisciplinary providers at the same time for efficient and comprehensive care. It is unknown whether HF-SMAs can improve overall and cardiac health status for high-risk patients with HF discharged from acute care., Methods and Results: A 3-site, open-label, randomized-controlled-trial was conducted. Participants within 12 weeks of HF acute care (emergency-room/hospitalization) requiring intravenous diuretic therapy were randomized to receive either HF-SMA or usual HF clinical care (usual-care) on a 1:1 ratio. The HF-SMA team, which consisted of a nurse, nutritionist, psychologist, nurse practitioner and/or a clinical pharmacist, provided four 2-hour session HF-SMAs that met every other week for 8 weeks. Primary outcomes were the overall health status measured by European Quality of Life Visual Analog Scale and cardiac health status by Kansas City Cardiomyopathy Questionnaire, 180 days postrandomization. Of the 242 patients enrolled (HF-SMA n=117, usual-care n=125, mean age 69.3±9.4 years, 71.5% White patients, 94.6% male), 84% of participants completed the study (n=8 HF-SMA and n=9 usual-care patients died). After 180 days, both HF-SMA and usual-care participants had significant improvements from baseline in Kansas City Cardiomyopathy Questionnaire that were not statistically different. Only HF-SMA participants had significant improvements in European Quality of Life Visual Analog Scale (mean change = 7.2±15.8 in HF-SMA versus -0.4±19.0 points in usual-care, P  < 0.001)., Conclusions: Both HF-SMA and usual-care in participants with HF achieved significant improvements in cardiac health status, but only a team approach through HF-SMA achieved significant improvements in overall health status. Future larger studies are needed to evaluate hospitalization and death outcomes., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02481921.

Background: Diabetes distress among adolescents with type 1 diabetes has been associated with suboptimal diabetes outcomes, including lower quality of life, increased diabetes self-management challenges, and suboptimal glycemic outcomes., Objective: This study examined the feasibility and acceptability of a scalable self-led mindfulness-based intervention to reduce diabetes distress in adolescents with type 1 diabetes., Methods: Adolescents (N=25) aged between 14 and 18 years diagnosed with type 1 diabetes completed a baseline assessment. Participants were randomized to receive a 10-week self-guided mindfulness-based stress reduction workbook program (e-book or paper option) immediately (n=15) or after a 10-week wait (n=10). During the intervention period, participants completed weekly assignments and feedback surveys. At 10 weeks and 20 weeks, follow-up assessments were completed., Results: Findings indicated that participants did not find the original intervention feasible or acceptable. Adolescents reported barriers to completing the weekly material, such as that they forgot or that the material was not sufficiently related to their diabetes management. Adolescents also reported that a digital format rather than a workbook or e-book may be more acceptable. Results from weekly surveys provided the foundation for recommendations for future iterations of the mindfulness-based intervention for adolescents with type 1 diabetes., Conclusions: Participant feedback informed recommendations for self-led mindfulness programs for youth with type 1 diabetes. Adolescents indicated that a shorter, digital mindfulness-based intervention focused on diabetes-specific behaviors may be more helpful., Trial Registration: ClinicalTrials.gov NCT05115175; https://clinicaltrials.gov/study/NCT05115175., (©Tori Humiston, Caroline Cummings, Stephen Suss, Laura B Cohen, Holly Hazlett-Stevens, Amy Hughes Lansing. Originally published in JMIR Formative Research (https://formative.jmir.org), 30.01.2024.)

The National i-THRIVE Programme seeks to evaluate the impact of the NHS England-funded whole system transformation on child and adolescent mental health services (CAMHS). This article reports on the design for a model of implementation that has been applied in CAMHS across over 70 areas in England using the 'THRIVE' needs-based principles of care. The implementation protocol in which this model, 'i-THRIVE' (implementing-THRIVE), will be used to evaluate the effectiveness of the THRIVE intervention is reported, together with the evaluation protocol for the process of implementation. To evaluate the effectiveness of i-THRIVE to improve care for children and young people's mental health, a cohort study design will be conducted. N = 10 CAMHS sites that adopt the i-THRIVE model from the start of the NHS England-funded CAMHS transformation will be compared to N = 10 'comparator sites' that choose to use different transformation approaches within the same timeframe. Sites will be matched on population size, urbanicity, funding, level of deprivation and expected prevalence of mental health care needs. To evaluate the process of implementation, a mixed-methods approach will be conducted to explore the moderating effects of context, fidelity, dose, pathway structure and reach on clinical and service level outcomes. This study addresses a unique opportunity to inform the ongoing national transformation of CAMHS with evidence about a popular new model for delivering children and young people's mental health care, as well as a new implementation approach to support whole system transformation. If the outcomes reflect benefit from i-THRIVE, this study has the potential to guide significant improvements in CAMHS by providing a more integrated, needs-led service model that increases access and involvement of patients with services and in the care they receive., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 A. et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Sensing smells of foods, prey, or predators determines animal survival. Olfactory sensory neurons in the olfactory epithelium (OE) detect odorants, where cAMP and Ca 2+ play a significant role in transducing odorant inputs to electrical activity. Here we show Anoctamin 9, a cation channel activated by cAMP/PKA pathway, is expressed in the OE and amplifies olfactory signals. Ano9-deficient mice had reduced olfactory behavioral sensitivity, electro-olfactogram signals, and neural activity in the olfactory bulb. In line with the difference in olfaction between birds and other vertebrates, chick ANO9 failed to respond to odorants, whereas chick CNGA2, a major transduction channel, showed greater responses to cAMP. Thus, we concluded that the signal amplification by ANO9 is important for mammalian olfactory transduction., (Copyright © 2022. Published by Elsevier Ltd.)

Introduction: Vaccine hesitancy is a growing threat to public health. The objective of this research was to investigate the effect of incorporating a learning unit on addressing vaccine hesitancy into a doctor of pharmacy immunization delivery course., Methods: The learning unit, implemented fall 2019 at the University of Rhode Island, involved two interactive lectures and an at-home assignment. A family medicine physician spoke about her experiences with vaccine-hesitant families, and students viewed video scenarios depicting a pharmacist talking with vaccine-hesitant patients followed by an in-class discussion. Data was collected using pre- and post-surveys and a one-year follow-up survey., Results: Out of 125 students enrolled in the course, 121 completed the pre-survey, 113 the post-survey, and 120 the follow-up survey. For pre-/post-survey comparison questions, statistically significant improvements were seen in 9 of 13 items. The follow-up survey showed 83.4% of students had applied knowledge and 85.7% had applied skills gained from the learning unit., Conclusion: Incorporating a learning unit on addressing vaccine hesitancy into a pharmacy immunization class resulted in improvements in student self-reported knowledge and comfort in talking with patients who are vaccine hesitant. Long-term use of self-reported knowledge and skills gained was seen one-year post-implementation., (Copyright © 2022 Elsevier Inc. All rights reserved.)

To identify potential regions of the voltage-sensing domain that could shift the voltage sensitivity of Ciona intestinalis based Genetically Encoded Voltage Indicators (GEVIs), we aligned the amino acid sequences of voltage-gated sodium channels from different organisms. Conserved polar residues were identified at multiple transmembrane/loop junctions in the voltage sensing domain. Similar conservation of polar amino acids was found in the voltage-sensing domain of the voltage-sensing phosphatase gene family. These conserved residues were mutated to nonpolar or oppositely charged amino acids in a GEVI that utilizes the voltage sensing domain of the voltage sensing phosphatase from Ciona fused to the fluorescent protein, super ecliptic pHluorin (A227D). Different mutations shifted the voltage sensitivity to more positive or more negative membrane potentials. Double mutants were then created by selecting constructs that shifted the optical signal to a more physiologically relevant voltage range. Introduction of these mutations into previously developed GEVIs resulted in Plos6-v2 which improved the dynamic range to 40% ΔF/F/100 mV, a 25% increase over the parent, ArcLight. The onset time constant of Plos6-v2 is also 50% faster than ArcLight. Thus, Plos6-v2 appears to be the GEVI of choice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sepehri Rad, Cohen and Baker.)

The present review is based on the research presented at the symposium dedicated to the legacy of the two scientists that made important discoveries in the field of alcohol-induced liver damage: Professors C.S. Lieber and S.W. French. The invited speakers described pharmacological, toxicological and patho-physiological effects of alcohol misuse. Moreover, genetic biomarkers determining adverse drug reactions due to interactions between therapeutics used for chronic or infectious diseases and alcohol exposure were discussed. The researchers presented their work in areas of alcohol-induced impairment in lipid protein trafficking and endocytosis, as well as the role of lipids in the development of fatty liver. The researchers showed that alcohol leads to covalent modifications that promote hepatic dysfunction and injury. We concluded that using new advanced techniques and research ideas leads to important discoveries in science., (Copyright © 2022 Elsevier Inc. All rights reserved.)

We examined the prospective associations of COVID-19 fears and behavior, and daily physical activity and dysregulated eating. Adolescents ( N = 31) aged 11-17 completed selected subscales of the Fear of Illness and Virus Evaluation and completed a 7-day health behavior diary. Greater fear of contamination was associated with lower daily physical activity. In contrast, greater COVID-19 precautionary behavior was associated with greater daily physical activity. COVID-19 fears and precautionary behaviors have differential associations with health promoting behavior engagement. Future studies should explore the mechanisms underlying these links to guide adaptation of health behavior interventions for this unique cohort.

Hepatic cells are sensitive to internal and external signals. Ethanol is one of the oldest and most widely used drugs in the world. The focus on the mechanistic engine of the alcohol-induced injury has been in the liver, which is responsible for the pathways of alcohol metabolism. Ethanol undergoes a phase I type of reaction, mainly catalyzed by the cytoplasmic enzyme, alcohol dehydrogenase (ADH), and by the microsomal ethanol-oxidizing system (MEOS). Reactive oxygen species (ROS) generated by cytochrome (CYP) 2E1 activity and MEOS contribute to ethanol-induced toxicity. We aimed to: (1) Describe the cellular, pathophysiological and clinical effects of alcohol misuse on the liver; (2) Select the biomarkers and analytical methods utilized by the clinical laboratory to assess alcohol exposure; (3) Provide therapeutic ideas to prevent/reduce alcohol-induced liver injury; (4) Provide up-to-date knowledge regarding the Corona virus and its affect on the liver; (5) Link rare diseases with alcohol consumption. The current review contributes to risk identification of patients with alcoholic, as well as non-alcoholic, liver disease and metabolic syndrome. Additional prevalence of ethnic, genetic, and viral vulnerabilities are presented.

Genetically encoded voltage indicators (GEVIs) allow optical recordings of membrane potential changes in defined cell populations. Transgenic reporter animals that facilitate precise and repeatable targeting with high expression levels would further the use of GEVIs in the in vivo mammalian brain. However, the literature on developing and applying transgenic mouse lines as vehicles for GEVI expression is limited. Here we report the first in vivo experiments using a transgenic reporter mouse for the GEVI ArcLight, which utilizes a Cre/tTA dependent expression system (TIGRE 1.0). We developed two mouse lines with ArcLight expression restricted to either olfactory receptor neurons, or a subpopulation of interneurons located in the granule and glomerular layers in the olfactory bulb. The ArcLight expression in these lines was sufficient for in vivo imaging of odorant responses in single trials using epifluorescence and 2-photon imaging. The voltage responses were odor-specific and concentration-dependent, which supported earlier studies about perceptual transformations carried out by the bulb that used calcium sensors of neural activity. This study demonstrates that the ArcLight transgenic line is a flexible genetic tool that can be used to record the neuronal electrical activity of different cell types with a signal-to-noise ratio that is comparable to previous reports using viral transduction., (© 2022. The Author(s).)

Defense against intracellular infection has been extensively studied in vertebrate hosts, but less is known about invertebrate hosts; specifically, the transcription factors that induce defense against intracellular intestinal infection in the model nematode Caenorhabditis elegans remain understudied. Two different types of intracellular pathogens that naturally infect the C. elegans intestine are the Orsay virus, which is an RNA virus, and microsporidia, which comprise a phylum of fungal pathogens. Despite their molecular differences, these pathogens induce a common host transcriptional response called the intracellular pathogen response (IPR). Here we show that zip-1 is an IPR regulator that functions downstream of all known IPR-activating and regulatory pathways. zip-1 encodes a putative bZIP transcription factor, and we show that zip-1 controls induction of a subset of genes upon IPR activation. ZIP-1 protein is expressed in the nuclei of intestinal cells, and is at least partially required in the intestine to upregulate IPR gene expression. Importantly, zip-1 promotes resistance to infection by the Orsay virus and by microsporidia in intestinal cells. Altogether, our results indicate that zip-1 represents a central hub for triggers of the IPR, and that this transcription factor has a protective function against intracellular pathogen infection in C. elegans., (© 2022. The Author(s).)

Objective: The development of habit (i.e., behavioral automaticity, the extent to which a behavior is performed with decreased thresholds for time, attention [effort], conscious awareness, and goal dependence), for goal-directed health behaviors facilitates health behavior engagement in daily life. However, there is a paucity of research examining automaticity for Type 1 diabetes self-management in adolescence. This study examined if greater perceived automaticity for diabetes self-management was associated with increased daily self-management, decreased daily self-regulation failures in glucose checking, and more optimal daily glycemic levels in adolescents with Type 1 diabetes., Method: Adolescents aged 13-17 and diagnosed with Type 1 diabetes ( n = 79) completed the Self-Report Behavioral Automaticity Index, a measure of automaticity of diabetes self-management (i.e., automaticity of glucose checking, carbohydrate counting, and insulin dosing), and a measure of perceived self-management at baseline. One to 3 months later, a subsample of teens ( n = 42) also completed a daily diary for a 7-day period including perceptions of daily self-management, daily self-regulation failures in glucose checking, and daily glucose levels., Results: Greater overall automaticity of diabetes self-management was associated with greater baseline and daily self-management, fewer daily self-regulation failures in glucose checking, and lower average daily mean blood glucose levels but not more optimal daily variations in blood glucose levels., Conclusions: Greater automaticity for diabetes self-management may support more optimal daily diabetes self-management in adolescence. Further research is needed to clarify the benefits and mechanisms of automaticity and explore possible interventions. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Males in the parasitoid wasp genus Nasonia have distinct, species-specific, head shapes. The availability of fertile hybrids among the species, along with obligate haploidy of males, facilitates analysis of complex gene interactions in development and evolution. Previous analyses showed that both the divergence in head shape between Nasonia vitripennis and Nasonia giraulti, and the head-specific developmental defects of F2 haploid hybrid males, are governed by multiple changes in networks of interacting genes. Here, we extend our understanding of the gene interactions that affect morphogenesis in male heads. Use of artificial diploid male hybrids shows that alleles mediating developmental defects are recessive, while there are diverse dominance relationships among other head shape traits. At the molecular level, the sex determination locus doublesex plays a major role in male head shape differences, but it is not the only important factor. Introgression of a giraulti region on chromsome 2 reveals a recessive locus that causes completely penetrant head clefting in both males and females in a vitripennis background. Finally, a third species (N. longicornis) was used to investigate the timing of genetic changes related to head morphology, revealing that most changes causing defects arose after the divergence of N. vitripennis from the other species, but prior to the divergence of N. giraulti and N. longicornis from each other. Our results demonstrate that developmental gene networks can be dissected using interspecies crosses in Nasonia, and set the stage for future fine-scale genetic dissection of both head shape and hybrid developmental defects., (© The Author(s) 2021. Published by Oxford University Press on behalf of Genetics Society of America.)

Hepatitis C virus (HCV)-induced liver disease contributes to chronic hepatitis. The immune factors identified in HCV include changes in the innate and adaptive immune system. The inflammatory mediators, known as "inflammasome", are a consequence of the metabolic products of cells and commensal or pathogenic bacteria and viruses. The only effective strategy to prevent disease progression is eradication of the viral infection. Immune cells play a pivotal role during liver inflammation, triggering fibrogenesis. The present paper discusses the potential role of markers in cell death and the inflammatory cascade leading to the severity of liver damage. We aim to present the clinical parameters and laboratory data in a cohort of 88 HCV-infected non-cirrhotic and 25 HCV cirrhotic patients, to determine the characteristic light microscopic (LM) and transmission electron microscopic (TEM) changes in their liver biopsies and to present the link between the severity of liver damage and the serum levels of cytokines and caspases. A matched HCV non-infected cohort was used for the comparison of serum inflammatory markers. We compared the inflammation in HCV individuals with a control group of 280 healthy individuals. We correlated the changes in inflammatory markers in different stages of the disease and the histology. We concluded that the serum levels of cytokine, chemokine, and cleaved caspase markers reveal the inflammatory status in HCV. Based upon the information provided by the changes in biomarkers the clinician can monitor the severity of HCV-induced liver damage. New oral well-tolerated treatment regimens for chronic hepatitis C patients can achieve cure rates of over 90%. Therefore, using the noninvasive biomarkers to monitor the evolution of the liver damage is an effective personalized medicine procedure to establish the severity of liver injury and its repair.

While humans and other mammals exhibit adaptation to odorants, the neural mechanisms and brain locations involved in this process are incompletely understood. One possibility is that it primarily occurs as a result of the interactions between odorants and odorant receptors on the olfactory sensory neurons in the olfactory epithelium. In this scenario, adaptation would arise as a peripheral phenomenon transmitted to the brain. An alternative possibility is that adaptation occurs because of processing in the brain. We made an initial test of these possibilities using a two-color imaging strategy to simultaneously measure the activity of the olfactory receptor nerve terminals (input to the bulb) and mitral/tufted cell apical dendrites (output from the bulb) in anesthetized and awake mice. Repeated odor stimulation at the same concentration resulted in a decline in the bulb output, while the input remained relatively stable. Thus, the mammalian olfactory bulb appears to participate in generating the perception of olfactory adaptation under this stimulus condition. Similar experiments conducted previously showed that the bulb may also participate in the perception of concentration invariance of odorant recognition (Storace and Cohen, 2017); thus, the bulb is simultaneously carrying out more than one computation, as is true of other mammalian brain regions and perhaps is the case for all animals with sophisticated nervous systems. However, in contrast with other sensory systems (Van Essen et al., 1992), the very first processing stage in the olfactory system has an output that may directly represent perceptions., (Copyright © 2021 Storace and Cohen.)

The fruit fly Drosophila melanogaster combats microbial infection by producing a battery of effector peptides that are secreted into the haemolymph. Technical difficulties prevented the investigation of these short effector genes until the recent advent of the CRISPR/CAS era. As a consequence, many putative immune effectors remain to be formally described, and exactly how each of these effectors contribute to survival is not well characterized. Here we describe a novel Drosophila antifungal peptide gene that we name Baramicin A. We show that BaraA encodes a precursor protein cleaved into multiple peptides via furin cleavage sites. BaraA is strongly immune-induced in the fat body downstream of the Toll pathway, but also exhibits expression in other tissues. Importantly, we show that flies lacking BaraA are viable but susceptible to the entomopathogenic fungus Beauveria bassiana. Consistent with BaraA being directly antimicrobial, overexpression of BaraA promotes resistance to fungi and the IM10-like peptides produced by BaraA synergistically inhibit growth of fungi in vitro when combined with a membrane-disrupting antifungal. Surprisingly, BaraA mutant males but not females display an erect wing phenotype upon infection. Here, we characterize a new antifungal immune effector downstream of Toll signalling, and show it is a key contributor to the Drosophila antimicrobial response., Competing Interests: The authors have declared that no competing interests exist.

Introduction: The aim of this study was to determine whether a pharmacist-led telehealth disease management program is superior to usual care of nurse-led telehealth in improving diabetes medication adherence, haemoglobin A1C (A1C), and depression scores in patients with concomitant diabetes and depression., Methods: Patients with diabetes and depression were randomized to pharmacist-led or nurse-led telehealth. Veterans with type 1 or type 2 diabetes, an A1C ≥ 7.5%, diagnosis of depression, and access to a landline phone were invited to participate. Patients were randomized to usual care of nurse-led telehealth or pharmacist-led telehealth. Patients were shown how to use the telehealth equipment by the nurse or pharmacist. In the pharmacist-led group, the patients received an in-depth medication review in addition to the instruction on the telehealth equipment., Results: After six months, the pharmacist-led telehealth arm showed significant improvements for cardiovascular medication adherence (14.0; 95% confidence interval (CI) 0.4 to 27.6), antidepressant medication adherence (26.0; 95% CI 0.9 to 51.2), and overall medication adherence combined (13.9; 95% CI 6.6 to 21.2) from baseline to six-month follow-up. There was a significant difference in A1C between each group at the six-month follow-up in the nurse-led telehealth group (6.9 ± 0.9) as compared to the pharmacist-led telehealth group (8.8 ± 2.0). There was no significance in the change in patient health questionnaire-9 (PHQ-9) and Center for Epidemiologic Studies Depression Scale (CES-D) from baseline to follow-up in both groups., Discussion: Pharmacist-led telehealth was efficacious in improving medication adherence for cardiovascular, antidepressants, and overall medications over a six-month period as compared to nurse-led telehealth. There was no significant improvement in overall depression scores.

Competing Interests: The authors have declared that no competing interests exist.

Background and Aims: Non-alcoholic steatohepatitis (NASH) has been associated with fibrosis that may progress to cirrhosis. The purpose of this study was to examine hepatocytes and perisinusoidal cells in liver biopsies of 3 families (3 males and 4 females) with non-cirrhotic and cirrhotic NASH to determine unique histological changes during a period of 2-7 years from diagnosis., Methods: In this study, hepatocytes, stellate cells and Kupffer cells were analyzed using light and electron microscopy, and immunohistochemistry with specific anti-macrophage antibody staining of liver biopsies., Results: Body mass index of all patients was over 28, and all viral, metabolic markers were negative. Alcohol consumption was insignificant. In all liver biopsies, diffuse, non-zonal macrovesicular steatosis involved 40-70% of liver samples. The lobular hepatocytes showed prominent ballooning hepatocyte degeneration. No Mallory Denk hyaline bodies (MDBs) were observed in three of the patients. MDBs developed in ballooned hepatocytes of four individuals that also presented foci of lobular inflammation. The apoptotic bodies were stained by cytokeratin 18. The trichrome stain revealed portal to portal bridging fibrosis. In one family, there was a three-fold increase in relative numbers of perisinusoidal macrophages in the older sister with NASH compared to livers of the younger siblings. The special finding in livers of patients with NASH was accumulation of groups of perisinusoidal macrophages, which was not associated with focal necrosis., Conclusion: Perisinusoidal macrophages appear to accumulate in NASH. It is possible that collections of macrophages are a response to chronic portal endotoxemia or lipotoxic activation of immuno-mediators. The persistent activation of these macrophages could lead to the chronic release of pro-inflammatory cytokines and contribute to chronic inflammation, fibrosis and cirrhosis leading to HCC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The work performed by Dr. Neuman was founded by In Vitro Drug Safety and Botechnology. Dr. Cohen acknowledge the contribution received from Mahaffy Gastroenterology grant., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The following review article presents clinical and experimental features of alcohol-induced liver disease (ALD). Basic aspects of alcohol metabolism leading to the development of liver hepatotoxicity are discussed. ALD includes fatty liver, acute alcoholic hepatitis with or without liver failure, alcoholic steatohepatitis (ASH) leading to fibrosis and cirrhosis, and hepatocellular cancer (HCC). ALD is fully attributable to alcohol consumption. However, only 10-20% of heavy drinkers (persons consuming more than 40 g of ethanol/day) develop clinical ALD. Moreover, there is a link between behaviour and environmental factors that determine the amount of alcohol misuse and their liver disease. The range of clinical presentation varies from reversible alcoholic hepatic steatosis to cirrhosis, hepatic failure, and hepatocellular carcinoma. We aimed to (1) describe the clinico-pathology of ALD, (2) examine the role of immune responses in the development of alcoholic hepatitis (ASH), (3) propose diagnostic markers of ASH, (4) analyze the experimental models of ALD, (5) study the role of alcohol in changing the microbiota, and (6) articulate how findings in the liver and/or intestine influence the brain (and/or vice versa) on ASH; (7) identify pathways in alcohol-induced organ damage and (8) to target new innovative experimental concepts modeling the experimental approaches. The present review includes evidence recognizing the key toxic role of alcohol in ALD severity. Cytochrome p450 CYP2E1 activation may change the severity of ASH. The microbiota is a key element in immune responses, being an inducer of proinflammatory T helper 17 cells and regulatory T cells in the intestine. Alcohol consumption changes the intestinal microbiota and influences liver steatosis and liver inflammation. Knowing how to exploit the microbiome to modulate the immune system might lead to a new form of personalized medicine in ALF and ASH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Fungal infections, widespread throughout the world, affect a broad range of life forms, including agriculturally relevant plants, humans, and insects. In defending against fungal infections, the fruit fly Drosophila melanogaster employs the Toll pathway to induce a large number of immune peptides. Some have been investigated, such as the antimicrobial peptides (AMPs) and Bomanins (Boms); many, however, remain uncharacterized. Here, we examine the role in innate immunity of two related peptides, Daisho1 and Daisho2 (formerly IM4 and IM14, respectively), found in hemolymph following Toll pathway activation. By generating a CRISPR/Cas9 knockout of both genes, Δ daisho , we find that the Daisho peptides are required for defense against a subset of filamentous fungi, including Fusarium oxysporum , but not other Toll-inducible pathogens, such as Enterococcus faecalis and Candida glabrata . Analysis of null alleles and transgenes revealed that the two daisho genes are each required for defense, although their functions partially overlap. Generating and assaying a genomic epitope-tagged Daisho2 construct, we detected interaction in vitro of Daisho2 peptide in hemolymph with the hyphae of F. oxysporum . Together, these results identify the Daisho peptides as a new class of innate immune effectors with humoral activity against a select set of filamentous fungi., (Copyright © 2020 Cohen, Lindsay, Xu, Lin and Wasserman.)