Phospholipid scramblase-1 regulates innate type 2 inflammation in mouse lungs via CRTH2-dependent mechanisms.

Exaggerated Type 2 immune responses play critical roles in the pathogenesis of a variety of diseases including asthma, allergy, and pulmonary fibrosis. Recent studies have highlighted the importance of innate type 2 immune responses and innate lymphoid 2 cells (ILC2s) in these disorders. However, the mechanisms that control the development of pulmonary innate type 2 responses (IT2IR) and the recruitment and/or activation of ILC2 cells are poorly understood. In mouse models of pulmonary IT2IR, we demonstrated that phospholipid scramblase-1 (PLSCR1), a type II transmembrane protein that mediates bidirectional and nonspecific translocation of phospholipids between the inner and outer leaflets of the plasma membrane, was a critical regulator of IT2IR in the lung. We further suggested that (a) PLSCR1 bound to and physically interacted with chemoattractant receptor-homologous molecule(CRTH2), which is a G-protein-coupled receptor that is expressed on TH2 cells and on multiple immune cells and is commonly used to identify ILC2 cells, and (b) the effects of PLSCR1 on ILC2 activation and IT2IR were mediated via CRTH2-dependent mechanisms. Overall, our studies demonstrated that PLSCR1 played an essential role in the pathogenesis of ILC2 responses, providing critical insights into biology and disease pathogenesis and identifying targets that can be manipulated in attempts to control IT2IR in chronic diseases such as asthma.

The Prevalence of Depression Symptoms and Frequency of Risk Factors in Medical and Nursing Students: A Descriptive Cross-sectional Study.

OBJECTIVE: Currently, in Puerto Rico, there is a paucity of data regarding emotional health and depression in health professionals, specifically regarding trainees such as medical students and nursing students. The study intended to shed light on the prevalence of depression symptoms among medical and nursing students at a school of medicine in Puerto Rico. METHODS: In the fall of 2019, a descriptive cross-sectional study that included nursing and medical students in their first, second, and third years was performed. A survey consisting of the Patient Health Questionnaire (PHQ-9) and sociodemographic questions were used for data collection. Logistic regression analyses were used to determine the association of PHQ-9 scores and the risk factors linked to depression symptoms. RESULTS: A total of 173 (83.2%) out of 208 enrolled students participated in the study. Of the participants, 75.7% were medical students and 24.3% were nursing students. Of the risk factors studied, feelings of regret and lack of sleep were associated with a higher frequency of depression symptoms in medical students. For the nursing student population, suffering from a chronic disease was associated with a higher frequency of depression symptoms. CONCLUSION: Due to the increased risk of depression in healthcare professionals, identifying risk factors that can be addressed through early changes in behavior, or in institutional policies, is important in terms of working to mitigate the risk of mental health problems in this vulnerable population.

Aberrant Multiciliogenesis in Idiopathic Pulmonary Fibrosis.

We previously identified a novel molecular subtype of idiopathic pulmonary fibrosis (IPF) defined by increased expression of cilium-associated genes, airway mucin gene MUC5B, and KRT5 marker of basal cell airway progenitors. Here we show the association of MUC5B and cilia gene expression in human IPF airway epithelial cells, providing further rationale for examining the role of cilium genes in the pathogenesis of IPF. We demonstrate increased multiciliogenesis and changes in motile cilia structure of multiciliated cells both in IPF and bleomycin lung fibrosis models. Importantly, conditional deletion of a cilium gene, Ift88 (intraflagellar transport 88), in Krt5 basal cells reduces Krt5 pod formation and lung fibrosis, whereas no changes are observed in Ift88 conditional deletion in club cell progenitors. Our findings indicate that aberrant injury-activated primary ciliogenesis and Hedgehog signaling may play a causative role in Krt5 pod formation, which leads to aberrant multiciliogenesis and lung fibrosis. This implies that modulating cilium gene expression in Krt5 cell progenitors is a potential therapeutic target for IPF.

Prehospital End-Tidal CO2: A Superior Marker for Mortality Risk in the Acutely Injured Patient.

BACKGROUND: Emergency medical personnel must expeditiously triage acutely injured patients to the appropriate medical facility. Efficient and objective variables to facilitate this process and provide information to the receiving trauma center are needed. Currently, multiple variables are used to prognosticate injury severity and risk of mortality including vital signs, mental status, lactate, and base excess. We investigated the prehospital use of end-tidal carbon dioxide (ETCO2) as a noninvasive physiologic measure that can be obtained in the acutely injured patient. METHODS: We performed a retrospective analysis of 557 acutely injured patients over 2 years at a Level 1 trauma center. All patients arriving as trauma activations with ETCO2 measurements were included in analysis. End-tidal carbon dioxide measurements were categorized as low, normal, and high based on reference levels. Mortality was the primary outcome. Secondary receiver operator curves (ROC) for base excess, venous lactate, blood pressure, and venous pH were compared. We hypothesized ETCO2 levels would be able to predict mortality. RESULTS: End-tidal carbon dioxide levels conferred a mortality rate of 38%, 17.3%, and 2.9% for low, normal, and high, respectively (P < .001). Receiver operator curve analysis produced an area under the curve predictive value for ETCO2 (.748) which was superior to lactate (.660), SBP (.578), pH (.560), and base excess (.497). DISCUSSION: End-tidal carbon dioxide is a more sensitive and specific predictor of mortality in the acutely injured patient compared to venous lactate, base deficit, blood pressure, or venous pH. Additional studies are needed to determine if ETCO2 can be used as an effective prehospital adjunct to prevent mortality in acutely injured patients.

Internet use during COVID-19 lockdown among young people in low- and middle-income countries: Role of psychological wellbeing.

Problematic internet use in adolescents has been shown to significantly increase over the past few years, with COVID-19 pandemic lockdowns reinforcing this phenomena globally. We sought to explore whether problematic internet use in specific countries was related to emotional well-being and importantly whether this is predicted by psychological distress. There is a growing number of studies showing that problematic internet use is increasingly prevalent in countries with emerging economies, however we have yet to find out to what extent other factors are influencing this behaviour in adolescents and young people. This study invited young people from countries such India, Mexico, Philippines and Turkey to complete a set of self-reports on their daily internet habits, social media use, alongside questions on psychological distress, self-esteem, loneliness and escapism. A total of 1182 young people aged between 16 and 25 years old completed these questionnaires online. The results showed that there were significant difference in problematic internet use scores among adolescents in the Philippines and Turkey. More specifically, social media use was significantly higher amongst young people from the Philippines whereas gaming addiction was significantly high in the Turkish sample. These findings also revealed that psychological distress, loneliness, and low self-esteem consistently predicted problematic internet use. Taken together these results emphasise that there are several factors underlying growing figures of problematic internet use in young people, these factors include emotional distress, need for escapism, loneliness, and social media use, however, going forward more nuanced cultural differences should also be considered.

Hermansky-Pudlak Syndrome and Lung Disease: Pathogenesis and Therapeutics.

Hermansky-Pudlak Syndrome (HPS) is a rare, genetic, multisystem disorder characterized by oculocutaneous albinism (OCA), bleeding diathesis, immunodeficiency, granulomatous colitis, and pulmonary fibrosis. HPS pulmonary fibrosis (HPS-PF) occurs in 100% of patients with subtype HPS-1 and has a similar presentation to idiopathic pulmonary fibrosis. Upon onset, individuals with HPS-PF have approximately 3 years before experiencing signs of respiratory failure and eventual death. This review aims to summarize current research on HPS along with its associated pulmonary fibrosis and its implications for the development of novel treatments. We will discuss the genetic basis of the disease, its epidemiology, and current therapeutic and clinical management strategies. We continue to review the cellular processes leading to the development of HPS-PF in alveolar epithelial cells, lymphocytes, mast cells, and fibrocytes, along with the molecular mechanisms that contribute to its pathogenesis and may be targeted in the treatment of HPS-PF. Finally, we will discuss emerging new cellular and molecular approaches for studying HPS, including lentiviral-mediated gene transfer, induced pluripotent stem cells (iPSCs), organoid and 3D-modelling, and CRISPR/Cas9-based gene editing approaches.

Microglial memory of early life stress and inflammation: Susceptibility to neurodegeneration in adulthood.

We review evidence supporting the role of early life programming in the susceptibility for adult neurodegenerative diseases while highlighting questions and proposing avenues for future research to advance our understanding of this fundamental process. The key elements of this phenomenon are chronic stress, neuroinflammation triggering microglial polarization, microglial memory and their connection to neurodegeneration. We review the mediating mechanisms which may function as early biomarkers of increased susceptibility for neurodegeneration. Can we devise novel early life modifying interventions to steer developmental trajectories to their optimum?

Post-Hurricane Distress Scale (PHDS): A Novel Tool for First Responders and Disaster Researchers.

OBJECTIVE: The aim of this study was the construction and validation of a novel research instrument to quantify the degree of post-hurricane trauma and distress in an affected population. The Post-Hurricane Distress Scale (PHDS) has quantitative measures of both acute and prolonged distress, attributable to meteorological and hydrological disasters. METHODS: A careful evaluation of existing questionnaires, as well as extensive canvasing of the post-Maria population of Puerto Rico, availed the construction of the PHDS. The PHDS consists of 20 items, organized into 4 subscales. The PHDS was pre-validated (n=79), revised, and then distributed to a broad sampling of the post-Hurricane Maria Puerto Rican population (n=597). Validation, including factor analysis, analyses of concurrent validity, discriminant validity, and internal reliability, was performed. RESULTS: After comparing various scales, factor loading profiles, concurrent validities, and models of fit, we show that the PHDS is best scored as a single 0-6 distress scale. When compared with the Traumatic Exposure Severity Scale, the PHDS shows superior concurrent validity, more accurately predicting scores for the Peritraumatic Distress Inventory, Impact of Event Scale - Revised, and Generalized Anxiety Disorder 7 Scale. The PHDS shows good internal reliability and discriminant validity. CONCLUSIONS: The PHDS represents a novel, useful instrument for disaster first-responders and researchers. The prompt identification of high-risk populations is possible using this instrument. (Disaster Med Public Health Preparedness. 2019;13:82-89).

Surface Modification of PVDF Membranes for Treating Produced Waters by Direct Contact Membrane Distillation.

Direct contact membrane distillation (DCMD) has been conducted to treat hydraulic fracturing-produced water using polyvinylidenedifluoride (PVDF) membranes. Tailoring the surface properties of the membrane is critical in order to reduce the rate of adsorption of dissolved organic species as well as mineral salts. The PVDF membranes have been modified by grafting zwitterion and polyionic liquid-based polymer chains. In addition, surface oxidation of the PVDF membrane has been conducted using KMnO4 and NaOH. Surface modification conditions were chosen in order to minimize the decrease in contact angle. Thus, the membranes remain hydrophobic, essential for suppression of wetting. DCMD was conducted using the base PVDF membrane as well as modified membranes. In addition, DCMD was conducted on the base membrane using produced water (PW) that was pretreated by electrocoagulation to remove dissolved organic compounds. After DCMD all membranes were analyzed by scanning electron microscopy imaging as well as Energy-Dispersive X-Ray spectroscopy. Surface modification led to a greater volume of PW being treated by the membrane prior to drastic flux decline. The results indicate that tailoring the surface properties of the membrane enhances fouling resistance and could reduce pretreatment requirements.

Evaluation of Biochemical and Epigenetic Measures of Peripheral Brain-Derived Neurotrophic Factor (BDNF) as a Biomarker in Huntington's Disease Patients.

Huntington's disease (HD) is an autosomal-dominant neurodegenerative movement disorder that presents with prominent cognitive and psychiatric dysfunction. Brain-derived neurotrophic factor (BDNF) plays an important role in the pathophysiology of HD, as well as other neurodegenerative and psychiatric disorders, and epigenetic alterations in the complex BDNF promoter have been associated with its deregulation in pathological conditions. BDNF has gained increased attention as a potential biomarker of disease; but currently, the conflicting results from measurements of BDNF in different biofluids difficult the assessment of its utility as a biomarker for HD. Here, we measured BDNF protein levels in plasma (n = 85) and saliva (n = 81) samples from premanifest and manifest HD patients and normal controls using ELISA assays. We further examined DNA methylation levels of BDNF promoter IV using DNA derived from whole blood of HD patients and healthy controls (n = 40) using pyrosequencing. BDNF protein levels were not significantly different in plasma samples across diagnostic groups. Plasma BDNF was significantly correlated with age in control subjects but not in HD patients, nor were significant gender effects observed. Similar to plasma, salivary BDNF was correlated with age only in control subjects, with no gender effects observed. Importantly, we detected significantly lower levels of salivary BDNF in premanifest and manifest HD patients compared to control subjects, with lower BDNF levels being observed in premanifest patients within a predicted 10 years to disease onset. Salivary and plasma BDNF levels were not significantly correlated with one another, suggesting different origins. DNA methylation at four out of the 12 CpG sites studied in promoter IV were significantly altered in HD patients in comparison to controls. Interestingly, methylation at three of these CpG sites was inversely correlated to the Hospital Anxiety and Depression Scale (HADS) scores. BDNF promoter methylation was not correlated with motor or cognitive scores in HD patients, and was not associated with sex or age in neither disease nor control groups. Conclusion: Our studies show that BDNF protein levels are decreased in saliva; and BDNF promoter methylation increased in blood in HD subjects when compared to controls. These findings suggest that salivary BDNF measures may represent an early marker of disease onset and DNA methylation at the BDNF promoter IV, could represent a biomarker of psychiatric symptoms in HD patients.

Beneficial effects of glatiramer acetate in Huntington's disease mouse models: Evidence for BDNF-elevating and immunomodulatory mechanisms.

Huntington's disease (HD) is a fatal, neurodegenerative movement disorder that has no cure and few treatment options. In these preclinical studies, we tested the effects of chronic treatment of glatiramer acetate (GA; Copaxone®), an FDA-approved drug used as first-line therapy for MS, in two different HD mouse models, and explored potential mechanisms of action of drug efficacy. Groups of CAG140 knock-in and N171-82Q transgenic mice were treated with GA for up to 1year of age (CAG140 knock-in mice) or 20weeks (N171-82Q mice). Various behavioral assays were measured over the course of drug treatment whereby GA treatment delayed the onset and reduced the severity of HD behavioral symptoms in both mouse models. The beneficial actions of GA were associated with elevated levels of promoter I- and IV-driven brain-derived neurotrophic factor (Bdnf) expression and reduced levels of cytokines, in particular, interleukins IL4 and IL12, in the brains of HD mice. In addition, the GA-induced effects on BDNF, IL4 and IL12 levels were detected in plasma from drug-treated mice and rats, suggesting utility as a peripheral biomarker of treatment effectiveness. These preclinical studies support the use of GA as a relevant clinical therapy for HD patients.

Impact of a pilot pharmacy health-care professional out-of-school time physical activity and nutrition education program with exercise on fourth and fifth graders in a rural Texas community.

OBJECTIVES: Childhood obesity continues to be a problem. Children in rural populations are more likely to be overweight or obese and a lack of resources in those areas may contribute to this problem. We aimed to assess the impact of a pilot pharmacy health-care professional out-of-school time vigorous physical activity and nutrition education program on fourth and fifth graders in a rural Texas community. METHODS: We conducted a prospective 12-week cohort study from August to November 2012. Thirty-three children, aged 8-11 years, in Bailey County, Texas, were enrolled in the study. Body mass index, body mass index percentile, blood pressure, waist circumference, and a diet preferences and activities knowledge survey were obtained at 0, 4, 8, and 12 weeks. Study participants completed a twice weekly physical activity and nutrition education program with exercise over weeks 1-4 with no intervention during weeks 5-12. RESULTS: Thirty-one (94%) of the 33 children, predominately Hispanic girls, completed the program. Body mass index (-0.30 (95% confidence interval, -0.44 to -0.17); P = <0.0001), body mass index percentile (-2.75 (95% confidence interval, -4.89 to -0.62); P = 0.0026), systolic blood pressure (-1.9 (95% confidence interval, -2.9 to -0.9); P = <0.0001), and waist circumference (-0.47 (95% confidence interval, -0.85 to -0.10); P = <0.0001) mean change decreased between baseline and week 12 with no intervention for 8 weeks. Positive survey results at 3 months indicated a decrease in fried/sweet foods; increase in exercise; decreases in video games and computer use; and a change in knowledge regarding the selection of the most healthy food group servings per day. CONCLUSION: In this pharmacy health-care directed pilot study, participants had a reduction of body mass index, body mass index percentile, systolic blood pressure, waist circumference, and improvement in certain survey results at the end of 12 weeks despite no further intervention after 4 weeks.

Evolution of phenolic compounds from color and flavor problems to health benefits.

Early studies focused on the negative effects on color and flavor of foods, followed by exploration of the antioxidant properties and the associated health benefits. The growing body of evidence suggests that plant-based polyphenols may help prevent or delay the onset of a multiplicity of diseases. Newer work suggests that a variety of polyphenols can alter the expression of genes in the inflammatory pathway. Data also show that the absorption of the polyphenols is very limited. Insulin resistance and endothelial and mitochondrial dysfunction are hallmarks of the metabolic syndrome and aging and occur at the early stages of the disease. There is limited clinical evidence that certain polyphenolic metabolites by virtue of their anti-inflammatory activities can improve insulin sensitivity and endothelial and mitochondrial function, suggesting that polyphenols are good for disease prevention. The goal of this review is to summarize the evolution and emphasize the potential benefits of polyphenols.