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Hypertriglyceridemia is an independent risk factor for cardiovascular disease, and plasma triglycerides (TGs) correlate strongly with plasma apolipoprotein C-III (ApoC-III) levels. Antisense oligonucleotides (ASOs) for ApoC-III reduce plasma TGs in primates and mice, but the underlying mechanism of action remains controversial. We determined that a murine-specific ApoC-III-targeting ASO reduces fasting TG levels through a mechanism that is dependent on low-density lipoprotein receptors (LDLRs) and LDLR-related protein 1 (LRP1). ApoC-III ASO treatment lowered plasma TGs in mice lacking lipoprotein lipase (LPL), hepatic heparan sulfate proteoglycan (HSPG) receptors, LDLR, or LRP1 and in animals with combined deletion of the genes encoding HSPG receptors and LDLRs or LRP1. However, the ApoC-III ASO did not lower TG levels in mice lacking both LDLR and LRP1. LDLR and LRP1 were also required for ApoC-III ASO-induced reduction of plasma TGs in mice fed a high-fat diet, in postprandial clearance studies, and when ApoC-III-rich or ApoC-III-depleted lipoproteins were injected into mice. ASO reduction of ApoC-III had no effect on VLDL secretion, heparin-induced TG reduction, or uptake of lipids into heart and skeletal muscle. Our data indicate that ApoC-III inhibits turnover of TG-rich lipoproteins primarily through a hepatic clearance mechanism mediated by the LDLR/LRP1 axis.

BACKGROUND:An association between cytomegalovirus (CMV) and acute severe inflammatory bowel disease (IBD) colitis has been demonstrated in prior studies. However, it is unclear whether this association indicates CMV as a causative pathogen in triggering severe flares. This study aimed to assess the incidence of CMV in IBD patients admitted to a community-based, safety-net hospital for acute severe colitis and evaluate risk factors and outcomes for CMV colitis.METHODS:A retrospective case control study involving all IBD patients admitted from 2013-2017 to a county hospital with acute severe colitis. Data was collected from the hospital's electronic medical record. Data extracted included demographics, IBD type, symptoms on admission, and types of medications used including steroids or biologic therapy. We calculated odds ratios (OR) and confidence intervals for multiple risk factors.RESULTS:Among 45 IBD patients, there were 80 separate hospitalizations that met criteria for acute severe colitis based on Truelove and Witt's criteria. CMV infection was detected in 3 out of 80 (4%) admissions. 67% and 33% of CMV cases had received prior treatment with high dose steroids & biologics respectively, compared to 33% & 29% of cases without CMV infection (OR 4.16, P-value 0.25; OR 1.25, P-value 0.86). Of patients with CMV infection, 67% had ulcerative colitis (UC), 33% Crohn's Disease (CD), 100% were age < 40, 33% were male and 67% female, none had cancer or HIV, and 33% had cytopenia. Of patients without CMV infection, 71% had UC, 29% had CD, 52% were age < 40, 58% were male and 42% female, 1% had cancer, 1% had HIV, and 8% had cytopenia. The course of CMV positive cases was similar to CMV negative cases: 1 of the 3 cases of CMV cases was steroid refractory, 1 of 3 cases was immediately treated with biologics, and no case progressed to colectomy. In CMV negative cases, 20 of 77 were steroid refractory, 32 of 77 received biologics, and 9 of 77 underwent colectomy.CONCLUSION(S):Three out of 80 cases of acute severe colitis were found to have CMV infection, a figure lower than in previous studies. In our study, CMV is infrequently associated with colitis and of those who had CMV, none required colectomy. Of the risk factors that were evaluated, none were significantly associated with CMV colitis though this may be due to the small number of cases. Of note, there was a non-significant trend towards CMV infection with prior high dose steroids, age < 40 years, and IBD duration < 1 year. More prospective studies are needed to evaluate the true risk of CMV infection in acute severe colitis.

Introduction: An association between cytomegalovirus (CMV) and acute severe inflammatory bowel disease (IBD) colitis has been demonstrated in prior studies. However, it is unclear whether this association indicates CMV as a causative pathogen in triggering severe flares. This study aimed to assess the incidence of CMV in IBD patients admitted to a community-based, safety-net hospital for acute severe colitis and evaluate risk factors for CMV colitis. Methods: A retrospective case control study involving all IBD patients admitted from 2013-2017 to a county hospital with acute severe colitis. Data was collected from the hospital's electronic medical record. Data extracted included demographics, IBD type, symptoms on admission, and types of medications used including steroids or biologic therapy. We calculated odds ratios (OR) and confidence intervals for multiple risk factors. Results: Among 45 IBD patients, there were 80 hospitalizations for acute severe colitis. CMV infection was detected in 3 out of 80 (4%) admissions. 67% and 33% of CMV cases had received prior treatment with high dose steroids & biologics respectively, compared to 33% & 29% of cases without CMV infection (OR 4.16, p-value 0.25; OR 1.25, p-value 0.86). Of patients with CMV infection, 67% had ulcerative colitis (UC), 33% Crohn's Disease (CD), 100% were age < 40, 33% were male & 67% female, none had cancer or HIV, and 33% had cytopenia. Of patients without CMV infection, 71% had UC, 29% had CD, 52% were age < 40, 58% were male & 42% female, 1% had cancer, 1% had HIV, and 8% had cytopenia. The course of CMV positive cases was similar to CMV negative cases: 1 of 3 cases of CMV cases was steroid refractory, 1 of 3 cases was immediately treated with biologics, and no case progressed to colectomy. In CMV negative cases, 20 of 77 were steroid refractory, 32 of 77 received biologics, and 9 of 77 underwent colectomy. Conclusion: Only 3 out of 80 cases of acute severe colitis were found to have CMV infection, a figure lower than in previous studies. In our study, there was a non-significant trend towards CMV infection with prior high dose steroids, age < 40 years, and IBD duration < 1 year. No risk factors were statistically significant, likely due to the small sample size. Additional studies are needed to readdress the issue of whether testing for CMV infection in a patient with acute severe colitis is beneficial.

Background/Objectives: We wished to raise awareness of Hereditary Spherocytosis (HS) as a potential cause of early and significant hemolytic newborn jaundice. Methods: We utilized three recent cases from our experience to discuss hyperbilirubinemia etiologies to be considered when a baby has hemolytic hyperbilirubinemia, including HS, and presented a review of the literature about this disorder including presentation and evaluation in the neonate. Results: We found that ABO hemolytic disease of the newborn (HDN) is often considered as the etiology for presumed hemolytic hyperbilirubinemia even when the direct antiglobulin test (DAT) is negative. When there is a mother-baby ABO mismatch and baby’sDAT is negative, another etiology should be sought. HS should be considered in these cases as the prevalence of HS is as frequent as 1 in 2000 in certain populations, it is the third most common hemolytic disorder after ABO isoimmunization and G6PD deficiency, and it is the most common cause of non-immune hemolytic hyperbilirubinemia in neonates with kernicterus. The indices to look for in the complete blood count that are suggestive for HS are MCHC > 36.5–37 g/dL, an MCHC:MCV ratio (HS Index) > 0.36, and increased RDW. The lack of spherocytes on the newborn peripheral blood smear, family history, initial anemia, and reticulocytosis do not eliminate the diagnosis of HS. Conclusions: HS is common and should be included in the differential diagnosis for hemolytic hyperbilirubinemia. Red blood cell indices can suggest the diagnosis of HS, and eosin 5’ maleimide (EMA) testing can be used to make the diagnosis. If DAT-negative ABO HDN is the leading diagnosis for hyperbilirbinemia, a different etiology should urgently be sought.

Objective To describe the population to which we administered recombinant erythropoietin and to determine the effectiveness of this treatment as quantified by the change in hematocrit. Study design This retrospective chart review study included infants who received erythropoietin for the treatment of anemia of prematurity. Results There were 132 infants representing 162 unique treatment courses included in the study. The average duration of therapy was 9 days (±7) and 6 doses (±2). The average change in hematocrit (Hct) was 6.2% (SD 3.9%, p  < 0.001). Rise in Hct was associated with a higher number of rEPO doses ( p  < 0.001) and higher postmenstrual age ( p  < 0.001). In our small cohort we did not find an association between the number of rEPO doses and retinopathy of prematurity (ROP) requiring treatment. Conclusion Erythropoietin is safe and effective at treating anemia of prematurity as evidenced by a clinically and statistically significant increase in Hct from baseline.

The primary objective of this research was to evaluate the use of intravenous immunoglobulin (IVIG) in infants with hemolytic disease, to assess compliance with the American Academy of Pediatrics (AAP) guideline recommendations, and to review the data on which the guidelines were based. This retrospective study evaluated all infants in the NICU (neonatal intensive care unit) who received IVIG between January 2018 and December 2020 (n = 71). Total serum bilirubin (TSB) levels surrounding the time of IVIG administration, rate of rise of bilirubin, and direct antiglobulin test (DAT) status were evaluated to determine the appropriateness of IVIG use based on the 2004 AAP recommendations that was current at the time of the study. Fifty-nine infants received IVIG for hyperbilirubinemia. Of them, 80% had an ABO mismatch, 19% had Rh mismatch, and 71% were DAT-positive. Phototherapy was started at an average of 7 h of age, and the first IVIG dose was administered at an average of 13 h of life; nearly 25% received a second IVIG dose. One infant (1.6%) met all three AAP guideline criteria of being DAT-positive, bilirubin within 3 of exchange level, and rising bilirubin despite intensive phototherapy. Twenty-five (42%) babies were DAT positive and met one of the other two criteria. Only 12% (n = 7) had a bilirubin within 3 of exchange level. Most infants who received IVIG for hyperbilirubinemia did not meet the AAP criteria, prompting us to develop an institution-specific IVIG clinical practice guideline. The 2022 AAP guideline was published after our study was completed, but it confirmed our belief that IVIG usage should be more restricted and the criteria more explicit.

Comprehensive and meaningful inclusion of marginalized communities within the research enterprise will be critical to ensuring an equitable, technology-informed, clean energy transition. We provide five key action items for government agencies and philanthropic institutions to operationalize the commitment to an equitable energy transition.

Abstract The ILHBN is funded by the National Institutes of Health to collaboratively study the interactive dynamics of behavior, health, and the environment using Intensive Longitudinal Data (ILD) to (a) understand and intervene on behavior and health and (b) develop new analytic methods to innovate behavioral theories and interventions. The heterogenous study designs, populations, and measurement protocols adopted by the seven studies within the ILHBN created practical challenges, but also unprecedented opportunities to capitalize on data harmonization to provide comparable views of data from different studies, enhance the quality and utility of expensive and hard-won ILD, and amplify scientific yield. The purpose of this article is to provide a brief report of the challenges, opportunities, and solutions from some of the ILHBN’s cross-study data harmonization efforts. We review the process through which harmonization challenges and opportunities motivated the development of tools and collection of metadata within the ILHBN. A variety of strategies have been adopted within the ILHBN to facilitate harmonization of ecological momentary assessment, location, accelerometer, and participant engagement data while preserving theory-driven heterogeneity and data privacy considerations. Several tools have been developed by the ILHBN to resolve challenges in integrating ILD across multiple data streams and time scales both within and across studies. Harmonization of distinct longitudinal measures, measurement tools, and sampling rates across studies is challenging, but also opens up new opportunities to address cross-cutting scientific themes of interest. Harmonization of intensive longitudinal data across heterogeneous study designs and participant characteristics within [Network] generated new tools and insights to facilitate future big data harmonization efforts. Lay Summary Health behavior changes, such as prevention of suicidal thoughts and behaviors, smoking, drug use, and alcohol use; and the promotion of mental health, sleep, and physical activities, and decreases in sedentary behavior, are difficult to sustain. The ILHBN is a cooperative agreement network funded jointly by seven participating units within the National Institutes of Health to collaboratively study how factors that occur in individuals’ everyday life and in their natural environment influence the success of positive health behavior changes. This article discusses how information collected using smartphones, wearables, and other devices can provide helpful active and passive reflections of the participants’ extent of risk and resources at the moment for an extended period of time. However, successful engagement and retention of participants also require tailored adaptations of study designs, measurement tools, measurement intervals, study span, and device choices that create hurdles in integrating (harmonizing) data from multiple studies. We describe some of the challenges, opportunities, and solutions that emerged from harmonizing intensive longitudinal data under heterogeneous study and participant characteristics within the ILHBN, and share some tools and recommendations to facilitate future data harmonization efforts.

In response to the COVID-19 pandemic, the Psychological Science Accelerator coordinated three large-scale psychological studies to examine the effects of loss-gain framing, cognitive reappraisals, and autonomy framing manipulations on behavioral intentions and affective measures. The data collected (April to October 2020) included specific measures for each experimental study, a general questionnaire examining health prevention behaviors and COVID-19 experience, geographical and cultural context characterization, and demographic information for each participant. Each participant started the study with the same general questions and then was randomized to complete either one longer experiment or two shorter experiments. Data were provided by 73,223 participants with varying completion rates. Participants completed the survey from 111 geopolitical regions in 44 unique languages/dialects. The anonymized dataset described here is provided in both raw and processed formats to facilitate re-use and further analyses. The dataset offers secondary analytic opportunities to explore coping, framing, and self-determination across a diverse, global sample obtained at the onset of the COVID-19 pandemic, which can be merged with other time-sampled or geographic data. Measurement(s) COVID-19 Protocols, Restrictions • Health Behaviors • Personality and Behavioral Change, CTCAE • Emotion • Message Framing • Self-Determination Technology Type(s) Survey • Experiment Design Type Factor Type(s) COVID-19 Protocols, Restrictions • Health Behaviors • Loss-Gain Framing • Cognitive Reappraisal • Self-Determination Messaging Sample Characteristic - Organism Homo Sample Characteristic - Environment Daily Life Sample Characteristic - Location North America • South America • Africa • Australia • Europe • United Kingdom • Asia