Search

Abstract Crohn’s disease (CD) is a complex chronic inflammatory disorder with both gastrointestinal and extra-intestinal manifestations associated immune dysregulation. Analyzing 202,359 cells from 170 specimens across 83 patients, we identify a distinct epithelial cell type in both terminal ileum and ascending colon (hereon as ‘LND’) with high expression of LCN2, NOS2, and DUOX2 and genes related to antimicrobial response and immunoregulation. LND cells, confirmed by in-situ RNA and protein imaging, are rare in non-IBD controls but expand in active CD, and actively interact with immune cells and specifically express IBD/CD susceptibility genes, suggesting a possible function in CD immunopathogenesis. Furthermore, we discover early and late LND subpopulations with different origins and developmental potential. A higher ratio of late-to-early LND cells correlates with better response to anti-TNF treatment. Our findings thus suggest a potential pathogenic role for LND cells in both Crohn’s ileitis and colitis.

People who experience a stroke are at a higher risk of recurrent stroke when compared with people who have not had a stroke. Addressing modifiable risk factors like physical inactivity and poor diet has been shown to improve blood pressure, a leading contributor to stroke. However, survivors of stroke often experience challenges with accessing risk reduction services including long wait lists, difficulty with transportation, fatigue, impaired function, and diminished exercise capacity. Providing health interventions via a website can extend the reach when compared with programs that are only offered face to face or via real-time telehealth. Given global challenges of accessing secondary prevention programs, it is important to consider alternative ways that this information can be made available to survivors of stroke worldwide. Using the “design thinking” framework and drawing on principles of the integrated knowledge translation approach, we adapted 2 co-designed telehealth programs called i-REBOUND – Let’s get moving (physical activity intervention) and i-REBOUND – Eat for health (diet Intervention) to create the i-REBOUND after stroke website. The aim of this paper is to describe the systematic process undertaken to adapt resources from the telehealth delivered i-REBOUND – Let’s get moving and i-REBOUND – Eat for health programs to a website prototype with a focus on navigation requirements and accessibility for survivors of stroke. We engaged a variety of key stakeholders with diverse skills and expertise in areas of stroke recovery, research, and digital health. We established a governance structure, formed a consumer advisory group, appointed a diverse project team, and agreed on scope of the project. Our process of adaptation had the following 3 phases: (1) understand, (2) explore, (3) materialize. Our approach considered the survivor of stroke at the center of all decisions, which helped establish guiding principles related to our prototype design. Careful and iterative engagement with survivors of stroke together with the application of design thinking principles allowed us to establish the functional requirements for our website prototype. Through user testing, we were able to confirm the technical requirements needed to build an accessible and easy-to-navigate website catering to the unique needs of survivors of stroke. We describe the process of adapting existing content and co-creating new digital content in partnership with, and featuring, people who have lived experience of stroke. In this paper, we provide a road map for the steps taken to adapt resources from 2 telehealth-delivered programs to a website format that meets specific navigation and accessibility needs of survivors of stroke.

Abstract Background Geospatial smartphone application alert systems are used in some communities to crowdsource community response for out-of-hospital cardiac arrest (OHCA). Although the clinical focus of this strategy is OHCA, dispatch identification of OHCA is imperfect so that activation may occur for the non-arrest patient. The frequency and clinical profile of such non-arrest patients has not been well-investigated. Methods We undertook a prospective 3-year cohort investigation of patients for whom a smartphone geospatial application was activated for suspected OHCA in four United States communities (total population ~1 million). The current investigation evaluates those patients with an activation for suspected OHCA who did not experience cardiac arrest. The volunteer response cohort included off-duty, volunteer public safety personnel (verified responders) notified regardless of location (public or private) and laypersons notified to public locations. The study linked the smartphone application information with the EMS records to report the frequency, condition type, and EMS treatment for these non-arrest patients. Results Of 1779 calls where volunteers were activated, 756 had suffered OHCA, resulting in 1023 non-arrest patients for study evaluation. The most common EMS assessments were syncope (15.9%, n=163), altered mental status (15.5%, n=159), seizure (14.3%, n=146), overdose (13.0%, n=133), and choking (10.5%, n=107). The assessment distribution was similar for private and public locations. Overall, the most common EMS interventions included placement of an intravenous line (43.1%, n=441), 12-Lead ECG(27.9%, n=285), naloxone treatment (9.8%, n=100), airway or ventilation assistance (8.7%, n=89), and oxygen administration (6.6%, n=68). Conclusions More than half of patients activated for suspected OHCA had conditions other than cardiac arrest. A subset of these conditions may benefit from earlier care that could be provided by both layperson and public safety volunteers if they were appropriately trained and equipped.

Structured health system-based programs, such as cardiac rehabilitation, may reduce the risk of recurrent stroke. This study aimed to co-design and evaluate a structured program of rehabilitation, developed based on insights from focus groups involving stroke survivors and health professionals. Conducted in Tasmania, Australia in 2019, the 7-week program comprised one hour of group exercise and one hour of education each week. Functional capacity (6 min walk test), fatigue, symptoms of depression (Patient Health Questionnaire), and lifestyle were assessed pre- and post-program, with a historical control group for comparison. Propensity score matching determined the average treatment effect (ATE) of the program. Key themes from the co-design focus groups included the need for coordinated care, improved psychosocial management, and including carers and peers in programs. Of the 23 people approached, 10 participants (70% men, mean age 67.4 ± 8.6 years) completed the program without adverse events. ATE analysis revealed improvements in functional capacity (139 m, 95% CI 44, 234) and fatigue (−5 units, 95% CI −9, −1), with a small improvement in symptoms of depression (−0.8 units, 95% CI −1.8, 0.2) compared to controls. The co-designed program demonstrated feasibility, acceptability, and positive outcomes, suggesting its potential to support stroke survivors.

BackgroundAdults with chronic health conditions need support to manage modifiable risk factors such as physical inactivity and poor diet. Disease-specific websites with health information on physical activity and diet quality may be effective in supporting adults in managing their chronic illnesses. ObjectiveThe primary aim of this review was to determine whether using websites with health information can lead to improvements in physical activity levels or diet quality in adults with chronic health conditions. MethodsRandomized controlled trials evaluating the effectiveness of website use on levels of physical activity or diet quality in adults with chronic health conditions were included. MEDLINE, Embase, CINAHL, and the Physiotherapy Evidence Database were searched from the earliest available record until February 2023. Data for outcomes measuring physical activity levels; diet quality; and, where reported, self-efficacy and quality of life were independently extracted by 2 reviewers. The risk of bias was assessed using the Physiotherapy Evidence Database scale, and the overall certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. Where values were presented as the same unit of measure, postintervention scores were pooled for meta-analysis to yield an overall mean difference (MD). A standardized MD (SMD) was calculated for the pooled data in which different units for the same outcome were used. Individual trial data were described in cases where the data of trials could not be pooled. ResultsA total of 29 trials (N=6418 participants) across 8 different disease groups with intervention periods ranging from 4 weeks to 12 months were included in the analysis. There was moderate-certainty evidence that using websites with health information increased levels of moderate to vigorous physical activity (MD=39 min/wk, 95% CI 18.60-58.47), quality of life (SMD=0.36, 95% CI 0.12-0.59), and self-efficacy (SMD=0.26, 95% CI 0.05-0.48) and high-certainty evidence for reduction in processed meat consumption (MD=1.1 portions/wk, 95% CI 0.70-1.58) when compared with usual care. No differences were detected in other measures of diet quality. There was no increased benefit for website users who were offered additional support. ConclusionsThe use of websites for risk factor management has the potential to improve physical activity levels, quality of life, and self-efficacy as well as reduce processed meat consumption for adults living with chronic health conditions when compared with usual care. However, it remains unclear whether using websites leads to meaningful and long-lasting behavior change. Trial RegistrationPROSPERO CRD42021283168; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=283168

Background and Aims: This study aimed to evaluate adherence to subcutaneous biologic therapy and impact of nonadherence including risk factors and outcomes in academic centers with integrated specialty pharmacies for patients with inflammatory bowel disease (IBD). Methods: This was a multicenter, retrospective cohort analysis of patients aged ≥18 years receiving care in 3 tertiary care outpatient IBD clinics with integrated specialty pharmacies. Subjects were prescribed injectable anti-TNF therapy (adalimumab, certolizumab, golimumab) or anti-IL 12/23 therapy (ustekinumab) with at least 3 consecutive prescription claims. The primary outcomes were medication possession ratio (MPR), percent achieving optimal adherence (MPR > 0.86); in addition, we sought to verify a prior risk factor model including smoking status, narcotic use, psychiatric history, and prior biologic use. Secondary outcomes included emergency department visits (ED) and IBD-related hospitalizations. Statistical analysis was performed using Wilcox rank sum test, Pearson’s Chi-squared test, and logistic regression model as an unordered, factor variable to flexibly estimate the probabilities of adherence. Results: Six hundred eight subjects were included. Overall median MPR was 0.95 (interquartile range 0.47, 1) and adherence was 68%–70%. When the number of risk factors for nonadherence increased, the likelihood of nonadherence increased (P < .05). In unadjusted and adjusted analysis, nonadherence increased the likelihood of ED visits [rate ratio 1.45 (95% confidence interval 1.05, 1.97)] and hospitalizations [rate ratio 1.60 (95% confidence interval 1.16, 2.10)]. Conclusion: Academic centers with integrated pharmacies had high adherence. Prior risk factors for nonadherence remained significant in this multicenter model. Nonadherence was associated with higher likelihood of hospitalizations and ED visits.

Summary: The ATP-sensitive K+ (KATP) channel is a key regulator of hormone secretion from pancreatic islet endocrine cells. Using direct measurements of KATP channel activity in pancreatic β cells and the lesser-studied α cells, from both humans and mice, we provide evidence that a glycolytic metabolon locally controls KATP channels on the plasma membrane. The two ATP-consuming enzymes of upper glycolysis, glucokinase and phosphofructokinase, generate ADP that activates KATP. Substrate channeling of fructose 1,6-bisphosphate through the enzymes of lower glycolysis fuels pyruvate kinase, which directly consumes the ADP made by phosphofructokinase to raise ATP/ADP and close the channel. We further show the presence of a plasma membrane-associated NAD+/NADH cycle whereby lactate dehydrogenase is functionally coupled to glyceraldehyde-3-phosphate dehydrogenase. These studies provide direct electrophysiological evidence of a KATP-controlling glycolytic signaling complex and demonstrate its relevance to islet glucose sensing and excitability.

Many stool-based gut microbiome studies have highlighted the importance of the microbiome. However, we hypothesized that stool is a poor proxy for the inner-colonic microbiome and that studying stool samples may be inadequate to capture the true inner-colonic microbiome. To test this hypothesis, we conducted prospective clinical studies with up to 20 patients undergoing an FDA-cleared gravity-fed colonic lavage without oral purgative pre-consumption. The objective of this study was to present the analysis of inner-colonic microbiota obtained non-invasively during the lavage and how these results differ from stool samples. The inner-colonic samples represented the descending, transverse, and ascending colon. All samples were analyzed for 16S rRNA and shotgun metagenomic sequences. The taxonomic, phylogenetic, and biosynthetic gene cluster analyses showed a distinctive biogeographic gradient and revealed differences between the sample types, especially in the proximal colon. The high percentage of unique information found only in the inner-colonic effluent highlights the importance of these samples and likewise the importance of collecting them using a method that can preserve these distinctive signatures. We proposed that these samples are imperative for developing future biomarkers, targeted therapeutics, and personalized medicine.

BackgroundRehabilitation provided via telehealth offers an alternative to currently limited in-person health care. Effective rehabilitation depends on accurate and relevant assessments that reliably measure changes in function over time. The reliability of a suite of relevant assessments to measure the impact of rehabilitation on physical function is unknown. ObjectiveWe aimed to measure the intrarater reliability of mobility-focused physical outcome measures delivered via Zoom (a commonly used telecommunication platform) and interrater reliability, comparing Zoom with in-person measures. MethodsIn this reliability trial, healthy volunteers were recruited to complete 7 mobility-focused outcome measures in view of a laptop, under instructions from a remotely based researcher who undertook the remote evaluations. An in-person researcher (providing the benchmark scores) concurrently recorded their scores. Interrater and intrarater reliability were assessed for Grip Strength, Functional Reach Test, 5-Time Sit to Stand, 3- and 4-Meter Walks and Timed Up and Go, using intraclass correlation coefficients (ICC) and Bland-Altman plots. These tests were chosen because they cover a wide array of physical mobility, strength, and balance constructs; require little to no assistance from a clinician; can be performed in the limits of a home environment; and are likely to be feasible over a telehealth delivery mode. ResultsA total of 30 participants (mean age 36.2, SD 12.5 years; n=19, 63% male) completed all assessments. Interrater reliability was excellent for Grip Strength (ICC=0.99) and Functional Reach Test (ICC=0.99), good for 5-Time Sit to Stand (ICC=0.842) and 4-Meter Walk (ICC=0.76), moderate for Timed Up and Go (ICC=0.64), and poor for 3-Meter Walk (ICC=–0.46). Intrarater reliability, accessed by the remote researcher, was excellent for Grip Strength (ICC=0.91); good for Timed Up and Go, 3-Meter Walk, 4-Meter Walk, and Functional Reach (ICC=0.84-0.89); and moderate for 5-Time Sit to Stand (ICC=0.67). Although recorded simultaneously, the following time-based assessments were recorded as significantly longer via Zoom: 5-Time Sit to Stand (1.2 seconds), Timed Up and Go (1.0 seconds), and 3-Meter Walk (1.3 seconds). ConclusionsUntimed mobility-focused physical outcome measures have excellent interrater reliability between in-person and telehealth measurements. Timed outcome measures took approximately 1 second longer via Zoom, reducing the reliability of tests with a shorter duration. Small time differences favoring in-person attendance are of a similar magnitude to clinically important differences, indicating assessments undertaken using telecommunications technology (Zoom) cannot be compared directly with face-to-face delivery. This has implications for clinicians using blended (ie, some face-to-face and some via the internet) assessments. High intrarater reliability of mobility-focused physical outcome measures has been demonstrated in this study.

The microbiome of the temperate coral Astrangia poculata was first described in 2017 using next-generation Illumina sequencing to examine the coral’s bacterial and archaeal associates across seasons and among hosts of differing symbiotic status. To assess the impact of methodology on the detectable diversity of the coral’s microbiome, we obtained near full-length Sanger sequences from clone libraries constructed from a subset of the same A. poculata samples. Eight samples were analyzed: two sets of paired symbiotic (brown) and aposymbiotic (white) colonies collected in the fall (September) and two sets collected in the spring (April). Analysis of the Sanger sequences revealed that the microbiome of A. poculata exhibited a high level of richness; 806 OTUs were identified among 1390 bacterial sequences. While the Illumina study revealed that A. poculata’s microbial communities did not significantly vary according to symbiotic state, but did vary by season, Sanger sequencing did not expose seasonal or symbiotic differences in the microbiomes. Proteobacteria dominated the microbiome, forming the majority (55% to 80%) of classifiable bacteria in every sample, and the five bacterial classes with the highest mean relative portion (5% to 35%) were the same as those determined by prior Illumina sequencing. Sanger sequencing also captured the same core taxa previously identified by next-generation sequencing. Alignment of all sequences and construction of a phylogenetic tree revealed that both sequencing methods provided similar portrayals of the phylogenetic diversity within A. poculata’s bacterial associates. Consistent with previous findings, the results demonstrated that the Astrangia microbiome is stable notwithstanding the choice of sequencing method and the far fewer sequences generated by clone libraries (46 to 326 sequences per sample) compared to next-generation sequencing (3634 to 48481 sequences per sample). Moreover, the near-full length 16S rRNA sequences produced by this study are presented as a resource for the community studying this model system since they provide necessary information for designing primers and probes to further our understanding of this coral’s microbiome.

Summary: The orosomucoid-like (Ormdl) proteins play a critical role in sphingolipid homeostasis, inflammation, and ER stress, all of which are associated with obesity and βcell dysfunction. However, their roles in β cells and obesity remain unknown. Here, we show that islets from overweight/obese human donors displayed marginally reduced ORMDL1-2 expression, whereas ORMDL3 expression was significantly downregulated compared with islets from lean donors. In contrast, Ormdl3 was substantially upregulated in the islets of leptin-deficient obese (ob/ob) mice compared with lean mice. Treatment of ob/ob mice and their islets with leptin markedly reduced islet Ormld3 expression. Ormdl3 knockdown in a β cell line induced expression of pro-apoptotic markers, which was rescued by ceramide synthase inhibitor fumonisin B1. Our results reveal differential expression of Ormdl3 in the islets of a mouse model and humans with obesity, highlight the potential effect of leptin in this differential regulation, and suggest a role for Ormdl3 in β cell apoptosis.

IntroductionSmoking is a strong risk factor for disease severity in Crohn's disease (CD) and cessation improves outcomes. The nicotine metabolite ratio (NMR) predicts cessation success with pharmacotherapy: varenicline doubles cessation over nicotine replacement therapy (NRT) for "normal", but not "slow" metabolizers. Varenicline side effects are heightened in slow metabolizers. Methods using NMR to optimize cessation pharmacotherapy have not been evaluated in CD.AimsWe aim to determine the prevalence of smoking in a CD population and then assess these smokers' attitudes toward a personalized metabolism-informed care (MIC) approach to cessation.MethodsIn this observational study, we surveyed 1098 patients visiting an inflammatory bowel disease center about their smoking history. We then evaluated a subgroup of individuals with CD (n = 32) who participated in a randomized controlled trial of smoking cessation using MIC versus usual care. For MIC, medication selection was informed by the NMR (normal ≥0.31 vs. slow ResultsThe baseline prevalence of smoking in our CD population was 13%. Intervention participants reported high rates of satisfaction (85%) and chose a medication that matched their NMR result more often in the MIC group (100% vs. 64%, p = 0.01). Six of 16 (37.5%) patients prescribed varenicline discontinued due to side effects.ConclusionMIC produced high rates of satisfaction and matching between NMR and medication in CD patients, supporting patient acceptance and feasibility of precision smoking cessation in this population. To reduce smoking in CD, therapies such as MIC are needed to maximize efficacy and minimize side effects.

The transition from β-cell compensation to β-cell failure is not well understood. Previous works by our group and others have demonstrated a role for Prostaglandin EP3 receptor (EP3), encoded by the Ptger3 gene, in the loss of functional β-cell mass in Type 2 diabetes (T2D). The primary endogenous EP3 ligand is the arachidonic acid metabolite prostaglandin E2 (PGE2). Expression of the pancreatic islet EP3 and PGE2 synthetic enzymes and/or PGE2 excretion itself have all been shown to be upregulated in primary mouse and human islets isolated from animals or human organ donors with established T2D compared to nondiabetic controls. In this study, we took advantage of a rare and fleeting phenotype in which a subset of Black and Tan BRachyury (BTBR) mice homozygous for the Leptinob/ob mutation—a strong genetic model of T2D—were entirely protected from fasting hyperglycemia even with equal obesity and insulin resistance as their hyperglycemic littermates. Utilizing this model, we found numerous alterations in full-body metabolic parameters in T2D-protected mice (e.g., gut microbiome composition, circulating pancreatic and incretin hormones, and markers of systemic inflammation) that correlate with improvements in EP3-mediated β-cell dysfunction.

Metabarcoding of marine environmental DNA (eDNA), originating from tissue, cells, or extracellular DNA, offers the opportunity to survey the biological composition of communities across multiple trophic levels from a non-invasive seawater sample. Here we compare results of eDNA metabarcoding of multiple trophic levels from individual seawater samples collected from a kelp forest in Monterey Bay, California in order to establish methods for future cross-trophic level eDNA analysis. Triplicate 1 L water samples were filtered using five different 47 mm diameter membrane filters (PVDF, PES, GFF, PCTE, and NC) and DNA was extracted from triplicates of each filter-type using three widely-used extraction methods (the DNeasy Blood and Tissue kit, the MoBio PowerWater DNA Isolation kit, and standard phenol/chloroform methods) resulting in 45 individual eDNA samples prepared with 15 workflow combinations. Each DNA extract was amplified using PCR primers for the 16S rRNA gene (microorganisms; Bacteria and Archaea), 18S rRNA gene (phytoplankton), and the 12S rRNA gene (vertebrates), and PCR products were sequenced on an Illumina MiSeq platform. The richness and community composition of microbial, phytoplankton, and vertebrate OTUs were not significantly different between any of the 0.2 μm pore-size filter types extracted with the DNeasy or MoBio kits. However, phenol/chloroform extraction resulted in significantly different community structures. This study provides insight into multiple choices for extraction and filtration methods to use eDNA metabarcoding for biodiversity assessment of multiple trophic levels from a single sample. We recommend any combination of either DNeasy or MoBio with PES, PCTE, PVDF, or NC filters for a cross trophic level comparison.

Objectives: To compare how people communicate about eating disorders on two popular social media platforms – Twitter and Tumblr.Materials and Methods: Thematic analysis was conducted to characterize the types of communications posted, and a content analysis was undertaken of between-platform differences.Results: Three types of content (pro-ana, anti-ana, and pro-recovery) were posted on each platform. Overall, across both platforms, extreme pro-ana posts were in the minority compared to anti-ana and pro-recovery. Pro-ana posts (including ‘thinspiration’) were more common on Twitter than Tumblr, whereas anti-ana and pro-recovery posts were more common on Tumblr.Conclusion: The findings have implications for future research and health care relating to the treatment and prevention of eating disorders. Developers of future interventions targeting negative pro-ana content should remain aware of the need to avoid any detrimental impact on positive online support.

Over the last decade, publications on deep-sea corals have tripled. Most attention has been paid to Lophelia pertusa, a globally distributed scleractinian coral that creates critical three-dimensional habitat in the deep ocean. The bacterial community associated with L. pertusa has been previously described by a number of studies at sites in the Mediterranean Sea, Norwegian fjords, off Great Britain, and in the Gulf of Mexico (GOM). However, use of different methodologies prevents direct comparisons in most cases. Our objectives were to address intra-regional variation and to identify any conserved bacterial core community. We collected samples from three distinct colonies of L. pertusa at each of four locations within the western Atlantic: three sites within the GOM and one off the east coast of the United States. Amplicon libraries of 16S rRNA genes were generated using primers targeting the V4–V5 hypervariable region and 454 pyrosequencing. The dominant phylum was Proteobacteria (75–96%). At the family level, 80–95% of each sample was comprised of five groups: Pirellulaceae, Pseudonocardiaceae, Rhodobacteraceae, Sphingomonadaceae, and unclassified Oceanospirillales. Principal coordinate analysis based on weighted UniFrac distances showed a clear distinction between the GOM and Atlantic samples. Interestingly, the replicate samples from each location did not always cluster together, indicating there is not a strong site-specific influence. The core bacterial community, conserved in 100% of the samples, was dominated by the operational taxonomic units of genera Novosphingobium and Pseudonocardia, both known degraders of aromatic hydrocarbons. The sequence of another core member, Propionibacterium, was also found in prior studies of L. pertusa from Norway and Great Britain, suggesting a role as a conserved symbiont. By examining more than 40,000 sequences per sample, we found that GOM samples were dominated by the identified conserved core sequences, whereas open Atlantic samples had a much higher proportion of locally consistent bacteria. Further, predictive functional profiling highlights the potential for the L. pertusa microbiome to contribute to chemoautotrophy, nutrient cycling, and antibiotic production.

Background Viruses strongly influence microbial population dynamics and ecosystem functions. However, our ability to quantitatively evaluate those viral impacts is limited to the few cultivated viruses and double-stranded DNA (dsDNA) viral genomes captured in quantitative viral metagenomes (viromes). This leaves the ecology of non-dsDNA viruses nearly unknown, including single-stranded DNA (ssDNA) viruses that have been frequently observed in viromes, but not quantified due to amplification biases in sequencing library preparations (Multiple Displacement Amplification, Linker Amplification or Tagmentation). Methods Here we designed mock viral communities including both ssDNA and dsDNA viruses to evaluate the capability of a sequencing library preparation approach including an Adaptase step prior to Linker Amplification for quantitative amplification of both dsDNA and ssDNA templates. We then surveyed aquatic samples to provide first estimates of the abundance of ssDNA viruses. Results Mock community experiments confirmed the biased nature of existing library preparation methods for ssDNA templates (either largely enriched or selected against) and showed that the protocol using Adaptase plus Linker Amplification yielded viromes that were ±1.8-fold quantitative for ssDNA and dsDNA viruses. Application of this protocol to community virus DNA from three freshwater and three marine samples revealed that ssDNA viruses as a whole represent only a minor fraction (

RELN encodes a large, secreted glycoprotein integral to proper neuronal positioning during development and regulation of synaptic function postnatally. Rare, homozygous, null mutations lead to lissencephaly with cerebellar hypoplasia, accompanied by developmental delay and epilepsy. Until recently, little was known about the frequency or consequences of heterozygous mutations. Several lines of evidence from multiple studies now implicate heterozygous mutations in RELN in autism spectrum disorders (ASD). RELN maps to the AUTS1 locus on 7q22, and at this time over 40 distinct mutations have been identified that would alter the protein sequence, four of which are de novo. The RELN mutations that are most clearly consequential are those that are predicted to inactivate the signaling function of the encoded protein, and those that fall in a highly conserved RXR motif found at the core of the 16 Reelin subrepeats. Despite the growing evidence of RELN dysfunction in ASD, it appears that these mutations in isolation are insufficient and that secondary genetic or environmental factors are likely required for a diagnosis.

Ulcerative colitis (UC) is associated with increased dietary intake of fat and n-6 polyunsaturated fatty acids (PUFA). Modification of fat metabolism may alter inflammation and disease severity. Our aim was to assess differences in dietary and serum fatty acid levels between control and UC subjects and associations with disease activity and inflammatory cytokines.Dietary histories, serum, and colonic tissue samples were prospectively collected from 137 UC subjects and 38 controls. Both histologic injury and the Mayo Disease Activity Index were assessed. Serum and tissue cytokines were measured by Luminex assay. Serum fatty acids were obtained by gas chromatography.UC subjects had increased total fat and oleic acid (OA) intake, but decreased arachidonic acid (AA) intake vs controls. In serum, there was less percent saturated fatty acid (SFA) and AA, with higher monounsaturated fatty acids (MUFA), linoleic acid, OA, eicosapentaenoic acid (EPA), and docosapentaenoic acid (DPA) in UC. Tissue cytokine levels were directly correlated with SFA and inversely correlated with PUFA, EPA, and DPA in UC subjects, but not controls. 5-aminosalicylic acid therapy blunted these associations.In summary, we found differences in serum fatty acids in UC subjects that correlated with pro-inflammatory tissue cytokines. We propose that fatty acids may affect cytokine production and thus be immunomodulatory in UC.

Gelatinous zooplankton, such as ctenophores and jellyfish, are important components of marine and brackish ecosystems and play critical roles in aquatic biogeochemistry. As voracious predators of plankton, ctenophores have key positions in aquatic food webs and are often successful invaders when introduced to new areas. Gelatinous zooplankton have strong impacts on ecosystem services, particularly in coastal environments. However, little is known about the factors responsible for regulating population dynamics of gelatinous organisms, including biological interactions that may contribute to bloom demise. Ctenophores are known to contain specific bacterial communities and a variety of invertebrate parasites and symbionts; however, no previous studies have examined the presence of viruses in these organisms. Building upon recent studies demonstrating a diversity of single-stranded DNA viruses that encode a replication initiator protein (Rep) in aquatic invertebrates, this study explored the presence of circular, Rep-encoding single-stranded DNA (CRESS-DNA) viruses in the ctenophores Mnemiopsis leidyi and Beroe ovata collected from the Skidaway River Estuary and Savannah River in Georgia, USA. Using rolling circle amplification followed by restriction enzyme digestion, this study provides the first evidence of viruses in ctenophores. Investigation of four CRESS-DNA viruses over an eight-month period using PCR demonstrated temporal trends in viral prevalence and indicated that some of the viruses may persist in ctenophore populations throughout the year. Although future work needs to examine the ecological roles of these ctenophore-associated viruses, this study indicates that viral infection may play a role in population dynamics of gelatinous zooplankton.

Deep sequencing of the viral phoH gene, a host-derived auxiliary metabolic gene, was used to track viral diversity throughout the water column at the Bermuda Atlantic Time-series Study (BATS) site in the summer (September) and winter (March) of three years. Viral phoH sequences reveal differences in the viral communities throughout a depth profile and between seasons in the same year. Variation was also detected between the same seasons in subsequent years, though these differences were not as great as the summer/winter distinctions. Over 3,600 phoH operational taxonomic units (OTUs; 97% sequence identity) were identified. Despite high richness, most phoH sequences belong to a few large, common OTUs whereas the majority of the OTUs are small and rare. While many OTUs make sporadic appearances at just a few times or depths, a small number of OTUs dominate the community throughout the seasons, depths, and years.

Accurate and high-throughput technologies are needed for identification of new therapeutic targets and for optimizing therapy in inflammatory bowel disease. Our aim was to assess multi-analyte protein-based assays of cytokines/chemokines using Luminex technology. We have reported that Luminex-based profiling was useful in assessing response to L-arginine therapy in the mouse model of dextran sulfate sodium colitis. Therefore, we studied prospectively collected samples from ulcerative colitis (UC) patients and control subjects. Serum, colon biopsies, and clinical information were obtained from subjects undergoing colonoscopy for evaluation of UC or for non-UC indications. In total, 38 normal controls and 137 UC cases completed the study. Histologic disease severity and the Mayo Disease Activity Index (DAI) were assessed. Serum and colonic tissue cytokine/chemokine profiles were measured by Luminex-based multiplex testing of 42 analytes. Only eotaxin-1 and G-CSF were increased in serum of patients with histologically active UC vs. controls. While 13 cytokines/chemokines were increased in active UC vs. controls in tissues, only eotaxin-1 was increased in all levels of active disease in both serum and tissue. In tissues, eotaxin-1 correlated with the DAI and with eosinophil counts. Increased eotaxin-1 levels were confirmed by real-time PCR. Tissue eotaxin-1 levels were also increased in experimental murine colitis induced by dextran sulfate sodium, oxazolone, or Citrobacter rodentium, but not in murine Helicobacter pylori infection. Our data implicate eotaxin-1 as an etiologic factor and therapeutic target in UC, and indicate that Luminex-based assays may be useful to assess IBD pathogenesis and to select patients for anti-cytokine/chemokine therapies.

Objective: International students in the US often adopt unhealthy dietary behaviors, perhaps due to lack of familiarity and social support. This study examined the impact of social support on international college students' dietary behaviors. Participants: This study surveyed international students (N = 318) from five public universities in one Midwest state. Methods: Participants completed an electronic survey assessing self-reported eating habits and perceived social support using the Social Support for Eating Habits and the Starting the Conversation (STC) scales. Data analyses included multiple linear regression and multiple logistic regression to test the study's hypotheses. Comparisons were made to explore the impact of perceived social support on international students' dietary behaviors. Results: Significant predictors of unhealthy dietary behaviors included region of origin (specifically, being from East Asia, Europe and North America) and having families that discouraged healthy eating habits. Additionally, living with immediate family members significantly decreased students' likelihood of having higher friend encouragement for healthy eating habits. Finally, the amount of time participants spent in the US significantly increased their likelihood of having more discouragement of healthy eating from their friends. Conclusions: International students' unhealthy eating habits increased when their families discouraged them from healthy eating. Interventions promoting healthy diet among international students should consider including family members to increase social support for healthy eating habits.

Purpose: Post-stroke fatigue is a research priority for stroke survivors and health professionals but there is limited evidence to guide management. We aimed to explore (1) the experience of post-stroke fatigue from the perspective of stroke survivors and their caregivers and (2) fatigue management strategies that are used. Materials and methods: This was a qualitative study using semi-structured interviews. People with self-reported post-stroke fatigue and caregivers were recruited using maximum variation sampling. Analysis was done via the framework approach. Results: We recruited 17 stroke survivors, nine male (53%), most under 65 years (n = 12, 76%), and greater than 1-year post-stroke (n = 16, 94%, range 10-months to 22-years). One-third of participants self-reported having aphasia (n = 5, 36%). We also recruited eight caregivers, most of whom were female (n = 7, 88%). We identified four themes: (1) fatigue is unexpected after stroke and symptoms vary; (2) the individual experience of fatigue is complex, influenced by multifactorial and biopsychosocial factors; (3) learning to adapt and accept fatigue; and (4) Strategies to manage fatigue and personal approaches to rest. Conclusions: Post-stroke fatigue experience varies presenting cognitively, physically, and psychologically according to a complex interplay of biopsychosocial factors and personal triggers. Self-management strategies are individualised and include organisation, medications, lifestyle modifications, and peer support. IMPLICATIONS FOR REHABILITATION: Post-stroke fatigue is a complex individual experience involving biopsychosocial factors, and stroke survivors need assistance to identify their triggers and support from family, peers, and the stroke community to live well with fatigue. Fatigue is not commonly discussed by health professionals and stroke survivors need simple, practical advice over the long-term to reduce fear and distress. There are a range of strategies that may be helpful. Stroke survivors may benefit from adopting problem-solving approaches, trial pacing, lifestyle modifications and planning, and find forms of rest that work for them. [ABSTRACT FROM AUTHOR]

Individuals with autism spectrum disorder (ASD) often have few employment opportunities and a lower job quality than individuals of typical development. Social deficits and lack of independence may contribute to underemployment and unemployment of individuals with ASD. The ability to solve problems might ameliorate some of these barriers. We taught four adolescents with ASD a problem-solving strategy (i.e., use of a textual activity schedule) to assist with independent completion of vocational tasks in the face of three types of problems (e.g., missing or broken items) and nonproblem situations. Following introduction of the problem-solving strategy, all four participants independently completed the tasks when a problem was presented and responding generalized to untaught vocational tasks.

The Florida Virtual Campus (FLVC), a statewide library consortium serving 40 public colleges and universities in Florida, implemented a new integrated library system for all libraries in 2020–2021. The scope and scale of the project were highly complex, requiring robust communication strategies and mechanisms for success. FLVC worked with its member libraries and other stakeholders to create an organizational framework for the project. After the completion of the project, FLVC surveyed project participants to assess the effectiveness of the organizational framework. Overall results were strongly positive, while some areas for improvement were identified. [ABSTRACT FROM AUTHOR]

This document is a letter written by a group of medical professionals expressing their concerns about an article titled "Recognition and Management of Delirium in the Neonatal Intensive Care Unit: Case Series From a Single-Center Level IV Intensive Care Unit." The authors of the letter raise concerns about the scientific premise, neurobiological assumptions, robustness of methods, and validity of the conclusions presented in the article. They argue that the diagnostic tools for delirium used in the article have not been adequately validated in the neonatal or infant population, and they caution against the use of antipsychotic medications in neonates and premature infants without robust preclinical and clinical data supporting their use. [Extracted from the article]

BackgroundViruses strongly influence microbial population dynamics and ecosystem functions. However, our ability to quantitatively evaluate those viral impacts is limited to the few cultivated viruses and double-stranded DNA (dsDNA) viral genomes captured in quantitative viral metagenomes (viromes). This leaves the ecology of non-dsDNA viruses nearly unknown, including single-stranded DNA (ssDNA) viruses that have been frequently observed in viromes, but not quantified due to amplification biases in sequencing library preparations (Multiple Displacement Amplification, Linker Amplification or Tagmentation).MethodsHere we designed mock viral communities including both ssDNA and dsDNA viruses to evaluate the capability of a sequencing library preparation approach including an Adaptase step prior to Linker Amplification for quantitative amplification of both dsDNA and ssDNA templates. We then surveyed aquatic samples to provide first estimates of the abundance of ssDNA viruses.ResultsMock community experiments confirmed the biased nature of existing library preparation methods for ssDNA templates (either largely enriched or selected against) and showed that the protocol using Adaptase plus Linker Amplification yielded viromes that were ±1.8-fold quantitative for ssDNA and dsDNA viruses. Application of this protocol to community virus DNA from three freshwater and three marine samples revealed that ssDNA viruses as a whole represent only a minor fraction (