Intestinal cell death is a defining feature of Crohn's disease (CD), a major form of inflammatory bowel disease. The focus on this aspect of enteric inflammation has mainly been on epithelial cells, while other cell types such as stromal and myeloid cells have received less attention. Hypothesising that decreased macrophage viability in an oxidative environment could be a contributing factor to the pathophysiology of CD, we found that monocyte-derived macrophages from individuals with active CD (but not those in clinical disease remission) have increased sensitivity to cell death induced by HO.
View Article and Find Full Text PDFThe disruption of the intestinal epithelial barrier leads to increased intestinal permeability (IP), allowing endotoxins and pathogens to enter the bloodstream contributing to chronic inflammation. Western diets are associated with increased IP, while diets rich in polyphenols, fiber, and omega-3 fats are linked to decreased IP. The relationship between diet, disease activity, and IP in ulcerative colitis (UC) is poorly understood.
View Article and Find Full Text PDFNeurodevelopmental disorders (NDDs) can severely impact functioning yet effective treatments are limited. Greater insight into the neurobiology underlying NDDs is critical to the development of successful treatments. Using a genetics-first approach, we investigated the potential of advanced diffusion-weighted imaging (DWI) techniques to characterize the neural microstructure unique to neurofibromatosis type 1 (NF1) and Noonan syndrome (NS).
View Article and Find Full Text PDFBackground/objectives: Food insecurity (FI) is defined as the lack of consistent access to enough food for an active and healthy life. FI affects over 30 million Americans and is associated with poor clinical outcomes and impaired quality of life and drives significant health inequities. Despite the rising prevalence of FI and the federal focus on improving access to healthy food, there is a paucity of research on FI in patients with inflammatory bowel disease (IBD).
View Article and Find Full Text PDFDietary intervention is a subject of growing interest in the management of inflammatory bowel disease (IBD), as new incident cases across the globe are rapidly rising, suggesting environmental factors as contributing elements. Dietary components and micronutrients have been associated with IBD pathogenesis or reductions in disease severity. Selenium, a diet-derived essential micronutrient that is important for proper immune system function, has received limited attention in the context of IBD.
View Article and Find Full Text PDFPeroxisomes are vital organelles involved in key metabolic functions in eukaryotic cells. Their significance is highlighted by peroxisome biogenesis disorders; severe childhood diseases marked by disrupted lipid metabolism. One mechanism regulating peroxisome abundance is through selective ubiquitylation of peroxisomal membrane proteins that triggers peroxisome degradation via selective autophagy (pexophagy).
View Article and Find Full Text PDFIntroduction: Recommendations to move to a race-free estimating equation for glomerular filtration rate (GFR) have gained increasing prominence since 2021. We wished to determine the impact of any future adoption upon the chronic kidney disease (CKD) patient population of a large teaching hospital, with a population breakdown largely similar to that of England as a whole.
Methods: We compared four estimating equations (Modification of Diet in Renal Disease [MDRD], CKD-EPI [2009], CKD-EPI [2021], and European Kidney Function Consortium [EKFC]) using the Bland-Altman method.
Noonan syndrome and neurofibromatosis type 1 are genetic conditions linked to pathogenic variants in genes of the Ras-mitogen-activated protein kinase signalling pathway. Both conditions hyper-activate signalling of the Ras-mitogen-activated protein kinase pathway and exhibit a high prevalence of neuropsychiatric disorders. Further, animal models of Noonan syndrome and neurofibromatosis type 1 and human imaging studies show white matter abnormalities in both conditions.
View Article and Find Full Text PDFCo-existing chronic hepatitis B virus (CHB) infection and metabolic dysfunction associated steatotic liver disease (MASLD) can exert complex effects on hepatic metabolism, requiring mechanistic study. CHB participants were assessed for MASLD and the impact of hepatic steatosis/metabolic syndrome (MetS) on novel viral and immunological markers. In this prospective, cohort study, untreated CHB subjects were assessed for liver disease by non-invasive tests (i.
View Article and Find Full Text PDFBackground: Intensive care unit (ICU) protein benchmarks are based on mortality and morbidity; whether these targets also support functional recovery is unknown. We assessed whether different protein doses influenced patients' functional capacity, measured by the Chelsea Physical Assessment score (CPAx).
Methods: Single-center retrospective cohort study on ICU survivors with length of stay ≥7 days admitted between October 2014 and September 2020.
Background: Colonoscopy is a key component of surveillance after colorectal cancer (CRC) resection. Surveillance intervals for colonoscopy vary across the world, with a limited evidence-base to support guidelines.
Objective: To evaluate the timing and outcome of colonoscopies after CRC resection.
The purpose of this narrative review was to comprehensively elaborate the various components of artificial intelligence (AI), their applications in spine surgery, practical concerns, and future directions. Over the years, spine surgery has been continuously transformed in various aspects, including diagnostic strategies, surgical approaches, procedures, and instrumentation, to provide better-quality patient care. Surgeons have also augmented their surgical expertise with rapidly growing technological advancements.
View Article and Find Full Text PDFBy deploying a multi-omics approach, we unraveled the mechanisms that might help rice to combat Yellow Stem Borer infestation, thus providing insights and scope for developing YSB resistant rice varieties. Yellow Stem Borer (YSB), Scirpophaga incertulas (Walker) (Lepidoptera: Crambidae), is a major pest of rice, that can lead to 20-60% loss in rice production. Effective management of YSB infestation is challenged by the non-availability of adequate sources of resistance and poor understanding of resistance mechanisms, thus necessitating studies for generating resources to breed YSB resistant rice and to understand rice-YSB interaction.
View Article and Find Full Text PDFBackground: Early identification of dysfunctional arteriovenous haemodialysis (HD) vascular access (VA) is important for timely referral and intervention.
Method: We retrospectively calculated VA risk score using Vasc-Alert surveillance software technology from HD treatment sessions in 2 satellite HD units over 18 months. We included in the analysis HD patients dialysing with arteriovenous fistula or graft (AVF/G) with available Vasc-Alert data for≥ 2 months.
Biol Psychiatry Cogn Neurosci Neuroimaging
September 2024
Background: RASopathies are a group of disorders characterized by pathogenic mutations in the Ras/mitogen-activated protein kinase (Ras/MAPK) signaling pathway. Distinct pathogenic variants in genes encoding proteins in the Ras/MAPK pathway cause Noonan syndrome (NS) and neurofibromatosis type 1 (NF1), which are associated with increased risk for autism spectrum disorder and attention-deficit/hyperactivity disorder.
Methods: This study examined the effect of RASopathies (NS and NF1) on human neuroanatomy, specifically on surface area (SA), cortical thickness (CT), and subcortical volumes.
Background: Fecal microbiota transplantation (FMT) is a promising treatment for active ulcerative colitis (UC). Understanding patient preferences can identify treatment features that may impact treatment decisions, improve shared decision-making, and contribute to patient-centered care, which is especially important in the context of novel treatments like FMT.
Objectives: We aimed to quantify preferences for active UC treatments, specifically FMT and biologics, and identify patient characteristics associated with different preference patterns.
Background: Nutrition and exercise are the mainstay of therapy for the prevention and treatment of frailty in cirrhosis. This pilot study assessed feasibility of the online delivery of an app-based semi-supervised nutrition and exercise intervention in this population.
Methods: The 11-week pilot recruited adults with cirrhosis who owned internet-connected devices.
A single Raman cell configuration useful for DIAL ozone lidar is designed and optimized. The conversion efficiency and flexibility of using a single Raman cell filled with a mixture of high pressure Raman active gases hydrogen ( ) and methane ( ) have been examined and reported. The stimulated Raman scattering (SRS) conversion efficiency of Raman active gases with different total cell pressures and the volume mixing ratio excited with a focused, frequency quadrupled Nd:YAG laser with a maximum pulse energy of 25 mJ and a pulse duration of 10 ns at 100 Hz repetition rate are examined in detail.
View Article and Find Full Text PDFMutations in the AAA+ ATPase p97 cause multisystem proteinopathy 1, which includes amyotrophic lateral sclerosis; however, the pathogenic mechanisms that contribute to motor neuron loss remain obscure. Here, we use two induced pluripotent stem cell models differentiated into spinal motor neurons to investigate how p97 mutations perturb the motor neuron proteome. Using quantitative proteomics, we find that motor neurons harboring the p97 R155H mutation have deficits in the selective autophagy of lysosomes (lysophagy).
View Article and Find Full Text PDFThe O-glycoprotein Mucin-2 (MUC2) forms the protective colon mucus layer. While animal models have demonstrated the importance of Muc2, few studies have explored human MUC2 in similar depth. Recent studies have revealed that secreted MUC2 is bound to human feces.
View Article and Find Full Text PDFER protein homeostasis (proteostasis) is essential for proper folding and maturation of proteins in the secretory pathway. Loss of ER proteostasis can lead to the accumulation of misfolded or aberrant proteins in the ER and triggers the unfolded protein response (UPR). In this study, we find that the p97 adaptor UBXN1 is an important negative regulator of the UPR.
View Article and Find Full Text PDFSARS-CoV-2 infections in children are generally asymptomatic or mild and rarely progress to severe disease and hospitalization. Why this is so remains unclear. Here we explore the potential for protection due to pre-existing cross-reactive seasonal coronavirus antibodies and compare the rate of antibody decline for nucleocapsid and spike protein in serum and oral fluid against SARS-CoV-2 within the pediatric population.
View Article and Find Full Text PDFBackground: Clostridioides difficile infection (CDI) is associated with considerable morbidity and mortality in hospitalized patients, especially among older adults. Probiotics have been evaluated to prevent hospital-acquired (HA) CDI in patients who are receiving systemic antibiotics, but the implementation of timely probiotic administration remains a challenge. We evaluated methods for effective probiotic implementation across a large health region as part of a study to assess the real-world effectiveness of a probiotic to prevent HA-CDI (Prevent CDI-55 +).
View Article and Find Full Text PDFInfect Control Hosp Epidemiol
April 2024
Objective: To evaluate the impact of administering probiotics to prevent infection (CDI) among patients receiving therapeutic antibiotics.
Design: Stepped-wedge cluster-randomized trial between September 1, 2016, and August 31, 2019.
Setting: This study was conducted in 4 acute-care hospitals across an integrated health region.