Metformin Is Associated With Improved Inflammatory Bowel Disease Outcomes in Patients With Type 2 Diabetes Mellitus: A Propensity-Matched Cohort Study.

BACKGROUND: Metformin exerts anti-inflammatory properties through a positive effect on oxidative stress, gut barrier integrity, and the gut microbiota. Our aim was to evaluate the influence of metformin on inflammatory bowel disease (IBD) outcomes in patients with type 2 diabetes mellitus (T2DM). METHODS: We conducted a retrospective cohort study using the TriNetX database in patients with IBD and T2DM who initiated metformin vs oral hypoglycemics or insulin (control cohort) between August 31, 2002, and August 31, 2022. One-to-one propensity score matching was performed. Primary outcomes were need for intravenous (IV) steroid use or IBD-related surgery within 1, 2, and 3 years after metformin initiation. RESULTS: Our cohorts included 1323 patients with ulcerative colitis (UC) (mean age 58.7 ±â€…12.2 years, 50.1% female, 77.3% White) and 1278 patients with Crohn's disease (CD) (mean age 56.3 ±â€…12.6 years, 58.2% female, 76.5% White). At 1 year, patients with UC and CD were less likely to require IV steroids (UC: adjusted odds ratio [aOR], 0.45; 95% confidence interval [CI], 0.34-0.59; P < .01; CD: aOR, 0.67; 95% CI, 0.53-0.85; P < .01). The decreased need for IV steroids persisted in all metformin groups at 2 and 3 years. Patients with CD were at a lower risk for IBD-related surgery at year 1 (aOR, 0.5; 95% CI, 0.31-0.81; P < .01), and this finding persisted at 3 years (aOR, 0.62; 95% CI, 0.43-0.89; P < .01). Metformin did not affect risk for surgery in patients with UC. CONCLUSIONS: Patients with IBD and T2DM on metformin had a decreased likelihood of worse IBD outcomes.

Our study shows that metformin is associated with decreased risk of corticosteroids in patients with ulcerative colitis and Crohn's disease and decreased risk of surgery in patients with Crohn's disease.

A review on vulnerable atmospheric aerosol nanoparticles: Sources, impact on the health, ecosystem and management strategies.

The Earth's atmosphere contains ultrafine particles known as aerosols, which can be either liquid or solid particles suspended in gas. These aerosols originate from both natural sources and human activities, termed primary and secondary sources respectively. They have significant impacts on the environment, particularly when they transform into ultrafine particles or aerosol nanoparticles, due to their extremely fine atomic structure. With this context in mind, this review aims to elucidate the fundamentals of atmospheric-derived aerosol nanoparticles, covering their various sources, impacts, and methods for control and management. Natural sources such as marine, volcanic, dust, and bioaerosols are discussed, along with anthropogenic sources like the combustion of fossil fuels, biomass, and industrial waste. Aerosol nanoparticles can have several detrimental effects on ecosystems, prompting the exploration and analysis of eco-friendly, sustainable technologies for their removal or mitigation.Despite the adverse effects highlighted in the review, attention is also given to the generation of aerosol-derived atmospheric nanoparticles from biomass sources. This finding provides valuable scientific evidence and background for researchers in fields such as epidemiology, aerobiology, and toxicology, particularly concerning atmospheric nanoparticles.

Risk of Small Intestine Cancer in Inflammatory Bowel Disease: A Propensity-Matched Study from a Large Multi-Center Database in the United States.

INTRODUCTION: The risk of small bowel cancer (SBC) in inflammatory bowel disease (IBD) is unclear. We compared the recent trends of SBC in patients with IBD and stratified them based on disease type. METHODS: We used TriNetX database to access the electronic health records for patients with IBD, ulcerative colitis (UC) and Crohn's disease (CD) from 2005-2024. We used propensity score matching to compare the rate of SBC in patients with IBD, UC, and CD compared to the general population. We adjusted for all known confounders. RESULTS: From 2010-2024, there was an increasing trend of diagnosed SBC in patients with IBD, with an Average Annual Percentage Change (AAPC) of 3.2% (P<0.001). Patients with CD (aHR = 4.83; 95% CI: 3.58 - 6.53; P < .0001) had an increased risk of SBC compared to the general population without IBD, as well as patients with UC (aHR = 2.28; 95% CI: 1.65 - 3.14; P < .0001). The ileum was the most common location across all subgroups. CONCLUSION: Both patients with CD and, interestingly, UC had an elevated risk for developing SBC compared to the general population.

Comparative Effectiveness of Upadacitinib and Tofacitinib in Ulcerative Colitis: A US Propensity-Matched Cohort Study.

INTRODUCTION: There are limited real-world data comparing the effectiveness of upadacitinib and tofacitinib in patients with ulcerative colitis (UC). METHODS: We conducted a retrospective cohort study using TriNetX, a multi-institutional database, to compare the effectiveness of upadacitinib and tofacitinib in patients with UC. The primary aim was to assess the risk of a composite outcome of hospitalization requiring intravenous steroids and/or colectomy within 6 and 12 months. One-to-one propensity score matching was performed for demographics, comorbid conditions, mean hemoglobin, C-reactive protein, albumin, and calprotectin, and prior UC medications including recent oral or intravenous steroid use between the cohorts. Risk was expressed as adjusted odds ratio (aOR) with 95% confidence intervals (CI). RESULTS: There were 526 patients in the upadacitinib cohort (mean age 40.4 ± 16.3, 44.8% female sex, 76.6% White race) and 1,149 patients in the tofacitinib cohort (mean age 42 ± 17.1, 41.9% female sex, 76% White race). After propensity score matching, there was no significant difference in the risk of the composite outcome of need for intravenous steroids and/or colectomy within 6 months (aOR 0.75, 95% CI 0.49-1.09). However, there was a lower risk of the composite outcome (aOR 0.63, 95% CI 0.44-0.89) in the upadacitinib cohort compared with the tofacitinib cohort within 12 months. There was no difference in the risk of intravenous steroid use (aOR 0.70, 95% CI 0.48-1.02) but lower risk of colectomy (aOR 0.46, 95% CI 0.27-0.79). In sensitivity analysis, there was also a lower risk of the composite outcome (aOR 0.64, 95% CI 0.44-0.94), including lower risk of intravenous steroid use (aOR 0.67, 95% CI 0.45-0.99) and colectomy (aOR 0.49, 95% CI 0.26-0.92) in the upadacitinib cohort compared with the tofacitinib cohort within 12 months. DISCUSSION: This study utilizing real-world data showed that upadacitinib was associated with improved disease-specific outcomes at 12 months compared with tofacitinib in patients with UC.

Pesticide Contamination in Native North American Crops, Part I-Development of a Baseline and Comparison of Honey Bee Exposure to Residues in Lowbush Blueberry and Cranberry.

A pesticide exposure baseline for honey bees was compiled for two New England cropping systems, the native North American plant species consisting of lowbush blueberry (Vaccinium angustifolium Aiton) and cranberry (Vaccinium macrocarpon Aiton). More unique pesticide compounds were applied in blueberry than cranberry, but the numbers of pesticides discovered in trapped honey bee pollen were similar between the two crop systems. Not all pesticides found in pollen were the result of the applications reported by growers of either crop. When comparing residues, number of pesticides detected, total concentration, and risk quotient varied between the two crops. Also, blueberry was dominated by fungicides and miticides (varroacides) and cranberry was dominated by insecticides and herbicides. When comparing reported grower applications that were matched with detection in residues, the proportion of pesticide numbers, concentrations, and risk quotients varied by crop system and pesticide class. In most cases, pesticide residue concentrations were of low risk (low risk quotient) to honey bees in these crops. Estimation of decay rates of some of the most common pesticide residues under field conditions could aid growers in selection of less persistent compounds, together with safe application dates, prior to bringing in honey bees for pollination.

Successful Preoperative Transjugular Intrahepatic Portosystemic Shunt for Portal Decompression in Patients With Inflammatory Bowel Disease and Cirrhosis Requiring Surgical Intervention.

Background: Colorectal surgery in patients with inflammatory bowel disease (IBD) and cirrhosis has increased morbidity, which may preclude surgery. Preoperative transjugular intrahepatic portosystemic shunt (TIPS) is postulated to reduce surgical risk. In this retrospective single-center study, we characterized perioperative outcomes in patients with IBD and cirrhosis who underwent preoperative TIPS. Methods: We identified patients with IBD and cirrhosis who had undergone preoperative TIPS for portal decompression between 2010 and 2023. All other indications for TIPS led to patient exclusion. Demographic and medical data were collected, including portal pressure measurements. Primary outcome of interest was perioperative outcomes. Results: Ten patients met the inclusion criteria. The most common surgical indications were dysplasia (50%) and refractory IBD (50%). TIPS was performed at a median of 47 days (IQR 34-80) before surgery, with reduction in portal pressures (22.5 vs. 18.5 mmHg, P < .01) and portosystemic gradient (12.5 vs. 5.5 mmHg, P < .01). Perioperative complications occurred in 80% of patients, including surgical site bleeding (30%), wound dehiscence (10%), systemic infection (30%), liver function elevation (50%), and coagulopathy (50%). No patients required re-operation, with median length of stay being 7 days (IQR 5.5-9.3). The 30-day readmission rate was 40%, most commonly for infection (75%), with 2 patients having intra-abdominal abscesses and 1 patient with concern for bowel ischemia. Ninety-day and one-year survival was 100% and 90%, respectively. Patients with primary sclerosing cholangitis (PSC)-cirrhosis were noted to have higher perioperative morbidity and a 30-day readmission rate. Conclusions: In patients with IBD and cirrhosis, preoperative TIPS facilitated successful surgical intervention despite heightened risk. Nevertheless, significant complications were noted, in particular for patients with PSC-cirrhosis.

The national burden of inflammatory bowel disease in the United States from 1990-2019: results from the Global Burden of Disease study database.

Background: Inflammatory bowel disease (IBD) epidemiology has changed rapidly in recent years. We aimed to provide a systematic report of the burden of IBD at a state level in the United States (US), and to study the age- and sex-specific trends of incidence, prevalence and mortality rates for the past 3 decades. Methods: Using the Global Burden of Disease (GBD) 2019 Study Database, we examined the incidence, prevalence and mortality rate, and the disability-adjusted life-years from GBD 2019 at national and state level from 1990-2019. Results: There was an overall decrease in incidence and prevalence rates of IBD in the US from 1990-2019, while a simultaneous increase in the overall mortality rates was identified. However, a distinct trend of increasing incidence and prevalence rates emerged starting in 2000, with incidence rates rising from 21 cases per 100,000 persons in 2000 to 23 cases per 100,000 persons in 2019. From 1990-2019, incidence and prevalence decreased in males at a higher rate than in females. However, mortality rates increased more in females than males. Incidence rates were highest in Midwestern and Eastern states, and were lowest across the northern Great Plains and Western states, with the highest incidence noted in Michigan (31 cases per 100,000 persons). California had the greatest decrease in incidence rates from 1990-2019 (-63.3%). Conclusion: Our results concerning recent trends and geographic variations in IBD offer policymakers crucial insights for informed decision-making in policy, research, and investment, facilitating more effective strategies and allocation of resources.

Does Timing of Ileal Pouch-Anal Anastomosis Matter in Patients With Primary Sclerosing Cholangitis and Orthotopic Liver Transplantation? A Systematic Review and Meta-analysis.

Introduction: Pouchitis is the most common complication in patients with ileal pouch-anal anastomosis (IPAA), which can develop in up to 66% of patients. There is limited data on the effect of orthoptic liver transplantation (OLT) on the risk of developing pouchitis. We aimed to objectively assess whether OLT itself significantly modifies the risk of developing pouchitis in patients with overlap PSC and inflammatory bowel disease (IBD). Method: We searched Medline, Scopus, and Embase databases from inception through September 2023 for studies that describe the outcomes of IPAA in patients with PSC and IBD who also have a history of OLT. Pooled proportions, Odds Ratio (OR), and 95% confidence intervals (CI) for data were calculated utilizing a random effects model. Using the Freeman-Turkey double arcsine transformation (FTT) method, the pooled weight-adjusted estimate of event rates for clinical outcomes in each group was also calculated. Heterogeneity between studies was assessed using the Cochrane Q statistic (I2). Results: Seven studies with a total of 291 patients with a history of PSC, IBD, and OLT were identified. The pooled overall risk of pouchitis in PSC/IBD patients with a history of OLT was 65% (95% CI: 0.57-0.72), with no heterogeneity observed in the analysis (I2 = 0%). In a subgroup analysis of patients who had IPAA followed by OLT, 3 studies with 28 patients were included; the pooled risk of pouchitis after IPAA and OLT was 83% (95% CI: 0.71-0.94; I2 = 0%), which was significantly higher (P < .001) than the OLT followed by IPAA group (59%; 95 CI: 0.48-0.71; I2 = 0%). There was no difference in the risk of pouchitis between OLT and non-OLT groups (OR = 1.36; 95% CI: 0.37-5.0). Conclusions: Our meta-analysis revelaed that pouchitis is common in patients who underwent OLT for PSC, especially in those who had IPAA before the OLT. OLT before IPAA may reduce the risk of pouchitis. Further larger studies are warranted to reproduce this and investigate the reason behind this difference.

Robotic Excision of Intravesical Mesh Following Transvaginal Mesh-Based Prolapse Repair.

INTRODUCTION AND HYPOTHESIS: We describe the surgical management of intravesical mesh perforation following transvaginal mesh surgery for pelvic organ prolapse. METHODS: A 73-year-old woman presented with intravesical mesh perforation 17 years following transvaginal mesh-based prolapse repair at an outside hospital. The patient presented with intermittent hematuria and recurrent urinary tract infections. Cystoscopy demonstrated an approximately 3-cm area of intravesical mesh with associated stone spanning from the bladder neck through the left trigone and ureteral orifice. A robotic-assisted transvesical mesh excision and left ureteroneocystostomy was carried out. Robotic-assisted repair was performed transvesically via transverse bladder dome cystotomy. Dissection was carried out circumferentially around the mesh in the vesicovaginal plane, including a 1-cm margin of healthy tissue. The eroded mesh was excised, and the vaginal wall and bladder were closed with running absorbable sutures. Given the location of the mesh excision and repair, a left ureteral reimplantation was performed. The transverse cystotomy was closed and retrograde bladder filling with methylene blue-stained saline confirmed watertight repairs, with no vaginal extravasation. RESULTS: The patient was discharged the following morning and had an uneventful recovery, including transurethral indwelling catheter removal at 2 weeks after CT cystogram and subsequent ureteral stent removal at 6 weeks postoperatively. At 2-month follow-up she had no new urinary symptoms or obstruction of the ureteral reimplantation on renal ultrasound. CONCLUSIONS: A robotic-assisted approach is a feasible option for managing transvaginal prolapse mesh perforation into the bladder. Pelvic surgeons must be well equipped to handle transvaginal mesh complications in a patient-specific manner.

Treatment of Chronic Pouchitis With JAK Inhibitors: Results from A Large Multicenter Database.

This retrospective study assessed the use of Janus kinase inhibitors in treating chronic pouchitis. While showing relative safety, Janus kinase inhibitors demonstrated effectiveness in <50% of cases, cautioning against their use as first-line agents. Larger randomized trials are recommended for further investigation.

Why does circadian timing of administration matter for immune checkpoint inhibitors' efficacy?

BACKGROUND: Tolerability and antitumour efficacy of chemotherapy and radiation therapy can vary largely according to their time of administration along the 24-h time scale, due to the moderation of their molecular and cellular mechanisms by circadian rhythms. Recent clinical data have highlighted a striking role of dosing time for cancer immunotherapy, thus calling for a critical evaluation. METHODS: Here, we review the clinical data and we analyse the mechanisms through which circadian rhythms can influence outcomes on ICI therapies. We examine how circadian rhythm disorders can affect tumour immune microenvironment, as a main mechanism linking the circadian clock to the 24-h cycles in ICIs antitumour efficacy. RESULTS: Real-life data from 18 retrospective studies have revealed that early time-of-day (ToD) infusion of immune checkpoint inhibitors (ICIs) could enhance progression-free and/or overall survival up to fourfold compared to late ToD dosing. The studies involved a total of 3250 patients with metastatic melanoma, lung, kidney, bladder, oesophageal, stomach or liver cancer from 9 countries. Such large and consistent differences in ToD effects on outcomes could only result from a previously ignored robust chronobiological mechanism. The circadian timing system coordinates cellular, tissue and whole-body physiology along the 24-h timescale. Circadian rhythms are generated at the cellular level by a molecular clock system that involves 15 specific clock genes. The disruption of circadian rhythms can trigger or accelerate carcinogenesis, and contribute to cancer treatment failure, possibly through tumour immune evasion resulting from immunosuppressive tumour microenvironment. CONCLUSIONS AND PERSPECTIVE: Such emerging understanding of circadian rhythms regulation of antitumour immunity now calls for randomised clinical trials of ICIs timing to establish recommendations for personalised chrono-immunotherapies with current and forthcoming drugs.

High Rates of Seroprotection to Hepatitis B After a Hepatitis B Challenge Dose in Previously Vaccinated Patients with Inflammatory Bowel Disease on Immunosuppressive Therapy.

BACKGROUND: Healthy populations have high rates of sustained vaccine-induced seroprotection to hepatitis B virus, but previous studies in immunosuppressed patients with inflammatory bowel disease (IBD) have shown suboptimal seroprotection rates. A challenge dose of hepatitis B vaccine (HepB) is recommended in previously vaccinated individuals who are seronegative to elicit an anamnestic response and determine if they are seroprotected. The aim of our study was to determine sustained seroprotection rates to hepatitis B vaccine (HepB) in patients with IBD. METHODS: This was a single-center prospective study of patients with IBD previously vaccinated with a three dose HepB series. Patients had a hepatitis B surface antibody (anti-HBs) drawn; if it was below 10 mIU/mL, they received a challenge dose of the HepB vaccine to assess for anamnestic response and sustained seroprotection. The primary outcome was to determine the rate of sustained seroprotection (anti-HBs ≥ 10). RESULTS: A total of 168 patients met inclusion criteria, mean age 35.7 years ± 13.6 standard deviation (SD). Initially 120 (71.4%) had anti-HBs ≥ 10 mIU/mL, with median anti-HBs of 37 mIU/mL (interquartile range 0-234); 48 (28.6%) needed a challenge dose, of which 34 responded with anti-HBs ≥ 10 mIU/mL. In total, 154 (91.7%) demonstrated sustained seroprotection to HepB. Those not seroprotected were more likely to have been vaccinated on immunosuppressive therapy or after their diagnosis of IBD. CONCLUSIONS: Most vaccinated patients with IBD maintain sustained seroprotection to HepB despite prolonged exposure to immunosuppression. This contradicts prior studies and shows that immunosuppression does not lead to loss of seroprotection.

Use of glucagon-like peptide-1 receptor agonists for type 2 diabetes mellitus and outcomes of inflammatory bowel disease.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RA) show anti-inflammatory properties. AIM: To evaluate their clinical impact on inflammatory bowel disease (IBD) outcomes. METHODS: Retrospective cohort study utilising the TriNetX database comparing IBD-specific outcomes in patients with ulcerative colitis (UC) or Crohn's disease (CD) and type 2 diabetes mellitus (T2DM) on GLP-1RA compared to oral hypoglycaemic agents. The primary outcome was hospitalisation requiring intravenous steroids and IBD-related surgery within 3 years. We performed 1:1 propensity score matching (PSM) for demographics, co-morbid conditions, BMI, laboratory values, HbA1c, and IBD medications including steroids. RESULTS: We identified 1130 patients in the UC GLP-1RA cohort (mean age: 58.9 ± 11.6 years, 56.3% female, 70.2% White, 57.2% with obesity) and 1140 patients in the CD GLP-1RA cohort (mean age: 56.7 ± 11.5, 61.9% female, 73.6% White, 56.2% with obesity). After PSM, there was no difference in the risk of intravenous steroid use (aHR: 1.21, 95% CI: 0.92-1.59) but a lower risk of colectomy (aHR: 0.37, 95% CI: 0.14-0.97) between the UC GLP-1RA and control cohort. There was no difference in the risk of intravenous steroid use (aHR: 1.04, 95% CI: 0.80-1.34) but a lower risk of surgery (aHR: 0.55, 95% CI: 0.36-0.84) between the CD GLP-1RA and CD control cohort. There was no difference in the risk of oral steroid use or advanced therapy initiation in the UC and CD GLP-1RA than control cohorts. CONCLUSIONS: We found an association between lower risk of IBD-related surgery and GLP-1RA use for T2DM in patients with UC or CD.

The Natural History After Ileal Pouch-Anal Anastomosis for Ulcerative Colitis: A Population-Based Cohort Study From the United States.

INTRODUCTION: There are limited data regarding the natural history after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC). The principal objectives of this study were to identify 4 key outcomes in the natural history after IPAA within 1, 3, 5, and 10 years: the incidence of pouchitis, Crohn's-like disease of the pouch, use of advanced therapies after IPAA, and pouch failure requiring excision in a network of electronic health records. METHODS: We performed a retrospective cohort study in TriNetX, a research network of electronic health records. In addition to evaluating incidence rates, we also sought to identify factors associated with pouchitis and advanced therapy use within 5 years of IPAA after 1:1 propensity score matching, expressed as adjusted hazard ratios (aHRs). RESULTS: Among 1,331 patients who underwent colectomy with IPAA for UC, the incidence of pouchitis increased from 58% in the first year after IPAA to 72% at 10 years after IPAA. After propensity score matching, nicotine dependence (aHR 1.61, 95% confidence interval [CI] 1.19-2.18), antitumor necrosis factor therapy (aHR 1.33, 95% CI 1.13-1.56), and vedolizumab prior to colectomy (aHR 1.44, 95% CI 1.06-1.96) were associated with an increased risk of pouchitis in the first 5 years after IPAA. The incidence of Crohn's-like disease of the pouch increased to 10.3% within 10 years of IPAA while pouch failure increased to 4.1%. The incidence of advanced therapy use peaked at 14.4% at 10 years after IPAA. DISCUSSION: The incidence of inflammatory conditions of the pouch remains high in the current era, with 14% of patients requiring advanced therapies after IPAA.

Sirolimus Use in Refractory Crohn's Disease.

Treatment options for patients with inflammatory bowel disease are constantly evolving; however, medication-refractory disease remains an issue. Pediatric case series show the potential benefit of sirolimus therapy in refractory Crohn's disease (CD); however, limited data exist in adult patients. As such, we retrospectively identified and report clinical outcomes for 4 patients prescribed sirolimus for treatment of refractory CD. Despite a median sirolimus therapy duration of 524 days and some therapeutic benefits, all patients discontinued therapy due to adverse effects. Our findings suggest that while sirolimus may have clinical utility, its role may be limited by treatment-derived adverse effects.

Utility of a Third Heplisav-B Dose in Patients With Inflammatory Bowel Disease Without Immunity After 2-Dose Heplisav-B Vaccination.

INTRODUCTION: Hepatitis B virus (HBV) vaccination is recommended in patients with inflammatory bowel disease (IBD). Although the 2-dose Heplisav-B vaccine has proven effective, more than 20% of patients with IBD do not seroconvert. We prospectively evaluated the effectiveness of a third Heplisav-B dose in patients with IBD lacking HBV immunity despite 2-dose vaccination. METHODS: Adults with IBD who had received 2-dose Heplisav-B vaccination between 2018 and 2023 were identified. Seroconversion was defined as hepatitis B surface antibody (HBsAb) ≥ 10 IU/L measured at ≥4 weeks after vaccination. Patients who did not seroconvert were prospectively offered a third Heplisav-B dose, followed by repeat HBsAb measurement. Demographic, clinical, medication, and vaccination data were compared between those who did and did not seroconvert. RESULTS: Of 192 patients identified, 71.9% (138/192) seroconverted after 2-dose Heplisav-B vaccination. The 54 patients (28.1%) who did not seroconvert were more likely to be male, have diabetes, chronic kidney disease, or elevated Charlson Comorbidity Index. Of the 54 patients, 30 (55.6%) elected to receive a third Heplisav-B dose, with 56.7% (17/30) achieving seroconversion (median HBsAb titer 376 IU/L, IQR 47-1,000 IU/L) despite a median intervaccination time of 416 days (IQR 90.8-667.8). No differences were noted between patients who did vs did not seroconvert after third-dose vaccination. DISCUSSION: In patients with IBD lacking HBV immunity despite 2-dose Heplisav-B vaccination, administration of a third dose resulted in a 56.7% seroconversion rate. Our results suggest that administration of an additional Heplisav-B dose may be an effective strategy in patients lacking immunity despite primary 2-dose vaccination.

Health promotion as the nexus of public health and clinical care: the case of a district hospital in southern Ghana.

This study explored the extent to which health promotion techniques and activities are incorporated into public health and clinical care at a District Hospital in the Greater Accra Region of Ghana, as well as the challenges that this process faces. Information was obtained at the hospital facility through direct observation, interviews and open-ended questionnaires. Findings showed that the process of incorporating health promotion activities into public health and clinical care at the hospital was underdeveloped. The challenges this process faces based on the research findings include structural challenges, inadequate logistics, increased workload, insufficient human resource capacity, lack of motivation for staff, lack of cooperation, teamwork and consultation, inadequate management and enforcement support, prolonged hospital hours for healthcare workers and patients, and inadequate knowledge of health promotion and training. To address these challenges, suggested measures include promoting teamwork and collaboration among healthcare professionals, training and continuous education, government involvement and enforcement of health promotion integration at the hospital, hospital management involvement, media sensitization and advocacy, provision of financial, material and human resources, motivation and encouragement of the process of health promotion integration, and patient involvement. Further research is also recommended to broaden the scope of this study by involving other health practitioner categories and health promotion stakeholders.

Clinical Decision Making in Inflammatory Bowel Disease Mimics: Practice Management from Inflammatory Bowel Disease LIVE.

Background: Since 2009, inflammatory bowel disease (IBD) specialists have utilized "IBD LIVE," a weekly live video conference with a global audience, to discuss the multidisciplinary management of their most challenging cases. While most cases presented were confirmed IBD, a substantial number were diseases that mimic IBD. We have categorized all IBD LIVE cases and identified "IBD-mimics" with consequent clinical management implications. Methods: Cases have been recorded/archived since May 2018; we reviewed all 371 cases from May 2018-February 2023. IBD-mimics were analyzed/categorized according to their diagnostic and therapeutic workup. Results: Confirmed IBD cases made up 82.5% (306/371; 193 Crohn's disease, 107 ulcerative colitis, and 6 IBD-unclassified). Sixty-five (17.5%) cases were found to be mimics, most commonly medication-induced (n = 8) or vasculitis (n = 7). The evaluations that ultimately resulted in correct diagnosis included additional endoscopic biopsies (n = 13, 21%), surgical exploration/pathology (n = 10, 16.5%), biopsies from outside the GI tract (n = 10, 16.5%), genetic/laboratory testing (n = 8, 13%), extensive review of patient history (n = 8, 13%), imaging (n = 5, 8%), balloon enteroscopy (n = 5, 8%), and capsule endoscopy (n = 2, 3%). Twenty-five patients (25/65, 38%) were treated with biologics for presumed IBD, 5 of whom subsequently experienced adverse events requiring discontinuation of the biologic. Many patients were prescribed steroids, azathioprine, mercaptopurine, or methotrexate, and 3 were trialed on tofacitinib. Conclusions: The diverse presentation of IBD and IBD-mimics necessitates periodic consideration of the differential diagnosis, and reassessment of treatment in presumed IBD patients without appropriate clinical response. The substantial differences and often conflicting treatment approaches to IBD versus IBD-mimics directly impact the quality and cost of patient care.

Molecular basis for pH sensing in the KDEL trafficking receptor.

Trafficking receptors control protein localization through the recognition of specific signal sequences that specify unique cellular locations. Differences in luminal pH are important for the vectorial trafficking of cargo receptors. The KDEL receptor is responsible for maintaining the integrity of the ER by retrieving luminally localized folding chaperones in a pH-dependent mechanism. Structural studies have revealed the end states of KDEL receptor activation and the mechanism of selective cargo binding. However, precisely how the KDEL receptor responds to changes in luminal pH remains unclear. To explain the mechanism of pH sensing, we combine analysis of X-ray crystal structures of the KDEL receptor at neutral and acidic pH with advanced computational methods and cell-based assays. We show a critical role for ordered water molecules that allows us to infer a direct connection between protonation in different cellular compartments and the consequent changes in the affinity of the receptor for cargo.

Effects of Partial-Body, Continuous/Pulse Irradiation at Dose Rates from FLASH to Conventional Rates on the Level of Surviving Blood Lymphocytes: Modeling Approach. I. Continuous Irradiation.

A mathematical model developed by Cucinotta and Smirnova is extended to describe effects of continuous, partial-body irradiation at high doses D and at dose rates N from FLASH to conventional rates on the level of surviving blood lymphocytes in humans and small laboratory animals (mice). Specifically, whereas the applicability of the model is limited to the exposure times shorter than a single cardiac cycle T0, the extended model is capable of describing such effects for the aforementioned and longer exposure times. The extended model is implemented as the algebraic equations. It predicts that the level of surviving blood lymphocytes in humans and mice increases with increasing the dose rate from N= D/T0 to FLASH rates and approaches the upper limiting level of 1-vR, where vR is the fraction of blood volume in the irradiated part of the blood circulatory system. Levels of surviving blood lymphocytes computed at doses from 10 Gy to 40 Gy and at dose rates N, which equal or exceed 40 Gy/s for humans and 400 Gy/s for mice, are nearly indistinguishable from the upper limiting level. In turn, the level of surviving blood lymphocytes in humans and mice decreases with decreasing the dose rate from N= D/T0 to conventional rates and approaches a lower limiting level. This level strongly depends on the dose D (it is smaller at larger values of D) with a slight dependence on the dose rate N. The model with the parameters specified for mice (together with the model of the dynamics of lymphopoietic system in mice after partial-body irradiation) reproduce, on a quantitative level, the experimental data, according to which the concentration of blood lymphocytes measured in mice in one day after continuous, partial-body irradiation at a high dose and conventional dose rate is smaller at the larger value of vR. Additionally, the model predicts at the same high dose (>10 Gy) a faster restoration of the blood lymphocyte population in humans exposed to continuous, partial-body irradiation at a FLASH dose rate compared to a conventional dose rate.