A novel mRNA multi-epitope vaccine of Acinetobacter baumannii based on multi-target protein design in immunoinformatic approach.

Acinetobacter baumannii is a gram-negative bacillus prevalent in nature, capable of thriving under various environmental conditions. As an opportunistic pathogen, it frequently causes nosocomial infections such as urinary tract infections, bacteremia, and pneumonia, contributing to increased morbidity and mortality in clinical settings. Consequently, developing novel vaccines against Acinetobacter baumannii is of utmost importance. In our study, we identified 10 highly conserved antigenic proteins from the NCBI and UniProt databases for epitope mapping. We subsequently screened and selected 8 CTL, HTL, and LBL epitopes, integrating them into three distinct vaccines constructed with adjuvants. Following comprehensive evaluations of immunological and physicochemical parameters, we conducted molecular docking and molecular dynamics simulations to assess the efficacy and stability of these vaccines. Our findings indicate that all three multi-epitope mRNA vaccines designed against Acinetobacter baumannii are promising; however, further animal studies are required to confirm their reliability and effectiveness.

Air pollution and risk of 32 health conditions: outcome-wide analyses in a population-based prospective cohort in Southwest China.

BACKGROUND: Uncertainty remains about the long-term effects of air pollutants (AP) on multiple diseases, especially subtypes of cardiovascular disease (CVD). We aimed to assess the individual and joint associations of fine particulate matter (PM2.5), along with its chemical components, nitrogen dioxide (NO2) and ozone (O3), with risks of 32 health conditions. METHODS: A total of 17,566 participants in Sichuan Province, China, were included in 2018 and followed until 2022, with an average follow-up period of 4.2 years. The concentrations of AP were measured using a machine-learning approach. The Cox proportional hazards model and quantile g-computation were applied to assess the associations between AP and CVD. RESULTS: Per interquartile range (IQR) increase in PM2.5 mass, NO2, O3, nitrate, ammonium, organic matter (OM), black carbon (BC), chloride, and sulfate were significantly associated with increased risks of various conditions, with hazard ratios (HRs) ranging from 1.06 to 2.48. Exposure to multiple air pollutants was associated with total cardiovascular disease (HR 1.75, 95% confidence intervals (CIs) 1.62-1.89), hypertensive diseases (1.49, 1.38-1.62), cardiac arrests (1.52, 1.30-1.77), arrhythmia (1.76, 1.44-2.15), cerebrovascular diseases (1.86, 1.65-2.10), stroke (1.77, 1.54-2.03), ischemic stroke (1.85, 1.61-2.12), atherosclerosis (1.77, 1.57-1.99), diseases of veins, lymphatic vessels, and lymph nodes (1.32, 1.15-1.51), pneumonia (1.37, 1.16-1.61), inflammatory bowel diseases (1.34, 1.16-1.55), liver diseases (1.59, 1.43-1.77), type 2 diabetes (1.48, 1.26-1.73), lipoprotein metabolism disorders (2.20, 1.96-2.47), purine metabolism disorders (1.61, 1.38-1.88), anemia (1.29, 1.15-1.45), sleep disorders (1.54, 1.33-1.78), renal failure (1.44, 1.21-1.72), kidney stone (1.27, 1.13-1.43), osteoarthritis (2.18, 2.00-2.39), osteoporosis (1.36, 1.14-1.61). OM had max weights for joint effects of AP on many conditions. CONCLUSIONS: Long-term exposure to increased levels of multiple air pollutants was associated with risks of multiple health conditions. OM accounted for substantial weight for these increased risks, suggesting it may play an important role in these associations.

Sex differences impact ergonomic endoscopic training for gastroenterology fellows.

BACKGROUND AND AIMS: Endoscopic-related injuries (ERIs) for gastroenterologists are common and can impact longevity of an endoscopic career. This study examines sex differences in the prevalence of ERIs and ergonomic training during gastroenterology fellowship. METHODS: A 56-item anonymous survey was sent to 709 general and advanced endoscopy gastroenterology fellows at 73 U.S. training programs between May and June 2022. Demographic information was collected along with questions related to endoscopic environment, ergonomic instruction, technique, equipment availability, and ergonomic knowledge. Responses of female and male gastroenterology fellows were compared using χ2 and Fisher exact tests. RESULTS: Of the 236 respondents (response rate, 33.9%), 113 (44.5%) were women and 123 (52.1%) were men. Female fellows reported on average smaller hand sizes and shorter heights. More female fellows reported endoscopic equipment was not ergonomically optimized for their use. Additionally, more female fellows voiced preference for same-gender teachers and access to dial extenders and well-fitting lead aprons. High rates of postendoscopy pain were reported by both sexes, with significantly more women experiencing neck and shoulder pain. Trainees of both sexes demonstrated poor ergonomic awareness with an average score of 68% on a 5-point knowledge-based assessment. CONCLUSIONS: Physical differences exist between male and female trainees, and current endoscopic equipment may not be optimized for smaller hand sizes. This study highlights the urgent need for formal ergonomic training for trainees and trainers with consideration of stature and hand size to enhance safety, comfort, and equity in the training and practice of endoscopy.

Design of Cryptococcus neoformans multi-epitope vaccine based on immunoinformatics method.

Cryptococcus neoformans is a widely distributed opportunistic pathogenic fungus. While C. neoformans commonly infects immunocompromised individuals, it can also affect those who are immunocompetent. Transmission of C. neoformans primarily occurs through the respiratory tract, leading to the development of meningitis. The mortality rate of Cryptococcal meningitis is high, and treatment options are limited. Cryptococcus neoformans infections pose a significant public health threat and currently lack targeted and effective response strategies. This study aimed to screen T lymphocyte (cytotoxic T lymphocyte and helper T lymphocyte) and B lymphocyte epitopes derived from four C. neoformans antigens and develop two multi-epitope vaccines by combining them with various adjuvants. Molecular docking results demonstrated that the vaccines bind stably to Toll-like receptor 4 ( and induce innate immunity. The credibility of the molecular docking results was validated through subsequent molecular dynamics simulations. Furthermore, the results of immune simulation analyses underscored the multi-epitope vaccine's capability to effectively induce robust humoral and cellular immune responses within the host organism. These two vaccines have demonstrated theoretical efficacy against C. neoformans infection as indicated by computer analysis. Nevertheless, additional experimental validation is essential to substantiate the protective efficacy of the vaccines.

A multi-epitope Cryptococcus neoformans vaccine covering the most common A and D phenotypes was designed using bioinformatics methods.

Digital Rectal Exams Are Infrequently Performed Prior to Anorectal Manometry.

BACKGROUND: Digital rectal examination should be performed prior to anorectal manometry; however, real-world data is lacking. AIMS: Characterize real world rates of digital rectal and their sensitivity for detecting dyssynergia compared to anorectal manometry and balloon expulsion test. METHODS: A retrospective single-center study was conducted to examine all patients who underwent anorectal manometry for chronic constipation between 2021 and 2022 at one tertiary center with motility expertise. Primary outcomes consisted of the rate of digital rectal exam prior to anorectal manometry; and secondary outcomes included the sensitivity of digital rectal exam for dyssynergic defecation. RESULTS: Only 42.3% of 142 patients had digital rectal examinations prior to anorectal manometry. Overall sensitivity for detecting dyssynergic defecation was 46.4%, but significantly higher for gastroenterology providers (p = .004), and highest for gastroenterology attendings (82.6%). CONCLUSIONS: Digital rectal examination is infrequently performed when indicated for chronic constipation. Sensitivity for detecting dyssynergic defecation may be impacted by discipline and level of training.

Distal esophageal spasm and gastroesophageal reflux disease: re-examining the association.

Distal esophageal spasm (DES) is a rare motility disorder presenting with dysphagia or chest pain. Although studies suggest a link between DES and gastroesophageal reflux disease (GERD), data supporting a distinct GERD-related phenotype are limited. This study aims to investigate demographic, symptomatic, and physiologic differences between DES subjects with and without GERD. A retrospective cohort analysis of DES patients determined by high resolution manometry (HRM) was conducted between February 2020 and January 2023. Demographics, medications, symptoms, and quantitative reflux testing data were collected. DES subjects with reflux (R-DES) were defined by presence of Los Angeles Grade B/C/D esophagitis, Barrett's metaplasia, or abnormal pH testing. DES subjects without reflux (NR-DES) had normal parameters. Statistical analysis employed two-sided or Wilcoxon Rank-Sum, Chi-squared, or Fisher's exact tests, and multivariate logistic regression. Of 69 DES subjects, 32 (46.3%) had GERD. R-DES and NR-DES patients had similar demographic variables except for higher BMI in R-DES (30.41 vs. 26.88, P = 0.01). R-DES and NR-DES shared similar symptom profiles (heartburn P = 0.67, dysphagia P = 0.448, chest pain P = 0.32). Proton pump inhibitor use was similar between groups (78.1% vs. 91.9%, P = 0.202). HRM metrics were comparable except for basal LES tone (20.7 mmHg vs. 32.99 mmHg, P = 0.03) and median IRP 11.82 mmHg versus 17.20 mmHg, P = 0.017). This study found no distinguishing clinical or physiologic differences between DES patients with and without GERD, challenging the historical emphasis of GERD in DES pathogenesis. The impact of GERD management on the natural history of DES remains uncertain.

Long-Term Efficacy and Safety of Fecal Microbiota Transplantation for C. difficile Infections Across Academic and Private Clinical Settings.

PURPOSE: Fecal microbiota transplant (FMT) is increasingly performed for Clostridioides difficile infection (CDI), although long-term efficacy and safety data are limited and are focused on results from academic medical centers rather than private settings where most patients receive care. METHODS: Medical records of 165 patients who received FMTs for CDI were reviewed from an academic medical center and an adjacent, unaffiliated private practice. Of these patients, 68 also completed a survey regarding their long-term disease course and interval health. RESULTS: CDI resolution occurred in 81.3% (100/123) at the academic center and 95.2% (40/42) in the private setting. Private practice patients were more likely to present with recurrent, rather than refractory, CDI (92.9% vs. 66.7% P <0.001). Those from the academic center were more likely to have comorbid IBD, recent hospitalization, recent proton pump inhibitor use, ongoing immunosuppression, and inpatient FMT (all P values <0.05).Among surveyed patients, 29.4% developed interval comorbidities or changes to pre-existing conditions after a median follow-up of 33.7 months (IQR 13.2 to 44.3 mo). Of 30 patients requiring subsequent antibiotics, 13.3% suffered CDI relapse. All subjects who had initially responded to FMT but had a subsequent CDI (17.9%, 10/56) responded to another FMT. CONCLUSIONS: In a real-world setting, patients who underwent FMT at academic centers differed significantly in clinical characteristics from those treated at a private practice. In both settings, FMT is an effective treatment for CDI not responding to standard therapies, even after subsequent antibiotic use. New diagnoses following FMT, however, are common and merit further exploration.

Fecal Microbiota Transplant for Clostridioides Difficile Infection Is Safe and Efficacious in an Immunocompromised Cohort.

BACKGROUND: Immunocompromised patients are particularly vulnerable to Clostridioides difficile infection (CDI), hospitalizations and recurrences. Studies have shown that fecal microbiota transplant (FMT) is safe and effective in immunocompromised patients. AIMS: To examine the outcomes of FMT for CDI in a diverse cohort of immunocompromised patients stratified by medication class. METHODS: We performed a retrospective, long-term follow-up study of FMT in immunocompromised patients, including those undergoing chemotherapy, with inflammatory bowel disease (IBD) on immunomodulators, prior solid organ transplant on immunosuppressants, on chronic steroids 20 mg/day or higher for a minimum of three months, or HIV positive. Primary outcomes included adjusted primary cure rate within 8 weeks, as well as rates of non-response, recurrences, relapses and adverse events. Secondary outcomes included adjusted overall cure rate. Primary cure rate was defined as patients not requiring repeat CDI treatment within 8 weeks after index FMT, and overall cure rate was defined as resolution of CDI symptoms after index FMT or second FMT. RESULTS: Our cohort included 77 immunosuppressed patients (53.2% female, median age 39.1 years, range 7-95 years). The majority of our cohort were IBD patients on biologics (62.3%). Adjusting for colectomies and deaths, our primary and overall cure rates were 85.1% and 86.5%, respectively. Twelve patients received FMT for severe or fulminant CDI with a 3-month survival rate of 91.7%. 11.7% of patients experienced serious adverse events following FMT. CONCLUSIONS: Our study supports the efficacy and safety of FMT in immunocompromised patients, though future research is needed to further ascertain the potential effects of immunosuppression on FMT outcomes.

Systematic Review with Meta-Analysis: Fecal Microbiota Transplantation for Severe or Fulminant Clostridioides difficile.

BACKGROUND: Severe and fulminant Clostridioides difficile infection (CDI) is associated with significant morbidity and mortality. While fecal microbiota transplantation (FMT) has proved to be a highly effective treatment for recurrent CDI, its efficacy in severe or fulminant CDI remains uncertain. AIMS: To perform a systematic review with meta-analysis evaluating clinical outcomes and safety of FMT in severe and fulminant CDI. METHODS: A systemic review with meta-analysis was performed through comprehensive search of Embase, Medline (Ovid), trial registers, and conference abstracts through January 2020. Studies on FMT in severe and fulminant CDI were included. Meta-analysis was done with random effects models given heterogeneity to estimate rates of cure, mortality, and colectomy. Publication bias was assessed using Egger's test. RESULTS: Sixteen studies comprised of one randomized controlled trial, four cohort studies, and eleven case series were analyzed. In total, 676 patients underwent FMT for severe or fulminant CDI. The overall rate of clinical cure after single FMT was 61.3% (95% CI 43.2-78.0%) with 10.9% (95% CI 0.2-30.2%) of patients experiencing major adverse events. The overall pooled colectomy rate after FMT was 8.2% (95% CI 0.1-23.7%) with a pooled all-cause mortality rate after FMT of 15.6% (95% CI 7.8-25.0%). CONCLUSION: Low-quality data support the use of fecal microbiota transplantation in patients with severe and fulminant Clostridioides difficile infection.

Oral Fecal Microbiota Transplant Capsules Are Safe and Effective for Recurrent Clostridioides difficile Infection: A Systematic Review and Meta-Analysis.

GOALS: We performed a systematic review with meta-analysis to examine the efficacy and safety of oral fecal microbiota transplantation (FMT) capsules for recurrent Clostridioides difficile infection (rCDI). BACKGROUND: FMT through colonoscopy is established as effective and safe in treating multiple recurrences of CDI, but consensus has not been established on delivery through oral capsules. STUDY: A systematic literature search was performed with multiple databases including MEDLINE and EMBASE to identify original studies including at least 10 patients that investigated the role of oral FMT capsules to treat rCDI. Cure rates were pooled by a random effects model and publication bias was assessed with the Egger test. Secondary analyses assessed for differences between capsule preparation (frozen vs. lyophilized stool) and delivery modality (capsule vs. colonoscopy). RESULTS: Fifteen studies (12 case series and 3 randomized controlled trials) encompassing 763 patients were identified for inclusion. Significant variability existed in baseline patient characteristics and protocols. Meta-analysis of proportions showed efficacy of oral FMT capsules to be 0.821 (95% confidence interval: 0.762-0.874). No evidence for publication bias was found (P=0.51). Secondary analyses did not find significant differences in efficacy. Fourteen adverse events leading to death or hospitalization were noted, none of which were attributed to FMT. CONCLUSIONS: Oral FMT capsules for rCDI are promising because of ease of administration and noninvasive delivery. We found an overall efficacy of 82.1% with a low rate of serious adverse events. Further studies are needed to optimize protocols and outcomes.

Fecal Transplants by Colonoscopy and Capsules Are Cost-Effective Strategies for Treating Recurrent Clostridioides difficile Infection.

BACKGROUND: Recurrent Clostridioides difficile infections (CDIs) occur frequently and pose a substantial economic burden on the US healthcare system. The landscape for the treatment of CDI is evolving. AIM: To elucidate the most cost-effective strategy for managing recurrent CDI. METHODS: A decision tree analysis was created from a modified third-party payer's perspective to compare the cost-effectiveness of five strategies for patients experiencing their first CDI recurrence: oral vancomycin, fidaxomicin, fecal microbiota transplant (FMT) via colonoscopy, FMT via oral capsules, and a one-time infusion of bezlotoxumab with vancomycin. Effectiveness measures were quality-adjusted life years (QALY). A willingness-to-pay (WTP) threshold of $100,000 per QALY was set. One-way and probabilistic sensitivity analyses were performed. RESULTS: Base-case analysis showed that FMT via colonoscopy was associated with the lowest cost at $5250 and that FMT via capsules was also a cost-effective strategy with an incremental cost-effectiveness ratio (ICER) of $31205/QALY. Sensitivity analyses demonstrated that FMT delivered by oral capsules and colonoscopy was comparable cost-effective modalities. At its current cost and effectiveness, bezlotoxumab was not a cost-effective strategy. CONCLUSIONS: FMT via oral capsules and colonoscopy is both cost-effective strategies to treat the first recurrence of CDI. Further real-world economic studies are needed to understand the cost-effectiveness of all available strategies.

Fecal Microbiota Transplantation for Clostridioides difficile in High-Risk Older Adults Is Associated with Early Recurrence.

BACKGROUND: Fecal microbiota transplantation (FMT) is highly effective for treating recurrent Clostridioides difficile infection (CDI). CDI disproportionately affects the elderly; however, there is a paucity of data on FMT effectiveness in older adults, especially subpopulations at highest risk for CDI-related morbidity and mortality. AIM: To assess the efficacy and safety of FMT for CDI in older adults. METHODS: A retrospective, long-term follow-up study was performed. The high-risk subpopulation included patients who were immunocompromised, patients with inflammatory bowel disease, and patients presenting with severe or fulminant colitis. Outcome measures included primary cure rates, early (< 12 weeks) and late (> 12 weeks) recurrence rates, adverse events, and subgroup analysis of higher-risk populations. RESULTS: Our cohort included 75 patients (72% female) with a mean age of 76.4 and Charlson comorbidity index score of 5.4. There were 34 patients in our higher-risk subpopulation as defined above with an adjusted recurrence rate of 32.1%. FMT was performed for severe or fulminant disease in 30.6% of patients with a 3-month survival rate of 73.9%. Overall, the adjusted primary cure rate was 67.2% and the adjusted CDI recurrence was 29.9% in our cohort (90% of recurrences occurred early). Most adverse events in our study were rehospitalizations for recurrent CDI. CONCLUSION: Compared with previous studies of FMT efficacy, our cohort had a lower primary cure rate and higher CDI recurrence rate than previously reported, likely driven by our higher-risk subpopulations. Nevertheless, FMT should be considered early to prevent progression of CDI severity and recurrence, especially in patients who present with severe and fulminant disease.

A novel strategy to produce high level and high purity of bioactive IL15 fusion proteins from mammalian cells.

IL15, a member of the common γ chain receptor (γc) cytokine family, is gaining attention in recent years as one of the most promising anti-tumor agents. IL15 regulates T cell activation and proliferation, promotes the survival of CD8+ CD44hi memory T cells and is also essential for NK cell expansion and development. Despite the attraction of developing IL15 as an anti-cancer agent, production of recombinant IL15 has proven to be difficult due to the stringent control of IL15 expression at the transcriptional, translational and the post-translational levels. Furthermore, the bioactivity of IL15 fused to an extra functional domain that is isolated from mammalian cells is generally inferior to recombinant IL15 produced by E. coli. In this study, we report that Lysine 86 in IL15 is responsible for the instability in mammalian cells when its C-terminus is fused to the albumin binding scFv (IL15-A10m3). We demonstrate that K86A or K86R mutants increased the expression of the fusion protein from HEK293 cells. When the wild type IL15 is used for the fusion, no recombinant IL15 fusion was detected in the culture media. Additionally, we determined that the residue 112 in IL15 is critical for the bioactivity of IL15-A10m3. Examination of single and double mutants provides a better understanding of how IL15 engages with its receptor complex to achieve full signaling capacity. The results of our experiments were successfully applied to scale up production to levels up to 50 mg/L and >10 mg/L of >95% pure monomeric recombinant fusion proteins after a 2-step purification from culture media. More importantly, the recombinant fusion protein produced is fully active in stimulating T cell proliferation, when compared to the recombinant wild type IL15.

The Relationship of E-Cigarette Use to Cigarette Quit Attempts and Cessation: Insights From a Large, Nationally Representative U.S. Survey.

Objectives: While cessation from cigarettes is a top priority for public health, controversy surrounds the role of e-cigarettes for quitting cigarettes. This study examines the role of e-cigarettes in quit attempts and 3-month cigarette abstinence using a large, recent nationally representative US sample. Methods: Data from the 2014/15 Tobacco Use Supplement-Current Population Survey (TUS-CPS) on cigarette and e-cigarette use and individual characteristics were supplemented with information on state tobacco control policies. We estimated frequencies and multivariate logistic equations for making a quit attempt among those who smoked 1 year earlier and for remaining abstinent at least 3 months among those making a quit attempt. These two outcomes were related to demographic characteristics, tobacco control policies and different frequency measures of e-cigarette use (ever, at least 1, 5, 20 of the last 30 days, a continuous measure of days use). Results: Having made a quit attempt was more likely among smokers using e-cigarettes than non-users. Among those making at least one quit attempt, quit success was lower among ever users, but higher among those with at least 5 days use of e-cigarettes in the last month. Both quit attempts and quit success were linearly related to the frequency of e-cigarette use. Conclusions: Consistent with randomized trials and those observational studies that measure frequency of e-cigarette use, both quit attempts and quit success were positively associated with increased frequency of e-cigarette use. Frequency of e-cigarette use was important in gauging the nature of these relationships. Implications: Previous studies have obtained mixed results regarding the relationship of e-cigarette use to cigarette smoking cessation. This study provides a more precise methodology for considering the relationship of e-cigarette use to quit attempts and to quit success, and finds that quit attempts and quit success increase with the number of days use in the past month.

Seven years of progress in tobacco control: an evaluation of the effect of nations meeting the highest level MPOWER measures between 2007 and 2014.

OBJECTIVE: Since WHO released the package of six MPOWER measures to assist nations with implementing the WHO Framework Convention for Tobacco Control (FCTC), 88 countries adopted at least one highest level MPOWER measure. We estimated the subsequent reduction in smoking-related deaths from all new highest level measures adopted between 2007 and 2014. METHODS: Policy effect sizes based on previously validated SimSmoke models were applied to the number of smokers in each nation to determine the reduction in the number of smokers from policy adoption. On the basis of research that half of all smokers die from smoking, we derived the smoking-attributable deaths (SADs) averted of those smokers alive today. FINDINGS: In total, 88 countries adopted at least one highest level MPOWER policy between 2007 and 2014, resulting in almost 22 million fewer projected SADs. The largest number of future SADs averted was due to increased cigarette taxes (7.0 million), followed by comprehensive smoke-free laws (5.4 million), large graphic health warnings (4.1 million), comprehensive marketing bans (3.8 million) and comprehensive cessation interventions (1.5 million). CONCLUSIONS: These findings demonstrate the immense public health impact of tobacco control policies adopted globally since the WHO-FCTC and highlight the importance of more countries adopting highest level MPOWER measures to reduce the global burden of tobacco use. Substantial additional progress could be made, especially if heavily populated nations with high smoking prevalence were to reach highest level MPOWER measures.

Potential deaths averted in USA by replacing cigarettes with e-cigarettes.

INTRODUCTION: US tobacco control policies to reduce cigarette use have been effective, but their impact has been relatively slow. This study considers a strategy of switching cigarette smokers to e-cigarette use ('vaping') in the USA to accelerate tobacco control progress. METHODS: A Status Quo Scenario, developed to project smoking rates and health outcomes in the absence of vaping, is compared with Substitution models, whereby cigarette use is largely replaced by vaping over a 10-year period. We test an Optimistic and a Pessimistic Scenario, differing in terms of the relative harms of e-cigarettes compared with cigarettes and the impact on overall initiation, cessation and switching. Projected mortality outcomes by age and sex under the Status Quo and E-Cigarette Substitution Scenarios are compared from 2016 to 2100 to determine public health impacts. FINDINGS: Compared with the Status Quo, replacement of cigarette by e-cigarette use over a 10-year period yields 6.6 million fewer premature deaths with 86.7 million fewer life years lost in the Optimistic Scenario. Under the Pessimistic Scenario, 1.6 million premature deaths are averted with 20.8 million fewer life years lost. The largest gains are among younger cohorts, with a 0.5 gain in average life expectancy projected for the age 15 years cohort in 2016. CONCLUSIONS: The tobacco control community has been divided regarding the role of e-cigarettes in tobacco control. Our projections show that a strategy of replacing cigarette smoking with vaping would yield substantial life year gains, even under pessimistic assumptions regarding cessation, initiation and relative harm.

Psychological comorbidities are more prevalent amongst pregnant and postpartum patients with irritable bowel syndrome.

BACKGROUND: There is a lack of data on the epidemiology of IBS in pregnant and postpartum patients in the United States. METHODS: A retrospective claims analysis was conducted in a cohort of 1,618,379 patients with ≥1 delivery hospitalization between 2013-2019 utilizing ICD-9 and ICD-10 codes after merging inpatient and outpatient claims. Obstetric, psychological, and other medical comorbidities were also examined. KEY RESULTS: The prevalence of IBS in our cohort was 1.38%. Pregnant and postpartum patients with IBS were more likely to have psychological comorbidities including depression (OR 2.93, CI 2.83-3.03), postpartum depression (OR 3.00, CI 2.91-3.09), and anxiety (OR 3.74, CI 3.64-3.84). They were also more likely to have migraines (OR 3.04, CI 2.94-3.15) and connective tissue disease or autoimmune disease (OR 3.54, CI 3.22-3.89). CONCLUSION: The prevalence of IBS in pregnant and postpartum patients in a large claims database was 1.38%. Pregnant and postpartum patients with IBS have a higher odd of psychological comorbidities in addition to medical comorbidities such as migraines, connective tissue, and autoimmune disease. Future studies should focus on validating and characterizing the impact and directionality of co-existing comorbidities on IBS severity and the development of new-onset IBS during pregnancy and the postpartum period.

Maternal mitochondrial function affects paternal mitochondrial inheritance in Drosophila.

The maternal inheritance of mitochondria is a widely accepted paradigm, and mechanisms that prevent paternal mitochondria transmission to offspring during spermatogenesis and postfertilization have been described. Although certain species do retain paternal mitochondria, the factors affecting paternal mitochondria inheritance in these cases are unclear. More importantly, the evolutionary benefit of retaining paternal mitochondria and their ultimate fate are unknown. Here we show that transplanted exogenous paternal D. yakuba mitochondria can be transmitted to offspring when maternal mitochondria are dysfunctional in D. melanogaster. Furthermore, we show that the preserved paternal mitochondria are functional, and can be stably inherited, such that the proportion of paternal mitochondria increases gradually in subsequent generations. Our work has important implications that paternal mitochondria inheritance should not be overlooked as a genetic phenomenon in evolution, especially when paternal mitochondria are of significant differences from the maternal mitochondria or the maternal mitochondria are functionally abnormal. Our results improve the understanding of mitochondrial inheritance and provide a new model system for its study.

Design of a cryptococcus neoformans vaccine by subtractive proteomics combined with immunoinformatics.

The emergence of Cryptococcus neoformans has posed an undeniable burden to many regions worldwide, with its strains mainly entering the lungs through the respiratory tract and spreading throughout the body. Limitations of drug regimens, such as high costs and limited options, have directed our attention toward the promising field of vaccine development. In this study, the subtractive proteomics approach was employed to select target proteins from databases that can accurately cover serotypes A and D of the Cryptococcus neoformans. Further, two multi-epitope vaccines consisting of T and B cell epitopes were demonstrated that they have good structural stability and could bind with immune receptor to induce desired immune responses in silico. After further evaluation, these vaccines show the potential for large-scale production and applicability to the majority of the population of the world. In summary, these two vaccines have been theoretically proven to combat Cryptococcus neoformans infections, awaiting further experimental validation of their actual protective effects.