Oronasal Fistula Closure and Defect Reconstruction: Two Case Reports Using Periodontal Plastic Surgery Principles.

OBJECTIVES: Oronasal fistulas are common sequelae following cleft lip and palate surgery and can significantly impact a patient's quality of life. They result from various factors, including surgical techniques, tissue management, and patient-specific factors. This case report explores the modern approach to oronasal fistula closure using periodontal plastic surgery principles. MATERIALS AND METHODS: The report presents two cases of patients with oronasal fistulas due to previous maxillofacial surgical intervention. These patients underwent microsurgical procedures that involved partial flap thickness preparation of the fistula areas, the use of connective tissue grafts from the palate, and meticulous suturing techniques to ensure graft integrity. The procedures were performed in stages, and postoperative care was provided. RESULTS: Both cases demonstrated successful fistula closure and graft survival. The patients reported improvements in breathing, speech, aesthetics, and quality of life. The second case also included guided bone regeneration and implant placement. CONCLUSIONS: Oronasal fistulas resulting from maxillofacial surgery can be effectively treated using periodontal plastic surgery techniques, significantly improving patients' quality of life and aesthetic outcomes. This approach represents a valuable addition to the existing repertoire of oronasal fistula closure methods.

Patient Time Spent With Professional Medical Interpreters and the Care Experiences of Patients With Limited English Proficiency.

INTRODUCTION/OBJECTIVES: More time spent with interpreters may support clinician-patient communication for patients with limited English proficiency (LEP), especially when interpreter support before and after clinical encounters is considered. We assessed whether more time spent with interpreters is associated with better patient-reported experiences of clinician-patient communication and interpreter support among patients with LEP. METHODS: Patients with LEP (n = 338) were surveyed about their experiences with both the clinician and interpreter. Duration of interpreter support during the encounter (in min) and auxiliary time spent before and after encounters supporting patients (in min) were documented by interpreters. Multivariable linear regression models were estimated to assess the association of the time duration of interpreter support and patient experiences of (1) clinician-patient communication, and (2) interpreter support, controlling for patient and encounter characteristics. RESULTS: The average encounter duration was 47.7 min (standard deviation, SD = 25.1), the average auxiliary time was 43.8 min (SD = 16.4), and the average total interpreter time was 91.1 min (SD = 28.6). LEP patients reported better experiences of interpreter support with a mean score of 97.4 out of 100 (SD = 6.99) compared to clinician-patient communication, with a mean score of 93.7 out of 100 (SD = 14.1). In adjusted analyses, total patient time spent with an interpreter was associated with better patient experiences of clinician-patient communication (ß = 7.23, P < .01) when auxiliary time spent by interpreters supporting patients before and after the encounter was considered, but not when only the encounter time was considered. CONCLUSIONS: Longer duration of time spent with an interpreter was associated with better clinician-patient communication for patients with LEP when time spent with an interpreter before and after the clinician encounter is considered. Policymakers should consider reimbursing health care organizations for time interpreters spend providing patient navigation and other support beyond clinical encounters.

Primary Care Practice Characteristics Associated With Medical Assistant Staffing Ratios.

This study characterized adult primary care medical assistant (MA) staffing. National Survey of Healthcare Organizations and Systems (n = 1,252) data were analyzed to examine primary care practice characteristics associated with MA per primary care clinician (PCC) staffing ratios. In 2021, few practices (11.4%) had ratios of 2 or more MAs per PCCs. Compared with system-owned practices, independent (odds ratio [OR] = 1.76, P <0.05) and medical group-owned (OR = 2.09, P <0.05) practices were more likely to have ratios of 2 or more MAs per PCCs, as were practices with organizational cultures oriented to innovation (P <0.05). Most primary care practices do not have adequate MA staffing.

Validation of a novel western blot assay to monitor patterns and levels of alpha dystroglycan in skeletal muscle of patients with limb girdle muscular dystrophies.

The cell membrane protein, dystroglycan, plays a crucial role in connecting the cytoskeleton of a variety of mammalian cells to the extracellular matrix. The α-subunit of dystroglycan (αDG) is characterized by a high level of glycosylation, including a unique O-mannosyl matriglycan. This specific glycosylation is essential for binding of αDG to extracellular matrix ligands effectively. A subset of muscular dystrophies, called dystroglycanopathies, are associated with aberrant, dysfunctional glycosylation of αDG. This defect prevents myocytes from attaching to the basal membrane, leading to contraction-induced injury. Here, we describe a novel Western blot (WB) assay for determining levels of αDG glycosylation in skeletal muscle tissue. The assay described involves extracting proteins from fine needle tibialis anterior (TA) biopsies and separation using SDS-PAGE followed by WB. Glycosylated and core αDG are then detected in a multiplexed format using fluorescent antibodies. A practical application of this assay is demonstrated with samples from normal donors and patients diagnosed with LGMD2I/R9. Quantitative analysis of the WB, which employed the use of a normal TA derived calibration curve, revealed significantly reduced levels of αDG in patient biopsies relative to unaffected TA. Importantly, the assay was able to distinguish between the L276I homozygous patients and a more severe form of clinical disease observed with other FKRP variants. Data demonstrating the accuracy and reliability of the assay are also presented, which further supports the potential utility of this novel assay to monitor changes in ⍺DG of TA muscle biopsies in the evaluation of potential therapeutics.

Long-term effects of gestational diabetes mellitus on the pancreas of female mouse offspring.

BACKGROUND: Prolonged fetal exposure to hyperglycemia may increase the risk of developing abnormal glucose metabolism and type-2 diabetes during childhood, adolescence, and adulthood; however, the mechanisms by which gestational diabetes mellitus (GDM) predisposes offspring to metabolic disorders remain unknown. AIM: To quantify the nerve axons, macrophages, and vasculature in the pancreas from adult offspring born from mouse dams with GDM. METHODS: GDM was induced by i.p. administration of streptozotocin (STZ) in ICR mouse dams. At 12 wk old, fasting blood glucose levels were determined in offspring. At 15 wk old, female offspring born from dams with and without GDM were sacrificed and pancreata were processed for immunohistochemistry. We quantified the density of sensory [calcitonin gene-related peptide (CGRP)] and tyrosine hydroxylase (TH) axons, blood vessels (endomucin), and macro-phages (CD68) in the splenic pancreas using confocal microscopy. RESULTS: Offspring mice born from STZ-treated dams had similar body weight and blood glucose values compared to offspring born from vehicle-treated dams. However, the density of CGRP+ and TH+ axons, endomucin+ blood vessels, and CD68+ macrophages in the exocrine pancreas was significantly greater in offspring from mothers with GDM vs control offspring. Likewise, the microvasculature in the islets was significantly greater, but not the number of macrophages within the islets of offspring born from dams with GDM compared to control mice. CONCLUSION: GDM induces neuronal, vascular, and inflammatory changes in the pancreas of adult progeny, which may partially explain the higher propensity for offspring of mothers with GDM to develop metabolic diseases.

Akkermansia muciniphila-induced trained immune phenotype increases bacterial intracellular survival and attenuates inflammation.

The initial exposure to pathogens and commensals confers innate immune cells the capacity to respond distinctively upon a second stimulus. This training capacity might play key functions in developing an adequate innate immune response to the continuous exposure to bacteria. However, the mechanisms involved in induction of trained immunity by commensals remain mostly unexplored. A. muciniphila represents an attractive candidate to study the promotion of these long-term responses. Here, we show that priming of macrophages with live A. muciniphila enhances bacterial intracellular survival and decreases the release of pro- and anti-inflammatory signals, lowering the production of TNF and IL-10. Global transcriptional analysis of macrophages after a secondary exposure to the bacteria showed the transcriptional rearrangement underpinning the phenotype observed compared to acutely exposed cells, with the increased expression of genes related to phagocytic capacity and those involved in the metabolic adjustment conducing to innate immune training. Accordingly, key genes related to bacterial killing and pro-inflammatory pathways were downregulated. These data demonstrate the importance of specific bacterial members in the modulation of local long-term innate immune responses, broadening our knowledge of the association between gut microbiome commensals and trained immunity as well as the anti-inflammatory probiotic potential of A. muciniphila.

Linguistic Disparities in Diabetes Care Quality in California Community Health Centers Before and During the COVID-19 Pandemic.

BACKGROUND: Disparities in diabetes care quality may have increased for patients with limited English language proficiency (LEP) compared to non-LEP patients during the COVID-19 pandemic. Changes in diabetes care quality for adult LEP and non-LEP patients of community health centers (CHCs) were examined from 2019 to 2020. METHODS: Adults with Type 2 diabetes (n = 15 965) of 88 CHC sites in California and with 1+ visit/year in 2019 and 2020 from OCHIN electronic health record data were included. Multivariable regression models estimated the association of LEP status and changes in diabetes care quality from 2019 to 2020, controlling for patient sociodemographic and clinical characteristics. Interaction terms (LEP × 2020) were used to estimate differential over time changes in (1) blood pressure screening, (2) blood pressure control (<140/90 mm Hg), and (3) hemoglobin A1c control (HbA1c <8%) for LEP versus non-LEP patients. RESULTS: LEP and non-LEP patients with diabetes had comparable blood pressure screening and control in 2019 and in 2020. LEP patients were less likely than non-LEP patients to have their HbA1c under control in 2019 (OR = 0.85, 95% CI = 0.77, 0.96, P = .006) and 2020 (OR = 0.83, 95% CI = 0.75, 0.92, P = .001). There were no differential changes in HbA1c control over time for LEP and non-LEP patients. DISCUSSION: Although LEP patients were less likely than non-LEP patients to have their HbA1c under control, CHCs maintained quality of care equally for LEP and non-LEP patients with diabetes during the early pandemic period.

Thermotolerance capabilities, blood metabolomics, and mammary gland hemodynamics and transcriptomic profiles of slick-haired Holstein cattle during mid lactation in Puerto Rico.

Holstein cattle carrying a prolactin receptor gene mutation (SLICK) exhibit short and sleek hair coats (short-haired Holstein [SLK]) enhancing thermotolerance and productivity compared with wild type-haired Holstein (WT) under tropical conditions. The objectives were to unravel the physiological and molecular mechanisms that confer an advantage to this slick genotype in Puerto Rico and determine potential correlations between metabolites and physiological variables. At 160 ± 3 DIM we compared vaginal temperatures (VT) and voluntary solar radiation exposure (VSRE) during 48 h between 9 SLK and 9 WT Holsteins, whereas a subsample of 7 SLK and 7 WT were used to assess udder skin temperature, mammary gland hemodynamics and transcriptomics, and blood plasma untargeted metabolomics at a single time point. The SLK cattle showed lower VT throughout the day and greater VSRE at 1000 h and 1100 h compared with their WT counterparts. Total mammary blood flow (MBF) was greater in SLK Holsteins compared with WT. The metabolite 9-nitrooctadecenoic acid was identified as a potential biomarker for MBF; moreover, SLK cattle had greater amounts of this metabolite in their plasma. Prostaglandin D2 synthase (PTGS) was upregulated in the slick mammary gland, while plasma prostaglandin D2 was positively correlated with milk yield and increased in SLK Holsteins compared with WT. Interestingly, the arachidonic acid metabolism pathway was enriched in the mammary gland transcriptome and perturbed in the blood metabolome in the SLK Holsteins. In conclusion, SLK Holsteins exhibited lower body temperatures, greater VSRE, enhanced blood supply to the mammary gland, and alterations in genes and metabolites involved in arachidonic acid metabolism at the mammary gland and blood plasma. The usage of the SLK Holstein cattle genetics in dairy operations could be a feasible alternative to mitigate the adverse consequences of heat stress.

Capacity of Aqueous Solutions of the Ionic Liquid 1-Ethyl-3-methylimidazolium Acetate to Partially Depolymerize Lignin at Ambient Temperature and Pressure.

Lignin is a very attractive and abundant biopolymer with the potential to be a biorenewable source of a large number of value-added organic chemicals. The current state-of-the-art methods fail to provide efficient valorization of lignin in this regard without the involvement of harsh conditions and auxiliary substances that compromise the overall sustainability of the proposed processes. Making an original approach from the set of mildest temperature and pressure conditions, this work identifies and explores the capacity of an aqueous solution of the nonvolatile ionic liquid 1-ethyl-3-methylimidazolium acetate ([C2mim][OAc]) to partially depolymerize technical lignin (Indulin AT) by means of a treatment consisting in the simple contact at ambient temperature and pressure. Among a considerable number of valuable phenolic molecules that were identified in the resulting fluid, vanillin (yield of about 3 g/kg) and guaiacol (yield of about 1 g/kg) were the monophenolic compounds obtained in a higher concentration. The properties of the post-treatment solids recovered remain similar to those of the original lignin, although with a relatively lower abundance of guaiacyl units (in agreement with the generation of guaiacyl-derived phenolic molecules, such as vanillin and guaiacol). The assistance of the treatment with UV irradiation in the presence of nanoparticle catalysts does not lead to an improvement in the yields of phenolic compounds.

Food phenolics and Lactiplantibacillus plantarum.

Phenolic compounds are important constituents of plant food products. These compounds play a key role in food characteristics such as flavor, astringency and color. Lactic acid bacteria are naturally found in raw vegetables, being Lactiplantibacillus plantarum the most commonly used commercial starter for the fermentation of plant foods. Hence, the metabolism of phenolic compounds of L. plantarum has been a subject of study in recent decades. Such studies confirm that L. plantarum, in addition to presenting catalytic capacity to transform aromatic alcohols and phenolic glycosides, exhibits two main differentiated metabolic routes that allow the biotransformation of dietary hydroxybenzoic and hydroxycinnamic acid-derived compounds. These metabolic pathways lead to the production of new compounds with new biological and organoleptic properties. The described metabolic pathways involve the action of specialized esterases, decarboxylases and reductases that have been identified through genetic analysis and biochemically characterized. The purpose of this review is to provide a comprehensive and up-to-date summary of the current knowledge of the metabolism of food phenolics in L. plantarum.

Hospital Capabilities Associated With Behavioral Health Integration Within Emergency Departments.

OBJECTIVES: To identify hospital capabilities associated with behavioral health (BH) processes in emergency departments (EDs). RESEARCH DESIGN: Six hundred two hospital responses to the 2017/2018 National Survey of Healthcare Organizations and Systems were linked to 2017 American Hospital Association Annual Survey data. Separate multivariable regressions estimated how hospital capabilities (the use of quality improvement methods, approaches to disseminate best patient-care practices, barriers to using care delivery innovations, and inpatient beds for psychiatric or substance use) were associated with each of 4 ED-based BH processes: mental health and substance use disorder screening, team-based approaches to BH, telepsychiatry, and direct referrals to community-based BH clinicians. Models controlled for hospital structural characteristics and area-level socioeconomic factors. RESULTS: Most hospitals screened for BH conditions and provided direct referrals to community-based BH clinicians. Approximately half of the hospitals used a team approach to BH. A minority had implemented telepsychiatry. Each additional process used to disseminate best patient-care practices was associated with more screening for BH conditions (an increase of 4.07 points on the screening index, P <0.01) and greater likelihood of using a team approach to BH [4.41 percentage point ( P <0.01) increase]. Hospitals reporting more barriers to the use of care delivery innovations reported less screening and use of a team approach [a decrease of 0.15 points on the screening index ( P <0.01) and 0.28 percentage points reduction in likelihood of team approach use ( P <0.001) for 1-point increase in the barrier index]. CONCLUSIONS: Research and interventions focused on removing innovation barriers or adding processes to disseminate best practices offer a path to accelerate BH integration in hospital EDs.

Telemedicine Implementation for Safety Net Populations: A Systematic Review.

Background: Telemedicine systems were rapidly implemented in response to COVID-19. However, little is known about their effectiveness, acceptability, and sustainability for safety net populations. This study systematically reviewed primary care telemedicine implementation and effectiveness in safety net settings. Methods: We searched PubMed for peer-reviewed articles on telemedicine implementation from 2013 to 2021. The search was done between June and December 2021. Included articles focused on health care organizations that primarily serve low-income and/or rural populations in the United States. We screened 244 articles from an initial search of 343 articles and extracted and analyzed data from N = 45 articles. Results: Nine (20%) of 45 articles were randomized controlled trials. N = 22 reported findings for at least one marginalized group (i.e., racial/ethnic minority, 65 years+, limited English proficiency). Only n = 19 (42%) included African American/Black patients in demographics descriptions, n = 14 (31%) LatinX/Hispanic patients, n = 4 (9%) Asian patients, n = 4 (9%) patients aged 65+ years, and n = 4 (9%) patients with limited English proficiency. Results show telemedicine can provide high-quality primary care that is more accessible and affordable. Fifteen studies assessed barriers and facilitators to telemedicine implementation. Common barriers were billing/administrative workflow disruption (n = 9, 20%), broadband access/quality (n = 5, 11%), and patient preference for in-person care (n = 4, 9%). Facilitators included efficiency gains (n = 6, 13%), patient acceptance (n = 3, 7%), and enhanced access (n = 3, 7%). Conclusions: Telemedicine is an acceptable care modality to deliver primary care in safety net settings. Future studies should compare telemedicine and in-person care quality and test strategies to improve telemedicine implementation in safety net settings.

Anatomical and physiological adaptation of the scrotal artery with muscular reinforcement in the middle layer and connective reinforcement of the adventitia.

The histology of blood vessels shows they are structured in three layers or tunics: tunica intima, which includes the internal limiting lamina with high elastin content; tunica media of smooth muscles fibers of circular disposition, which includes the external limiting lamina; and tunica adventitia of connective tissue. The vascular system is essential in regulating body temperature, especially in the scrotum and testis. This study aimed to analyze the histology of the scrotal arteries and their possible relationship to testicular temperature homeostasis. This study used scrotal samples from human adults, anonymized and obtained from the University of Chile's teaching bank. The control group corresponds to an arteriole of muscle tissue. The results show that the middle layer of the scrotal artery is made up of smooth muscle fibers distributed in two layers: a longitudinal inner sublayer and a circular outer sublayer, different from the findings in muscle tissue arteries, with a single, circularly arranged muscle layer. This arrangement could be related to testicular temperature homeostasis by reducing the temperature of the testis and seminiferous tubules. The results described in this work suggest that these anatomical adaptations may be very significant in the face of the constant increase in global temperature. Further and better research is required to understand the mechanisms of thermoregulation in human reproduction and the histological particularities of the tissues that form the scrotum. RESEARCH HIGHLIGHTS: The human scrotal artery has a histological composition adapted for regulation of testicular temperature. The muscular double middle layer of the scrotal artery retains intravascular temperature.

Conjoint Analysis of Telemedicine Preferences for Hypertension Management Among Adult Patients.

Background: Telemedicine has been differentially utilized by different demographic groups during COVID-19, exacerbating inequities in health care. We conducted conjoint and latent class analyses to understand factors that shape patient preferences for hypertension management telemedicine appointments. Methods: We surveyed 320 adults, oversampling participants from households that earned <$50K per year (77.2%) and speak a language other than English at home (68.8%). We asked them to choose among 2 hypothetical appointments through 12 conjoint tasks measuring 6 attributes. Individual utilities for attributes were constructed using logit estimation, and latent classes were identified and compared by demographic and clinical characteristics. Results: Respondents preferred in-person visits (0.353, standard error [SE] = 0.039) and video appointments conducted through a secure patient portal (0.002, SE = 0.040). Respondents also preferred seeing a clinician with whom they have an established relationship (0.168, SE = 0.021). We found four latent classes: "in-person" (26.5% of participants) who strongly weighted in-person appointments, "cost conscious" (8.1%) who prioritized the lowest copay ($0 to $10), "expedited" (19.7%) who prioritized getting the earliest appointment possible (same/next day or at least within the next week), and "comprehensive" (45.6%) who had preferences for in-person care and telemedicine appointments through a secure portal, low copayments, and the ability to see a familiar clinician. Conclusions: Appointment preferences for hypertension management can be segmented into four groups that prioritize (1) in-person care, (2) low copayments, (3) expedited care, and (4) balanced preferences for in-person and telemedicine appointments. Evidence is needed to clarify whether aligning appointment offerings with patients' preferences can improve care quality, equity, and efficiency.

Síndrome de Mirizzi, complicación inusual de la colelitiasis / Mirizzi Syndrome, a Rare Complication of Cholelithiasis

Introducción: El síndrome de Mirizzi es una entidad clínica rara y difícil de tratar; sin embargo, los avances tecnológicos recientes han brindado a los cirujanos nuevas opciones para un diagnóstico y tratamiento más efectivos de esta afección. Objetivo: Presentar el caso de síndrome de Mirizzi, complicación inusual de la colelitiasis. Presentación del caso: Se presenta una paciente femenina, de 56 años de edad, que acude a nuestra institución por presentar ictericia intermitente, dolor en el hipocondrio derecho, coluria y acolia. Conclusiones: El síndrome de Mirizzi, complicación de la colelitiasis, es una entidad poco frecuente, de difícil diagnóstico preoperatorio, por lo que en un gran porcentaje de los casos se diagnostica intraoperatoriamente. Su tratamiento es quirúrgico(AU)

Introduction: Mirizzi syndrome is a rare condition, difficult to treat; however, recent technological advances have provided surgeons with new options for diagnosing and treating this condition more effectively. Objective: To present a case of Mirizzi syndrome, an unusual complication of cholelithiasis. Case presentation: The case is presented of a 56-year-old female patient, who comes to our institution with intermittent jaundice, right hypochondrium pain, choluria and acholia. Conclusions: Mirizzi syndrome, a complication of cholelithiasis, is a rare entity, difficult to diagnose preoperatively; therefore, a large percentage of it's cases are diagnosed intraoperatively. Its treatment is surgical(AU)

Improving health equity through health care systems research.

OBJECTIVE: To describe health equity research priorities for health care delivery systems and delineate a research and action agenda that generates evidence-based solutions to persistent racial and ethnic inequities in health outcomes. DATA SOURCES AND STUDY SETTING: This project was conducted as a component of the Agency for Healthcare Research and Quality's (AHRQ) stakeholder engaged process to develop an Equity Agenda and Action Plan to guide priority setting to advance health equity. Recommendations were developed and refined based on expert input, evidence review, and stakeholder engagement. Participating stakeholders included experts from academia, health care organizations, industry, and government. STUDY DESIGN: Expert group consensus, informed by stakeholder engagement and targeted evidence review. DATA COLLECTION/EXTRACTION METHODS: Priority themes were derived iteratively through (1) brainstorming and idea reduction, (2) targeted evidence review of candidate themes, (3) determination of preliminary themes; (4) input on preliminary themes from stakeholders attending AHRQ's 2022 Health Equity Summit; and (5) and refinement of themes based on that input. The final set of research and action recommendations was determined by authors' consensus. PRINCIPAL FINDINGS: Health care delivery systems have contributed to racial and ethnic disparities in health care. High quality research is needed to inform health care delivery systems approaches to undo systemic barriers and inequities. We identified six priority themes for research; (1) institutional leadership, culture, and workforce; (2) data-driven, culturally tailored care; (3) health equity targeted performance incentives; (4) health equity-informed approaches to health system consolidation and access; (5) whole person care; (6) and whole community investment. We also suggest cross-cutting themes regarding research workforce and research timelines. CONCLUSIONS: As the nation's primary health services research agency, AHRQ can advance equitable delivery of health care by funding research and disseminating evidence to help transform the organization and delivery of health care.

A Bivalent Omicron-BA.4/BA.5-Adapted BNT162b2 Booster in ≥12-Year-Olds.

BACKGROUND: Protection against contemporary SARS-CoV-2 variants requires sequence-adapted vaccines. METHODS: In this ongoing phase 2/3 trial, 12-17-year-olds (n=108), 18-55-year-olds (n=313), and >55-year-olds (n=306) who previously received 3 original BNT162b2 30-µg doses, received a fourth dose (second booster) of 30-µg bivalent original/Omicron-BA.4/BA.5-adapted BNT162b2 (BNT162b2-Omi.BA.4/BA.5). For comparisons with original BNT162b2, participants were selected from another phase 3 trial. Immunologic superiority 1-month post-vaccination, with respect to 50% neutralizing titers (GMR lower bound [LB] 2-sided 95%CI >1), and noninferiority with respect to seroresponse rates (rate-difference LB 2-sided 95%CI >-5%), for Omicron BA.4/BA.5 were assessed in >55-year-olds versus original BNT162b2 as a second booster. Noninferiority with respect to neutralizing titer level (GMR LB 2-sided 95%CI >0.67) and seroresponse rate (rate-difference LB 2-sided 95%CI >-10%) of Omicron BA.4/BA.5 immune response for BNT162b2-Omi.BA.4/BA.5 in 18‒55-year-olds versus >55-year-olds was assessed. RESULTS: One-month post-vaccination in >55-year-olds, model-adjusted GMR of Omicron BA.4/BA.5 neutralizing titers for the BNT162b2-Omi.BA.4/BA.5 versus BNT162b2 group (2.91; 95%CI 2.45-3.44) demonstrated superiority of BNT162b2-Omi.BA.4/BA.5. Adjusted difference in percentages of >55-year-olds with seroresponse (26.77%; 95%CI 19.59-33.95) showed noninferiority of BNT162b2-Omi.BA.4/BA.5 to BNT162b2. Noninferiority of BNT162b2-Omi.BA.4/BA.5 in 18‒55-year-olds to >55-year-olds was met for model-adjusted GMR and seroresponse. GMTs in 12-17-year-olds increased from baseline to 1-month post-vaccination. The BNT162b2-Omi.BA.4/BA.5 safety profile was similar to booster doses of bivalent Omicron BA.1-modified BNT162b2 and original BNT162b2 reported in previous studies. CONCLUSIONS: Based on immunogenicity and safety data up to 1-month post-vaccination in participants who previously received 3 original BNT162b2 doses, a BNT162b2-Omi.BA.4/BA.5 30 µg booster has a favorable benefit-risk profile. CLINICAL TRIAL REGISTRATION: NCT05472038.

Mitochondrial dysfunction promotes microbial composition that negatively impacts on ulcerative colitis development and progression.

Recent evidence demonstrates potential links between mitochondrial dysfunction and inflammatory bowel diseases (IBD). In addition, bidirectional interactions between the intestinal microbiota and host mitochondria may modulate intestinal inflammation. We observed previously that mice deficient in the mitochondrial protein MCJ (Methylation-controlled J protein) exhibit increased susceptibility to DSS colitis. However, it is unclear whether this phenotype is primarily driven by MCJ-/- associated gut microbiota dysbiosis or by direct effects of MCJ-deficiency. Here, we demonstrate that fecal microbiota transplantation (FMT) from MCJ-deficient into germ-free mice was sufficient to confer increased susceptibility to colitis. Therefore, an FMT experiment by cohousing was designed to alter MCJ-deficient microbiota. The phenotype resulting from complex I deficiency was reverted by FMT. In addition, we determined the protein expression pathways impacted by MCJ deficiency, providing insight into the pathophysiology of IBD. Further, we used magnetic activated cell sorting (MACS) and 16S rRNA gene sequencing to characterize taxa-specific coating of the intestinal microbiota with Immunoglobulin A (IgA-SEQ) in MCJ-deficient mice. We show that high IgA coating of fecal bacteria observed in MCJ-deficient mice play a potential role in disease progression. This study allowed us to identify potential microbial signatures in feces associated with complex I deficiency and disease progression. This research highlights the importance of finding microbial biomarkers, which might serve as predictors, permitting the stratification of ulcerative colitis (UC) patients into distinct clinical entities of the UC spectrum.