Post-polypectomy surveillance: follow-up recommendations from the Alberta Colorectal Cancer Screening Program.

In 2013, the Alberta Colorectal Cancer Screening Program (ACRCSP) initially published recommendations for post-colonoscopy follow-up and polypectomy. Over time, emerging evidence and evolving surveillance guidelines from various expert groups necessitated a comprehensive review to align with the healthcare landscape in Alberta. To accomplish this, an expert panel was convened. Using the Agree II tool, we identified high-quality Clinical Practice Guidelines that were relevant to the Alberta medical context. Recommendations from these guidelines were adapted to fit the specific needs of Alberta. Recognizing inconsistencies and gaps within the existing guidelines, we conducted targeted literature reviews to ensure a comprehensive and evidence-based approach to our recommendations. Our revised recommendations build upon the assumption that a high-quality index colonoscopy has been performed at baseline. They are intended to enhance the quality of care and reduce unnecessary procedures. As well, they align with the growing consensus in the scientific literature that individuals with low-risk tubular adenomas may not require aggressive colonoscopy surveillance. The updated Alberta recommendations aim to provide clear recommendations for practicing endoscopists, referring physicians, and their patients. They address crucial questions such as determining which patients should commence surveillance via colonoscopy and which individuals should return to average-risk screening using the fecal immunochemical test (FIT). Additionally, our recommendations outline the appropriate surveillance intervals for those requiring continued monitoring.

Evaluation of viral suppression and medication-related burden among HIV-infected adults in a secondary care facility.

Background: People living with HIV/AIDS (PLHIV) are prone to other health issues that may result from the disease or antiretroviral medicines. These persons experience other psychosocial aspects of the illness, which may negatively affect their quality of life and overall treatment outcomes. This study assessed the medication-related burden and virological response of adult PLHIV. Method: This cross-sectional study involved 417 HIV-positive adults who had been on combined antiretroviral therapy for at least a year at the State Specialist Hospital Gombe. Nigeria. Patient medication experience was measured using the Living with Medication Questionnaire version-3 (LMQ-3). Virological suppression was assessed at viral loads <1000 copies/ml and 20 copies/ml for undetectable HIV RNA levels. The LMQ-3 scores were compared with the participants' characteristics using independent t-tests or one-way analysis of variance (ANOVA). Regression analyses was employed to identify the predictors of viral suppression and medication-related burden. P value <0.05 at 95% confidence interval was considered statistically significant. Results: Of the 417 PLHIV included in this study, 271 (65%) were classified as WHO Stage 1 ART initiation, 93.8% achieved viral suppression with 291 (69.5%) whom were females. The majority of patients 382 (91.6%) were on a dolutegravir-based regimen, had no tuberculosis diagnosis at antiretroviral therapy (ART) initiation (82.5%) and were 6-10 years on ART (46.3%). Only 67.6% of the population had a moderate medication-related burden. Female sex (p < 0.0005), unsuppressed viral load (p = 0.01), second-line ART (p = 0.03), tuberculosis at ART initiation (p = 0.02), and employment (p = 0.003) were significantly associated with medication-related burden. The predictor of viral suppression was high degree of medication-related burden (AOR, 0.12; 95% CI, 0.02-0.59) while unsuppressed viral load (p = 0.01) and female gender (p = 0.002) were independent predictors of medication related burden. Conclusion: The findings from this study revealed that majority of the patients achieved viral suppression with moderate degree of medication-related burden. Targeted interventions should be directed toward younger patients, females and patients with unsuppressed viral loads.

A phase I randomized study to evaluate safety, pharmacokinetics, and pharmacodynamics of SIR2446M, a selective RIPK1 inhibitor, in healthy participants.

Activation of receptor-interacting protein kinase 1 (RIPK1), a broadly expressed serine/threonine protein kinase, by pro-inflammatory cytokines and pathogens can result in apoptosis, necroptosis, or inflammation. RIPK1 inhibition has been shown to reduce inflammation and cell damage in preclinical studies and may have therapeutic potential for degenerative and inflammatory diseases. SIR2446 is a potent and selective novel small molecule RIPK1 kinase inhibitor. This phase I, randomized, double-blind, placebo-controlled study in Australia (ACTRN12621001621808) evaluated the safety (primary objective), pharmacokinetics, and pharmacodynamics of single (3-600 mg) and multiple (5-400 mg for 10 days) ascending oral doses of SIR2446M (SIR2446 magnesium salt form) in healthy adults from Nov 24, 2021, until May 01, 2023. All treatment-emergent adverse events (TEAEs) were mild/moderate. The most reported TEAEs were vascular access site pain, headache, and rash morbilliform. SIR2446M plasma half-lives ranged from 11 to 19 h and there were no major deviations from dose proportionality for maximum concentration and area under the curve across doses. Renal excretion of unchanged SIR2446 was minimal. No marked accumulation was observed (mean accumulation ratio, 1.2-1.6) after multiple daily doses. A high-fat meal mildly reduced the exposure but was not considered clinically significant. SIR2446M had a rapid and sustained inhibitory effect on the activity of RIPK1, with an overall 90% target engagement at repeated doses ranging from 30 to 400 mg in peripheral blood mononuclear cells ex vivo stimulated to undergo necroptosis. The favorable safety, pharmacokinetic, and pharmacodynamic profile of SIR2446M in healthy participants supports its further clinical development in patients with degenerative and inflammatory diseases.

A highly resolved network reveals the role of terrestrial herbivory in structuring aboveground food webs.

Comparative studies suggest remarkable similarities among food webs across habitats, including systematic changes in their structure with diversity and complexity (scale-dependence). However, historic aboveground terrestrial food webs (ATFWs) have coarsely grouped plants and insects such that these webs are generally small, and herbivory is disproportionately under-represented compared to vertebrate predator-prey interactions. Furthermore, terrestrial herbivory is thought to be structured by unique processes compared to size-structured feeding in other systems. Here, we present the richest ATFW to date, including approximately 580 000 feeding links among approximately 3800 taxonomic species, sourced from approximately 27 000 expert-vetted interaction records annotated as feeding upon one of six different resource types: leaves, flowers, seeds, wood, prey and carrion. By comparison to historical ATFWs and null ecological hypotheses, we show that our temperate forest web displays a potentially unique structure characterized by two properties: (i) a large fraction of carnivory interactions dominated by a small number of hyper-generalist, opportunistic bird and bat predators; and (ii) a smaller fraction of herbivory interactions dominated by a hyper-rich community of insects with variably sized but highly specific diets. We attribute our findings to the large-scale, even resolution of vertebrate, insect and plant guilds in our food web.This article is part of the theme issue 'Connected interactions: enriching food web research by spatial and social interactions'.

Insulin receptor orchestrates kidney antibacterial defenses.

Urinary tract infection (UTI) commonly afflicts people with diabetes. This augmented infection risk is partly due to deregulated insulin receptor (IR) signaling in the kidney collecting duct. The collecting duct is composed of intercalated cells (ICs) and principal cells (PCs). Evidence suggests that ICs contribute to UTI defenses. Here, we interrogate how IR deletion in ICs impacts antibacterial defenses against uropathogenic Escherichia coli. We also explore how IR deletion affects immune responses in neighboring PCs with intact IR expression. To accomplish this objective, we profile the transcriptomes of IC and PC populations enriched from kidneys of wild-type and IC-specific IR knock-out mice that have increased UTI susceptibility. Transcriptomic analysis demonstrates that IR deletion suppresses IC-integrated stress responses and innate immune defenses. To define how IR shapes these immune defenses, we employ murine and human kidney cultures. When challenged with bacteria, murine ICs and human kidney cells with deregulated IR signaling cannot engage central components of the integrated stress response-including activating transcriptional factor 4 (ATF4). Silencing ATF4 impairs NFkB activation and promotes infection. In turn, NFkB silencing augments infection and suppresses antimicrobial peptide expression. In diabetic mice and people with diabetes, collecting duct cells show reduced IR expression, impaired integrated stress response engagement, and compromised immunity. Collectively, these translational data illustrate how IR orchestrates collecting duct antibacterial responses and the communication between ICs and PCs.

Ecological drivers of ultraviolet colour evolution in snakes.

Ultraviolet (UV) colour patterns invisible to humans are widespread in nature. However, research bias favouring species with conspicuous colours under sexual selection can limit our assessment of other ecological drivers of UV colour, like interactions between predators and prey. Here we demonstrate widespread UV colouration across Western Hemisphere snakes and find stronger support for a predator defence function than for reproduction. We find that UV colouration has evolved repeatedly in species with ecologies most sensitive to bird predation, with no sexual dichromatism at any life stage. By modelling visual systems of potential predators, we find that snake conspicuousness correlates with UV colouration and predator cone number, providing a plausible mechanism for selection. Our results suggest that UV reflectance should not be assumed absent in "cryptically coloured" animals, as signalling beyond human visual capacities may be a key outcome of species interactions in many taxa for which UV colour is likely underreported.

Diabetes, hypertension, and other cardiovascular disease risk factors among adults in an urban underprivileged community in Bangalore city, India.

Aim: Diabetes and hypertension are major risk factors of cardiovascular disease, which is known to be the leading cause of global mortality in the world today. Studies have shown that the prevalence of these risk factors is on the rise, with the burden of diabetes alone increasing by 80% in the last two decades. Complications of diabetes and hypertension result in huge public health challenges for the country and catastrophic medical expenditures for families among the urban poor. Our study aims to estimate the prevalence of diabetes, hypertension, and other cardiovascular risk factors among adults in an urban underprivileged community of Bengaluru city. Objectives and Methods: A cross-sectional study was conducted over a period of 6 months where 2245 individuals aged 30 or older were interviewed using a structured interviewer-administered questionnaire used to capture sociodemographic details that assessed modifiable risk factors for diabetes and hypertension. Inclusion criteria for diabetes were considered if the random blood sugar reading was ≥200 mg/dL, whereas a diagnosis of hypertension was taken into consideration if the systolic blood pressure reading was ≥140 mmHg and/or diastolic blood pressure was ≥90 mmHg. Results: Among the 2245 participants that took part in the study, 15.5% were diabetics and 17.2% were hypertensive. There was a strong association of diabetes among consumers of alcohol, with more than one-third having a high prevalence of the disease (odds ratio (OR): 2.09, 95% confidence interval (95% CI): 1.1-3.9). More than half the population were consumers of junk food; the prevalence of diabetes in this group was 1.35 times higher than that in their counterparts (OR: 1.35, 95% CI: 1.0-1.8). A significant association of diabetes was also seen among those identified with central obesity (OR: 1.83, 95% CI: 1.4-2.5). One-third of the population who consumed alcohol were found to be diagnosed with hypertension (OR: 3.08, 95% CI: 1.6-5.9), and one-fifth of individuals who were regular consumers of junk food had a higher prevalence of hypertension (OR: 1.41, 95% CI: 1.1-1.8). A higher prevalence of hypertension was also seen among individuals with central obesity or a body mass index (BMI) of >30 (OR: 1.59, 95% CI: 1.2-2.1; OR: 1.92, 95% CI: 1.4-2.6). Conclusion: The findings from our study conducted in an urban underprivileged area of Bengaluru city shed light on the significant associations between diabetes and hypertension and various demographic and lifestyle factors. Specifically, male gender and lower educational status were found to have a significant association with diabetes, whereas being unmarried and having a high BMI status were strongly linked to hypertension. In addition, the study revealed that elderly individuals, alcohol consumers, junk food eaters, and those with central obesity demonstrated an increased risk for both diabetes and hypertension. By identifying these risk factors, targeted interventions can be developed to address the unique challenges faced by this vulnerable section of society. Strategies can be designed to raise awareness, encourage healthier lifestyle choices, and improve access to healthcare services to effectively prevent and manage diabetes and hypertension in this community.

Hydrodynamic and thermodynamic analysis of PEGylated human serum albumin.

Covalent labeling of therapeutic drugs and proteins with polyethylene glycol (PEGylation) is an important modification for improving stability, solubility, and half-life. PEGylation alters protein solution behavior through its impact on thermodynamic nonideality by increasing the excluded volume, and on hydrodynamic nonideality by increasing the frictional drag. To understand PEGylation's impact, we investigated the thermodynamic and hydrodynamic properties of a model system consisting of PEGylated human serum albumin derivatives using analytical ultracentrifugation (AUC) and dynamic light scattering (DLS). We constructed PEGylated human serum albumin derivatives of single, linear 5K, 10K, 20K, and 40K PEG chains and a single branched-chain PEG of 40K (2 × 20K). Sedimentation velocity (SV) experiments were analyzed using SEDANAL direct boundary fitting to extract ideal sedimentation coefficients so, hydrodynamic nonideality ks, and thermodynamic nonideality 2BM1SV terms. These quantities allow the determination of the Stokes radius Rs, the frictional ratio f/fo, and the swollen or entrained volume Vs/v, which measure size, shape, and solvent interaction. We performed sedimentation equilibrium experiments to obtain independent measurements of thermodynamic nonideality 2BM1SE. From DLS measurements, we determined the interaction parameter, kD, the concentration dependence of the apparent diffusion coefficient, D, and from extrapolation of D to c = 0 a second estimate of Rs. Rs values derived from SV and DLS measurements and ensemble model calculations (see complementary study) are then used to show that ks + kD = theoretical 2B22M1. In contrast, experimental BM1 values from SV and sedimentation equilibrium data collectively allow for similar analysis for protein-PEG conjugates and show that ks + kD = 1.02-1.07∗BM1, rather than the widely used ks + kD = 2BM1 developed for hard spheres. The random coil behavior of PEG dominates the colloidal properties of PEG-protein conjugates and exceeds the sum of a random coil and hard-sphere volume due to excess entrained water.

Plasticity of Gene Expression and Thermal Tolerance: Implications for Climate Change Vulnerability in a Tropical Forest Lizard.

AbstractTropical ectotherms are thought to be especially vulnerable to climate change because they have evolved in temporally stable thermal environments and therefore have decreased tolerance for thermal variability. Thus, they are expected to have narrow thermal tolerance ranges, live close to their upper thermal tolerance limits, and have decreased thermal acclimation capacity. Although models often predict that tropical forest ectotherms are especially vulnerable to rapid environmental shifts, these models rarely include the potential for plasticity of relevant traits. We measured phenotypic plasticity of thermal tolerance and thermal preference as well as multitissue transcriptome plasticity in response to warmer temperatures in a species that previous work has suggested is highly vulnerable to climate warming, the Panamanian slender anole lizard (Anolis apletophallus). We found that many genes, including heat shock proteins, were differentially expressed across tissues in response to short-term warming. Under long-term warming, the voluntary thermal maxima of lizards also increased, although thermal preference exhibited only limited plasticity. Using these data, we modeled changes in the activity time of slender anoles through the end of the century under climate change and found that plasticity should delay declines in activity time by at least two decades. Our results suggest that slender anoles, and possibly other tropical ectotherms, can alter the expression of genes and phenotypes when responding to shifting environmental temperatures and that plasticity should be considered when predicting the future of organisms under a changing climate.

Understanding Breast Cancer Images in Art History as a Form of Health Communication.

Can art and visual images meant for public consumption (museums, galleries, social media platforms) serve as a critical form of health communication for breast cancer patients? For their clinicians? For the population at large? Art history research methods are applied to a range of breast cancer images in western art in order to understand what the images communicate to us about patient experience, agency, and inequity in health care at the time of their construction. The following is a selective look at western art as it reflects and informs our understanding of breast cancer over time.

Allergic bronchopulmonary aspergillosis in a lung transplant recipient treated with mepolizumab.

Allergic bronchopulmonary aspergillosis (ABPA) is a complex hypersensitivity reaction to Aspergillus spp. ABPA diagnosis may be challenging due to its non-specific presentation. Standard ABPA treatment consists of systemic corticosteroids and antifungal agents. Mepolizumab, a monoclonal antibody against interleukin-5 seems to be a promising treatment for ABPA. Data about ABPA following lung transplantation (LuTx) are scarce. LuTx recipients are at higher risk for adverse effects of ABPA treatment compared to the general population. Here we present a case of a LuTx recipient who was successfully treated with mepolizumab for ABPA following LuTx. Prolonged administration of high dose prednisone was thus avoided. To our knowledge, this is the first case describing mepolizumab administration following LuTx. Mepolizumab seems particularly attractive as a corticosteroid-sparing agent or as an alternative option to antifungal treatments, because of its excellent safety profile and low risk of drug interactions.

Outcome of tenoscopically guided palmar/plantar annular ligament desmotomy for the treatment of palmar/plantar annular ligament constriction without concurrent intrathecal soft-tissue injury in a UK horse population.

OBJECTIVE: To determine the outcome of tenoscopically guided palmar/plantar annular ligament (PAL) desmotomy to treat PAL constriction without concurrent intrathecal soft-tissue injury, notably of the digital flexor tendons and manica flexoria. STUDY DESIGN: Retrospective multicenter cohort study. ANIMALS: Sixty-five horses. METHODS: Horses from four UK equine hospitals, with digital flexor tendon sheath (DFTS) tenosynovitis, which underwent tenoscopically guided PAL desmotomy for treatment of PAL constriction between 2017 and 2022 were included. All horses had lameness isolated to the DFTS/PAL, and PAL constriction was diagnosed tenoscopically when there was difficulty maneuvering the endoscope into or through the fetlock canal. Horses with tearing of the digital flexor tendons and/or manica flexoria, or any other intrathecal pathology, were excluded. Follow up was via structured telephone questionnaire. RESULTS: Follow up (median 25 months) was available for 61 horses with cobs and ponies predominating. Forty-two returned to their previous level of work, or a higher level, postoperatively and 50 owners were satisfied with the outcome of surgery. Eleven horses returned to lower level exercise, and six were retired/euthanized as they did not regain soundness. Fifty-two horses achieved soundness (median 3 months postoperatively). CONCLUSION: Tenoscopically guided PAL desmotomy for the treatment of PAL constriction in the absence of intrathecal soft tissue injury had a good prognosis for return to previous levels of exercise in a UK horse population. CLINICAL SIGNIFICANCE: The prognosis for horses undergoing tenoscopically guided PAL desmotomy to treat PAL constriction in the absence of intrathecal injury is better than previously described. Cobs and ponies seem to be predisposed to PAL constriction in agreement with the previous literature.

Current and emerging strategies to curb antibiotic-resistant urinary tract infections.

Rising rates of antibiotic resistance in uropathogenic bacteria compromise patient outcomes and prolong hospital stays. Consequently, new strategies are needed to prevent and control the spread of antibiotic resistance in uropathogenic bacteria. Over the past two decades, sizeable clinical efforts and research advances have changed urinary tract infection (UTI) treatment and prevention strategies to conserve antibiotic use. The emergence of antimicrobial stewardship, policies from national societies, and the development of new antimicrobials have shaped modern UTI practices. Future UTI management practices could be driven by the evolution of antimicrobial stewardship, improved and readily available diagnostics, and an improved understanding of how the microbiome affects UTI. Forthcoming UTI treatment and prevention strategies could employ novel bactericidal compounds, combinations of new and classic antimicrobials that enhance bacterial killing, medications that prevent bacterial attachment to uroepithelial cells, repurposing drugs, and vaccines to curtail the rising rates of antibiotic resistance in uropathogenic bacteria and improve outcomes in people with UTI.

Murine Ribonuclease 6 Limits Bacterial Dissemination during Experimental Urinary Tract Infection.

INTRODUCTION: The ribonuclease (RNase) A superfamily encodes cationic antimicrobial proteins with potent microbicidal activity toward uropathogenic bacteria. Ribonuclease 6 (RNase6) is an evolutionarily conserved, leukocyte-derived antimicrobial peptide with potent microbicidal activity toward uropathogenic Escherichia coli (UPEC), the most common cause of bacterial urinary tract infections (UTIs). In this study, we generated Rnase6-deficient mice to investigate the hypothesis that endogenous RNase 6 limits host susceptibility to UTI. METHODS: We generated a Rnase6EGFP knock-in allele to identify cellular sources of Rnase6 and determine the consequences of homozygous Rnase6 deletion on antimicrobial activity and UTI susceptibility. RESULTS: We identified monocytes and macrophages as the primary cellular sources of Rnase6 in bladders and kidneys of Rnase6EGFP/+ mice. Rnase6 deficiency (i.e., Rnase6EGFP/EGFP) resulted in increased upper urinary tract UPEC burden during experimental UTI, compared to Rnase6+/+ controls. UPEC displayed increased intracellular survival in Rnase6-deficient macrophages. CONCLUSION: Our findings establish that RNase6 prevents pyelonephritis by promoting intracellular UPEC killing in monocytes and macrophages and reinforce the overarching contributions of endogenous antimicrobial RNase A proteins to host UTI defense.

Chondronecrosis of the cricoid treated with hyperbaric oxygen therapy: A case series.

We present two cases of cricoid chondronecrosis treated with hyperbaric oxygen (HBO2) therapy. Both patients presented with biphasic stridor and dyspnea several weeks after an intubation event. Tracheostomy was ultimately performed for airway protection, followed by antibiotic treatment and outpatient HBO2 therapy. Both patients were decannulated within six months of presentation and after at least 20 HBO2 therapy sessions. Despite a small sample size, our findings are consistent with data supporting HBO2 therapy's effects on tissue edema, neovascularization, and HBO2 potentiation of antibiotic treatment and leukocyte function. We suggest HBO2 therapy may have accelerated airway decannulation by way of infection resolution as well as the revitalization of upper airway tissues, ultimately renewing the structural integrity of the larynx. When presented with this rare but significant clinical challenge, physicians should be aware of the potential benefits of HBO2 therapy.

Intravenous Versus Subcutaneous Infliximab in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Subcutaneous (SC) infliximab may provide multiple benefits over intravenous (IV) formulations. However, studies for efficacy and safety in inflammatory bowel disease (IBD) have been constrained by small sizes that limit the interpretation of outcomes, especially for subgroups potentially at high-risk of disease relapse. METHODS: We conducted a systematic review and random-effects meta-analysis up to January 2023 to evaluate the change in clinical remission after transitioning from IV to SC infliximab in patients with IBD in clinical remission. The primary outcome was measured using the relative risk for meta-analysis. RESULTS: 15 studies of patients established ≥3 months on IV infliximab were identified, consisting of 1371 patients and 840 patient-years of follow-up. There was no loss of clinical remission in the IBD cohort overall, Crohn's disease (CD), and perianal CD p=0.55 & p=0.11 at 9-12 months, and p=0.50 at 6 months respectively). Neither prior IV dose (≤10mg/kg 6-weekly) (p=0.48) nor IBD disease subtype was associated with an increased clinical relapse rate at 6 months (p=0.48 and p=0.45 (UC vs CD), respectively). CONCLUSION: Changing patients established on IV infliximab to an SC formulation is associated with a high ongoing clinical remission and low adverse event rate. Furthermore, there are no signals for adverse outcomes among different IBD disease subtypes, nor in those on escalated IV infliximab dosing schedules up to 10mg/kg 6-weekly. This data should provide patients and clinicians alike with confidence in SC infliximab use in IBD.

Impact of SARS-CoV-2 vaccines on Covid-19 incidence and mortality in the United States.

BACKGROUND: Given the waning of vaccine effectiveness and the shifting of the most dominant strains in the U.S., it is imperative to understand the association between vaccination coverage and Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) disease and mortality at the community levels and whether that association might vary according to the dominant SARS-CoV-2 strains in the U.S. METHODS: Generalized estimating equations were used to estimate associations between U.S. county-level cumulative vaccination rates and booster distribution and the daily change in county-wide Coronavirus 2019 disease (COVID-19) risks and mortality during Alpha, Delta and Omicron predominance. Models were adjusted for potential confounders at both county and state level. A 2-week lag and a 4-week lag were introduced to assess vaccination rate impact on incidence and mortality, respectively. RESULTS: Among 3,073 counties in 48 states, the average county population complete vaccination rate of all age groups was 50.79% as of March 11th, 2022. Each percentage increase in vaccination rates was associated with reduction of 4% (relative risk (RR) 0.9607 (95% confidence interval (CI): 0.9553, 0.9661)) and 3% (RR 0.9694 (95% CI: 0.9653, 0.9736)) in county-wide COVID-19 cases and mortality, respectively, when Alpha was the dominant variant. The associations between county-level vaccine rates and COVID-19 incidence diminished during the Delta and Omicron predominance. However, each percent increase in people receiving a booster shot was associated with reduction of 6% (RR 0.9356 (95% CI: 0.9235, 0.9479)) and 4% (RR 0.9595 (95% CI: 0.9431, 0.9761)) in COVID-19 incidence and mortality in the community, respectively, during the Omicron predominance. CONCLUSIONS: Associations between complete vaccination rates and COVID-19 incidence and mortality appeared to vary with shifts in the dominant variant, perhaps due to variations in vaccine efficacy by variant or to waning vaccine immunity over time. Vaccine boosters were associated with notable protection against Omicron disease and mortality.

Age-Dependent RGS5 Loss in Pericytes Induces Cardiac Dysfunction and Fibrosis.

BACKGROUND: Pericytes are capillary-associated mural cells involved in the maintenance and stability of the vascular network. Although aging is one of the main risk factors for cardiovascular disease, the consequences of aging on cardiac pericytes are unknown. METHODS: In this study, we have combined single-nucleus RNA sequencing and histological analysis to determine the effects of aging on cardiac pericytes. Furthermore, we have conducted in vivo and in vitro analysis of RGS5 (regulator of G-protein signaling 5) loss of function and finally have performed pericytes-fibroblasts coculture studies to understand the effect of RGS5 deletion in pericytes on the neighboring fibroblasts. RESULTS: Aging reduced the pericyte area and capillary coverage in the murine heart. Single-nucleus RNA sequencing analysis further revealed that the expression of Rgs5 was reduced in cardiac pericytes from aged mice. In vivo and in vitro studies showed that the deletion of RGS5 impaired cardiac function, induced fibrosis, and morphological changes in pericytes characterized by a profibrotic gene expression signature and the expression of different ECM (extracellular matrix) components and growth factors, for example, TGFB2 and PDGFB. Indeed, culturing fibroblasts with the supernatant of RGS5-deficient pericytes induced their activation as evidenced by the increased expression of αSMA (alpha smooth muscle actin) in a TGFß (transforming growth factor beta)2-dependent mechanism. CONCLUSIONS: Our results have identified RGS5 as a crucial regulator of pericyte function during cardiac aging. The deletion of RGS5 causes cardiac dysfunction and induces myocardial fibrosis, one of the hallmarks of cardiac aging.

Urinary Tract Infections in Children.

Despite the American Academy of Pediatrics guidelines for the evaluation, treatment, and management of urinary tract infections (UTIs), UTI diagnosis and management remains challenging for clinicians. Challenges with acute UTI management stem from vague presenting signs and symptoms, diagnostic uncertainty, limitations in laboratory testing, and selecting appropriate antibiotic therapy in an era with increasing rates of antibiotic-resistant uropathogens. Recurrent UTI management remains difficult due to an incomplete understanding of the factors contributing to UTI, when to assess a child with repeated infections for kidney and urinary tract anomalies, and limited prevention strategies. To help reduce these uncertainties, this review provides a comprehensive overview of UTI epidemiology, risk factors, diagnosis, treatment, and prevention strategies that may help pediatricians overcome the challenges associated with acute and recurrent UTI management.

Thyroid Cancer Prevalence, Risk Exposure, and Clinical Features Among Transgender Female Veterans.

Purpose: Transgender women experience higher-than-average rates of multiple medical conditions. Thyroid cancer occurs more frequently in those assigned female at birth than in those assigned male at birth. We sought to characterize thyroid cancer among transgender female veterans. Methods: We reviewed charts of veterans who were (1) seen in Veterans Affairs clinics across the United States from July 2017 to December 2022, (2) had an International Classification of Diseases, revision 10, diagnosis code for thyroid cancer, and (3) had an International Classification of Diseases, revision 10, diagnosis code for gender dysphoria or were assigned male at birth and ever had a prescription for estrogens. Charts of cisgender veterans were also reviewed for comparison. Results: Compared with calculated estimates of 0.641% (95% CI, 0.572-0.724) among cisgender females and 0.187% (95% CI, 0.156-0.219) among cisgender males, the measured prevalence among transgender female veterans was 0.341% (34/9988). Average age at thyroid cancer diagnosis in this population was 53.8 (± SEM 2.61) years. A total of 32.3% (11/34) of these patients had extrathyroidal disease at diagnosis. Discussion: To our knowledge, this study represents the first report of thyroid cancer prevalence among transgender women in the United States. Risk exposure among all transgender veterans including further assessment of the possible contributions of obesity, smoking, and gender-affirming hormone therapy are important future analyses.