COVID-19 vaccine acceptance and uptake among caregivers of children aged 5-11 years in Ontario, Canada: A cross-sectional survey.

INTRODUCTION: Although COVID-19 vaccine safety in 5-11-year-old children has been documented, half of Ontarian children this age remain unvaccinated. This study aimed to assess caregivers' vaccine acceptance for 5-11-year-old children and identify factors associated with vaccine non-acceptance. METHODS: A multi-language self-administered survey was sent to caregivers of 5-11-year-old children through schools and community health centers within the Greater Toronto Area from April-July 2022. Sociodemographic characteristics and immunization behaviours were collected for caregivers, their 5-11-year-old children, and any older siblings. The primary outcome, COVID-19 vaccine acceptance, was previous uptake of COVID-19 vaccine or caregiver intent to vaccinate for their 5-11-year-old child. Data were analyzed using descriptive statistics and multivariable logistic regression. RESULTS: In total, 807 caregivers were included in analysis. Although 93 % of caregivers had received two doses of COVID-19 vaccine, 77 % had a 5-11-year-old child who received at least one dose of vaccine. Caregivers age was associated with vaccine acceptance (vs. < 40 years; adjusted odds ratio [aOR] 2.1, 95 % confidence interval [CI] 1.4-3.1 for ages 40-49; aOR 2.8, 95 % CI 1.1-7.1 for ages ≥50 years). Immunization factors associated with vaccine acceptance included caregiver COVID-19 vaccination (aOR 38.1 vs. unvaccinated caregivers; 95 % CI 15.8-92.3), older siblings COVID-19 vaccination (aOR 49.2 vs. unvaccinated siblings; 95 % CI 18.3-132.3), and recent influenza vaccination for the child (aOR 6.9 vs. no influenza vaccine; 95 % CI 4.6-10.5). Among 189 caregivers with unvaccinated 5-11-year-old children, the most common reasons for non-acceptance were concerns about long-term side effects (59 %), lack of experience vaccinating children (41 %), and concerns that vaccines were developed too quickly (39 %). CONCLUSION: Acceptance of COVID-19 vaccination for 5-11-year-old children were associated with caregiver vaccine behaviors and sociodemographic factors. These findings highlight groups of caregivers that can be targeted for educational interventions and concerns that may be addressed to increase vaccine confidence.

Association between physical fitness and executive functions in cognitively healthy female older adults: a cross-sectional study.

Cardiovascular endurance and muscular fitness seem to impact specific cognitive components in older females. However, it remains uncertain whether these relate to executive functions or if these correlations are limited to specific physical fitness indicators. This study aimed to determine the association between specific physical fitness components and executive functions in community-dwelling older females. Thirty-five cognitively healthy community-dwelling older females (71.5 ± 5.7 years) underwent a series of physical fitness tests. These included the handgrip strength test (HGT), the 6-min walk test (6MWT), the 8-foot up-and-go test (8FUGT), and the chair stand test (CST). Participants also completed trail A and trail B of the cognitive trail making test. Results showed that trail B reaction time had a negative association with both HGT (r = - 0.502; p = 0.002) and 6MWT (r = - 0.543; p < 0.001). Together, the HGT and 6MWT results explained 39% of the variation in trail B reaction times: HGT accounted for 18% and 6MWT for 21%. Better scores on the 6MWT and HGT-but not on the 8FUGT and CST-correlated with enhanced executive function in cognitively healthy community-dwelling older females. The results of this study underscore the importance of specific physical assessments, like the 6MWT and HGT, as potential indicators of executive function, offering targeted strategies for maintaining cognitive health in aging females.

Identification and Economic Evaluation of Differentiated Thyroid Cancer Care Consumption Patterns Using Sequence Analysis.

Objectives: This study aims to assess the impact of care consumption patterns and individual characteristics on the cost of treating differentiated thyroid carcinoma (DTC), in France, with a specific emphasis on socioeconomic position. Methods: The methodology involved a net cost approach utilising cases from the EVATHYR cohort and controls from the French National Health Insurance database. Care consumption patterns were created using Optimal Matching and clustering techniques. The individual characteristics influence on patterns was assessed using multinomial logistic regression. The individual characteristics and patterns influence on care costs was assessed using generalised estimating equations. Results: The findings revealed an average cost of €13,753 per patient during the initial 3 years. Regression models suggested the main predictors of high DTC specific care consumption tended to include having a high risk of cancer recurrence (OR = 4.97), being a woman (OR = 2.00), and experiencing socio-economic deprivation (OR = 1.26), though not reaching statistical significance. Finally, high DTC-specific care consumers also incurred higher general care costs (RR = 1.35). Conclusion: The study underscores the increased costs of managing DTC, shaped by consumption habits and socioeconomic position, emphasising the need for more nuanced DTC management strategies.

DEPDC5 protects CD8+ T cells from ferroptosis by limiting mTORC1-mediated purine catabolism.

Peripheral CD8+ T cell number is tightly controlled but the precise molecular mechanism regulating this process is still not fully understood. In this study, we found that epilepsy patients with loss of function mutation of DEPDC5 had reduced peripheral CD8+ T cells, and DEPDC5 expression positively correlated with tumor-infiltrating CD8+ T cells as well as overall cancer patient survival, indicating that DEPDC5 may control peripheral CD8+ T cell homeostasis. Significantly, mice with T cell-specific Depdc5 deletion also had reduced peripheral CD8+ T cells and impaired anti-tumor immunity. Mechanistically, Depdc5-deficient CD8+ T cells produced high levels of xanthine oxidase and lipid ROS due to hyper-mTORC1-induced expression of ATF4, leading to spontaneous ferroptosis. Together, our study links DEPDC5-mediated mTORC1 signaling with CD8+ T cell protection from ferroptosis, thereby revealing a novel strategy for enhancing anti-tumor immunity via suppression of ferroptosis.

Lasers in the management of alopecia: a review of established therapies and advances in treatment.

Alopecia, also known as hair loss, is a highly prevalent condition affecting millions of men and women in the United States and worldwide, making it one of the most common complaints by patients presenting to a dermatologist. The symptomology on the presentation of alopecia can be highly variable, ranging from diffuse thinning of hair, discrete and localized patches completely absent of hair, or noticing significant shedding when brushing and showering. Although alopecia does not have a direct negative health impact on patients, it is nonetheless a debilitating disease as it can profoundly impact an individual's self-image and psychosocial well-being. There are multiple treatment options available to patients with alopecia, and they are typically tailored to the patient's needs and preferences. The most common of these is the Food and Drug Administration-approved drugs for alopecia, minoxidil, and finasteride. However, both of these are known to be partially efficacious for all patients, so clinicians often use different modalities in conjunction with them, in particular laser-based therapies. This review article will provide a comprehensive assessment of lasers and other light therapies that may be used to manage the two most common types of alopecia: androgenetic alopecia and alopecia areata.

Detection of OXA-181 Carbapenemase in Shigella flexneri.

We report the detection of OXA-181 carbapenemase in an azithromycin-resistant Shigella spp. bacteria in an immunocompromised patient. The emergence of OXA-181 in Shigella spp. bacteria raises concerns about the global dissemination of carbapenem resistance in Enterobacterales and its implications for the treatment of infections caused by Shigella bacteria.

Renal tubule-specific Atgl deletion links kidney lipid metabolism to glucagon-like peptide 1 and insulin secretion independent of renal inflammation or lipotoxicity.

OBJECTIVE: Lipotoxic injury from renal lipid accumulation in obesity and type 2 diabetes (T2D) is implicated in associated kidney damage. However, models examining effects of renal ectopic lipid accumulation independent of obesity or T2D are lacking. We generated renal tubule-specific adipose triglyceride lipase knockout (RT-SAKO) mice to determine if this targeted triacylglycerol (TAG) over-storage affects glycemic control and kidney health. METHODS: Male and female RT-SAKO mice and their control littermates were tested for changes in glycemic control at 10-12 and 16-18 weeks of age. Markers of kidney health and blood lipid and hormone concentrations were analyzed. Kidney and blood lysophosphatidic acid (LPA) levels were measured, and a role for LPA in mediating impaired glycemic control was evaluated using the LPA receptor 1/3 inhibitor Ki-16425. RESULTS: All groups remained insulin sensitive, but 16- to 18-week-old male RT-SAKO mice became glucose intolerant, without developing kidney inflammation or fibrosis. Rather, these mice displayed lower circulating insulin and glucagon-like peptide 1 (GLP-1) levels. Impaired first-phase glucose-stimulated insulin secretion was detected and restored by Exendin-4. Kidney and blood LPA levels were elevated in older male but not female RT-SAKO mice, associated with increased kidney diacylglycerol kinase epsilon. Inhibition of LPA-mediated signaling restored serum GLP-1 levels, first-phase insulin secretion, and glucose tolerance. CONCLUSIONS: TAG over-storage alone is insufficient to cause renal tubule lipotoxicity. This work is the first to show that endogenously derived LPA modulates GLP-1 levels in vivo, demonstrating a new mechanism of kidney-gut-pancreas crosstalk to regulate insulin secretion and glucose homeostasis.

Single-cell RNA-sequencing of PBMCs from SAVI patients reveals disease-associated monocytes with elevated integrated stress response.

Gain-of-function mutations in stimulator of interferon gene 1 (STING1) result in STING-associated vasculopathy with onset in infancy (SAVI), a severe autoinflammatory disease. Although elevated type I interferon (IFN) production is thought to be the leading cause of the symptoms observed in patients, STING can induce a set of pathways, which have roles in the onset and severity of SAVI and remain to be elucidated. To this end, we performed a multi-omics comparative analysis of peripheral blood mononuclear cells (PBMCs) and plasma from SAVI patients and healthy controls, combined with a dataset of healthy PBMCs treated with IFN-ß. Our data reveal a subset of disease-associated monocyte, expressing elevated CCL3, CCL4, and IL-6, as well as a strong integrated stress response, which we suggest is the result of direct PERK activation by STING. Cell-to-cell communication inference indicates that these monocytes lead to T cell early activation, resulting in their senescence and apoptosis. Last, we propose a transcriptomic signature of STING activation, independent of type I IFN response.

Case Report: Coronaro-bronchial fistula vascularizing a squamous cell lung cancer.

Coronary fistulas are rare, having been described for the first time by Krauss in 1865 in postmortem. They are commonly asymptomatic and can be caused by congenital or acquired malformations. We present the case of a 65-year-old patient who was treated for squamous cell lung cancer with chemoimmunotherapy and presented with angina. The coronary angiography showed a coronaro-bronchial fistula that arises from a branch of the right coronary artery and is associated with lung cancer.

Vascular Complications Following Transcatheter Aortic Valve Implantation, Using MANTA (Collagen Plug-Based) versus PROSTAR (Suture-Based), from a French Single-Center Retrospective Registry.

TAVI requires a large-bore arteriotomy. Closure is usually performed by the suture system. Some studies report a vascular complication rate of up to 21%. MANTA is a recently developed percutaneous closure system dedicated to large caliber vessels based on an anchoring system. Early studies report a lower rate of vascular complications with MANTA devices. This single-center retrospective study included all patients who underwent femoral TAVI at the Brest University Hospital from 20 November 2019 to 31 March 2021. The primary endpoint is the rate of vascular complications (major and minor) pre and post-TAVI procedure. In total, 264 patients were included. There were no significant differences in vascular complications (major and minor) between the two groups (13.6% in the MANTA group versus 21.2% in the PROSTAR group; p = 0.105), although there was a tendency to have fewer minor vascular complications in the Manta group (12.1% versus 20.5%; p = 0.067). Manta was associated with a lower rate of bleeding complications (3.8% versus 15.2%; p = 0.002), predominantly minor complications with fewer closure failures (4.5% versus 13.6%; p = 0.01), less use of covered stents (4.5% versus 12.9%; p = 0.016), and with no difference in the need for vascular surgery compared to the Prostar group (1.5% versus 2.3%; p = 0.652). On the other hand, Manta was associated with a higher rate of femoral stenosis (4.5% versus 0%; p = 0.013) without clinical significance (1.5% versus 0%; p = 0.156). The Manta and Prostar devices are equivalent in terms of vascular complications. The Manta, compared to the Prostar, is associated with fewer bleeding complications.

COVID-19 vaccine equity: a retrospective population-based cohort study examining primary series and first booster coverage among persons with a history of immigration and other residents of Ontario, Canada.

Introduction: Immigrants were disproportionately impacted by COVID-19 and experience unique vaccination barriers. In Canada (37 million people), 23% of the population is foreign-born. Immigrants constitute 60% of the country's racialized (non-white) population and over half of immigrants reside in Ontario, the country's most populous province. Ontario had several strategies aimed at improving vaccine equity including geographic targeting of vaccine supply and clinics, as well as numerous community-led efforts. Our objectives were to (1) compare primary series vaccine coverage after it was widely available, and first booster coverage 6 months after its availability, between immigrants and other Ontario residents and (2) identify subgroups experiencing low coverage. Materials and methods: Using linked immigration and health administrative data, we conducted a retrospective population-based cohort study including all community-dwelling adults in Ontario, Canada as of January 1, 2021. We compared primary series (two-dose) vaccine coverage by September 2021, and first booster (three-dose) coverage by March 2022 among immigrants and other Ontarians, and across sociodemographic and immigration characteristics. We used multivariable log-binomial regression to estimate adjusted risk ratios (aRR). Results: Of 11,844,221 adults, 22% were immigrants. By September 2021, 72.6% of immigrants received two doses (vs. 76.4%, other Ontarians) and by March 2022 46.1% received three doses (vs. 58.2%). Across characteristics, two-dose coverage was similar or slightly lower, while three-dose coverage was much lower, among immigrants compared to other Ontarians. Across neighborhood SARS-CoV-2 risk deciles, differences in two-dose coverage were smaller in higher risk deciles and larger in the lower risk deciles; with larger differences across all deciles for three-dose coverage. Compared to other Ontarians, immigrants from Central Africa had the lowest two-dose (aRR = 0.60 [95% CI 0.58-0.61]) and three-dose coverage (aRR = 0.36 [95% CI 0.34-0.37]) followed by Eastern Europeans and Caribbeans, while Southeast Asians were more likely to receive both doses. Compared to economic immigrants, resettled refugees and successful asylum-claimants had the lowest three-dose coverage (aRR = 0.68 [95% CI 0.68-0.68] and aRR = 0.78 [95% CI 0.77-0.78], respectively). Conclusion: Two dose coverage was more equitable than 3. Differences by immigrant region of birth were substantial. Community-engaged approaches should be re-invigorated to close gaps and promote the bivalent booster.

Alternative Antimicrobial Irrigation Strategies for the Treatment of Infections in Children: A Review of the Existing Literature.

As a synergistic treatment approach with systemic antimicrobial therapy or a systemic antibiotic-sparing strategy, the local administration of antimicrobial agents has been proposed as an alternative route for complicated infections. With the rationale of concentrating the active principle in the desired target site, avoiding potentially toxic systemic levels and bypassing anatomical and physiological barriers, local irrigation or infusion of antibiotics may effectively shorten the antimicrobial therapy course and reduce both infection-related and systemic therapy-related complications. Although evidence from the adult population supports its use in selected patients with an acceptable safety profile, data specifically focused on the pediatric population are limited. To provide a rapid and easily accessible tool for clinical practice, we synthesized the most relevant evidence on the use of local antimicrobial agents in common severe infections in children: meningitis, mediastinitis, pleural infections, recurrent urinary infections, and peritonitis. A literature search was performed using predefined combined keywords through an electronic research database (PubMed). Described molecules, dosages, routes, treated age groups, and related efficacy have been summarized for prompt application to clinical practice. It should, however, be noted that the evidence for the pediatric population remains limited, and the local administration of several molecules remains off-label. A careful multidisciplinary and patient-tailored evaluation, as well as a rational use of available guidelines, should always be the basis of clinical decision making in settings where local administration of antibiotics may be considered.

Bacteria stretch and bend oil to feed their appetite.

Microbes reshape oil droplets to speed biodegradation.

Prevention and treatment of traumatic brain injury-related delirium: a systematic review.

BACKGROUND: Our systematic review examines the effectiveness and safety of non-pharmacologic and pharmacologic interventions in preventing or treating traumatic brain injury (TBI)-related delirium in acute care. METHODS: We searched four electronic databases (MEDLINE, EMBASE, CENTRAL/CDSR, and PsycINFO) to identify randomized controlled trials (RCTs), quasi-experimental, and observational studies. Eligible studies included adults with TBI, at least one comparator group, delirium as an outcome and took place in acute care. Two reviewers independently completed all study screening, data abstraction, and risk of bias assessment using the Cochrane risk of bias 2 tool for RCTs or risk of bias in non-randomized studies-of interventions tool for observational studies. We implemented the PROGRESS-Plus framework to describe social determinants of health (SDoH) reporting. RESULTS: We identified 20,022 citations, reviewed 301 in full text, and included eight studies in the descriptive synthesis. The mean age of study participants ranged from 32 to 62 years. 12.5% of included studies reported SDoH. Included studies had moderate-to-high risk of bias. Studies compared reorientation programs and an intervention bundle to usual care, but these interventions were not better than usual care in treating TBI-related delirium. Individual studies found that rosuvastatin and aripiprazole were more efficacious than placebo, and dexmedetomidine was more efficacious than propofol and haloperidol for preventing TBI-related delirium. No studies reported safety as the primary outcome. CONCLUSIONS: We identified efficacious pharmacologic interventions for preventing TBI-related delirium, but these studies were at moderate-to-high risk of bias, which limits our confidence in these findings. Future studies should incorporate safety outcomes, and a diverse study population, including older adults.

Agent based modeling in health care economics: examples in the field of thyroid cancer.

Although they remain little used in the field of Health Care Economics, Agent Based Models (ABM) are potentially powerful decision-making tools that open up great prospects. The reasons for this lack of popularity are essentially to be found in a methodology that should be further clarified. This article hence aims to illustrate the methodology by means of two applications to medical examples. The first example of ABM illustrates the construction of a Baseline Data Cohort by means of a Virtual Baseline Generator. The aim is to describe the prevalence of thyroid cancer in the French population over the long term according to different scenarios of evolution of this population. The second study considers a setting where the Baseline Data Cohort is an established cohort of (real) patients: the EVATHYR cohort. The aim of the ABM is to describe the long-term costs associated with different scenarios of thyroid cancer management. The results are evaluated using several simulation runs in order to observe the variability of simulations and to derive prediction intervals. The ABM approach is very flexible since several sources of data can be involved and a large variety of simulation models can be calibrated to generate observations according to different evolution scenarios.

Association between physical activity education and prescription during prenatal care and maternal and fetal health outcomes: a quasi-experimental study.

BACKGROUND: Physical activity (PA) during pregnancy is associated with healthy gestational weight gain (GWG) and a reduced risk of developing gestational diabetes (GD), gestational hypertension (GHT) and fetal macrosomia. However, in Canada, less than 20% of pregnant women meet PA recommendations. This study assessed associations between an intervention including PA education by prenatal nurses and a PA prescription delivered by physicians and fetal and maternal outcomes. METHODS: This is a quasi-experimental study. Two groups of women who received their prenatal care at the obstetrics clinic of a university hospital were created. In the first group, 394 pregnant women followed at the clinic received standard care. In the second group, 422 women followed at the clinic received standard care supplemented with education on the relevance of PA during pregnancy and a prescription for PA. Data for both study groups were obtained from the medical records of the mothers and their newborns. Logistic regressions were used to compare the odds of developing excessive GWG, GD, GHT, and fetal macrosomia between the two study groups. RESULTS: The addition of PA education and PA prescription to prenatal care was associated with 29% lower odds of developing excessive GWG (adjusted odds ratios (OR) 0.71, 95% confidence intervals (CI) 0.51-0.99), 73% lower odds of developing GHT (0.27, 0.14-0.53), 44% lower odds of fetal macrosomia (> 4 kg) (0.56, 0.34-0.93), and 40% lower odds of being large for gestational age (0.60, 0.36-0.99). The intervention was not associated with a difference in odds of developing GD (0.48, 0.12-1.94). CONCLUSIONS: The inclusion of education and prescription of PA as part of routine prenatal care was associated with improvements in maternal and fetal health outcomes, including significantly lower odds of GWG, GHT and macrosomia.