The Impact of Glucomannan, Inulin, and Psyllium Supplementation (SolowaysTM) on Weight Loss in Adults with FTO, LEP, LEPR, and MC4R Polymorphisms: A Randomized, Double-Blind, Placebo-Controlled Trial.

This study aimed to determine the impact of a fiber supplement on body weight and composition in individuals with obesity with specific genetic polymorphisms. It involved 112 adults with obesity, each with at least one minor allele in the FTO, LEP, LEPR, or MC4R polymorphism. Participants were randomized to receive either a fiber supplement (glucomannan, inulin, and psyllium) or a placebo for 180 days. The experimental group showed significant reductions in body weight (treatment difference: -4.9%; 95% CI: -6.9% to -2.9%; p < 0.01) and BMI (treatment difference: -1.4 kg/m2; 95% CI: -1.7 to -1.2; p < 0.01) compared to placebo. Further significant decreases in fat mass (treatment difference: -13.0%; 95% CI: -14.4 to -11.7; p < 0.01) and visceral fat rating (treatment difference: -1.3; 95% CI: -1.6 to -1.0; p < 0.01) were noted. Homozygous minor allele carriers experienced greater decreases in body weight (treatment difference: -3.2%; 95% CI: -4.9% to -1.6%; p < 0.01) and BMI (treatment difference: -1.2 kg/m2; 95% CI: -2.0 to -0.4; p < 0.01) compared to heterozygous allele carriers. These carriers also had a more significant reduction in fat mass (treatment difference: -9.8%; 95% CI: -10.6 to -9.1; p < 0.01) and visceral fat rating (treatment difference: -0.9; 95% CI: -1.3 to -0.5; p < 0.01). A high incidence of gastrointestinal events was reported in the experimental group (74.6%), unlike the placebo group, which reported no side effects. Dietary supplementation with glucomannan, inulin, and psyllium effectively promotes weight loss and improves body composition in individuals with obesity, particularly those with specific genetic polymorphisms.

COVID-19-Related Age Profiles for SARS-CoV-2 Variants in England and Wales and States of the USA (2020 to 2022): Impact on All-Cause Mortality.

Since 2020, COVID-19 has caused serious mortality around the world. Given the ambiguity in establishing COVID-19 as the direct cause of death, we first investigate the effects of age and sex on all-cause mortality during 2020 and 2021 in England and Wales. Since infectious agents have their own unique age profile for death, we use a 9-year time series and several different methods to adjust single-year-of-age deaths in England and Wales during 2019 (the pre-COVID-19 base year) to a pathogen-neutral single-year-of-age baseline. This adjusted base year is then used to confirm the widely reported higher deaths in males for most ages above 43 in both 2020 and 2021. During 2020 (+COVID-19 but no vaccination), both male and female population-adjusted deaths significantly increased above age 35. A significant reduction in all-cause mortality among both males and females aged 75+ could be demonstrated in 2021 during the widespread COVID-19 vaccination period; however, deaths below age 75 progressively increased. This finding arises from a mix of vaccination coverage and year-of-age profiles of deaths for the different SARS-CoV-2 variants. In addition, specific effects of age around puberty were demonstrated, where females had higher deaths than males. There is evidence that year-of-birth cohorts may also be involved, indicating that immune priming to specific pathogen outbreaks in the past may have led to lower deaths for some birth cohorts. To specifically identify the age profile for the COVID-19 variants from 2020 to 2023, we employ the proportion of total deaths at each age that are potentially due to or 'with' COVID-19. The original Wuhan strain and the Alpha variant show somewhat limited divergence in the age profile, with the Alpha variant shifting to a moderately higher proportion of deaths below age 84. The Delta variant specifically targeted individuals below age 65. The Omicron variants showed a significantly lower proportion of overall mortality, with a markedly higher relative proportion of deaths above age 65, steeply increasing with age to a maximum around 100 years of age. A similar age profile for the variants can be seen in the age-banded deaths in US states, although they are slightly obscured by using age bands rather than single years of age. However, the US data shows that higher male deaths are greatly dependent on age and the COVID variant. Deaths assessed to be 'due to' COVID-19 (as opposed to 'involving' COVID-19) in England and Wales were especially overestimated in 2021 relative to the change in all-cause mortality. This arose as a by-product of an increase in COVID-19 testing capacity in late 2020. Potential structure-function mechanisms for the age-specificity of SARS-CoV-2 variants are discussed, along with potential roles for small noncoding RNAs (miRNAs). Using data from England, it is possible to show that the unvaccinated do indeed have a unique age profile for death from each variant and that vaccination alters the shape of the age profile in a manner dependent on age, sex, and the variant. The question is posed as to whether vaccines based on different variants carry a specific age profile.

Evaluating the Impact of Omega-3 Fatty Acid (SolowaysTM) Supplementation on Lipid Profiles in Adults with PPARG Polymorphisms: A Randomized, Double-Blind, Placebo-Controlled Trial.

Emerging evidence suggests that PPARG gene polymorphisms may influence lipid metabolism and cardiovascular risk, with omega-3 fatty acids proposed to modulate these effects. This study aims to assess the effects of fish oil supplementation on cardiovascular markers among adults with PPARG gene polymorphisms in a randomized, double-blind, placebo-controlled trial. A cohort of 102 patients with LDL-C 70-190 mg/dL was randomized to receive either 2000 mg of omega-3 fatty acids or a placebo daily for 90 days. In the omega-3 group with PPARG polymorphisms, LDL-C was reduced by 15.4% (95% CI: -19.8% to -11.0%), compared with a 2.6% decrease in the placebo group (95% CI: -4.1% to -1.1%; p < 0.01). In the omega-3 group without PPARG polymorphisms, LDL-C was reduced by 3.7% (95% CI: -6.9% to -0.6%), not significantly different from the placebo group's reduction of 2.9% (95% CI: -5.1% to -0.8%; p = 0.28). The reduction in LDL-C was notably 11.7% greater in those with PPARG polymorphisms than in those without (95% CI: -19.3% to -4.0%; p < 0.01). Triglycerides decreased by 21.3% in omega-3 recipients with PPARG polymorphisms (95% CI: -26.5% to -16.2%; p < 0.01), with no significant changes in HDL-C, total cholesterol, or hsCRP levels in any groups. Minor allele frequencies and baseline characteristics were comparable, ensuring a balanced genetic representation. Omega-3 fatty acids significantly reduce LDL-C and triglycerides in carriers of PPARG polymorphisms, underlining the potential for genetic-driven personalization of cardiovascular interventions.

Roles for Pathogen Interference in Influenza Vaccination, with Implications to Vaccine Effectiveness (VE) and Attribution of Influenza Deaths.

Pathogen interference is the ability of one pathogen to alter the course and clinical outcomes of infection by another. With up to 3000 species of human pathogens the potential combinations are vast. These combinations operate within further immune complexity induced by infection with multiple persistent pathogens, and by the role which the human microbiome plays in maintaining health, immune function, and resistance to infection. All the above are further complicated by malnutrition in children and the elderly. Influenza vaccination offers a measure of protection for elderly individuals subsequently infected with influenza. However, all vaccines induce both specific and non-specific effects. The specific effects involve stimulation of humoral and cellular immunity, while the nonspecific effects are far more nuanced including changes in gene expression patterns and production of small RNAs which contribute to pathogen interference. Little is known about the outcomes of vaccinated elderly not subsequently infected with influenza but infected with multiple other non-influenza winter pathogens. In this review we propose that in certain years the specific antigen mix in the seasonal influenza vaccine inadvertently increases the risk of infection from other non-influenza pathogens. The possibility that vaccination could upset the pathogen balance, and that the timing of vaccination relative to the pathogen balance was critical to success, was proposed in 2010 but was seemingly ignored. Persons vaccinated early in the winter are more likely to experience higher pathogen interference. Implications to the estimation of vaccine effectiveness and influenza deaths are discussed.

Impact of anticoagulation strategy after left atrial appendage occlusion in patients requiring direct current cardioversion.

INTRODUCTION: Current guidelines recommend adequate anticoagulation for at least 3 weeks pre- and 4 weeks post-direct current cardioversion (DCCV) to reduce thrombo-embolic risk in patients with atrial fibrillation (AF) lasting greater than 48 h. No specific recommendations exist for DCCV in patients that have undergone left atrial appendage occlusion (LAAO), many of whom are ineligible for anticoagulation. This study aims to observe the efficacy and safety of DCCV post-LAAO in everyday clinical practice. METHODS: This prospective multicenter registry included DCCVs in patients post-LAAO. Imaging strategy or anticoagulation treatment around DCCV were analyzed. Complications during 30-day follow-up were registered. DCCVs performed in accordance with current guidelines for the general AF population were compared to DCCVs performed deviating from these guidelines. RESULTS: In 93 patients (age 65 ± 17 years, CHA2 DS2 -VASC 3.0 ± 1.3) 284 DCCVs were performed between 2010 and 2018, in 271 sinus rhythm was restored. A wide variety of imaging or anticoagulation strategies around DCCV was observed; in 128 episodes strategies deviated from current guidelines. No thrombo-embolic events were observed after any DCCV during 30-day follow-up. In 34 DCCVs trans-esophageal echocardiography (TOE) was performed before DCCV to exclude cardiac thrombi and/or (re-)verify adequate device positioning. In two patients without post-LAAO imaging before DCCV, a device rotation or embolization was observed during scheduled TOE after LAAO. CONCLUSION: DCCV in AF patients after LAAO is highly effective. No thrombo-embolic events were observed in any patient in this observational cohort, regardless of the periprocedural anticoagulation or imaging strategy. Confirmation of adequate device positioning at least once before DCCV seems recommendable.