Search

Abstract Background We systematically reviewed Mendelian randomization (MR) studies and summarized evidence on the potential effects of different antihypertensive drugs on health. Methods We searched PubMed and Embase for MR studies evaluating the effects of antihypertensive drug classes on health outcomes until 22 May 2024. We extracted data on study characteristics and findings, assessed study quality, and compared the evidence with that from randomized controlled trials (RCTs). Results We identified 2643 studies in the search, of which 37 studies were included. These studies explored a wide range of health outcomes including cardiovascular diseases and their risk factors, psychiatric and neurodegenerative diseases, cancer, immune function and infection, and other outcomes. There is strong evidence supporting the protective effects of genetically proxied antihypertensive drugs on cardiovascular diseases. We found strong protective effects of angiotensin-converting enzyme (ACE) inhibitors on diabetes whereas beta-blockers showed adverse effects. ACE inhibitors might increase the risk of psoriasis, schizophrenia, and Alzheimer’s disease but did not affect COVID-19. There is strong evidence that ACE inhibitors and calcium channel blockers (CCBs) are beneficial for kidney and immune function, and CCBs showed a safe profile for disorders of pregnancy. Most studies have high quality. RCT evidence supports the beneficial effects of ACE inhibitors and CCBs on stroke, diabetes, and kidney function. However, there is a lack of reliable RCTs to confirm the associations with other diseases. Conclusions Evidence of the benefits and off-target effects of antihypertensive drugs contribute to clinical decision-making, pharmacovigilance, and the identification of drug repurposing opportunities.

Abstract We assessed the causal relation of four glycemic traits and type 2 diabetes liability with 167 metabolites using Mendelian randomization with various sensitivity analyses and a reverse Mendelian randomization analysis. We extracted instruments for fasting glucose, 2-h glucose, fasting insulin, and glycated hemoglobin from the Meta-Analyses of Glucose and Insulin-related traits Consortium (n = 200,622), and those for type 2 diabetes liability from a meta-analysis of multiple cohorts (148,726 cases, 965,732 controls) in Europeans. Outcome data were from summary statistics of 167 metabolites from the UK Biobank (n = 115,078). Fasting glucose and 2-h glucose were not associated with any metabolite. Higher glycated hemoglobin was associated with higher free cholesterol in small low-density lipoprotein. Type 2 diabetes liability and fasting insulin were inversely associated with apolipoprotein A1, total cholines, lipoprotein subfractions in high-density-lipoprotein and intermediate-density lipoproteins, and positively associated with aromatic amino acids. These findings indicate hyperglycemia-independent patterns and highlight the role of insulin in type 2 diabetes development. Further studies should evaluate these glycemic traits in type 2 diabetes diagnosis and clinical management.

Abstract Background Mental disorders are among the top causes of disease burden worldwide. Existing evidence regarding the repurposing of antihypertensives for mental disorders treatment is conflicting and cannot establish causation. Methods We used Mendelian randomization to assess the effects of angiotensin-converting-enzyme inhibitors (ACEIs), beta blockers (BBs), and calcium channel blockers (CCBs) on risk of bipolar disorder (BD), major depression disorder (MDD), and schizophrenia (SCZ). We used published genetic variants which are in antihypertensive drugs target genes and correspond to systolic blood pressure (SBP) in Europeans and East Asians, and applied them to summary statistics of BD (cases = 41,917; controls = 371,549 in Europeans), MDD (cases = 170,756; controls = 329,443 in Europeans and cases = 15,771; controls = 178,777 in East Asians), and SCZ (cases = 53,386; controls = 77,258 in Europeans and cases = 22,778; controls = 35,362 in East Asians) from the Psychiatric Genomics Consortium. We used inverse variance weighting with MR-Egger, weighted median, weighted mode, and Mendelian Randomization Pleiotropy RESidual Sum and Outlier. We performed gene-specific analysis and utilized various methods to address potential pleiotropy. Results After multiple testing correction, genetically proxied ACEIs were associated with an increased risk of SCZ in Europeans (odds ratio (OR) per 5 mmHg lower in SBP 2.10, 95% CI 1.54 to 2.87) and East Asians (OR per 5 mmHg lower in SBP 2.51, 95% CI 1.38 to 4.58). Genetically proxied BBs were not associated with any mental disorders in both populations. Genetically proxied CCBs showed no benefits on mental disorders. Conclusions Antihypertensive drugs have no protection for mental disorders but potential harm. Their long-term use among hypertensive patients with, or with high susceptibility to, psychiatric illness needs careful evaluation.

Аim: to present the difficulties of surgical treatment of patients with multiple and combined echinococcal lesions. Key points. A 47-year-old patient who lived in Central Asia for up to 29 years of age was diagnosed with multiple echinococcosis of the abdominal cavity (CE1-2): II, Ivb, V, VI, VII segments of the liver, upper and lower poles of the spleen, lesser and greater omentum, small intestine, subphrenic space, area of the hepatoduodenal ligament, gastrocolic ligament. Surgical intervention was performed: atypical resection of liver segments V, VI, VII, subtotal pericystectomy, cholecystectomy, subtotal pericystectomy of cysts of II and IVb liver segments, subtotal pericystectomy of splenic cysts, resection of the greater omentum, echinococcectomy of the lesser omentum, mesentery of the small intestine, hepatoduodenal ligament, gastrocolic ligament, drainage of the abdominal cavity. Pericystectomy was carried out according to the technique of the National Medical Research Center of Surgery named after A. Vishnevsky.Conclusion. Due to the peculiarities of the course of helminthiasis and the pronounced variability of the lesion, it is extremely difficult to develop universal and effective treatment algorithms. The presented clinical observation demonstrates an example of the successful use of special surgical tactics for the treatment of “complex” echinococcosis of the abdominal cavity with good long-term follow-up results.

Background: Few studies have examined the role of outdoor air pollution exposure in sarcopenia in Asia. We aimed to investigate the association of outdoor air pollutants exposure with sarcopenia among Chinese adults. Methods: This nationally population-representative study used data from the China Health and Retirement Longitudinal Study (CHARLS) in 2015, 11,700 participants at least 45 years old from 125 Chinese cities were included. Sarcopenia status was identified according to the Asian Working Group for Sarcopenia 2019 (AWGS 2019) criteria. Ambient annual average air pollutants including fine particulate matter (PM2.5), inhalable particles (PM10), coarse particulate matter (PMcoarse), nitrogen dioxide (NO2), sulfur dioxide (SO2), and carbon monoxide (CO) were estimated by satellite models and ground-based measurements. Multinomial logistic regression models were performed to examine the associations of air pollutants exposure with different status of sarcopenia (including possible sarcopenia and sarcopenia). Stratified analyses were utilized to assess the effect modifiers. Results: Among the 11,700 participants (52.6% women), the average age was 61.0 years. Each 10 μg/m3 increment of annual PMcoarse was associated with a higher risk of possible sarcopenia (odds ratio (OR) = 1.08, 95% confidence interval (CI) 1.04–1.11). Stratified analyses showed a positive risk of possible sarcopenia in women after exposure to PM10, PMcoarse, and NO2. Ambient NO2 exposure was positively associated with sarcopenia (OR = 1.13, 95% CI 1.04–1.22) in those aged 65 years and older. However, we have not observed differences by sex, age, residence, smoking, and drinking. Robustness results were found for PMcoarse in the sensitivity analyses. Conclusion: This nationwide study suggested that long-term exposure to outdoor air pollution, especially for PMcoarse, was associated with the risk of sarcopenia among Chinese adults. Our findings provide epidemiological implications for protecting healthy ageing by improving air quality.

Alzheimer's disease (AD) is the most common global dementia and is universally fatal. Most late-stage AD disease-modifying therapies are intravenous and target amyloid beta (Aβ), with only modest effects on disease progression: there remains a high unmet need for convenient, safe, and effective therapeutics. Senescent cells (SC) and the senescence-associated secretory phenotype (SASP) drive AD pathology and increase with AD severity. Preclinical senolytic studies have shown improvements in neuroinflammation, tau, Aβ, and CNS damage; most were conducted in transgenic rodent models with uncertain human translational relevance. In this study, aged cynomolgus monkeys had significant elevation of biomarkers of senescence, SASP, and neurological damage. Intermittent treatment with the senolytic navitoclax induced modest reversible thrombocytopenia; no serious drug-related toxicity was noted. Navitoclax reduced several senescence and SASP biomarkers, with CSF concentrations sufficient for senolysis. Finally, navitoclax reduced TSPO-PET frontal cortex binding and showed trends of improvement in CSF biomarkers of neuroinflammation, neuronal damage, and synaptic dysfunction. Overall, navitoclax administration was safe and well tolerated in aged monkeys, inducing trends of biomarker changes relevant to human neurodegenerative disease., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Edward Greenberg, MD reports financial support was provided by AbbVie Inc. Edward Greenberg MD reports a relationship with AbbVie Inc that includes: employment, equity or stocks, and funding grants. EFG, MV, AS, DRR, YZ, JQW, DWW, EA, MH, CH, RD, MT, KO, WA, LD, HK, JSS, YH, KM, VZ, SY, JM, YF, AV, SW, MD, SJF, and HF are employees of AbbVie and may hold stock. KD was an employee of AbbVie at the time of the study and may hold stock. The design, study conduct, and all funding for this research was provided by AbbVie, the maker of navitoclax (ABT-263). AbbVie participated in the interpretation of data, review, and approval of the publication. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Infectious disease dynamics are driven by the complex interplay of epidemiological, ecological, and evolutionary processes. Accurately modeling these interactions is crucial for understanding pathogen spread and informing public health strategies. However, existing simulators often fail to capture the dynamic interplay between these processes, resulting in oversimplified models that do not fully reflect real-world complexities in which the pathogen's genetic evolution dynamically influences disease transmission. We introduce the epidemiological-ecological-evolutionary simulator (e3SIM), an open-source framework that concurrently models the transmission dynamics and molecular evolution of pathogens within a host population while integrating environmental factors. Using an agent-based, discrete-generation, forward-in-time approach, e3SIM incorporates compartmental models, host-population contact networks, and quantitative-trait models for pathogens. This integration allows for realistic simulations of disease spread and pathogen evolution. Key features include a modular and scalable design, flexibility in modeling various epidemiological and population-genetic complexities, incorporation of time-varying environmental factors, and a user-friendly graphical interface. We demonstrate e3SIM's capabilities through simulations of realistic outbreak scenarios with SARS-CoV-2 and Mycobacterium tuberculosis , illustrating its flexibility for studying the genomic epidemiology of diverse pathogen types.