Search

Unhealthy alcohol use, smoking, and depressive symptoms are risk factors for cardiovascular disease (CVD). Little is known about their co-occurrence - termed a syndemic, defined as the synergistic effect of two or more conditions-on CVD risk in people with HIV (PWH). We used data from 5621 CVD-free participants (51% PWH) in the Veterans Aging Cohort Study-8, a prospective, observational study of veterans followed from 2002 to 2014 to assess the association between this syndemic and incident CVD by HIV status. Diagnostic codes identified cases of CVD (acute myocardial infarction, stroke, heart failure, peripheral artery disease, and coronary revascularization). Validated measures of alcohol use, smoking, and depressive symptoms were used. Baseline number of syndemic conditions was categorized (0, 1, ≥ 2 conditions). Multivariable Cox Proportional Hazards regressions estimated risk of the syndemic (≥ 2 conditions) on incident CVD by HIV-status. There were 1149 cases of incident CVD (52% PWH) during the follow-up (median 10.1 years). Of the total sample, 64% met our syndemic definition. The syndemic was associated with greater risk for incident CVD among PWH (Hazard Ratio [HR] 1.87 [1.47-2.38], p

BackgroundInsomnia may be a risk factor for cardiovascular disease in HIV (HIV-CVD); however, mechanisms have yet to be elucidated.MethodsWe examined cross-sectional associations of insomnia symptoms with biological mechanisms of HIV-CVD (immune activation, systemic inflammation, and coagulation) among 1,542 people with HIV from the Veterans Aging Cohort Study (VACS) Biomarker Cohort. Past-month insomnia symptoms were assessed by the item, "Difficulty falling or staying asleep?," with the following response options: "I do not have this symptom" or "I have this symptom and…" "it doesn't bother me," "it bothers me a little," "it bothers me," "it bothers me a lot." Circulating levels of the monocyte activation marker soluble CD14 (sCD14), inflammatory marker interleukin-6 (IL-6), and coagulation marker D-dimer were determined from blood specimens. Demographic- and fully-adjusted (CVD risk factors, potential confounders, HIV-related factors) regression models were constructed, with log-transformed biomarker variables as the outcomes. We present the exponentiated regression coefficient (exp[b]) and its 95% confidence interval (CI).ResultsWe observed no significant associations between insomnia symptoms and sCD14 or IL-6. For D-dimer, veterans in the "Bothers a Lot" group had, on average, 17% higher D-dimer than veterans in the "No Difficulty Falling or Staying Asleep" group in the demographic-adjusted model (exp[b] = 1.17, 95%CI = 1.01-1.37, p = .04). This association was nonsignificant in the fully-adjusted model (exp[b] = 1.09, 95%CI = 0.94-1.26, p = .27).ConclusionWe observed little evidence of relationships between insomnia symptoms and markers of biological mechanisms of HIV-CVD. Other mechanisms may be responsible for the insomnia-CVD relationship in HIV; however, future studies with comprehensive assessments of insomnia symptoms are warranted.

BACKGROUND: The prevalence and risk of concurrent unhealthy drinking, cigarette use, and depression on mortality among persons living with HIV (PLWH) is unclear. This study applied a syndemic framework to assess whether these co-occurring conditions increase mortality and whether such risk is differential by HIV status. METHODS: We evaluated 6721 participants (49.8% PLWH) without baseline cancer from the Veterans Aging Cohort Study, a prospective, observational cohort of PLWH and matched uninfected veterans enrolled in 2002 and followed through 2015. Multivariable Cox proportional hazards regressions estimated risk of a syndemic score (number of conditions: that is, unhealthy drinking, cigarette use, and depressive symptoms) on all-cause mortality by HIV status, adjusting for demographic, health status, and HIV-related factors. RESULTS: Fewer than 10% of participants had no conditions; 25.6% had 1, 51.0% had 2, and 15.0% had all 3. There were 1747 deaths (61.9% PLWH) during the median follow-up (11.4 years). Overall, age-adjusted mortality rates/1000 person-years increased with a greater number of conditions: (0: 12.0; 1: 21.2; 2: 30.4; 3: 36.3). For 3 conditions, the adjusted hazard ratio of mortality was 36% higher among PLWH compared with uninfected participants with 3 conditions (95% confidence interval, 1.07-1.72; P = .013), after adjusting for health status and HIV disease progression. Among PLWH and uninfected participants, mortality risk persisted after adjustment for time-updated health status. CONCLUSIONS: Syndemic unhealthy drinking, cigarette use, and depression are common and are associated with higher mortality risk among PLWH, underscoring the need to screen for and treat these conditions.

Introduction The understanding of novel drug targets encoded by the human genome is a prerequisite for the development of novel and effective therapeutics. Therefore, the discovery of novel drug targets [...], Over the last few decades, substantial progress has been made towards the understanding of cardiovascular diseases. In-depth mechanistic insights have also provided opportunities to explore novel therapeutic targets and to discover new treatment regimens. Therapeutic enzymes are examples of such opportunities. The enzymes protect against a variety of cardiovascular diseases, however, even minor malfunctioning of these enzymes may lead to deleterious outcomes. Owing to their great versatility, the inhibition and activation of these enzymes are key regulatory approaches to counter the onset and progression of several cardiovascular impairments. While cardiovascular remedies are already available in excess and are efficacious, a comprehensive description of novel therapeutic enzymes to combat cardiovascular diseases would still be of great benefit. In the light of this, the regulation of functional activities of these enzymes also opens a new avenue for the treatment approaches to be employed. This review describes the importance of non-conventional enzymes such as nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX), phosphodiesterase (PDE), arginase, superoxide dismutase (SOD), thioredoxin reductase (TXNRD) and selenoprotein T (SELENOT), cytochrome b5 reductase 3 (CYB5R3), epoxide hydrolase (EHs), xanthine oxidoreductase (XOR), matrix metalloprotease (MMPs), and dopamine beta hydroxylase (DBH), as potential candidates in several cardiovascular disorders while highlighting some of the recently targeted therapeutic enzymes in cardiovascular diseases. We also discuss the role of intrinsic antioxidant defense system involved in cardioprotection followed by addressing some of the clinical investigations considering the use of antioxidant as a preferred therapy of cardiovascular complications. Key words: therapeutic enzymes, inhibitors, cardiovascular impairments, cardiovascular diseases. Au cours des quelques dernieres decennies, des progres substantiels ont ete accomplis vers la comprehension des maladies cardiovasculaires. Des connaissances en profondeur des modes d&apos;action ont aussi fourni des opportunites d&apos;explorer de nouvelles cibles et schemas therapeutiques a decouvrir. Les traitements enzymatiques sont des exemples de telles opportunites. Le fonctionnement equilibre de tels enzymes apporte une protection contre diverses maladies cardiovasculaires, tandis que par ailleurs, meme un dysfonctionnement mineur de ces enzymes peut entrainer des resultats deleteres. Eu egard a leur grande versatilite, l&apos;inhibition et l&apos;activation de ces enzymes representent des approches regulatrices cles en vue de contrer l&apos;apparition et l&apos;evolution de plusieurs troubles cardiovasculaires. Meme si des medicaments cardiovasculaires sont deja disponibles jusqu&apos;a l&apos;exces et qu&apos;ils sont bien entendu efficaces, une description globale de nouveaux traitements enzymatiques en vue de combattre les maladies cardiovasculaires se fait urgente. A la lumiere de cela, la regulation de l&apos;activite fonctionnelle de ces enzymes ouvre aussi une nouvelle voie pour les approches therapeutiques a employer. Cet article de synthese decrit l&apos;importance d&apos;enzymes non conventionnels comme l&apos;oxydase de la NADPH (pour<< nicotinamide adenine dinucleotide phosphate >>) ou NOX, la phosphodiesterase (PDE), l&apos;arginase, la superoxyde dismutase (SOD), la thioredoxine reductase (TXNRD) et la selenoproteine T (SELENOT), la cytochrome b5 reductase 3 (CYB5R3), l&apos;epoxyde hydrolase (EHs), la xanthine oxydoreductase (XOR), les metalloproteinases matricielles (MMP) et la dopamine beta hydroxylase (DBH) en tant que candidates eventuelles dans plusieurs troubles cardiovasculaires, tout en mettant l&apos;emphase sur certains traitements enzymatiques cibles dernierement dans les maladies cardiovasculaires. Nous discutons egalement du role du systeme de defense antioxydant intrinseque dans la cardioprotection, pour nous pencher ensuite sur certaines etudes cliniques portant sur l&apos;utilisation d&apos;antioxydants comme medicaments privilegies dans les complications cardiovasculaires. [Traduit par la Redaction] Mots-cles: traitements enzymatiques, inhibiteurs, troubles cardiovasculaires, maladies cardiovasculaires.

Previous studies demonstrated that Leptospira biflexa, a saprophytic species, triggers innate immune responses in the host during early infection. This raised the question of whether these responses could suppress a subsequent challenge with pathogenic Leptospira. We inoculated C3H/HeJ mice with a single or a double dose of L. biflexa before challenge with a pathogenic serovar, Leptospira interrogans serovar Copenhageni FioCruz (LIC). Pre-challenge exposure to L. biflexa did not prevent LIC dissemination and colonization of the kidney. However, it rescued weight loss and mouse survival thereby mitigating disease severity. Unexpectedly, there was correlation between rescue of overall health (weight gain, higher survival, lower kidney fibrosis marker ColA1) and higher shedding of LIC in urine. This stood in contrast to the L. biflexa unexposed LIC challenged control. Immune responses were dominated by increased frequency of effector T helper (CD4+) cells in spleen, as well as significant increases in serologic IgG2a. Our findings suggest that exposure to live saprophytic Leptospira primes the host to develop Th1 biased immune responses that prevent severe disease induced by a subsequent challenge with a pathogenic species. Thus, mice exposed to live saprophytic Leptospira before facing a pathogenic serovar may withstand infection with far better outcomes. Furthermore, a status of homeostasis may have been reached after kidney colonization that helps LIC complete its enzootic cycle. [ABSTRACT FROM AUTHOR]

ABSTRACT: Introduction: Similar presenting manifestations in early phase and lack of awareness of aetiology of acute febrile illness (AFI) are major challenges in management of AFI. Material and Methods: This was a retrospective observational cross-sectional study conducted in the Department of Microbiology, NRS Medical College, from 1 July 2022 to 30 June 2023 in serologically diagnosed febrile patients attending the outpatient department or admitted. Clinical and epidemiological data and laboratory parameters were recorded in a pretested structured questionnaire study tool, and collected data were analysed on MS-Excel sheets with various charts and tables. Results: A total of 1711 serologically diagnosed febrile patients showed preponderance of dengue (38.3%), followed by leptospirosis (25%), scrub typhus (23.9%), malaria (12.6%), and enteric fever (1.92%). A majority of cases were male, less than 40 years of age, and from the rural population (73.2%), except in malaria (urban = 79.6%). The mean duration of fever was 9 days. Febrile cases were recorded maximum during the monsoon and postmonsoon periods (66.5%). The common manifestations are fever, headache (46.2%), pain abdomen (7.8%), nausea, and vomiting (9.4%). Thrombocytopenia with bleeding manifestation was higher in dengue (18%) cases. Mortality in dengue cases was recorded with multiorgan dysfunction syndrome (MODS). Scrub typhus cases showed seizure (8.3%) and altered sensorium (5%) due to fatal meningoencephalitis. Fatality in leptospirosis was mostly due to acute kidney injury (29.5%) and Weil's disease (4.4%). Conclusion: Misdiagnosis or incorrect diagnosis and delay in initiation of appropriate treatment results in increased morbidity and mortality in AFI. Determination of epidemiological features and clinical manifestations of AFI along with timely correct diagnosis will benefit clinicians in proper treatment initiation, thereby reducing morbidity and mortality. [ABSTRACT FROM AUTHOR]