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528 result(s) for "Laws, L."
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Lipid droplets and lipid mediators in viral infection and immunity
ABSTRACT Lipid droplets (LDs) contribute to key pathways important for the physiology and pathophysiology of cells. In a homeostatic view, LDs regulate the storage of neutral lipids, protein sequestration, removal of toxic lipids and cellular communication; however, recent advancements in the field show these organelles as essential for various cellular stress response mechanisms, including inflammation and immunity, with LDs acting as hubs that integrate metabolic and inflammatory processes. The accumulation of LDs has become a hallmark of infection, and is often thought to be virally driven; however, recent evidence is pointing to a role for the upregulation of LDs in the production of a successful immune response to viral infection. The fatty acids housed in LDs are also gaining interest due to the role that these lipid species play during viral infection, and their link to the synthesis of bioactive lipid mediators that have been found to have a very complex role in viral infection. This review explores the role of LDs and their subsequent lipid mediators during viral infections and poses a paradigm shift in thinking in the field, whereby LDs may play pivotal roles in protecting the host against viral infection. Lipid droplets are key organelles in multiple cellular processes; recent advances in the field have demonstrated that they together with their lipid mediators may play pivotal roles in the outcome of viral infection.
Integrative proteomics and lipidomics reveals dual roles for lipid droplets in the host cell antiviral response
Lipid droplets (LDs), once viewed as inert lipid storage sites, are now recognised as dynamic organelles central to cellular signalling and immunity. This study presents a dual-omics approach, integrating proteomics and lipidomics, to investigate LDs in the host antiviral response. In vivo and in vitro RNA viral infection models demonstrate that LDs rapidly remodel both their proteome and lipidome. The antiviral proteins RIG-I, MDA5, STAT1, STAT2, and viperin are specifically recruited to virus-induced LDs. Simultaneously, the LD lipidome shifts toward enrichment in long-chain polyunsaturated fatty acids and bioactive phospholipids, likely enhancing membrane dynamics and protein recruitment. Correlation analysis of matched proteomic and lipidomic datasets revealed extensive lipid–protein co-regulation on LDs and identified distinct correlation networks in which immune and antiviral proteins preferentially aligned with neutral lipid species. Enzymes involved in lipid metabolism and post-translational modifications are also upregulated, suggesting a mechanistic link between lipid remodeling and protein localisation. Functional assays utilizing artificial LDs revealed that arachidonic-acid and eicosapentaenoic-acid suppress viral replication and enhance type I and III interferon responses. These findings position LDs as key immunometabolic platforms in early antiviral defence. Dual proteomics–lipidomics demonstrates that virus-induced lipid droplets rapidly recruit antiviral proteins and remodel lipids. These lipid–protein networks form signalling hubs, while specific long chain fatty acids enhance interferon responses and restrict viral replication.
Occupational exposures and mitigation strategies among homeless shelter workers at risk of COVID-19
To describe the work environment and COVID-19 mitigation measures for homeless shelter workers and assess occupational risk factors for COVID-19. Between June 9-August 10, 2020, we conducted a self-administered survey among homeless shelter workers in Washington, Massachusetts, Utah, Maryland, and Georgia. We calculated frequencies for work environment, personal protective equipment use, and SARS-CoV-2 testing history. We used generalized linear models to produce unadjusted prevalence ratios (PR) to assess risk factors for SARS-CoV-2 infection. Of the 106 respondents, 43.4% reported frequent close contact with clients; 75% were worried about work-related SARS-CoV-2 infections; 15% reported testing positive. Close contact with clients was associated with testing positive for SARS-CoV-2 (PR 3.97, 95%CI 1.06, 14.93). Homeless shelter workers may be at risk of being exposed to individuals with COVID-19 during the course of their work. Frequent close contact with clients was associated with SARS-CoV-2 infection. Protecting these critical essential workers by implementing mitigation measures and prioritizing for COVID-19 vaccination is imperative during the pandemic.
Factors associated with unawareness of HIV-positive status among individuals aged ≥ 15 years in Tanzania: Evidence from the Tanzania HIV Impact Survey 2022–2023
Introduction In Tanzania, despite the progress in HIV testing and counseling, 39.4% of people living with HIV aged ≥ 15 years were unaware of their HIV status in 2017. HIV testing is a crucial entry point for prevention, early diagnosis, and treatment of HIV to increase survival, improve quality of life, and prevent further transmission. This analysis aimed to estimate the proportion of individuals aged ≥ 15 years living with HIV in Tanzania who were unaware of their HIV status and to determine factors associated with unawareness of HIV-positive status. Methods We analyzed data from the Tanzania HIV Impact Survey 2022–2023, a nationally representative cross-sectional survey which employed a two-stage cluster sampling design and included HIV testing at the household with laboratory confirmation. This analysis focused on individuals aged ≥ 15 years who tested HIV-positive during the survey. Weighted percentages were calculated to summarize demographic information and the proportion unaware of their HIV-positive status. Logistic regression accounting for complex survey design was used to determine factors associated with unawareness of HIV-positive status. Results A total of 1,850 individuals aged ≥ 15 years tested HIV positive, among which 266 (17.3%) were unaware of their HIV-positive status. Males were more likely to be unaware of their HIV-positive status than females (21.6%, aOR = 1.67, 95% CI: 1.06–2.61, p  = 0.029 vs. 15.2%). Young people aged 15 − 24 years were over five times more likely to be unaware of their HIV-positive status (aOR = 5.61, 95% CI: 2.12–14.84, p  = 0.001) compared to individuals aged ≥ 55 years. Individuals who reported not using a condom at last sexual intercourse in the past year were more likely to be unaware of their HIV status than those who reported condom use (aOR = 2.36, 95% CI: 1.32–4.20, p  = 0.005). Those with at least one partner living with HIV were less likely to be unaware of their HIV-positive status compared to individuals with all sexual partners who were HIV negative (aOR = 0.04, 95% CI: 0.00-0.42, p  = 0.009). Conclusion Despite robust HIV case-finding interventions in Tanzania, 1 in 6 PLHIV were unaware of their HIV-positive status. Targeted HIV case-finding interventions should continue with a focus on reaching men and young people who were more likely to be unaware of their status. HIV prevention strategies, such as condom use, remain crucial, since individual behaviors were linked to awareness of HIV status.
Dysuria, heat stress, and muscle injury among Nicaraguan sugarcane workers at risk for Mesoamerican nephropathy
Objectives Nicaraguan sugarcane workers, particularly cane cutters, have an elevated prevalence of chronic kidney disease of unknown origin, also referred to as Mesoamerican nephropathy (MeN). The pathogenesis of MeN may include recurrent heat stress, crystalluria, and muscle injury with subsequent kidney injury. Yet, studies examining the frequency of such events in long-term, longitudinal studies are limited. Methods Using employment and medical data for male workers at a Nicaraguan sugarcane company, we classified months of active work as either work as a cane cutter or other sugarcane job and determined occurrence of dysuria, heat events and muscle events. Work months and events occurred January 1997 to June 2010. Associations between cane cutting and each outcome were analyzed using logistic regression based on generalized estimating equations for repeated events, controlling for age. Results Among 242 workers with 7257 active work months, 19.5% of person-months were as a cane cutter. There were 160, 21, and 16 episodes of dysuria, heat events, and muscle events, respectively. Compared with work months in other jobs, cane cutting was associated with an elevated odds of dysuria [odds ratio 2.40 (95% confidence interval 1.56-3.68)]. The number of heat and muscle events by cane cutter and other job were limited. Conclusions Working as a cane cutter compared with other jobs in the sugarcane industry was associated with increased dysuria, supporting the hypothesis that cane cutters are at increased risk of events suspected of inducing or presaging clinically evident kidney injury.
Progress Toward Regional Measles Elimination — Worldwide, 2000–2017
In 2010, the World Health Assembly set three milestones for measles prevention to be achieved by 2015: 1) increase routine coverage with the first dose of measles-containing vaccine (MCV1) among children aged 1 year to ≥90% at the national level and to ≥80% in every district; 2) reduce global annual measles incidence to less than five cases per million population; and 3) reduce global measles mortality by 95% from the 2000 estimate (1).* In 2012, the World Health Assembly endorsed the Global Vaccine Action Plan (GVAP), with the objective of eliminating measles in four of the six World Health Organization (WHO) regions by 2015 and in five regions by 2020. Countries in all six WHO regions have adopted goals for measles elimination by 2020. This report describes progress toward global measles control milestones and regional measles elimination goals during 2000-2017 and updates a previous report (2). During 2000-2017, estimated MCV1 coverage increased globally from 72% to 85%; annual reported measles incidence decreased 83%, from 145 to 25 cases per million population; and annual estimated measles deaths decreased 80%, from 545,174 to 109,638. During this period, measles vaccination prevented an estimated 21.1 million deaths. However, measles elimination milestones have not been met, and three regions are experiencing a large measles resurgence. To make further progress, case-based surveillance needs to be strengthened, and coverage with MCV1 and the second dose of measles-containing vaccine (MCV2) needs to increase; in addition, it will be important to maintain political commitment and ensure substantial, sustained investments to achieve global and regional measles elimination goals.
Factors associated with awareness of and willingness to use PrEP among stable, heterosexual HIV‐serodifferent couples in seven African countries, 2019–2022
Introduction HIV pre‐exposure prophylaxis (PrEP) is an effective biomedical intervention for preventing HIV; however, PrEP adoption initially lagged across sub‐Saharan Africa (SSA) and may have been affected by barriers to engagement in PrEP care. Stable, heterosexual HIV‐serodifferent couples are a priority population of PrEP expansion efforts. We assessed factors associated with PrEP awareness and willingness among HIV‐serodifferent couples in SSA to guide PrEP interventions for this population. Methods We conducted a cross‐sectional analysis using pooled data from nationally representative, two‐stage cluster sampling, HIV‐focused household surveys completed during 2019–2022 in seven African countries. We analysed data from 1738 persons without HIV aged ≥15 years in stable, heterosexual HIV‐serodifferent couples and included clinical information from their partners with HIV. Higher HIV risk was defined by unawareness of a partner's HIV‐positive status or having a partner with an unsuppressed viral load (≥200 copies/ml). Lower HIV risk was defined by awareness of a partner's HIV‐positive status and having a partner with a suppressed viral load (<200 copies/ml). We conducted multivariable logistic regression using survey weights and jackknife variance estimation to assess factors associated with PrEP awareness and willingness. Results Overall, 18.1% were aware of PrEP, 69.1% were willing to use PrEP and 5.1% had ever used PrEP. Forty‐four percent had higher HIV risk. Higher odds of PrEP awareness were associated with being female (adjusted odds ratio [aOR]: 1.73; 95% confidence interval [CI]: 1.15–2.59), secondary education or higher (aOR: 6.42; 95% CI: 2.97–13.91) and lower HIV risk (aOR: 1.58; 95% CI: 1.00–2.48). Higher odds of PrEP willingness were associated with employment in the past year (aOR: 1.55; 95% CI: 1.01–2.37), previous PrEP awareness (aOR: 2.44; 95% CI: 1.36–4.36) and lower HIV risk (aOR: 1.70; 95% CI: 1.07–2.70). Conclusions Persons in stable, heterosexual HIV‐serodifferent couples with lower HIV risk were more aware of and willing to use PrEP than those with higher risk. Our findings highlight the importance of encouraging HIV status disclosure, educating about HIV‐serodifference and PrEP, and providing PrEP linkage during HIV testing and prevention counselling to increase PrEP awareness, willingness and use among HIV‐serodifferent couples in SSA.
Hormonal Changes after Roux-en Y Gastric Bypass for Morbid Obesity and the Control of Type-II Diabetes Mellitus
Morbid obesity (MO) is associated with diabetes mellitus-type II (DM-II). Roux-en Y gastric bypass (RNY) has been shown to normalize glucose intolerance in these patients through an incompletely understood mechanism. Gastrointestinal hormonal changes have been suggested as an explanation for resolution of DM II. Preoperatively, 20 MO patients with DM-II were evaluated for demographics and fasting levels of the following: glucose, insulin, C-peptide, glucagon, Cortisol, gastric inhibitory polypeptide (GIP), and glucagon-like peptide-1 (GLP-1). Each patient underwent RNY with a 15-cc gastric pouch and 150-cm Roux limb. Postoperatively, each of the variables was measured at 2 weeks, 6 weeks, and 12 weeks and compared with the preoperative result using Student t test with significance, P = 0.05. Results are expressed as mean ± SD. Twenty patients (5 male and 15 female), age 40.3 ± 7.9 years, weight 146.3 ± 34.0 kg, height 158.7 ± 18.7 cm, and BMI 52.7 ± 8.8, were enrolled in this IRB-approved protocol. Weight and BMI decreased progressively (117.5 ± 26.9 kg and 47.0 ± 7.4, P = 0.01, respectively) during the study but reached significance only at 12 weeks. Fasting plasma glucose decreased significantly within 2 weeks after RNY. Insulin and Cortisol both approached, but never achieved, significant changes over 12 weeks. GLP-1 increased initially, but not significantly. GIP and C-peptide both decreased significantly. Glucagon remained essentially unchanged over 12 weeks. RNY rapidly normalizes fasting plasma glucose in morbidly obese patients with DM-II. GIP, a gactor in the enteroinsulin axis, decreases and may play a role in the correction of DM-II after gastric bypass.
Chest Pain in a Psychiatric Patient Due to Clozapine-Induced Myopericarditis
Drug-induced myocarditis is a rare, but underrecognized complication of clozapine therapy for schizophrenia. We present a case of clozapine-induced myocarditis with recovery of cardiac function after drug cessation and summarize the literature to highlight the variable presentation of this condition.
Human Systemic Immune Response to Ingestion of the Oral Probiotic Streptococcus salivarius BLIS K12
Streptococcus salivarius K12 is an oral probiotic known to contribute to protection against oral pathogenic bacteria in humans. Studies of immune responses to S. salivarius K12 have focused on the oral cavity, and systemic immune responses have not yet been reported. The aim of this study was to identify acute systemic immune responses to the commercial product, S. salivarius BLIS K12, in a double-blinded, placebo-controlled human clinical trial. It was hypothesised that consumption of S. salivarius BLIS K12 would induce an anti-inflammatory response and a decrease in pro-inflammatory cytokines. Blood samples were obtained from participants prior to a single dose of S. salivarius BLIS K12 or a placebo and then secondary blood samples were obtained 24 h and 7 days post-consumption. Samples were analysed using multi-parametric flow cytometry, to quantify immune cell frequency changes, and by a LEGENDplex assay of human inflammatory cytokines. Consumption of S. salivarius BLIS K12 was associated with increased levels of IL-8 at 24 h. The frequency of Tregs increased in samples taken 7 days after probiotic consumption, and IL-10 concentrations were higher at 7 days than 24 h after consumption. There was no difference in the frequency and/or activation of CD4 + T cells, CD8 + T cells, B cells and NK cells. Interestingly, there was an increase in IL-12, 7 days after the consumption of S. salivarius BLIS K12. Collectively, this research demonstrates that ingestion of the probiotic S. salivarius K12 can induce changes in the systemic immune response. The implications of the generation and type of immune response warrant further study to determine potential health benefits.