Cardiometabolic health in people with HIV: expert consensus review.

OBJECTIVES: To develop consensus data statements and clinical recommendations to provide guidance for improving cardiometabolic health outcomes in people with HIV based on the knowledge and experience of an international panel of experts. METHODS: A targeted literature review including 281 conference presentations, peer-reviewed articles, and background references on cardiometabolic health in adults with HIV published between January 2016 and April 2022 was conducted and used to develop draft consensus data statements. Using a modified Delphi method, an international panel of 16 experts convened in workshops and completed surveys to refine consensus data statements and generate clinical recommendations. RESULTS: Overall, 10 data statements, five data gaps and 14 clinical recommendations achieved consensus. In the data statements, the panel describes increased risk of cardiometabolic health concerns in people with HIV compared with the general population, known risk factors, and the potential impact of antiretroviral therapy. The panel also identified data gaps to inform future research in people with HIV. Finally, in the clinical recommendations, the panel emphasizes the need for a holistic approach to comprehensive care that includes regular assessment of cardiometabolic health, access to cardiometabolic health services, counselling on potential changes in weight after initiating or switching antiretroviral therapy and encouraging a healthy lifestyle to lower cardiometabolic health risk. CONCLUSIONS: On the basis of available data and expert consensus, an international panel developed clinical recommendations to address the increased risk of cardiometabolic disorders in people with HIV to ensure appropriate cardiometabolic health management for this population.

Dosimetry in cranial photobiomodulation therapy: effect of cranial thickness and bone density.

This research aims to examine the influence of human skull bone thickness and density on light penetration in PBM therapy across different wavelengths, focusing on how these bone characteristics affect the absorption of therapeutic light. Analyses explored the effect of skull bone density and thickness on light penetration in PBM, specifically using Low-Level Laser Therapy (LLLT) for efficacy prediction. Measurements of bone thickness and density were taken using precise tools. This approach emphasizes LLLT's significance in enhancing PBM outcomes by assessing how bone characteristics influence light penetration. The study revealed no significant correlation between skull bone density and thickness and light penetration capability in photobiomodulation (PBM) therapy, challenging initial expectations. Wavelengths of 405 nm and 665 nm showed stronger correlations with bone density, suggesting a significant yet weak impact. Conversely, wavelengths of 532 nm, 785 nm, 810 nm, 830 nm, 980 nm, and 1064 nm showed low correlations, indicating minimal impact from bone density variations. However, data variability (R2 < 0.4) suggests that neither density nor thickness robustly predicts light power traversing the bone, indicating penetration capability might be more influenced by bone thickness at certain wavelengths. The study finds that the effectiveness of photobiomodulation (PBM) therapy with bone isn't just based on bone density and thickness but involves a complex interplay of factors. These include the bone's chemical and mineral composition, light's wavelength and energy dose, treatment duration and frequency, and the precise location where light is applied on the skull.

Unreported ent-rosane diterpenes from Croton niveus Jacq. (Euphorbiaceae). Cytotoxic activity and docking studies.

From the bioactive extract of the euphorbiaceous Croton niveus Jacq., three previously unreported ent-rosane diterpenes have been isolated and characterized by conventional methods, in addition to the known compounds lupeol, cajucarinolide and some phytosterols. Two of the ent-rosane diterpenes displayed activity against HCT-15 and PC-3 cancer cell lines, and the results of docking calculations of these compounds with NF-κB and STAT3 receptors agreed with the proposed mode of action of diterpenes against PC-3 cells.

PrEP program experience in a hospital HIV unit. Description of baseline user profile and identification of opportunities for improvement.

INTRODUCTION: Pre-Exposure Prophylaxis (PrEP) is a biomedical intervention to prevent HIV infection in seronegative people at high risk of becoming infected. This strategy was endorsed in October 2019 by the Spanish Ministry of Health. OBJECTIVE: To present the PrEP initial experience in the HIV Unit of the Hospital Clínic of Barcelona, paying special attention to the analysis of the vulnerability factors in the cohort. MATERIALS AND METHODS: Retrospective, descriptive study. The epidemiological, sociodemographic, and clinical characteristics of the users included in the program during the first year are analyzed, paying particular attention to Infections, risky practices, and substance use. RESULTS: 190 individuals were included, 177 men and 12 trans women with a mean age of 35 years (8 SD). 70% had higher education, and half had Spanish nationality. An average of 10 couples per trimester and 60% reported unprotected anal sex. 31% had at least one positive PCR for STIs, with N. gonorrhoeae being the most prevalent microorganism (51%) and the rectal sample the most affected (21%). 63% reported chemsex use, 19% polydrug use, and 8% "slamming". Half expressed concern about consumption and/or sexual practices and 25% the need for help. CONCLUSIONS: The PrEP user profile attended in our Hospital Unit justifies the creation of multidisciplinary teams that allow us to provide holistic attention to the sexual life of these people.

Factors associated with admission to the intensive care unit and mortality in patients with COVID-19, Colombia.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has affected millions of people worldwide, and several sociodemographic variables, comorbidities and care variables have been associated with complications and mortality. OBJECTIVE: To identify the factors associated with admission to intensive care units (ICUs) and mortality in patients with COVID-19 from 4 clinics in Colombia. METHODS: This was a follow-up study of a cohort of patients diagnosed with COVID-19 between March and August 2020. Sociodemographic, clinical (Charlson comorbidity index and NEWS 2 score) and pharmacological variables were identified. Multivariate analyses were performed to identify variables associated with the risk of admission to the ICU and death (p<0.05). RESULTS: A total of 780 patients were analyzed, with a median age of 57.0 years; 61.2% were male. On admission, 54.9% were classified as severely ill, 65.3% were diagnosed with acute respiratory distress syndrome, 32.4% were admitted to the ICU, and 26.0% died. The factors associated with a greater likelihood of ICU admission were severe pneumonia (OR: 9.86; 95%CI:5.99-16.23), each 1-point increase in the NEWS 2 score (OR:1.09; 95%CI:1.002-1.19), history of ischemic heart disease (OR:3.24; 95%CI:1.16-9.00), and chronic obstructive pulmonary disease (OR:2.07; 95%CI:1.09-3.90). The risk of dying increased in those older than 65 years (OR:3.08; 95%CI:1.66-5.71), in patients with acute renal failure (OR:6.96; 95%CI:4.41-11.78), admitted to the ICU (OR:6.31; 95%CI:3.63-10.95), and for each 1-point increase in the Charlson comorbidity index (OR:1.16; 95%CI:1.002-1.35). CONCLUSIONS: Factors related to increasing the probability of requiring ICU care or dying in patients with COVID-19 were identified, facilitating the development of anticipatory intervention measures that favor comprehensive care and improve patient prognosis.

3ß-Palmitoyloxy-olean-12-ene analogs from Sapium lateriflorum (Euphorbiaceae): Their cytotoxic and anti-inflammatory properties and docking studies.

Ten compounds, including a new anti-inflammatory acyl triterpene, 3ß-palmitoyloxy-1ß,11α-dihydroxy-olean-12-ene, were isolated from the bioactive organic extract prepared from the leaves of Sapium lateriflorum (syn: S. nitidum). The isolated compounds were screened for their cytotoxic activity against selected human cancer cell lines and did not display significant activity. They were also evaluated as anti-inflammatory agents in mouse models (TPA-induced edema in the ear and in a carrageenan-induced paw edema model). The results indicated that the new compound, 3ß-palmitoyloxy-1ß,11α-dihydroxy-olean-12-ene, was the compound with major anti-inflammatory activity similar to that of indomethacin, being the hydroxyl at C-11 important for the observed activity. The results of docking studies of the 3ß-palmitoyloxy esters of olean-12-ene with NF-κB and with COX-2 receptors were consistent with possible molecular mechanisms of the anti-inflammatory activity.

PrEP program experience in a hospital HIV unit. Description of baseline user profile and identification of opportunities for improvement. / Experiencia de un programa de profilaxis preexposición en una unidad de virus de la inmunodeficiencia humana hospitalaria. Descripción del perfil basal del usuario e identificación de oportunidades de mejora.

INTRODUCTION: Pre-Exposure Prophylaxis (PrEP) is a biomedical intervention to prevent HIV infection in seronegative people at high risk of becoming infected. This strategy was endorsed in October 2019 by the Spanish Ministry of Health. OBJECTIVE: To present the PrEP initial experience in the HIV Unit of the Hospital Clínic of Barcelona, paying special attention to the analysis of the vulnerability factors in the cohort. MATERIALS AND METHODS: Retrospective, descriptive study. The epidemiological, sociodemographic, and clinical characteristics of the users included in the program during the first year are analyzed, paying particular attention to Infections, risky practices, and substance use. RESULTS: 190 individuals were included, 177 men and 12 trans women with a mean age of 35 years (8 SD). 70% had higher education, and half had Spanish nationality. An average of 10 couples per trimester and 60% reported unprotected anal sex. 31% had at least one positive PCR for STIs, with N. gonorrhoeae being the most prevalent microorganism (51%) and the rectal sample the most affected (21%). 63% reported chemsex use, 19% polydrug use, and 8% "slamming". Half expressed concern about consumption and/or sexual practices and 25% the need for help. CONCLUSIONS: The PrEP user profile attended in our Hospital Unit justifies the creation of multidisciplinary teams that allow us to provide holistic attention to the sexual life of these people.

Development of a G118R mutation in HIV-1 integrase following a switch to dolutegravir monotherapy leading to cross-resistance to integrase inhibitors.

OBJECTIVES: Dolutegravir shows a high barrier to resistance with no previously reported cases of acquired integrase mutations during first-line therapy. In this study, rapid development of the G118R mutation arose following a switch from first-line elvitegravir/cobicistat/tenofovir disoproxil fumarate/emtricitabine to dolutegravir monotherapy. The G118R mutation also arose in a treatment-experienced patient switched to dolutegravir monotherapy. The genetic basis for G118R selection and potential phenotypic outcome was ascertained. PATIENT AND METHODS: Genotypic analysis was performed on patients with virological failure (<1000 copies/mL) on dolutegravir-containing regimens. The Los Alamos database was queried for glycine codon 118 polymorphisms. Cell culture selections and phenotypic drug susceptibility assays assessed resistance via the G118R pathway. RESULTS: We report on two patients who developed viral failure while on dolutegravir monotherapy. Both patients had been on a current or previous regimen containing integrase inhibitors. Virological failure (<1000 copies/mL) emerged early within 2 months following the dolutegravir switch. The appearance of G118R in these two cases and subtype C and CRF02_AG in vitro selections were related to a rare GGA natural polymorphism at codon 118 (1.5% prevalence), facilitating a GGA to AGA transition. Cell culture selections were used to assess the in vitro progression of the G118R pathway leading to cross-resistance to all integrase inhibitors. CONCLUSIONS: Although resistance to dolutegravir is typically rare, genetic polymorphisms and monotherapy can facilitate the acquisition of G118R.

A consistent S-Adenosylmethionine force field improved by dynamic Hirshfeld-I atomic charges for biomolecular simulation.

S-Adenosylmethionine (AdoMet) is involved in many biological processes as cofactor in enzymes transferring its sulfonium methyl group to various substrates. Additionally, it is used as drug and nutritional supplement to reduce the pain in osteoarthritis and against depression. Due to the biological relevance of AdoMet it has been part of various computational simulation studies and will also be in the future. However, to our knowledge no rigorous force field parameter development for its simulation in biological systems has been reported. Here, we use electronic structure calculations combined with molecular dynamics simulations in explicit solvent to develop force field parameters compatible with the AMBER99 force field. Additionally, we propose new dynamic Hirshfeld-I atomic charges which are derived from the polarized electron density of AdoMet in aqueous solution to describe its electrostatic interactions in biological systems. The validation of the force field parameters and the atomic charges is performed against experimental interproton NOE distances of AdoMet in aqueous solution and crystal structures of AdoMet in the cavity of three representative proteins.

Use of diet, nutritional supplements and exercise in HIV-infected patients receiving combination antiretroviral therapies: a systematic review.

BACKGROUND: The use of combination antiretroviral therapy (cART) has improved the prognosis of HIV infection, but it has also been linked to a spectrum of body composition changes and metabolic alterations known as the lipodystrophy syndrome. Nutritional status could influence body composition changes. METHODS: We performed a systematic search of published peer-reviewed data on the effects of diet, nutrition support and exercise on body composition and metabolic complications in patients receiving cART. RESULTS: Few controlled studies, most of them with small sample size, were found. Oral nutritional support increases protein and energy intake, and results in body weight and fat mass gains. Resistance exercise, with or without an aerobic component, increases lean mass and can improve insulin resistance. Low-fat diets or exercise can result in loss of fat mass, and they should be used with caution in subjects with lipoatrophy. CONCLUSIONS: Nutritional support and exercise result in small but significant body composition changes and can be used as complementary interventions. There is a need for further research on nutritional interventions in HIV-infected patients receiving cART.

Effect of penicillin resistance of Streptococcus pneumoniae on the presentation, prognosis, and treatment of pneumococcal endocarditis in adults.

We performed a clinical study of pneumococcal endocarditis (PE) in adults at 15 major Spanish hospitals during a 21-year period (1978-1998). During this time, 63 patients had PE due to Streptococcus pneumoniae diagnosed. Of the 63 isolates recovered from these patients, 24 (38%) and 6 (10%) showed resistance to penicillin (minimum inhibitory concentration [MIC], 0.1-4 microg/mL) and cefotaxime (MIC, 1 microg/mL), respectively. Twenty-two (35%) of the patients died. Left-side heart failure, but not penicillin resistance, was independently associated with a higher risk of death (odds ratio, 1.33; 95% confidence interval, 1.04-1.71; P=.026). Patients without meningitis who had PE due to penicillin-resistant S. pneumoniae could be treated with high-dose penicillin or a third-generation cephalosporin if the MIC for penicillin was < or =1 microg/mL. For patients with concurrent meningitis, high doses of cefotaxime could be used if the MIC for cefotaxime was < or =1 microg/mL. Early recognition of heart failure and surgery may help to decrease mortality.