Prevalence, risk factors and the impact of tenofovir treatment in SARS-CoV-2 infection and COVID-19 disease among people living with HIV. A cross-sectional population-based study.

The prevalence and risk factors of SARS-CoV-2 infection among unvaccinated people living with HIV (PWH) are not well understood, and the protective role of tenofovir remains controversial. This study aimed to assess the SARS-CoV-2 prevalence and associated risk factors among unvaccinated PWH, and to evaluate the impact of tenofovir. We conducted as a cross-sectional study between November 2020 and May 2021. Plasma samples from 4,400 of 5,476 PWH were tested for total antibodies, IgG, IgM, and IgA. Among the participants (median age 48 years, 84% male), 92% had undetectable HIV viral loads and 5% had syphilis. The prevalence of SARS-CoV-2 infection was 18% (95% CI 17-19), with 1,180 individuals showing antibodies (IgG 13%, IgA 10%, IgM 11%). Of those seropositive for SARS-CoV-2, 67.5% were asymptomatic, 29% had mild disease, and 3.5% had severe/critical conditions. Risk factors included younger age, being female, men who have sex with men (MSM) status, non-European origin, and a history of syphilis. Neither antiretrovirals nor tenofovir provided protection against SARS-CoV-2 infection or COVID-19 disease. Ongoing surveillance and tailored interventions are crucial for at-risk PWH amid evolving SARS-CoV-2 variants.

SEED: A novel web-based data visualization platform to visualize, communicate, and explore social, environmental, and equity drivers of health.

Multisector stakeholders, including, community-based organizations, health systems, researchers, policymakers, and commerce, increasingly seek to address health inequities that persist due to structural racism. They require accessible tools to visualize and quantify the prevalence of social drivers of health (SDOH) and correlate them with health to facilitate dialog and action. We developed and deployed a web-based data visualization platform to make health and SDOH data available to the community. We conducted interviews and focus groups among end users of the platform to establish needs and desired platform functionality. The platform displays curated SDOH and de-identified and aggregated local electronic health record data. The resulting Social, Environmental, and Equity Drivers (SEED) Health Atlas integrates SDOH data across multiple constructs, including socioeconomic status, environmental pollution, and built environment. Aggregated health prevalence data on multiple conditions can be visualized in interactive maps. Data can be visualized and downloaded without coding knowledge. Visualizations facilitate an understanding of community health priorities and local health inequities. SEED could facilitate future discussions on improving community health and health equity. SEED provides a promising tool that members of the community and researchers may use in their efforts to improve health equity.

Barriers and Strategies to Optimize the Use of Glucagon-Like Peptide 1 Receptor Agonists in People with Type 2 Diabetes and High Cardiovascular Risk or Established Cardiovascular Disease: A Delphi Consensus in Spain.

INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are effective for glycemic control, with many also demonstrating cardiovascular (CV) benefit, in people with type 2 diabetes (T2D). This study aimed to find a consensus on the barriers and strategies for the optimal use of GLP-1 RAs in people with T2D and high CV risk or established cardiovascular disease (CVD) in Spain. METHODS: A two-round Delphi survey (53 questions) was conducted among members of four national scientific societies in Spain, including physicians experienced in the management of people with T2D. The degree of consensus was evaluated with a 7-point Likert scale, establishing consensus when ≥ 70% of the panelists agreed (6-7) or disagreed (1-2). RESULTS: A total of 97 physicians participated in the first round (endocrinology: 34%, family and community medicine: 21%, internal medicine: 23%, and cardiology: 23%), and 96 in the second round. The main barriers identified were: therapeutic inertia and late use of GLP-1 RAs; lack of a comprehensive approach to CV risk; lack of knowledge on the usefulness of GLP-1 RAs in CVD prevention and treatment; and economic/administrative barriers. Strategies with a highest consensus included: the need to establish simple protocols that integrate awareness of CV risk monitoring; training professionals and patients; and the use of new technologies. CONCLUSION: Physicians identified clinical, healthcare, and economic/administrative barriers that limit the use of GLP-1 RAs in people with T2D and high CV risk or established CVD in Spain, highlighting the importance of integrating these therapies according to clinical practice guidelines.

Sensory Polymers: Trends, Challenges, and Prospects Ahead.

In recent years, sensory polymers have evolved significantly, emerging as versatile and cost-effective materials valued for their flexibility and lightweight nature. These polymers have transformed into sophisticated, active systems capable of precise detection and interaction, driving innovation across various domains, including smart materials, biomedical diagnostics, environmental monitoring, and industrial safety. Their unique responsiveness to specific stimuli has sparked considerable interest and exploration in numerous applications. However, along with these advancements, notable challenges need to be addressed. Issues such as wearable technology integration, biocompatibility, selectivity and sensitivity enhancement, stability and reliability improvement, signal processing optimization, IoT integration, and data analysis pose significant hurdles. When considered collectively, these challenges present formidable barriers to the commercial viability of sensory polymer-based technologies. Addressing these challenges requires a multifaceted approach encompassing technological innovation, regulatory compliance, market analysis, and commercialization strategies. Successfully navigating these complexities is essential for unlocking the full potential of sensory polymers and ensuring their widespread adoption and impact across industries, while also providing guidance to the scientific community to focus their research on the challenges of polymeric sensors and to understand the future prospects where research efforts need to be directed.

Characteristics and rates of infection by HIV in people receiving non-occupational post-exposure prophylaxis (nPEP) against HIV.

INTRODUCTION/OBJECTIVES: The use of non-occupational post-exposure prophylaxis (nPEP) emerges as a strategic intervention to reduce HIV infection risk following sexual encounters in our setting. Notwithstanding, there is a scarcity of contemporary data regarding adherence to this treatment, its effectiveness and tolerance. Our study aims to delve into these factors among individuals who have resorted to nPEP after high-risk sexual encounters. METHODS: We conducted a retrospective observational study of cases administered nPEP for HIV from 1 January 2018 to 31 December 2021 at a tertiary hospital in Madrid. The study included all adults over 18 years who sought care at the emergency department of the Fundación Jiménez Díaz Hospital following a risky sexual encounter and were subsequently recommended HIV nPEP treatment. RESULTS: 878 individuals received nPEP for HIV and underwent initial serological tests. Of these, 621 had comprehensive follow-ups. The prescribed regimen for all was raltegravir (RAL) 1200 mg combined with tenofovir/emtricitabine (TDF/FTC) 245/200 mg daily for 28 days. The study revealed a 1.1% rate (n=10) of previously undetected infection and a 0.16% (n=1) failure rate of nPEP. Regarding regimen tolerability, 5.6% (n=35) experienced symptoms linked to the treatment, yet none necessitated discontinuation of the regimen. On the contrary, six per cent (n=53) reported symptoms consistent with an STI during one of the medical visits; specifically, 4.4% had urethritis, and 1.6% had proctitis. CONCLUSION: nPEP with RAL/TDF/FTC demonstrates high efficacy and safety, contingent on proper adherence. There is an observed increase in STI prevalence in this cohort, with nearly half of the participants not engaging in appropriate follow-up after initiating nPEP.

Post-event follow-up costs in patients with atherosclerotic cardiovascular disease in Spain.

Introduction: Atherosclerotic cardiovascular disease (ASCVD) is one of the main causes of morbidity and mortality in developed countries and entails high resources use and costs for health systems. The risk of suffering future cardiovascular (CV) events and the consequent resources use is higher in those patients who have already had a previous cardiovascular event. The objective of the study was to determine the average annual cost of patients with a new or recurrent atherosclerotic CV event during the 2 years after the event. Methodology: Retrospective observational study of electronic medical records of patients from the BIG-PAC® database (7 integrated health areas of 7 Autonomous Communities; n = 1.8 million). Patients with a new or recurrent episode of ASCVD (angina, acute myocardial infarction, transient ischemic attack, stroke, or peripheral arterial disease) between 1-Jan-2017 and 31-Dec-2018 were included. The resources use within two years of the diagnosis was estimated in order to estimate the average cost of patient follow-up. Results: A total of 26,976 patients with an ASCVD episode were identified during the recruitment period; Out of them, 6,798 had a recurrent event during the follow-up period and 2,414 died. The average costs per patient were €11,171 during the first year and €9,944 during the second year. Discussion: Patients with ASCVD represent a significant economic burden for the health system and for society. Despite the perception that drug costs in the follow-up of chronic patients imply a high percentage of the costs, these accounted for only one tenth of the total amount. Implementing preventive programs and increasing the control of cardiovascular risk factors may have a significant social and health impact by helping to reduce mortality and costs for the Spanish National Health System. The costs derived from pharmacological treatments were obtained from the NHS pricing nomenclator database (https://www.sanidad.gob.es/profesionales/nomenclator.do).

Multidisciplinary Panel Consensus for the Management of Patients with Type 2 Diabetes: A Delphi Study.

AIM: To reach a multidisciplinary consensus on managing patients with type 2 diabetes among specialists in family medicine, cardiology, endocrinology, internal medicine, and nephrology. METHODS: A two-round Delphi study was conducted using a questionnaire with 68 positive/negative statements distributed in four thematic blocks on diabetes management: early diagnosis and prediabetes, referral criteria, treatment and comorbidities, and clinical management. The expert panel was composed of 105 physicians from different specialties (family medicine, cardiology, endocrinology, internal medicine, and nephrology) with experience in managing patients with diabetes and who were members of a diabetes-related society. RESULTS: Response rates for the first and second rounds were 86.7 and 75.2%, respectively. After both rounds, a consensus was reached on 52 (76.5%) items. The recommendations with the highest degree of consensus (median = 10, IQR = 0.00) were related to anti-smoking education, cardiovascular risk factor target control, and diabetic kidney disease. There were significant differences between family physicians and other specialties for some items. CONCLUSIONS: This study provides a set of recommendations for diabetes management agreed upon by specialists from different healthcare settings.

Consensus document for lipid profile testing and reporting in Spanish clinical laboratories: what parameters should a basic lipid profile include?

Cardiovascular diseases (CVD) continue to be the main cause of death in our country. Adequate control of lipid metabolism disorders is a key challenge in cardiovascular prevention that is far from being achieved in real clinical practice. There is a great heterogeneity in the reports of lipid metabolism from Spanish clinical laboratories, which may contribute to its poor control. For this reason, a working group of the main scientific societies involved in the care of patients at vascular risk, has prepared this document with a consensus proposal on the determination of the basic lipid profile in cardiovascular prevention, recommendations for its realization and unification of criteria to incorporate the lipid control goals appropriate to the vascular risk of the patients in the laboratory reports.

Consensus document for lipid profile determination and reporting in Spanish clinical laboratories. What parameters should be included in a basic lipid profile?

Cardiovascular diseases (CVD) continue to be the main cause of death in our country. Adequate control of lipid metabolism disorders is a key challenge in cardiovascular prevention that is far from being achieved in real clinical practice. There is a great heterogeneity in the reports of lipid metabolism from Spanish clinical laboratories, which may contribute to its poor control. For this reason, a working group of the main scientific societies involved in the care of patients at vascular risk, has prepared this document with a consensus proposal on the determination of the basic lipid profile in cardiovascular prevention, recommendations for its realization and unification of criteria to incorporate the lipid control goals appropriate to the vascular risk of the patients in the laboratory reports.

Dendritic Cell-Mediated Cross-Priming by a Bispecific Neutralizing Antibody Boosts Cytotoxic T Cell Responses and Protects Mice against SARS-CoV-2.

Administration of neutralizing antibodies (nAbs) has proved to be effective by providing immediate protection against SARS-CoV-2. However, dual strategies combining virus neutralization and immune response stimulation to enhance specific cytotoxic T cell responses, such as dendritic cell (DC) cross-priming, represent a promising field but have not yet been explored. Here, a broadly nAb, TNT , are first generated by grafting an anti-RBD biparatopic tandem nanobody onto a trimerbody scaffold. Cryo-EM data show that the TNT structure allows simultaneous binding to all six RBD epitopes, demonstrating a high-avidity neutralizing interaction. Then, by C-terminal fusion of an anti-DNGR-1 scFv to TNT , the bispecific trimerbody TNT DNGR-1 is generated to target neutralized virions to type 1 conventional DCs (cDC1s) and promote T cell cross-priming. Therapeutic administration of TNT DNGR-1, but not TNT , protects K18-hACE2 mice from a lethal SARS-CoV-2 infection, boosting virus-specific humoral responses and CD8+ T cell responses. These results further strengthen the central role of interactions with immune cells in the virus-neutralizing antibody activity and demonstrate the therapeutic potential of the Fc-free strategy that can be used advantageously to provide both immediate and long-term protection against SARS-CoV-2 and other viral infections.

Direct synthesis of haloaromatics from nitroarenes via a sequential one-pot Mo-catalyzed reduction/Sandmeyer reaction.

Herein, we report the direct synthesis of a wide variety of functionalized aromatic bromides, chlorides, iodides, and fluorides from nitroarenes in a sequential one-pot operation. This protocol is based on an air- and moisture-tolerant dioxomolybdenum-catalyzed reduction of nitroaromatics, employing pinacol as a reducing agent, which enables subsequent diazotization and halogenation steps. This methodology represents a step-economical, practical, and alternative procedure for synthesizing haloaromatics directly from nitroaromatics.

Membrane binding and pore formation is Ca 2+ -dependent for the Clostridioides difficile binary toxin.

The C. difficile binary toxin (CDT) enters host cells via endosomal delivery like many other 'AB'-type binary toxins. In this study, the cell-binding component of CDT, termed CDTb, was found to bind and form pores in lipid bilayers upon depleting free Ca 2+ ion concentrations, and not by lowering pH, as found for other binary toxins (i.e., anthrax). Cryoelectron microscopy, nuclear magnetic resonance spectroscopy, surface plasmon resonance, electrochemical impedance spectroscopy, CDT toxicity studies, and site directed mutagenesis show that dissociation of Ca 2+ from a single site in receptor binding domain 1 (RBD1) of CDTb is consistent with a molecular mechanism in which Ca 2+ dissociation from RBD1 induces a "trigger" via conformational exchange that enables CDTb to bind and form pores in endosomal membrane bilayers as free Ca 2+ concentrations decrease during CDT endosomal delivery.

Neurologic complications in herpes simplex encephalitis: clinical, immunological and genetic studies.

Patients with herpes simplex virus (HSV) encephalitis (HSE) often develop neuronal autoantibody-associated encephalitis (AE) post-infection. Risk factors of AE are unknown. We tested the hypotheses that predisposition for AE post-HSE may be involved, including genetic variants at specific loci, human leucocyte (HLA) haplotypes, or the blood innate immune response against HSV, including type I interferon (IFN) immunity. Patients of all ages with HSE diagnosed between 1 January 2014 and 31 December 2021 were included in one of two cohorts depending on whether the recruitment was at HSE onset (Spanish Cohort A) or by the time of new neurological manifestations (international Cohort B). Patients were assessed for the type of neurological syndromes; HLA haplotypes; blood type I-IFN signature [RNA quantification of 6 or 28 IFN-response genes (IRG)] and toll-like receptor (TLR3)-type I IFN-related gene mutations. Overall, 190 patients (52% male) were recruited, 93 in Cohort A and 97 in Cohort B. Thirty-nine (42%) patients from Cohort A developed neuronal autoantibodies, and 21 (54%) of them developed AE. Three syndromes (choreoathetosis, anti-NMDAR-like encephalitis and behavioural-psychiatric) showed a high (≥95% cases) association with neuronal autoantibodies. Patients who developed AE post-HSE were less likely to carry the allele HLA-A*02 (4/21, 19%) than those who did not develop AE (42/65, 65%, P = 0.0003) or the Spanish general population (2005/4335, 46%, P = 0.0145). Blood IFN signatures using 6 or 28 IRG were positive in 19/21 (91%) and 18/21 (86%) patients at HSE onset, and rapidly decreased during follow-up. At Day 21 after HSE onset, patients who later developed AE had higher median IFN signature compared with those who did not develop AE [median Zs-6-IRG 1.4 (0.6; 2.0) versus 0.2 (-0.4; 0.8), P = 0.03]. However, a very high median Zs-6-IRG (>4) or persistently increased IFN signature associated with uncontrolled viral infection. Whole exome sequencing showed that the percentage of TLR3-IFN-related mutations in patients who developed AE was not different from those who did not develop AE [3/37 (8%) versus 2/57 (4%), P = 0.379]. Multivariate logistic regression showed that a moderate increase of the blood IFN signature at Day 21 (median Zs-6-IRG >1.5 but <4) was the most important predictor of AE post-HSE [odds ratio 34.8, interquartile ratio (1.7-691.9)]. Altogether, these findings show that most AE post-HSE manifest with three distinct syndromes, and HLA-A*02, but not TLR3-IFN-related mutations, confer protection from developing AE. In addition to neuronal autoantibodies, the blood IFN signature in the context of HSE may be potentially useful for the diagnosis and monitoring of HSE complications.

Comprehensive Cardiovascular and Renal Protection in Patients with Type 2 Diabetes.

Type 2 diabetes (T2DM) is one of the main public health care problems worldwide. It is associated with a marked increased risk of developing atherosclerotic vascular disease, heart failure, chronic kidney disease and death. It is essential to act during the early phases of the disease, through the intensification of lifestyle changes and the prescription of those drugs that have been shown to reduce these complications, with the aim not only of achieving an adequate metabolic control, but also a comprehensive vascular risk control. In this consensus document, developed by the different specialists that treat these patients (endocrinologists, primary care physicians, internists, nephrologists and cardiologists), a more appropriate approach in the management of patients with T2DM or its complications is provided. A particular focus is given to the global control of cardiovascular risk factors, the inclusion of weight within the therapeutic objectives, the education of patients, the deprescription of those drugs without cardiovascular benefit, and the inclusion of GLP-1 receptor agonists and SGLT2 inhibitors as cardiovascular protective drugs, at the same level as statins, acetylsalicylic acid, or renin angiotensin system inhibitors.

Consensus document for lipid profile testing and reporting in Spanish clinical laboratories: What parameters should a basic lipid profile include?

Cardiovascular diseases (CVD) continue to be the main cause of death in our country. Adequate control of lipid metabolism disorders is a key challenge in cardiovascular prevention that is far from being achieved in real clinical practice. There is a great heterogeneity in the reports of lipid metabolism from Spanish clinical laboratories, which may contribute to its poor control. For this reason, a working group of the main scientific societies involved in the care of patients at vascular risk, has prepared this document with a consensus proposal on the determination of the basic lipid profile in cardiovascular prevention, recommendations for its realization and unification of criteria to incorporate the lipid control goals appropriate to the vascular risk of the patients in the laboratory reports.

Consensus document for lipid profile testing and reporting in Spanish clinical laboratories.

Cardiovascular diseases (CVD) continue to be the main cause of death in our country. Adequate control of lipid metabolism disorders is a key challenge in cardiovascular prevention that is far from being achieved in real clinical practice. There is a great heterogeneity in the reports of lipid metabolism from Spanish clinical laboratories, which may contribute to its poor control. For this reason, a working group of the main scientific societies involved in the care of patients at vascular risk, has prepared this document with a consensus proposal on the determination of the basic lipid profile in cardiovascular prevention, recommendations for its realization and unification of criteria to incorporate the lipid control goals appropriate to the vascular risk of the patients in the laboratory reports.

Impact of physician's perception about LDL cholesterol control in clinical practice when treating patients in Spain.

BACKGROUND AND AIMS: We aimed to understand the impact of physicians' perception about LDL-cholesterol (LDLc) control on the management of patients with dyslipidemia in Spain. METHODS: We performed a cross-sectional and multicenter study, in which 435 healthcare professionals participated in face-to-face meetings, collecting qualitative and quantitative information related to hypercholesterolemia management. Additionally, aggregated anonymized data of the last 10 patients with hypercholesterolemia attended by each physician were collected. RESULTS: A total of 4,010 patients (8%, 13%, 16% and 61% with low, moderate, high, and very high cardiovascular [CV] risk) were included. Physicians' perception was that 62% of their patients attained LDLc goals (66%, 63%, 61% and 56%, for low, moderate, high and very high CV risk, respectively). However, when looking into the data only 31% (vs 62% p<0.01) of patients attained the LDLc goals (47%, 36%, 22% and 25%, respectively). Overall, 33% of patients were taking high intensity statins, 32% statin/ezetimibe, 21% low/moderate intensity statins and 4% PCSK9 inhibitors. These numbers were 38%, 45%, 8% and 6% for very high risk patients and 44%, 21%, 21% and 4% for high CV risk patients. In 32% of patients, a change in lipid lowering therapy was performed after the visit, mainly combining statins/ezetimibe (55%). CONCLUSIONS: In Spain, most patients with dyslipidemia do not achieve the recommended LDLc goals because of an insufficient intensification of lipid lowering therapy. On the one hand, this is in part due to physicians misperception on preventive LDLc control and the need for repeated advice to patient, and, on the other, to the lack of patient adherence.

Synthesis of 1,4-ketoaldehydes and 1,4-diketones by Mo-catalyzed oxidative cleavage of cyclobutane-1,2-diols.

A new two-step procedure for the synthesis of 1,4-dicarbonyls has been developed involving an efficient and clean Mo-catalyzed oxidative cleavage of cyclobutane-1,2-diols with DMSO, which is used as solvent and oxidant. The required starting glycols were prepared by nucleophilic additions of organolithiums and Grignard reagents to easily available 2-hydroxycyclobutanones.