Subclinical choroidal involvement in Systemic Lupus Erythematosus.

PURPOSE: To assess the choroidal status of Systemic Lupus Erythematosus (SLE) patients using Optical Coherence Tomography (OCT) and OCT-Angiography. METHODS: SLE patients with disease duration < 10 years, no disease activity and no ocular involvement were recruited and cross-sectionally evaluated. A demographically similar cohort of healthy subjects was used for comparison. The main outcome is choroidal vascularity index (CVI). As secondary outcomes, choriocapillaris parameters and choroidal thickness (CT) were evaluated. RESULTS: Forty eyes of 40 subjects (20 SLE patients and 20 healthy subjects) were studied with a mean ± SD age of 36.7 ± 9.9 years. In the SLE group, the mean ± SD duration of disease was 7.35 ± 2.21 years. Increased CVI was found in the SLE group (p = 0.022). Considering the choriocapillaris, SLE patients presented a lower number (p = 0.037) and a smaller total area (p = 0.041) of signal voids. No differences between groups were found in CT. For SLE patients, CT at subfoveal, temporal and inferior locations presented a negative moderate correlation with disease duration. A strong correlation between choriocapillaris parameters and age was demonstrated for both groups. CONCLUSIONS: This study provides evidence of subclinical choroidal changes in adult SLE patients with inactive disease and no overt ocular manifestation. Increased CVI and fewer and smaller flow voids in choriocapillaris with normal CT suggest increased choroidal vascularity in SLE.

Predicted impact of banning nonessential, energy-dense food and beverages in schools in Mexico: A microsimulation study.

BACKGROUND: Childhood obesity is a growing concern worldwide. School-based interventions have been proposed as effective means to improve nutritional knowledge and prevent obesity. In 2023, Mexico approved a reform to the General Education Law to strengthen the ban of sales and advertising of nonessential energy-dense food and beverages (NEDFBs) in schools and surroundings. We aimed to predict the expected one-year change in total caloric intake and obesity prevalence by introducing the ban of NEDFBs sales in schools, among school-aged children and adolescents (6 to 17 years old) in Mexico. METHODS AND FINDINGS: We used age-specific equations to predict baseline fat-free mass (FFM) and fat mass (FM) and then estimated total energy intake (TEI) per day. The TEI after the intervention was estimated under 4 scenarios: (1) using national data to inform the intervention effect; (2) varying law compliance; (3) using meta-analytic data to inform the intervention effect size on calories; and (4) using national data to inform the intervention effect by sex and socioeconomic status (SES). We used Hall's microsimulation model to estimate the potential impact on body weight and obesity prevalence of children and adolescents 1 year after implementing the intervention in Mexican schools. We found that children could reduce their daily energy intake by 33 kcal/day/person (uncertainty interval, UI, [25, 42] kcal/day/person), reducing on average 0.8 kg/person (UI [0.6, 1.0] kg/person) and 1.5 percentage points (pp) in obesity (UI [1.1, 1.9] pp) 1 year after implementing the law. We showed that compliance will be key to the success of this intervention: considering a 50% compliance the intervention effect could reduce 0.4 kg/person (UI [0.3, 0.5] kg/person). Our sensitivity analysis showed that the ban could reduce body weight by 1.3 kg/person (UI [0.8, 1.8] kg/person) and up to 5.4 kg/person (UI [3.4, 7.5] kg/person) in the best-case scenario. Study limitations include assuming that obesity and the contribution of NEDFBs consumed at school remain constant over time, assuming full compliance, and not considering the potential effect of banning NEDFBs in stores near schools. CONCLUSIONS: Even in the most conservative scenario, banning sales of NEDFBs in schools is expected to significantly reduce obesity, but achieving high compliance will be key to its success. WHY WAS THIS STUDY DONE?: - School-based interventions have been recognized as effective means to improve nutritional knowledge and prevent obesity-related diseases.- In December 2023, the Chamber of Representatives of Mexico approved an amendment that strengthens and updates the General Education Law (Article 75) and nutritional guidelines to ban the sales and advertising of nonessential energy-dense food and beverages (NEDFBs) in schools. WHAT DID THE RESEARCHERS DO AND FIND?: - We used age-specific equations to predict baseline fat-free mass (FFM) and fat mass (FM) and total energy intake (TEI) per day.- We used microsimulation modeling to predict body weight and obesity prevalence of children and adolescents 1 year after implementing the intervention in Mexican schools.- Our modeling study suggests that an important impact on obesity prevalence can be expected if the law is implemented and enforced as intended. WHAT DO THESE FINDINGS MEAN?: - If successful, this law could serve as an example beyond Mexico on how to achieve changes in body weight through school food regulation.- An important limitation of our main scenario is that we assumed full compliance of schools with the law, yet lower compliance will reduce its impact. We also did not consider historical trends on obesity or NEDFBs consumed in schools during our 1 year simulation, and we considered only the ban impact inside schools, excluding effects near and outside schools.

Cardiopulmonary exercise testing in clinical practice: Principles, applications, and basic interpretation.

Cardiopulmonary exercise testing (CPET) provides a noninvasive and integrated assessment of the response of the respiratory, cardiovascular, and musculoskeletal systems to exercise. This information improves the diagnosis, risk stratification, and therapeutic management of several clinical conditions. Additionally, CPET is the gold standard test for cardiorespiratory fitness quantification and exercise prescription, both in patients with cardiopulmonary disease undergoing cardiac or pulmonary rehabilitation programs and in healthy individuals, such as high-level athletes. In this setting, the relevance of practical knowledge about this exam is useful and of interest to several medical specialties other than cardiology. However, despite its multiple established advantages, CPET remains underused. This article aims to increase awareness of the value of CPET in clinical practice and to inform clinicians about its main indications, applications, and basic interpretation.

Who is getting COVID-19 boosters? A latent class analysis in a nationally representative sample of Mexican adults 60 years and over.

OBJECTIVE: Estimate COVID-19 vaccine booster uptake and identify sociodemographic profiles associated with vaccine booster uptake in Mexican adults aged 60 and older. METHODS: Using data from the 2022 National Health and Nutrition Survey, we estimated COVID-19 booster uptake in Mexican adults 60 and older. We conducted a latent class analysis using sociodemographic characteristics and then estimated group-specific booster prevalence. RESULTS: Adults aged 60 and older with a completed vaccination schedule had 80.3% booster coverage. Two groups showed the lowest coverage: 1) unemployed and informal working men with elementary education with low socioeconomic status (73.8% boosted), and 2) female homekeepers with elementary education or less living in rural areas (77.0% boosted). CONCLUSIONS: Our analysis points to the need to reach out to men and women with elementary education or less who live in rural areas to strengthen booster campaigns in the future.

An Approach for Engineering Peptides for Competitive Inhibition of the SARS-COV-2 Spike Protein.

SARS-CoV-2 is the virus responsible for a respiratory disease called COVID-19 that devastated global public health. Since 2020, there has been an intense effort by the scientific community to develop safe and effective prophylactic and therapeutic agents against this disease. In this context, peptides have emerged as an alternative for inhibiting the causative agent. However, designing peptides that bind efficiently is still an open challenge. Here, we show an algorithm for peptide engineering. Our strategy consists of starting with a peptide whose structure is similar to the interaction region of the human ACE2 protein with the SPIKE protein, which is important for SARS-COV-2 infection. Our methodology is based on a genetic algorithm performing systematic steps of random mutation, protein-peptide docking (using the PyRosetta library) and selecting the best-optimized peptides based on the contacts made at the peptide-protein interface. We performed three case studies to evaluate the tool parameters and compared our results with proposals presented in the literature. Additionally, we performed molecular dynamics (MD) simulations (three systems, 200 ns each) to probe whether our suggested peptides could interact with the spike protein. Our results suggest that our methodology could be a good strategy for designing peptides.

Training and attitudes concerning cardiac rehabilitation in Portugal: A national survey of physician members of the Portuguese Society of Cardiology.

INTRODUCTION AND OBJECTIVES: Cardiac rehabilitation (CR) is a central component in the management of cardiovascular disease. While its potential benefits have been extensively explored and confirmed, its implementation is still suboptimal, due to various possible barriers. This study aimed to assess training and attitudes concerning CR among physicians in a Portuguese setting. METHODS: An online questionnaire structured in three parts (participant characteristics, training and attitudes concerning CR, and a brief general knowledge assessment) was developed and sent to members of the Portuguese Society of Cardiology. The study population encompassed physicians with a medical specialty or residents from the third year onward of a specialty program. RESULTS: A total of 97 individuals (57.7% male, 61.9% aged ≤50 years) presented valid answers. CR was available at the workplace of 54.6% of participants. Most of them considered that the time allocated to CR training during residency was inadequate, and thought that more time was needed for this purpose. Most had not dedicated (or intended to dedicate) time for CR training, with lack of time being the most frequently attributed reason. In terms of referral, a substantial proportion of subjects did not refer patients, with lack of CR centers and human resources being the most frequent reasons. CONCLUSIONS: This survey provides contemporary data on CR training and attitudes, highlighting areas of potential improvement, such as time allocated to training in this area. These results could provide a useful pragmatic framework for optimization of training and awareness in this pivotal field of cardiovascular medicine.

Exploring Biginelli-based scaffolds as A2B adenosine receptor antagonists: Unveiling novel structure-activity relationship trends, lead compounds, and potent colorectal anticancer agents.

Antagonists of the A2B adenosine receptor have recently emerged as targeted anticancer agents and immune checkpoint inhibitors within the realm of cancer immunotherapy. This study presents a comprehensive evaluation of novel Biginelli-assembled pyrimidine chemotypes, including mono-, bi-, and tricyclic derivatives, as A2BAR antagonists. We conducted a comprehensive examination of the adenosinergic profile (both binding and functional) of a large compound library consisting of 168 compounds. This approach unveiled original lead compounds and enabled the identification of novel structure-activity relationship (SAR) trends, which were supported by extensive computational studies, including quantum mechanical calculations and free energy perturbation (FEP) analysis. In total, 25 molecules showed attractive affinity (Ki < 100 nM) and outstanding selectivity for A2BAR. From these, five molecules corresponding to the new benzothiazole scaffold were below the Ki < 10 nM threshold, in addition to a novel dual A2A/A2B antagonist. The most potent compounds, and the dual antagonist, showed enantiospecific recognition in the A2BAR. Two A2BAR selective antagonists and the dual A2AAR/A2BAR antagonist reported in this study were assessed for their impact on colorectal cancer cell lines. The results revealed a significant and dose-dependent reduction in cell proliferation. Notably, the A2BAR antagonists exhibited remarkable specificity, as they did not impede the proliferation of non-tumoral cell lines. These findings support the efficacy and potential that A2BAR antagonists as valuable candidates for cancer therapy, but also that they can effectively complement strategies involving A2AAR antagonism in the context of immune checkpoint inhibition.

Sequential therapy with topical clobetasol for 14 days followed by hydroquinone versus hydroquinone alone in facial melasma treatment: a randomized, double-blind, controlled clinical trial.

BACKGROUND: Clobetasol has demonstrated remarkable results in treating melasma within a short time frame; however, its use is limited because of the risk of local side effects. To date, there is no controlled trial on sequential clobetasol/hydroquinone for melasma. This study aimed to investigate the tolerability and efficacy of 0.05% clobetasol followed by 4% hydroquinone (CLOB-HQ) in comparison to the isolated use of 4% hydroquinone (HQ). METHODS: A double-blinded, randomized clinical trial involving 50 women with facial melasma was performed. They were directed to apply 0.05% clobetasol every night for 14 days, followed by 4% hydroquinone for 46 days (CLOB-HQ group), or the use of hydroquinone for 60 days (HQ group). Evaluations were carried out at inclusion, and after 14 and 60 days of treatment, measuring modified Melasma Area and Severity Index (mMASI), Melasma Quality of Life scale (MELASQoL), and colorimetry. The Global Aesthetic Improvement Scale (GAIS) was assessed by a blinded evaluator. RESULTS: There was no difference in the main outcomes at D14 and D60 (P > 0.1). For CLOB-HQ, the mean (CI 95%) reduction in mMASI was 13.2% (5.1-21.3%) and 43.1% (32.2-54.0%) at D14 and D60, and for HQ, they were 10.6% (5.9-27.5%) and 44.8% (33.2-52.3%). The MELASQoL, colorimetric luminosity, and GAIS showed a progressive improvement for both groups despite no difference between them. No severe side effects were identified. No cases of telangiectasias, atrophy, or perioral dermatitis were associated with the use of CLOB. CONCLUSION: The sequential CLOB-HQ regimen was safe and well tolerated, even though its efficacy was not different from HQ after 14 or 60 days of treatment. Based on these findings, the use of clobetasol 14 days before hydroquinone is not advisable for the treatment of melasma.

Long-Term Refractive Outcomes and Visual Quality of Multifocal Intraocular Lenses Implantation in High Myopic Patients: A Multimodal Evaluation.

Purpose: To perform a multimodal assessment of refractive outcomes and quality of vision (QoV) in patients with high myopia submitted to multifocal intraocular lens (IOL) implantation. Methods: Retrospective study that included consecutive eyes with high myopia (axial length [AL] >26.00mm) submitted to multifocal IOL implantation between January 2014 and February 2020. Minimum follow-up time was 3 years. QoV was evaluated with the Objective Scatter Index (OSI) and the Modular Transfer Function (MTF) by HD Analyzer®. Two QoV questionnaires were applied to patients in which both eyes were included: the McAlinden and the Catquest-9 SF. Results: We included 50 eyes (28 patients). The mean follow-up time was 5.4±1.0 years. Comparing to month 1 after surgery, at the last follow-up visit, there was a decrease in the uncorrected visual acuity (0.14±0.13 vs 0.08±0.09 LogMAR, p=0.024), a negative increase in the spherical equivalent (-0.31±0.60 vs -0.02±0.20, p=0.006) and no changes in the best-corrected visual acuity (p>0.999). An uncorrected near visual acuity of at least J2 was achieved in 89% of eyes one month after surgery and in 91% of eyes at the last follow-up visit (p=0.829). At the last follow-up, the mean OSI was 5.1±1.8 and the mean MTF was 17.5±10.6. Some degree of near vision difficulty was reported by 91% of patients, and 74% of patients reported photic phenomena (halos, glare, starbursts). However, most patients reported that these symptoms caused none to little bothersome. At the last follow-up, 87% of patients were at least fairly satisfied with the surgery. Conclusion: Even after a mean follow-up time of 5 years, patients maintained good uncorrected visual acuity. Even though most patients experienced some degree of near vision difficulty and visual symptoms, globally, our patients were satisfied with their current vision, and the experienced symptoms did not have a significant impact on their daily lives.

Promoting healthy populations as a pandemic preparedness strategy: a simulation study from Mexico.

Background: The underlying health status of populations was a major determinant of the impact of the COVID-19 pandemic, particularly obesity prevalence. Mexico was one of the most severely affected countries during the COVID-19 pandemic and its obesity prevalence is among the highest in the world. It is unknown by how much the COVID-19 burden could have been reduced if systemic actions had been implemented to reduce excess weight in Mexico before the onset of the pandemic. Methods: Using a dynamic epidemic model based on nationwide data, we compare actual deaths with those under hypothetical scenarios assuming a lower body mass index in the Mexican population, as observed historically. We also model the number of deaths that would have been averted due to earlier implementation of front-of-pack warning labels or due to increases in taxes on sugar-sweetened beverages and non-essential high-energy foods in Mexico. Findings: We estimate that 52.5% (95% prediction interval (PI) 43.2, 61.6%) of COVID-19 deaths were attributable to obesity for adults aged 20-64 and 23.8% (95% PI 18.7, 29.1%) for those aged 65 and over. Had the population BMI distribution remained as it was in 2000, 2006, or 2012, COVID-19 deaths would have been reduced by an expected 20.6% (95% PI 16.9, 24.6%), 9.9% (95% PI 7.3, 12.9%), or 6.9% (95% PI 4.5, 9.5%), respectively. If the food-labelling intervention introduced in 2020 had been introduced in 2018, an expected 6.2% (95% PI 5.2, 7.3%) of COVID-19 deaths would have been averted. If taxes on sugar-sweetened beverages and high-energy foods had been doubled, trebled, or quadrupled in 2018, COVID-19 deaths would have been reduced by an expected 4.1% (95% PI 2.5, 5.7%), 7.9% (95% PI 4.9, 11.0%), or 11.6% (95% PI 7.3, 15.8%), respectively. Interpretation: Public health interventions targeting underlying population health, including non-communicable chronic diseases, is a promising line of action for pandemic preparedness that should be included in all pandemic plans. Funding: This study received funding from Bloomberg Philanthropies, awarded to Juan A. Rivera from the National Institute of Public Health; Community Jameel, the UK Medical Research Council (MRC), Kenneth C Griffin, and the World Health Organization.

Amphotericin B-loaded natural latex dressing for treating Candida albicans wound infections using Galleria mellonella model.

Amphotericin B (AmB) is the gold standard for antifungal drugs. However, AmB systemic administration is restricted because of its side effects. Here, we report AmB loaded in natural rubber latex (NRL), a sustained delivery system with low toxicity, which stimulates angiogenesis, cell adhesion and accelerates wound healing. Physicochemical characterizations showed that AmB did not bind chemically to the polymeric matrix. Electronic and topographical images showed small crystalline aggregates from AmB crystals on the polymer surface. About 56.6% of AmB was released by the NRL in 120 h. However, 33.6% of this antifungal was delivered in the first 24 h due to the presence of AmB on the polymer surface. The biomaterial's excellent hemo- and cytocompatibility with erythrocytes and human dermal fibroblasts (HDF) confirmed its safety for dermal wound application. Antifungal assay against Candida albicans showed that AmB-NRL presented a dose-dependent behavior with an inhibition halo of 30.0 ± 1.0 mm. Galleria mellonella was employed as an in vivo model for C. albicans infection. Survival rates of 60% were observed following the injection of AmB (0.5 mg.mL-1) in G. mellonella larvae infected by C. albicans. Likewise, AmB-NRL (0.5 mg.mL-1) presented survival rates of 40%, inferring antifungal activity against fungus. Thus, NRL adequately acts as an AmB-sustained release matrix, which is an exciting approach, since this antifungal is toxic at high concentrations. Our findings suggest that AmB-NRL is an efficient, safe, and reasonably priced ($0.15) dressing for the treatment of cutaneous fungal infections.

Use of Light Protection Equipment at Night Reduces Time Until Discharge From the Neonatal Intensive Care Unit: A Randomized Interventional Study.

Newborn infants' circadian systems are not completely developed and rely on external temporal cues for synchronizing their biological rhythms to the environment. In neonatal intensive care units (NICUs), lighting is usually continuous or irregular and infants are exposed to artificial light at night, which can have negative health consequences. Therefore, the aim of this study was to evaluate the impact of the use of individual light protection equipment at night on the development and growth of preterm neonates. Infants born at less than 37 gestational weeks who no longer needed constant intensive care were admitted into a newborn nursery and randomized to either use eye masks at night (intervention, n = 21) or not (control, n = 20). Infants who used eye protection at night were discharged earlier than those in the control group (8 [5] vs 12 [3.75] days; p < 0.05). A greater variation within the day in heart rate was observed in the intervention group, with lower values of beats per minute at 1400 and 2000 h. There was no significant difference in weight gain between groups. In view of our results and of previous findings present in the literature, we suggest that combining a darkened environment at night with individual light protection devices creates better conditions for the development of preterm infants in the NICU. In addition, eye masks are an affordable and simple-to-use tool that can reduce hospitalization costs by decreasing the number of days spent in the NICU.

Human social isolation and stress: a systematic review of different contexts and recommendations for future studies

Abstract Objectives The emergence of the coronavirus disease 2019 (COVID-19) pandemic and subsequent lockdowns and social distancing measures adopted worldwide raised questions about the possible health effects of human social isolation. Methods We conducted a systematic review on PubMed, Scopus, and Embase electronic databases using terms related to human social isolation - defined as the isolation of an individual from regular routines and usual social contact - and psychological stress, searching for simulated or naturalistic isolation environments. We present the main results, as well as the validity and limitations of each model. PROSPERO registry number: CRD42021241880. Results Despite the diversity of contexts reviewed, some outcomes almost ubiquitously relate to psychological stress, i.e., longer periods, expectation of a longer period, confinement, lack of social interaction, and support. Based on the results, and considering that most studies were not designed for the purpose of understanding isolation itself, we propose a group of recommendations for future experimental or naturalistic research on the topic. Conclusion Evidence on the impact of different situations in which individuals are subjected to social isolation can assist in development of directed preventive strategies to support people under similar circumstances. Such strategies might increase the general public's compliance with social distancing as a non-pharmacological intervention for emerging infectious diseases.

Taking biological rhythms into account: From study design to results reporting.

Numerous physiological and behavioral processes in living organisms exhibit strong rhythmicity and are regulated within a 24-hour cycle. These include locomotor activity and sleep patterns, feeding-fasting cycles, hormone synthesis, body temperature, and even mood and cognitive abilities, all of which are segregated into different phases throughout the day. These processes are governed by the internal timing system, a hierarchical multi-oscillator structure conserved across all organisms, from bacteria to humans. Circadian rhythms have been seen across multiple taxonomic kingdoms. In mammals, a hierarchical internal timing system is comprised of so-called central and periphereal clocks. Although these rhythms are intrinsic, they are under environmental influences, such as seasonal temperature changes, photoperiod variations, and day-night cycles. Recognizing the existence of biological rhythms and their primary external influences is crucial when designing and reporting experiments. Neglecting these physiological variations may result in inconsistent findings and misinterpretations. Thus, here we propose to incorporate biological rhythms into all stages of human and animal research, including experiment design, analysis, and reporting of findings. We also provide a flowchart to support decision-making during the design process, considering biological rhythmicity, along with a checklist outlining key factors that should be considered and documented throughout the study. This comprehensive approach not only benefits the field of chronobiology but also holds value for various other research disciplines. The insights gained from this study have the potential to enhance the validity, reproducibility, and overall quality of scientific investigations, providing valuable guidance for planning, developing, and communicating scientific studies.

Barriers, refusal and a hypothetical monetary incentive for Covid-19 vaccination in Mexican adults.

OBJECTIVE: To estimate vaccine uptake and assess sociodemographic conditions associated with vaccination barriers and refusal and to explore the effect of a monetary incentive to overcome them. MATERIALS AND METHODS: We used data from adults from the 2021 National Continuous Health and Nutrition Survey conducted during August-October 2021. We evaluated if an hypothetical monetary incentive between 50-650 MXN (~2.5-31 USD) would overcome barriers or refusal. RESULTS: 73.9% were vaccinated with at least one dose, 7.5% refused, 4.8% reported barriers and 13.8% were ineligible at the time of the survey. Refusal and barriers were more frequent in men, older age, lower education and socioeconomic status, unemployed and informal workers. In people with barriers and refusal, the hypothetical incentive increased the acceptance in 57.6% (95%CI 50.7,64.4%) and 17.4% (95%CI 13.2,21.7%) in people with barriers and refusal, respectively. CONCLUSION: Understanding the reasons for barriers and refusal is crucial for future Covid-19 vaccination campaigns or epidemics. A monetary incentive might increase vaccination uptake, although, cost-effectiveness analyses are needed.

Tamizaje, prevalencia, diagnóstico previo, tratamiento y control de hipertensión, hipercolesterolemia y diabetes en adultos mexicanos. Ensanut 2022.

OBJETIVO: Describir las estimaciones de tamizaje, prevalencia, diagnóstico previo, tratamiento y control de hipertensión, hipercolesterolemia y diabetes, así como sus factores asociados en los adultos mexicanos. Material y métodos. Se utilizó información de los adultos de 20 años o más participantes de la Encuesta Nacional de Salud y Nutrición 2022 (Ensanut 2022). Se presentan estimaciones de prevalencias con sus intervalos de confianza al 95%, y modelos de regresión logística múltiple para cada padecimiento, con factores asociados al tamizaje, diagnóstico previo, tratamiento y control. RESULTADOS: El tamizaje de estas tres enfermedades es bajo, menor a 15%. La prevalencia de hipercolesterolemia y de diabetes es de 18% y la de hipertensión es 27.8%; cerca de la mitad conoce su diagnóstico. La proporción de pacientes con tratamiento farmacológico ha incrementado, pero menos de la mitad está en control. Conclusión. Es recomendable que la detección de estas enfermedades se haga de manera integrada con otros factores de riesgo cardiovascular. Se necesita aumentar los porcentajes de tamizaje, incrementar la proporción de enfermos con diagnóstico previo, mejorar el porcentaje de tratamiento médico de estas enfermedades y, sobre todo, aumentar la proporción de enfermos con tratamiento en control metabólico.