In vitro higher-order oligomeric assembly of the respiratory syncytial virus M2-1 protein with longer RNAs.

The respiratory syncytial virus (RSV) M2-1 protein is a transcriptional antitermination factor crucial for efficiently synthesizing multiple full-length viral mRNAs. During RSV infection, M2-1 exists in a complex with mRNA within cytoplasmic compartments called inclusion body-associated granules (IBAGs). Prior studies showed that M2-1 can bind along the entire length of viral mRNAs instead of just gene-end (GE) sequences, suggesting that M2-1 has more sophisticated RNA recognition and binding characteristics. Here, we analyzed the higher oligomeric complexes formed by M2-1 and RNAs in vitro using size exclusion chromatography (SEC), electrophoretic mobility shift assays (EMSA), negative stain electron microscopy (EM), and mutagenesis. We observed that the minimal RNA length for such higher oligomeric assembly is about 14 nucleotides for polyadenine sequences, and longer RNAs exhibit distinct RNA-induced binding modality to M2-1, leading to enhanced particle formation frequency and particle homogeneity as the local RNA concentration increases. We showed that particular cysteine residues of the M2-1 cysteine-cysteine-cystine-histidine (CCCH) zinc-binding motif are essential for higher oligomeric assembly. Furthermore, complexes assembled with long polyadenine sequences remain unaffected when co-incubated with ribonucleases or a zinc chelation agent. Our study provided new insights into the higher oligomeric assembly of M2-1 with longer RNA.IMPORTANCERespiratory syncytial virus (RSV) causes significant respiratory infections in infants, the elderly, and immunocompromised individuals. The virus forms specialized compartments to produce genetic material, with the M2-1 protein playing a pivotal role. M2-1 acts as an anti-terminator in viral transcription, ensuring the creation of complete viral mRNA and associating with both viral and cellular mRNA. Our research focuses on understanding M2-1's function in viral mRNA synthesis by modeling interactions in a controlled environment. This approach is crucial due to the challenges of studying these compartments in vivo. Reconstructing the system in vitro uncovers structural and biochemical aspects and reveals the potential functions of M2-1 and its homologs in related viruses. Our work may contribute to identifying targets for antiviral inhibitors and advancing RSV infection treatment.

Impact of pregnancy on women's health-related lifestyle habits: Diet, physical activity, alcohol consumption, and smoking.

OBJECTIVES: To explore health-related lifestyles in women before and during pregnancy, and to determine the potential differences between both and the relevant factors. MATERIALS AND METHODS: A cross-sectional observational study including 348 women with a child <5 years of age was conducted in six health areas. The following variables were recorded: sociodemographic (age, educational level, marital status, social class, type of cohabitation, nationality), health-related habits (physical activity, diet, tobacco use, alcohol consumption), health conditions, and medication intake. RESULTS: Four lifestyle habits were compared between the pre-conception and pregnancy periods: diet, physical activity, and alcohol and tobacco use. The proportion of women who consumed alcohol (42.8 % vs 3.4 %) or smoked (19.3 % vs 12.4 %) was significantly higher before conception (p < 0.01). Conversely, the proportion of inactive women was lower before pregnancy, with 23.3 % (CI95%: 18.7-27.9) formerly classified as active versus 35.3 % (CI95%: 30.2-40.5) (p < 0.01). Similarly, adherence to the Mediterranean diet increased during pregnancy (62.9 % vs 75.0 %; p < 0.01). Furthermore, 53.2 % (CI95%: 47.8-58.5) of women reported a change from non-healthy to healthy in at least one of the evaluated habits. Logistic regression analyses revealed the variables associated with a positive change, which were being national Spanish (OR: 6.9) and experiencing the first pregnancy (OR: 1.8). CONCLUSIONS: The lifestyles of women undergo changes between the pre-gestation and pregnancy periods. However, such variations do not affect all health-related habits similarly. A positive change was observed in diet, alcohol consumption, and smoking habit, whereas pregnancy negatively impacted on physical activity and sedentary behaviours.

LAM Test: A New Cognitive Marker for Early Detection in Preclinical Alzheimer's Disease.

Background: With the arrival of disease-modifying treatments, it is mandatory to find new cognitive markers that are sensitive to Alzheimer's disease (AD) pathology in preclinical stages. Objective: To determine the utility of a newly developed Learning and Associative Memory face test: LAM test. This study examined the relationship between AD cerebrospinal fluid (CSF) biomarkers and performance on LAM test, and assessed its potential clinical applicability to detect subtle changes in cognitively healthy subjects at risk for AD. Methods: We studied eighty cognitively healthy volunteers from the Valdecilla cohort. 61% were women and the mean age was 67.34 years (±6.416). All participants underwent a lumbar puncture for determination of CSF biomarkers and an extensive neuropsychological assessment, including performance on learning and associative memory indices of the LAM-test after 30 min and after 1 week, and two classic word lists to assess verbal episodic memory: the Rey Auditory Verbal Learning Test (RAVLT) and the Free and Cued Selective Reminding Test (FCSRT). We analyzed cognitive performance according to amyloid status (A+ versus A-) and to ATN model (A-T-N-; A+T-N-; A+T+N-/A+T+N+). Results: Performance on the LAM-test was significantly correlated with CSF Aß ratio. A+ participants performed worse on both learning (mean difference = 2.19, p = 0.002) and memory LAM measures than A- (mean difference = 2.19, p = 0.004). A decline in performance was observed along the Alzheimer's continuum, with significant differences between ATN groups. Conclusions: Our findings suggest that LAM test could be a useful tool for the early detection of subjects within the AD continuum, outperforming classical memory tests.

Toward the European Health Data Space: The IMPaCT-Data secure infrastructure for EHR-based precision medicine research.

BACKGROUND: Art. 50 of the proposal for a Regulation on the European Health Data Space (EHDS) states that "health data access bodies shall provide access to electronic health data only through a secure processing environment, with technical and organizational measures and security and interoperability requirements". OBJECTIVE: To identify specific security measures that nodes participating in health data spaces shall implement based on the results of the IMPaCT-Data project, whose goal is to facilitate the exchange of electronic health records (EHR) between public entities based in Spain and the secondary use of this information for precision medicine research in compliance with the General Data Protection Regulation (GDPR). DATA AND METHODS: This article presents an analysis of 24 out of a list of 72 security measures identified in the Spanish National Security Scheme (ENS) and adopted by members of the federated data infrastructure developed during the IMPaCT-Data project. RESULTS: The IMPaCT-Data case helps clarify roles and responsibilities of entities willing to participate in the EHDS by reconciling technical system notions with the legal terminology. Most relevant security measures for Data Space Gatekeepers, Enablers and Prosumers are identified and explained. CONCLUSION: The EHDS can only be viable as long as the fiduciary duty of care of public health authorities is preserved; this implies that the secondary use of personal data shall contribute to the public interest and/or to protect the vital interests of the data subjects. This condition can only be met if all nodes participating in a health data space adopt the appropriate organizational and technical security measures necessary to fulfill their role.

Determinants of plasma levels of proglucagon and the metabolic impact of glucagon receptor signalling: a UK Biobank study.

AIMS/HYPOTHESES: Glucagon and glucagon-like peptide-1 (GLP-1) are derived from the same precursor; proglucagon, and dual agonists of their receptors are currently being explored for the treatment of obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). Elevated levels of endogenous glucagon (hyperglucagonaemia) have been linked with hyperglycaemia in individuals with type 2 diabetes but are also observed in individuals with obesity and MASLD. GLP-1 levels have been reported to be largely unaffected or even reduced in similar conditions. We investigated potential determinants of plasma proglucagon and associations of glucagon receptor signalling with metabolic diseases based on data from the UK Biobank. METHODS: We used exome sequencing data from the UK Biobank for ~410,000 white participants to identify glucagon receptor variants and grouped them based on their known or predicted signalling. Data on plasma levels of proglucagon estimated using Olink technology were available for a subset of the cohort (~40,000). We determined associations of glucagon receptor variants and proglucagon with BMI, type 2 diabetes and liver fat (quantified by liver MRI) and performed survival analyses to investigate if elevated proglucagon predicts type 2 diabetes development. RESULTS: Obesity, MASLD and type 2 diabetes were associated with elevated plasma levels of proglucagon independently of each other. Baseline proglucagon levels were associated with the risk of type 2 diabetes development over a 14 year follow-up period (HR 1.13; 95% CI 1.09, 1.17; n=1562; p=1.3×10-12). This association was of the same magnitude across strata of BMI. Carriers of glucagon receptor variants with reduced cAMP signalling had elevated levels of proglucagon (ß 0.847; 95% CI 0.04, 1.66; n=17; p=0.04), and carriers of variants with a predicted frameshift mutation had higher levels of liver fat compared with the wild-type reference group (ß 0.504; 95% CI 0.03, 0.98; n=11; p=0.04). CONCLUSIONS/INTERPRETATION: Our findings support the suggestion that glucagon receptor signalling is involved in MASLD, that plasma levels of proglucagon are linked to the risk of type 2 diabetes development, and that proglucagon levels are influenced by genetic variation in the glucagon receptor, obesity, type 2 diabetes and MASLD. Determining the molecular signalling pathways downstream of glucagon receptor activation may guide the development of biased GLP-1/glucagon co-agonist with improved metabolic benefits. DATA AVAILABILITY: All coding is available through https://github.com/nicwin98/UK-Biobank-GCG.

Oculomotor Dysfunction in Idiopathic and LRRK2-Parkinson's Disease and At-Risk Individuals.

Background: Video-oculography constitutes a highly-sensitive method of characterizing ocular movements, which could detect subtle premotor changes and contribute to the early diagnosis of Parkinson's disease (PD). Objective: To investigate potential oculomotor differences between idiopathic PD (iPD) and PD associated with the G2019S variant of LRRK2 (L2PD), as well as to evaluate oculomotor function in asymptomatic carriers of the G2019S variant of LRRK2. Methods: The study enrolled 129 subjects: 30 PD (16 iPD, 14 L2PD), 23 asymptomatic carriers, 13 non-carrier relatives of L2PD patients, and 63 unrelated HCs. The video-oculographic evaluation included fixation, prosaccade, antisaccade, and memory saccade tests. Results: We did not find significant differences between iPD and L2PD. Compared to controls, PD patients displayed widespread oculomotor deficits including larger microsaccades, hypometric vertical prosaccades, increased latencies in all tests, and lower percentages of successful antisaccades and memory saccades. Non-carrier relatives showed oculomotor changes with parkinsonian features, such as fixation instability and hypometric vertical saccades. Asymptomatic carriers shared multiple similarities with PD, including signs of unstable fixation and hypometric vertical prosaccades; however, they were able to reach percentages of successful antisaccade and memory saccades similar to controls, although at the expense of longer latencies. Classification accuracy of significant oculomotor parameters to differentiate asymptomatic carriers from HCs ranged from 0.68 to 0.74, with BCEA, a marker of global fixation instability, being the parameter with the greatest classification accuracy. Conclusions: iPD and LRRK2-G2019S PD patients do not seem to display a differential oculomotor profile. Several oculomotor changes in asymptomatic carriers of LRRK2 mutations could be considered premotor biomarkers.

Exploring the influence of dietary habits on foot risk in type 2 diabetes patients: An observational study.

BACKGROUND & AIM: To date, there are no studies demonstrating the impact of the Mediterranean diet on the risk of diabetic foot ulcer. The aim of this research was to examine the connection between adherence to the Mediterranean diet and the level of risk of diabetic foot ulcers in individuals with type 2 diabetes. METHODS: Observational pilot study collecting sociodemographic, anthropometric, lifestyle, and type 2 diabetes-related data. Loss of protective sensation was assessed using the Semmes Weinstein 5.07-10 g monofilament, considered altered when not perceived in four points. Vascular status was assessed by palpating pulses and ankle-brachial index, indicating peripheral arterial disease if ankle-brachial index was less than 0.9 or if both pulses were absent. Foot deformities were recorded. The risk of diabetic foot ulcers was stratified into two categories: no risk and risk of diabetic foot ulcers. Adherence to the Mediterranean diet was evaluated using the Mediterranean Diet Adherence Screener-14 questionnaire (good adherence with score >7). RESULTS: Of the 174 patients with type 2 diabetes mellitus who participated (61.5% men and 38.5% women) with a mean age of 69.56 ± 8.86 years and a mean duration of type 2 diabetes of 15.34 ± 9.83 years. Non-adherent patients to the Mediterranean diet exhibited a higher association of diabetic foot ulcers (p = 0.030) and a lower average score on the Mediterranean Diet Adherence Screener-14 (p = 0.011). Additionally, a lower incidence of diabetic foot ulcers was observed in those who consumed nuts three or more times a week (p = 0.003) and sautéed foods two or more times a week (p = 0.003). Multivariate analysis highlighted the importance of physical activity (OR = 0.25, 95% CI 0.11-0.54; p < 0.001), podiatric treatment (OR = 2.59, 95% CI 1.21-5.56; p = 0.014), and duration of type 2 diabetes (OR = 3.25, 95% CI 1.76-5.99; p < 0.001) as significantly associated factors related to the risk of diabetic foot ulcers. CONCLUSIONS: Adhering to the Mediterranean diet correlates with a lower incidence of diabetic foot ulcers in individuals diagnosed with type 2 diabetes mellitus. Furthermore, factors such as regular physical activity, podiatric treatment, and the duration of type 2 diabetes mellitus emerge as pivotal in preventing diabetic foot ulcers.

Platypnea-Orthodeoxia Syndrome and COVID-19 Successfully Treated With Percutaneous Patent Foramen Ovale Closure: A Report of Two Cases and Literature Review.

Platypnea-orthodeoxia syndrome (POS) is a rare clinical condition characterized by positional dyspnea and/or hypoxia. We report two cases of patients with COVID-19 bronchopneumonia with a torpid evolution. Due to clinical suspicion of POS, a diagnostic workup was performed, including a bubble echocardiography, which revealed a patent foramen ovale (PFO) with early and massive passage of bubbles to the left cavities. Both patients underwent percutaneous PFO closure with a resolution of POS. Here, we present the second and third cases of POS associated with PFO successfully closed during the acute phase of COVID-19. This suggests that PFO closure could be a potential treatment option for this condition.

Recent Research Trends in Neuroinflammatory and Neurodegenerative Disorders.

Neuroinflammatory and neurodegenerative disorders including Alzheimer's disease (AD), Parkinson's disease (PD), traumatic brain injury (TBI) and Amyotrophic lateral sclerosis (ALS) are chronic major health disorders. The exact mechanism of the neuroimmune dysfunctions of these disease pathogeneses is currently not clearly understood. These disorders show dysregulated neuroimmune and inflammatory responses, including activation of neurons, glial cells, and neurovascular unit damage associated with excessive release of proinflammatory cytokines, chemokines, neurotoxic mediators, and infiltration of peripheral immune cells into the brain, as well as entry of inflammatory mediators through damaged neurovascular endothelial cells, blood-brain barrier and tight junction proteins. Activation of glial cells and immune cells leads to the release of many inflammatory and neurotoxic molecules that cause neuroinflammation and neurodegeneration. Gulf War Illness (GWI) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are chronic disorders that are also associated with neuroimmune dysfunctions. Currently, there are no effective disease-modifying therapeutic options available for these diseases. Human induced pluripotent stem cell (iPSC)-derived neurons, astrocytes, microglia, endothelial cells and pericytes are currently used for many disease models for drug discovery. This review highlights certain recent trends in neuroinflammatory responses and iPSC-derived brain cell applications in neuroinflammatory disorders.

Plasma Phosphorylated Tau 231 Increases at One-Year Intervals in Cognitively Unimpaired Subjects.

Background: Plasma biomarkers of Alzheimer's disease (AD) constitute a non-invasive tool for diagnosing and classifying subjects. They change even in preclinical stages, but it is necessary to understand their properties so they can be helpful in a clinical context. Objective: With this work we want to study the evolution of p-tau231 plasma levels in the preclinical stages of AD and its relationship with both cognitive and imaging parameters. Methods: We evaluated plasma phosphorylated (p)-tau231 levels in 146 cognitively unimpaired subjects in sequential visits. We performed a Linear Mixed-effects Model to analyze their rate of change. We also correlated their baseline levels with cognitive tests and structural and functional image values. ATN status was defined based on cerebrospinal fluid biomarkers. Results: Plasma p-tau231 showed a significant rate of change over time. It correlated negatively with memory tests only in amyloid-positive subjects. No significant correlations were found with any imaging measures. Conclusions: Increases in plasma p-tau231 can be detected at one-year intervals in cognitively healthy subjects. It could constitute a sensitive marker for detecting early signs of neuronal network impairment by amyloid.

Where Should I Draw the Line: PET-Driven, Data-Driven, or Manufacturer Cut-Off?

Background: The optimal cut-off for Alzheimer's disease (AD) CSF biomarkers remains controversial. Objective: To analyze the performance of cut-off points standardized by three methods: one that optimized the agreement between 11C-Pittsburgh compound B PET (a-PET) and CSF biomarkers (Aß1-42, pTau, tTau, and Aß1-42/Aß1-40 ratio) in our population, called PET-driven; an unbiased cut-off using data from a healthy research cohort, called data-driven, and that provided by the manufacturer. We also compare changes in ATN classification. Methods: CSF biomarkers measured by the LUMIPULSE G600II platform and qualitative visualization of amyloid positron emission tomography (a-PET) were performed in all the patients. We established a cut-off for each single biomarker and Aß1-42/Aß1-40 ratio that optimized their agreement with a-PET using ROC curves. Sensitivity, Specificity, and Overall Percent of Agreement are assessed using a-PET or clinical diagnosis as gold standard for every cut-off. Also, we established a data-driven cut-off from our cognitively unimpaired cohort. We then analyzed changes in ATN classification. Results: One hundred and ten patients were recruited. Sixty-six (60%) were a-PET positive. PET-driven cut-offs were: pTau > 57, tTau > 362.62, Aß1-42/Aß1-40 < 0.069. For a single biomarker, pTau showed the highest accuracy (AUC 0.926). New PET-driven cut-offs classified patients similarly to manufacturer cut-offs (only two patients changed). However, 20 patients (18%) changed when data-driven cut-offs were used. Conclusions: We established our sample's best CSF biomarkers cut-offs using a-PET as the gold standard. These cut-offs categorize better symptomatic subjects than data-driven in ATN classification, but they are very similar to the manufacturer's.

Síndrome de Alicia en el País de las Maravillas secundario a infección por SARS-CoV-2 / Alice in Wonderland syndrome in SARS-CoV-2 infection

El síndrome de Alicia en el País de las Maravillas es un conjunto de trastornos complejos de la percepción visual con múltiples etiologías, siendo las infecciones las más frecuentes en Pediatría. Es un cuadro poco frecuente, pero es importante conocerlo por su carácter generalmente autolimitado. Presentamos el caso de un niño de 11 años que, a las 48 horas de infección por SARS-CoV-2, inició distorsión visual de la forma corporal, micropsias y macropsias. Se descartaron otras causas orgánicas, manteniéndose actitud expectante dada su evolución benigna. Se destaca la aparición de este síndrome en contexto clínico de infección por SARS-CoV-2, no habiendo sido descrita hasta ahora su asociación en la literatura. (AU)

The Alice in Wonderland syndrome is defined by the presence of visual perception disorders with several etiologies, being infectious the most frequent in pediatrics. It is a rare clinical condition, but it is important to recognize it because of the generally self-limited nature. We present an 11 years old child who presented visual body distortions, micropsia and macropsia 48 after SARS-CoV-2 infection. Other organic causes were discarded, maintaining an expectant treatment because of its benign evolution. It is noteworthy that this syndrome associated with SARS-CoV-2 infection has not yet been published. (AU)

Bronquiolitis obliterante posinfecciosa secundaria a adenovirus / Post-infectious bronchiolitis obliterans secondary to adenovirus

La bronquiolitis obliterante es una rara enfermedad respiratoria obstructiva crónica, secundaria a una agresión de las vías respiratorias inferiores que provoca inflamación y obliteración, parcial o total, de las mismas. Existen diferentes causas que la provocan, siendo la infecciosa la más frecuente en Pediatría, principalmente, por adenovirus. Se presenta el caso de un lactante varón de 18 meses de edad, con el antecedente de ingreso a los 8 meses en la unidad de cuidados intensivos pediátricos por bronquitis secundaria a virus respiratorio sincitial y adenovirus. Posteriormente a este episodio, presenta de forma persistente dificultad respiratoria y auscultación pulmonar patológica. La tomografía computarizada pulmonar de alta resolución muestra patrón en mosaico con áreas de atrapamiento aéreo y disminución del calibre vascular en las zonas afectas, hallazgos sugestivos de bronquiolitis obliterante. (AU)

Bronchiolitis obliterans is a rare chronic obstructive respiratory disease secondary to damage of the lower respiratory tract causing inflammation and partial or total obliteration of it. There are different causes, being infectious the most frequent in pediatrics, mainly due to adenovirus. We present the case of an 18-month-old male infant with a history of admission to the Pediatric Intensive Care Unit at 8 months of age due to bronchitis secondary to respiratory syncytial virus and adenovirus. After this episode, he presented persistent respiratory distress and pathological pulmonary auscultation. High resolution pulmonary computed tomography showed a mosaic pattern with areas of air trapping and decreased vascular caliber in the affected areas, findings suggestive of bronchiolitis obliterans. (AU)

Influence of Physiological Variables and Comorbidities on Plasma Aß40, Aß42, and p-tau181 Levels in Cognitively Unimpaired Individuals.

Plasma biomarkers for Alzheimer's disease (AD) are a promising tool that may help in early diagnosis. However, their levels may be influenced by physiological parameters and comorbidities that should be considered before they can be used at the population level. For this purpose, we assessed the influences of different comorbidities on AD plasma markers in 208 cognitively unimpaired subjects. We analyzed both plasma and cerebrospinal fluid levels of Aß40, Aß42, and p-tau181 using the fully automated Lumipulse platform. The relationships between the different plasma markers and physiological variables were studied using linear regression models. The mean differences in plasma markers according to comorbidity groups were also studied. The glomerular filtration rate showed an influence on plasma Aß40 and Aß42 levels but not on the Aß42/Aß40 ratio. The amyloid ratio was significantly lower in diabetic and hypertensive subjects, and the mean p-tau181 levels were higher in hypertensive subjects. The glomerular filtration rate may have an inverse relationship on plasma Aß40 and Aß42 levels but not on the amyloid ratio, suggesting that the latter is a more stable marker to use in the general population. Cardiovascular risk factors might have a long-term effect on the amyloid ratio and plasma levels of p-tau181.

Traditional Atlantic Diet and Its Effect on Health and the Environment: A Secondary Analysis of the GALIAT Cluster Randomized Clinical Trial.

Importance: The universal call to action for healthier and more sustainable dietary choices is the framework of the United Nations's Sustainable Development Goals. The Atlantic diet, originating from the northwest of the Iberian Peninsula, represents an example of a traditional diet that aligns with these principles. Objective: To explore a 6-month intervention based on the Atlantic diet's effects on metabolic and environmental health, assessing metabolic syndrome (MetS) incidence and the carbon footprint. Design, Setting, and Participants: The Galician Atlantic Diet study was a 6-month randomized clinical trial designed to assess the effects of this regional traditional diet on families' eating habits. The study was conducted from March 3, 2014, to May 29, 2015, at a local primary health care center in the rural town of A Estrada in northwestern Spain and involved a multisectoral collaboration. Families were randomly selected from National Health System records and randomized 1:1 to an intervention or control group. This secondary analysis of the trial findings was performed between March 24, 2021, and November 7, 2023. Interventions: Over 6 months, families in the intervention group received educational sessions, cooking classes, written supporting material, and foods characteristic of the Atlantic diet, whereas those randomized to the control group continued with their habitual lifestyle. Main Outcomes and Measures: The main outcomes were MetS incidence, defined per National Cholesterol Education Program Adult Treatment Panel III guidelines, and carbon footprint emissions as an environmental metric using life cycle assessment with daily dietary intake as the functional unit. Results: Initially, 250 families were randomized (574 participants; mean [SD] age, 46.8 [15.7] years; 231 males [40.2%] and 343 females [59.8%]). The intervention group included 126 families (287 participants) and the control group, 124 families (287 participants). Ultimately, 231 families completed the trial. The intervention significantly reduced the risk of incident cases of MetS (rate ratio, 0.32; 95% CI, 0.13-0.79) and had fewer MetS components (proportional odds ratio, 0.58; 95% CI, 0.42-0.82) compared with the control condition. The intervention group did not have a significantly reduced environmental impact in terms of carbon footprint emissions compared with the control group (-0.17 [95% CI, -0.46 to 0.12] kg CO2 equivalents/person/d). Conclusions and Relevance: These findings provide important evidence that a family-focused dietary intervention based on a traditional diet can reduce the risk of incident MetS. Further research is needed to understand the underlying mechanisms and determine the generalizability to other populations, taking into account regional cultural and dietary variations. Trial Registration: ClinicalTrials.gov Identifier: NCT02391701.

El uso diario de la profilaxis preexposición para el VIH en hombres gais, bisexuales y otros hombres que tienen sexo con hombres en España: prevalencia y factores asociados / Daily use of HIV pre-exposure prophylaxis among gay, bisexual and other men who have sex with men in Spain: Prevalence and associated factors

Objetivo: Estimar la prevalencia de uso diario de profilaxis preexposición (PrEP) frente al VIH 6 meses después de aprobarse su financiación pública en España e identificar los factores asociados en una muestra nacional de hombres gais, bisexuales y otros hombres que tienen sexo con hombres (GBHSH). Material y métodos: Se analizaron 4.692 hombres GBHSH no diagnosticados de VIH reclutados mediante un cuestionario online difundido a nivel nacional a través de apps y webs de contacto gay entre mayo y julio de 2020. Se estimó la proporción de participantes que usaban PrEP diaria y se identificaron factores asociados mediante regresión de Poisson con variancia robusta. Resultados: El 2,8% (IC 95% 2,3-3,3) de los participantes refirió usar PrEP diariamente. El uso diario de PrEP se asoció de forma independiente con: haber sido reclutado en programas comunitarios, ser mayor de 30 años, residir en grandes ciudades, vivir abiertamente su vida sexual con hombres, haber tenido relaciones anales sin preservativo con más de 10 parejas sexuales, haber consumido drogas para sexo, especialmente drogas chemsex, y haber sido diagnosticado de alguna infección de transmisión sexual. Conclusión: Transcurridos 6 meses desde la aprobación de la PrEP en España, se observa una baja prevalencia de uso diario en una muestra nacional de hombres GBHSH. Es necesario promover el acceso, la demanda y el interés por la PrEP, especialmente entre los hombres GBHSH jóvenes, residentes en ciudades pequeñas y medianas y los que ocultan sus relaciones con otros hombres.(AU)

Objective: We aim to estimate the prevalence of daily HIV pre-exposure prophylaxis (PrEP) use 6 months after public funding approval in Spain and identify associated factors in a national sample of gay, bisexual and other men who have sex with men (GBMSM). Material and methods: We analysed 4692 HIV-undiagnosed GBMSM men recruited via an online questionnaire distributed nationally via gay contact apps and websites between May and July 2020. We estimated the proportion of participants using daily PrEP and identified associated factors using Poisson regression with robust variance. Results: Daily PrEP use was reported by 2.8% (95% CI 2.3-3.3) of all participants. Daily PrEP use was independently associated with being recruited into community programmes, being older than 30 years, living in a large city, living with men, having condomless anal intercourse with more than 10 sexual partners, using drugs for sex, especially chemsex drugs, and being diagnosed with a sexually transmitted infection. Conclusion: Six months after PrEP was approved in Spain, the prevalence of daily use is low in a national sample of GBMSM men. There is a need to promote access, demand and interest in PrEP, especially among young GBMSM men, those living in small and medium-sized cities, and those who hide their relationships with other men.(AU)

Adherence to a healthy lifestyle behavior composite score and cardiometabolic risk factors in Spanish children from the CORALS cohort.

To assess the associations between the adherence to a composite score comprised of 6 healthy lifestyle behaviors and its individual components with several cardiometabolic risk factors in Spanish preschool children. Cross-sectional analyses were conducted in 938 participants included in the CORALS cohort aged 3-6 years. Six recognized healthy lifestyle behaviors (breastfeeding, sleep duration, physical activity, screentime, adherence to the Mediterranean diet, and eating speed) were assessed in a composite score. Multiple linear and logistic regression models were fitted to assess the associations with cardiometabolic risk factors (weight status, waist circumference, fat mass index, blood pressure, fasting plasma glucose, and lipid profile). In the adjusted multiple linear and logistic regression models, compared with the reference category of adherence to the healthy lifestyle behavior composite score, those participants in the category of the highest adherence showed significant decreased prevalence risk of overweight or obesity [OR (95% CI), 0.4 (0.2, 0.6)] as well as significant lower waist circumference, fat mass index (FMI), systolic blood pressure and fasting plasma glucose concentration [ß (95% CI), - 1.4 cm (- 2.5, - 0.4); - 0.3 kg/m2 (- 0.5, - 0.1); and - 3.0 mmHg (- 5.2, - 0.9); - 1.9 mg/dL (- 3.5, - 0.4), respectively]. Slow eating speed was individually associated with most of the cardiometabolic risk factors.   Conclusions: Higher adherence to the healthy lifestyle behavior composite score was associated with lower waist circumference, FMI, other cardiometabolic risk factors, and risk of overweight or obesity in Spanish preschool children. Further studies are required to confirm these associations. What is Known: • Lifestyle is a well-recognized etiologic factor of obesity and its comorbidities. • Certain healthy behaviors such as adhering to a healthy diet, increasing physical activity, and decreasing screentime are strategies for prevention and treatment of childhood obesity. What is New: • Higher adherence to the healthy lifestyle behavior composite score to 6 healthy behaviors (breastfeeding, sleep duration, physical activity, screentime, eating speed, and adherence to the Mediterranean diet) was associated with decreased adiposity, including prevalence risk of overweight or obesity, and cardiometabolic risk in preschool children. • Slow eating and greater adherence to the Mediterranean diet were mainly associated to lower fasting plasma and serum triglycerides concentration, respectively.

Direct Decarboxylation of Trifluoroacetates Enabled by Iron Photocatalysis.

Trifluoroacetates are the most abundant and accessible sources of trifluoromethyl groups, which are key components in pharmaceuticals and agrochemicals. The generation of trifluoromethyl reactive radicals from trifluoroacetates requires their decarboxylation, which is hampered by their high oxidation potential. This constitutes a major challenge for redox-based methods, because of the need to pair the redox potentials with trifluoroacetate. Here we report a strategy based on iron photocatalysis to promote the direct photodecarboxylation of trifluoroacetates that displays reactivity features that escape from redox limitations. Our synthetic design has enabled the use of trifluoroacetates for the trifluoromethylation of more easily oxidizable organic substrates, offering new opportunities for late-stage derivatization campaigns using chemical feedstocks, Earth-abundant catalysts, and visible-light.