A Mediterranean lifestyle reduces the risk of cardiovascular disease in the “Seguimiento Universidad de Navarra” (SUN) cohort

Background and aims: A healthy lifestyle is essential to prevent cardiovascular disease (CVD). However, beyond dietary habits, there is a scarcity of studies comprehensively assessing the typical traditional Mediterranean lifestyle with a multi-dimensional index. We assessed the association between the Mediterranean lifestyle (measured with the MEDLIFE index including diet, physical activity, and other lifestyle factors) and the incidence of CVD. Methods and results: The “Seguimiento Universidad de Navarra” (SUN) project is a prospective, dynamic and multipurpose cohort of Spanish university graduates. We calculated a MEDLIFE score, composed of 28 items on food consumption, dietary habits, physical activity, rest, social habits, and conviviality, for 18,631 participants by assigning 1 point for each typical Mediterra- nean lifestyle factor achieved, for a theoretically possible final score ranging from 0 to 28 points. During an average follow-up of 11.5 years, 172 CVD cases (myocardial infarction, stroke or cardio- vascular death) were observed. An inverse association between the MEDLIFE score and the risk of primary cardiovascular events was observed, with multivariable-adjusted hazard ratio (HR) Z 0.50; (95% confidence interval, 0.31e0.81) for the highest MEDLIFE scores (14e23 points) compared to the lowest scores (0e9 points), p (trend) Z 0.004. Conclusion: A higher level of adherence to the Mediterranean lifestyle was significantly associ- ated with a lower risk of CVD in a Spanish cohort. Public health strategies should promote the Mediterranean lifestyle to preserve cardiovascular health

Intervencionismo coronario percutáneo en Navarra. Resultados de un centro de bajo volumen intervencionista

Fundamento. El intervencionismo coronario percutáneo (PCI) es una opción terapéutica fundamental en pacientes con enfermedad coronaria. Para realizarla los especialistas deben formarse y acreditarse. Se sabe que el número de procedimientos realizados al año influye en los resultados. Pretendemos mostrar que con un bajo volumen de PCI algunos centros obtienen buenos resultados. Método. Análisis prospectivo de las características clínicas y resultados inmediatos obtenidos en nuestro centro con el PCI entre 2006 y 2012 y análisis retrospectivo de la supervivencia global, supervivencia libre de eventos y reestenosis de los PCI realizados entre 2006 y 2009. Se compararon las características clínicas, los eventos agudos y a largo plazo (complicaciones, supervivencia y mortalidad) entre nuestros pacientes y los de algunos trabajos publicados. Resultados. Nuestra probabilidad de tener cualquier complicación en un PCI fue del 9% con una mortalidad global del 2%. La mortalidad del PCI en situación estable fue del 0,43% y en el síndrome coronario agudo del 6,25%. Las complicaciones en el lugar del acceso vascular fueron del 1,44% y la incidencia de reestenosis a los nueve meses, en pacientes sometidos por primera vez a PCI, fue del 5,2%. Conclusiones. Aunque el alto volumen intervencionista ha demostrado ser importante para tener una baja tasa de complicaciones y una buena evolución a largo plazo, hay centros con bajo volumen intervencionista que por sus características pueden obtener resultados equiparables a los de alto volumen.Background. Percutaneous coronary intervention (PCI) is currently a basic therapeutic option in patients with coronary artery disease. To carry this out specialists must be trained and accredited. It is known that the number of procedures performed each year influences results. We suggest that some low volume centres may also get good results. Methods. Prospective analysis of clinical features and immediate results obtained in our centre following PCI performed between 2006 and 2012 and retrospective analysis of overall survival, outcome-free survival and restenosis in patients treated between 2006 and 2009. The clinical features, acute and long-term events (complications, survival and mortality) of our group were compared with other published studies. Results. In our centre the likelihood of complications in a PCI was 9% with an overall mortality of 2%. PCI mortality in stable coronary disease was 0.43% and in acute coronary syndrome 6.25%. Complications at the vascular access site was 1.44% and restenosis at nine months, in patients undergoing PCI for the first time, was 5.2%. Conclusions. Although a high interventionist volume has been shown to reduce the rate of complications and improve long-term evolution, some low volume interventional centres can obtain similar results to those of high volume interventional centres

Smoking and incidence of glaucoma The SUN Cohort

Smoking is a serious global public health concern that has been related to many chronic diseases. However, the effect of smoking on eye disorders has been less studied. The aim of this cohort study was to assess the association between current tobacco smokers and the risk of developing glaucoma and furthermore to evaluate the relationship between passive or former smokers and glaucoma. In this prospective and dynamic cohort, 16,797 participants initially who were found not to have glaucoma were followed up for a median of 8.5 years. Validated data on lifestyle, including tobacco consumption, were assessed at baseline. Information about new diagnosis of glaucoma was collected by follow-up questionnaires every 2 years. The outcome was the incidence of self-reported glaucoma during the follow-up. A subsample was used to validate the glaucoma diagnosis. During the 8.5 years of follow-up, 184 new glaucoma cases were identified. Current smokers had a significantly higher risk of glaucoma compared to participants who had never smoked after controlling for potential confounders (Hazard ratio [HR] 1.88 [95% coefficient interval (CI): 1.26–2.81]; P=0.002). A nonsignificant increased risk was found among former smokers (HR 1.27 [95% CI: 0.88–1.82]; P=0.198). When we assessed the exposure as per the number of cigarette pack-years, a dose–response relationship between pack-years and the risk of glaucoma was found (HR for the 5th quintile versus the 1st quintile: 1.70 [95% IC: 1.10–2.64], P for trend, 0.009). However, no relationship was found between passive smokers and glaucoma. (HR 0.67 [95% CI: 0.37–1.21]; P=0.189). Our results suggest a direct association between current smokers and the incidence of glaucoma. In particular, this association was related to the number of pack-years, which was not found in the case of former smokers nor in the case of passive smokers. Abbreviations: IOP = intraocular pressure, POAG = primary open angle glaucoma, SUN = Seguimiento Universidad de Navarra

COVID-19 symptoms predictive of healthcare workers' SARS-CoV-2 PCR results

Background Coronavirus 2019 disease (COVID-19) is caused by the virus SARS-CoV-2, transmissible both person-to-person and from contaminated surfaces. Early COVID-19 detection among healthcare workers (HCWs) is crucial for protecting patients and the healthcare workforce. Because of limited testing capacity, symptom-based screening may prioritize testing and increase diagnostic accuracy. Methods and findings We performed a retrospective study of HCWs undergoing both COVID-19 telephonic symptom screening and nasopharyngeal SARS-CoV-2 assays during the period, March 9.April 15, 2020. HCWs with negative assays but progressive symptoms were re-tested for SARSCoV- 2. Among 592 HCWs tested, 83 (14%) had an initial positive SARS-CoV-2 assay. Fiftynine of 61 HCWs (97%) who were asymptomatic or reported only sore throat/nasal congestion had negative SARS-CoV-2 assays (P = 0.006). HCWs reporting three or more symptoms had an increased multivariate-adjusted odds of having positive assays, 1.95 (95% CI: 1.10.3.64), which increased to 2.61 (95% CI: 1.50.4.45) for six or more symptoms. The multivariate-adjusted odds of a positive assay were also increased for HCWs reporting fever and a measured temperature . 37.5°C (3.49 (95% CI: 1.95.6.21)), and those with myalgias (1.83 (95% CI: 1.04.3.23)). Anosmia/ageusia (i.e. loss of smell/loss of taste) was reported less frequently (16%) than other symptoms by HCWs with positive assays, but was associated with more than a seven-fold multivariate-adjusted odds of a positive test: OR = 7.21 (95% CI: 2.95.17.67). Of 509 HCWs with initial negative SARS-CoV-2 assays, nine had symptom progression and positive re-tests, yielding an estimated negative predictive value of 98.2% (95% CI: 96.8-99.0%) for the exclusion of clinically relevant COVID-19. Conclusions Symptom and temperature reports are useful screening tools for predicting SARS-CoV-2 assay results in HCWs. Anosmia/ageusia, fever, and myalgia were the strongest independent predictors of positive assays. The absence of symptoms or symptoms limited to nasal congestion/sore throat were associated with negative assays

The methylation status of the embryonic limb skeletal progenitors determines their cell fate in chicken

Digits shape is sculpted by interdigital programmed cell death during limb development. Here, we show that DNA breakage in the periphery of 5-methylcytosine nuclei foci of interdigital precursors precedes cell death. These cells showed higher genome instability than the digit-forming precursors when exposed to X-ray irradiation or local bone morphogenetic protein (BMP) treatments. Regional but not global DNA methylation differences were found between both progenitors. DNA-Methyl-Transferases (DNMTs) including DNMT1, DNMT3B and, to a lesser extent, DNMT3A, exhibited well-defined expression patterns in regions destined to degenerate, as the interdigital tissue and the prospective joint regions. Dnmt3b functional experiments revealed an inverse regulation of cell death and cartilage differentiation, by transcriptional regulation of key genes including Sox9, Scleraxis, p21 and Bak1, via differential methylation of CpG islands across their promoters. Our findings point to a regulation of cell death versus chondrogenesis of limb skeletal precursors based on epigenetic mechanisms.We thank Prof. Miguel Lafarga for helpful comments and advice. We thank Dr Jose E Gomez-Arozamena for helping us with the irradiation experiments. We are grateful to Montse Fernandez Calderon, Susana Dawalibi, and Sonia Perez Mantecon, for excellent technical assistance. This work was supported by a Grant (BFU2017–84046-P) from the Spanish Science and Innovation Ministry to JAM. C.S.F is recipient of a FPI grant (BES-2015–074267)

The effect of early treatment with ivermectin on viral load, symptoms and humoral response in patients with non-severe COVID-19: A pilot, double-blind, placebo-controlled, randomized clinical trial.

Background Ivermectin inhibits the replication of SARS-CoV-2 in vitro at concentrations not readily achievable with currently approved doses. There is limited evidence to support its clinical use in COVID-19 patients. We conducted a Pilot, randomized, double-blind, placebo-controlled trial to evaluate the efficacy of a single dose of ivermectin reduce the transmission of SARS-CoV-2 when administered early after disease onset. Methods Consecutive patients with non-severe COVID-19 and no risk factors for complicated disease attending the emergency room of the Clínica Universidad de Navarra between July 31, 2020 and September 11, 2020 were enrolled. All enrollments occurred within 72 h of onset of fever or cough. Patients were randomized 1:1 to receive ivermectin, 400 mcg/kg, single dose (n = 12) or placebo (n = 12). The primary outcome measure was the proportion of patients with detectable SARS-CoV-2 RNA by PCR from nasopharyngeal swab at day 7 post-treatment. The primary outcome was supported by determination of the viral load and infectivity of each sample. The differences between ivermectin and placebo were calculated using Fisher's exact test and presented as a relative risk ratio. This study is registered at ClinicalTrials.gov: NCT04390022. Findings All patients recruited completed the trial (median age, 26 [IQR 19-36 in the ivermectin and 21-44 in the controls] years; 12 [50%] women; 100% had symptoms at recruitment, 70% reported headache, 62% reported fever, 50% reported general malaise and 25% reported cough). At day 7, there was no difference in the proportion of PCR positive patients (RR 0·92, 95% CI: 0·77-1·09, p = 1·0). The ivermectin group had non-statistically significant lower viral loads at day 4 (p = 0·24 for gene E; p = 0·18 for gene N) and day 7 (p = 0·16 for gene E; p = 0·18 for gene N) post treatment as well as lower IgG titers at day 21 post treatment (p = 0·24). Patients in the ivermectin group recovered earlier from hyposmia/anosmia (76 vs 158 patient-days; p < 0.001). Interpretation Among patients with non-severe COVID-19 and no risk factors for severe disease receiving a single 400 mcg/kg dose of ivermectin within 72 h of fever or cough onset there was no difference in the proportion of PCR positives. There was however a marked reduction of self-reported anosmia/hyposmia, a reduction of cough and a tendency to lower viral loads and lower IgG titers which warrants assessment in larger trials. Funding ISGlobal, Barcelona Institute for Global Health and Clínica Universidad de Navarra

Effects of a healthy lifestyle intervention and COVID-19-adjusted training curriculum on firefighter recruits

There are knowledge gaps regarding healthy lifestyle (HLS) interventions in fire academy settings and also concerning the impacts of the pandemic on training. We enrolled fire recruits from two fire academies (A and B) in New England in early 2019 as the historical control group, and recruits from academies in New England (B) and Florida (C), respectively, during the pandemic as the intervention group. The three academies have similar training environments and curricula. The exposures of interest were a combination of (1) an HLS intervention and (2) impacts of the pandemic on training curricula and environs (i.e. social distancing, masking, reduced class size, etc.). We examined the health/fitness changes throughout training. The follow-up rate was 78%, leaving 92 recruits in the historical control group and 55 in the intervention group. The results show an HLS intervention improved the effects of fire academy training on recruits healthy behaviors (MEDI-lifestyle score, 0.5 ± 1.4 vs. - 0.3 ± 1.7), systolic blood pressure (- 7.2 ± 10.0 vs. 2.9 ± 12.9 mmHg), and mental health (Beck Depression score, - 0.45 ± 1.14 vs. - 0.01 ± 1.05) (all P < 0.05). The associations remained significant after multivariable adjustments. Moreover, a 1-point MEDI-lifestyle increment during academy training is associated with about 2% decrement in blood pressures over time, after multivariable adjustments (P < 0.05). Nonetheless, the impacts of pandemic restrictions on academy procedures compromised physical fitness training, namely in percent body fat, push-ups, and pull-ups

Transforming growth factor beta signaling: The master sculptor of fingers

Transforming growth factor beta (TGF?) constitutes a large and evolutionarily conserved superfamily of secreted factors that play essential roles in embryonic development, cancer, tissue regeneration, and human degenerative pathology. Studies of this signaling cascade in the regulation of cellular and tissue changes in the three-dimensional context of a developing embryo have notably advanced in the understanding of the action mechanism of these growth factors. In this review, we address the role of TGF? signaling in the developing limb, focusing on its essential function in the morphogenesis of the autopod. As we discuss in this work, modern mouse genetic experiments together with more classical embryological approaches in chick embryos, provided very valuable information concerning the role of TGF? and Activin family members in the morphogenesis of the digits of tetrapods, including the formation of phalanxes, digital tendons, and interphalangeal joints. We emphasize the importance of the Activin and TGF? proteins as digit inducing factors and their critical interaction with the BMP signaling to sculpt the hand and foot morphology