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Alpha-synuclein aggregation is a hallmark of Parkinson's disease (PD). Mutants A30P and A53T alpha-synuclein are known to exacerbate the toxicity of alpha-synuclein, which includes oxidative stress, mitochondrial and endoplasmic reticulum (ER) dysfunction. Saccharomyces cerevisiae (budding yeast) is a cellular model widely used to investigate mechanisms underlying neurodegenerative disorders, such as PD. In yeast, Gem1 (Miro/Rhot mammalian orthologue) coordinates mitochondrial dynamics and ER homeostasis, which is impaired in the presence of mutant alpha-synuclein and can lead to cell death. In this study, A30P or A53T alpha-synuclein were expressed in wild type or ΔGem (deletion of Gem1 gene) yeast strains. ΔGem cells presented decreased viability and increased mitochondrial H2O2 production and ER stress compared to wild type cells. However, in the presence of mutant alpha-synuclein, ΔGem cells showed increased growth compared to cells that do not express mutant alpha-synuclein. ΔGem cells expressing A53T alpha-synuclein also presented reduced ER stress and increased ability to deal with oxidative stress. Together, our results suggest that deletion of Gem1 activates pathways that strengthen cells against other stressful agents such as the presence of mutant alpha-synuclein.

Alvarez waves are local rhythmic contractions of the myometrium with high frequency and low intensity. They can be detected using internal or external tocography and electrohysterography. Some researchers correlate these small contractions with the initiation of labor, since they have been described as a pattern representing the uterine response to prostaglandin production. Other authors either do not validate a causality relation between Alvarez waves and labor or suggest that they have low predictive value for preterm labor. Alvarez waves' research has become a multidisciplinary subject with inputs ranging from medical science, biomedical engineering, and related areas. A comprehensive review is herein conducted to summarize the state of the art regarding Alvarez waves and their role in the initiation of labor, namely in preterm birth. The results show that a large number of studies have analyzed and characterized Alvarez waves without necessarily digging into their relationship with labor. Publications were categorized in three groups: (A) reports about morphology and characterization of Alvarez waves; (B) publications reporting a positive causality relation between Alvarez waves and labor; and (C) publications reporting an absence of causality regarding the previous hypothesis. Studies in group B outnumbered those in group C. A critical analysis is presented. info:eu-repo/semantics/publishedVersion

Funding Acknowledgements Type of funding sources: None. OnBehalf GENEMACOR Introduction After the diagnosis of coronary artery disease (CAD), traditional risk factors such as diabetes mellitus, dyslipidemia, hypertension and smoking have been used to assess the risk of major cardiovascular adverse events (MACE). However, despite reduction of these factors, presence of MACE remains high. It is necessary to identify other causal risk factors for MACE in coronary patients and increased plasma Homocysteine (Hcy) level seems to be a likely candidate. However, the influence of Hcy levels in the prognosis of coronary patients presents a limited knowledge. Objective To evaluate the influence of high level of Hcy in MACE (defined as a composite endpoint of cardiovascular death, acute myocardial infarction, stroke, admission for heart failure and need to revascularization) of coronary artery patients. Materials and Methods Study analyses of 1687 patients selected from GENEMACOR study population, with at least one > 75% coronary stenosis by angiography. That population was divided in three terciles according to the Hcy level and the population of the 2nd tercil (Hcy 11.1-13.6mmol/L) was excluded. The end population of 1118 patients was a median age of 53.1 ± 7.9 years and 77.6% were men. We compared patients in the 1st (Hcy < 11.1mmol/L) and 3rd tercil (Hcy > 13.6mmol/L) during a mean follow up of 5.0 ± 4.8 years. Results 560 (50.1%) patients were included in the 1st tercil group (median age 51.6 ± 3 years, 72.0% men) and 558 (49.9%) patients were in the 3rd tercil group (median age 54.6 ± 3 years, 83.3% men). In our population, high levels of Hcy were associated with MACE (OR 1.43, 95% CI: 1.12-1.83, p 0.004). Conclusion In our population a higher level of Hcy was associated with adverse prognosis and increased occurrence of MACE. Knowing that elevated homocysteine levels are associated with increased risk of MACE, in these patients is essential to have a more intensive therapeutic strategy.

Funding Acknowledgements Type of funding sources: None. Introduction Coronary artery disease (CAD) remains a leading cause of morbidity and mortality worldwide. We know that plasma level of LDL cholesterol (LDL-C) is strongly associated with atherosclerosis, and its reduction with statins has led to a decrease in the incidence and complications of CAD. According to the 2019 ESC guidelines, in high-risk patient the aim is to achieve an absolute LDL-C treatment goal of Objective To evaluate the degree of LDL-C control in coronary artery disease patients according to ESC guidelines. Materials and Methods Study analyses of 1687 patients selected from GENEMACOR study population, with at least one > 75% coronary stenosis by angiography (median age 53.3 ± 3 years and 54.8% men). LDL-C was determined by chemical methods and all patients were statin treated. The population was divided in four groups according to LDL-C levels: inferior to 55mg/dL, inferior to 70mg/dL, inferior to 115mg/dL and superior to 115mg/dL. Results LDL-C mean value was 108.7mg/dL, median 105.1mg/dL (P25 83.0 and P75 127.4mg/dL). 150 (8.9%) patients had LDL-C < 55mg/dL vs 1537 (91.1%) with LDL-C ≥ 55 mg/dl. 275 (16.3%) patients had LDL-C < 70 mg/dL vs 1412 (83.7%) with LDL-C ≥ 70 mg/dL. 1084 (64.3%%) patients had LDL < 115 mg/dL vs 603 (35.7%) with LDL-C ≥ 115 mg/dL. Conclusion In our population LDL-C control levels was low, with 91.1% patients with LDL-C ≥ 55mg/dL and 83.7% patients with LDL ≥ 70 mg/dL. It is interesting to note that most of our patients have LDL-C levels above the recommend by the newest and, surprisingly, the 2016 dyslipidemia guidelines. It is therefore important to implement a more intensive treatment strategy of dyslipidemia in coronary patients.

There are several sources of heavy metal exposures whether occupational or environmental. These are connected both with the existence of natural reservoirs of metal toxicants or human activity such as mining, welding and construction. In general, exposure to heavy metals, such as cadmium (Cd), mercury (Hg), nickel (Ni), lead (Pb) and metalloids, such as arsenic (As), has been associated with diseases including neurodegenerative diseases, diabetes and cancer. Common to these diseases is the loss of cellular physiologic performance and phenotype required for proper function. On the metal side, electrophilic behavior that disrupts the electronic (or redox) state of cells is a common feature. This suggests that there may be a connection between changes to the redox equilibrium of cells caused by environmental exposures to heavy metals and the pathogenic effects of such exposures. In this mini-review, we will focus on two environmental contaminants cadmium (a metal) and arsenic (a metalloid) and explore their interactions with living organisms from the perspective of their electrophilic chemical reactivity that underlies both their potential as carcinogens and as drivers of more aggressive tumor phenotypes.

Cardiovascular diseases are the main cause of mortality worldwide, and childhood excess weight/obesity are strong correlators of accumulated risk in later life. A relationship between maternal preeclampsia and offspring’s childhood obesity is recognized, but most studies fail to control for strong confounders. Our goal is to analyze the association between preeclampsia and childhood excess weight/obesity, after accounting for important confounders. We recruited 5133 women with singleton pregnancies during admission for delivery. Sixty-seven pregnancies were complicated by preeclampsia. Maternal and children outcomes were assessed at 10 years of age. We analyzed the association between preeclampsia and childhood excess weight/obesity by fitting a linear regression model (using offspring body mass index (BMI) z-score at 10 years of age) and a logistic regression model (using excess weight/obesity status). We then controlled both models for known confounders, namely maternal prepregnancy BMI, parity, and smoking during pregnancy. At 10 years of age, offspring of preeclamptic mothers had a higher BMI z-score and were more likely classified as overweight/obese, but these differences were not statistically significant. After controlling for maternal prepregnancy BMI, parity, and smoking during pregnancy, there was a high magnitude change in the beta coefficient of preeclampsia in the linear (0.175; −0.014) and the logistic regression models (1.48; 1.23) suggesting that the association between preeclampsia and childhood excess weigh/obesity is significantly confounded by these variables. These confounders also showed a significant association with childhood obesity. This finding suggests that in utero exposure to preeclampsia seems to have less impact in childhood obesity than the previously described confounders. This work was funded by Programa Operacional de Saúde – Saúde XXI, Quadro Comunitário de Apoio III and Administração Regional de Saúde Norte (Regional Department of Ministry of Health); FEDER through the Operational Programme Competitiveness and Internationalization and national funding from the Foundation for Science and Technology – FCT (Portuguese Ministry of Science, Technology and Higher Education) (POCI- 01- 0145-FEDER-016837), under the project “PathMOB.: Risco cardiometabólico na infância: desde o início da vida ao fim da infância” (Ref. FCT PTDC/DTP-EPI/3306/2014); Unidade de Investigação em Epidemiologia -Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (POCI-01-0145-FEDER-006862; Ref. info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID/DTP/04750/2013/PT).

Systemic lupus erythematosus (SLE) is a chronic, autoimmune disease associated with major obstetrical complications such as gestational loss, preterm delivery, fetal growth restriction (FGR) and preeclampsia. Published literature is not consensual regarding the main risk factors for each of these outcomes. Our goal with this study was to determine the most important predictors for each of the main adverse pregnancy outcomes in this population. We conducted a retrospective cohort study of unifetal pregnancies of women with the diagnosis of SLE followed in our unit between January 1994 and December 2016. We excluded elective terminations of pregnancy and cases lost to follow-up and we analyzed 157 pregnancies (128 women). Multiple logistic regression models for the outcomes gestational loss, preterm delivery, fetal growth restriction, and preeclampsia were built. Two-sided p-values of

Introduction After the World Health Organization declared COVID-19 a pandemic, the Simulation Center of Rosario (Ce.Si.R), Argentina, under the authority of the College of Physicians, decided to foster a training program for collegiate physicians to continue strengthening their skills in the advanced airway management and the proper uses of Protective Personal Equipment, with a focus on in situ simulations for health staff in care centers. Aims Train health teams from transdisciplinary paradigms and expand learnings in the strategic management of social and sanitary care actions, by assessing the participants strengths, and weaknesses, and by developing an improvement plan to implement in each institution or work equipment. Understand how the clinical simulation was perceived. Methods After the beginning of the pandemic, the Simulation Center delivered some sessions to explain the theoretical and practical approaches of the project; 8 hospitals and 9 primary care centers were selected for the in situ simulations, mostly aimed at strengthening the daily tasks of all those involved in the patient care process: stretcher handlers, nurses, physicians, housekeepers, and administrative staff. Either actors, manikins, or part-task trainers portrayed COVID-19 patients. Results and Discussion 1789 health workers were trained. The in situ simulation disclosed the need to revisit technical and non-technical skills in real-time. Process non-apparent errors were detected: physical space, resources, signs, inter-service communication as well as the participants’ strengths and weaknesses. The simulation helps creating and recreating the necessary conditions to bond and produce knowledge from simple to complex scenarios. The project intends to directly improve patients and health workers’ safety by highlighting the relevance of teamwork and enhanced staff trust in the institutions. To the best of our knowledge, this innovative activity is unprecedented on such a big scale.

Background Despite being a controversial subject, multiple guidelines mention the use of Coronary Artery Calcification (CAC) scoring in the cardiovascular risk prediction, in asymptomatic population. The inclusion of CAC scoring in traditional risk models may help in decision-make providing better cardiovascular risk stratification. Purpose The aim of our study is to estimate the impact of CAC scoring in cardiovascular events risk prediction in a model based on traditional risk factors (TRFs). Methods and results The study consisted of 1052 asymptomatic individuals free of known coronary heart disease, enrolled from GENEMACOR study and referred for computed tomography for the CAC scoring assessment. A cohort of 952 was followed for a mean of 5.2±3.2 years for the primary endpoint of all-cause of cardiovascular events. The following traditional risk factors were considered: (1) current cigarette smoking, (2) dyslipidemia, (3) diabetes mellitus, (4) hypertension and (5) family history of coronary heart disease. Among this population, the extent of CAC differs significantly between men and women in the same age group. Therefore, the distribution of CAC score by age and gender was done by using the Hoff's nomogram (a). According to this nomogram, 3 categories were created: low CAC (0≤CAC75). Two Cox regression models were created, the first only with TRFs and the second adding the CAC severity categories. When including CAC categories to the TRFs, the higher severity level presented a significant risk of MACE occurrence with an HR of 4.39 (95% CI 1.83–10.52; p=0.001). Conclusion Our results point to the importance of the inclusion of CAC in both primary and secondary prevention to an improved risk stratification. Larger prospective multicentre cohorts with longer follow-up should reproduce and validate these findings. Funding Acknowledgement Type of funding source: None

Background TCF21 gene, encodes a basic-helix- loop- helix transcription factor, playing a critical action in the development of epicardial progenitor cells that give rise to coronary artery smooth muscle cells (SMC) and cardiac fibroblasts. Recent data suggest that TCF21 may play a role in the state of differentiation of SMC precursor cells that migrate to vascular lesions and contribute to fibrous cap. Purpose Investigate the association of TCF21 rs12190287G>C variant with coronary artery disease (CAD) in a Portuguese population and its role on the prognosis. Methods Case-control study with 3120 participants, 1687 coronary patients with at least 75% obstruction of a major coronary artery and 1433 controls. Genotyping used the TaqMan technique (Applied Biosystems) and then a univariate and multivariate logistic regression analysis were performed. After a mean follow-up of 5.01±4.2 years (interquartile range 1.96–7.57), the occurrence of the combined Major Adverse Cardiovascular Events (MACE) (Cardiovascular Mortality, non-fatal Myocardial Infarction, new Revascularization, Cerebrovascular Disease and Peripheric Vascular Disease) were registered and analysed by Cox regression. Finally, Kaplan-Meier survival estimate was performed. Results In the total population, GC+CC genotype was found to be associated with CAD with an OR of 1.285; CI: 1.022–1.614; p=0.031. After multivariate logistic regression, adjusted to traditional risk factors, the association with CAD remained significant for this genotype (OR=1.340; CI: 1.042–1.723; p=0.022).After Cox regression adjusted for confounding variables (age and sex, hypertension, diabetes, smoking, dyslipidemia, eGFR, Ejection fraction Conclusion The mutated TCF21 variant can provide a new marker to identify patients at high cardiovascular risk and may representa potential target for gene therapy in future. Figure 1 Funding Acknowledgement Type of funding source: None

Electrohysterography (EHG) is a promising technique for pregnancy monitoring and preterm risk evaluation. It allows for uterine contraction monitoring as early as the 20th gestational week, and it is a non-invasive technique based on recording the electric signal of the uterine muscle activity from electrodes located in the abdominal surface. In this work, EHG-based contraction detection methodologies are applied using signal envelope features. Automatic contraction detection is an important step for the development of unsupervised pregnancy monitoring systems based on EHG. The exploratory methodologies include wavelet energy, Teager energy, root mean square (RMS), squared RMS, and Hilbert envelope. In this work, two main features were evaluated: contraction detection and its related delineation accuracy. The squared RMS produced the best contraction (97.15 &plusmn, 4.66%) and delineation (89.43 &plusmn, 8.10%) accuracy and the lowest false positive rate (0.63%). Despite the wavelet energy method having a contraction accuracy (92.28%) below the first-rated method, its standard deviation was the second best (6.66%). The average false positive rate ranged between 0.63% and 4.74%&mdash, a remarkably low value.

The SARS-COV2 outbreak began as a zoonotic transmission, with Chinese horseshoe bats (Rhinolophus sinicus) and pangolins being the most likely origin of the infection. Once the patient has been infected, the virus is significantly present in the nasopharyngeal and salivary secretions. The professionals who are most directly exposed to the risk of contagion are dentists since the evolutionary process of virus infection occurs due to the inhalation of particles in the dental environment, the formation of aerosols during practice, and what is more important, in the expectorations emitted by the patients. Therefore, it is necessary to act diligently in professional practice, as well as take the necessary preventive measures to avoid the spread of the infection. The appearance of this new disease forces us to modify all the sanitary measures that have been taken concerning dental care by the professional, as well as auxiliary personnel and the protection of patients, requiring strict sanitary control by the authorities of health. In the university environment, the changes that must be made to allow an open channel of communication between students, teaching, administrative and hygiene personnel must continue to prevent this and future diseases. The aim of this article is to propose a protocol for dental clinical care, considering the real conditions and needs that prevail in our practice, highlighting the risk and preventive measures that the dental professional must consider, as well as the management of patients.

Inorganic arsenic (iAs/As2 O3 2- ) is an environmental toxicant found in watersheds around the world including in densely populated areas. iAs is a class I carcinogen known to target the skin, lungs, bladder, and digestive organs, but its role as a primary breast carcinogen remains controversial. Here, we examined a different possibility: that exposure to iAs promotes the transition of well-differentiated epithelial breast cancer cells characterized by estrogen and progesterone receptor expression (ER+/PR+), to more basal phenotypes characterized by active proliferation, and propensity to metastasis in vivo. Our results indicate two clear phenotypic responses to low-level iAs that depend on the duration of the exposure. Short-term pulses of iAs activate ER signaling, consistent with its reported pseudo-estrogen activity, but longer-term, chronic treatments for over 6 months suppresses both ER and PR expression and signaling. In fact, washout of these chronically exposed cells for up to 1 month failed to fully reverse the transcriptional and phenotypic effects of prolonged treatments, indicating durable changes in cellular physiologic identity. RNA-seq studies found that chronic iAs drives the transition toward more basal phenotypes characterized by impaired hormone receptor signaling despite the conservation of estrogen receptor expression. Because treatments for breast cancer patients are largely designed based on the detection of hormone receptor expression, our results suggest greater scrutiny of ER+ cancers in patients exposed to iAs, because these tumors may spawn more aggressive phenotypes than unexposed ER+ tumors, in particular, basal subtypes that tend to develop therapy resistance and metastasis.

El cultivo de la “cachama” Piaractus branchypomus(Pisces: Characiformes), es una actividad que genera ingresos economicos en algunas personas de etnia Kichwaen la amazonia ecuatoriana. El objetivo del presente trabajo fue realizar actividades de vinculacion con la ictioparasitologia en los peces cultivados en las comunidades de San Jose y Santa Rita pertenecientes al Canton Archidona, como parte de la colaboracion de un convenio interinstitucional entre la Universidad Regional Amazonica Ikiam y la Fundacion Centro Lianas, para fortalecer el cultivo piscicola mediante la vinculacion. Se realizaron controles de ciertos parametros fisico-quimicos en el agua (carbonatos, oxigeno disuelto), tambien se superviso la calidad de la carne de la cachama y se evaluaron las condiciones sanitarias de los estanques. Se identifico la presencia de monogeneos con el 5,5% de Prevalencia en peces juveniles y adultos colectados en la comuna San Jose y se hallaron quistes de protozoarios como las Myxosporas con 11,10 % de Prevalencia, provenientes de los peces colectados en los estanques dela comunidad de Santa Rita. Ademas, se observo que los niveles de carbonatos son altos en los efluentes, en relacion con los mostrados en otros estudios. Finalmente, se capacito en el manejo tecnico y sanitario del cutivo a los productores, se asistio, acompano y recomendo acciones para reducir los resultados identificados.

Epidemiologic studies in diabetic patients as well as research in model organisms have indicated the potential of metformin as a drug candidate for the treatment of various types of cancer, including breast cancer. To date most of the anti-cancer properties of metformin have, in large part, been attributed either to the inhibition of mitochondrial NADH oxidase complex (Complex I in the electron transport chain) or the activation of AMP-activated kinase (AMPK). However, it is becoming increasingly clear that AMPK activation may be critical to alleviate metabolic and energetic stresses associated with tumor progression suggesting that it may, in fact, attenuate the toxicity of metformin instead of promoting it. Here, we demonstrate that AMPK opposes the detrimental effects of mitochondrial complex I inhibition by enhancing glycolysis at the expense of, and in a manner dependent on, pyruvate availability. We also found that metformin forces cells to rewire their metabolic grid in a manner that depends on AMPK, with AMPK-competent cells upregulating glycolysis and AMPK-deficient cell resorting to ketogenesis. In fact, while the killing effects of metformin were largely rescued by pyruvate in AMPKcompetent cells, AMPK-deficient cells required instead acetoacetate, a product of fatty acid catabolism indicating a switch from sugar to fatty acid metabolism as a central resource for ATP production in these cells. In summary, our results indicate that AMPK activation is not responsible for metformin anticancer activity and may instead alleviate energetic stress by activating glycolysis.

Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. The uterine electromyogram, also called electrohysterogram (EHG), is the electrical signal generated by uterine contractile activity. The EHG has been considered an expanding technique for pregnancy monitoring and preterm risk evaluation. Data were collected on the abdominal surface. It has been speculated the effect of the placenta location on the characteristics of the EHG. In this work, a preliminary exploration method is proposed using the average spectra of Alvarez waves contractions of subjects with anterior and non-anterior placental position as a basis for the triple-dispersion Cole model that provides a best fit for these two cases. This leads to the uterine impedance estimation for these two study cases. Non-linear least square fitting (NLSF) was applied for this modelling process, which produces electric circuit fractional models’ representations. A triple-dispersion Cole-impedance model was used to obtain the uterine impedance curve in a frequency band between 0.1 and 1 Hz. A proposal for the interpretation relating the model parameters and the placental influence on the myometrial contractile action is provided. This is the first report regarding in silico estimation of the uterine impedance for cases involving anterior or non-anterior placental positions. publishersversion published

IntroductionInsomnia has been related to a more severe substance use disorder presentation (1). There are few longitudinal studies in outpatients center for SUD treatment that evaluate how insomnia impacts on relapses.ObjectivesTo analyze how insomnia impacts on the time of the first substance relapse in SUD outpatients after the onset of addiction treatment.MethodsThis is a one-year follow-up study performed on 116 patients (73.3% males; mean age 43.4±14.3) for whom we had information from baseline insomnia and the time for the first relapse. A Kaplan-Meier survival analysis was performed. This is part of a greater research on Alexithymia in SUD in a longitudinal study.ResultsThe initial sample consisted of 116 patients, information on relapses was available for 113 patients. The main substances used at baseline were alcohol (62.1%), cocaine (56.0%), cannabis (42.2%), and opiates (30.2%).ConclusionsIt is important to evaluate insomnia at the onset of addiction treatment because insomnia may be related to earlier relapses. Furthermore, it should be analyzed further on how insomnia treatment impact on substance relapses. REFERENCES 1. Miller MB, Donahue ML, Carey KB, Scott-Sheldon LAJ. Insomnia treatment in the context of alcohol use disorder: A systematic review and meta-analysis. Drug Alcohol Depend. 2017;181:200-207. doi:10.1016/j.drugalcdep.2017.09.029

IntroductionPatients with substance use disorders (SUD) have higher alexithymia levels and present frequently suicidal ideation (SI) and suicide (SA) [1,2]. Beside, alexithymia has been related to suicidal behaviors in several psychiatric disorders[3]. Although, there are some studies on alexithymia and suicidality in SUD patients, to our knowledge there are no studies on this issue in Spanish population.ObjectivesTo compare the alexithymia levels in SUD patients with and without SI and SA in an outpatient addiction treatment center in Spain.MethodsThis is a cross-sectional study performed on 110 patients (74.3%males; mean age 43.6±14.5years old) for whom we had information from the Toronto Alexithymia Scale(TAS-20) and the presence or not of lifetime SI and SA.ResultsLifetime SI and SA were present in 55.5% and 35.5% of the sample respectively. The mean score of TAS-20, difficulties identifying feelings (DIF), difficulties describing feelings (DDT), and externally-oriented thinking(EOT) were 57.2±13.3, 20.0±7.0, 14.7±4.5, and 22.5±4.5 respectively.ConclusionsSI and SA may be related to alexithymia levels. Hence, alexithymia should be further analyzed in SUD patients in longitudinal studies in order to analyze the bilateral association with suicidal spectrum behaviors. REFERENCES Rodríguez-Cintas L, et al. Factors associated with lifetime suicidal ideation and suicide attempts in outpatients with substance use disorders. Psychiatry Res. 2018;262:440-5. Morie KP, et al. Alexithymia and Addiction: A Review and Preliminary Data Suggesting Neurobiological Links to Reward/Loss Processing. Curr Addict Rep. 2016;3(2):239-48. Hemming L, et al. A systematic review and meta-analysis of the association between alexithymia and suicide ideation and behaviour. J Affect Disord. 2019;254:34-48.

Introduction Coronary artery disease (CAD) is the leading cause of death worldwide, placing a major economic and resource burden on health and public health systems, so efforts are being made to accurately predict risk for major adverse cardiac events (MACE). The field of risk prediction and CAD prevention continues to evolve with the identification of novel risk factors and biomarkers, such as lipoprotein a [Lp)a]. Almost 20% of the population has elevated circulating levels of Lp(a), which is recognized as an independent risk factor for CAD, stroke, peripheral arterial disease, and aortic stenosis. Importantly, studies showed that this was particularly true for women. Objective To evaluate if the elevation of Lp(a) is associated with MACE in female, male or both. Materials and methods Case control study of 3050 subjects from the GENEMACOR study population. In female population (n=676): cases were 341 patients with at least one >75% coronary stenosis (median age 55.7±7.2) and 335 normal controls (median age 55.8±6) adjusted by age with cases. In male population (n=2374): 1278 patients with at least one >75% coronary stenosis (median age 52.7±8) and 1096 controls (median age 51.9±8) also adjusted by age. χ2 and T student tests were used to analyze the demographic, laboratorial, angiographic and anthropometric characteristics of the population. Lipoprotein (a) was determined by immunoturbidimetry. High Lp(a) level was considered if superior to 30 mg/dl. Logistic regression was used to evaluate Lp(a) as a risk factor for CAD in total, female and male populations. Results In female population 44.0% patients vs 21.2% controls (p30mg/dl. In male population 39.4% patients vs 23.8% controls (p30mg/dl. In total population Lp(a)>30mg/dl was a predictor for CAD (OR 2.24, 95% CI: 1.91–2.62, p30mg/dl was also a predictor for CAD either in male (OR 2.08, 95% CI: 1.74–2.5, p Conclusions As opposed to other studies, in our population elevated Lp(a) levels (>30mg/dl) were associated with elevated CAD risk, in both men and women. We conclude that Lp(a) can be considered an independent risk factor for CAD disease in our population, and further strategies for Lp(a) reduction may indeed translate in improved outcomes in CAD disease.

A recent GWAS study found a significant association between the BUD13-ZNF259 rs964184 polymorphism, dyslipidemia and the onset of coronary disease (CAD). This variant encoding zinc finger protein (ZPR1) interacts with the receptor tyrosine kinase at cellular level, increasing oxidative stress, inflammatory response and atherogenesis. There are no studies of the effect of this variant on the Portuguese population. Objective Investigate the association of BUD13-ZNF259 rs964184 with dyslipidemia and its impact on CAD risk. Evaluate its impact in different age groups of our population. Methods A case-control study was performed with 3050 subjects (1619 coronary patients with 53.3±8 years; 78.9% male and 1431 controls with 52.8±8 years; 76.6% male) from the GENEMACOR study population. Traditional risk factors (smoking, dyslipidemia, diabetes, family history, hypertension, body mass index, alcohol consumption, physical inactivity) and others considered new, such as creatinine clearance, pulse wave velocity, homocysteine, fibrinogen, lipoprotein (a), APOB and PCR (hs) were investigated. BUD13-ZNF259 variant was genotyped and analyzed using the dominant model (CG + GG vs. CC). Bivariate and multivariate analyzes (logistic regression) were used to estimate the ORs and 95% CI, after adjusting for potential confounding factors, in 3 different age groups (55). Results BUD13-ZNF259 polymorphism presented an independent and significant risk of CAD (OR=1.58; 95% CI: 1.07–2.32; p=0.019) only in the group of young coronary patients Conclusion BUD13-ZNF259 rs964184 variant showed a significant risk for the onset of CAD in the young population (

Introduction The complex interaction between genes and environmental factors contribute to individual-level risk of coronary artery disease (CAD), often resulting in premature CAD. The role for genetic risk scores in premature CAD is still controversial. Objective To evaluate the importance of conventional risk factors and of a genetic risk score in younger and older patients with coronary artery disease Methods From a group of 1619 pts with angiographic documented CAD from the GENEMACOR study, we selected 1276 pts admitted for ACS and analysed them in 2 groups (group A: ≤50 years, n=491 pts, 87.2% male, mean age 44±4.9 and group B: >50 years, n=785 pts, 75.2% male, mean age 57±4.2). Univariate analysis was used to characterize the traits of each group and we used ROC curves and respective AUCs to evaluate the power of genetics in the prediction of CAD, through a Genetic Risk Score (GRS). Results 99.3% of the young patients had at least one modifiable risk factor, 18.4% had 2 modifiable risk factors and 75.2% had 3 or more modifiable risk factors. The pattern of risk factors contributing to CAD were different among groups: family history (A: 27.5%, B: 21.4%, p=0.015) and smoking habits (A: 64.8%, B: 42.9%, p0.805, p=0.0178 and 0.748->0.761, p=0.0007 in patients under and over 50, respectively). Conclusion Coronary artery disease is not all the same, as premature CAD shares a unique and specific pattern of risk factors, clinical presentation, angiographic severity and prognosis. Genetics should not be used as an excuse to justify premature CAD, as there is frequently more than one potentially reversible risk factor present even in young patients and the additive predictive value of GRS is modest.

Type 2 Diabetes (T2D) is a risk factor for dysregulation of glomerular filtration rate (GFR) and albuminuria. However, it remains unclear whether this association is only causal. Genetic variants are inherited independent of potential confounding factors and represent a lifetime exposure. Aim Investigate whether the reduction of GFR is a direct consequence of T2D or there are other genetic mechanisms involved in the pathophysiology of the evolution to chronic kidney disease. Methods Cross-sectional study with a total of 2579 individuals was performed, of which 735 patients had T2D. Subjects were classified as `'diabetic” if they were taking oral anti-diabetic medication or insulin or if their fasting plasma glucose was higher than 7.0 mmol/l or 126 mg/dl. Within the diabetic group, we considered those with (n=63) and without (n=627) decreased GFR. GFR was calculated through the Cockcroft and Gault formula and decreased GFR was defined as GFR120 mg/ml, dyslipidemia, alcohol consumption, CAD diagnosis). A logistic regression was performed firstly with the risk factors solely; and secondly adding the genetic variants in order to evaluate the independent predictors of progression to renal failure in T2D. Results After the first multivariate logistic regression with all the risk factors for decreased GFR, only CAD remained in the equation, showing to be an independent risk factor for progression to renal failure, in T2D (OR=4.17; 95% CI: 1.64–10.59; p=0.003). In the second logistic regression, including risk factors and the genetic variants, only ZNF259 rs964184 showed an independent and significant association with the risk of decreased GFR (OR=3.03; 95% CI: 1.06–8.70; p=0.039). Conclusion This study shows that the variant ZNF259 rs964184 is associated with decreased kidney function, independently of other risk factors. This finding needs further investigation to clarify the genetic mechanism behind the association of rs964184 with decreased GFR, in Type 2 diabetes.

Introduction Coronary artery disease (CAD) is a multifactorial process with substantial genetic contribution. However, genetic predisposition among patients with a different number of lifestyle factors and premature CAD, remains a complex and thoroughly unexplored topic. Objective To evaluate, in a young population, the importance of conventional risk factors as well as of a genetic risk score in the appearance of CAD. Methods A case-control study was conducted with 1075 patients from the GENEMACOR study population, under 50 years-old (555 cases, 86.8% male, mean age 44.1±4.9 years and 520 controls, 86.2% male, mean age 44.3±4.8 years). Univariate analysis addressed the association of different modifiable risk factors with premature CAD. Genetic risk score (GRS) was computed comprising 33 genetic risk variants in a multiplicative method. GRS was evaluated according to the number of traditional risk factors and risk for premature CAD was estimated and its independent predictive value estimated by logistic regression. Results 72.6% of patients had ≥3 risk factors vs 31.2% of controls (p Conclusion In our population, GRS was an independent predictor for premature CAD. In young patients with ≥3 risk factors, genetics play a less decisive role in the development of CAD. Even in young patients, modifiable risk factors should be addressed aggressively as they may represent a higher burden than genetic predisposition itself.

Uterine contractions’ monitoring has been pointed out as an important tool that may be useful in the preterm risk assessment, term birth estimation and uterine physiology investigation. The multichannel EHG provides a mapping of the myometrium electrical activity projection on the selected channels, providing a wealth of information, including pacemaker regions, signal propagation and contraction amplitude and spectral characteristics. The EHG multichannel data representation, regarding contractile activity, presents an interpretation challenge, given the presence of the multiple contractions of, possibly, different types, in the respective acquisition channels, for different recording sessions and gestational ages of one or multiple pregnant subjects. Typically, an EHG dataset contains data from various subjects, for which multiple recording sessions could be performed, possibly leading to hundreds of recordings. The post-processing step of this data for contraction retrieval may result in multidimensional datasets, requiring interpretation in multiple research scenarios. In this work, a novel representation method is introduced, the Contractiongram, an intuitive graphical tool to facilitate the interpretation of the EHG contractile data for a subject or a whole dataset, throughout the pregnancy, including multisession acquisition scenarios. An application example is presented for a widely used open access EHG database. A contraction detection and classification were a result of a previous research work and used as a data pool for this study. The graphical representation obtained in the current study is a suitable tool for the identification of uterine contraction patterns in selected channels corresponding to different myometrial regions, in designated gestational ages.

IntroductionCOVID19 keeps being a challenge, not only facing the outbreak and the treatment of the cases, but also in the education sector. Most learning centres and high schools in the world are closed to avoid further outbreaks, as well as institutes for psychotherapy throughout the world.ObjectivesTo gain a better knowledge and understanding about alternatives identified in the scope of psychiatric trainee training, through the support provided by digital resources.MethodsSystematic review on PubMed and Uptodate databases since declaration of the COVID-19 pandemic in March 2020 was performed using the keywords: Distance Education, Pandemia, COVID-19, Medical Residency. Discussing online-learning.ResultsThe described European countries (Germany, Spain, United Kingdom) used different strategies to maintain the e-learning. Practical undergraduate education was replaced in countries like Spain by “problem-based learning” tasks, clarifying and commenting case reports or videos through working groups. The increase of the resources from teachers and trainers wasn´t taken in account for the preparation of the digital program. Social inequities for the digital access for groups of students or clients were also claimed.ConclusionsEach of the described countries adopted different strategies regarding continuing training of residents, their assessment and their certification. Covid-19 should set down a trend of social collaborative learning as part of resident training and asset hybrid or even digital methods for the mental health training.

For many students, school-organized sports play an important role in students' academic and social experiences. This study focuses on the effects of participation in school-organized sports on academic achievement and students' perceptions of family support, teacher and community support, and school safety. Data were obtained from the 2010 administration of the Minnesota Student Survey, resulting in a total sample of 29,535 12th grade students of which 12,849 participated regularly (at least 1–2 times per week) in school-organized sports. Propensity score matching was used to match similar students who voluntarily participated in school sports with those who were not involved in any school sports. Participation in school sports was associated with higher GPAs, favorable perceptions of school safety, and increased perceptions of family and teacher/community support. Guidance for parents, educators, and policymakers on how to further promote students' academic and social success are discussed.

Summary In September 2015, a confirmed case of Middle East respiratory syndrome (MERS) was diagnosed in a healthcare worker in Jeddah, Saudi Arabia. Given the absence of confirmed MERS cases in Jeddah at the time, an epidemiological index case investigation took place. The investigation identified a probable source of an index case who had been in hospital in Jordan in August 2015 while there was an ongoing MERS outbreak and who then subsequently sought medical care in Jeddah.

The uterine electromyogram, also named Electrohysterogram (EHG), is a non-invasive technique that has been used for pregnancy and labour monitoring as well as for research work on uterine physiology. This technique is well established in this field. There is however a vast unexplored potential in the EHG that is currently the subject of interdisciplinary research work involving different scientific fields such as medicine, engineering, physics and mathematics. In this paper, an unsupervised clustering method is applied to a previously obtained set of frequency spectral representations of the respective EHG signal contractions that were previously automatically detected and delineated. An innovative approach using the complete spectrum projection is described, rather than a set of relevant points. The feasibility of the method is established despite the concerns of possible computational burden incurred by the processing of the whole spectrum. Given the unsupervised nature of this classification, a validation procedure was performed whereas the obtained clusters were labelled through the correlation with the common knowledge about the most relevant uterine contraction types, as described in the literature. As a result of this study, a spectral description of the Alvarez contractions was obtained where it was possible to breakdown these important events in two different types according to their spectrum. Spectral estimates of Braxton-Hicks contractions were also obtained and associated to one of the clusters. This led to a full spectral characterization of these uterine events.

This paper presents a bioarchaeology of care case study based on the skeletonized remains of an elderly female with a congenital condition that compromised both mobility and independence in undertaking certain basic tasks, and which generated requirements for long-term care in the form of both direct support and accommodation. The remains show evidence of bilateral cervical ribs, severe osteoarthritic destruction in the right shoulder joint, and a healed skull trepanation. The remains were recovered from a cemetery dating to the initial part of the Late Intermediate Period at the archaeological site of Pachacamac, Peru. The subject has been identified as belonging to an Ychsma ayllu. This paper applies the bioarchaeology of care methodology in considering the implications of care provision within the Ychsma socialcontext, and suggests that caregiving may have been a relatively common practice in this complex society. This case study is a good example of how the application of social theory through the bioarchaeology of care approach can enrich bioarchaeological studies.