The complexities in genotyping of congenital adrenal hyperplasia: 21-hydroxylase deficiency

The deficiency of 21-hydroxylase due to CYP21A2 pathogenic variants is a rather frequent disease with serious consequences, going from a real mortality risk to infertility and to milder symptoms, nevertheless important for affecting the patients’ self-esteem. In the most severe cases life-threatening adrenal salt wasting crises may occur. Significant morbidity including the possibility of mistaken gender determination, precocious puberty, infertility and growth arrest with consequent short stature may also affect these patients. In the less severe cases milder symptoms like hirsutism will likely affect the image of the self with strong psychological consequences. Its diagnosis is confirmed by 17OH-progesterone dosages exceeding the cut-off value of 10/15 ng/ml but genotyping is progressively assuming an essential role in the study of these patients particularly in confirming difficult cases, determining some aspects of the prognosis and allowing a correct genetic counseling. Genotyping is a difficult process due to the occurrence of both a gene and a highly homologous pseudo gene. However, new tools are opening new possibilities to this analysis and improving the chances of a correct diagnosis and better understanding of the underlying mechanisms of the disease. Beyond the 10 classic pathogenic variants usually searched for in most laboratories, a correct analysis of 21OH-deficiency cases implies completely sequencing of the entire gene and the determination of gene duplications. These are now recognized to occur frequently and can be responsible for some false positive cases. And finally, because gene conversions can include several pathogenic variants one cannot be certain of identifying that both alleles are affected without studying parental DNA samples. A complete genotype characterization should be considered essential in the preparation for pregnancy, even in the case of parents with milder forms of the disease, or even just carriers, since it has been reported that giving birth to progeny with the severe classic forms occurs with a much higher frequency than expected.The work was supported by the Foundation for Science and Technology (FCT) (PTDC/MEC-ONC/31384/2017). SG was funded through FCT grant SFRH/BPD/1117441/2015

Lymphopenia in Patients Submitted to Assisted Ventilation Due to Aggravated Chronic Respiratory Failure: a Prospective Study

Objectivo: avaliar e caracterizar a linfopenia em doentes admitidos numa unidade de cuidados intensivos para suporte ventilatório por exacerbação de insuficiência respiratória crónica e eventual relação com a gravidade da doença. Material e métodos: estudo prospectivo com 6 meses de duração e mais 6 meses de seguimento após alta da unidade. Incluídos 24 doentes, 22 homens, com APACHE II médio de 19,7, 3 dos quais com possibilidade de seguimento após a alta. Foram colhidas análises para determinação das subpopulações linfocitárias na admissão e a cada 7 dias de ventilação mecânica. Excluídos doentes com sinais de infecção ou imunossupressão prévia, à excepção dos corticóides. Resultados: a linfopenia foi encontrada em 79,2 % dos doentes com depleção de todas as subpopulações linfocitárias sendo mais expressiva a depleção de linfócitos B CD19+. Esta linfopenia não se relacionou com os níveis séricos de cortisol, e apesar de se relacionar com uma maior gravidade clínica não esteve associada a uma maior mortalidade. O registo evolutivo no internamento mostrou tendencialmente uma recuperação da linfopenia. Conclusões: a linfopenia é frequente em doentes ventilados por exacerbação de doença respiratória crónica. Trata-se de uma linfopenia não selectiva, que recupera ao longo do internamento, mais acentuada ao nível dos linfócitos B CD19+. Estes doentes apresentam índices de gravidade maior mas sem diferenças na mortalidade. O seguimento ambulatório destes doentes mostrou-se difícil e foi inconclusivo

Longitudinal study of individual exercises in elite rhythmic gymnastics

[Abstract] The performance evolution in rhythmic gymnastics depends on changes in code of points. At the beginning of each Olympic cycle the code of points changes and therefore, the content of the competition exercises, as well. This study aimed to analyze – for each apparatus – the evolution of number of technical elements and final score over the last two decades (last 13 world championships), how they have been affected by changed code of points, and how the final score relates to the number of technical elements performed. The sample consisted of 416 exercises in five apparatus: ball (96), rope (40), hoop (96), ribbon (88), and clubs (96). The following variables were gathered: code of points, apparatus, technical group, total number of elements, final classification, and final score. Linear mixed-effects models were used to examine the effects on the number of elements and final score in each apparatus. The number of technical elements increased in all apparatus, between 7.4 and 20% over a 10-year period. There were mixed evolutions of final score between the different apparatus, between 6.3 and 14% over a 10-year period. There is small increase in number of elements in hoop and a small decrease in rope after a code change. There was a small decrease in final score in championships after a code change in hoop, moderate in clubs and ribbon, and large in rope. There was a negative relationship between number of elements performed and final score in clubs. In conclusion, the code change generally effects the final score negatively, but there were apparatus specific effects of code change on number of elements and relationship between number of elements and final score

Seasonal prediction of the boreal winter stratosphere

The predictability of the Northern Hemisphere stratosphere and its underlying dynamics are investigated in five state-of-the-art seasonal prediction systems from the Copernicus Climate Change Service (C3S) multi-model database. Special attention is devoted to the connection between the stratospheric polar vortex (SPV) and lower-stratosphere wave activity (LSWA). We find that in winter (December to February) dynamical forecasts initialised on the first of November are considerably more skilful than empirical forecasts based on October anomalies. Moreover, the coupling of the SPV with mid-latitude LSWA (i.e., meridional eddy heat flux) is generally well reproduced by the forecast systems, allowing for the identification of a robust link between the predictability of wave activity above the tropopause and the SPV skill. Our results highlight the importance of November-to-February LSWA, in particular in the Eurasian sector, for forecasts of the winter stratosphere. Finally, the role of potential sources of seasonal stratospheric predictability is considered: we find that the C3S multi-model overestimates the stratospheric response to El Niño–Southern Oscillation (ENSO) and underestimates the influence of the Quasi–Biennial Oscillation (QBO)

COVID-19 attributed mortality and ambient temperature: a global ecological study using a two-stage regression model

A negative correlation between ambient temperature and COVID-19 mortality has been observed. However, the World Meteorological Organization (WMO) has reinforced the importance of government interventions and warned countries against relaxing control measures due to warmer temperatures. Further understanding of this relationship is needed to help plan vaccination campaigns opportunely. Using a two-stage regression model, we conducted cross-sectional and longitudinal analyses to evaluate the association between monthly ambient temperature lagged by one month with the COVID-19 number of deaths and the probability of high-level of COVID-19 mortality in 150 countries during time t = 60, 90, and 120 days since the onset. First, we computed a log-linear regression to predict the pre-COVID-19 respiratory disease mortality to homogenize the baseline disease burden within countries. Second, we employed negative binomial and logistic regressions to analyze the linkage between the ambient temperature and our outcomes, adjusting by pre-COVID-19 respiratory disease mortality rate, among other factors. The increase of one Celsius degree in ambient temperature decreases the incidence of COVID-19 deaths (IRR = 0.93; SE: 0.026, p-value<0.001) and the probability of high-level COVID-19 mortality (OR = 0.96; SE: 0.019; p-value<0.001) over time. High-income countries from the northern hemisphere had lower temperatures and were most affected by pre-COVID respiratory disease mortality and COVID-19 mortality. This study provides a global perspective corroborating the negative association between COVID-19 mortality and ambient temperature. Our longitudinal findings support the statement made by the WMO. Effective, opportune, and sustained reaction from countries can help capitalize on higher temperatures’ protective role including the timely rollout of vaccination campaigns

The Influence of Thermal Comfort on the Quality of Life of Nursing Home Residents

Thermal comfort (TC) parameters were measured in 130 rooms from nursing homes (NH), following ISO 7730:2005 in order to evaluate the influence of winter season TC indices on quality of life (QoL) in older individuals. Mean radiant temperature (mrT), predicted mean vote (PMV) and predicted percent of dissatisfied people (PPD) indices, and the respective measurement uncertainties were calculated using Monte Carlo Method. The WHOQOL-BREF questionnaire was conducted from September 2012 to April 2013, during the winter season TC sampling campaign. Winter PMV and PPD indices showed significant differences between seasons in median values for comfort. There were also significant differences between seasons for air temperature, air velocity, mrT, and relative humidity. The winter PMV index displayed a “slightly cool” [≤−1] to “cool” [≤−2] in thermal sensation scale [−3 to 3]. PPD index reflected this discomfort as evidenced by a high rate of predicted dissatisfied occupants (64%). The influence of winter season TC on older individual QoL results demonstrated that values of PMV above −0.7 had higher mean score of QoL (coefficient estimate: 11.13 units) compared with values of PMV below −0.7. These findings are of relevance to public health and may be useful for understanding NH indoor environment variables thus implementing preventive policies in terms of standards and guidelines for these susceptible populations.This work was supported by GERIA Project (www.geria.webnode.com): PTDC/SAU-SAP/116563/2010 and a PhD Grant (SFRH/BD/72399/2010) from Foundation for Science and Technology (Fundação para a Ciência e Tecnologia - FCT) through Operational Competitiveness Programme (COMPETE) as part of the National Strategic Reference Framework. SB work was supported by a grant funded by AIRC (Associazione Italiana per la Ricerca sul Cancro)

The threat of climate change on population health and the urgent need to act

Climate change is associated with negative health outcomes, such as cardiovascular and respiratory diseases. This article analyses the threat of climate change on population health and the urgent need to implement measures to avoid this damage. Heat vulnerability, heatwave exposures, and wildfire exposure to forest fires have increased in Chile. In 2018, the annual mean concentration of fine particulate matter (PM2.5) exceeded the safe level proposed by the World Health Organization, increasing the risk of negative health outcomes. Thus, multidisciplinary and intersectoral mitigation and adaptation policies are needed. Among other elements, mental health impacts of climate change, health education provided by health workers to reduce negative health impacts of climate change, greater engagement of academia to generate evidence useful for policy-making processes and a better articulation between central and local governments should be considered. Finally, achieving a healthy population should be the aim of all these policies and efforts

Maternal exposure to a high-magnitude earthquake during pregnancy influences pre-reading skills in early childhood

Exposure to an adverse prenatal environment can influence fetal development and result in long-lasting changes in the offspring. However, the association between maternal exposure to stressful events during pregnancy and the achievement of pre-reading skills in the offspring is unknown. Here we examined the association between prenatal exposure to the Chilean high-magnitude earthquake that occurred on February 27th, 2010 and the development of early reading precursors skills (listening comprehension, print knowledge, alphabet knowledge, vocabulary, and phonological awareness) in children at kindergarten age. This multilevel retrospective cohort study including 3280 children, of whom 2415 were unexposed and 865 were prenatally exposed to the earthquake shows substantial evidence that maternal exposure to an unambiguously stressful event resulted in impaired pre-reading skills and that a higher detrimental effect was observed in those children who had been exposed to the earthquake during the first trimester of gestation. In addition, females were more significantly affected by the exposure to the earthquake than their male peers in alphabet knowledge; contrarily, males were more affected than females in print knowledge skills. These findings suggest that early intervention programs for pregnant women and/or children exposed to prenatal stress may be effective strategies to overcome impaired pre-reading skills in children