How hydrolytic exoribonucleases impact human disease: Two sides of the same story.

RNAs are extremely important molecules inside the cell, which perform many different functions. For example, messenger RNAs, transfer RNAs and ribosomal RNAs are involved in protein synthesis, whereas noncoding RNAs have numerous regulatory roles. Ribonucleases (RNases) are the enzymes responsible for the processing and degradation of all types of RNAs, having multiple roles in every aspect of RNA metabolism. However, the involvement of RNases in disease is still not well understood. This review focuses on the involvement of the RNase II/RNB family of 3'-5' exoribonucleases in human disease. This can be attributed to direct effects, whereby mutations in the eukaryotic enzymes of this family [defective in sister chromatid joining (Dis3; or Rrp44), Dis3-like exonuclease 1 (Dis3L1; or Dis3L) and Dis3-like exonuclease 2 (Dis3L2)] are associated with a disease, or indirect effects, whereby mutations in the prokaryotic counterparts of RNase II/RNB family (RNase II and/or RNase R) affect the physiology and virulence of several human pathogens. In this review, we compare the structural and biochemical characteristics of the members of the RNase II/RNB family of enzymes. The outcomes of mutations impacting enzymatic function are revisited, in terms of both the direct and indirect effects on disease. Furthermore, we also describe the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral exoribonuclease and its importance to combat the COVID-19 pandemic. As a result, RNases may be a good therapeutic target to reduce bacterial and viral pathogenicity. These are the two perspectives on RNase II/RNB family enzymes that are presented in this review.

Lifestyle changes and mental health during the COVID-19 pandemic: A repeated, cross-sectional web survey.

BACKGROUND: This study aimed to compare self-reported changes on lifestyle behaviors during two phases of the COVID-19 pandemic in Spain, and to evaluate clinical and sociodemographic factors associated with lifestyles. METHODS: Two cross-sectional web surveys were conducted during lockdown (April 15-May 15, 2020) and seven months later (November 16-December 16, 2020). Lifestyle behaviors were self-reported by a multidimensional scale (SMILE-C). Two separate samples of respondents were analyzed. A multivariate regression model was performed to evaluate the association of SMILE-C scores with demographic and clinical variables. RESULTS: The sample comprised, 3412 participants from the first survey (S1) and in the S1 and 3635 from the second (S2). SMILE-C score decreased across surveys (p < 0.001). The rates of positive screenings for depression and anxiety were similar between the surveys, whereas those for alcohol abuse decreased (p < 0.001). Most participants in S2 reported that their lifestyle had not changed compared to those before the pandemic. Variables independently associated with an unhealthier lifestyle were working as an essential worker, lower educational level, previous mental disease, worse self-rated health, totally/moderate changes on diet, sleep or social support, as well as positive screenings for alcohol abuse, anxiety and depression. LIMITATIONS: The cross-sectional design and recruitment by non-probabilistic methods limit inferring causality and the external validity of the results. CONCLUSIONS: Overall lifestyle worsened seven months after the lockdown in Spain. Several demographic and clinical factors were associated with lifestyle scores. The contribution of common mental disorders to unhealthier lifestyles should be considered in order to prevent the negative impact of the pandemic.

Lifestyle in Undergraduate Students and Demographically Matched Controls during the COVID-19 Pandemic in Spain.

Few studies have used a multidimensional approach to describe lifestyle changes among undergraduate students during the COVID-19 pandemic or have included controls. This study aimed to evaluate lifestyle behaviors and mental health of undergraduate students and compare them with an age and sex-matched control group. A cross-sectional web survey using snowball sampling was conducted several months after the beginning of COVID-19 pandemic in Spain. A sample of 221 students was recruited. The main outcome was the total SMILE-C score. Students showed a better SMILE-C score than controls (79.8 + 8.1 vs. 77.2 + 8.3; p < 0.001), although these differences disappeared after controlling for covariates. While groups did not differ in the screenings of depression and alcohol abuse, students reported lower rates of anxiety (28.5% vs. 37.1%; p = 0.042). A lower number of cohabitants, poorer self-perceived health and positive screening for depression and anxiety, or for depression only were independently associated (p < 0.05) with unhealthier lifestyles in both groups. History of mental illness and financial difficulties were predictors of unhealthier lifestyles for students, whereas totally/moderate changes in substance abuse and stress management (p < 0.05) were predictors for the members of the control group. Several months after the pandemic, undergraduate students and other young adults had similar lifestyles.

Impact of SARS-CoV-2 pandemic on ST-elevation myocardial infarction admissions and outcomes in a Portuguese primary percutaneous coronary intervention center: Preliminary Data.

INTRODUCTION: Coronavirus disease (COVID-19) has led to significant changes in healthcare systems and its impact on the treatment of cardiovascular conditions, such as ST-elevation myocardial infarction (STEMI), is unknown in countries where the healthcare systems were not saturated, as was the case in Portugal. As such, we aimed to assess the effect on STEMI admissions and outcomes in Portuguese centers. METHODS: We conducted a single-center, observational, retrospective study including all patients admitted to our hospital due to STEMI between the date of the first SARS-CoV-2 case diagnosed in Portugal and the end of the state of emergency (March and April 2020). Patient characteristics and outcomes were assessed and compared with the same period of 2019. RESULTS: A total of 104 STEMI patients were assessed, 55 in 2019 and 49 in 2020 (-11%). There were no significant differences between groups regarding age (62±12 vs. 65±14 years, p=0.308), gender (84.8% vs. 77.6% males, p=0.295) or comorbidities. In the 2020 group, there was a significant decrease in the proportion of patients transported to the hospital in pre-hospital emergency medical transportation (38.2% vs. 20.4%, p=0.038), an increase in system delay (49 [30-110.25] vs. 140 [90-180] minutes, p=0.019), a higher Killip-Kimball class, with a decrease in class I (74.5% vs. 51%) and an increase in class III (1.8% vs. 8.2%) and IV (5.5% vs. 18.4%) (p=0.038), a greater incidence of vasoactive support (3.7% vs. 26.5%, p=0.001), invasive mechanic ventilation usage (3.6% vs. 14.3%, p=0.056), and an increase in severe left ventricular dysfunction at hospital discharge (3.6% vs. 16.3%, p=0.03). In-hospital mortality was 14.3% in the 2020 group and 7.3% in the 2019 group p=0.200). CONCLUSION: Despite a lack of significant variation in the absolute number of STEMI admissions, there was an increase in STEMI clinical severity and significantly worse outcomes during the SARS-CoV-2 pandemic. An increase in system delay, impaired pre-hospital care and patient fear of in-hospital infection can partially justify these results and should be the target of future actions in further waves of the pandemic.

INTRODUÇÃO: A doença por coronavírus 2019 (COVID-19) originou alterações significativas nos sistemas de saúde e a sua influência no tratamento da patologia cardiovascular, como no caso do enfarte agudo do miocárdio com supradesnivelamento do segmento ST (EAMcSST), é desconhecida em países onde não ocorreu saturação da capacidade dos sistemas de saúde, como é o caso de Portugal. Assim, o nosso objetivo foi determinar o efeito nas admissões por EAMcSST e no seu prognóstico intra-hospitalar na região Centro de Portugal. MÉTODOS: Realizou-se um estudo unicêntrico, observacional e retrospetivo, incluindo todos os doentes admitidos no nosso hospital por EAMcSST entre a data do primeiro caso de SARS-CoV-2 em Portugal e o término do estado de emergência (março e abril de 2020). Foram avaliadas as características e os resultados dos doentes e foi realizada uma comparação com o período homólogo de 2019. RESULTADOS: Foram incluídos 104 doentes com EAMcSST, 55 em 2019 e 49 em 2020 (-11%). Não se verificaram diferenças significativas entre os grupos relativamente à idade (62±12 versus 65±14 anos, p=0,308), género (84,8% mulheres versus 77,6% homens, p=0,295) ou comorbilidades. No grupo de doentes de 2020 verificou-se uma diminuição significativa na proporção de doentes transportados para o hospital pela viatura médica do Instituto Nacional de Emergência Médica (38,2% versus 20,4%, p=0,038), um aumento no atraso do sistema de saúde (49 [30-110,25] versus 140 [90-180] minutos, p=0,019), uma maior classe Killip-Kimball, com uma redução de doentes em classe I (74,5% versus 51%) e um aumento na classe III (1,8% versus 8,2%) e IV (5,5% versus 18,4%) (p=0,038), uma maior incidência de suporte vasoativo (3,7% versus 26,5%, p=0,001), de ventilação mecânica invasiva (3,6% versus 14,3%, p=0,056) e um aumento da proporção de doentes com disfunção ventricular esquerda grave na alta hospitalar (3,6% versus 16,3%, p=0,03). A mortalidade intra-hospitalar foi de 14,3% no grupo de 2020 e de 7,3% no grupo de 2019 (p=0,200). CONCLUSÃO: Apesar de não se ter verificado uma variação significativa no número de admissões por EAMcSST, existiu um aumento da gravidade, com um prognóstico intra-hospitalar significativamente mais adverso durante a pandemia por SARS-CoV-2. Um aumento no atraso do sistema de saúde, um compromisso nos serviços pré-hospitalares e o receio por parte dos doentes de contraírem uma eventual infeção hospitalar podem justificar parcialmente estes resultados e devem ser planeadas ações para diminuir o seu efeito em novos surtos pandémicos.

Psychiatric Clinical Profiles and Pharmacological Interactions in COVID-19 Inpatients Referred to a Consultation Liaison Psychiatry Unit: a Cross-Sectional Study.

The Coronavirus Disease 2019 (COVID-19) can affect mental health in different ways. There is little research about psychiatric complications in hospitalized patients with COVID-19. The aim of the study was to describe the psychiatric clinical profile and pharmacological interactions in COVID-19 inpatients referred to a Consultation-Liaison Psychiatry (CLP) unit. This is a cross-sectional study, carried out at a tertiary hospital in Spain, in inpatients admitted because of COVID-19 and referred to our CLP Unit from March 17,2020 to April 28,2020. Clinical data were extracted from electronic medical records. The patients were divided in three groups depending on psychiatric diagnosis: delirium, severe mental illness (SMI) and non-severe mental illness (NSMI). Of 71 patients included (median [ICR] age 64 [54-73] years; 70.4% male), 35.2% had a delirium, 18.3% had a SMI, and 46.5% had a NSMI. Compared to patients with delirium and NSMI, patients with SMI were younger, more likely to be institutionalized and were administered less anti-COVID19 drugs. Mortality was higher among patients with delirium (21.7%) than those with SMI (0%) or NSMI (9.45%). The rate of side effects due to interactions between anti-COVID19 and psychiatric drugs was low, mainly drowsiness (4.3%) and borderline QTc prolongation (1.5%). Patients affected by SMI were more often undertreated for COVID-19. However, the rate of interactions was very low, and avoidable with a proper evaluation and drug-dose adjustment. Half of the patients with SMI were institutionalized, suggesting that living conditions in residential facilities could make them more vulnerable to infection.