Assessment of Covid-19 vaccine confidence among healthcare personnel in the safety-net sector in the United States and Puerto Rico.

BACKGROUND: This study aimed to assess COVID-19 vaccine confidence among healthcare personnel in the safety net sector of the United States and Puerto Rico. This study aimed to examine the extent to which increased knowledge and positive attitudes toward COVID-19 vaccine safety and efficacy were associated with healthcare workers' COVID-19 vaccination status and their recommendation of the vaccine to all patients. METHODS: Online survey data were collected from health care workers working in Free and Charitable Clinics across the United States and Federally Qualified Health Centers in Puerto Rico. The survey consisted of 62 questions covering various demographic measures and constructs related to healthcare workers' vaccination status, beliefs, and recommendations for COVID-19 vaccination. Statistical analyses, including multivariate analysis, were conducted to identify the factors associated with the COVID-19 vaccine status and recommendations among healthcare personnel. RESULTS: Among the 2273 respondents, 93% reported being vaccinated against COVID-19. The analysis revealed that respondents who believed that COVID-19 vaccines were efficacious and safe were three times more likely to be vaccinated and twice as likely to recommend them to all their patients. Respondents who believed they had received adequate information about COVID-19 vaccination were 10 times more likely to be vaccinated and four times more likely to recommend it to all their patients. CONCLUSIONS: The study results indicate that healthcare workers' confidence in COVID-19 vaccines is closely tied to their level of knowledge, positive beliefs, and attitudes about vaccine safety and efficacy. The study emphasizes the significance of healthcare workers feeling well informed and confident in their knowledge to recommend the vaccine to their patients. These findings have important implications for the development of strategies to boost COVID-19 vaccine confidence among healthcare workers and increase vaccine uptake among patients.

Integrating Large-Scale Protein Structure Prediction into Human Genetics Research.

The last five years have seen impressive progress in deep learning models applied to protein research. Most notably, sequence-based structure predictions have seen transformative gains in the form of AlphaFold2 and related approaches. Millions of missense protein variants in the human population lack annotations, and these computational methods are a valuable means to prioritize variants for further analysis. Here, we review the recent progress in deep learning models applied to the prediction of protein structure and protein variants, with particular emphasis on their implications for human genetics and health. Improved prediction of protein structures facilitates annotations of the impact of variants on protein stability, protein-protein interaction interfaces, and small-molecule binding pockets. Moreover, it contributes to the study of host-pathogen interactions and the characterization of protein function. As genome sequencing in large cohorts becomes increasingly prevalent, we believe that better integration of state-of-the-art protein informatics technologies into human genetics research is of paramount importance.

Autoejercitación del ejercicio físico en los estudiantes de Educación Física de la Educación Superior

La atención a la habilidad auto ejercitación del ejercicio físico constituye punto de referencia para el cumplimiento de los objetivos estratégicos planteados por las universidades cubanas, particularmente en la disciplina Educación Física del Plan de estudios E, como un contenido del currículo que favorece el protagonismo del estudiante en su propio proceso de aprendizaje, constituye una necesidad antes los cambios que se operan en el sistema de Educación Superior Cubano, dado fundamentalmente por condiciones que surgieron de aislamiento físico provocado por la COVID 19, unido a la falta de habilidades para realizar actividad física y por garantizar una educación inclusiva, equitativa y de calidad. El objetivo de este trabajo consiste en elaborar una estrategia didáctica para la formación de la habilidad auto ejercitación del ejercicio físico; en la investigación se emplean métodos cualitativos y cuantitativos. Se inicia con el diagnóstico, utilizándose diferentes métodos y técnicas, como la encuesta, la entrevista. Además, se aplica los test para evaluar la condición física y de las insuficiencias que presenta los estudiantes de Educación Física de la carrera de Medicina Veterinaria de la Universidad Agraria de La Habana. La sistematización y los fundamentos teóricos y metodológicos analizados permitieron diseñar una estrategia didáctica, la cual cuenta de cuatro etapas, cada una de ellas con su objetivo y sistema de acciones, las cuales se ofrecen como resultado para la formación de la habilidad auto ejercitación del ejercicio físico en los estudiantes objetos de estudio. La evidencia de los aprendizajes adquiridos por los estudiantes, la valoración de especialistas indica una mejora de los niveles de condición física, las acciones propuestas responden al propósito para el cual fue concebida la estrategia.

A atenção à habilidade de autoexercício do exercício físico constitui um ponto de referência para o cumprimento dos objetivos estratégicos traçados pelas universidades cubanas, particularmente na disciplina de Educação Física do Currículo E, como conteúdo do currículo que favorece o protagonismo do aluno. o seu próprio processo de aprendizagem, constitui uma necessidade face às mudanças que estão a ocorrer no sistema de ensino superior cubano, dadas fundamentalmente pelas condições que surgiram do isolamento físico causado pela COVID 19, juntamente com a falta de competências para a realização de actividade física e garantir uma educação inclusiva, equitativa e de qualidade. O objetivo deste trabalho é desenvolver uma estratégia didática para o treinamento da habilidade de autoexercício do exercício físico; Métodos qualitativos e quantitativos são utilizados na pesquisa. Começa com o diagnóstico, utilizando diferentes métodos e técnicas, como inquéritos e entrevistas. Além disso, são aplicados testes para avaliar a condição física e as insuficiências apresentadas pelos estudantes de Educação Física da carreira de Medicina Veterinária da Universidade Agrária de Havana. A sistematização e os fundamentos teóricos e metodológicos analisados permitiram o desenho de uma estratégia didática, que conta com quatro etapas, cada uma delas com seu objetivo e sistema de ações, que são oferecidas como resultado para a formação da habilidade de autoexercício do exercício físico nos alunos estudados. A evidência das aprendizagens adquiridas pelos alunos, a avaliação dos especialistas indica uma melhoria nos níveis de aptidão física, as ações propostas respondem ao propósito para o qual a estratégia foi concebida.

Attention to the self-exercise skill of physical exercise constitutes a point of reference for the fulfillment of the strategic objectives set by Cuban universities, particularly in the Physical Education discipline of Study Plan E, as a content of the curriculum that favors the student's protagonism in his/her own learning process, constitutes a necessity in the face of the changes that are taking place in the Cuban Higher Education system, given fundamentally by conditions that arose from physical isolation caused by COVID 19, coupled with the lack of skills to perform physical activity and to guarantee inclusive, equitable and quality education. The objective of this work is to develop a didactic strategy for the training of the self-exercise skill of physical exercise; qualitative and quantitative methods are used in the research. It begins with the diagnosis, using different methods and techniques, such as surveys and interviews. In addition, tests are applied to evaluate the physical condition and insufficiencies presented by Physical Education students of the Veterinary Medicine career at the Agrarian University of Havana. The systematization and the theoretical and methodological foundations analyzed allowed the design of a didactic strategy, which has four stages, each of them with its objective and system of actions, which are offered as a result for the formation of the self-exercise skill of the physical exercise in the students studied. The evidence of the learning acquired by the students, the assessment of specialists indicates an improvement in physical fitness levels, the proposed actions respond to the purpose for which the strategy was conceived.

Protein interaction mapping reveals widespread targeting of development-related host transcription factors by phytoplasma effectors.

Phytoplasmas are pathogenic bacteria that reprogram plant host development for their own benefit. Previous studies have characterized a few different phytoplasma effector proteins that destabilize specific plant transcription factors. However, these are only a small fraction of the potential effectors used by phytoplasmas; therefore, the molecular mechanisms through which phytoplasmas modulate their hosts require further investigation. To obtain further insights into the phytoplasma infection mechanisms, we generated a protein-protein interaction network between a broad set of phytoplasma effectors and a large, unbiased collection of Arabidopsis thaliana transcription factors and transcriptional regulators. We found widespread, but specific, interactions between phytoplasma effectors and host transcription factors, especially those related to host developmental processes. In particular, many unrelated effectors target specific sets of TCP transcription factors, which regulate plant development and immunity. Comparison with other host-pathogen protein interaction networks shows that phytoplasma effectors have unusual targets, indicating that phytoplasmas have evolved a unique and unusual infection strategy. This study contributes a rich and solid data source that guides further investigations of the functions of individual effectors, as demonstrated for some herein. Moreover, the dataset provides insights into the underlying molecular mechanisms of phytoplasma infection.

Toward Understanding the Biochemical Determinants of Protein Degradation Rates.

Protein degradation is a key component of the regulation of gene expression and is at the center of several pathogenic processes. Proteins are regularly degraded, but there is large variation in their lifetimes, and the kinetics of protein degradation are not well understood. Many different factors can influence protein degradation rates, painting a highly complex picture. This has been partially unravelled in recent years thanks to invaluable advances in proteomics techniques. In this Mini-Review, we give a global vision of the determinants of protein degradation rates with the backdrop of the current understanding of proteolytic systems to give a contemporary view of the field.

Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms.

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a grave threat to public health and the global economy. SARS-CoV-2 is closely related to the more lethal but less transmissible coronaviruses SARS-CoV-1 and Middle East respiratory syndrome coronavirus (MERS-CoV). Here, we have carried out comparative viral-human protein-protein interaction and viral protein localization analyses for all three viruses. Subsequent functional genetic screening identified host factors that functionally impinge on coronavirus proliferation, including Tom70, a mitochondrial chaperone protein that interacts with both SARS-CoV-1 and SARS-CoV-2 ORF9b, an interaction we structurally characterized using cryo-electron microscopy. Combining genetically validated host factors with both COVID-19 patient genetic data and medical billing records identified molecular mechanisms and potential drug treatments that merit further molecular and clinical study.

The Global Phosphorylation Landscape of SARS-CoV-2 Infection.

The causative agent of the coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected millions and killed hundreds of thousands of people worldwide, highlighting an urgent need to develop antiviral therapies. Here we present a quantitative mass spectrometry-based phosphoproteomics survey of SARS-CoV-2 infection in Vero E6 cells, revealing dramatic rewiring of phosphorylation on host and viral proteins. SARS-CoV-2 infection promoted casein kinase II (CK2) and p38 MAPK activation, production of diverse cytokines, and shutdown of mitotic kinases, resulting in cell cycle arrest. Infection also stimulated a marked induction of CK2-containing filopodial protrusions possessing budding viral particles. Eighty-seven drugs and compounds were identified by mapping global phosphorylation profiles to dysregulated kinases and pathways. We found pharmacologic inhibition of the p38, CK2, CDK, AXL, and PIKFYVE kinases to possess antiviral efficacy, representing potential COVID-19 therapies.

Coevolution-based prediction of protein-protein interactions in polyketide biosynthetic assembly lines.

MOTIVATION: Polyketide synthases (PKSs) are enzymes that generate diverse molecules of great pharmaceutical importance, including a range of clinically used antimicrobials and antitumor agents. Many polyketides are synthesized by cis-AT modular PKSs, which are organized in assembly lines, in which multiple enzymes line up in a specific order. This order is defined by specific protein-protein interactions (PPIs). The unique modular structure and catalyzing mechanism of these assembly lines makes their products predictable and also spurred combinatorial biosynthesis studies to produce novel polyketides using synthetic biology. However, predicting the interactions of PKSs, and thereby inferring the order of their assembly line, is still challenging, especially for cases in which this order is not reflected by the ordering of the PKS-encoding genes in the genome. RESULTS: Here, we introduce PKSpop, which uses a coevolution-based PPI algorithm to infer protein order in PKS assembly lines. Our method accurately predicts protein orders (93% accuracy). Additionally, we identify new residue pairs that are key in determining interaction specificity, and show that coevolution of N- and C-terminal docking domains of PKSs is significantly more predictive for PPIs than coevolution between ketosynthase and acyl carrier protein domains. AVAILABILITY AND IMPLEMENTATION: The code is available on http://www.bif.wur.nl/ (under 'Software'). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Improved inference of intermolecular contacts through protein-protein interaction prediction using coevolutionary analysis.

MOTIVATION: Predicting residue-residue contacts between interacting proteins is an important problem in bioinformatics. The growing wealth of sequence data can be used to infer these contacts through correlated mutation analysis on multiple sequence alignments of interacting homologs of the proteins of interest. This requires correct identification of pairs of interacting proteins for many species, in order to avoid introducing noise (i.e. non-interacting sequences) in the analysis that will decrease predictive performance. RESULTS: We have designed Ouroboros, a novel algorithm to reduce such noise in intermolecular contact prediction. Our method iterates between weighting proteins according to how likely they are to interact based on the correlated mutations signal, and predicting correlated mutations based on the weighted sequence alignment. We show that this approach accurately discriminates between protein interaction versus non-interaction and simultaneously improves the prediction of intermolecular contact residues compared to a naive application of correlated mutation analysis. This requires no training labels concerning interactions or contacts. Furthermore, the method relaxes the assumption of one-to-one interaction of previous approaches, allowing for the study of many-to-many interactions. AVAILABILITY AND IMPLEMENTATION: Source code and test data are available at www.bif.wur.nl/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Sequence-based analysis of protein degradation rates.

Protein turnover is a key aspect of cellular homeostasis and proteome dynamics. However, there is little consensus on which properties of a protein determine its lifetime in the cell. In this work, we exploit two reliable datasets of experimental protein degradation rates to learn models and uncover determinants of protein degradation, with particular focus on properties that can be derived from the sequence. Our work shows that simple sequence features suffice to obtain predictive models of which the output correlates reasonably well with the experimentally measured values. We also show that intrinsic disorder may have a larger effect than previously reported, and that the effect of PEST regions, long thought to act as specific degradation signals, can be better explained by their disorder. We also find that determinants of protein degradation depend on the cell types or experimental conditions studied. This analysis serves as a first step towards the development of more complex, mature computational models of degradation of proteins and eventually of their full life cycle. Proteins 2017; 85:1593-1601. © 2017 Wiley Periodicals, Inc.

Scimitar syndrome in an asymptomatic adult: fortuitous diagnosis by imaging technique.

Congenital cardiopathies in adults are a rare clinical entity in the cardiology consultations. Advances in imaging techniques allow the fortuitous diagnosis of mild forms of these congenital abnormalities. We describe a case of an asymptomatic 41-year-old man, with a medical history of recurrent pneumonia during childhood and an established diagnosis of scimitar syndrome by computed tomography.

Diabetes alters cardiovascular responses to anaesthetic induction agents in STZ-diabetic rats.

BACKGROUND: People with diabetes are at increased risk of cardiovascular (CV) morbidity and mortality during surgery. The most appropriate anaesthetic induction agent for these patients is unknown. METHODS AND RESULTS: We assessed the CV effects of propofol, etomidate and ketamine in streptozotocin (65 mg/kg, IP) diabetic rats. In non-diabetic rats, none of these anaesthetics significantly modified cardiac output, heart rate or stroke volume, but ketamine increased systolic blood pressure (SBP) compared to etomidate and propofol (89.6 ± 2.4 mmHg, vs. 72.7 ± 3.0 and 75.4 ± 1.9; p < 0.05). In diabetic rats, by contrast, cardiac output was lower with ketamine (82.6 ± 14 ml/min) and etomidate (78.2 ± 15.8 ml/min) than with propofol (146 ± 21 ml/min, N = 8, p < 0.01). SBP, however, was higher in the propofol-treated group (93.3 ± 3.4 mmHg, p < 0.05). CONCLUSION: These results suggest that hyperglycaemia modifies CV responses to induction anaesthetics.

Influence of gender on long-term prognosis of patients with chronic heart failure seen in heart failure clinics.

BACKGROUND: Controversy exists concerning the influence of gender in the prognosis of patients with heart failure and no evidence is available from specific heart failure clinics. HYPOTHESIS: Women with ambulatory heart failure are managed differently than men, although their prognosis might be better than men. METHODS AND RESULTS: We analyzed the clinical characteristics, complementary test results, treatment, and prognosis in 4720 patients with chronic heart failure seen in 62 specialized clinics forming part of a multicenter registry during a mean follow-up of 40 months. The mean age was 65 +/- 12 years and 71% were men. The men were younger than the women and more often had a history of hyperlipidemia and ischemic heart disease. The men had a more advanced heart failure New York Heart Association (NYHA) functional class (III-IV) than the women and a greater frequency of systolic ventricular dysfunction. The men more often received treatment with beta-blockers, vasodilators, and antiplatelet aggregators as well as higher mean doses as compared with the women. The overall survival after the follow-up was similar for both genders, although the women had lower rates of survival free of admission for heart failure. CONCLUSIONS: Despite the mortality of women and men with heart failure being similar, the rate of readmission for heart failure is greater in women in specialized heart failure clinics. These results may be associated with the pharmacological treatment differences observed.

Preinfarction angina prior to first myocardial infarction does not influence long-term prognosis: a retrospective study with subgroup analysis in elderly and diabetic patients.

BACKGROUND AND HYPOTHESIS: Although prodromal angina occurring shortly before an acute myocardial infarction (MI) has protective effects against in-hospital complications, this effect has not been well documented after initial hospitalization, especially in older or diabetic patients. We examined whether angina 1 week before a first MI provides protection in these patients. METHODS: A total of 290 consecutive patients, 143 elderly (>64 years of age) and 147 adults (<65 years of age), 68 of whom were diabetic (23.4%) and 222 nondiabetic (76.6%), were examined to assess the effect of preceding angina on long-term prognosis (56 months) after initial hospitalization for a first MI. RESULTS: No significant differences were found in long-term complications after initial hospitalization in these adult and elderly patients according to whether or not they had prodromal angina (44.4% with angina vs 45.4% without in adults; 45.5% vs 58% in elderly, P < 0.2). Nor were differences found according to their diabetic status (61.5% with angina vs 72.7% without in diabetics; 37.3% vs 38.3% in nondiabetics; P = 0.4). CONCLUSION: The occurrence of angina 1 week before a first MI does not confer long-term protection against cardiovascular complications after initial hospitalization in adult or elderly patients, whether or not they have diabetes.

[Effect of angina in the week before myocardial infarction on long-term cardiovascular morbidity and mortality after hospital discharge]. / Influencia de la angina preinfarto en la semana previa en la morbimortalidad cardiovascular tardía tras el alta hospitalaria.

The occurrence of angina in the week preceding myocardial infarction is associated with a reduction in cardiovascular complications in the acute phase. However, little is known about it relationship with prognosis after hospitalization (e.g., cardiovascular death and the development of heart failure or ischemic cardiomyopathy). The study included 290 consecutive patients admitted for a first myocardial infarction: 107 (36.9%) had preceding angina while 183 did not. Those with a history of ischemic cardiomyopathy of more than 1 week or structural cardiopathy were excluded. There was no difference in baseline characteristics between the two groups. Moreover, there was no difference in the rates of cardiovascular complications after hospital discharge: cardiovascular death (7% vs. 12.6%; P=.3), heart failure (7.4% vs. 11.6%; P=.2), and myocardial ischemia, including myocardial infarction and unstable angina, requiring hospitalization (41.2% vs. 31.3%; P=.3). The occurrence of angina in the week before a first myocardial infarction did not influence cardiovascular complications after hospital discharge (odds ratio = 0.75 [0.51-1.11]; P=.15).

Bladder pheochromocytoma: case presentation and the use of OctreoScan for localization of extra-adrenal tumor sites in a pediatric patient.

An eleven year old boy presented with headaches and dizziness associated to micturition. On radiologic imaging, he was found with a bladder mass. The biochemical work up was suggestive of pheochromocytoma. An OctreoScan (111In-pentreotide) was used to rule out metastatic extension or other extra-adrenal locations of the pheochromocytoma. OctreoScan data correlated well with other radiologic studies, operative findings and with the final diagnosis, validating its use on pediatric patients.

[Use of polymerase chain reaction for the diagnosis of central nervous system infections]. / Utilización de la reacción en cadena de la polimerasa para el diagnóstico de infecciones del sistema nervioso central.

In the present work, the polymerase chain reaction (PCR) assay and his variants RT-PCR and Multiplex PCR were applied for the detection of specific sequences of Enterovirus, Human Herpes viruses (Herpes simple virus, Human Herpes virus type 6, Cytomegalovirus, Epstein Barr virus, and Varicella Zoster), Human Immunodeficiency virus, Toxoplasma gondii, Mycobacterium tuberculosis and Mycoplasma pneumoniae in patients' cohorts grouped by medical suspicion of meningoencephalitis. Of 326 samples of processed cerebrospinal fluid (CSF), 93 samples (28.5%) were positive for the different infectious agents. In the group of patients with clinical diagnosis of viral meningoencephalitis (n=212), there was obtained a whole of 73 positive samples (34.4%), of which 37 patients were positive to Enterovirus (50.7%), 19 were positive to VHS (26%) and 10 patients (13.7%) were positive to CMV. Other viral agents as VZV, EBV and HVH6 were detected in minor frequency. The 114 remaining samples were analyzed applying specific PCR to each pathogen for strict medical indication, being able to detect the presence of Human Immunodeficiency Virus (40%), Mycoplasma pneumoniae (40%), Toxoplasma gondii (14%) and Mycobacterium tuberculosis (12%) in CSF samples. The results obtained in this study demonstrate the convenience of the application of the molecular assays in the laboratory diagnosis of the meningoencefalitis of different etiology. Besides this, it is also a very valuable tool for the clinical management of the patients and for the execution of the epidemiological studies.