Development of a low-cost congenital abdominal wall defect simulator (wall-go) for undergraduate medical education: a validation study.

BACKGROUND: Congenital Anomalies were responsible for 303,000 deaths in the neonatal period, according to the WHO, they are among the world's top 20 causes of morbidity and mortality. Expensive simulators demonstrate several diseases, but few are related to congenital anomalies. This study aims to develop, validate, and evaluate low-cost simulator models (WALL-GO) of the most common abdominal wall defects, gastroschisis, and omphalocele, to enable diagnosis through an accessible tool with study value and amenable to replication. METHODS: Market research was conducted to find materials to build low-cost models. The researchers built the model and underwent validation assessment of the selected experts who scored five or more in the adapted Fehring criteria. The experts were assessed through a 5-point Likert scale to 7 statements (S1-7). Statements were assigned values according to relevance in face and transfer validities. Concomitantly, the model was also evaluated by students from 1st to 5th year with the same instruments. Content Validity Indexes (CVIs) were considered validated between groups with concordance greater than 90%. Text feedback was also collected. Each statement was subjected to Fisher's Exact Test. RESULTS: Gastroschisis and omphalocele model costs were US $15 and US $27, respectively. In total, there were 105 simulator evaluators. 15 experts were selected. Of the 90 students, there were 16 (1st year), 22 (2nd), 16 (3rd), 22 (4th), and 14 (5th). Students and experts obtained CVI = 96.4% and 94.6%, respectively. The CVIs of each statement were not significantly different between groups (p < 0,05). CONCLUSIONS: The WALL-GO models are suitable for use and replicable at a manufacturable low cost. Mannequins with abdominal wall defects are helpful in learning to diagnose and can be applied in teaching and training health professionals in developing and low-income countries.

Flebite associada a cateter venoso periférico e a administração de medicamentos: Análise retrospetiva de incidentes / Peripheral intravenous catheter-associated phlebitis and drug administration: Retrospective incident analysis / Flebitis asociada al catéter venoso periférico y a la administración de fármacos: Análisis retrospectivo de incidentes

Resumo Enquadramento: A flebite é uma complicação associada à utilização de cateter venoso periférico, classificada como evento adverso. Objetivos: Analisar os incidentes de flebite associada ao cateter venoso periférico e aos medicamentos administrados em doentes adultos internados e as suas consequências. Metodologia: Estudo quantitativo, retrospetivo, descritivo e transversal. Técnica de amostragem não probabilística por conveniência sendo selecionados 96 doentes adultos internados em 2019, na área da medicina de um Centro Hospitalar em Lisboa. O grau de flebite foi avaliado pela escala Visual Infusion Phlebitis Score Português Portugal (VIP PT-PT) traduzida e adaptada para Português Europeu. O dano foi categorizado de acordo com a classificação internacional sobre segurança do doente (CISD). Resultados: Dos incidentes de flebite documentados, 78% classificados com score 2 pela escala VIP PT-PT. Pela CISD, 87,5% resultaram em dano ligeiro e 12,5% em moderado. Os antibióticos foram o grupo terapêutico mais frequente. Conclusão: A flebite tem impacto na segurança do doente. Reforça-se a importância dos cuidados de enfermagem com enfoque na vigilância e deteção precoce de flebite.

Abstract Background: Phlebitis is a complication associated with peripheral intravenous catheters and an adverse event. Objective: To analyze peripheral intravenous catheter-associated phlebitis incidents associated and drug administration to adult inpatients and their consequences. Methodology: Quantitative, retrospective, descriptive, and cross-sectional study. Non-probabilistic convenience sampling technique was used, with 96 adult patients hospitalized in 2019 selected in the area of medicine at a Hospital Center in Lisbon. The type of phlebitis incident was characterized using the Visual Infusion Phlebitis scale adapted and translated to European Portuguese. Patient harm was categorized according to the International Classification for Patient Safety (ICPS). Results: Of the documented phlebitis incidents, 78% obtained a score 2 on the VIP PT-PT scale. According to the ICPS, 87.5% resulted in mild harm and 12.5% in moderate harm. Antibiotics were the most frequent therapeutic group. Conclusion: Phlebitis has an impact on patient safety. The importance of nursing care is reinforced, with a focus on surveillance and early detection of phlebitis to prevent complications.

Resumen Marco contextual: La flebitis es una complicación asociada al uso de catéteres venosos periféricos clasificada como acontecimiento adverso. Objetivos: Analizar los incidentes de flebitis asociada al empleo de catéteres venosos periféricos y a la administración de fármacos en pacientes adultos hospitalizados y sus consecuencias. Metodología: Estudio cuantitativo, retrospectivo, descriptivo y transversal. Técnica de muestreo no probabilístico por conveniencia, se seleccionaron 96 pacientes adultos ingresados en 2019 en el área médica de un centro hospitalario de Lisboa. El grado de flebitis se evaluó mediante la escala Visual Infusion Phlebitis Score Portugués Portugal (VIP PT-PT), traducida y adaptada al portugués europeo. El daño se categorizó según la Clasificación Internacional sobre Seguridad del Paciente (CISD). Resultados: De los incidentes de flebitis documentados, el 78% se clasificó con una puntuación de 2 según la escala VIP PT-PT. Por la CISD, el 87,5% resultó en daño leve y el 12,5% en moderado. Los antibióticos fueron el grupo terapéutico más frecuente. Conclusión: La flebitis repercute en la seguridad del paciente. Se refuerza la importancia de los cuidados de enfermería centrados en la vigilancia y la detección precoz de la flebitis.

Aplicação da Medication Fall Risk Score em doentes com notificação de incidente de queda: Análise retrospetiva / Application of the Medication Fall Risk Score in patients will fall notification: A retrospective analysis / Aplicación de la Medication Fall Risk Score en pacientes con incidente de caída notificado: Análisis retrospectivo

Resumo Enquadramento: As quedas em contexto hospitalar são eventos adversos frequentes, sendo os medicamentos um importante fator contribuinte. Objetivo: Analisar notificações de queda de doentes internados e caracterizar o risco de queda com foco na terapia farmacológica, através da aplicação da Medication Fall Risk Score. Metodologia: Estudo observacional, descritivo e retrospetivo realizado num centro hospitalar português. Aplicada a Medication Fall Risk Score, numa amostra de 183 notificações de queda ocorridas no primeiro trimestre de 2021. Resultados: A Medication Fall Risk Score identificou 60,6% dos doentes com "sim" para o alto risco de queda. Relativamente à avaliação de risco de queda registada nas notificações com recurso a outra escala, identificou-se que 65,8% dos doentes foram classificados como "baixo risco" ou "sem risco". Desses, 53,9% foram classificados com "sim" para o alto risco através da Medication Fall Risk Score. Conclusão: A Medication Fall Risk Score poderá contribuir para melhorar a deteção de doentes com "alto risco" de queda, permitindo uma gestão mais segura dos medicamentos para a prevenção das quedas.

Abstract Background: Falls in hospital settings are frequent adverse events, with medications contributing significantly. Objective: To analyze inpatient fall notifications and characterize fall risk with a focus on drug therapy by applying the Medication Fall Risk Score. Methodology: An observational, descriptive, and retrospective study was conducted in a Portuguese hospital center. The Medication Fall Risk Score was applied to a sample of 183 patient fall notifications in the first quarter of 2021. Results: The Medication Fall Risk Score identified 60.6% of patients with "yes" for high fall risk. Regarding fall risk assessment recorded in the notifications using another scale, 65.8% of patients were classified as "low risk" or "no risk." Of these, 53.9% were classified as "yes" for high risk using the Medication Fall Risk Score. Conclusion: The Medication Fall Risk Score may help to improve the detection of patients at "high risk" of falling, allowing safer medication practices for fall prevention.

Resumen Marco contextual: Las caídas en los hospitales son eventos adversos frecuentes y la medicación es un factor importante. Objetivo: Analizar las notificaciones de caída de pacientes hospitalizados y caracterizar el riesgo de caída centrándose en el tratamiento farmacológico, mediante la aplicación de la Medication Fall Risk Score. Metodología: Estudio observacional, descriptivo y retrospectivo realizado en un centro hospitalario portugués. Aplicada la Medication Fall Risk Score en una muestra de 183 notificaciones de caída ocurridas en el primer trimestre de 2021. Resultados: La Medication Fall Risk Score identificó al 60,6% de los pacientes con un "sí" para riesgo de caída elevado. En cuanto a la evaluación del riesgo de caída registrada en las notificaciones mediante otra escala, el 65,8% de los pacientes fueron clasificados como de "riesgo bajo" o "sin riesgo". De ellos, el 53,9% se clasificaron con un "sí" para riesgo elevado a través de la Medication Fall Risk Score. Conclusión: La Medication Fall Risk Score podría ayudar a mejorar la detección de pacientes con "riesgo elevado" de caída, lo que permitiría una gestión más segura de los medicamentos para prevenirla.

miRNA-143 expression is associated with inflammation and time of exposure to amniotic fluid in experimental gastroschisis.

OBJECTIVE: Gastroschisis (GS) is a congenital anomaly in the abdominal wall with the intestinal loops exiting laterally to the umbilicus. The contact of the loops with Amniotic Fluid (AF) causes an inflammatory process in the exposed part, leading to an extended hospital stay and an increased risk of morbidity due to alterations related to intestinal motility. The authors aimed to evaluate the time of exposure to the AF in the experimental GS and to search for potential biomarkers of intestinal inflammation by measuring microRNAs. METHODS: Rat fetuses were divided into three groups: a) CONTROL, b) GS reared on day 18 (GS = 18), and c) GS reared on day 19.5 (GS = 19) (term = 22 days). On day 21.5, the fetuses were removed for biometric parameters and biochemical analyses: 1) Biometrics: Body and Intestinal Weight (BW, IW), and intestinal-body weight ratio (IW/BW); 2) Descriptive histopathology and 3) miR-143 quantification by real-time Polymerase Chain Reaction (PCR). RESULTS: BW was higher in CONTROL than GS 18 and G19 (p < 0.05). IW, IW/BW, intestinal water, and mRNA-143 were higher in GS 18 and GS 19 than in CONTROL, and GS 18 was higher than GS 19 (p < 0.05). The average of the inflammation score from the intestinal wall with mucosal inflammation and intra-epithelial lymphocytes shows worst in GS 18 and GS 19 vs. CONTROL (p < 0.05). CONCLUSIONS: The tissue expression of mRNA-143 and the morphological changes in the intestine of GS worsened according to the time of exposure to AF, which could be a possible marker of fetal intestinal damage.

Titanium abutment background masking using highly opaque cements for implant prosthetics.

PURPOSE: To evaluate the capacity of highly opaque cements on masking titanium abutment background. METHODS: Dentin and titanium specimens were used to simulate respectively, a natural dental background and an implant abutment. To simulate the full-crowns, Y-TZP zirconia (ZC), lithium disilicate (LD), and resin composite (RC) blocks were used. The titanium specimens were divided into six cementation groups (n=10): two regular cements (BQM and RX); three opaque cements (MHA; VA and BHA); and a clear liquid (CL). The masking capacity of each cement was calculated as the color difference between the color of the crowns over dentin with clear liquid (reference) and the color of the crowns over the titanium with the different cements (ΔEab). Data were statistically analyzed using two-way ANOVA and Tukey test (α= 0.05). RESULTS: Significant differences (P= 0.0001) were observed for both factors, cement and crown, and for the interactions between them. The results of Tukey test for cement were: BHA-2.25(0.98), MHA-2.94 (1.03), VA-3.45 (1.67), BQM-9.55 (2.77), RX-9.88 (3.12), CL-10.41 (3.47). The cements BHA, MHA and VA showed significantly smaller means than BQM, RX and CL. The results for crown were: ZC-3.66 (2.37), LD-7.50 (4.08), RC-8.08 (4.67). The means for all crown materials were significantly different. Highly opaque cements were more efficient on background masking than regular cements. Zirconia promoted the higher color masking while the resin composite the lowest. CLINICAL SIGNIFICANCE: The use of a highly opaque cement can reduce the color interference of the titanium abutment background, favoring the esthetic outcome of metal-free cemented crowns.

Effect of Bioactive Filler Addition on the Mechanical and Biological Properties of Resin-Modified Glass Ionomer.

The maintenance of affected dentin can promote the greater conservation of tooth structure. The development of materials that have properties capable of reducing the demineralizing potential and/or even helping in dental remineralization is important for conservative dentistry. This study aimed to evaluate, in vitro, the alkalizing potential, fluoride as well as calcium ion release ability, antimicrobial activity, and dentin remineralization properties of resin-modified glass ionomer cement (RMGIC) incorporated with a bioactive filler (niobium phosphate (NbG) and bioglass (45S5)). The study samples were grouped into RMGIC, NbG, and 45S5. The materials' alkalizing potential, ability to release calcium as well as fluoride ions, and antimicrobial properties concerning Streptococcus mutans UA159 biofilms were analyzed. The remineralization potential was evaluated using the Knoop microhardness test, which was performed at different depths. The alkalizing and fluoride release potential was higher for the 45S5 group (p < 0.001) over time. An increase in the microhardness of demineralized dentin was observed in the 45S5 and NbG groups (p < 0.001). No differences in biofilm formation were observed between the bioactive materials, although 45S5 exhibited lower biofilm acidogenicity at different time points (p < 0.001) and greater calcium ion release in the microbial environment. A resin-modified glass ionomer cement enriched with bioactive glasses, particularly 45S5, is a promising alternative for the treatment of demineralized dentin.

A Systematic Review of Benefits and Risks of Fetal Surgery for Congenital Cardiac Defects Such as Pulmonary Valve Stenosis and Critical Aortic Stenosis.

INTRODUCTION: Congenital heart diseases (CHDs) constitute the most prevalent congenital pathology, and they are a consequence of structural and functional abnormalities during fetal development. The etiology of CHD involves the interaction of genetic and environmental factors. Fetal cardiac surgery aims at preventing natural pathways of CHD in utero, mitigating progression to more complex abnormalities. The goal of this review was to demonstrate the benefits and risks of fetal interventions in the two most prevalent CHDs, pulmonary stenosis and pulmonary atresia with an intact ventricular septum, but also critical aortic stenosis and hypoplastic left heart syndrome. METHODS: Original and relevant articles were selected by meta-aggregation to perform a qualitative analysis of fetal cardiac interventions for pulmonary stenosis and critical aortic stenosis. The Joanna Briggs Institute's Qualitative Assessment and Review Instrument (or JBI-QARI) was used for data quality appraisal. RESULTS: Of 61 potential articles, 13 were selected, and nine were finally included. Discussion: The present review demonstrated that fetal cardiac surgery increases right ventricular growth and hemodynamic flow in pulmonary stenosis, whereas in critical aortic stenosis it enables growth of the left ventricle and increases left ventricular pressure. However, it has a high complication rate, along with considerable morbidity and mortality. CONCLUSION: The benefits of fetal cardiac surgery for pulmonary stenosis and critical aortic stenosis are well-described in the literature; however, there is a significant risk of complications which can be reduced by the surgeon's technical expertise and well-structured hospital facilities.

Postural control is altered in females with excessive medial knee displacement.

Knee valgus motion observed during landing tasks has been proposed as a predictor of future knee injury. It mainly involves excess motion in the frontal plane and is known to be greater in individuals with excessive medial knee displacement (MKD). This affects postural control during sports manoeuvres. Previous sports medicine-related research suggests that the nature of these fluctuations provide rich and more sensitive information to identify risk of (re)injury. We aimed to investigate the fluctuations of the centre of pressure (CoP) in individuals with and without excessive MKD. Twenty females (12 controls; 8 excessive MKD) were instructed to perform single-leg landing tasks from three different directions. The participants landed on a force plate and stayed still for 20 seconds. The fluctuations of the anterior-posterior and medial-lateral directions of the CoP were determined through the calculation of Sample Entropy. Mixed-model ANOVAs (3 [Landing Direction] x 2 [Group]) were used. We have found that only the entropy of the medial-lateral direction was different between groups. Individuals with excessive MKD exhibited an increase in entropy values, indicating greater randomness in CoP fluctuations. This suggests a decreased ability to adapt to environmental demands that likely result in an increased risk of injury.

Dissimilarity between Wrist Trajectories in Basketball Dribbling: Hypothetical Differences Not Available to the Human Eye.

Previous research identified the stability of wrist position as a performance indicator in a static basketball dribbling task performance under different experimental conditions since professionals displayed higher stability values than amateurs. We hypothesized that the trajectories of this cyclical task may be different between amateurs and professionals under downward peripheral vision occlusion and auditory occlusion. A modified version of the Procrustes analysis was used to quantify the dissimilarity between wrist trajectories along time. Results showed that peripheral vision occlusion caused dissimilarity in amateurs' dribbling trajectories almost four times larger than professionals'; however, auditory occlusion did not affect neither amateur nor professionals' performance. There were no cumulative effects on performance when the individual was submitted to both occlusions simultaneously.

miRNA-143 expression is associated with inflammation and time of exposure to amniotic fluid in experimental gastroschisis

Abstract Objective Gastroschisis (GS) is a congenital anomaly in the abdominal wall with the intestinal loops exiting laterally to the umbilicus. The contact of the loops with Amniotic Fluid (AF) causes an inflammatory process in the exposed part, leading to an extended hospital stay and an increased risk of morbidity due to alterations related to intestinal motility. The authors aimed to evaluate the time of exposure to the AF in the experimental GS and to search for potential biomarkers of intestinal inflammation by measuring microRNAs. Methods Rat fetuses were divided into three groups: a) CONTROL, b) GS reared on day 18 (GS = 18), and c) GS reared on day 19.5 (GS = 19) (term = 22 days). On day 21.5, the fetuses were removed for biometric parameters and biochemical analyses: 1) Biometrics: Body and Intestinal Weight (BW, IW), and intestinal-body weight ratio (IW/BW); 2) Descriptive histopathology and 3) miR-143 quantification by real-time Polymerase Chain Reaction (PCR). Results BW was higher in CONTROL than GS 18 and G19 (p < 0.05). IW, IW/BW, intestinal water, and mRNA-143 were higher in GS 18 and GS 19 than in CONTROL, and GS 18 was higher than GS 19 (p < 0.05). The average of the inflammation score from the intestinal wall with mucosal inflammation and intra-epithelial lymphocytes shows worst in GS 18 and GS 19 vs. CONTROL (p < 0.05). Conclusions The tissue expression of mRNA-143 and the morphological changes in the intestine of GS worsened according to the time of exposure to AF, which could be a possible marker of fetal intestinal damage.

A Systematic Review of Benefits and Risks of Fetal Surgery for Congenital Cardiac Defects Such as Pulmonary Valve Stenosis and Critical Aortic Stenosis

ABSTRACT Introduction: Congenital heart diseases (CHDs) constitute the most prevalent congenital pathology, and they are a consequence of structural and functional abnormalities during fetal development. The etiology of CHD involves the interaction of genetic and environmental factors. Fetal cardiac surgery aims at preventing natural pathways of CHD in utero, mitigating progression to more complex abnormalities. The goal of this review was to demonstrate the benefits and risks of fetal interventions in the two most prevalent CHDs, pulmonary stenosis and pulmonary atresia with an intact ventricular septum, but also critical aortic stenosis and hypoplastic left heart syndrome. Methods: Original and relevant articles were selected by meta-aggregation to perform a qualitative analysis of fetal cardiac interventions for pulmonary stenosis and critical aortic stenosis. The Joanna Briggs Institute's Qualitative Assessment and Review Instrument (or JBI-QARI) was used for data quality appraisal. Results: Of 61 potential articles, 13 were selected, and nine were finally included. Discussion: The present review demonstrated that fetal cardiac surgery increases right ventricular growth and hemodynamic flow in pulmonary stenosis, whereas in critical aortic stenosis it enables growth of the left ventricle and increases left ventricular pressure. However, it has a high complication rate, along with considerable morbidity and mortality. Conclusion: The benefits of fetal cardiac surgery for pulmonary stenosis and critical aortic stenosis are well-described in the literature; however, there is a significant risk of complications which can be reduced by the surgeon's technical expertise and well-structured hospital facilities.

Prevalência de eventos vasculares associados a pacientes com COVID-19 em um hospital público* / Prevalencia de eventos vasculares asociados a pacientes con COVID-19 en un hospital público / Prevalence of vascular events associated with COVID-19 patients in a public hospital

Objetivo: verificar a prevalência dos principais eventos vasculares associados a pacientes com COVID-19 admitidos em um hospital público do Recife. Método: trata-se de um estudo transversal descritivo, realizado por meio das bases de dados epidemiológicos e prontuários eletrônicos de pacientes, no período de março de 2020 a agosto de 2021. Resultados: analisaram-se 1122 pacientes, (58,8%) com diagnóstico positivo para COVID-19. Os principais eventos vasculares evidenciados foram: Tromboembolismo Venoso Profundo (4,55%); Tromboembolismo Pulmonar (2,5%); Oclusão Arterial Aguda (0,98%) e Isquemia Crítica de Membro Inferior a mais prevalente, sendo 17,64% dos casos. Conclusão: foi possível apontar a prevalência de eventos vasculares associados a pacientes com COVID-19, admitidos em um hospital público do Recife, tal como classificar os principais eventos vasculares, sua repercussão e evolução. Assim, o conhecimento acerca do perfil desses pacientes no contexto da pandemia pode contribuir para o desenvolvimento de novas pesquisas na área de saúde.

Objective: to verify the prevalence of the main vascular events associated with patients with COVID-19 admitted to a public hospital in Recife. Method: this is a descriptive cross-sectional study, carried out through epidemiological databases and electronic patient records, from March 2020 to August 2021. Results: 1122 patients (58.8%) with a positive diagnosis for COVID-19 were analyzed. The main vascular events evidenced were: Deep Venous Thromboembolism (4.55%); Pulmonary Thromboembolism (2.5%); Acute Arterial Occlusion (0.98%) and Critical Lower Limb Ischemia, the most prevalent, being 17.64% of the cases. Conclusion: it was possible to point out the prevalence of vascular events associated with patients with COVID-19, admitted to a public hospital in Recife, as well as to classify the main vascular events, their repercussion and evolution. Thus, knowledge about the profile of these patients in the context of the pandemic can contribute to the development of new research in the health area.

Objetivo: verificar la prevalencia de los principales eventos vasculares asociados a pacientes con COVID-19 ingresados en un hospital público de Recife. Método: se trata de un estudio descriptivo transversal, realizado a través de bases de datos epidemiológicas y registros electrónicos de pacientes, de marzo de 2020 a agosto de 2021. Resultados: se analizaron 1122 pacientes (58,8%) con diagnóstico positivo para COVID-19. Los principales eventos vasculares evidenciados fueron: Tromboembolismo Venoso Profundo (4,55%); Tromboembolismo Pulmonar (2,5%); Oclusión Arterial Aguda (0,98%) e Isquemia Crítica de Miembros Inferiores el más prevalente, con el 17,64% de los casos. Conclusión: fue posible señalar la prevalencia de eventos vasculares asociados a pacientes con COVID-19, ingresados en un hospital público de Recife, así como clasificar los principales eventos vasculares, sus repercusiones y evolución. Así, el conocimiento del perfil de estos pacientes en el contexto de la pandemia puede contribuir para el desarrollo de nuevas investigaciones en el área de salud.

High Instantaneous Inhibitory Potential of Bictegravir and the New Spiro-ß-Lactam BSS-730A for HIV-2 Isolates from RAL-Naïve and RAL-Failing Patients.

Integrase inhibitors (INIs) are an important class of drugs for treating HIV-2 infection, given the limited number of drugs active against this virus. While the clinical efficacy of raltegravir and dolutegravir is well established, the clinical efficacy of bictegravir for treating HIV-2 infected patients has not been determined. Little information is available regarding the activity of bictegravir against HIV-2 isolates from patients failing raltegravir-based therapy. In this study, we examined the phenotypic and matched genotypic susceptibility of HIV-2 primary isolates from raltegravir-naïve and raltegravir-failing patients to raltegravir, dolutegravir, and bictegravir, and to the new spiro-ß-lactam BSS-730A. The instantaneous inhibitory potential (IIP) was calculated to help predict the clinical activity of bictegravir and BSS-730A. Isolates from raltegravir-naïve patients were highly sensitive to all INIs and BSS-730A. Combined integrase mutations E92A and Q148K conferred high-level resistance to raltegravir, and E92Q and T97A conferred resistance to raltegravir and dolutegravir. The antiviral activity of bictegravir and BSS-730A was not affected by these mutations. BSS-730A displayed strong antiviral synergism with raltegravir. Mean IIP values at Cmax were similar for all INIs and were not significantly affected by resistance mutations. IIP values were significantly higher for BSS-730A than for INIs. The high IIP values of bictegravir and BSS-730A for raltegravir-naïve and raltegravir-resistant HIV-2 isolates highlight their potential value for treating HIV-2 infection. Overall, the results are consistent with the high clinical efficacy of raltegravir and dolutegravir for HIV-2 infection and suggest a promising clinical profile for bictegravir and BSS-730A.

Implications of lower extremity muscle power and force for walking and fatigability in multiple sclerosis - An exploratory pilot-study.

BACKGROUND: Limitations in physical function are common in Multiple Sclerosis (MS), yet it is neither clear how muscle power implicates physical function and walking-fatigability. This pilot-study aims to investigate (1) deficits in muscle power/force alongside walking in persons with MS; (2) associations between muscle power/force and physical functions and (3) the impact of prolonged walking in muscle power/force. METHODS: 30 relapse-remitting persons with MS and 28 healthy controls performed chair rise and plantar flexion on a force platform before and after 12-minutes of intermittent walking to measure lower extremity muscle power/force. GaitRite measured walking speed. The percentage change in distance walked was also calculated. Persons with MS were classified into subgroups according to walking-fatigability and mobility disability status (Patient Determined Disease Steps). FINDINGS: Higher deficits in muscle power compared to force were observed in persons with MS vs. healthy controls particularly in persons with MS having higher disability. Muscle power and force were associated with walking capacity, mobility disability and subjective fatigue, but not with percentage change in distance walked. Persons with MS slowed down over the course of the 12-min intermittent walking, whereas decrements in walking speed and muscle power/force (derived from chair rise) were observed in persons with MS presenting walking-fatigability only. INTERPRETATION: Muscle power and force are impaired in persons with MS and appear to be critical for physical function in MS. This exploratory pilot study further suggests that muscle power/force from chair rise could contributes to walking-fatigability which therefore offer future treatment targets.

Atomic and Specificity Details of Mucin 1 O-Glycosylation Process by Multiple Polypeptide GalNAc-Transferase Isoforms Unveiled by NMR and Molecular Modeling.

The large family of polypeptide GalNAc-transferases (GalNAc-Ts) controls with precision how GalNAc O-glycans are added in the tandem repeat regions of mucins (e.g., MUC1). However, the structural features behind the creation of well-defined and clustered patterns of O-glycans in mucins are poorly understood. In this context, herein, we disclose the full process of MUC1 O-glycosylation by GalNAc-T2/T3/T4 isoforms by NMR spectroscopy assisted by molecular modeling protocols. By using MUC1, with four tandem repeat domains as a substrate, we confirmed the glycosylation preferences of different GalNAc-Ts isoforms and highlighted the importance of the lectin domain in the glycosylation site selection after the addition of the first GalNAc residue. In a glycosylated substrate, with yet multiple acceptor sites, the lectin domain contributes to orientate acceptor sites to the catalytic domain. Our experiments suggest that during this process, neighboring tandem repeats are critical for further glycosylation of acceptor sites by GalNAc-T2/T4 in a lectin-assisted manner. Our studies also show local conformational changes in the peptide backbone during incorporation of GalNAc residues, which might explain GalNAc-T2/T3/T4 fine specificities toward the MUC1 substrate. Interestingly, we postulate that a specific salt-bridge and the inverse γ-turn conformation of the PDTRP sequence in MUC1 are the main structural motifs behind the GalNAc-T4 specificity toward this region. In addition, in-cell analysis shows that the GalNAc-T4 isoform is the only isoform glycosylating the Thr of the immunogenic epitope PDTRP in vivo, which highlights the relevance of GalNAc-T4 in the glycosylation of this epitope. Finally, the NMR methodology established herein can be extended to other glycosyltransferases, such as C1GalT1 and ST6GalNAc-I, to determine the specificity toward complex mucin acceptor substrates.

Interrogating the Inhibition Mechanisms of Human Aldehyde Oxidase by X-ray Crystallography and NMR Spectroscopy: The Raloxifene Case.

Human aldehyde oxidase (hAOX1) is mainly present in the liver and has an emerging role in drug metabolism, since it accepts a wide range of molecules as substrates and inhibitors. Herein, we employed an integrative approach by combining NMR, X-ray crystallography, and enzyme inhibition kinetics to understand the inhibition modes of three hAOX1 inhibitors-thioridazine, benzamidine, and raloxifene. These integrative data indicate that thioridazine is a noncompetitive inhibitor, while benzamidine presents a mixed type of inhibition. Additionally, we describe the first crystal structure of hAOX1 in complex with raloxifene. Raloxifene binds tightly at the entrance of the substrate tunnel, stabilizing the flexible entrance gates and elucidating an unusual substrate-dependent mechanism of inhibition with potential impact on drug-drug interactions. This study can be considered as a proof-of-concept for an efficient experimental screening of prospective substrates and inhibitors of hAOX1 relevant in drug discovery.

Structural Insights into the Molecular Recognition Mechanism of the Cancer and Pathogenic Epitope, LacdiNAc by Immune-Related Lectins.

Interactions of glycan-specific epitopes to human lectin receptors represent novel immune checkpoints for investigating cancer and infection diseases. By employing a multidisciplinary approach that combines isothermal titration calorimetry, NMR spectroscopy, molecular dynamics simulations, and X-ray crystallography, we investigated the molecular determinants that govern the recognition of the tumour and pathogenic glycobiomarker LacdiNAc (GalNAcß1-4GlcNAc, LDN), including their comparison with the ubiquitous LacNAc epitope (Galß1-4GlcNAc, LN), by two human immune-related lectins, galectin-3 (hGal-3) and the macrophage galactose C-type lectin (hMGL). A different mechanism of binding and interactions was observed for the hGal-3/LDN and hMGL/LDN complexes, which explains the remarkable difference in the binding specificity of LDN and LN by these two lectins. The new structural clues reported herein are fundamental for the chemical design of mimetics targeting hGal-3/hMGL recognition process.

Crystal Structure of the Carbohydrate Recognition Domain of the Human Macrophage Galactose C-Type Lectin Bound to GalNAc and the Tumor-Associated Tn Antigen.

The human macrophage galactose lectin (MGL) is an endocytic type II transmembrane receptor expressed on immature monocyte-derived dendritic cells and activated macrophages and plays a role in modulating the immune system in response to infections and cancer. MGL contains an extracellular calcium-dependent (C-type) carbohydrate recognition domain (CRD) that specifically binds terminal N-acetylgalactosamine glycan residues such as the Tn and sialyl-Tn antigens found on tumor cells, as well as other N- and O-glycans displayed on certain viruses and parasites. Even though the glycan specificity of MGL is known and several binding glycoproteins have been identified, the molecular basis for substrate recognition has remained elusive due to the lack of high-resolution structures. Here we present crystal structures of the MGL CRD at near endosomal pH and in several complexes, which reveal details of the interactions with the natural ligand, GalNAc, the cancer-associated Tn-Ser antigen, and a synthetic GalNAc mimetic ligand. Like the asialoglycoprotein receptor, additional calcium atoms are present and contribute to stabilization of the MGL CRD fold. The structure provides the molecular basis for preferential binding of N-acetylgalactosamine over galactose and prompted the re-evaluation of the binding modes previously proposed in solution. Saturation transfer difference nuclear magnetic resonance data acquired using the MGL CRD and interpreted using the crystal structure indicate a single binding mode for GalNAc in solution. Models of MGL1 and MGL2, the mouse homologues of MGL, explain how these proteins might recognize LewisX and GalNAc, respectively.

Podemos falar de segurança do paciente durante uma pandemia? Uma experiência portuguesa / Can we talk about patient safety during a pandemia? A portuguese experience / ¿Podemos hablar sobre seguridad del paciente durante una pandemia? Una experiencia portuguesa

Objetivo: enumerar medidas governativas e de saúde pública implementadas em Portugal decorrentes da pandemia pelo vírus SARS-CoV-2 e descrever a atuação do Gabinete de Segurança do Paciente do Centro Hospitalar Universitário de Lisboa Central (CHULC), referência nacional na resposta à situação de emergência de saúde pública. Métodos: utilizou-se como método a análise normativa, documental, além de relato de caso por pesquisa-ação. Resultados: em Portugal, documentaram-se os primeiros casos de infeção por SARS-CoV-2 a 2 de março de 2020. Os processos assistenciais são geridos pelo Ministério da Saúde e Direção Geral da Saúde, abrangendo o Sistema Nacional de Saúde (universal) e o sector privado. O Gabinete de Segurança do Doente do CHULC, participou na redefinição dos processos, criação de vias alternativas de informação entre as várias estruturas, implementação de inovações no uso de tecnologias e vigilância clínica, gestão dos equipamentos de proteção, motivação e suporte emocional dos profissionais e na consolidação das principais metas de segurança do doente (ex. identificação do doente, medicação e cirurgia segura). A aprendizagem feita com os erros contribui para a melhoria contínua dos processos. Conclusão: em Portugal e no mundo a pandemia por COVID-19 não terminou. Compreendemos que é tempo de refletir e voltar aos princípios básicos da segurança, como a higiene das mãos, a etiqueta respiratória e o controlo ambiental. Na gestão do risco e segurança do paciente em situação de crise, é necessário, mais do que nunca, inovar e aprender com os erros.

Objective: to enumerate governmental and public health measures implemented in Portugal resulting from the SARS-CoV-2 virus pandemic and describe the work of the Patient Safety Office of the Centro Hospitalar Universitário de Lisboa Central (CHULC), a national reference in the response to the situation of public health emergency. Methods: normative, documentary analysis was used as a method, in addition to case reports by action research. Results: in Portugal, the first cases of SARS-CoV-2 infection were documented on March 2, 2020. Assistance processes are managed by the Ministry of Health and the General Directorate of Health, covering the National Health System (universal) and the private sector. The CHULC Patient Safety Office, participated in the redefinition of processes, creation of alternative information routes between the various structures, implementation of innovations in the use of technologies and clinical surveillance, management of protective equipment, motivation and emotional support from professionals and consolidating the main patient safety goals (eg patient identification, medication and safe surgery). Learning from mistakes contributes to the continuous improvement of processes. Conclusion: In Portugal and in the world, the COVID-19 pandemic has not ended. We understand that it is time to reflect and return to the basic principles of safety, such as hand hygiene, respiratory etiquette and environmental control. In the management of risk and safety of patients in crisis situations, it is necessary, more than ever, to innovate and learn from mistakes.

Objetivo: enumerar las medidas gubernamentales y de salud pública implementadas en Portugal como resultado de la pandemia del virus SARS-CoV-2 y describir el trabajo de la Oficina de Seguridad del Paciente del Centro Hospitalar Universitário de Lisboa Central (CHULC), una referencia nacional en la respuesta a la situación de emergencia de salud pública. Métodos: se utilizó como método el análisis documental, normativo, además de los reportes de casos por investigación-acción. Resultados: en Portugal se documentaron los primeros casos de infección por SARS-CoV-2 el 2 de marzo de 2020. Los procesos de atención son gestionados por el Ministerio de Salud y la Dirección General de Salud, abarcando el Sistema Nacional de Salud (universal) y el privado. sector. La Oficina de Seguridad del Paciente del CHULC, participó en la redefinición de procesos, creación de rutas alternativas de información entre las distintas estructuras, implementación de innovaciones en el uso de tecnologías y vigilancia clínica, manejo de equipos de protección, motivación y apoyo emocional de los profesionales y consolidando las principales objetivos de seguridad del paciente (por ejemplo, identificación del paciente, medicación y cirugía segura). Aprender de los errores contribuye a la mejora continua de los procesos. Conclusión: En Portugal y en el mundo, la pandemia de COVID-19 no ha terminado. Entendemos que es hora de reflexionar y volver a los principios básicos de seguridad, como la higiene de manos, la etiqueta respiratoria y el control ambiental. En la gestión del riesgo y la seguridad de los pacientes en situaciones de crisis, es necesario, más que nunca, innovar y aprender de los errores.

The role of variability in the control of the basketball dribble under different perceptual setups.

When executing a sport-specific movement, athletes cannot use all perceptual resources to control their actions. The complexity of a basketball match, demands that individuals command their attention towards the context to make decisions. The dependency on the perceptual sources to control a movement should be kept to a minimum. During a match due to situational constraints, players often see themselves with impaired perceptual sources (e.g. auditory and peripheral vision occlusions). Assuming that professional basketball players are more skilled than amateurs, we analysed how both groups were affected by perceptual impairment, within and in-between groups in a dribbling task. A variability analysis (correlation dimension, approximate entropy and Lyapunov exponent) was used to evaluate how an increased variability or stability, in a specific joint movement, contributes to a better adaptive behaviour when facing perceptual impairment. Professionals showed a significantly lower variability of the wrist movements, but had a significantly higher value of variability in the shoulder horizontal movements (anterior-posterior and lateral), and also in the lateral elbow movements when their downwards peripheral vision was impaired. The increase in variability in such joint movements reflects adaptive behaviour and might be a performance factor.