Physical Activity Levels and Body Mass Index in Sport Education. Is There a Difference?

Purpose: The goals of this study were: (1) to assess students' physical activity levels in a sport education season according to the phases of the model, adjusted for body mass index; (2) to uncover the contribution of the phases of the model to the World Health Organization recommendations; (3) to understand its impact in students with overweight/obesity. Methods: A total of 42 primary education students with a mean age of 10.68 ± 0.69 years, enrolled in one year 5 (10-11 years) and one year 6 (11-12 years). Physical Education lessons of the same school agreed to participate. Students in both groups experienced a 14-lesson learning unit in team handball through the sport education. Each participant wore an ActiGraph GT3X accelerometer to measure physical activity levels, counts/minute and steps counted. Cole and Lobstein cutoff points were used to determine groups based on body mass index (thin, normal-weight, overweight/obese). Results: The results showed that the overweight/obese group achieved scores for moderate to vigorous physical activity and sedentary time that were not significantly different from the normal-weight group. According to the phases, the preseason was the most active and contributed most to the World Health Organization recommendations in all groups. Conclusions: Sport education could be considered an appropriate pedagogical framework to help overweight/obese children achieve moderate-to-vigorous physical activity and sedentary scores similar to their normal-weight classmates. Key elements of sport education include performing roles, learning work routines, and having the autonomy to choose games/tasks, all of which promote physical activity amongst all students.

Corrigendum: In-contest body acceleration profiles for the judo male and female weight divisions.

[This corrects the article DOI: 10.3389/fspor.2024.1372314.].

Prevention of motor ascending branch of the rectus femoris injuries in Bernese periacetabular osteotomy: a cadaveric study.

The Bernese periacetabular osteotomy (PAO) is a surgical procedure used to treat hip dysplasia in young adults, but it carries the risk of neurological complications, including injury to the motor ascending branch of the rectus femoris (MABRF). This study aimed to describe anatomical considerations to prevent MABRF injuries during PAO. A cadaveric study was conducted on seven specimens. The original and modified PAO approaches were used, with and without disinsertion of the rectus femoris muscle origin. The femoral nerve was dissected in all specimens from the endopelvic position to the MABRF origin (T-point). The average distance from the anterosuperior iliac spine to the T-point was 10.2 ± 0.4 cm. To protect the MABRF, a safety zone was identified for the osteotome placement during the ischial cut. The osteotome was slid over the joint capsule, deflecting the iliocapsularis muscle medially and distally. This manoeuvre shields the MABRF with the iliocapsularis muscle, reducing the risk of neurological injury. Both the original and modified PAO approaches were considered safe techniques with low risk to the rectus femoris innervation. These findings offer valuable insights for surgeons performing PAO, emphasizing the significance of understanding anatomical relationships and implementing protective measures to enhance patient outcomes and minimize complications. In conclusion, implementing these anatomical considerations can help prevent MABRF injuries during PAO, contributing to safer and more successful surgical interventions for hip dysplasia in young adults.

In-contest body acceleration profiles for the judo male and female weight divisions.

Introduction: This study aimed to determine the body accelerations (BA) profile of the judo contest of the male and female weight divisions and to ascertain the involvement of the vertical, mediolateral and anteroposterior axes in it. Methods: Forty-eight male and forty-eight female national and international level athletes (some of them medalists in World, European and national championships) participated in a 5-min simulated contest (official fight time plus breaks) against an opponent of the same sex and weight division, wearing an accelerometer. Heart rate, blood lactate and ratings of perceived exertion were recorded to certify that the athletes performed the fullest. Results: The t2way test expressed differences in the athletes' BA (p = 0.001) and three profiles were identified: the light/middle weight male divisions, the light/middle weight female divisions and the heavy male and female ones. Athletes of all weight divisions performed their BA during the contest in all three directions (the one-sample Person's chi-square did not detect any significantly predominant one: p = 0.400, p = 0.631, p = 0.844, p = 0.749, p = 0.644 and p = 0.895, for male light, moderate and heavy, female light, moderate and heavyweight athletes, respectively). Monte Carlo method simulations suggested as the most likely scenarios those with BA involving all axes, with a slight preference of the anteroposterior and mediolateral ones. Discussion: These results suggest that the demands on judo athletes in a contest differ between weight classes and sexes.

Construction and Assessment of the Physical Activity and Physical Education Importance for Parents Scale.

A recent systematic review reported positive associations between parents and children's physical activity participation. Moreover, parents' perceptions of the importance and value of physical activity can influence their children's participation in it. Our aim in this study was to develop and validate an instrument to assess parents' perceptions of the importance of physical activity and physical education. After first creating the instrument, we conducted content and exploratory factorial validation and reliability analyses of it with 93 parents (M age = 44.76, SD = 6.05, range = 31-66 years; 73 females, 20 males). The result was a 9-item instrument, with items assessed on a 5-point Likert scale and grouped into three factors: (a) importance of physical education; (b) importance of engaging in physical activity or sport; and (c) importance of joining your children in physical activity or sport. In a second confirmatory factor analysis with 224 parents (M age = 44.53, SD = 6.07; 174 or 77.7% females and 50 or 22.3% males) we confirmed the factor validity and reliability previously analyzed (χ2 = 42.77, df = 24, p = .011, GFI = 0.96, NFI = 0.98, NNFI = 0.99, CFI = 0.99, RMSEA = 0.06 (90% CI: 0,04, 0.08), SRMR = 0.04, ECVI = 0.04, CR = 0.70-0.87). Thus, the new Physical Activity and Physical Education Importance for Parents Scale (PAPEIPS) is a valid and reliable instrument for measuring parents' perceived importance of physical activity and physical education.

Human occupations of upland and cold environments in inland Spain during the Last Glacial Maximum and Heinrich Stadial 1: The new Magdalenian sequence of Charco Verde II.

The settlement of cold and arid environments by Pleistocene hunter-gatherers has been a heated topic in Paleolithic Archaeology and the Quaternary Sciences for years. In the Iberian Peninsula, a key area for studying human adaptations to such environments is composed by the large interior and upland regions of the northern and southern plateaus (Mesetas) and bordering areas. As, traditionally, these regions have been relatively under-investigated compared to the ecologically more favored coastal areas of the peninsula, our knowledge of the human settlement of the whole Iberian hinterland remains scarce for the Last Glacial. In this paper we present the discovery and first geoarcheological, paleoenvironmental and chronometric evidence obtained at Charco Verde II, a new site close to the southwestern foothills of the Iberian system range (Guadalajara province, Spain), bearing a sequence of Magdalenian human occupations starting at least at 20.8-21.4 ka cal BP during the Last Glacial Maximum, and covering Greenland Stadial 2 until ∼15.1-16.6 ka cal BP, including Heinrich stadial 1. As this site is located in an upland region which today faces one of the harshest climates in Iberia, such occupation sequence, occurred during some of the coldest and most arid phases of the Last Glacial, has relevant implications for our understanding of human-environment-climate interactions and population dynamics in Iberia and Western Europe. These findings support the hypothesis that the Iberian hinterland was not avoided by Upper Paleolithic hunter-gatherers due to ecological constraints, but it hosted a complex and relatively dense settlement at least in some areas, even during cold periods. This suggest, one more time, that the historical scarcity of Upper Paleolithic sites in inland Iberia is, to a significant extent, an artifact of research bias.

Network analysis of physical activity and depressive and affective symptoms during COVID-19 home confinement.

INTRODUCTION: The aim of this study was to analyze the network structure of physical activity, frequency, depressive, and affective symptoms in people under home isolation due to COVID-19. METHOD: A longitudinal study was conducted in two phases (beginning (March 19, 2020) and end of home confinement (April 8, 2020)). The sample consisted of 579 participants from Spain (250 men and 329 women) aged 16 to 92 years (overall sample: M = 47.06, SD = 14.52). A network analysis was performed. RESULTS: Four clusters emerged (PA, depressive symptoms, positive affect, and negative affect). A higher frequency of physical activity was related to better-sustained attention, increased alertness, and enthusiasm. In addition, feelings of guilt and shame were mitigated, and confinement distress and irritability were reduced. Physical activity also mitigated fatigue in women, whereas feelings of unhappiness were reduced in men. CONCLUSION: Physical activity seems to be an effective option for mitigating the negative effects of the COVID-19 pandemic. Public health policymakers should develop programs to promote physical activity in order to be able to cope with confinement or similar scenarios in the future.

How class cohesion and teachers' relatedness supportive/thwarting style relate to students' relatedness, motivation, and positive and negative outcomes in physical education.

The main goal of this study was to examine the links between class cohesion and teachers' relatedness teaching style with students' relatedness needs, motivation, and positive and negative outcomes in Physical Education. A total of 1294 students 10-18 years old (M = 14.40, SD = 1.99), 613 males (M = 14.48, SD = 1.95) and 681 females (M = 14.33, SD = 2.02), agreed to participate. They were enrolled in 88 classes belonging to 13 different primary and secondary schools in southwestern Spain. The study followed a correlational research design. Results of the multilevel path model showed a positive relationship between teachers' relatedness support and class cohesion and behavioral and emotional engagement through relatedness need satisfaction and autonomous and controlled motivation. Results also showed a positive relationship between teachers' relatedness thwarting and disruptive behaviors and problematic relationships through relatedness need frustration and amotivation. In conclusion, teachers' relatedness behaviors and class cohesion can significantly impact the students' relatedness and motivation, which in turn will affect their engagement and behaviors. A whole cascade of consequences begins with the way teachers teach and the cohesion generated in class. These first steps cannot be overlooked.

Outcomes of Percutaneous Access to the First Versus Third Segment of Axillary Artery During Aortic Procedures.

PURPOSE: This article aims at investigating the outcomes of percutaneous access via the first versus third axillary artery (AXA) segments with closure devices during aortic procedures. MATERIALS AND METHODS: All patients receiving percutaneous AXA access closed with Perclose ProGlide device (Abbott, Santa Clara, California) from 2008 to 2021 were included in a retrospective multicenter registry (NCT: 04589962). Efficacy endpoint was the technically successful percutaneous procedure (no open conversion). Safety endpoints were stroke and access complications according to the Valve Academic Research Consortium-3 reporting standards. The first (AXA1) or third (AXA3) axillary puncture sites were compared. RESULTS: A total of 412 percutaneous AXA accesses were included: 172 (42%) in AXA1 and 240 (58%) in AXA3. Left AXA was catheterized in 363 cases (76% of AXA1 vs 97% of AXA3, p<0.001) and 91% of fenestrated/branched endovascular repair (F/BEVAR) procedures were conducted from the left. A ≥12F internal diameter (ID) sheath was used in 49% of procedures. Open conversion rate was 1%, no major vascular complications occurred, and only one major non-vascular complication was recorded. Primary closure failure occurred in 18 AXA1 (11%) and 32 AXA3 accesses (13%), treated by covered (8.3%) or bare-metal (2.7%) stenting. Bailout stent patency was 100% at median follow-up of 12 months, with 6 of 6 stents still patent after >36 months of follow-up. Stroke rate was 4.4%. An introducer sheath >12F was independently associated with both access complications (p<0.001) and stroke (p=0.005), while a right-side access was associated with stroke only (p=0.034). Even after adjustment for covariates, AXA1 versus AXA3 showed an equal success rate (odds ratio [OR]=0.537, 95% confidence interval [CI]=0.011-1.22 for AXA3, p=0.104). The combination of AXA3 and a >10F introducer sheath provided worse outcomes compared with >10F sheaths through AXA1 (OR for success=0.367, 95% CI=0.176-0.767, p=0.008). This was not confirmed for >12F sheaths, associated with similar outcomes (p=0.31 AXA 1 vs AXA 3). CONCLUSION: Major local complications with the percutaneous axillary approach and ≤12F sheaths are infrequent and solvable by complementary endovascular interventions. Stroke risk remains an issue. First and third AXA segments are both amenable for access with good results, but larger sheaths (12F) perform better in AXA1. CLINICAL IMPACT: Percutaneous access with vascular closure devices at the first or third axillary artery (AXA) segments during aortic procedures is burdened by a negligible risk of open conversion. Local complications with the percutaneous axillary approach are infrequent and solvable by complementary endovascular interventions. First and third AXA segments are both amenable to access with excellent results, but larger sheaths (12F) perform better in the wider first AXA segment. In this setting, bailout stenting does not appear to be associated with mid-term stent occlusion.

Comparative study on the impact of equally stressful environmental sporulation conditions on thermal inactivation kinetics of B. subtilis spores.

Control of bacterial spores continues to be one of the main challenges for the food industry due to their wide dissemination and extremely high resistance to processing methods. Furthermore, the large variability in heat resistance in spores that contaminate foods makes it difficult to establish general processing conditions. Such heterogeneity not only derives from inherent differences among species and strains, but also from differences in sporulation environments that are generally ignored in spores encountered in foods. We evaluated heat inactivation kinetics and the thermodependency of resistance parameters in B. subtilis 168 spores sporulated at adverse temperatures, water activity (aw), and pH, applying an experimental approach that allowed us to quantitatively compare the impact of each condition. Reduction of incubation temperature from the optimal temperature dramatically reduced thermal resistance, and it was the most influential factor, especially at the highest treatment temperatures. These spores were also more sensitive to chemicals presumably acting in the inner membrane. Reducing sporulation aw increased heat resistance, although the magnitude of that effect depended on the solute and the treatment temperature. Thus, changes in sporulation environments varied 3D100°C values up to 10.4-fold and z values up to 1.7-fold, highlighting the relevance of taking such a source of variability into account when setting heat processing conditions. UV-C treatment and sodium hypochlorite efficiently inactivated all spore populations, including heat-resistant ones produced at low aw.

Charge Engineering of the Nucleic Acid Binding Cleft of a Thermostable HIV-1 Reverse Transcriptase Reveals Key Interactions and a Novel Mechanism of RNase H Inactivation.

Coupled with PCR, reverse transcriptases (RTs) have been widely used for RNA detection and gene expression analysis. Increased thermostability and nucleic acid binding affinity are desirable RT properties to improve yields and sensitivity of these applications. The effects of amino acid substitutions in the RT RNase H domain were tested in an engineered HIV-1 group O RT, containing mutations K358R/A359G/S360A and devoid of RNase H activity due to the presence of E478Q (O3MQ RT). Twenty mutant RTs with Lys or Arg at positions interacting with the template-primer (i.e., at positions 473-477, 499-502 and 505) were obtained and characterized. Most of them produced significant amounts of cDNA at 37, 50 and 65 °C, as determined in RT-PCR reactions. However, a big loss of activity was observed with mutants A477K/R, S499K/R, V502K/R and Y505K/R, particularly at 65 °C. Binding affinity experiments confirmed that residues 477, 502 and 505 were less tolerant to mutations. Amino acid substitutions Q500K and Q500R produced a slight increase of cDNA synthesis efficiency at 50 and 65 °C, without altering the KD for model DNA/DNA and RNA/DNA heteroduplexes. Interestingly, molecular dynamics simulations predicted that those mutations inactivate the RNase H activity by altering the geometry of the catalytic site. Proof of this unexpected effect was obtained after introducing Q500K or Q500R in the wild-type HIV-1BH10 RT and mutant K358R/A359G/S360A RT. Our results reveal a novel mechanism of RNase H inactivation that preserves RT DNA binding and polymerization efficiency without substituting RNase H active site residues.

Physical Activity and Nighttime Sleep in Adolescents.

BACKGROUND: Previous studies show contradictory results regarding the bidirectional association between physical activity and nighttime sleep. The objective of the present study was to add knowledge to these possible relationships using autoregressive models. METHOD: 214 adolescents (117 boys and 97 girls), with a mean age of 13.31 years agreed to participate. The study variables were measured with accelerometers for 7 full days over three consecutive years. The mlVAR package was used to compute estimates from multivariate vector autoregression models. RESULTS: The 5-delay models showed a better fit. Autoregressive effects were observed in sleep onset, sleep offset and sedentary behavior, which could explain the relationships found in previous studies between physical activity and sleep. Sleep onset, total sleep time, and sleep efficiency had direct effects on sedentary behavior. Moderate-to-vigorous physical activity was not related to any of the sleep variables. CONCLUSIONS: The hypothesis that there are bidirectional/reciprocal relationships between physical activity and sleep cannot be accepted.

Cooperative Learning, Emotions, and Academic Performance in Physical Education: A Serial Multiple Mediation Model / El aprendizaje cooperativo, las emociones y el rendimiento académico en educación física: un modelo de mediación serial múltiple

Based on the control-value theory, this study examined connections between the perceived in-class degree of cooperation and academic performance mediated through the students’ negative and positive emotions in physical education. Students (N = 620, 55.5% girls; Mage = 13.01, SD = 2.10) reported on their perceptions of the degree of cooperation and the negative (shame, hopelessness, anxiety, boredom) and positive (confidence, pride, enjoyment, calmness) emotions in physical education classes. Academic performance was obtained from their school’s administrators. Results from the multiple lineal regression analyses, considering the in-class degree of cooperation and the negative and positive emotions as predictor variables, showed a significantly positive link between the in-class degree of cooperation and the dependent variable academic performance, and between positive emotions and academic performance. These findings elucidate the impact of cooperative learning contexts and emotions on academic performance. Educational implications and future research are discussed.(AU)

Basado en la teoría del control-valor, este estudio examinó las conexiones entre el grado de cooperación percibido en clase y el rendimiento académico mediado por las emociones negativas y positivas de los estudiantes en educación física. Los participantes (N = 620, 55.5% niñas; Medad = 13.01, DT = 2.10) informaron sobre su percepción del grado de cooperación, emociones negativas (vergüenza, desesperanza, ansiedad, aburrimiento) y emociones positivas (confianza, orgullo, disfrute, tranquilidad) en las clases de educación física. El rendimiento académico se obtuvo de la dirección de los centros educativos. Los resultados de los análisis de regresión lineal múltiple, considerando el grado de cooperación en el aula y las emociones negativas y positivas como variables predictoras, mostraron un vínculo significativamente positivo entre el grado de cooperación en el aula y la variable dependiente rendimiento académico y entre las emociones positivas y el rendimiento académico. Estos resultados explican la repercusión de los contextos de aprendizaje cooperativo y las emociones en el rendimiento académico. Se discuten las implicaciones educativas y la investigación futura.(AU)

Effectiveness of interventions using apps to improve physical activity, sedentary behavior and diet: An umbrella review.

Technology has been recently found to be an effective tool to deliver public health interventions [1]. More specifically, the effects of interventions using apps to improve health have been targeted lately [2]. The goal of the present study was to conduct a systematic review of systematic reviews to summarize the scientific evidence. Three research questions were formulated to guide the research: RQ1. Are interventions using apps effective to improve PA? RQ2. Are interventions using apps effective to improve sedentary behavior? RQ3. Are interventions using apps effective to improve diet? This review of reviews was registered with PROSPERO (CRD42022345909). Systematic reviews were included following the PICOTS framework (population, intervention, comparator, outcomes, time and setting). In addition, reviews with several research objectives were included only when they comprised more than two-thirds of the studies analyzing one or more of the objectives of this review. As a result, 12 systematic reviews were selected for data extraction. Findings uncovered that apps could be effective to improve individuals' PA, sedentary behavior and diet. However, elements like the intervention components, the context/environment/setting, the length of the intervention or the population targeted should be carefully considered in future studies.

Self-made material in physical education: Teacher perceptions of the use of an emerging pedagogical model before and during the COVID-19 pandemic.

The COVID-19 pandemic caused drastic changes in education, which had to adapt to changing scenarios (online, face-to-face, hybrid teaching). Within physical education (PE), strategies such as 'do not use or share equipment' were proposed to avoid infections. These strategies fit with an emerging pedagogical model called the Self-made Material Model (SMM), which involves students creating their own PE equipment. The objectives of the present study were: (a) to analyse PE teachers' beliefs about the use of self-made material in their classes, (b) to evaluate teachers' perceptions of the impact of the use of self-made material in PE lessons during the pandemic and (c) to examine gender/age differences. A quantitative, snowball research design was followed. The Self-made Material Questionnaire ( Méndez-Giménez and Fernández-Río, 2011) comprising two scales (41 items) was adapted: Teachers' beliefs about the use of self-made material scale and Teachers' perceptions of the impact of self-made material usage during the pandemic scale. In total, 1093 in-service teachers (443 women, 40.5%; M = 41.39, SD = 9.54) from 13 Ibero-American countries participated. Descriptive statistics were calculated, Student's T test was conducted for comparisons by gender and one-way analysis of variance (ANOVA) was run for comparisons by age ranges. Overall, the scores were high, emphasising the potential to promote recycling and students' creativity and respect for the material. Women scored higher in items such as promoting interdisciplinarity, equality, attention to disability and education in values. In total, 833 (76.21%) teachers used self-made material during the pandemic and reported high levels of satisfaction, expectations of use, usefulness and profitability. No gender differences were found. In the COVID-19 era, the SMM is playing a relevant role as a meaningful framework and a helpful teaching methodology in different educational scenarios.

Physical Activity and Nighttime Sleep in Adolescents / Actividad Física y Sueño Nocturno en Adolescentes

Background: Previous studies show contradictory results regarding the bidirectional association between physicalactivity and nighttime sleep. The objective of the present study was to add knowledge to these possible relationshipsusing autoregressive models. Method: 214 adolescents (117 boys and 97 girls), with a mean age of 13.31 years agreedto participate. The study variables were measured with accelerometers for 7 full days over three consecutive years. ThemlVAR package was used to compute estimates from multivariate vector autoregression models. Results: The 5-delaymodels showed a better fit. Autoregressive effects were observed in sleep onset, sleep offset and sedentary behavior,which could explain the relationships found in previous studies between physical activity and sleep. Sleep onset,total sleep time, and sleep efficiency had direct effects on sedentary behavior. Moderate-to-vigorous physical activitywas not related to any of the sleep variables. Conclusions: The hypothesis that there are bidirectional/reciprocalrelationships between physical activity and sleep cannot be accepted.(AU)

Antecedentes: Los resultados de estudios previos sobre la asociación bidireccional entre actividad física y sueñonocturno son contradictorios. El objetivo del presente estudio es intentar dar una mejor explicación a estas posiblesrelaciones utilizando modelos autorregresivos. Método: Participaron 214 jóvenes (117 varones y 97 mujeres), con unamedia de edad de 13,31 años. Las variables del estudio se midieron con acelerómetros durante 7 días completos, en tresaños consecutivos. Se utilizó el paquete mlVAR para calcular las estimaciones de modelos vectoriales de autorregresiónmultivariables. Resultados: Los modelos de 5 retrasos fueron los que mostraron un mejor ajuste. Se observaron efectosautorregresivos en el inicio del sueño nocturno, el final del sueño nocturno y los comportamientos sedentarios, quepodrían explicar las relaciones encontradas en estudios previos entre actividad física y sueño. Se observaron efectosdirectos entre el inicio, la duración y la eficiencia del sueño nocturno sobre los comportamientos sedentarios. Laactividad física moderada-vigorosa no se relacionó con ninguna variable de sueño nocturno. Conclusiones: No se puedeaceptar la hipótesis de que existen relaciones bidireccionales/recíprocas, entre la actividad física y el sueño.(AU)

IL-15/IL-15Rα in SJS/TEN: Relevant Expression of IL15 and IL15RA in Affected Skin.

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a life-threatening hypersensitivity reaction to medications characterized by keratinocyte apoptosis and skin detachment. IL-15 serum levels have been associated with severity and prognosis of SJS/TEN. We have measured IL-15 concentrations in serum and blister fluid (BF) from patients with SJS/TEN by ELISA and used quantitative RT-PCR to analyze the expression of IL15 and IL15RA (encoding for IL-15 Receptor-α chain) genes in peripheral blood and BF cells, including isolated monocytes, and in affected skin. A positive correlation was found between IL-15 serum levels and a percent of detached skin. BF concentrations were higher, but no correlation was found. Higher IL15 and IL15RA gene expression levels were found in skin-infiltrating blister fluid cells compared to peripheral mononuclear cells. Moreover, IL15RA transcripts were barely detected in healthy skin, being the highest expression levels found in samples from two SJS/TEN patients who did not survive. The cutaneous expression of IL-15Rα in SJS/TEN may provide an explanation to the tissue-specific immune cytotoxic response in this clinical entity, and the results suggest that the effects of IL-15 in SJS/TEN patients may be dependent on the expression of its private receptor IL-15Rα in affected skin.

Design, synthesis, and biological evaluation of novel double-winged galloyl derivatives as HIV-1 RNase H inhibitors.

Human immunodeficiency virus (HIV) reverse transcriptase (RT)-associated ribonuclease H (RNase H) remains as the only enzyme encoded within the viral genome not clinically validated as an antiviral target. We have previously reported that the galloyl derivative II-25 had RNase H inhibitory activity in enzymatic assays but showed weak antiviral activity in phenotypic assays due its large polarity and poor membrane permeability. In this report, we report on a series of II-25 derivatives, obtained by addition of different hydrophobic moieties ("the wings") at the C-2 and C-3 positions of the piperazine ring that showed improved RNase H inhibitory activity. Six compounds showed strong inhibitory activity and were found to be more potent than ß-thujaplicinol in enzymatic assays. The most potent compound was IA-6 and exhibited the best inhibitory activity (IC50 = 0.067 ± 0.02 µM). IA-6 was around 11 and 30 times more potent than II-25 and ß-thujaplicinol, respectively. Molecular modeling studies predict a strong hydrophobic interaction between the furylmethylaminyl group of IA-6 and the side chain of His539, explaining the potent HIV-1 RNase H inhibition. Unfortunately, none of the derivatives showed significant antiviral activity in cell culture. It is worth emphasizing that most of the obtained compounds show low cytotoxicity (CC50 > 20 µM), which confirms the significance of identifying galloyl derivatives as valuable leads for further optimization.

Impact of a Home Telehealth Program After a Hospitalized COPD Exacerbation: A Propensity Score Analysis

Introduction: Currently there is lack of data regarding the impact of a home telehealth program on readmissions and mortality rate after a COPD exacerbation-related hospitalization. Objective: To demonstrate if a tele-monitoring system after a COPD exacerbation admission could have a favorable effect in 1-year readmissions and mortality in a real-world setting. Methods: This is an observational study where we compared an intervention group of COPD patients treated after hospitalization that conveyed a telehealth program with a followance period of 1 year with a control group of patients evaluated during one year before the intervention began. A propensity-score analyses was developed to control for confounders. The main clinical outcome was 1-year all-cause mortality or COPD-related readmission. Results: The analysis comprised 351 telemonitoring patients and 495 patients in the control group. The intervention resulted in less mortality or readmission after 12 months (35.2% vs. 45.2%; hazard ratio [HR] 0.71 [95% CI=0.56–0.91]; p=0.007). This benefit was maintained after the propensity score analysis (HR=0.66 [95% CI=0.51–0.84]). This benefit, which was seen from the first month of the study and during its whole duration, is maintained when mortality (HR=0.54; 95% CI=[0.36–0.82]) or readmission (subdistribution hazard ratio [SHR] 0.66; 95% CI=[0.50–0.86]) are analyzed separately. Conclusion: Telemonitoring after a severe COPD exacerbation is associated with less mortality or readmissions at 12 months in a real world clinical setting. (AU)

Novel RNase H Inhibitors Blocking RNA-directed Strand Displacement DNA Synthesis by HIV-1 Reverse Transcriptase.

In retroviruses, strand displacement DNA-dependent DNA polymerization catalyzed by the viral reverse transcriptase (RT) is required to synthesize double-stranded proviral DNA. In addition, strand displacement during RNA-dependent DNA synthesis is critical to generate high-quality cDNA for use in molecular biology and biotechnology. In this work, we show that the loss of RNase H activity due to inactivating mutations in HIV-1 RT (e.g. D443N or E478Q) has no significant effect on strand displacement while copying DNA templates, but has a large impact on DNA polymerization in reactions carried out with RNA templates. Similar effects were observed with ß-thujaplicinol and other RNase H active site inhibitors, including compounds with dual activity (i.e., characterized also as inhibitors of HIV-1 integrase and/or the RT DNA polymerase). Among them, dual inhibitors of HIV-1 RT DNA polymerase/RNase H activities, containing a 7-hydroxy-6-nitro-2H-chromen-2-one pharmacophore were found to be very potent and effective strand displacement inhibitors in RNA-dependent DNA polymerization reactions. These findings might be helpful in the development of transcriptomics technologies to obtain more uniform read coverages when copying long RNAs and for the construction of more representative libraries avoiding biases towards 5' and 3' ends, while providing valuable information for the development of novel antiretroviral agents.