Diploid genome assembly of the Malbec grapevine cultivar enables haplotype-aware analysis of transcriptomic differences underlying clonal phenotypic variation.

To preserve their varietal attributes, established grapevine cultivars (Vitis vinifera L. ssp. vinifera) must be clonally propagated, due to their highly heterozygous genomes. Malbec is a France-originated cultivar appreciated for producing high-quality wines and is the offspring of cultivars Prunelard and Magdeleine Noire des Charentes. Here, we have built a diploid genome assembly of Malbec, after trio binning of PacBio long reads into the two haploid complements inherited from either parent. After haplotype-aware deduplication and corrections, complete assemblies for the two haplophases were obtained with a very low haplotype switch-error rate (<0.025). The haplophase alignment identified > 25% of polymorphic regions. Gene annotation including RNA-seq transcriptome assembly and ab initio prediction evidence resulted in similar gene model numbers for both haplophases. The annotated diploid assembly was exploited in the transcriptomic comparison of four clonal accessions of Malbec that exhibited variation in berry composition traits. Analysis of the ripening pericarp transcriptome using either haplophases as a reference yielded similar results, although some differences were observed. Particularly, among the differentially expressed genes identified only with the Magdeleine-inherited haplotype as reference, we observed an over-representation of hypothetically hemizygous genes. The higher berry anthocyanin content of clonal accession 595 was associated with increased abscisic acid responses, possibly leading to the observed overexpression of phenylpropanoid metabolism genes and deregulation of genes associated with abiotic stress response. Overall, the results highlight the importance of producing diploid assemblies to fully represent the genomic diversity of highly heterozygous woody crop cultivars and unveil the molecular bases of clonal phenotypic variation.

CoMentG: comprehensive retrieval of generic relationships between biomedical concepts from the scientific literature.

The CoMentG resource contains millions of relationships between terms of biomedical interest obtained from the scientific literature. At the core of the system is a methodology for detecting significant co-mentions of concepts in the entire PubMed corpus. That method was applied to nine sets of terms covering the most important classes of biomedical concepts: diseases, symptoms/clinical signs, molecular functions, biological processes, cellular compartments, anatomic parts, cell types, bacteria and chemical compounds. We obtained more than 7 million relationships between more than 74 000 terms, and many types of relationships were not available in any other resource. As the terms were obtained from widely used resources and ontologies, the relationships are given using the standard identifiers provided by them and hence can be linked to other data. A web interface allows users to browse these associations, searching for relationships for a set of terms of interests provided as input, such as between a disease and their associated symptoms, underlying molecular processes or affected tissues. The results are presented in an interactive interface where the user can explore the reported relationships in different ways and follow links to other resources. Database URL: https://csbg.cnb.csic.es/CoMentG/.

Screening of Galician grapevine varieties by SNPs, phenotypic traits, and phytopathology.

The genetic erosion of the European grapevine diversity in the last century has promoted the conservation of varieties in germplasm banks to prevent their disappearance. The study of these varieties is necessary as it would allow the diversification of the wine market, as well as provide a source of genes to face new pathogens or climate constraints. In this work, the grapevine varieties preserved in the "Estación de Viticultura e Enoloxía de Galicia" (EVEGA) Germplasm Bank (Ourense, Spain) were widely characterized, combining ampelography, ampelometry, agronomy, and phytopathology. Moreover, genetic characterization was carried out through the analysis of 48 single-nucleotide polymorphisms (SNPs). A Bayesian analysis based on the SNP data was carried out to define the genetic structure of the EVEGA Germplasm Bank, which allowed the differentiation of two main reconstructed panmictic populations (RPPs), confirming previous results obtained based on microsatellite markers (SSRs). A great diversity between varieties was found for almost every parameter evaluated for ampelography, ampelometry, phytopatology, phenology, and berry quality. A principal component analysis (PCA) performed with these phenotypical data allowed discrimination among some groups of varieties included in different genetic populations. This study allowed us to evaluate the grapevine diversity maintained in the EVEGA Germplasm Bank and characterize varieties of potential value for breeding programs of interest for the Galician viticulture.

Effects of multicomponent training and HMB supplementation on disability, cognitive and physical function in institutionalized older adults aged over 70 years: a cluster-randomized controlled trial.

OBJECTIVES: To investigate the synergist effects of exercise and ß-hydroxy ß-methylbutyrate (HMB) supplementation on disability, cognitive and physical function, and muscle power in institutionalized older people. DESIGN: Cluster-randomized controlled trial. PARTICIPANTS: Seventy-two institutionalized older adults (age = 83 ± 10 years old; 63% women) were randomized in four groups: exercise plus placebo (EX), HMB supplementation, EX plus HMB supplementation (EX + HMB), and control (CT). INTERVENTION: The exercising participants completed a 12-week tailored multicomponent exercise intervention (Vivifrail; 5 days/week of an individualized resistance, cardiovascular, balance and flexibility program), whereas the HMB groups received a drink containing 3 g/day of HMB. MEASUREMENTS: Participants were assessed Pre and Post intervention for disability and cognitive function (validated questionnaires), physical function (short physical performance battery, SPPB), handgrip strength and sit-to-stand relative muscle power. Linear mixed-effect models were used to compare changes among groups. RESULTS: Compared to baseline, both EX and EX + HMB improved cognitive function (+2.9 and +1.9 points; p < 0.001), SPPB score (+2.9 points and +2.4 points; p < 0.001) and relative muscle power (+0.64 and +0.48 W·kg-1; p < 0.001), while CT and HMB remained unchanged (p > 0.05). Significant between-group differences were noted between CT, EX and EX + HMB for cognitive function (p < 0.01), between CT and EX + HMB for physical function (p = 0.043), and between CT, EX and EX + HMB for relative muscle power (p < 0.001). CONCLUSION: The Vivifrail exercise program was effective in improving cognitive and physical function, and muscle power in nursing home residents, while HMB supplementation did not provide additional benefits when combined with exercise. These results emphasize the importance of physical exercise interventions in very old people as an essential basis for improving their overall health and quality of life.

Sequential Mapping of Game Patterns in Men and Women Professional Padel Players.

PURPOSE: This study analyzed the sequences of actions in professional men and women padel players to identify common game patterns. METHODS: The sample comprised 17,557 stroke-by-stroke actions (N = 1640 rallies) of the championship World Padel Tour. Multistep Markov chains were used to calculate the conditional probabilities of occurrence of actions during the rally. RESULTS: Results revealed that men's and women's padel is mainly defined by 36 patterns constituting 55% and 63% of all actions in the game, respectively, with the 10 most common sequences accounting for 42% to 45% of the game. There were recurrent technical-tactical actions with specific offensive and defensive functions that were constantly reiterated during the rallies. In men, the use of smash, volley, bandeja, direct, back wall, back-wall lobs, and direct lobs followed a foreseeable pattern up to 8 lags, whereas women described predictable interactions for volley, bandeja, direct, lobs, and direct lobs up to 5 lags and for smash and back wall up to 4 lags. CONCLUSIONS: The ability of padel players to recall these patterns and enhance their anticipation skills may potentially improve their performance. These findings contribute to a better knowledge of professional padel game dynamics while providing coaches and players with useful information to optimize training and decision-making strategies.

Integrative non-pharmacological care for individuals at risk of rheumatoid arthritis.

There is increasing knowledge in the recognition of individuals at risk for progression to rheumatoid arthritis (RA) before the clinical manifestation of the disease. This prodromal phase preceding the manifestation of RA may represent a "window of opportunity" for preventive interventions that may transform the clinical approach to this disease. However, limited evidence exists in support of effective interventions to delay the onset or even halt the manifestation of RA. Given the multifactorial nature of RA development and disease progression, the latest guidelines for established RA stress the use of integrative interventions and multidisciplinary care strategies, combining pharmacologic treatment with non-pharmacological approaches. Accordingly, individuals at risk of RA could be offered an integrative, multifactorial intervention approach. Current data point toward pharmacological intervention reverting the subclinical inflammation and delay in the disease onset. In addition, targeting life style modifiable factors (smoking cessation, dental health, physical activity, and diet) may presumably improve RA prognosis in individuals at risk, mainly by changes in epigenetics, autoantibodies, cytokines profiles, and microbiome. Nonetheless, the benefits of multidisciplinary interventions to halt the manifestation of RA in at-risk individuals remain unknown. As there is a growing knowledge of possible pharmacological intervention in the preclinical phase, this narrative review aims to provide a comprehensive overview of non-pharmacological treatments in individuals at risk of RA. Considering the mechanisms preceding the clinical manifestation of RA we explored all aspects that would be worth modifying and that would represent an integrative non-pharmacological care for individuals at risk of RA.

Differences in the Levels of Physical Activity and Sport Habits between Men and Women in Cartagena (Spain).

Scientific evidence proves the importance of physical activity and sports in decreasing morbidity and mortality rates and health-related costs. Public and stakeholder involvement is vital in the sustainable promotion of physical activity and sports practice in local settings. The aim of this study was to identify the levels of physical activity and sports habits of the population of the city Cartagena (Spain). The short version of the International Questionnaire of Physical Activity was used (IQPA) and a virtual questionnaire on sports habits was sent to 1450 citizens. Responses from 248 people (162 men and 86 women), with ages ranging from 18 to 77 years old (average age = 41 ± 17 years old), were collected. The results showed low to moderate levels of physical activity with no considerable differences between men and women for the population of Cartagena. Women were shown to engage in higher intensity practice of physical activity, whereas men were shown to be more consistent and have a significantly higher participation rate in sports events, both those with free entry and those that require the acquisition of a ticket. Men were also shown to have a higher rate of media sport use. This information may assist in the development of effective political actions to promote physical activity and sports in local settings.

Reduced Match Exposure in the Previous 2 Matches Accounts for Hamstring Muscle Injury Incidence in Professional Football Players.

BACKGROUND: Hamstring strain injuries are one of the most prevalent injuries in football (soccer). We examined the influence of accumulated match-play exposure on the occurrence of hamstring strain injury in professional football from 2 teams (Spanish 1st Division, LaLiga) over 3 seasons, and determined specific cut-off points as indicators of injury risk. HYPOTHESIS: Overloaded players would be more likely to sustain a hamstring injury. STUDY DESIGN: Prospective, controlled, observational study. LEVEL OF EVIDENCE: Level 2b. METHODS: Playing time, total running distance, and high-speed running (>24 km/h) distance during official matches of players that sustained a hamstring injury were compared with uninjured, paired controls. Cumulative playing time and running performance of 4 matches before the injury was computed. Relative risk (RR) of injury occurrence was estimated by generalized estimating equations. Diagnostic accuracy was determined by receiver operating characteristics and the area under the curve. RESULTS: Thirty-seven hamstring strain injuries occurred, representing 23 ± 18 absence days per injury. Thirty-seven controls (uninjured players) were used as comparators. Low match-play exposures during 1 and 2 matches before injury were likely to explain injury occurrence (RR: 14-53%; P < 0.01). Metrics from the match before the hamstring muscle strain demonstrated the best accuracy to predict injury occurrence: high-speed running distance ≤328 m (sensitivity, 64%; specificity, 84%), playing time ≤64 min (sensitivity, 36%; specificity, 97%), and running distance ≤5.8 km (sensitivity, 39%; specificity, 97%). CONCLUSION: Relatively reduced competitive exposure in the previous 2 matches was associated with higher hamstring injury risk in professional football players. CLINICAL RELEVANCE: Screening simple metrics such as the accumulated match exposure during official matches and considering specific cut-off points for some running variables may be good indicators of injury risk and may assist in better individual injury management in professional soccer players.

Proof of concept of prehabilitation: a combination of education and behavioural change, to promote physical activity in people with fibromyalgia.

OBJECTIVES: To establish proof of concept of a prehabilitation intervention, a combination of education and behavioural change, preceding a physical activity programme in people with fibromyalgia (FM). SETTINGS: Open-label, feasibility clinical trial. PARTICIPANTS: Eleven people with FM (10 women). INTERVENTIONS: The prehabilitation intervention consisted of 4 weeks, 1 weekly session (~1 to 1.5 hours), aimed to increase self-efficacy and understand why and how to engage in a gentle and self-paced physical activity programme (6 weeks of walking with telephone support). PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was the acceptability and credibility of the intervention by means of the Credibility/Expectancy Questionnaire. Secondary outcomes comprised scales to measure FM severity, specific symptoms and sedentary behaviour. An exit interview was conducted to identify the strengths and weaknesses and barriers to the intervention. RESULTS: One participant dropped out due to finding the walking programme excessively stressful. Participants expected the intervention would improve their symptoms by 22%-38% but resulted in 5%-26% improvements. Participants would be confident in recommending this intervention to a friend who experiences similar problems. The interviews suggested that the fluctuation of symptoms should be considered as an outcome and that the prehabilitation intervention should accomodate these fluctuation. Additional suggestions were to incorporate initial interviews (patient-centred approach), to tailor the programmes to individuals' priorities and to offer a variety of physical activity programmes to improve motivation. CONCLUSIONS: This feasibility study demonstrated that our novel approach is acceptable to people with FM. Future interventions should pay attention to flexibility, symptoms fluctuation and patients support. TRIAL REGISTRATION NUMBER: NCT03764397.

Simultaneous pancreas-kidney transplantation: which graft warns the most?

BACKGROUND: Simultaneous pancreas-kidney transplantation (SPK) is still characterized by high rates of postoperative complications. This study aims to offer an in-depth characterization of early, medium-term, and late complications following SPK to derive insights for postoperative management and follow-up. METHODS: Consecutive SPK transplantations were analysed. Pancreatic graft (P-graft)- and kidney graft (K-graft)-related complications were analysed separately. The global postoperative course was assessed in three timeframes (early, medium-term, and late) using the comprehensive complication index (CCI). Predictors of complications and early graft loss were explored. RESULTS: Complications occurred in 61.2% of patients, and the 90-day mortality was 3.9%. The overall burden of complications was significantly high during admission (CCI 22.4 ± 21.1) and decreased gradually afterwards. P-graft-related complications burdened the most in the early postoperative course (CCI 11.6 ± 13.8); postoperative ileus and perigraft fluid collection were the most frequent complications, and pseudoaneurysms, haemorrhages, and bowel leaks were the major concerns. K-related complications were milder but represented the largest proportion of the CCI in the late postoperative timeframe (CCI 7.6 ± 13.6). No predictors of P-graft- or K-graft-related complications were found. CONCLUSION: Pancreas graft-related complications represent the largest part of the clinical burden in the early postoperative timeframe but are negligible after 3 months. Kidney grafts have a relevant impact in the long term. The multidisciplinary approach to SPK recipients should be driven based on all graft-specific complications and tailored on a time-dependent basis.

MBROLE3: improved functional enrichment of chemical compounds for metabolomics data analysis.

MBROLE (Metabolites Biological Role) facilitates the biological interpretation of metabolomics experiments. It performs enrichment analysis of a set of chemical compounds through statistical analysis of annotations from several databases. The original MBROLE server was released in 2011 and, since then, different groups worldwide have used it to analyze metabolomics experiments from a variety of organisms. Here we present the latest version of the system, MBROLE3, accessible at http://csbg.cnb.csic.es/mbrole3. This new version contains updated annotations from previously included databases as well as a wide variety of new functional annotations, such as additional pathway databases and Gene Ontology terms. Of special relevance is the inclusion of a new category of annotations, 'indirect annotations', extracted from the scientific literature and from curated chemical-protein associations. The latter allows to analyze enriched annotations of the proteins known to interact with the set of chemical compounds of interest. Results are provided in the form of interactive tables, formatted data to download, and graphical plots.

Implementing climate change projections in System Dynamics models.

Desertification is the degradation of drylands, which occupy an increasing proportion of the Earth's surface due to global warming. It is currently the most extensive biome on Earth, occupying 45% and one out of every three inhabitants of the planet live in them. One of the most effective ways to face desertification, as Land Degradation Neutrality points out, is prevention. For this purpose, simulation models are very useful tools. Specifically, System Dynamics models are particularly effective, since they allow bringing together the biophysical and socioeconomic variables involved in the formation of the problem. These integrative models, coupled with other tools such as sensitivity analyses, are used to generate desertification early warning indicators. The objective of this programming routine is to implement climate change scenarios in these simulation models. The script presented here was used to evaluate the sensitivity of dehesa rangelands productivity to the increase in the frequency and intensity of droughts due to climate change.•Integrated simulation models are useful tools to understand complex socioecosystems.•Land-use changes foster the alteration of key hydro-bio-geochemical processes.•By means of automated import processes and data analysis programming, it is possible to implement desertification early warning systems.

Review: Status and prospects of association mapping in grapevine.

Thanks to current advances in sequencing technologies, novel bioinformatics tools, and efficient modeling solutions, association mapping has become a widely accepted approach to unravel the link between genotype and phenotype diversity in numerous crops. In grapevine, this strategy has been used in the last decades to understand the genetic basis of traits of agronomic interest (fruit quality, crop yield, biotic and abiotic resistance), of special relevance nowadays to improve crop resilience to cope with future climate scenarios. Genome-wide association studies have identified many putative causative loci for different traits, some of them overlapping well-known causal genes identified by conventional quantitative trait loci studies in biparental progenies, and/or validated by functional approaches. In addition, candidate-gene association studies have been useful to pinpoint the causal mutation underlying phenotypic variation for several traits of high interest in breeding programs (like berry color, seedlessness, and muscat flavor), information that has been used to develop highly informative and useful markers already in use in marker-assisted selection processes. Thus, association mapping has proved to represent a valuable step towards high quality and sustainable grape production. This review summarizes current applications of association mapping in grapevine research and discusses future prospects in view of current viticulture challenges.

Two stage hepatectomy (TSH) versus ALPPS for initially unresectable colorectal liver metastases: A systematic review and meta-analysis.

BACKGROUND: Although numerous comparisons between conventional Two Stage Hepatectomy (TSH) and Associating Liver Partition and Portal Vein Ligation for staged hepatectomy (ALPPS) have been reported, the heterogeneity of malignancies previously compared represents an important source of selection bias. This systematic review and meta-analysis aimed to compare perioperative and oncological outcomes between TSH and ALPPS to treat patients with initially unresectable colorectal liver metastases (CRLM). METHODS: Main electronic databases were searched using medical subject headings for CRLM surgically treated with TSH or ALPPS. Patients treated for primary or secondary liver malignancies other than CRLM were excluded. RESULTS: A total of 335 patients from 5 studies were included. Postoperative major complications were higher in the ALPPS group (relative risk [RR] 1.46, 95% confidence interval [CI] 1.04-2.06, I2 = 0%), while no differences were observed in terms of perioperative mortality (RR 1.53, 95% CI 0.64-3.62, I2 = 0%). ALPPS was associated with higher completion of hepatectomy rates (RR 1.32, 95% CI 1.09-1.61, I2 = 85%), as well as R0 resection rates (RR 1.61, 95% CI 1.13-2.30, I2 = 40%). Nevertheless, no significant differences were achieved between groups in terms of overall survival (OS) (RR 0.93, 95% CI 0.68-1.27, I2 = 52%) and disease-free survival (DFS) (RR 1.08, 95% CI 0.47-2.49, I2 = 54%), respectively. CONCLUSION: ALPPS and TSH to treat CRLM seem to have comparable operative risks in terms of mortality rates. No definitive conclusions regarding OS and DFS can be drawn from the results.

Effects of a concurrent training, respiratory muscle exercise, and self-management recommendations on recovery from post-COVID-19 conditions: the RECOVE trial.

The aim of this study was to determine the effectiveness of physical exercise, respiratory muscle training, and the self-management World Health Organization (WHO) recommendations leaflet on the recovery of physical fitness, quality of life, and symptom status in people with post-COVID-19 conditions. Eighty nonhospitalized adults with a post-COVID-19 condition were randomly assigned to one of four 8-wk parallel intervention groups: 1) multicomponent exercise program based on concurrent training (CT, number of subjects (n) = 20; 3 resistance and endurance supervised sessions per week at low-moderate intensity); 2) inspiratory muscle training (RM, n = 17; 2 standardized daily sessions); 3) a combination of both of the above (CTRM, n = 23); and 4) control group (CON, n = 20; following the WHO guidelines for post-COVID-19-related illness rehabilitation). No significant differences between groups were detected at baseline. Although no significant differences between interventions were detected in the V̇o2max, significant individual improvements were identified in the CT (7.5%; effect size, ES = 0.28) and CTRM (7.8%; ES = 0.36) groups. Lower body muscle strength significantly improved in the CT and CTRM (14.5%-32.6%; ES = 0.27-1.13) groups compared with RM and CON (-0.3% to 11.3%; ES = 0.10-0.19). The CT and CTRM groups improved significantly for dyspnea and fatigue, as did the health status. In addition, significant differences between interventions were described in fatigue and depression scales favoring CT and CTRM interventions. An individualized and supervised concurrent training with or without inspiratory muscle training was safe and more effective than self-care recommendations and inspiratory muscle training alone, to regain cardiovascular and muscular fitness, improve symptom severity, and health status in outpatients with post-COVID-19 conditions.NEW & NOTEWORTHY Eight weeks of concurrent training, with or without inspiratory muscle exercise, was better than WHO "Support for Rehabilitation: Self-Management after COVID-19-Related Illness" recommendations or inspiratory muscle training alone to improve cardiopulmonary fitness, strength, and symptom severity, in a safe and effective manner. The RECOVE trial proved the benefits and utility of a supervised exercise program in people with post-COVID-19 conditions after mild COVID-19 in an ambulatory setting.

Analyzing the role of reoperation in recurrent glioblastoma: a 15-year retrospective study in a single institution.

BACKGROUND: Multiple treatment options at glioblastoma progression exist, including reintervention, reirradiation, additional systemic therapy, and novel strategies. No alternative has been proven to be superior in terms of postprogression survival (PPS). A second surgery has shown conflicting evidence in the literature regarding its prognostic impact, possibly affected by selection bias, and might benefit a sparse subset of patients with recurrent glioblastoma. The present study aims to determine the prognostic influence of salvage procedures in a cohort of patients treated in the same institution over 15 years. METHODS: Three hundred and fifty patients with confirmed primary glioblastoma diagnosed and treated between 2005 and 2019 were selected. To examine the role of reoperation, we intended to create comparable groups, previously excluding all diagnostic biopsies and patients who were not actively treated after the first surgery or at disease progression. Uni- and multivariate Cox proportional hazards regression models were employed, considering reintervention as a time-fixed or time-dependent covariate. The endpoints of the study were overall survival (OS) and PPS. RESULTS: At progression, 33 patients received a second surgery and 84 were treated with chemotherapy only. Clinical variables were similar among groups. OS, but not PPS, was superior in the reintervention group. Treatment modality had no impact in our multivariate Cox regression models considering OS or PPS as the endpoint. CONCLUSIONS: The association of reoperation with improved prognosis in recurrent glioblastoma is unclear and may be influenced by selection bias. Regardless of our selective indications and high gross total resection rates in second procedures, we could not observe a survival advantage.

Appraising pancreatic fistula in pancreas transplantation: A comprehensive complication index based analysis of postoperative outcomes and predictors of graft survival.

BACKGROUND: A definition of pancreatic fistula specifically addressing pancreas transplantation (PT) is lacking. This study sought to characterize pancreatic fistula in this setting and to define its clinical relevance on the postoperative course and long-term graft survival (GS). METHODS: Consecutive simultaneous pancreas and kidney transplantations were analysed. The global postoperative course was assessed through the comprehensive complication index (CCI). PF was defined according to the original International Study Group for Pancreatic Surgery (ISGPS) definition. Predictors of poor postoperative course and GS were explored. RESULTS: Seventy-eight patients were analysed. Surgical morbidity was 48.7%, with severe complications occurring in 39.7%. Ninety-day mortality was 2.6%. PF occurred in 56.6% of patients, although its average clinical burden was low and did not correlate with either early or long-term outcomes. Peri-graft fluid collections, postoperative day (POD) 1 drain fluid amylase (DFA) ≥ 2200 U/L, and POD 5 DFA/serum amylase ratio ≥7.0 independently correlated with poor postoperative course. Perigraft fluid collections were associated with reduced GS. CONCLUSION: Conventionally defined pancreatic fistula is frequent following PT, although its clinical impact is negligible. To define clinically relevant PF, novel cut-offs for DFA might be pondered in a future series, while perigraft fluid collections should be strongly considered.

Rehabilitation for post-COVID-19 condition through a supervised exercise intervention: A randomized controlled trial.

PURPOSE: The aim of the study was to compare the outcomes of patients with post-COVID-19 condition undergoing supervised therapeutic exercise intervention or following the self-management WHO (World Health Organization) rehabilitation leaflet. METHODS: A randomized controlled trial was carried out that included 39 participants with post-COVID-19 condition who had a chronic symptomatic phase lasting >12 weeks. Comprehensive medical screening, patient-reported symptoms, and cardiorespiratory fitness and muscular strength were assessed. Patients were randomly assigned to a tailored multicomponent exercise program based on concurrent training for 8 weeks (two supervised sessions per week comprised resistance training combined with aerobic training [moderate intensity variable training], plus a third day of monitored light intensity continuous training), or to a control group which followed the WHO guidelines for rehabilitation after COVID-19. RESULTS: After follow-up, there were changes in physical outcomes in both groups, however, the magnitude of the change pre-post intervention favored the exercise group in cardiovascular and strength markers: VO2 max +5.7%, sit-to-stand -22.7% and load-velocity profiles in bench press +6.3%, and half squat +16.9%, (p < 0.05). In addition, exercise intervention resulted in a significantly better quality of life, less fatigue, less depression, and improved functional status, as well as in superior cardiovascular fitness and muscle strength compared to controls (p < 0.05). No adverse events were observed during the training sessions. CONCLUSION: Compared to current WHO recommendations, a supervised, tailored concurrent training at low and moderate intensity for both resistance and endurance training is a more effective, safe, and well-tolerated intervention in post-COVID-19 conditions.

A PfSPZ vaccine immunization regimen equally protective against homologous and heterologous controlled human malaria infection.

Immunization with radiation-attenuated Plasmodium falciparum (Pf) sporozoites (SPZ) in PfSPZ Vaccine, has provided better vaccine efficacy (VE) against controlled human malaria infection (CHMI) with the same parasites as in the vaccine (homologous) than with genetically distant parasites (heterologous). We sought to identify an immunization regimen that provided similar VE against CHMI with homologous and heterologous Pf for at least 9 weeks in malaria-naïve adults. Such a regimen was identified in part 1 (optimization), an open label study, and confirmed in part 2 (verification), a randomized, double-blind, placebo-controlled study in which VE was assessed by cross-over repeat CHMI with homologous (PfNF54) and heterologous (Pf7G8) PfSPZ at 3 and 9-10 weeks. VE was calculated using Bayesian generalized linear regression. In part 1, vaccination with 9 × 105 PfSPZ on days 1, 8, and 29 protected 5/5 (100%) subjects against homologous CHMI at 3 weeks after the last immunization. In part 2, the same 3-dose regimen protected 5/6 subjects (83%) against heterologous CHMI at both 3 and 9-10 weeks after the last immunization. Overall VE was 78% (95% predictive interval: 57-92%), and against heterologous and homologous was 79% (95% PI: 54-95%) and 77% (95% PI: 50-95%) respectively. PfSPZ Vaccine was safe and well tolerated. A 4-week, 3-dose regimen of PfSPZ Vaccine provided similar VE for 9-10 weeks against homologous and heterologous CHMI. The trial is registered with ClinicalTrials.gov, NCT02704533.