Correction: Silva-Filho et al. Eoscyphella luciurceolata gen. and sp. nov. (Agaricomycetes) Shed Light on Cyphellopsidaceae with a New Lineage of Bioluminescent Fungi. J. Fungi 2023, 9, 1004.

In the original publication [...].

Eoscyphella luciurceolata gen. and sp. nov. (Agaricomycetes) Shed Light on Cyphellopsidaceae with a New Lineage of Bioluminescent Fungi.

During nocturnal field expeditions in the Brazilian Atlantic Rainforest, an unexpected bioluminescent fungus with reduced form was found. Based on morphological data, the taxon was first identified as belonging to the cyphelloid genus Maireina, but in our phylogenetic analyses, Maireina was recovered and confirmed as a paraphyletic group related to genera Merismodes and Cyphellopsis. Maireina filipendula, Ma. monacha, and Ma. subsphaerospora are herein transferred to Merismodes. Based upon morphological and molecular characters, the bioluminescent cyphelloid taxon is described as the new genus Eoscyphella, characterized by a vasiform to urceolate basidiomata, subglobose to broadly ellipsoid basidiospores, being pigmented, weakly to densely encrusted external hyphae, regularly bi-spored basidia, unclamped hyphae, and an absence of both conspicuous long external hairs and hymenial cystidia. Phylogenetic analyses based on ITS rDNA and LSU rDNA support the proposal of the new genus and confirm its position in Cyphellopsidaceae. Eoscyphella luciurceolata represents a new lineage of bioluminescent basidiomycetes with reduced forms.

Metaprofiling of the Bacterial Community in Colonized Compost Extracts by Agaricus subrufescens.

It is well-known that bacteria and fungi play important roles in the relationships between mycelium growth and the formation of fruiting bodies. The sun mushroom, Agaricus subrufescens, was discovered in Brazil ca. 1960 and it has become known worldwide due to its medicinal and nutritional properties. This work evaluated the bacterial community present in mushroom-colonized compost extract (MCCE) prepared from cultivation of A. subrufescens, its dynamics with two different soaking times and the influence of the application of those extracts on the casing layer of a new compost block for A. subrufescens cultivation. MCCEs were prepared through initial submersion of the colonized compost for 1 h or 24 h in water followed by application on casing under semi-controlled conditions. Full-length 16S rRNA genes of 1 h and 24 h soaked MCCE were amplified and sequenced using nanopore technology. Proteobacteria, followed by Firmicutes and Planctomycetes, were found to be the most abundant phyla in both the 1 h and 24 h soaked MCCE. A total of 275 different bacterial species were classified from 1 h soaked MCCE samples and 166 species from 24 h soaked MCCE, indicating a decrease in the bacterial diversity with longer soaking time during the preparation of MCCE. The application of 24 h soaked MCCE provided increases of 25% in biological efficiency, 16% in precociousness, 53% in the number of mushrooms and 40% in mushroom weight compared to control. Further investigation is required to determine strategies to enhance the yield and quality of the agronomic traits in commercial mushroom cultivation.

Immunomodulatory Effect of Polysaccharides from the Mushroom-Forming Basidiomycete Gymnopilus imperialis (Agaricomycetes, Basidiomycota).

Gymnopilus consists of a widely distributed genus of basidiomycetes, especially in tropical regions of the world, such as Japan, Australia, Paraguay, and Brazil. This genus biosynthesizes interesting bioactive compounds, such as sesquiterpenoids, oligoisoprenoids, styrylpyrones, and lectins. In the present study, the aqueous extract of the basidiomata of Gymnopilus imperialis (Basidiomycota, Agaricomycetes, Agaricales, Hymenogastraceae) was obtained by using the accelerated solvent extraction (ASE) technique, followed by the precipitation of polysaccharide fraction with ethanol. Further purification by freeze-thawing processes, Fehling solution precipitation, and membrane dialysis with different pore sizes yield three main polysaccharide fractions (Gi-MRSW, Gi-PFME, and Gi-SFME). According to monosaccharide composition and 13C-NMR data, the Gi-MRSW and Gi-SFME fractions showed to be composed mainly of ß-glucans and Gi-PFME by a heterogalactan. Moreover, the immunomodulatory potential of Gi-MRSW was evaluated using RAW 264.7 murine macrophage as a study model. The nitric oxide production was significantly increased in treated samples, and the expression of inducible nitric oxide synthase (iNOS) showed that the fraction Gi-MRSW from G. imperialis induces the M1 polarization phenotype.

Fungal bioassays for environmental monitoring.

Environmental pollutants are today a major concern and an intensely discussed topic on the global agenda for sustainable development. They include a wide range of organic compounds, such as pharmaceutical waste, pesticides, plastics, and volatile organic compounds that can be found in air, soil, water bodies, sewage, and industrial wastewater. In addition to impacting fauna, flora, and fungi, skin absorption, inhalation, and ingestion of some pollutants can also negatively affect human health. Fungi play a crucial role in the decomposition and cycle of natural and synthetic substances. They exhibit a variety of growth, metabolic, morphological, and reproductive strategies and can be found in association with animals, plants, algae, and cyanobacteria. There are fungal strains that occur naturally in soil, sediment, and water that have inherent abilities to survive with contaminants, making the organism important for bioassay applications. In this context, we reviewed the applications of fungal-based bioassays as a versatile tool for environmental monitoring.

Association of polymorphisms in the erythropoietin gene with diabetic retinopathy: a case-control study and systematic review with meta-analysis.

BACKGROUND: Diabetic retinopathy (DR) is characterized by ischemia, hypoxia, and angiogenesis. Erythropoietin (EPO), an angiogenic hormone, is upregulated in DR, and the association of EPO genetic variants with DR is still uncertain, as conflicting results have been reported. Therefore, we performed a case-control study followed by a meta-analysis to investigate whether the rs1617640, rs507392, and rs551238 polymorphisms in EPO gene are associated with DR. METHODS: The case-control study included 1042 Southern Brazilians with type 2 diabetes (488 without DR and 554 with DR). Eligible studies for the meta-analysis were searched from electronic databases up to June 1, 2021. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for five genetic inheritance models. RESULTS: The minor alleles of the EPO polymorphisms had nearly the same frequency in all groups of patients (35%), and no association was detected with DR in the case-control study. The meta-analysis included 14 independent sets of cases and controls with 9117 subjects for the rs1617640 polymorphism and nine independent sets with more than 5000 subjects for the rs507392 and rs551238 polymorphisms. The G allele of the rs1617640 polymorphism was suggestively associated with DR under the dominant (OR = 0.82, 95% CI: 0.68-0.98), heterozygous additive (OR = 0.82, 95% CI: 0.69-0.97), and overdominant (OR = 0.88, 95% CI: 0.79-0.97) models. In the subgroup analyses, the G allele was also suggestively associated with proliferative DR (PDR), non-proliferative DR (NPDR), and DR (PDR + NPDR) among patients with type 1 diabetes (T1DM) or non-Asian ancestry. After considering the Bonferroni correction for multiple comparisons, the G allele remained associated with NPDR and DR in T1DM. Regarding the rs507392 and rs551238 polymorphisms, no association was found between these variants and DR. CONCLUSION: Our findings provide additional support to EPO as a susceptibility gene for DR, with the rs1617640 polymorphism deserving further investigation.

Reannotation of Fly Amanita l-DOPA Dioxygenase Gene Enables Its Cloning and Heterologous Expression.

The l-DOPA dioxygenase of Amanita muscaria (AmDODA) participates in the biosynthesis of betalain- and hygroaurin-type natural pigments. AmDODA is encoded by the dodA gene, whose DNA sequence was inferred from cDNA and gDNA libraries almost 30 years ago. However, reports on its heterologous expression rely on either the original 5'-truncated cDNA plasmid or artificial gene synthesis. We provide unequivocal evidence that the heterologous expression of AmDODA from A. muscaria specimens is not possible by using the coding sequence previously inferred for dodA. Here, we rectify and reannotate the full-length coding sequence for AmDODA and express a 205-aa His-tagged active enzyme, which was used to produce the l-DOPA hygroaurin, a rare fungal pigment. Moreover, AmDODA and other isozymes from bacteria were submitted to de novo folding using deep learning algorithms, and their putative active sites were inferred and compared. The wide catalytic pocket of AmDODA and the presence of the His-His-His and His-His-Asp motifs can provide insight into the dual cleavage of l-DOPA at positions 2,3 and 4,5 as per the mechanism proposed for nonheme dioxygenases.

Metabolomics of the wild mushroom Gymnopilus imperialis (Agaricomycetes, Basidiomycota) by UHPLC-HRMS/MS analysis and molecular network.

Gymnopilus consists in a widely distributed genus of mushroom-forming fungi, especially in tropical regions of the world. Literature on Gymnopilus representatives reports the presence of oligoisoprenoids, and styrylpyrones. Considering the large number of secondary metabolites that basidiomycetes might contain, dereplication tools such as GNPS (Global Natural Products Social Molecular Networking), has become important in prospecting metabolites, saving time and work on isolation and characterization of natural products. Thus, this work identified the wild mushroom Gymnopilus imperialis and dereplicated their extracts with the aid of GNPS to annotate oligoisoprenoids. It was possible to annotate 24 oligoisoprenoids from methanol, dichloromethaneand ethyl acetate extracts of G. imperialis, 4 of them from GNPS spectral library match, and 20 from prediction based on molecular network. Moreover HRMS-ESI-(+) dereplication of the acetate extract annotated bisnoryangonin and hispidin. To the best of our knowledge, this is the first report on the annotation of a series of gymnopilins analogues based on GNPS molecular network. Our findings suggest that GNPS might be an effective, rapid, and open-source device to identify compounds and predict analogues.

Influence of strains and environmental cultivation conditions on the bioconversion of ergosterol and vitamin D2 in the sun mushroom.

BACKGROUND: The fungus Agaricus subrufescens is grown commercially in China, the USA, Brazil, Taiwan and Japan, among others. However, each country adopts a cultivation system that significantly influences the agronomical parameters and chemical composition of the harvested mushrooms. In this study, the influence of the cultivation process on the content of ergosterol and vitamin D2 was evaluated. RESULTS: Four commercial strains of A. subrufescens (ABL 04/49, ABL CS7, ABL 18/01 and ABL 19/01) and two environmental cultivation conditions (in the field and a controlled chamber with the absence of sunlight) were used. Infield cultivation, ABL CS7 and ABL 19/01 strains presented better agronomic parameters, whereas in a protected environment ABL 19/01, ABL 04/49 and ABL 18/01 demonstrated better performance, respectively. The highest biological efficiency value (64%) was provided by ABL 19/01 strain in a controlled environment. CONCLUSION: The highest content in ergosterol (990 mg kg-1 ) and vitamin D2 (36.8 mg kg-1 ) were observed in mushrooms obtained in the field from strain ABL 04/49, which presents reasonable agronomic parameters for cultivation. © 2021 Society of Chemical Industry.

Optimized methodology for obtention of high-yield and -quality RNA from the mycelium of the bioluminescent fungus Neonothopanus gardneri.

Neonothopanus gardneri, also known as coconut flower mushroom (flor-de-coco), is a Brazilian bioluminescent basidiomycete found in Palm Forest, a transitional biome between the Amazonian Forest and Caatinga (Savanna-like vegetation) in Northeast Brazil, especially in Piauí State. Recent advances toward the elucidation of fungal bioluminescence have contributed to the discovery of four genes (hisps, h3h, luz and cph) involved with the bioluminescence process, the so-called Caffeic Acid Cycle (CAC) and to develop biotechnological applications such autoluminescent tobacco plants and luciferase-based reporter genes. High-yield and -quality RNA-extraction methods are required for most of these purposes. Herein, four methods for RNA isolation from the mycelium of N. gardneri were evaluated: RNeasy® kit (QIAGEN), TRI+, TRI18G+, and TRI26G+. Highest RNA yield was observed for TRI18G+ and TRI26G+ methods, an increase of ~130% in comparison to the RNeasy® method and of ~40% to the TRI+ protocol. All the RNA samples showed good purity and integrity, except by gDNA contamination in RNA samples produced with the RNeasy® method. High quality of RNA samples was confirmed by successful cDNA synthesis and PCR amplification of the coding sequence of h3h gene, responsible for the hydroxylation of the precursor of fungal luciferin (3-hydroxyhispidin). Similarly, RT-qPCR amplification of ef-tu gene, related to the protein biosynthesis in the cell, was demonstrated from RNA samples. This is the first report of a reproducible, time-saving and low-cost optimized method for isolation of high-quality and -yield, DNA-free RNA from a bioluminescent fungus, but that can also be useful for other basidiomycetes.

Study of anesthetics for euthanasia in rats and mice: A systematic review and meta-analysis on the impact upon biological outcomes (SAFE-RM).

AIM: To summarize the knowledge on the effect of anesthetics employed right before euthanasia on biological outcomes. DATA SOURCE: A systematic review of the literature to find studies with isoflurane, ketamine, halothane, pentobarbital, or thiopental just before euthanasia of laboratory rats or mice. STUDY SELECTION: Controlled studies with quantitative data available. DATA EXTRACTION: The search, data extraction, and risk of bias (RoB) were performed independently by two reviewers using a structured form. For each outcome, an effect size (ES) was calculated relative to the control group. Meta-analysis was performed using robust variance meta-regression for hierarchical data structures, with adjustment for small samples. DATA SYNTHESIS: We included 20 studies with 407 biological outcomes (110 unique). RoB analysis indicated that 87.5% of the domains evaluated showed unclear risk, 2% high risk, and 10.5% low risk. The effect size for all anesthetics considered together was 0.99 (CI95% = 0.75-1.23; p < 0.0001). Sub-analyses indicate high effect sizes for pentobarbital (1.14; CI95% = 0.75-1.52; p < 0.0001), and isoflurane (1.01; CI95% = 0.58-1.44; p = 0.0005) but not for ketamine (1.49; CI95% = -7.95-10.9; p = 0.295). CONCLUSION: We showed that anesthetics interfere differently with the majority of the outcomes assessed. However, our data did not support the use of one anesthetic over others or even the killing without anesthetics. We conclude that outcomes cannot be compared among studies without considering the killing method. This protocol was registered at Prospero (CRD42019119520). FUNDING: There was no direct funding for this research.

Association of physical activity levels and the prevalence of COVID-19-associated hospitalization.

OBJECTIVES: We compared physical activity levels before the outbreak and quarantine measures with COVID-19-associated hospitalization prevalence in surviving patients infected with SARS-CoV-2. Additionally, we investigated the association of physical activity levels with symptoms of the disease, length of hospital stay, and mechanical ventilation. DESIGN: Observational, cross-sectional. METHODS: Between June 2020 and August 2020, we invited Brazilian survivors and fully recovered patients infected with SARS-CoV-2 to respond to an online questionnaire. We shared the electronic link to the questionnaire on the internet. We collected data about clinical outcomes (symptoms, medications, hospitalization, and length of hospital stay) and cofactors, such as age, sex, ethnicity, preexisting diseases, socioeconomic and educational, and physical activity levels using the International Physical Activity Questionnaire (IPAQ short version). RESULTS: Out of 938 patients, 91 (9.7%) were hospitalized due to COVID-19. In a univariate analysis, sex, age, and BMI were all associated with hospitalizations due to COVID-19. Men had a higher prevalence of hospitalization (66.6%, p = 0.013). Patients older than 65 years, obese, and with preexisting disease had a higher prevalence of COVID-19-related hospitalizations. In a multivariate regression model, performance of at least 150 min/wk (moderate) and/or 75 min/wk (vigorous) physical activity was associated with a lower prevalence of hospitalizations after adjustment for age, sex, BMI, and preexisting diseases (PR = 0.657; p = 0.046). CONCLUSIONS: Sufficient physical activity levels were associated with a lower prevalence of COVID-19-related hospitalizations. Performing at least 150 min a week of moderate-intensity, or 75 min a week of vigorous-intensity physical activity was associated with 34.3% reduction in prevalence.

Prevalence and predictors of treatment-resistant schizophrenia in a tertiary hospital in Northeast Brazil.

OBJECTIVE: To investigate epidemiological factors related to treatment-resistant schizophrenia (TRS) in Northeast Brazil, a region where data about mental health are still scarce. METHODS: This retrospective cross-sectional study included all patients with schizophrenia currently receiving treatment at the outpatient psychiatric clinic of a tertiary hospital in Northeast Brazil. They were divided into TRS and treatment-responsive groups, and epidemiological characteristics of both groups were compared. A logistic regression model investigated factors related to treatment resistance. RESULTS: Two hundred and five patients were included, 155 treatment-resistant and 50 treatment-responsive. The TRS group had higher use of benzodiazepines (36.1 vs. 18%, p = 0.017) and antiepileptics (36.8 vs. 8.0%, p < 0.001), antipsychotic polypharmacy (28.6 vs. 8%, p = 0.003) and suicide attempts (35.6 vs. 20%, p = 0.04). Age at onset was younger (19.7±7.3 vs. 24.6±8.6 years, p = 0.001) and CGI was higher in TRS (3.72±1.00 vs. 3.16±1.00, p = 0.001). In logistic regression, being married was a protector (odds ratio [OR] = 0.248, 95% confidence interval [95%CI] 0.091-0.679, p = 0.007) and younger age at onset was a predictor (OR = 1.076, 95%CI 1.034-1.120, p < 0.001) of treatment resistance. CONCLUSION: Early onset of disease was associated with more treatment resistance, while being married with less resistance. Clinicians should identify early predictors of resistance in order to reduce unfavorable outcomes.

Incidence of injuries in soccer players - mappingfoot: a prospective cohort study / Incidencia de lesiones en jugadores de fútbol - mappingfoot: un estudio de cohorte prospectivo / Incidência de lesões em jogadores de futebol - mappingfoot: um estudo de coorte prospectivo

ABSTRACT Introduction: Although the positive effects of physical activity on global health are well documented, sports practice is associated with a greater risk of injury; in professional soccer in particular, the risk is substantial. Objective: The primary objective of this study was to investigate the incidence of injuries among male athletes competing in the regional soccer championship. The secondary objective was to determine the prevalence of injuries. Methods: In this prospective cohort study, level of evidence II, the incidence and prevalence of injuries were assessed using an adapted version of the UEFA Champions League Study questionnaire. Results: This study included 310 male athletes from ten teams, aged 26.53±4.75 years, height 180.93±6.49 cm, and weight 79.32±8.29 kg, with a 4-month follow-up. Ninety-two injuries were recorded, representing a prevalence of 29.68% injuries. The body part most frequently injured was the lower limbs (86.9%). The main types of injuries were muscle tear/strain (37.0%), sprain/ligament (19.6%), and other injuries (14.1%). The injuries were mainly caused during run/sprint (33.7%), kick (12.0%) and jumping/landing (6.5%). The incidences of injuries were 15.88±8.57, 2.04±1.09, and 3.65±1.50 injuries/1000h of exposure during matches, training, and matches/training, respectively. Time-loss over the season was between 1 and 50 days, and the severity of the injuries was as follows: light (25%), minor (22.8%), moderate (43.5%) and severe (8.7%). Conclusion: This study suggests that there is a higher incidence of injuries during matches compared to training, among male regional soccer championship players. The lower limbs are the body part most affected, with a higher prevalence of rupture/strain in the thigh region, during running/sprinting. Level of evidence II; Prospective Cohort Study .

RESUMEN Introducción: Aunque los efectos positivos de la actividad física en la salud global estén bien documentados, la práctica deportiva está asociada a un riesgo mayor de lesiones; especialmente en el fútbol profesional, el riesgo es sustancial. Objetivo: El objetivo primario de este estudio fue investigar la incidencia de lesiones en atletas del sexo masculino que compiten en campeonatos regionales de fútbol. El resultado secundario fue determinar la prevalencia de lesiones. Métodos: En este estudio de cohorte prospectivo, nivel de evidencia II, la incidencia y la prevalencia de lesiones fueron evaluadas usando una versión adaptada del cuestionario de estudio de la Liga de Campeones de la UEFA. Resultados: Este estudio incluyó a 310 atletas del sexo masculino de 10 equipos, edad 26,53 ± 4,75 años, estatura 180,93 ± 6,49 cm y peso 79,32 ± 8,29 kg, durante 4 meses de acompañamiento. Se registraron 92 lesiones, lo que representa una prevalencia de 29,68%. La parte del cuerpo que tuvo lesiones más frecuentes fueron los miembros inferiores (86,9%). Los principales tipos de lesión fueron rotura/distensión muscular (37,0%), esguince/ligamento (19,6%) y otras lesiones (14,1%). Las lesiones fueron causadas principalmente durante carrera/sprint (33,7%), puntapié (12,0%) y salto/aterrizaje (6,5%). La incidencia de lesiones fue de 15,88 ± 8,57, 2,04 ± 1,09 y 3,65 ± 1,50 lesiones/1000 horas de exposición durante partidos, entrenamientos y partidos/entrenamientos, respectivamente. El tiempo de alejamiento en la temporada varió de 1 a 50 días, y la gravedad de las lesiones fue la siguiente: leve (25%), menor (22,8%), moderada (43,5%) y grave (8,7%). Conclusión: El presente estudio sugiere que existe mayor incidencia de lesiones durante los partidos en comparación con los entrenamientos entre jugadores del sexo masculino en campeonatos regionales de fútbol. Los miembros inferiores son la región más acometida, con mayor prevalencia de rotura/distensión en la región del muslo durante la carrera/sprint. Nivel de evidencia II, Estudio de cohorte prospectivo .

RESUMO Introdução: Embora os efeitos positivos da atividade física na saúde global sejam bem documentados, a prática esportiva está associada a um risco maior de lesões; especialmente no futebol profissional, o risco é substancial. Objetivo: O objetivo primário deste estudo foi investigar a incidência de lesões em atletas do sexo masculino que competem em campeonatos regionais de futebol. O objetivo secundário foi determinar a prevalência de lesões. Métodos: Neste estudo de coorte prospectivo, nível de evidência II, a incidência e a prevalência de lesões foram avaliados usando uma versão adaptada do questionário de estudo da Liga dos Campeões da UEFA. Resultados: Este estudo incluiu 310 atletas do sexo masculino de 10 equipes, com idade 26,53 ± 4,75 anos, estatura 180,93 ± 6,49 cm e peso 79,32 ± 8,29 kg, durante 4 meses de acompanhamento. Foram registradas 92 lesões, o que representa uma prevalência de 29,68%. A parte do corpo que teve lesões mais frequentes foram os membros inferiores (86,9%). Os principais tipos de lesão foram ruptura/distensão muscular (37,0%), entorse/ligamento (19,6%) e outras lesões (14,1%). As lesões foram causadas principalmente durante corrida/sprint (33,7%), chute (12,0%) e salto/aterrissagem (6,5%). A incidência de lesões foi de 15,88 ± 8,57, 2,04 ± 1,09 e 3,65 ± 1,50 lesões/1.000 horas de exposição durante jogos, treinamento e jogos/treinamento, respectivamente. O tempo de afastamento na temporada variou de 1 a 50 dias e a gravidade das lesões foi a seguinte: leve (25%), menor (22,8%), moderada (43,5%) e grave (8,7%). Conclusão: O presente estudo sugere que existe maior incidência de lesões durante os jogos em comparação com os treinos entre jogadores do sexo masculino em campeonatos regionais de futebol. Os membros inferiores são a região mais acometida, com maior prevalência de ruptura/distensão na região da coxa durante a corrida/sprint. Nível de evidência II; Estudo de coorte prospectivo .

Cardiac pathology in mucopolysaccharidosis I mice: Losartan modifies ERK1/2 activation during cardiac remodeling.

Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disorder caused by mutations in the IDUA gene, that codifies the alpha-L-iduronidase enzyme, which deficiency leads to storage of glycosaminoglycans, with multiple clinical manifestations. One of the leading causes of death in MPS I patients are cardiac complications such as cardiac valve thickening, conduction abnormalities, myocardial dysfunction, and cardiac hypertrophy. The mechanism leading to cardiac dysfunction in MPS I is not entirely understood. In a previous study, we have demonstrated that losartan and propranolol improved the cardiac function in MPS I mice. Thus, we aimed to investigate whether the pathways influenced by these drugs may modulate the cardiac remodeling process in MPS I mice. According to our previous observation, losartan and propranolol restore the heart function, without altering valve thickness. MPS I mice presented reduced activation of AKT and ERK1/2, increased activity of cathepsins, but no alteration in metalloproteinase activity was observed. Animals treated with losartan showed a reduction in cathepsin activity and restored ERK1/2 activation. While both losartan and propranolol improved heart function, no mechanistic evidence was found for propranolol so far. Our results suggest that losartan or propranolol could be used to ameliorate the cardiac disease in MPS I and could be considered as adjuvant treatment candidates for therapy optimization.

Exercise training modalities for heart transplant recipients: a systematic review and network meta-analysis protocol.

INTRODUCTION: Heart transplantation is the gold standard treatment for selected patients with end-stage heart failure. Although this procedure can improve quality and prolong life expectancy, several of these patients persist with decreased exercise tolerance. Evidence suggests that exercise training can bring multifactorial benefits to heart transplant (HTx) recipients. However, it is unclear that exercise modality should be preferred. Therefore, the aim of this systematic review and network meta-analysis is to compare the efficacy and safety of different training modalities in HTx recipients. METHODS AND ANALYSIS: We will perform a comprehensive literature search in PubMed/MEDLINE, Embase, The Cochrane Library, CINAHL, Scopus, SportDISCUS, Web of Science Core Collection and PEDro from inception until November 2020. Two registries (ClinicalTrials.gov and REBEC) will also be searched for potential results in unpublished studies. There will be no restriction on language, date of publication, publication status or sample size. We will include randomised controlled trials enrolling adult HTx recipients with the presence of at least one exercise training group, which might be compared with another training modality and/or a non-exercise control group for a minimum of 4 weeks of intervention. The primary outcomes will be peak oxygen consumption and occurrence of adverse events. As secondary outcomes, the interaction between pulmonary ventilation, pulmonary perfusion and cardiac output, oxygen uptake efficiency slope, heart rate response, oxygen pulse, peak blood pressure and peak subjective perception of effort. In addition, we will evaluate the 6 min walking distance, health-related quality of life, endothelial function, muscle strength, body fat percentage and lean mass. Risk of bias will be assessed using the Cochrane RoB V.2.0 tool, and we plan to use the Confidence in Network Meta-Analysis tool to assess confidence in the results. All materials (raw data, processed data, statistical code and outputs) will be shared in a public repository. ETHICS AND DISSEMINATION: Given the nature of this study, no ethical approval will be required. We believe that the findings of this study may show which is the most efficacious and safe physical training modality for HTx recipients. The completed systematic review and network meta-analysis will be submitted to a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42020191192.

Intradialytic training in patients with end-stage renal disease: a systematic review and meta-analysis of randomized clinical trials assessing the effects of five different training interventions.

OBJECTIVE: Patients with end-stage renal disease (ESRD) undergoing hemodialysis may have reduced dialysis adequacy (Kt/V), low cardiorespiratory fitness, and worse prognosis. Different types of intradialytic training (IDT) may serve as an adjunct therapy for the management of the ESRD. This systematic review and meta-analysis aimed to assess the impact of different types of IDT on clinical outcomes and functional parameters in ESRD. METHODS: PubMed, Embase, CINAHL, Cochrane CENTRAL, Scopus, SPORTDiscus, and Google Scholar were searched for randomized clinical trials in adult patients with ESRD which compared IDT with usual care (UC), without language restrictions and published up to July 2019; a handsearch of references was also performed. Certainty of evidence was assessed using GRADE, and risk of bias in primary studies with the RoB 1.0 tool. RESULTS: Fifty studies were included (n = 1757). Compared to UC, aerobic IDT improved Kt/V (WMD = 0.08), VO2peak (WMD = 2.07 mL/kg/min), 6-minute walk test (6MWT) distance (64.98 m), reduced systolic blood pressure (- 10.07 mmHg) and C-reactive protein (- 3.28 mg/L). Resistance training increased 6MWT distance (68.50 m). Combined training increased VO2peak (5.41 mL/kg/min) and reduced diastolic blood pressure (- 5.76 mmHg). Functional electrostimulation (FES) and inspiratory muscle training (IMT) improved 6MWT distance (54.14 m and 117.62 m, respectively). There was no impact on total cholesterol, interleukin-6, or hemoglobin levels. There was no difference in incidence of adverse events between the IDT and control groups. The certainty of evidence was variable according to the GRADE scale, with most outcomes rated very low certainty. The risk of bias assessment of primary studies showed unclear risk in most. CONCLUSIONS: Aerobic, resistance, and combined training during hemodialysis, as well as FES and IMT, demonstrated to be effective for the treatment of the patient with ESRD. Our data should be interpreted in light of the unclear risk of bias of most evaluated articles and the low to very low certainty of evidence for evaluated outcomes. PROSPERO REGISTRATION ID: CRD42017081338. DATA SHARING REPOSITORY: https://osf.io/fpj54/.