Antifungal, molecular docking and cytotoxic effect of the essential oil of Cymbopogon citratus (DC) Stapf. and Cymbopogon nardus (L.) Rendle against Candida albicans.

Brazil is renowned for its extensive plant biodiversity, with emphasis on Cymbopogon, C. citratus and C. nardus, with broad antimicrobial potential. Candidemias caused by Candida albicans are highly prevalent in immunosuppressed individuals and are associated with infections by biofilms on medical devices. The aim of this study was to evaluate the antimicrobial potential of essential oils C. citratus and C. nardus against C. albicans in planktonic and biofilm forms. Essential oils were obtained by hydrodistillation and chemical composition evaluated by GC-FID and GC-MS. The minimum inhibitory concentration was determined by the broth microdilution method and the synergy effect of essential oils and amphotericin B were evaluated by the checkerboard test. Biofilm activity was determined by the XTT assay. Cytotoxicity assays performed with VERO cells and molecular docking were performed to predict the effect of oil interaction on the SAP-5 enzyme site. The results showed activity of essential oils against planktonic cells and biofilm of C. albicans. Furthermore, the oils had a synergistic effect, and low cytotoxicity. Molecular docking showed interaction between Cadinene, Caryophyllen oxide, Germacrene D with SAP-5. The results indicate that Cymbopogon spp. studied are anti-Candida, with potential for further application in therapy against infections caused by C. albicans.

Exploring the osteogenic potential of semisynthetic triterpenes from Combretum leprosum: An in vitro and in silico study.

Combretum leprosum Mart. is a plant of the Combretaceae family, widely distributed in the Northeast region of Brazil, popularly used as an anti-inflammatory agent, and rich in triterpenes. This study evaluated in vitro and in silico potential osteogenic of two semisynthetic triterpenes (CL-P2 and CL-P2A) obtained from the pentacyclic triterpene 3ß,6ß,16ß-trihydroxylup-20(29)-ene (CL-1) isolated from C. leprosum. Assays were carried out in cultured murine osteoblasts (OFCOL II), first investigating the possible toxicity of the compounds on these cells through viability assays (MTT). Cell proliferation and activation were investigated by immunohistochemical evaluation of Ki-67, bone alkaline phosphatase (ALP) activity, and mineralization test by Von Kossa. Molecular docking analysis was performed to predict the binding affinity of CL-P2 and CL-P2A to target proteins involved in the regulation of osteogenesis, including: bone morphogenetic protein 2 (BMP-2), proteins related to Wingless-related integration (WNT) pathway (Low-density lipoprotein receptor-related protein 6-LRP6 and sclerostin-SOST), and receptor activator of nuclear factor (NF)-kB-ligand (RANK-L). Next, Western Blot and immunofluorescence investigated BMP-2, WNT, RANK-L, and OPG protein expressions in cultured murine osteoblasts (OFCOL II). None of the CL-P2 and CL-P2A concentrations were toxic to osteoblasts. Increased cell proliferation, ALP activity, and bone mineralization were observed. Molecular docking assays demonstrated interactions with BMP-2, LRP6, SOST, and RANK-L/OPG. There was observed increased expression of BMP-2, WNT, and RANK-L/OPG proteins. These results suggest, for the first time, the osteogenic potential of CL-P2 and CL-P2A.

Development of silanized bacterial cellulose aerogels for the incorporation of natural oils with healing properties: Copaiba (Copaifera officinalis), bourbon geranium (Pelargonium X ssp.) essential oils and buriti (Mauritia flexuosa) vegetable oil.

Bacterial cellulose (BC) represents a promising biomaterial, due to its unique and versatile properties. We report, herein, on purposely-designed structural modifications of BC that enhance its application as a wound dressing material. Chemical modification of the functional groups of BC was performed initially to introduce a hydrophobic/oleophilic character to its surface. Specifically, silanization was carried out in an aqueous medium using methyltrimethoxisilane (MTMS) as the silanizing agent, and aerogels were subsequently prepared by freeze-drying. The BC-MTMS aerogel obtained displayed a highly porous (99 %) and lightweight structure with an oil absorption capacity of up to 52 times its dry weight. The XRD pattern indicated that the characteristic crystallographic planes of the native BC were maintained after the silanization process. Thermal analysis showed that the thermal stability of the BC-MTMS aerogel increased, as compared to the pure BC aerogel (pBC). Moreover, the BC-MTMS aerogel was not cytotoxic to fibroblasts and keratinocytes. In the second step of the study, the incorporation of natural oils into the aerogel's matrix was found to endow antimicrobial and/or healing properties to BC-MTMS. Bourbon geranium (Pelargonium X ssp.) essential oil (GEO) was the only oil that exhibited antimicrobial activity against the tested microorganisms, whereas buriti (Mauritia flexuosa) vegetable oil (BVO) was non-cytotoxic to the cells. This study demonstrates that the characteristics of the BC structure can be modified, while preserving its intrinsic features, offering new possibilities for the development of BC-derived materials for specific applications in the biomedical field.

National survey regarding obstetricians' perspective of obstetric emergencies in Brazil.

INTRODUCTION: The maternal mortality rate in developing countries, such as Brazil, has significantly increased since 2020. Obstetric Emergencies (OE) account for 72.5% of these deaths. A national survey was conducted in Brazil to evaluate how gynecologists and obstetricians deal with OE and identify the main difficulties regarding theoretical/practical knowledge and structural resources. METHODS: An electronic questionnaire assessing resource availability, health teams, institutional protocols, and provision of OE training courses was completed by Brazilian obstetricians. RESULTS: More than 90 % of the questionnaire respondents reported treating a pregnant and/or puerperal patient with severe morbidity and that their health network has human resources, trained professionals, and structural resources required for this type of care. However, few respondents participate in continuing education programs (36 %) or specific training for the medical team (61.41 %). The implementation rates of obstetric risk identification protocols (33.09 %), a rapid response team (46.54 %), and boxes and emergency cart assembly teams (71.68 %) were determined. CONCLUSION: A high Maternal Mortality Ratio (MMR) may be related to disorganized healthcare systems, low implementation of risk classification protocols for the care of severe maternal and fetal conditions, and lack of access to continued/specific training programs. The Brazilian MMR is multifactorial. According to obstetricians, Brazilian health services include care teams, essential medications, obstetric centers, and clinical analysis laboratories, though they lack systematized processes and permanent professional training for qualified care of OE.

What exercise programme is the most appropriate to mitigate anterior cruciate ligament injury risk in football (soccer) players? A systematic review and network meta-analysis.

OBJECTIVES: To examine the effectiveness of different exercise-based interventions to mitigate the risk of anterior cruciate ligament injury in football players, and to determine which is the most appropriate for them, specifically for female football players. DESIGN: Four databases were accessed in July 2023 using the keywords football, soccer, athletic injuries, anterior cruciate ligament, knee injuries, injury prevention, exercise-based programme, and risk factor. METHODS: Randomised controlled trials that evaluated any exercise-based injury prevention intervention compared with a control group on the prevention of anterior cruciate ligament injury in football players were included. RESULTS: Eleven studies were included. Data were presented as logarithm hazard ratio, credible intervals and standard deviation. FIFA 11+ was the most effective in reducing anterior cruciate ligament injury risk in football players (logarithm hazard ratio = -1.23 [95% credible intervals: -2.20, -0.35]; SD = 0.47), followed by the Knäkontroll programme (logarithm hazard ratio = -0.76 [95% credible intervals: -1.60, -0.03]; standard deviation = 0.42). For females, only Knäkontroll had a significant impact on reducing the risk of anterior cruciate ligament injury (logarithm hazard ratio = -0.62 [95% credible intervals: -1.71, 0.62]; standard deviation = 0.58). CONCLUSIONS: Our results support the use of FIFA 11+ and Knäkontroll to mitigate injury incidence at overall level. However, the effectiveness of these interventions changed when adjusting for females. Knäkontroll is postulated as the programme with the greatest preventive nature, although these results should be interpreted with caution due to the lack of the sample.

Unveiling the strong positive relationship: Maternal characteristics and neonatal outcomes in the Better Outcomes in Labour Difficulty (BOLD) study - a secondary analysis validating neonatal near miss classification.

Background: The near miss concept, denoting near collisions between aircraft, originated in aeronautics, but has recently been transferred to the neonatal context as a way of evaluating the quality of health services for newborns, especially in settings with reduced child mortality. However, there is yet no consensus regarding the underlying criteria. The most common indicators used to assess health care quality include mortality (maternal and neonatal) and life-threatening conditions. Using the World Health Organization (WHO) Better Outcomes in Labour Difficulty (BOLD) prospective cohort study data set, we conducted a secondary analysis to validate the near miss concept and explore the association between maternal and neonatal outcomes. Methods: We studied 10 203 singleton mothers treated between December 2014 and November 2015 in nine Nigerian and four Ugandan hospitals. We validated the near miss concept by testing the diagnostic accuracy (sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and odds ratio (OR)) using death as the reference variable and calculating the maternal and neonatal case fatality rates. We performed ordinal and binomial logistic regression, with the independent variables being those that had P < 0.1 in the univariate analyses. We considered the significance level of 5%. Results: We validated the neonatal near miss concept using the BOLD study data. We observed maternal and neonatal case fatality rates of 70.2% and 6.5%, with an increasing severity relationship between maternal and neonatal outcomes (P < 0.05). Ordinal logistic regression showed that gestational age <37 or >41 weeks and <8 antenatal consultations were related to a higher risk of neonatal severe outcomes, while maternal age between 30 and 34 years functioned as a protective factor against severe neonatal outcomes (SNO). Binomial logistic regression showed gestational age <37(OR = 1.46; 95% confidence interval (CI) = 1.07-1.94) or >41 weeks (OR = 2.26; 95% CI = 1.55-3.20), low educational level (OR = 1.76; 95% CI = 1.12-2.69), overweight/obesity (OR = 1.23; 95% CI = 1.02-1.47), one previous cesarean section (OR = 1.90; 95% CI = 1.36-2.61), one previous abortion (OR = 1.25; 95% CI = 1.00-1.56), and previous chronic condition (OR = 1.83; 95% CI = 1.37-2.41) were risk factors for SNO. Conclusions: The neonatal near miss concept could be used as a parameter for analysis in different health systems, to ensure that measuring of neonatal severity is comparable across health care units. In this analysis, we observed a progressive association between maternal severity and the severity of the newborns' outcomes.

Optimal Dose and Type of Physical Activity to Improve Glycemic Control in People Diagnosed With Type 2 Diabetes: A Systematic Review and Meta-analysis.

BACKGROUND: The optimal dose or type of physical activity to control glycosylated hemoglobin (HbA1c) in people with diabetes remains unknown. Current guidelines do not include consideration of baseline HbA1c for activity prescription. PURPOSE: To examine the dose-response relationship between physical activity and HbA1c (%) in individuals with type 2 diabetes. DATA SOURCES: A systematic search was performed in Embase, MEDLINE, Scopus, CINAHL, SPORTDiscus, and Web of Science. STUDY SELECTION: We included trials that involved participants diagnosed with type 2 diabetes that included any type of physical activity as intervention. DATA EXTRACTION: Pre- and postintervention HbA1c data, population and interventions characteristics, and descriptive statistics were collected to calculate change scores for each study arm. DATA SYNTHESIS: We used Bayesian random-effects meta-analyses to summarize high-quality evidence from 126 studies (6,718 participants). The optimal physical activity dose was 1,100 MET min/week, resulting in HbA1c reductions, ranging from -1.02% to -0.66% in severe uncontrolled diabetes, from -0.64% to -0.49% in uncontrolled diabetes, from -0.47% to -0.40% in controlled diabetes, and from -0.38% to -0.24% in prediabetes. LIMITATIONS: The time required to achieve these HbA1c reductions could not be estimated due to the heterogeneity between interventions' duration and protocols and the interpersonal variability of this outcome. CONCLUSIONS: The result of this meta-analysis provide key information about the optimal weekly dose of physical activity for people with diabetes with consideration of baseline HbA1c level, and the effectiveness of different types of active interventions. These results enable clinicians to prescribe tailored physical activity programs for this population.

Optimal dose and type of physical activity to improve functional capacity and minimise adverse events in acutely hospitalised older adults: a systematic review with dose-response network meta-analysis of randomised controlled trials.

OBJECTIVE: To identify the optimal dose and type of physical activity to improve functional capacity and reduce adverse events in acutely hospitalised older adults. DESIGN: Systematic review and Bayesian model-based network meta-analysis. DATA SOURCES: Four databases were searched from inception to 20 June 2022. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials that assessed the effectiveness of a physical activity-based intervention on at least one functional outcome in people aged ≥50 years hospitalised due to an acute medical condition were included. Pooled effect estimates (ie, standardised mean differences for functional capacity and the ratio of means for adverse events) were calculated using random treatment effects network meta-analysis models. RESULTS: Nineteen studies (3842 participants) met the inclusion criteria. Approximately 100 Metabolic Equivalents of Task per day (METs-min/day) (~40 min/day of light effort or ~25 min/day of moderate effort activities) was the minimal dose to improve the functional capacity of acute hospitalised older adults (standardised mean difference (SMD)=0.28, 95% credible interval (CrI) 0.01 to 0.55). The optimal dose was estimated at 159 METs-min/day (~70 min/day of light effort or ~40 min/day of moderate effort activities; SMD=0.41, 95% CrI 0.08 to 0.72). Ambulation was deemed the most efficient intervention, and the optimal dose was reached at 143 METs-min/day (~50 min/day of slow-paced walking; SMD=0.76, 95% CrI 0.35 to 1.16), showing a high evidential power (87.68%). The minimal effective ambulation dose was estimated at 74 METs-min/day (~25 min/day of slow-paced walking; SMD=0.25, 95% CrI 0.01 to 0.41). Physical activity interventions resulted in a decrease in the rate of adverse events compared with usual care at discharge (ratio of means=0.96, 95% CrI 0.95 to 0.97; median time 7 days). CONCLUSIONS: This meta-analysis yielded low to moderate evidence supporting the use of in-hospital supervised physical activity programmes in acutely hospitalised older adults. As little as ~25 min/day of slow-paced walking is sufficient to improve functional capacity and minimise adverse events in this population. TRIAL REGISTRATION NUMBER: PROSPERO CRD42021271999.

Exercise to treat psychopathology and other clinical outcomes in schizophrenia: A systematic review and meta-analysis.

BACKGROUND: Psychopathology and side effects of antipsychotic drugs contribute to worsening physical health and long-term disability, and increasing the risk of mortality in these patients. The efficacy of exercise on these factors is not fully understood, and this lack of knowledge may hamper the routine application of physical activity as part of the clinical care of schizophrenia. AIMS: To determine the effect of exercise on psychopathology and other clinical markers in patients with schizophrenia. We also looked at several moderators. METHOD: MEDLINE, Web of Science, Scopus, CINAHL, SPORTDiscus, PsycINFO, and Cochrane Library databases were systematically searched from inception to October 2022. Randomized controlled trials of exercise interventions in patients 18-65 years old diagnosed with schizophrenia disorder were included. A multilevel random-effects meta-analysis was conducted to pool the data. Heterogeneity at each level of the meta-analysis was estimated via Cochran's Q, I2, and R2. RESULTS: Pooled effect estimates from 28 included studies (1,460 patients) showed that exercise is effective to improve schizophrenia psychopathology (Hedges' g = 0.28, [95% CI 0.14, 0.42]). Exercise presented stronger effects in outpatients than inpatients. We also found exercise is effective to improve muscle strength and self-reported disability. CONCLUSIONS: Our meta-analysis demonstrated that exercise could be an important part in the management and treatment of schizophrenia. Considering the current evidence, aerobic and high-intensity interval training exercises may provide superior benefits over other modalities. However, more studies are warranted to determine the optimal type and dose of exercise to improve clinical outcomes in people with schizophrenia.

Functional impairment and post-stroke depression: a 6-month longitudinal study.

BACKGROUND: In recent decades, considerable advances have been made in the treatment of acute ischemic stroke (IS) and its prevention. However, even after treatment, approximately two-thirds of patients with IS have some degree of disability that requires rehabilitation, along with an increased possibility of developing psychiatric disorders, particularly depression. OBJECTIVE: To determine the predictors of post-stroke depression in a 6-month period in patients with IS. METHOD: Ninety-seven patients with IS without previous depression were included in the study. The study protocol was applied during hospitalization and at 30, 90, and 180 days after hospital discharge. A binary logistic regression was then used. Age, sex, marital status, occupation, education, thrombolysis, National Institute of Health Stroke Scale, modified Rankin scale (mRS) score, Barthel index, and Mini-Mental State Examination score were included as independent variables. RESULTS: Of the 97 patients, 24% of patients developed post-stroke depression. In the longitudinal follow-up, an mRS score of > 0 was the lone significant predictor of depression development (odds ratio = 5.38; 95% confidence interval: 1.25-23.12; p < 0.05). CONCLUSION: Our results showed that in patients without previous depression, functional impairment of any degree has a 5-fold greater chance of leading to depression development in the first 6 months post-stroke as compared to that in patients without functional impairment.

Pentacyclic triterpene-loaded emulsion stabilized by Agaricus blazei Murill polysaccharides: Factorial design and cytoprotection study.

In this study, pentacyclic triterpene-loaded emulsions were stabilized by polysaccharides from Agaricus blazei Murill mushroom (PAb). The drug-excipient compatibility results by Fourier Transform Infrared Spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC) showed the absence of physicochemical incompatibilities. The use of these biopolymers at 0.75 % led to obtaining emulsions with droplets smaller than 300 nm, moderate polydispersity, and ζ-potential >30 mV in modulus. The emulsions presented high encapsulation efficiency, suitable pH for topical application, and absence of macroscopic signs of instability during 45 days. Morphological analysis suggested the deposition of thin layers of PAb around the droplets. The encapsulation of pentacyclic triterpene in emulsions, stabilized by PAb, improved the cytocompatibility of this drug against PC12 and murine astrocyte cells. There was a reduction in cytotoxicity, which resulted in a lower accumulation of intracellular reactive oxygen species and maintenance of the mitochondrial transmembrane potential. Based on these results, it is estimated that PAb are promising biopolymers for the emulsions' stabilization by improving their physicochemical and biological properties.

Clinical Outcomes of Arthroscopic Revision Rotator Cuff Repair.

Aims: Multiple studies have shown excellent clinical results in primary rotator cuff repairs; however, not much evidence is available in the literature on the outcomes of arthroscopic revision rotator cuff repairs. The purpose of this study was to report a cohort of patients who underwent revision arthroscopic rotator cuff repair and identify factors that may influence its outcomes. Methods: We examined a cohort of 62 patients which underwent revision arthroscopic rotator cuff repair in a single UK institution with a minimum of 24 months follow-up. Active shoulder movements including forward flexion, abduction and external rotation were evaluated, as well as Oxford Shoulder Score (OSS). Further subgroup analysis was performed looking of the effects of age, size of tear, obesity and diabetes mellitus had on clinical outcomes. Results: 59 patients were available for final review. 39 male and 23 were female. The mean age was 64 years. Overall, significant improvements were seen in terms of OSS (p < 0.05), active forward flexion (p < 0.05), active abduction (p < 0.05) and active external rotation (p < 0.05). Our study showed that a significant proportion of patients undergoing arthroscopic revision rotator cuff repair achieve good outcomes. Repairing small- and medium-size tears was successful, diabetics had no post-operative improvements, obese patients achieved significant improvement in range of movement and age was not a predictor of surgical success. Conclusion: Overall, arthroscopic revision surgery is a successful option; however, appropriate patient selection and counselling is paramount.

Low re-dislocation rate following Bereiter trochleoplasty for recurrent patellar instability with severe trochlear dysplasia.

PURPOSE: Trochlear dysplasia is an independent risk factor for recurrent patellar instability with evidence demonstrating its presence in up to 85% of patients with patellar instability. Severe trochlear dysplasia can be treated with trochleoplasty to improve engagement of the patella in the trochlear groove and prevent future dislocations. The aim of this study was to determine the clinical outcome of Bereiter trochleoplasty in patients with recurrent patellar instability and severe trochlear dysplasia. METHODS: This was a retrospective case series of all trochleoplasties performed in our institution from 2008-2019. All clinical records and pre-operative MRI scans were reviewed to assess for trochlear dysplasia, tibial tuberosity to trochlear groove distance (TTTG) and patella height using patella trochlear index (PTI). Trochlear dysplasia was classified using Dejour classification. Incidence of re-dislocation, infection, arthrofibrosis, chondral necrosis and re-operation were recorded. All patients were invited to complete a post-operative visual analog score for pain (VAS-P) and Banff Patella Instability Instrument (BPII). RESULTS: Fifty-eight trochleoplasties were performed in fifty patients during this period. All trochleoplasties were combined with additional procedures. 93% had concomitant medial patellofemoral ligament (MPFL) reconstructions and 47% had tibial tuberosity transfer. The mean follow-up period was 36.8 months. The rate of dislocation and arthrofibrosis were 5% each. There were no chondral necrosis or nonunion. The mean post-operative BPII was 58.4 and VAS-P was 30.4. CONCLUSIONS: Bereiter trochleoplasty, often combined with MPFL reconstruction and/or tibial tuberosity transfer results in low re-dislocation and complication rate. LEVEL OF EVIDENCE: IV.

Effects of physical exercise on aerobic capacity and quality oflife in patients diagnosed with asthma: A systematic review andmeta-analysis / Efectos del ejercicio físico en la capacidad aeróbica y la calidad de vida enpacientes diagnosticados con asma: revisión sistemática y meta-análisis

Introduction: Nowadays, asthma is a disabling disease with no cure, and the development of effective non-pharmacological treatments which can alleviate side effects of drugs and pathological symptoms is urgent. Some studies have shown that physical exercise may have beneficial effects in patients with asthma, but results were controversial and inconsistent. More evidence is needed to ensure exercise as possible effective treatment in people with asthma.Objectives: To examine the effects of physical exercise on aerobic capacity and quality of life in patients with asthma. Also, we analyze the possible moderation effects of the selected covariates. As a final aim, we verified if a correlation exists between benefits on aerobic capacity and those obtained on quality of life.Material and method: We followed the PRISMA statement to search for randomized controlled trials that used physical exercise as intervention to improve aerobic capacity or quality of life in patients diagnosed with asthma. After data extraction, we conducted a random-effects meta-analysis model with moderation analysis. Then, we inspected the correlation between both outcomes through a multivariate approach. Finally, we performed some additional analyses: methodological quality analysis through the PEDro scale, publication bias analysis through funnel asymmetry tests and funnel plot visualization, and sensitivity analyses by outliers and influential cases detection.(AU)

Introducción: Actualmente, el asma es una enfermedad incapacitante sin cura, y urge el desarrollo de tratamientos no farmacológicos eficaces que puedan aliviar los efectos secundarios de los fármacos y los síntomas patológicos. Algunos estudios han demostrado que el ejercicio físico puede tener efectos beneficiosos en pacientes con asma, pero los resultados fueron controvertidos e inconsistentes. Se necesita más evidencia para garantizar que el ejercicio sea un posible tratamiento eficaz en personas con asma. Objetivos: Examinar los efectos del ejercicio físico sobre la capacidad aeróbica y la calidad de vida en pacientes con asma. Además, analizamos los posibles efectos de moderación de las covariables seleccionadas. Como objetivo final, verificamos si existe una correlación entre los beneficios en la capacidad aeróbica y los obtenidos sobre la calidad de vida.Material y método: Seguimos la declaración PRISMA para buscar ensayos controlados aleatorios que utilizaran el ejercicio físico como intervención para mejorar la capacidad aeróbica o la calidad de vida en pacientes con diagnóstico de asma. Después de la extracción de datos, realizamos un modelo de meta-análisis de efectos aleatorios con análisis de moderación. Luego, inspeccionamos la correlación entre ambos resultados a través de un enfoque multivariado. Finalmente, realizamos algunos análisis adicionales: análisis de calidad metodológica a través de la escala PEDro, análisis de sesgos de publicación a través de pruebas de asimetría de embudo y visualización de gráficos de embudo, y análisis de sensibilidad mediante la detección de ‘outliers’ y de casos influyentes. Resultados: El ejercicio físico tuvo efectos beneficiosos en la capacidad aeróbica y en la calidad de vida. Ninguna de las covariables presentó un efecto moderador significativo. Encontramos una correlación positiva entre los efectos del ejercicio sobre la capacidad aeróbica y los provocados en la calidad de vida.(AU)

Cancer survivor inspiratory muscle training: systematic review and Bayesian meta-analysis.

BACKGROUND: The long-term impact of cancer treatment is associated with respiratory dysfunction and physical fitness impairment. Although inspiratory muscle training (IMT) has been shown as an effective exercise therapy in cancer survivors, there is no evidence on the optimal dose, application moment nor specific population effects of this intervention. The main objective of this meta-analysis is to analyse the effects of IMT on pulmonary function, physical fitness and quality of life (QoL) in cancer survivors. METHODS: This systematic review and meta-analysis was preregistered in the International Prospective Register of Systematic Reviews (PROSPERO) register and conducted according to the Preferred Reporting for Systematic Reviews and Meta-analysis statement. We used a Bayesian multilevel random-effects meta-analysis model to pool the data. Multilevel metaregression models were used to examine the conditional effects of our covariates. Convergence and model fit were evaluated through specific model parameters. Sensitivity analyses removing influential cases and using a frequentist approach were carried out. RESULTS: Pooled data showed that IMT intervention is effective to improve pulmonary function (standardised mean difference=0.53, 95% credible interval 0.13 to 0.94, SE=0.19). However, IMT did not present statistically significant results on physical fitness and QoL. Metaregression analyses found that the type of cancer, the moment of application and the evaluation tool used had significant moderation effects on pulmonary function. CONCLUSION: IMT could be an important part in the management of side effects suffered by cancer survivors. Considering the current evidence, this intervention is highly recommended in patients diagnosed with oesophageal and lung cancers. IMT may provide superior benefits before the biological treatment and after the surgery. PROSPERO REGISTRATION NUMBER: 304909.

Optimal Number of Steps per Day to Prevent All-Cause Mortality in People With Prediabetes and Diabetes.

OBJECTIVE: We aimed to examine the dose-response associations between the number of steps per day and all-cause mortality among adults with prediabetes and diabetes. RESEARCH DESIGN AND METHODS: This prospective study used data from 1,194 U.S. adults with prediabetes and 493 with diabetes for whom accelerometer-derived steps per day could be retrieved. Mortality was ascertained through the National Death Index (February 25, 2019). Splines were used to assess the dose-response associations between steps per day and all-cause mortality. RESULTS: Over ∼9 years of follow-up, 200 adults with prediabetes and 138 with diabetes died. Nonlinear associations akin to an L shape were observed. We estimated an optimal dose of ∼10,000 steps per day to reduce the risk of all-cause mortality for both individuals with prediabetes and those with diabetes. CONCLUSIONS: Accumulating more steps per day up to ∼10,000 steps per day may lower the risk of all-cause mortality of adults with prediabetes and diabetes.

Biological and Molecular Docking Evaluation of a Benzylisothiocyanate Semisynthetic Derivative From Moringa oleifera in a Pre-clinical Study of Temporomandibular Joint Pain.

Objective: Moringa oleifera possesses multiple biological effects and the 4-[(4'-O-acetyl-α-L- rhamnosyloxy) benzyl] isothiocyanate accounts for them. Based on the original isothiocyanate molecule we obtained a semisynthetic derivative, named 4-[(2',3',4'-O-triacetyl-α-L-rhamnosyloxy) N-benzyl] hydrazine carbothioamide (MC-H) which was safe and effective in a temporomandibular joint (TMJ) inflammatory hypernociception in rats. Therefore, considering that there is still a gap in the knowledge concerning the mechanisms of action through which the MC-H effects are mediated, this study aimed to investigate the involvement of the adhesion molecules (ICAM-1, CD55), the pathways heme oxygenase-1 (HO-1) and NO/cGMP/PKG/K+ ATP, and the central opioid receptors in the efficacy of the MC-H in a pre-clinical study of TMJ pain. Methods: Molecular docking studies were performed to test the binding performance of MC-H against the ten targets of interest (ICAM-1, CD55, HO-1, iNOS, soluble cGMP, cGMP-dependent protein kinase (PKG), K+ ATP channel, mu (µ), kappa (κ), and delta (δ) opioid receptors). In in vivo studies, male Wistar rats were treated with MC-H 1 µg/kg before TMJ formalin injection and nociception was evaluated. Periarticular tissues were removed to assess ICAM-1 and CD55 protein levels by Western blotting. To investigate the role of HO-1 and NO/cGMP/PKG/K+ ATP pathways, the inhibitors ZnPP-IX, aminoguanidine, ODQ, KT5823, or glibenclamide were used. To study the involvement of opioid receptors, rats were pre-treated (15 min) with an intrathecal injection of non-selective inhibitor naloxone or with CTOP, naltrindole, or norbinaltorphimine. Results: All interactions presented acceptable binding energy values (below -6.0 kcal/mol) which suggest MC-H might strongly bind to its molecular targets. MC-H reduced the protein levels of ICAM-1 and CD55 in periarticular tissues. ZnPP-IX, naloxone, CTOP, and naltrindole reversed the antinociceptive effect of MC-H. Conclusion: MC-H demonstrated antinociceptive and anti-inflammatory effects peripherally by the activation of the HO-1 pathway, as well as through inhibition of the protein levels of adhesion molecules, and centrally by µ and δ opioid receptors.

Whole cells of recombinant CYP153A6-E. coli as biocatalyst for regioselective hydroxylation of monoterpenes.

Optimized recombinant whole cells of E. coli bearing CYP153A6 were employed for catalyzing the hydroxylation of different monoterpene derivatives. In most cases, high selectivity was observed with exclusive hydroxylation of the allylic methyl group bound to the aliphatic ring. In the case of (R)- and (S)-carvone, hydroxylation occurred also on the other allylic methyl group, although to a lesser extent. Biotransformations carried out in fed-batch mode on (S)-limonene and α-terpineol showed that recombinant whole cells retained activity for at least 24 h, allowing for the recovery of 3.25 mg mL-1 of (S)-perillyl alcohol and 5.45 mg mL-1 of 7-hydroxy-α-terpineol, respectively.

Replacing Sedentary Behavior With Physical Activity of Different Intensities: Implications for Physical Function, Muscle Function, and Disability in Octogenarians Living in Long-Term Care Facilities.

BACKGROUND: We investigated the associations of replacing sedentary behavior (SB) with physical activity of different intensities on the physical function of octogenarians living in long-term care facilities. METHODS: This pooled study recruited 427 older adults aged 80 years and older (69.1% female; body mass index: 27.53). For 345 participants who provided valid data, we assessed device-measured time spent in SB, light-intensity physical activity (LIPA), and moderate to vigorous physical activity (MVPA). We assessed lower limb physical function, strength, mobility, and disability. We used compositional data analysis to investigate the associations of replacing SB with physical activity on the outcomes. RESULTS: Reallocation of SB to LIPA and MVPA was associated with a higher number of 30-second Chair Stand cycles (LIPA: +0.21, MVPA: +1.81; P < .001), greater peak force (LIPA: +11.96 N, MVPA: +27.68 N; P < .001), peak power (LIPA: +35.82 W, MVPA: +92.73 W; P < .001), peak velocity (LIPA: +0.03 m/s, MVPA: +0.12 m/s; P < .001), higher levels of grip strength (LIPA: +0.68 kg, MVPA: +2.49 kg; P < .001), and less time in the Time Up and Go (LIPA: -7.63 s, MVPA: -12.43 s; P < .001). CONCLUSIONS: Replacing SB with LIPA or MVPA is associated with physical function and disability of older adults living in long-term care facilities.

Optimal dose and type of exercise to improve cognitive function in older adults: A systematic review and bayesian model-based network meta-analysis of RCTs.

OBJECTIVE: To examine the dose-response relationship between overall and specific types of exercise with cognitive function in older adults. DESIGN: Systematic Review and Bayesian Model-Based Network Meta-Analysis. DATA SOURCES: Systematic search of MEDLINE, Web of Science, Scopus, PsycINFO and SPORTDiscus. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomized controlled trials of exercise interventions in participants aged 50 years or over, and that reported on at least one global cognition outcome. RESULTS: The search returned 1998 records, of which 44 studies (4793 participants; 102 different effect sizes) were included in this review with meta-analysis. There was a non-linear, dose-response association between overall exercise and cognition. We found no minimal threshold for the beneficial effect of exercise on cognition. The estimated minimal exercise dose associated with clinically relevant changes in cognition was 724 METs-min per week, and doses beyond 1200 METs-min per week provided less clear benefits. We also found that the dose-response association was exercise type dependent, and our results show that clinically important effects may occur at lower doses for many types of exercise. Our findings also highlighted the superior effects of resistance exercises over other modalities. CONCLUSIONS: If provided with the most potent modalities, older adults can get clinical meaningful benefits with lower doses than the WHO guidelines. Findings support the WHO recommendations to emphasise resistance training as a critical component of interventions for older adults.