Dose-Response Modelling of Resistance Exercise Across Outcome Domains in Strength and Conditioning: A Meta-analysis.

BACKGROUND: Resistance exercise is the most common training modality included within strength and conditioning (S&C) practice. Understanding dose-response relationships between resistance training and a range of outcomes relevant to physical and sporting performance is of primary importance for quality S&C prescription. OBJECTIVES: The aim of this meta-analysis was to use contemporary modelling techniques to investigate resistance-only and resistance-dominant training interventions, and explore relationships between training variables (frequency, volume, intensity), participant characteristics (training status, sex), and improvements across a range of outcome domains including maximum strength, power, vertical jump, change of direction, and sprinting performance. METHODS: Data were obtained from a database of training studies conducted between 1962 and 2018, which comprised healthy trained or untrained adults engaged in resistance-only or resistance-dominant interventions. Studies were not required to include a control group. Standardized mean difference effect sizes were calculated and interventions categorized according to a range of training variables describing frequency (number of sessions per week), volume (number of sets and repetitions performed), overall intensity (intensity of effort and load, categorised as low, medium or high), and intensity of load (represented as % of one-repetition maximum [1RM] prescribed). Contemporary modelling techniques including Bayesian mixed-effects meta-analytic models were fitted to investigate linear and non-linear dose-responses with models compared based on predictive accuracy. RESULTS: Data from a total of 295 studies comprising 535 groups and 6,710 participants were included with analyses conducted on time points ≤ 26 weeks. The best performing model included: duration from baseline, average number of sets, and the main and interaction effects between outcome domain and intensity of load (% 1RM) expressed non-linearly. Model performance was not improved by the inclusion of participant training status or sex. CONCLUSIONS: The current meta-analysis represents the most comprehensive investigation of dose-response relationships across a range of outcome domains commonly targeted within strength and conditioning to date. Results demonstrate the magnitude of improvements is predominantly influenced by training intensity of load and the outcome measured. When considering the effects of intensity as a % 1RM, profiles differ across outcome domains with maximum strength likely to be maximised with the heaviest loads, vertical jump performance likely to be maximised with relatively light loads (~ 30% 1RM), and power likely to be maximised with low to moderate loads (40-70% 1RM).

Biological ammonium transporters: evolution and diversification.

Although ammonium is the preferred nitrogen source for microbes and plants, in animal cells it is a toxic product of nitrogen metabolism that needs to be excreted. Thus, ammonium movement across biological membranes, whether for uptake or excretion, is a fundamental and ubiquitous biological process catalysed by the superfamily of the Amt/Mep/Rh transporters. A remarkable feature of the Amt/Mep/Rh family is that they are ubiquitous and, despite sharing low amino acid sequence identity, are highly structurally conserved. Despite sharing a common structure, these proteins have become involved in a diverse range of physiological process spanning all domains of life, with reports describing their involvement in diverse biological processes being published regularly. In this context, we exhaustively present their range of biological roles across the domains of life and after explore current hypotheses concerning their evolution to help to understand how and why the conserved structure fulfils diverse physiological functions.

Cyanotoxin Analysis of Air Samples from the Great Salt Lake.

The Great Salt Lake in Utah is the largest saline lake in the Western hemisphere and one of the largest terminal lakes in the world. Situated at the eastern edge of the Great Basin, it is a remnant of the freshwater Lake Bonneville whose water level precipitously lowered about 12,000 years ago due to a natural break in Red Rock pass to the north. It contains a diverse assemblage of cyanobacteria which vary spatially dependent on salinity. In 1984, the waters of the Great Salt Lake occupied 8500 km2. Nearly four decades later, the waters occupy 2500 km2-a reduction in surface area of 71%. With predominantly westerly winds, there is a potential for the adjacent metropolitan residents to the east to be exposed to airborne cyanobacteria- and cyanotoxin-containing dust. During the summer and fall months of 2022, air and dried sediment samples were collected and assessed for the presence of BMAA which has been identified as a risk factor for ALS. Collection of air samples equivalent to a person breathing for 1 h resulted in BMAA and isomers being found in some air samples, along with their presence in exposed lakebed samples. There was no clear relationship between the presence of these toxins in airborne and adjacent lakebed samples, suggesting that airborne toxins may originate from diffuse rather than point sources. These findings confirm that continued low water levels in the Great Salt Lake may constitute an increasing health hazard for the 2.5 million inhabitants of communities along the Wasatch Front.

Exercise therapy for tendinopathy: a mixed-methods evidence synthesis exploring feasibility, acceptability and effectiveness.

Background: Tendinopathy is a common, painful and functionally limiting condition, primarily managed conservatively using exercise therapy. Review questions: (i) What exercise interventions have been reported in the literature for which tendinopathies? (ii) What outcomes have been reported in studies investigating exercise interventions for tendinopathy? (iii) Which exercise interventions are most effective across all tendinopathies? (iv) Does type/location of tendinopathy or other specific covariates affect which are the most effective exercise therapies? (v) How feasible and acceptable are exercise interventions for tendinopathies? Methods: A scoping review mapped exercise interventions for tendinopathies and outcomes reported to date (questions i and ii). Thereafter, two contingent systematic review workstreams were conducted. The first investigated a large number of studies and was split into three efficacy reviews that quantified and compared efficacy across different interventions (question iii), and investigated the influence of a range of potential moderators (question iv). The second was a convergent segregated mixed-method review (question v). Searches for studies published from 1998 were conducted in library databases (n = 9), trial registries (n = 6), grey literature databases (n = 5) and Google Scholar. Scoping review searches were completed on 28 April 2020 with efficacy and mixed-method search updates conducted on 19 January 2021 and 29 March 2021. Results: Scoping review - 555 included studies identified a range of exercise interventions and outcomes across a range of tendinopathies, most commonly Achilles, patellar, lateral elbow and rotator cuff-related shoulder pain. Strengthening exercise was most common, with flexibility exercise used primarily in the upper limb. Disability was the most common outcome measured in Achilles, patellar and rotator cuff-related shoulder pain; physical function capacity was most common in lateral elbow tendinopathy. Efficacy reviews - 204 studies provided evidence that exercise therapy is safe and beneficial, and that patients are generally satisfied with treatment outcome and perceive the improvement to be substantial. In the context of generally low and very low-quality evidence, results identified that: (1) the shoulder may benefit more from flexibility (effect sizeResistance:Flexibility = 0.18 [95% CrI 0.07 to 0.29]) and proprioception (effect sizeResistance:Proprioception = 0.16 [95% CrI -1.8 to 0.32]); (2) when performing strengthening exercise it may be most beneficial to combine concentric and eccentric modes (effect sizeEccentricOnly:Concentric+Eccentric = 0.48 [95% CrI -0.13 to 1.1]; and (3) exercise may be most beneficial when combined with another conservative modality (e.g. injection or electro-therapy increasing effect size by ≈0.1 to 0.3). Mixed-method review - 94 studies (11 qualitative) provided evidence that exercise interventions for tendinopathy can largely be considered feasible and acceptable, and that several important factors should be considered when prescribing exercise for tendinopathy, including an awareness of potential barriers to and facilitators of engaging with exercise, patients' and providers' prior experience and beliefs, and the importance of patient education, self-management and the patient-healthcare professional relationship. Limitations: Despite a large body of literature on exercise for tendinopathy, there are methodological and reporting limitations that influenced the recommendations that could be made. Conclusion: The findings provide some support for the use of exercise combined with another conservative modality; flexibility and proprioception exercise for the shoulder; and a combination of eccentric and concentric strengthening exercise across tendinopathies. However, the findings must be interpreted within the context of the quality of the available evidence. Future work: There is an urgent need for high-quality efficacy, effectiveness, cost-effectiveness and qualitative research that is adequately reported, using common terminology, definitions and outcomes. Study registration: This project is registered as DOI: 10.11124/JBIES-20-00175 (scoping review); PROSPERO CRD 42020168187 (efficacy reviews); https://osf.io/preprints/sportrxiv/y7sk6/ (efficacy review 1); https://osf.io/preprints/sportrxiv/eyxgk/ (efficacy review 2); https://osf.io/preprints/sportrxiv/mx5pv/ (efficacy review 3); PROSPERO CRD42020164641 (mixed-method review). Funding: This project was funded by the National Institute for Health and Care Research (NIHR) HTA programme and will be published in full in HTA Journal; Vol. 27, No. 24. See the NIHR Journals Library website for further project information.

Tendons are cords of strong, flexible tissue that attach muscles to bones, allowing joints to move. Tendinopathy is a common condition that can affect any tendon in the body, causing pain and limiting function. Exercise is often used to treat tendinopathy. We examined over 500 research papers on exercise for tendinopathy. The most common tendons to be studied were the calf (Achilles), knee (patellar), elbow and shoulder. Strengthening exercise was studied most often, especially in lower-limb tendinopathy. Other types of exercise such as stretching, balance and aerobic activity were less common, but were used to some extent in the upper and lower limbs. We found that exercise therapy is safe and beneficial for the tendinopathies that have been studied to date. Exercise may be most beneficial when combined with another intervention such as injection or electro-therapy. Strengthening exercise may be most beneficial for lower-limb tendinopathies. However, more research is needed on the type of strengthening and the dosage, such as how many exercises and how much resistance to use. Shoulder tendinopathies may benefit from exercise that targets joint flexibility and position more than strengthening. We also found that people who receive exercise therapy for tendinopathy are generally satisfied with the effect it has on their symptoms. Finally, we found that an individualised, person-centred approach to delivering exercise therapy is valued by people with tendinopathy. They also believe that the patient-healthcare provider relationship is important for promoting the confidence and motivation people need to continue with exercise programmes, especially when they complete them independently. Although we examined a lot of papers, many of the studies were low quality. This means there is still a need for high-quality studies to tell us how effective specific types of exercise are for specific tendinopathies. There is also a need for more studies on patients' and professionals' experiences of receiving or providing exercise for tendinopathy.

Low muscle mass measured at T12 is a prognostic biomarker in unresectable oesophageal cancers receiving chemoradiotherapy.

BACKGROUND AND PURPOSE: Low muscle mass is an imaging biomarker of patient frailty that has been associated with increased toxicity and decreased survival in a number of cancers. Patients with unresectable oesophageal cancer receive chemoradiotherapy as standard of care. Muscle mass is not yet an established prognostic marker in this population. Muscle mass is usually assessed by segmenting skeletal muscle at the L3 vertebral level. But radiotherapy planning scans for oesophageal cancers do not always image this level, which has limited previous studies of body composition. Skeletal muscle is known to regulate immune function, but the association of muscle mass with lymphopenia in cancer patients has not been shown. MATERIALS AND METHODS: We retrospectively analyse 135 oesophageal cancer patients who received chemoradiotherapy and investigate the prognostic value of skeletal muscle area assessed at T12. We also examine the association between muscle mass and radiation-induced lymphopenia. RESULTS: We find that low muscle mass is associated with poorer overall survival (hazard ratio [95% confidence interval]: 0.72 [0.53-0.97]). However, this effect interacts with body mass index (BMI) such that the prognostic value of low muscle mass is removed by high BMI. In our study, patients with low muscle mass were more prone to radiation-induced lymphopenia (75% vs. 50% in patients with high muscle mass). A significant decrease in circulating lymphocytes was associated with poorer overall survival (hazard ratio [95% confidence interval]: 0.68 [0.47-0.99]). CONCLUSION: Our study shows that assessing muscle mass at T12 is feasible and provides prognostic information. Low muscle mass at T12 is associated with poorer overall survival and increased risk of radiation-induced lymphopenia. Muscle mass provides additional information over performance status and BMI. Low BMI patients are most affected by low muscle mass, highlighting the importance of close nutritional support in this population.

L1CAM immunocapture generates a unique extracellular vesicle population with a reproducible miRNA fingerprint.

Micro RNAs (miRNAs) are short, non-coding RNAs with significant potential as diagnostic and prognostic biomarkers. However, a lack of reproducibility across studies has hindered their introduction into clinical settings. Inconsistencies between studies include a lack of consensus on the miRNAs associated with a specific disease and the direction of regulation. These differences may reflect the heterogenous nature of pathologies with multiple phenotypes, such as amyotrophic lateral sclerosis (ALS). It is also possible that discrepancies are due to different sampling, processing, and analysis protocols across labs. Using miRNA extracted from L1CAM immunoaffinity purified extracellular vesicles (neural-enriched extracellular vesicles or NEE), we thrice replicated an 8-miRNA fingerprint diagnostic of ALS, which includes the miRNA species and direction of regulation. We aimed to determine if the extra purification steps required to generate NEE created a unique extracellular vesicle (EV) fraction that might contribute to the robustness and replicability of our assay. We compared three fractions from control human plasma: 1) total heterogenous EVs (T), 2) L1CAM/neural enriched EVs (NEE), and 3) the remaining total-minus-NEE fraction (T-N). Each fraction was characterized for size, total protein content, and protein markers, then total RNA was extracted, and qPCR was run on 20 miRNAs. We report that the miRNA expression within NEE was different enough compared to T and T-N to justify the extra steps required to generate this fraction. We conclude that L1CAM immunocapture generates a unique fraction of EVs that consistently and robustly replicates a miRNA fingerprint which differentiates ALS patients from controls.

Fifteen-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer.

BACKGROUND: Between 1999 and 2009 in the United Kingdom, 82,429 men between 50 and 69 years of age received a prostate-specific antigen (PSA) test. Localized prostate cancer was diagnosed in 2664 men. Of these men, 1643 were enrolled in a trial to evaluate the effectiveness of treatments, with 545 randomly assigned to receive active monitoring, 553 to undergo prostatectomy, and 545 to undergo radiotherapy. METHODS: At a median follow-up of 15 years (range, 11 to 21), we compared the results in this population with respect to death from prostate cancer (the primary outcome) and death from any cause, metastases, disease progression, and initiation of long-term androgen-deprivation therapy (secondary outcomes). RESULTS: Follow-up was complete for 1610 patients (98%). A risk-stratification analysis showed that more than one third of the men had intermediate or high-risk disease at diagnosis. Death from prostate cancer occurred in 45 men (2.7%): 17 (3.1%) in the active-monitoring group, 12 (2.2%) in the prostatectomy group, and 16 (2.9%) in the radiotherapy group (P = 0.53 for the overall comparison). Death from any cause occurred in 356 men (21.7%), with similar numbers in all three groups. Metastases developed in 51 men (9.4%) in the active-monitoring group, in 26 (4.7%) in the prostatectomy group, and in 27 (5.0%) in the radiotherapy group. Long-term androgen-deprivation therapy was initiated in 69 men (12.7%), 40 (7.2%), and 42 (7.7%), respectively; clinical progression occurred in 141 men (25.9%), 58 (10.5%), and 60 (11.0%), respectively. In the active-monitoring group, 133 men (24.4%) were alive without any prostate cancer treatment at the end of follow-up. No differential effects on cancer-specific mortality were noted in relation to the baseline PSA level, tumor stage or grade, or risk-stratification score. No treatment complications were reported after the 10-year analysis. CONCLUSIONS: After 15 years of follow-up, prostate cancer-specific mortality was low regardless of the treatment assigned. Thus, the choice of therapy involves weighing trade-offs between benefits and harms associated with treatments for localized prostate cancer. (Funded by the National Institute for Health and Care Research; ProtecT Current Controlled Trials number, ISRCTN20141297; ClinicalTrials.gov number, NCT02044172.).

Detection of ß-N-methylamino-l-alanine in postmortem olfactory bulbs of Alzheimer's disease patients using UHPLC-MS/MS: An autopsy case-series study.

Introduction: Cyanobacterial blooms produce toxins that may become aerosolized, increasing health risks through inhalation exposures. Health related effects on the lower respiratory tract caused by these toxins are becoming better understood. However, nasal exposures to cyanotoxins remain understudied, especially for those with neurotoxic potential. Here, we present a case series study evaluating exposure to ß-N-methylamino-l-alanine (BMAA), a cyanobacterial toxin linked to neurodegenerative disease, in postmortem olfactory tissues of individuals with varying stages of Alzheimer's disease (AD). Methods: Olfactory bulb (Ob) tissues were collected during autopsies performed between 2014 and 2017 from six South Florida brain donors (ages 47-78) with residences less than 140 m from a freshwater body. A triple quadrupole tandem mass spectrometry (UHPLC-MS/MS) method validated according to peer AOAC International guidelines was used to detect BMAA and two BMAA isomers: 2,4-diaminobutyric acid (2,4-DAB) and N-(2-aminoethyl)glycine (AEG). Quantitative PCR was performed on the contralateral Ob to evaluate the relative expression of genes related to proinflammatory cytokines (IL-6 & IL-18), apoptotic pathways (CASP1 & BCL2), and mitochondrial stress (IRF1 & PINK1). Immunohistochemistry was also performed on the adjacent olfactory tract (Ot) to evaluate co-occurring neuropathology with BMAA tissue concentration. Results: BMAA was detected in the Ob of all cases at a median concentration of 30.4 ng/g (Range

Antileishmanial Activity of Clinanthus milagroanthus S. Leiva & Meerow (Amaryllidaceae) Collected in Peru.

Leishmaniasis is a worldwide infectious parasitic disease caused by different species of protozoa of the genus Leishmania, which are transmitted to animals and humans through the bite of insects of the Psychodidae family. In the present work, the antileishmanial activity of an alkaloid extract of the bulbs of Clinanthus milagroanthus S. Leiva & Meerow (Amaryllidaceae) was evaluated in vitro, in vivo, and in silico against the parasite Leishmania braziliensis, and the chemical profile of the sample was determined by GC-MS analysis. At concentrations of 1, 10, and 100 µg·mL−1, the alkaloid extract presented inhibition percentages of 8.7%, 23.1%, and 98.8%, respectively, against L. braziliensis with a p < 0.05, and IC50 values of 18.5 ± 0.3 µg·mL−1. Furthermore, at a dose of 1.0 mg·kg−1, a greater decrease in lesion size was observed (90%) for in vivo assays, as well as a decrease in infection (96%), finding no significant differences (p > 0.05) in comparison with amphotericin B (92% and 98%, respectively). Eleven alkaloids were identified in C. milagroanthus bulbs: galanthamine, vittatine/crinine, 8-O-demethylmaritidine, anhydrolycorine, 11,12-dehydroanhydrolycorine, hippamine, lycorine, 2-hydroxyanhydrolycorine, 7-hydroxyclivonine, 2α-hydroxyhomolycorine, and 7-hydroxyclivonine isomer. A molecular model of Leishmania braziliensis trypanothione reductase (TRLb) was built using computational experiments to evaluate in silico the potential of the Amaryllidaceae alkaloid identified in C. milagroanthus toward this enzyme. The structures galanthamine, 7-hydroxyclivonine isomer, and crinine showed better estimated free energy of binding than the reference compound, amphotericin B. In conclusion, this is the first in vitro, in vivo, and in silico report about the antileishmanial potential and alkaloid profiling of the extract of C. milagroanthus bulbs, which could become an interesting source of bioactive molecules.

Reliability of spatial-temporal metrics used to assess collective behaviours in football: an in-silico experiment.

BACKGROUND: The purpose of this study was to investigate the reliability of spatio-temporal measurements applied within collective behaviour research in football. METHODS: In silico experiments were conducted introducing positional errors (0.5, 2 and 4 m) representative of commercial tracking systems to match data from the 2020 European Championship qualifiers. Ratios of the natural variance ('signal') of spatio-temporal metrics obtained throughout sections of each game relative to the variance created by positional errors ('noise') were taken to calculate reliability. The effects of error magnitude and time of analysis (1, 5 and 15 mins; length of attack: <10, 10-20, >20 s) were assessed and compared using Cohen's f2 effect size. RESULTS: Error magnitude was found to exert greater influence on reliability (f2 = 0.15 to 0.81) compared with both standard time of analysis (f2 = 0.03 to 0.08) and length of attacks (f2 = 0.15 to 0.32). DISCUSSION: The results demonstrate that technologies generating positional errors of 0.5 m or less should be expected to produce spatio-temporal metrics with high reliability. However, technologies that generate errors of 2 m or greater may produce unreliable values, particularly when analyses are conducted over discrete events such as attacks, which although critical, are often short in duration.

Patient-Reported Outcomes 12 Years after Localized Prostate Cancer Treatment.

Outcomes after Localized Prostate Cancer TreatmentDonovan et al. present the long-term patient-reported outcomes of 1643 randomly assigned participants in the ProtecT (Prostate Testing for Cancer and Treatment) trial. Functional and quality-of-life impacts of prostatectomy, radiotherapy with neoadjuvant androgen deprivation, and active monitoring are described. Over the trial period from 7 to 12 years, generic quality-of-life scores were similar among all groups, with varying degrees of impact on urinary leakage, sexual function, and fecal leakage depending on the treatment group.

Factores sociodemográficos y salud mental en estudiantes de enfermería en tiempos de COVID-19 / Sociodemographic Factors and Mental Health in Nursing Students in Times of COVID-19

Introducción: La salud mental ha sido afectada durante la pandemia por COVID-19, también en los estudiantes de enfermería se ha observado un efecto negativo sobre sus niveles de depresión y ansiedad. Objetivo: Describir la relación existente entre los factores sociodemográficos y la salud mental de estudiantes de enfermería en tiempos de COVID-19. Métodos: Estudio cuantitativo, descriptivo, transversal, cuya población fue de 577 estudiantes de enfermería de una universidad privada de Trujillo, Perú, matriculados en el semestre 2021-01. Se tomó una muestra de 328 estudiantes mediante muestreo no probabilístico por conveniencia. Los datos se recolectaron mediante los cuestionarios para evaluar síntomas de ansiedad (GAD-7) y depresión (PHQ-9), estos instrumentos fueron enviados mediante un formulario de Google. Los datos fueron procesados y descritos en frecuencias absolutas y porcentajes; para el análisis inferencial se utilizó la prueba de Chi cuadrado de Pearson. Resultados: Los factores sociodemográficos muestran que 31,10 por ciento pertenecía al primer ciclo, 95,70 por ciento era de género femenino, 31,40 por ciento tenía edades de hasta 18 años, 92,10 por ciento era soltero, 68,90 por ciento profesaba la religión católica y 85,40 por ciento indicó residir en el departamento de La Libertad. Asimismo, se encontró que 45,40 por ciento de los estudiantes tenía nivel leve de ansiedad y 19,80 por ciento nivel severo; además, 39,60 por ciento no presentó síntomas depresivos, 18,90 por ciento presentó depresión mayor leve y 2,10 por ciento depresión mayor severa, se encontró solo una relación estadística significativa entre el factor género y los síntomas depresivos (p < 0,05). Conclusiones: No se encontró relación entre los factores sociodemográficos y los síntomas de ansiedad(AU)

Introduction: Mental health has been affected during the pandemic by COVID-19, also in nursing students a negative effect on their levels of depression and anxiety has been observed. Objective: To describe the relationship between sociodemographic factors and mental health of nursing students in times of COVID-19. Methods: Quantitative, descriptive, cross-sectional study, whose population was 577 nursing students of a private university in Trujillo, Peru, enrolled in the semester 2021-01. A sample of 328 students was taken by non-probabilistic convenience sampling. Data were collected using the questionnaires to evaluate anxiety symptoms (GAD-7) and depression (PHQ-9), these instruments were sent through a Google form. Data were processed and described in absolute frequencies and percentages; Pearson's Chi-square test was used for inferential analysis. Results: The sociodemographic factors show that 31.10 percent belonged to the first cycle, 95.70 percent were female, 31.40 percent were aged up to 18 years, 92.10 percent were single, 68.90 percent professed the Catholic religion and 85.40 percent indicated residing in the department of La Libertad. It was also found that 45.40 percent of the students had mild anxiety and 19.80 percent severe anxiety; in addition, 39.60 percent did not present depressive symptoms, 18.90 percent presented mild major depression and 2.10 percent severe major depression; only a significant statistical relationship was found between the gender factor and depressive symptoms (p < 0.05). Conclusions: No relationship was found between sociodemographic factors and anxiety symptoms(AU)

Interpreting magnitude of change in strength and conditioning: Effect size selection, threshold values and Bayesian updating.

The magnitude of change following strength and conditioning (S&C) training can be evaluated comparing effect sizes to thresholds. This study conducted a series of meta-analyses and compiled results to identify thresholds specific to S&C, and create prior distributions for Bayesian updating. Pre- and post-training data from S&C interventions were translated into standardised mean difference (SMDpre) and percentage improvement (%Improve) effect sizes. Bayesian hierarchical meta-analysis models were conducted to compare effect sizes, develop prior distributions, and estimate 0.25-, 0.5-, and 0.75-quantiles to determine small, medium, and large thresholds, respectively. Data from 643 studies comprising 6574 effect sizes were included in the analyses. Large differences in distributions for both SMDpre and %Improve were identified across outcome domains (strength, power, jump and sprint performance), with analyses of the tails of the distributions indicating potential large overestimations of SMDpre values. Future evaluations of S&C training will be improved using Bayesian approaches featuring the information and priors developed in this study. To facilitate an uptake of Bayesian methods within S&C, an easily accessible tool employing intuitive Bayesian updating was created. It is recommended that the tool and specific thresholds be used instead of isolated effect size calculations and Cohen's generic values when evaluating S&C training.

miRNA extracted from extracellular vesicles is a robust biomarker of amyotrophic lateral sclerosis.

BACKGROUND AND OBJECTIVES: We examined miRNA biomarkers for ALS extracted from extracellular vesicles in blood samples using a large and diverse patient and control population. Different blood collection and storage protocols by different investigators could impact repeatability of miRNA analysis. We tested the hypotheses that miRNA extracted from extracellular vesicles using immunoaffinity purification techniques are robust and repeatable across investigators, laboratories and in a broad ALS population. METHODS: De-identified patient blood plasma samples obtained from the U.S. National ALS Biorepository were compared with plasma from non-ALS controls. Extracellular vesicles were extracted and isolated using L1CAM immunoaffinity purification. Total RNA was extracted, and miRNA quantified using qPCR following careful quality control measures. Gene fold expressions of eight miRNAs were compared using a Mann-Whitney two-tailed test. RESULTS: One hundred blinded, blood plasma samples were analyzed. Thirty-five men and 15 women with ALS were compared with controls consisting of 30 men and 20 women. None of the ALS patient cohort reported family members with ALS suggesting sporadic ALS. Five of the eight biomarkers previously published were found to significantly discriminate ALS patient samples from control samples. DISCUSSION: The methods used in this study provide a repeatable measure of miRNA biomarkers that statistically differentiate ALS patient samples from control samples. The broad inclusion criteria for both the ALS patient cohort and controls along with the collection of blood samples by different investigators suggest that these methods are robust and represent good candidates for further research and development aimed at clinical application.

Mindfulness-based online intervention for mental health during times of COVID-19.

Background: As the COVID-19 pandemic progresses, mental health begins to be affected. In this sense, practical and low-cost solutions are necessary to minimize the impact on the population. Aim: This study aimed to determine the effect of a mindfulness-based online intervention for mental health during times of COVID-19. Method: A quasi-experimental study was carried out with pre-test and post-test measurements in a sample of 62 participants divided into an experimental group whose members were administered a 12-session mindfulness online program, and a control group on the waiting list. The Zung Self-Rating Anxiety Scale (SAS) was used to assess anxiety, the Zung Self-Rating Depression Scale (SDS) to measure depression, and the Perceived Stress Scale (PSS-14) to determine stress levels. Results: The levels of anxiety, depression, and stress decreased after the intervention, finding significant differences between the groups and study phases (P < 0.05). In addition, moderate changes in anxiety (d = 0.849, g = 0.847) and depression (d = 0.533, g = 0.530) were found, as well as important changes in stress reduction (d = 1.254, g = 1.240). Conclusion: There is evidence of a potential for the use of mindfulness program to reduce stress, anxiety, and depressive symptoms in stressful situations such as the COVID-19 pandemic.

A possible blood plasma biomarker for early-stage Alzheimer's disease.

We sought to identify a usable biomarker from blood samples to characterize early-stage Alzheimer's disease (AD) patients, in order to facilitate rapid diagnosis, early therapeutic intervention, and monitoring of clinical trials. We compared metabolites from blood plasma in early-stage Alzheimer's disease patients with blood plasma from healthy controls using two different analytical platforms: Amino Acid Analyzer and Tandem Mass-Spectrometer. Early-stage Alzheimer's patient blood samples were obtained during an FDA-approved Phase IIa clinical trial (Clinicaltrial.gov NCT03062449). Participants included 25 early-stage Alzheimer's patients and 25 healthy controls in the United States. We measured concentrations of 2-aminoethyl dihydrogen phosphate and taurine in blood plasma samples. We found that plasma concentrations of a phospholipid metabolite, 2-aminoethyl dihydrogen phosphate, normalized by taurine concentrations, distinguish blood samples of patients with early-stage AD. This possible new Alzheimer's biomarker may supplement clinical diagnosis for early detection of the disease.

Evaluation of the Melbourne Rapid Fields Test Procedure.

SIGNIFICANCE: Both the Melbourne Rapid Fields (MRF) tablet and home versions are easy-to-use, portable, and low-cost and accurate methods of evaluating visual fields. PURPOSE: This study aimed to investigate the clinical capabilities of the MRF perimetry test by comparing it with the Humphrey Field Analyzer (HFA), determine MRF consistency, assess the influence of refractive error, ascertain ambient illumination effects, and evaluate the consistency between the tablet and Internet Web site versions of the MRF. METHODS: Forty healthy young participants with normal visual function (33 female, 7 male; average age, 24 years) underwent two MRF office-based tablet, two HFA tests, and two MRF Web site-based tests, one in our laboratory and one at home on their own computer using the 24-2 test pattern each time. An additional six healthy participants with normal visual function performed the 24-2 test with varying amounts of blur. RESULTS: The average individual sensitivity values of MRF and HFA were within 4.02 dB (right eye) and 4.15 dB (left eye). The dynamic range of the MRF was smaller (30 dB) than that of the HFA. When sensitivity values greater than 30 dB were excluded, the sensitivity differences were within 2.2 dB (right eye) and 2.46 dB (left eye) of each other. Only a small number of cases produced reliability values (false positives, false negatives, fixation losses) that were outside of normal limits. There was a high correlation between test results obtained with the tablet version of the MRF test when compared with the Internet-based Web site version. CONCLUSIONS: Quantitative visual field testing and perimetric screening procedures can be performed effectively and can provide results that are comparable with bowl perimeter test results.

Functional and quality of life outcomes of localised prostate cancer treatments (Prostate Testing for Cancer and Treatment [ProtecT] study).

OBJECTIVE: To investigate the functional and quality of life (QoL) outcomes of treatments for localised prostate cancer and inform treatment decision-making. PATIENTS AND METHODS: Men aged 50-69 years diagnosed with localised prostate cancer by prostate-specific antigen testing and biopsies at nine UK centres in the Prostate Testing for Cancer and Treatment (ProtecT) trial were randomised to, or chose one of, three treatments. Of 2565 participants, 1135 men received active monitoring (AM), 750 a radical prostatectomy (RP), 603 external-beam radiotherapy (EBRT) with concurrent androgen-deprivation therapy (ADT) and 77 low-dose-rate brachytherapy (BT, not a randomised treatment). Patient-reported outcome measures (PROMs) completed annually for 6 years were analysed by initial treatment and censored for subsequent treatments. Mixed effects models were adjusted for baseline characteristics using propensity scores. RESULTS: Treatment-received analyses revealed different impacts of treatments over 6 years. Men remaining on AM experienced gradual declines in sexual and urinary function with age (e.g., increases in erectile dysfunction from 35% of men at baseline to 53% at 6 years and nocturia similarly from 20% to 38%). Radical treatment impacts were immediate and continued over 6 years. After RP, 95% of men reported erectile dysfunction persisting for 85% at 6 years, and after EBRT this was reported by 69% and 74%, respectively (P < 0.001 compared with AM). After RP, 36% of men reported urinary leakage requiring at least 1 pad/day, persisting for 20% at 6 years, compared with no change in men receiving EBRT or AM (P < 0.001). Worse bowel function and bother (e.g., bloody stools 6% at 6 years and faecal incontinence 10%) was experienced by men after EBRT than after RP or AM (P < 0.001) with lesser effects after BT. No treatment affected mental or physical QoL. CONCLUSION: Treatment decision-making for localised prostate cancer can be informed by these 6-year functional and QoL outcomes.

Cyclotides Chemosensitize Glioblastoma Cells to Temozolomide.

Glioblastoma multiforme (GBM) is the most aggressive cancer originating in the brain, with a median survival of 12 months. Most patients do not respond to or develop resistance to the only effective chemotherapeutic drug, temozolomide (TMZ), used to treat gliomas. Novel treatment methods are critically needed. Cyclotides are plant peptides that may be promising adjuvants to TMZ chemotherapy. They exhibit antitumor activity and chemosensitize cells to doxorubicin in breast cancer studies. During this research, we optimized cyclotide isolation techniques, and several cyclotides (CyO2, CyO13, kalata B1, and varv peptide A) exhibited dose-dependent cytotoxicity in MTT assays with IC50 values of 2.15-7.92 µM against human brain astrocytoma cells (U-87 MG) and human bone marrow derived neuroblastoma cells (SH-SY5Y). CyO2 and varv peptide A increased TMZ-induced cell death in U-87 MG cultures alone and when coexposed with CyO2 or varv peptide A plus TMZ. Phase contrast microscopy of glioblastoma cells exposed to cyclotides alone and coexposed to TMZ indicated shrunken, granular cells with blebbing, and the most pronounced effects were observed with coexposure treatments of cyclotides and TMZ. Cumulative results provide the proof-of-concept that cyclotides may enhance TMZ chemotherapy, and in vivo pharmacokinetic investigations of cyclotides are warranted with respect to GBM.

Sodium bicarbonate supplementation and the female athlete: A brief commentary with small scale systematic review and meta-analysis.

ABSTRACTSodium bicarbonate (SB) is considered an effective ergogenic supplement for improving high-intensity exercise capacity and performance, although recent data suggests that women may be less amenable to its ergogenic effects than men. Currently, an apparent paucity of data on women means no consensus exists on whether women benefit from SB supplementation. The aim of the current study was to quantify the proportion of the published literature on SB supplementation that includes women, and to synthesise the evidence regarding its effects on blood bicarbonate and exercise performance in women by performing a systematic review and meta-analysis. Electronic searches of the literature were undertaken using three databases (MEDLINE, Embase, SPORTDiscus) to identify relevant articles. All meta-analyses were performed within a Bayesian framework. A total of 149 SB articles were identified, 11 of which contained individual group data for women. Results indicated a pooled blood bicarbonate increase of 7.4 [95%CrI: 4.2-10.4 mmol·L-1] following supplementation and a pooled standardised exercise effect size of 0.37 [95%CrI: -0.06-0.92]. The SB literature is skewed, with only 20% (30 studies) of studies employing female participants, of which only 11 studies (7.4%) provided group analyses exclusively in women. Despite the small amount of available data, results are consistent in showing that SB supplementation in women leads to large changes in blood bicarbonate and that there is strong evidence for a positive ergogenic effect on exercise performance that is likely to be small to medium in magnitude.HighlightsThis study aimed to quantify the proportion of the published literature on sodium bicarbonate supplementation that includes women and to synthesise the evidence regarding its ergogenic effect on women, using a systematic review and meta-analytic approach.The sodium bicarbonate literature is skewed, with only 30 studies (20%) employing female participants, of which only 11 studies (7.4%) provided group analyses exclusively in women.Despite the small amount of available data, results are consistent in showing that sodium bicarbonate supplementation in women leads to large changes in blood bicarbonate and that there is strong evidence for a positive ergogenic effect on exercise performance that is likely small to medium in magnitude.Based on these findings, we do not believe there is any evidence to support sex-specific sodium bicarbonate dosing recommendations and that current recommendations of 0.2-0.3 g·kg-1BM of SB taken 60-180 min prior to high-intensity exercise appear appropriate for the female athlete.