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Abstract BackgroundMobile apps represent accessible and cost-effective tools to improve nutrition and prevent chronic diseases. However, most of these apps have been characterized as having limited functionality, raising concerns about their effectiveness, acceptability, and efficacy. ObjectiveThe aims of the study were to assess the quality of popular nutrition-related app platforms in Spain and to describe their characteristics and functionalities. MethodsWe screened apps providing information on dietary advice, food advice, and nutritional content in the Apple App Store and Google Play Store in Spain from March 2 to March 16, 2024. Apps with a star rating of ≥4 (of 5 stars), those available in Spanish, those that were free of charge, those last updated after January 2022, those with >500 reviews, and those with >500,000 downloads were included. The quality of apps was assessed using the user version of the Mobile App Rating Scale (uMARS). General characteristics and nutritional, health, and market-related functionalities of the nutrition-related apps were described. Correlations among total and uMARS sections, star ratings, and number of reviews and downloads were evaluated. ResultsAmong the 1460 apps identified in the search, 42 apps met the criteria. The majority of these (n=20, 48%) aimed at recording and analyzing food intake, followed by those providing nutritional plans or diets (n=9, 21%), advising on healthy habits (n=7, 17%), and offering recipes (n=6, 14%). The most prevalent nutritional functionalities offered were recording and monitoring body measurements (n=30, 71%), food tracking (n=26, 62%), and dietary analysis (n=25, 60%), whereas nutrition education was less common (n=16, 38%). Among market-related functionalities, advertisements were the most common among the study apps (n=30, 71%), followed by the option of sharing on social media (n=29, 69%) and customizable reminders (n=26, 62%). Sharing the recorded information in the app with health professionals was infrequent (n=1, 2%). The mean (SD) total uMARS score (maximum 5 points) was 3.78 (0.35), while the mean (SD) uMARS scores for functionality, aesthetics, engagement, and information were 4.21 (0.38), 3.94 (0.54), 3.51 (0.46), and 3.48 (0.44), respectively. Lower mean scores were observed for the subjective quality (mean 2.65, SD 0.56) and perceived impact (mean 3.06, SD 0.67). Moderate to strong positive significant correlations were mostly observed between total uMARS and section-specific uMARS scores, while the correlations between the uMARS section scores were mostly moderate positive. Total uMARS scores were very weakly correlated with user rating, number of reviews, and number of downloads. ConclusionsThe quality of popular nutrition-related app platforms in Spain was acceptable, with observed remarkable differences between sections. The majority of the apps were appealing due to their user-friendly interfaces. Only a few apps, however, provided dietary structure analysis or nutritional education. Further research is needed to assess the long-term impact of these apps on users.

Sarcopenia is linked to the decline in muscle mass, strength and function during aging. It affects the quality and life expectancy and can lead to dependence. The biological process underlying sarcopenia is unclear, but the proteins myostatin and follistatin are involved in the balance between muscle breakdown and synthesis. While myostatin promotes muscle breakdown, follistatin promotes muscle growth, but several works have shown an inconsistent association of these proteins with aging-related parameters in serum of older people. We aimed to know the evolution of these putative sarcopenia biomarkers along muscle aging in an in vitro model. We created and phenotyped a longitudinal murine model (C2C12 cells). Then, we analyzed the protein and genetic expression of myostatin and follistatin as well as the signaling pathway regulators mTOR and RPS6KB1. Myostatin and RPS6KB1 showed a similar tendency in both protein and genetic expression with aging (basal–up–down). Follistatin, on the other hand, shows the opposite tendency (basal–down–up). Regarding mTOR, the tendencies differ when analyzing proteins (basal–up–down) or genes (basal–down–down). Our work demonstrates a U-shape tendency for myostatin and follistatin and for the signaling pathway regulators. These results could be of the utmost importance when designing further research on seeking molecular biomarkers and/or targets for sarcopenia.

Abstract Background Adherence to treatment, a public health issue, is of particular importance in chronic disease therapies. Primary care practices offer ideal venues for the effective care and management of these conditions. The aim of this study is to assess adherence to treatment and related-factors among patients with chronic conditions in primary care settings. Methods A cross-sectional study was conducted among 299 adult patients with ≥1 chronic condition(s) and prescribed medication in primary healthcare centers of Spain. The Morisky-Green-Levine questionnaire was used to assess medication adherence via face-to-face interviews. Crude and adjusted multivariable logistic regression models were used to analyze factors associated with adherence using the Multidimensional Model proposed by the World Health Organization — social and economic, healthcare team and system-related, condition-related, therapy-related, and patient-related factors. Results The proportion of adherent patients to treatment was 55.5%. Older age (adjusted odds ratio 1.31 per 10-year increment, 95% CI 1.01–1.70), lower number of pharmacies used for medication refills (0.65, 95% CI 0.47–0.90), having received complete treatment information (3.89, 95% CI 2.09–7.21), having adequate knowledge about medication regimen (4.17, 95% CI 2.23–7.80), and self-perception of a good quality of life (2.17, 95% CI 1.18–4.02) were independent factors associated with adherence. Conclusions Adherence to treatment for chronic conditions remained low in primary care. Optimal achievement of appropriate levels of adherence through tailored multifaceted interventions will require attention to the multidimensional factors found in this study, particularly those related to patients’ education and their information needs.

IntroductionWith an increasing prevalence, dementia is one of the most disabling diseases among the elderly. Impaired cognitive function and behavioral and psychological symptoms predispose patients to medication non-adherence, resulting in increased morbidity, mortality, and healthcare costs. The aim of this study was to estimate the prevalence of non-adherence to antidementia medications and to identify the main predictors.MethodsA population-based registry study was conducted in 2022 in Castile and Leon, Spain. A total of 17,563 patients with dementia were included. The medication possession ratio (MPR) was used as an indirect method to measure adherence. The cut-off point for determining that a patient was nonadherent was 80% of MPR. Multivariate logistic regression was used to identify predictors of nonadherence based on sociodemographic and health-related variables.ResultsIn 2022, 6.2% of the population over 80 years old used antidementia medications. Of these patients, 70% were women, 28.15% were institutionalized, and over 90% were polymedicated and had multiple prescribers. The most used medicines were donepezil (43.49%), rivastigmine (36.84%), and memantine (30.7%). The combined use of an acetylcholinesterase inhibitor plus memantine was relevant (13.33%). Men were less adherent than women, and the prevalence of non-adherence decreased with age. The medication associated with the highest prevalence of non-adherence was rivastigmine (19%), followed by donepezil (17%) and memantine (13.23%). Institutionalized patients (13%) and patients on combination therapy (13.29%) had the lowest prevalence of non-adherence. Protective factors against non-adherence include institutionalization, polymedication, use of memantine or combination therapy, and comorbid mental illness.ConclusionsIn Castile and Leon, one in six patients were non-adherent to antidementia medications. Younger male patients with cardiometabolic disease are more likely to be non-adherent to antidementia medications. On the other hand, institutionalization is a protective factor against non-adherence, but still 10% of nursing home patients are non-adherent to antidementia medications.

Background and Objectives: Alzheimer’s dementia is a progressive neurodegenerative disease that affects memory abilities due to genetic and environmental factors. A well-known gene that influences the risk of Alzheimer’s disease is the apolipoprotein E (APOE) gene. The APOE gene is involved in the production of a protein that helps transport cholesterol and other types of fat in the bloodstream. Problems in this process are thought to contribute to the development of Alzheimer’s disease. APOE comes in several forms, which are called alleles (ε2, ε3, ε4). Materials and Methods: Therefore, our study aims to identify those subjects with a higher genetic risk through the polymorphism of the APOE gene, using a population screening in patients with a clinical diagnosis of AD in a region of Spain, Castilla y León, as potential biomarkers and to identify individuals at increased genetic risk by polymorphism of the APOE gene. An observational case-control study was conducted in Castilla y León (Spain). Saliva samples were collected and the ApoE gene was analyzed by PCR and agarose gel electrophoresis, respecting ethical criteria. Results: In the Alzheimer’s population in Castilla y León, a high prevalence of ApoE3 (74%) was found, followed by ApoE4 (22%); in addition, a higher presence of the ε4 allele was found in the Alzheimer’s disease (AD) group than in the control group. It was also observed that the ε2/ε2 genotype was not found in any individual with AD but was found in healthy subjects and that the opposite was observed for the ε4/ε4 genotype. The odds ratio (OR) indicated a risk four times greater of having AD if having the ε4 allele. Conclusions: The demonstrated relation between the different isoforms and the likelihood of developing AD has led to its consideration as a biomarker and a potential pre-symptomatic therapy. The molecular mechanisms that confer a disruptive and protective role to ApoE4 and ApoE2, respectively, are still being studied.

Childhood obesity is a major public health burden. The prevalence of weight excess for children and the adolescent population (8 to 16 years) is 34.9%. During childhood, lifestyles are acquired, which are developed in adulthood. In this context, the role of parents is crucial, since they are the model to imitate. We aimed to evaluate the current evidence on the effects of family-based interventions as a tool in the treatment of childhood obesity. We reviewed studies indexed in several databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Original articles published from 1 January 2014 to 30 May 2024 with a controlled trial design were considered, in which family-based interventions were carried out compared to a control group or to data before the intervention. Although 148 records were identified in the search, 6 studies met inclusion criteria. Overall, studies reported beneficial effects of family-based interventions on improving anthropometric parameters: BMI z-score, BMI, waist circumference, and body fat percentage. Regarding nutritional and physical activity guidelines, general recommendations must consider increased consumption of fruits and vegetables, reducing sugary drinks, controlled screen time, and 30–60 min of physical activity/day. Thus, family-based interventions could be an effective non-pharmacological strategy for modulating childhood obesity, allowing families to modify their lifestyles.

Introduction: Non-adherence to antidepressants is associated with worse disease outcomes (morbidity and mortality) and correlates with higher healthcare resource utilization and costs.Methods: A population-based registry study was conducted to assess non-adherence and to analyze the economic burden of treatment and from non-adherence to antidepressants in 2021. Non-adherence was measured by the Medication Possession Ratio and those below 80% were classified as non-adherent.Results: In 2021, 246,718 patients (10.60% [95% CI: 10.48–10.72]) received antidepressants at a cost of €29 million. The median antidepressant cost per patient/year was €70.08€, ranging from €7.58 for amitriptyline to €396.66 for agomelatine. Out-of-pocket costs represented 6.09% of total expenditures, with a median copayment of €2.78 per patient. The 19.87% [95% CI 19.52–20.22)] of patients were non-adherent to antidepressants, costing €3.9 million (13.30% of total antidepressant costs). Non-adherence rates exceeded 20% for the tricyclic antidepressants, fluoxetine (23.53%), fluvoxamine (22.42%), and vortioxetine (20.58%). Venlafaxine (14.64%) and citalopram (14.88%) had the lowest non-adherence rates, of less than 15%. The median cost of non-adherent medications per patient/year was €18.96 and ranged from €2.50 (amitriptyline) to €133.42 (agomelatine).Conclusion: Reducing non-adherence to antidepressants is critical to improving clinical and economic outcomes. The implementation of interventions and standardized measures, including early detection indicators, is urgently needed. Antidepressants differ with regard to non-adherence and their cost, and this should be considered when prescribing this medication. The Medication Possession Ratio could be used by the healthcare provider and clinician to identify non-adherent patients for monitoring, and to take necessary corrective actions.

BackgroundThe lockdown imposed during the COVID-19 pandemic led to social isolation and prevented patients with dementia from receiving a suite of non-pharmacological interventions (NPIs) that prevent cognitive decline. This discontinuation of NPIs could substantially affect the mental health status of people with dementia in social care settings, such as adult day care centers (ADCs).ProposeThe study aimed to evaluate the effects of the COVID-19 lockdown on mental health and cognitive impairment in patients with dementia who could not attend their usual ADCs and did not receive our NPIs, based on World Health Organization (WHO) Guidelines.MethodsObservational, longitudinal, retrospective study carried out in an adult day center in Spain and reported it in accordance with the Strengthening Reporting of Observational Studies in Epidemiology (STROBE) statement. Cognitive status was assessed using the Mini-Mental State Examination (MMSE) in 80 patients attending the ADC of the “Leonese Association of Dementia Patients” (León, Spain), who had been evaluated with this instrument before the COVID-19 lockdown.ResultsWe observed a 0.4-point decrease in MMSE score/month (IQR = 1.4) during lockdown versus a 0.1-point decrease/month (IQR = 0.3) before this period (p = 0.038). Notably, this translated to >10-point decreases in MMSE score/year in 33.8% of participants during lockdown versus 5.5% earlier (p

Billions of cells die in us every hour, and our tissues do not shrink because there is a natural regulation where Cell Death (CD) is balanced with cell division. The process in which cells eliminate themselves in a controlled manner is called Programmed Cell Death (PCD). The PCD plays an important role during embryonic development, in maintaining homeostasis of the body’s tissues, and in the elimination of damaged cells, under a wide range of physiological and developmental stimuli. A multitude of protein mediators of PCD have been identified and signals have been found to utilize common pathways elucidating the proteins involved. This narrative review focuses on caspase-dependent and caspase-independent PCD pathways. Included are studies of caspase-dependent PCD such as Anoikis, Catastrophe Mitotic, Pyroptosis, Emperitosis, Parthanatos and Cornification, and Caspase-Independent PCD as Wallerian Degeneration, Ferroptosis, Paraptosis, Entosis, Methuosis, and Extracellular Trap Abnormal Condition (ETosis), as well as neutrophil extracellular trap abnormal condition (NETosis) and Eosinophil Extracellular Trap Abnormal Condition (EETosis). Understanding PCD from those reported in this review could shed substantial light on the processes of biological homeostasis. In addition, identifying specific proteins involved in these processes is mandatory to identify molecular biomarkers, as well as therapeutic targets. This knowledge could provide the ability to modulate the PCD response and could lead to new therapeutic interventions in a wide range of diseases.

Lower back pain (LBP) describes pain of indeterminate duration between the lower edge of the ribs and the buttocks. LBP hinders movement, quality of life, and mental well-being, and limits work activities and engagement with family and friends. LBP represents a public health problem, and most workers are expected to experience LBP symptoms throughout their working lives. The study’s main objective was to characterize LBP in the hospitality population of the province of León, Spain, determining the risk factors. A pilot study with a cross-sectional observational design was developed following the guidelines of Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) for 150 Spanish hotel workers. Sociodemographic and lifestyle, occupational, and clinical data related to LBP were obtained through surveys. The annual prevalence of LBP in this study was 87.1% which was higher in women. A significant relationship (p < 0.05) was obtained between sex, income, smoking, sleep quality, and all labor variables with LBP. In addition, the Fear Avoidance Beliefs Questionnaire (FABQ) results revealed that 49% of the participants had a score > 14. Also, 83.3% of patients with >6 annual LBP crises suffered from sciatica. Once the results were known, preventive intervention would be needed to reduce these main risk factors for LBP for hospitality workers.

Vitamin D substantially influences sports performance and post-exercise recovery because it offers anti-inflammatory, antioxidant and cellular protective properties. However, deficient levels of 25-hydroxyvitamin D 25(OH)D (25(OH)D) (® practitioners. Knowing these relationships could be instrumental for personalized vitamin D supplementation and training strategies. Using a standardized commercial enzyme-linked immunosorbent assay procedure, the concentrations of 25(OH)D were determined and the genotyping procedures for each SNPs were carried out using specific assays with the KASpar® test. The 25(OH)DA performance level in grades was established based on the CrossFit® Total score (sum in kilograms of one Repetition Max Squat, Press and Deadlift). Significant differences (p < 0.05) in 25(OH)D concentration were found between each of the SNPs of CYP2R1 and GC with 25(OH)D. We discovered statistically significant weak positive correlations (p < 0.05) between 25(OH)D and AA-alleles of the CYP2R1 and VDR genes, and TT-alleles of the GC gene. Additionally, AA (rs10741657 and rs2228570) and TT (rs2282679) have a probability between 2 and 4 of having major concentrations of 25(OH)D and 25(OH)D25(OH)D. Conversely, GG alleles present a probability of suboptimum values of 25(OH)D of 69%, 34% and 24% for VDR, GC and CYP2R1, respectively, showing a strong moderate positive correlation (r = 0.41) between the degrees of sports performance and 25(OH)D25(OH)D plasma levels. The different polymorphisms of our three candidate genes CYP2R1 (rs10741657), GC (rs2282679) and VDR (rs2228570) disturb 25(OH)D concentration and play a critical role in the sports performance of elite CrossFit® practitioners. These results could highlight that the evaluation of genetic factors is key to designing a vitamin D supplementation strategy to improve sports performance.

Low back pain (LBP) is a health problem that affects 70–80% of the population in Western countries. Because of the biomechanical relationship between the lumbar region and the hip, it is thought that strengthening the muscles of this joint could improve the symptoms of people with LBP. The objective of this study is to evaluate the current evidence on the efficacy of hip strengthening exercises to reduce pain and disability in people with LBP. Clinical trials were collected from the PubMed, PEDro, and Scopus databases published up to September 2022. Based on the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines and using CASP and PEDro tools for methodological quality assessment, we selected studies that included hip strengthening exercises as part of LBP treatment and measured pain and/or disability parameters. Among the 966 records identified in the search, a total of 7 studies met the established selection criteria. Overall, participants who performed hip strengthening exercises had significantly improved in pain and disability. The methodological quality of the included studies was assessed as “good”. In conclusion, the addition of hip muscle strengthening exercises iterating interacted with LBP, effectively improving pain and disability.

Supplementation with probiotics in sports is on the rise with the aim of improving health and athletic performance. Since intense exercise-induced muscle damage leads to an inflammatory process by increasing circulating inflammatory cytokines, probiotic supplementation may modulate and correct the inflammation. We systematically reviewed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in the Scopus, Web of Science, and Medline databases for the 10 years until January 2023. This review aimed to evaluate probiotic supplementation as a strategy for modulating inflammation in healthy physically active adults or athletes. Studies were indexed to assess the effect of probiotic supplementation on cytokine behavior in the inflammatory response in physically active individuals. Of the 136 studies identified in the search, 13 met the inclusion criteria, and their quality was assessed using the McMaster Critical Review Form. The results of these trials indicated a significant improvement in inflammatory cytokines in probiotic-supplemented participants, with a significant increase in anti-inflammatory cytokines (IL-10) and a significant decrease in proinflammatory cytokines (IL-6, TNF-α, and IL-8). This would create uncertainty about probiotics’ effect on interleukins’ behavior after exercise, and further clinical trials are needed to establish a solid basis.

The European DRUID (Drive Under the Influence of drugs, alcohol, and medicines) program classifies medications into three categories according to their effect on one’s fitness to drive. The trend in the use of driving-impairing medicines (DIMs) in a region of Spain between 2015 and 2019 was analyzed through a population-based registry study. Pharmacy dispensing records for DIMs are provided. The use of DIMs on drivers was weighted according to the national driver’s license census. The analysis was performed considering the population distribution by age and sex, treatment length, and the three DRUID categories. DIMs were used by 36.46% of the population and 27.91% of drivers, mainly chronically, with considerable daily use (8.04% and 5.34%, respectively). Use was more common in females than in males (42.28% vs. 30.44%) and increased with age. Among drivers, consumption decreases after 60 years of age for females and after 75 years of age for males. There was a 34% increase in the use of DIMs between 2015 and 2019, with a focus on daily use (>60%). The general population took 2.27 ± 1.76 DIMs, fundamentally category II (moderate influence on fitness to drive) (20.3%) and category III (severe influence on fitness to drive) (19.08%). The use of DIMs by the general population and drivers is significant and has increased in recent years. The integration of the DRUID classification into electronic prescription tools would assist physicians and pharmacists in providing adequate information to the patient about the effects of prescribed medications on their fitness to drive.

Exercise capacity is limited by environmental heat stress because thermoregulatory systems are altered and cannot prevent the elevation of body temperature due to a complex interplay of physiological, physical, and perceptual alterations. Cooling is an effective strategy to attenuate the temperature rise. Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the PEDro scale for assessing methodological quality, we systematically reviewed studies indexed in Medline, Web of Science, EMBASE, Science Direct, Sportdiscus, and Scopus, to evaluate the effects of the cooling vest (CVs) on perceptual response, physiological behavior, and sports performance in adult physical activity practitioners under heat stress conditions. Among the 711 studies identified in the search, 10 studies for the systematic review and eight for the meta-analysis met the inclusion and exclusion criteria. Overall, the use of CVs showed improvements in certain sports performance indicators, being significant (p < 0.05) in test time and substantial in peak power that could be influenced directly by the significant reduction (p < 0.05) in skin temperature and indirectly by the significant improvement (p < 0.05) in thermal and exertional perceptual responses, without the involvement of core temperature. In conclusion, the use of CVs is a cooling technique that influences perceptual response, thermo-physiological behavior, and sports performance. However, further studies are needed to elucidate the relevance of its application to CVs.

Scleroderma or systemic sclerosis (SSc) is an autoimmune disease affecting the connective tissue, characterized by fibrosis of the skin and internal organs. There is currently no curative treatment available, so therapeutic action is aimed at a symptomatic treatment of the affected organs. The development of biotechnology has made it possible to implement certain biological drugs that could represent a window of opportunity to modulate the evolution and symptomatology of scleroderma with greater efficacy and less toxicity than conventional treatments. This study aimed to review the current evidence critically and systematically on the effects of biological drugs on the pulmonary function, skin disease, and health status of patients afflicted by diffuse cutaneous systemic sclerosis (dcSSc). Three electronic databases (Pubmed, Dialnet, and Cochrane Library Plus) were systematically searched until the cut-off date of October 2022. The review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and included original articles in English and Spanish with a controlled trial design, comparing biological drug treatments (tocilizumab, belimumab, riociguat, abatacept, and romilkimab) with a control group. The methodological quality of the studies was assessed using the McMaster quantitative form and the PEDro scale. A total of 383 studies were identified, 6 of them met the established criteria and were included in the present systematic review. A total of 426 patients treated with tocilizumab, belimumab, riociguat, abatacept, and romilkimab were included. The results showed substantial non-significant (p < 0.05) improvement trends after treatment with the biological drugs included in this review for the modified Rodnan Scale Value, Forced Vital Capacity, and Carbon Monoxide Diffusion Test; however, no benefits were shown on the Health Assessment Questionnaire–Disability Index when compared to the control group. Biological drugs, therefore, maybe a new therapeutic strategy for dcSSc and could be recommended as an additional and/or adjunctive treatment that promotes anti-fibrotic activity. This review could further define the clinical rationale for the use of biologics in the treatment of dcSSc and could provide key details on the study protocol, design, and outcome reporting.

Antidepressants are a commonly prescribed psychotropic medication, and their use has increased in recent years. Medication non-adherence in patients with mental disorders is associated with worse health outcomes. A population-based registry study to assess antidepressant non-adherence during 2021 has been carried out. An indirect method based on the medication possession ratio (MPR) has been utilized. Patients with a MPR under 80% were classified as non-adherent. A multivariate logistic regression to identify non-adherence predictors has been used, considering sociodemographic (age, sex, institutionalization and urbanicity) and health related variables (diagnostics, antidepressant class, multiple prescribers, and polypharmacy). In 2021, 10.6% of the Castile and Leon population used antidepressants. These patients were institutionalized (7.29%), living in urban areas (63.44%), polymedicated with multiple prescribers (57.07%), and using serotonin selective reuptake inhibitors (SSRIs) (54.77%), other antidepressants (46.82%) or tricyclic antidepressants (TCAs) (13.76%). Antidepressants were prescribed mainly for depression (36.73%) and anxiety (29.24%). Non-adherence to antidepressants was more frequent in men (20.56%) than in woman (19.59%) and decreased with increasing age (32% up to 17 years old vs. 13.76% over 80 years old). TCAs were associated with the highest prevalence of non-adherence (23.99%), followed by SSRIs (20.19%) and other antidepressants (18.5%). Predictors of non-adherence in patients on antidepressants were: living in urban areas, using TCAs, and pain occurrence. Non-adherence to antidepressants decreases with aging. Being female, institutionalization, being polymedicated and having depression/anxiety alongside another psychiatric diagnosis are protective factors against non-adherence. The MPR is a robust indicator for the clinician to identify non-adherent patients for monitoring, and adopt any necessary corrective actions.

In the current global scenario, many COVID-19 survivors present a severe deterioration in physical strength, respiratory function, and quality of life due to persistent symptoms and post-acute consequences of SARS-CoV-2 infection. These alterations are known as post-COVID-19 syndrome for which there is no specific and effective treatment for their management. Currently, therapeutic exercise strategies (ThEx) are effective in many diseases by reducing the appearance of complications and side effects linked to treatment, and are consequently of great relevance. In this study, we review the effect of ThEX in reversing decreased strength, impaired respiratory function, decreased physical fitness, and decreased quality of life (QoL) caused by post-COVID-19 syndrome. A literature search was conducted through the electronic databases, Medline (PubMed), SciELO and Cochrane Library Plus for this structured narrative review for studies published from database retrieval up till 12 December 2022. A total of 433 patients with post-COVID-19 syndrome condition (60% women) were included in the nine studies which met the inclusion/exclusion criteria. Overall, post-COVID-19 syndrome patients who followed a ThEx intervention showed improvements in strength, respiratory function, physical fitness and QoL, with no exercise-derived side effects. Thus, ThEx based on strength, aerobic and respiratory training could be an adjuvant non-pharmacological tool in the modulation of post-COVID-19 syndrome.

Sports performance in athletes can be limited by respiratory factors, so it is understandable to propose that inspiratory muscle training (IMT) can improve respiratory function and exercise performance. Power-Breathe® (PwB) is a sectorized respiratory muscle training tool that uses a resistive load to train IMT. There is currently a growing interest in respiratory muscle training, so we set out to systematically assess the effects of IMT with PwB on respiratory parameters and athletic performance in physically active, healthy adults. Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline, the Cochrane and PEDro scales to assess methodological quality, effect size using the Rosenthal formula, and the Cochrane tool for estimation of risk of bias, studies searchable in Medline, Web of Science, and Cochrane. In addition, for the performance of the meta-analysis, the documentation and quantification of the heterogeneity in each meta-analysis were directed through the Cochran’s Q test and the I2 statistic; in addition, a publication bias analysis was performed using funnel plots. Of the total of 241 studies identified in the search, 11 studies for the systematic review and nine for the meta-analysis met the exclusion and/or inclusion criteria. IMT, with PwB, showed significant improvements in maximal inspiratory pressure (MIP) and substantial improvements in forced vital capacity (FVC) in the meta-analysis results. Also, sports performance was significantly increased by IMT with PwB. In conclusion, the use of PwB is an IMT tool that improves respiratory and sports performance.

El entrenamiento en altitud y el entrenamiento en hipoxia simulada producen adaptaciones fisiológicas y bioquímicas en el músculo esquelético como la capacidad oxidativa, así como modificaciones de la actividad mitocondrial, en el metabolismo aerobio y en el contenido de mioglobina. El propósito de esta revisión fue analizar las adaptaciones del músculo esquelético en respuesta a la exposición temporal a la hipoxia combinada con ejercicios de fuerza y resistencia. Según los hallazgos de numerosos autores, las adaptaciones estructurales del músculo son similares en la hipoxia y en la ‘normoxia’, con excepción de un aumento en el volumen muscular y en el área de la sección transversal de la fibra muscular, que son mayores en la hipoxia. En conclusión, la sinergia del entrenamiento de fuerza y resistencia y la hipoxia normobárica produce mejores y mayores adaptaciones, ganancias y cambios fisiológicos beneficiosos en el tejido muscular, lo cual genera cambios fenotípicos favorables, como la hipertrofia del músculo esquelético.

The world is currently experiencing the coronavirus disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome-2 (SARS-CoV-2). Its global spread has resulted in millions of confirmed infections and deaths. While the global pandemic continues to grow, the availability of drugs to treat COVID-19 infections remains limited to supportive treatments. Moreover, the current speed of vaccination campaigns in many countries has been slow. Natural substrates with biological immunomodulatory activity, such as glucans, may represent an adjuvant therapeutic agent to treat SARS-CoV-2. AM3, a natural glycophosphopeptical, has previously been shown to effectively slow, with no side effects, the progression of infectious respiratory diseases by regulating effects on innate and adaptive immunity in experimental models. No clinical studies, however, exist on the use of AM3 in SARS-CoV-2 infected patients. This review aims to summarize the beneficial effects of AM3 on respiratory diseases, the inflammatory response, modulation of immune response, and attenuation of muscle. It will also discuss its potential effects as an immune system adjuvant for the treatment of COVID-19 infections and adjuvant for SARS-CoV-2 vaccination.

Sarcopenia (Sp) is the loss of skeletal muscle mass associated with aging which causes an involution of muscle function and strength. Satellite cells (Sc) are myogenic stem cells, which are activated by injury or stress, and repair muscle tissue. With advancing age, there is a decrease in the efficiency of the regenerative response of Sc. Diagnosis occurs with the Sp established by direct assessments of muscle. However, the detection of biomarkers in real-time biofluids by liquid biopsy could represent a step-change in the understanding of the molecular biology and heterogeneity of Sp. A total of 13 potential proteogenomic biomarkers of Sp by their physiological and biological interaction with Sc have been previously described in the literature. Increases in the expression of GDF11, PGC-1α, Sirt1, Pax7, Pax3, Myf5, MyoD, CD34, MyoG, and activation of Notch signaling stimulate Sc activity and proliferation, which could modulate and delay Sp progression. On the contrary, intensified expression of GDF8, p16INK4a, Mrf4, and activation of the Wnt pathway would contribute to early Sp development by directly inducing reduced and/or altered Sc function, which would attenuate the restorative capacity of skeletal muscle. Additionally, tissue biopsy remains an important diagnostic tool. Proteomic profiling of aged muscle tissues has shown shifts toward protein isoforms characteristic of a fast-to-slow transition process and an elevated number of oxidized proteins. In addition, a strong association between age and plasma values of growth differentiation factor 15 (GDF-15) has been described and serpin family A member 3 (serpin A3n) was more secreted by atrophied muscle cells. The identification of these new biomarkers holds the potential to change personalized medicine because it could predict in real time the course of Sp by monitoring its evolution and assessing responses to potential therapeutic strategies.

The literature suggests that real-world data on the effectiveness and safety of the BNT162b2 vaccine depend on the characteristics of the vaccinated volunteers. The purpose of this study was to evaluate antibody responses and kinetics, established association with sociodemographic and clinical characteristics, and adverse reactions after complete vaccination with the BNT162b2 vaccine. A single-center prospective case series study was conducted with 112 eligible volunteers who were institutionalized elderly and health care workers with had a negative anti-SARS-CoV-2 IgG test prior to receiving the first dose of vaccine. At least one serological antibody test after each dose of vaccine was performed. Volunteers with a positive SARS-CoV-2 PCR test before vaccination were excluded. A chemiluminescent immunoassay anti-S1 antibody assay performed a serological evaluation. Both vaccine doses elicited positive IgG antibodies 3799.0 ± 2503.0 AU/mL and 8212.0 ± 4731.0 AU/mL after 20 days of the first and second doses of BNT162b2, respectively. Comirnaty® vaccine induced an immune response with antibody production against SARS-CoV-2 in 100% of participants, regardless of age (Spearman rho = −0.10, p-value = 0.312), body mass index (Spearman rho = 0.05, p-value = 0.640), blood group first dose (p-value for Kruskal–Wallis test = 0.093) and second dose (p-value for Kruskal–Wallis test = 0. 268), number of drugs (Spearman rho = −0.07, p-value = 0.490), and number of chronic diseases first dose (p-value for Kruskal–Wallis test = 0.632) and second dose (p-value for Kruskal–Wallis test = 0.510). IgG antibodies to SARS-CoV-2 were intensely elevated after the second administration of the BNT162b2 vaccine. The higher the titer of anti-peptide IgG antibodies generated after the first dose of vaccine, the higher the titer generated by the second dose of vaccine (Spearman rho = 0.86, p-value < 0.001) and the total antibody titer (Spearman rho = 0.93, p-value < 0.001). Furthermore, no serious adverse effects were reported among participants, although mild to moderate adverse effects (local or systemic) were reported after both doses of the BNT162b2 vaccine, being more frequent after the first dose of the vaccine. No participants showed a positive PCR. The BNT162b2 vaccine induces a robust and rapid antibody response regardless of participant characteristics. The second dose might be especially important because of the increased immunogenicity it produces and the possible temporal distancing of the interval between doses. In general, the vaccines were well tolerated.

Coronavirus 2019 disease (COVID-19) represents one of the largest pandemics the world has faced, and it is producing a global health crisis. To date, the availability of drugs to treat COVID-19 infections remains limited to supportive care although therapeutic options are being explored. Some of them are old strategies for treating infectious diseases. convalescent plasma (CP) therapy has been used successfully in other viral outbreaks in the 20th century. In this study, we systematically evaluated the effect and safety of CP therapy on hospitalized COVID-19 patients. A structured search was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines using Medline (PubMed), SciELO, Cochrane Library Plus, Web of Science, and Scopus. The search included articles published up to January 2022 and was restricted to English- and Spanish-language publications. As such, investigators identified six randomized controlled trials that met the search criteria. The results determined that in hospitalized COVID-19 patients the administration of CP therapy with a volume between 200–500 mL and a single transfusion performed in 1–2 h, compared to the control group, decreased viral load, symptomatology, the period of infection, and mortality, without serious adverse effects. CP did influence clinical outcomes and may be a possible treatment option, although further studies will be necessary.

Citrulline (CIT) and nitrate-rich beetroot extract (BR) are widely studied ergogenic aids. Nevertheless, both supplements have been studied in short-term trials and separately. To the best of the authors’ knowledge, the effects of combining CIT and BR supplementation on recovery status observed by distance covered in the Cooper test, exercise-induced muscle damage (EIMD) and anabolic/catabolic hormone status have not been investigated to date. Therefore, the main purpose of this research was to assess the effect of the long-term (9 weeks) mixture of 3 g/day of CIT plus 2.1 g/day of BR (300 mg/day of nitrates (NO3−)) supplementation on recovery by distance covered in the Cooper test, EIMD markers (urea, creatinine, AST, ALT, GGT, LDH and CK) and anabolic/catabolic hormones (testosterone, cortisol and testosterone/cortisol ratio (T/C)) in male trained triathletes. Thirty-two triathletes were randomized into four different groups of eight triathletes in this double-blind, placebo-controlled trial: placebo group (PLG), CIT group (CITG; 3 g/day of CIT), BR group (BRG; 2.1 g/day of BR (300 mg/day of NO3−)) and CIT-BR group (CIT-BRG; 3 g/day of CIT plus 2.1 g/day of BR (300 mg/day of NO3−)). Distance covered in the Cooper test and blood samples were collected from all participants at baseline (T1) and after 9 weeks of supplementation (T2). There were no significant differences in the interaction between group and time in EIMD markers (urea, creatinine, AST, ALT, GGT, LDH and CK) (p > 0.05). However, significant differences were observed in the group-by-time interaction in distance covered in the Cooper test (p = 0.002; η2p = 0.418), cortisol (p = 0.044; η2p = 0.247) and T/C (p = 0.005; η2p = 0.359). Concretely, significant differences were observed in distance covered in the Cooper test percentage of change (p = 0.002; η2p = 0.418) between CIT-BRG and PLG and CITG, in cortisol percentage change (p = 0.049; η2p = 0.257) and in T/C percentage change (p = 0.018; η2p = 0.297) between CIT-BRG and PLG. In conclusion, the combination of 3 g/day of CIT plus 2.1 g/day of BR (300 mg/day of NO3−) supplementation for 9 weeks did not present any benefit for EIMD. However, CIT + BR improved recovery status by preventing an increase in cortisol and showing an increase in distance covered in the Cooper test and T/C.

Coronavirus disease 2019 (COVID-19) is a multisystem disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), that primarily causes respiratory symptoms. However, an increasing number of cutaneous manifestations associated with this disease have been reported. The aim of this study is to analyze the scientific literature on cutaneous manifestations associated with SARS-CoV-2 by means of a narrative literature review until June 2021. The search was conducted in the following electronic databases: Medline (PubMed), SciELO, and Cochrane Library Plus. The most common cutaneous manifestations in patients with COVID-19 are vesicular eruptions, petechial/purpuric rashes, acral lesions, liveoid lesions, urticarial rash, and maculopapular-erythematous rash. These manifestations may be the first presenting symptoms of SARS-CoV-2 infection, as is the case with acral lesions, vesicular eruptions, and urticaria. In relation to severity, the presence of liveoid lesions may be associated with a more severe course of the disease. Treatment used for dermatological lesions includes therapy with anticoagulants, corticosteroids, and antihistamines. Knowledge of the dermatologic manifestations associated with SARS-CoV-2 contributes to the diagnosis of COVID-19 in patients with skin lesions associated with respiratory symptoms or in asymptomatic patients. In addition, understanding the dermatologic lesions associated with COVID-19 could be useful to establish a personalized care plan.

The term liquid biopsy (LB) refers to the study of circulating tumor cells, circulating tumors nucleic acids free of cells or contained in exosomes, and information about platelets associated with tumors. LB can be performed in different biofluids and allows the limitations of tissue biopsy to be overcome offering possibilities of tumor identification reflecting in real time tumor heterogeneity. In addition, LB allows screening and early detection of cancer, real-time monitoring of therapy, stratification and therapeutic intervention, a therapeutic target and resistance mechanism, and a risk of metastatic relapse. Currently, LB has been shown to be effective for its application in different types of tumors including lung, colorectal, prostate, melanoma, breast and pancreatic cancer, by the determination and identification of biomarkers that with a high probability have the potential to change the way in which medical oncology could predict the course of the disease. These biomarkers make it possible to capture the heterogeneity of the cancer, monitor its clonal evolution, indicate new treatments or retreatments and evaluate the responses to different evolutionary and/or therapeutic pressures in the cancer disease.

In recent years, there has been an increase in knowledge of cancer, accompanied by a technological development that gives rise to medical oncology. An instrument that allows the implementation of individualized therapeutic strategies is the liquid biopsy. Currently, it is the most innovative methodology in medical oncology. Its high potential as a tool for screening and early detection, the possibility of assessing the patient’s condition after diagnosis and relapse, as well as the effectiveness of real-time treatments in different types of cancer. Liquid biopsy is capable of overcoming the limitations of tissue biopsies. The elements that compose the liquid biopsy are circulating tumor cells, circulating tumor nucleic acids, free of cells or contained in exosomes, microvesicle and platelets. Liquid biopsy studies are performed on various biofluids extracted in a non-invasive way, and they can be performed both from the blood and in urine, saliva or cerebrospinal fluid. The development of genotyping techniques, using the elements that make up liquid biopsy, make it possible to detect mutations, intertumoral and intratumoral heterogeneity, and provide molecular information on cancer for application in medical oncology in an individualized way in different types of tumors. Therefore, liquid biopsy has the potential to change the way medical oncology could predict the course of the disease.

Creatine monohydrate (CrM) and β-hydroxy β-methylbutyrate (HMB) are widely studied ergogenic aids. However, both supplements are usually studied in an isolated manner. The few studies that have investigated the effect of combining both supplements on exercise-induced muscle damage (EIMD) and hormone status have reported controversial results. Therefore, the main purpose of this study was to determine the effect and degree of potentiation of 10 weeks of CrM plus HMB supplementation on EIMD and anabolic/catabolic hormones. This study was a double-blind, placebo-controlled trial where participants (n = 28) were randomized into four different groups: placebo group (PLG; n = 7), CrM group (CrMG; 0.04 g/kg/day of CrM; n = 7), HMB group (HMBG; 3 g/day of HMB; n = 7), and CrM-HMB group (CrM-HMBG; 0.04 g/kg/day of CrM plus 3 g/day of HMB; n = 7). Before (baseline, T1) and after 10 weeks of supplementation (T2), blood samples were collected from all rowers. There were no significant differences in the EIMD markers (aspartate aminotransferase, lactate dehydrogenase, and creatine kinase) among groups. However, we observed significant differences in CrM-HMBG with respect to PLG, CrMG, and HMBG on testosterone (p = 0.006; η2p = 0.454) and the testosterone/cortisol ratio (T/C; p = 0.032; η2p = 0.349). Moreover, we found a synergistic effect of combined supplementation on testosterone (CrM-HMBG = −63.85% vs. CrMG + HMBG = −37.89%) and T/C (CrM-HMBG = 680% vs. CrMG + HMBG = 57.68%) and an antagonistic effect on cortisol (CrM-HMBG = 131.55% vs. CrMG + HMBG = 389.99%). In summary, the combination of CrM plus HMB showed an increase in testosterone and T/C compared with the other groups after 10 weeks of supplementation. Moreover, this combination presented a synergistic effect on testosterone and T/C and an antagonistic effect on cortisol compared with the sum of individual or isolated supplementation.

Background Although the majority of patients with acute myeloid leukemia initially respond to conventional chemotherapy, relapse is still the leading cause of death, probably because of the presence of leukemic stem cells that are insensitive to current therapies. We investigated the antileukemic activity and mechanism of action of zalypsis, a novel alkaloid of marine origin.Design and Methods The activity of zalypsis was studied in four acute myeloid leukemia cell lines and in freshly isolated blasts taken from patients with acute myeloid leukemia before they started therapy. Zalypsis-induced apoptosis of both malignant and normal cells was measured using flow cytometry techniques. Gene expression profiling and western blot studies were performed to assess the mechanism of action of the alkaloid.Results Zalypsis showed a very potent antileukemic activity in all the cell lines tested and potentiated the effect of conventional antileukemic drugs such as cytarabine, fludarabine and daunorubicin. Interestingly, zalypsis showed remarkable ex vivo potency, including activity against the most immature blast cells (CD34+ CD38− Lin−) which include leukemic stem cells. Zalypsis-induced apoptosis was the result of an important deregulation of genes involved in the recognition of double-strand DNA breaks, such as Fanconi anemia genes and BRCA1, but also genes implicated in the repair of double-strand DNA breaks, such as RAD51 and RAD54. These gene findings were confirmed by an increase in several proteins involved in the pathway (pCHK1, pCHK2 and pH2AX).Conclusions The potent and selective antileukemic effect of zalypsis on DNA damage response mechanisms observed in acute myeloid leukemia cell lines and in patients’ samples provides the rationale for the investigation of this compound in clinical trials.

Background Combinations of drug treatments based on bortezomib or lenalidomide plus steroids have resulted in very high response rates in multiple myeloma. However, most patients still relapse, indicating the need for novel combination partners to increase duration of response or to treat relapsed disease. We explored the antimyeloma activity of triple combinations of these well-established schemes with panobinostat, a novel deacetylase inhibitor with a multi-targeted profile.Design and Methods The activity of these combinations was explored in vitro in cell lines by using MTT and annex-in V, ex vivo by flow cytometry, and in vivo using two different murine models of human myeloma: one bearing a subcutaneous plasmacytoma and another with a disseminated myeloma. Moreover, gene expression profiling and immunohistochemical studies were performed.Results The addition of panobinostat (LBH589) to dexamethasone and either bortezomib or lenalidomide resulted in clear potentiation in multiple myeloma cell lines, freshly isolated plasma cells, and murine models of multiple myeloma. The quantification of the potency of these combinations by using the Chou-Talalay method showed synergistic combination indices for all of them. This effect derived from the deregulation of a cluster of genes that was completely different from the sum of genes affected by the single agents (895 and 1323 genes exclusively deregulated by panobinostat and dexamethasone plus bortezomib or lenalidomide, respectively). Functional experiments, such as annexin V staining, cell cycle analysis, and immunohistochemical studies also supported this potentiation. Anti-myeloma efficacy was confirmed in an extramedullary plasmacytoma model and a disseminated luciferized model, in which panobinostat also provided a marked benefit in bone disease.Conclusions The potent activity, together with the exclusive mechanistic profile, provides the rationale for the clinical evaluation of these drug combinations in multiple myeloma.