The Mechanisms of Regulated Cell Death: Structural and Functional Proteomic Pathways Induced or Inhibited by a Specific Protein-A Narrative Review.

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.

Online information and availability of three doping substances (anabolic agents) in sports: role of pharmacies.

Background: The Internet has become an important source for easy access to doping substances, where people and athletes may acquire, outside pharmacies and without a (medical) prescription. These online websites do not always offer quality-assured products, and are outside the regular distribution channels of medicines. The aim of this study was to estimate the availability and accessible information on the Internet about the sale of three doping substances (oxandrolone, DHEA, androstenedione). Methods: Cross-sectional exploratory study, being an observation at a point in time of the online availability of these three doping substances (WADA S1 category: anabolic agents), purchased from Spain, Puerto Rico, Canada, United States, Ukraine and Russia. The characteristics of the websites, the countries the webs sold to, the pharmaceutical forms offered and the recommendations for its use were analyzed by using a computer tool designed ad hoc. Results: There were significant differences between countries in the number of webpages that sold the products (Chi-square test, p < 0.05). Oxandrolone was available for purchase mainly when buying from Spain (27.12%) and Ukraine (26.58%), in websites dedicated to sports (77.26%). For DHEA, most of the pages offered it if the search was done from Canada (23.34%) and Russia (21.44%). Products containing androstenedione or DHEA are claimed to enhance sports performance or for sports use without providing details. Compared to the total number of websites checked, the proportion of pharmacies offering these products was low, ranging from 4.86% for DHEA to 15.79% for androstenedione. Conclusion: The three substances selected are easily available without control through the Internet. Only a small number of websites offering them were online pharmacies, and requested a prescription. Most of the doping substances are purchased from the country where they are requested. Product information described benefits for sports performance, but did not do the same with their side effects. It would be advisable for these products to be sold through pharmacies, to guarantee their quality and provide evidence-based information on their safe use, benefits and risks, and only with a prescription. Athletes should be encouraged to consult health professionals about those supplements suitable for their type of training and sports objectives.

Therapeutic Exercise Intervention Using Vibration Platforms for Glycemic Control in Type 2 Diabetes: A Pilot Study.

Diabetes generates a great impact on society, as well as a concern for health professionals due to its high and increasing prevalence; there are several studies that demonstrate the effectiveness of vibration platforms and their benefits at a physiological level. The aim of this study will be to analyze the decrease in glycosylated hemoglobin and glycemia levels after the use of whole-body vibration platforms and the possible inclusion of this therapeutic option within the usual treatments. This is a double-blind, randomized controlled trial with parallel group design in a 1:1 ratio. The sample will be composed of people diagnosed with type 2 diabetes mellitus in in the Plasencia area (Cáceres, Extremadura). Participants will be randomly assigned to the intervention or control group using a randomization list and will follow the inclusion criteria: type 2 diabetics between 50 and 60 years of age and not taking diabetes medication. All participants will undergo a determination of glycosylated hemoglobin, blood pressure, lipid profile, weight and height, and different functional tests such as Time Up and Go, 10 Meters Walk Test, and 5 Sit To Stand. The experimental group will perform a whole-body vibration intervention on an oscillating platform for 12 weeks with a weekly frequency of three nonconsecutive days and a duration of 12 min. The exercises will consist of 60 s of work and 60 s with rest. The control group will carry out their normal life insisting on the importance of glycemic controls before and after their daily physical exercise. This study has been registered at clinical.trial.org, ID: NCT05968222. Whole-body vibration platforms have demonstrated their effectiveness in different pathologies such as stroke, fibromyalgia, sclerosis multiple, or Parkinson's. For that reason, an improvement in glycemic and lipid values and body composition are expected in people with diabetes after a whole-body vibration intervention for 12 weeks' duration. In addition, whole-body vibration platforms could be postulated as an alternative to usual treatments.

Psychometric Properties of the Italian Version of the Toileting Habit Profile Questionnaire-Revised (THPQ-R) in Children with Autism Spectrum Disorder.

INTRODUCTION: Children with autism spectrum disorder (ASD) often seem not to feel the need to go to the bathroom in whatever context they are in and may suffer from hypo-responsiveness. Recent studies show a correlation between sensory problems, constipation, and fecal incontinence in children. This requires an assessment tool to identify evacuation issues in children with sensory dysfunction. Therefore, the purpose of this study is to validate the Italian version of The Toileting Habit Profile Questionnaire-Revised (THPQ-R) in children with ASD. METHODS: The inclusion criteria were a confirmed diagnosis of ASD and an age between 3 and 8 years old. The Toileting Habit Profile Questionnaire Revised (THPQ-R) was recently validated in the Italian language on a healthy population. The Italian version has 17 items with two alternative response options, frequently/always or never/rarely, based on how often the behavior occurs. The THPQ-R questionnaire is easy to administer, interpret, and manage. For concurrent validity, we used the Italian version of the Sensory Processing Measure and Sensory Processing Measure-Preschool. RESULTS: For the THPQ-R validation, 43 participants were recruited. The internal consistency, reporting an α value of 0.763, showed that the THPQ-R was a very reliable scale. The THPQ-R appears to be correlated only with the domains "Social Participation T-point", "Hearing T-point", and "Planning and Ideas T-point". However, these correlations are not statistically significant. Conclusion: The THPQ-R highlights positive results regarding validity and reliability and shows a positive correlation between defecation disorders and social participation.

Impact of discontinuing non-pharmacological interventions on cognitive impairment in dementia patients by COVID-19 lockdown. A pilot observational, longitudinal, retrospective study carried out in an adult day center in Spain during the COVID-19 pandemic.

Background: The 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). Propose: The 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. Methods: Observational, 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. Results: We 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 < 0.001). No statistically significant associations (p < 0.05) were found between the individual characteristics of the caregivers and the occurrence of the event. Conclusion: The reported declines in MMSE scores reveal a significant acceleration of cognitive decline during the period of inactivity. This could suggest that our NPIs, focused on slowing cognitive decline, are beneficial and, therefore, necessary in patients with dementia.

Explanatory Capacity of Postural Control and Physical Fitness in Cognitive Impairment and Support Needs among Individuals with Intellectual Disabilities-A Cross-Sectional Pilot Study.

Postural control is a skill associated with most motor activities and is essential for the performance of activities of daily living. People with intellectual disabilities (ID) present postural control deficits that can be attributed to several causes. The aim of this study was to determine whether postural control and physical fitness could explain the cognitive impairment and support needs in this population. A cross-sectional pilot study was conducted with 18 people with ID. Data collection was based on assessments for postural control (Mini BESTest and Berg Balance Scale) and physical fitness (Senior Fitness Test). The data were analyzed using linear regression models. Anticipatory postural adjustments were associated with support needs, explaining up to 45% of these. Consecutive postural adjustments and upper limb strength were less significantly associated with support needs. However, none of the variables used explained cognitive impairment in ID. Knowledge of the relationships and behavior of the different measurement tools is essential for the development of appropriate interventions in this population.

Influence of Transcranial Direct Current Stimulation and Exercise on Physical Capacity and Gait in Multiple Sclerosis: A Cross-Over Pilot Study.

Physical capacity provides a link between disease or impairment and limitations in activity; in multiple sclerosis (MS), it is limited and decreased. The aim of this study was to study the effects of exercise and transcranial direct current stimulation (tDCS) on the left dorsolateral prefrontal cortex area in MS patients with fatigue and an impaired gait ability. A cross-over design was carried out on fifteen patients with two disability associations, but three were excluded. Before and after each intervention, the 6 min walk test (6MWT) and the 2 min walk test (2MWT) were used to assess walking ability and the Modified Fatigue Impact Scale (MFIS) was used to assess fatigue. A total of twelve patients were enrolled (48.0 median age, Kurtzke Disability Scale (EDSS) 3.66 ± 1.3): five females and seven males. After the application of the exercise program, significant improvements were observed in the 6MWT (p < 0.001, g = 0.159) and 2MWT (p < 0.001, g = 0.182). Furthermore, fatigue was significantly reduced after the application of the exercise program (p < 0.05, g = 0.742) and after tDCS (p < 0.05, g = 0.525). We could consider therapeutic exercise in the future to improve the walking ability and fatigue in MS patients. Furthermore, tDCS did not exert a significant improvement in walking ability, but it appeared to influence fatigue. Clinical trial registration code: ACTRN12622000264785.

Efectos del rodillo de espuma o foam roller sobre el rango de movimiento, la flexibilidad, la fuerza y el dolor muscular de inicio retardado en deportistas de alto rendimiento / Effects of the use of foam rollers by high-performance athletes on range of motion, flexibility, strength and delayed onset muscle soreness

Introducción: El rodillo de espuma o Foam Roller (FR) es un instrumento de liberación miofascial autoinducida, para aplicarpresión de forma directa sobre la musculatura diana. FR es ampliamente empelado por deportistas como herramienta deauto-masaje. Objetivo: Evaluar la evidencia actual sobre el impacto del FR, sobre el sistema musculoesquelético, en deportistas, tratandode identificar los mecanismos que influyen sobre los tejidos miofasciales.Material y método: Basándonos en las directrices de los Elementos de Información Preferidos para Revisiones Sistemáticas yMetaanálisis (PRISMA), revisamos sistemáticamente estudios indexados en Web of Science, Cochrane y PubMed, para evaluarlos efectos del FR en el rango articular de movimiento (ROM), la flexibilidad, la fuerza y el dolor muscular de inicio retardado(DOMS) en deportistas de alto rendimiento. Se incluyeron artículos originales publicados desde el 2018 hasta el 30 de septiembre de 2022, con diseño de ensayo controlado o pre-post intervención, en los que se comparó la intervención de FR conun grupo control. Se utilizó la escala PEDro para evaluar de la calidad metodológica.Resultados: Entre los 141 registros identificados en la búsqueda, un total de 10 estudios cumplieron los criterios de inclusióny exclusión. En general, el uso de FR, en los deportistas de alto rendimiento, mostró mejoras significativas sobre el ROM yflexibilidad, y efectos notablemente beneficiosos sobre el DOMS y la fuerza, sin efectos adversos en el tejido miofascial. El FRpuede actuar mejorando la arquitectura tisular miofascial, atenuando el efecto inflamatorio y nociceptivo. Conclusión: El uso FR, parece seguro, es un instrumento efectivo para la mejora de las cualidades físicas de movilidad, fuerzay flexibilidad, y disminuir el DOMS incrementando del rendimiento deportivo.(AU)

Introduction: The Foam Roller (FR) is a self-induced myofascial release instrument to apply pressure directly on the targetmusculature. FR is widely used by athletes as a self-massage tool. Objective: We evaluate the current evidence on the impact of FR on the musculoskeletal system in athletes, trying to identifythe mechanisms that influence myofascial tissues.Material and method: Based on the Preferred Reporting Item Guidelines for Systematic Reviews and Meta-Analyses (PRISMA),we systematically reviewed studies indexed in Web of Science, Cochrane, and PubMed to evaluate the effects of FR on jointrange of motion (ROM), flexibility, strength, and delayed onset muscle soreness (DOMS) in high-performance athletes. Originalarticles published from 2018 through September 30, 2022, with controlled trial or pre-post intervention design, in which theFR intervention was compared to a control group, were included. The PEDro scale was used to assess methodological quality. Results: Among the 141 records identified in the search, a total of 10 studies met the inclusion and exclusion criteria. Ingeneral, the use of FR, in high performance athletes, showed significant improvements on ROM and flexibility, and markedlybeneficial effects on DOMS and strength, with no adverse effects on myofascial tissue. FR may act by improving myofascialtissue architecture, attenuating the inflammatory and nociceptive effect. Conclusion: The use of FR seems to be safe; it is an effective tool for the improvement of the physical qualities of mobility,strength, and flexibility, and to decrease DOMS and increase sports performance.(AU)

Nutrition, Nutritional Status and Functionality.

A good quality of life means obtaining adequate nutrition and regular physical activity [...].

Is the Cooling Vest an Ergogenic Tool for Physically Active Individuals? Assessment of Perceptual Response, Thermo-Physiological Behavior, and Sports Performance: A Systematic Review and Meta-Analysis.

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.

An Evaluation of Serological Tests to Determine Postvaccinal Immunity to SARS-CoV-2 by mRNA Vaccines.

BACKGROUND: The duration of the protective efficacy of vaccines against SARS-CoV-2 is unknown. Thus, an evaluation of the clinical performance of available tests is required. OBJECTIVES: To evaluate the clinical performance of LFIA immunoassay compared to ELIA and CLIA immunoassays available in Europe for the detection of IgG antibodies generated by mRNA vaccines against SARS-CoV-2. METHODS: Two automated immunoassays (the EUROIMMUN anti-SARS-CoV-2 IgG S1 ELISA and the LIAISON de Diasorin anti-SARS-CoV-2 IgG S1/S2 test) and a lateral flow immunoassay (the Livzon LFIA anti-SARS-CoV-2 IgG S test) were tested. We analyzed 300 samples distributed in three groups: 100 subjects aged over 18 years and under 45 years, 100 subjects aged between 45 and 65 years, and 100 subjects aged over 65 years. The samples were collected before vaccination; at 21 days; and then at 1, 2, 3, and 6 months after vaccination. The sensitivity, specificity, positive predictive value, negative predictive value, positive probability quotient, negative probability quotient, and concordance (kappa index) were calculated for each serological test. RESULTS: The maximum sensitivity values for IgG were 98.7%, 98.1%, and 97.8% for the EUROIMMUN ELISA, Abbott CLIA, and Livzon LFIA tests, respectively, and the maximum specificity values for IgG were 99.4%, 99.9%%, and 98.4% for the ELISA, CLIA, and LFIA tests, respectively, at the third month after vaccination, representing a decrease in the antibody levels after the sixth month. The best agreement was observed between the ELISA and CLIA tests at 100% (k = 1.00). The agreement between the ELIA, CLIA, and LFIA tests was 99% (k = 0.964) at the second and third month after vaccination. Seroconversion was faster and more durable in the younger age groups. CONCLUSION: Our study examined the equivalent and homogeneous clinical performance for IgG of three immunoassays after vaccination and found LFIA to be the most cost-effective, reliable, and accurate for routine use in population seroconversion and seroprevalence studies.

Efficacy of Therapeutic Exercise in Reversing Decreased Strength, Impaired Respiratory Function, Decreased Physical Fitness, and Decreased Quality of Life Caused by the Post-COVID-19 Syndrome.

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.

6-Week Supplementation with Tribulus terrestris L. to Trained Male CrossFit® Athletes on Muscle, Inflammation, and Antioxidant Biomarkers: A Randomized, Single-Blind, Placebo-Controlled Trial.

Tribulus terrestris L. (TT) ingredients have anti-inflammatory and antioxidant activities, but their effects on exercise-induced muscle damage (EIMD) in trained athletes are uncertain. The purpose of this single-blind placebo-controlled trial, in accordance with CONSORT guidelines, was to examine the effect of 6 weeks of TT supplementation on muscle metabolism, inflammation biomarkers, and oxidant status. Thirty trained male CrossFit® athletes were randomly assigned to be supplemented with 770 mg/day of TT (intervention group (IG)) or receive a placebo daily (control group (CG)) for 6 weeks. Muscle damage enzymes, inflammation biomarkers, and Total Antioxidant Status (TAS) were assessed at baseline (T1), 21 days after baseline (T2), and after 42 days (T3). Grace, a Workout of the Day, was measured in T1 and T3. Statistical significance (p < 0.05) was found between IG and CG in Lactate Dehydrogenase (LDH), C-reactive protein (CRP), and TAS levels at the end of the follow-up. Furthermore, TAS levels were significantly (p < 0.05) lower at T2 and T3 relative to baseline in the IG, also LDH and CRP increased significantly (p < 0.05) at T2 and T3 relative to baseline in the CG. No significant (p > 0.05) decreases in muscle damage or inflammation biomarkers were observed, although a slight downward trend was observed after 6 weeks for supplemented athletes. TT supplementation could attenuate the CrossFit® training program-induced oxidative stress, muscle damage, and inflammation which could be due to the natural antioxidant and anti-inflammatory properties of TT.

Duchenne de Boulogne: el camino de la ciencia al arte / Duchenne de Boulogne: the road from science to art

La obra de Guillaume Benjamín Amand Duchenne (1806-1871) ha sido ampliamente recogida y analizada. La mayoría de sus biógrafos destacan a un extraordinario científico y clínico, que revolucionó el campo de la neurología y la electroterapia. Sin embargo, se considera que no ha sido suficientemente destacada su mayor aportación: ser el nexo entre dos campos que habían sido independientes hasta ese momento, la electrofisiología y la fotografía artística. La culminación de esta simbiosis sería la publicación de Mécanisme De La Physionomie Humaine: Où, Analyse Électro-Physiologique De L’expression Des Passions, publicada en 1862. Para los autores del presente trabajo, el objetivo final de la obra de Duchenne no fue solo el de un científico y clínico, fue también el de un artista, empeñado en reflejar y desentrañar los mecanismos de la emoción y del sentimiento. Incluso, pretendió establecer un canon estético en la pintura y escultura en la expresión facial, que reflejase su ideal de belleza. Su obra, tuvo importantes repercusiones en la neurología y la electroterapia, en la fotografía médica y en el desarrollo de un nuevo espacio escénico: la representación del movimiento corporal provocado por corrientes eléctricas, el denominado Electric Performance Art.(AU)

The work of Guillaume Benjamin Amand Duchenne (1806-1871) has been widely collected and analyzed. Most of his biographers highlight an extraordinary scientific and clinician, who revolutionized the field of neurology and electrotherapy. It is considered though that his most important contribution has not been sufficiently highlighted: he was the nexus of union between two fields independent until then, electrophysiology and artistic photograph. The culmination of this symbiosis is the publication of Mécanisme De La Physionomie Humaine: Où, Analyse Électro-Physiologique De L’expression Des Passions published in 1862. To the authors of the present study, the goal of Duchenne’s work was not only that of a scientific and clinician but also that of an artist, determined to reflect and unravel the mechanisms of emotion and feeling. He even intended to establish an aesthetic canon in painting and sculpture in facial expression, reflecting his ideal of beauty. His work had important repercussions in neurology and electrotherapy, in medical photography and in the development of a new scenic space: the representation of body movement provoked by electric currents, named Electric Performance Art.(AU)

25-Hydroxyvitamin D Serum Levels Linked to Single Nucleotide Polymorphisms (SNPs) (rs2228570, rs2282679, rs10741657) in Skeletal Muscle Aging in Institutionalized Elderly Men Not Supplemented with Vitamin D.

Sarcopenia (Sp) is the loss of skeletal muscle mass associated with aging that results in an involution of muscle function and strength. Vitamin D deficiency is a common health problem worldwide, especially among the elderly, and hypovitaminosis D leads to musculoskeletal disorders. The aim of this study was to evaluate the impact and presence of a possible linkage between Single Nucleotide Polymorphisms (SNPs) CYP2R1 (rs10741657), GC (rs2282679), and VDR (rs2228570), serum 25-OH/D concentrations and the link with the degree of sarcopenia in 19 institutionalized elderly men not supplemented with vitamin D. Levels of 25-OH vitamin D were quantified with a commercial enzyme-linked immunosorbent assay kit and 3 SNPs were genotyped with KASPar assays. Significant differences in 25-OH/D concentration were determined between the bi-allelic combinations of rs228679 and rs228570. We detected statistically significant weak positive correlations between the AA (rs10741657 and rs228570) and TT (rs228679) and alleles and 25-OH/D and the probability of having higher 25-OH/D concentrations was 2- to 3-fold higher. However, the GG alleles of the 3 SNPs showed that the probability of having optimal 25-0H/D concentrations decreases by 32% for rs10741657, 38% for rs228679, and 74% for rs228570, showing a strong negative correlation between the degree of sarcopenia and 25-OH/D levels. Allelic variations in CYP2R1 (rs10741657), GC (rs2282679), and VDR (rs10741657) affect vitamin D levels and decisively influence the degree of sarcopenia in institutionalized elderly people.

Application of a person-centered prescription model improves pharmacotherapeutic indicators and reduces costs associated with pharmacological treatment in hospitalized older patients at the end of life.

Objective: This study sought to investigate whether applying an adapted person-centered prescription (PCP) model reduces the total regular medications in older people admitted in a subacute hospital at the end of life (EOL), improving pharmacotherapeutic indicators and reducing the expense associated with pharmacological treatment. Design: Randomized controlled trial. The trial was registered with ClinicalTrials.gov (NCT05454644). Setting: A subacute hospital in Basque Country, Spain. Subjects: Adults ≥65 years (n = 114) who were admitted to a geriatric convalescence unit and required palliative care. Intervention: The adapted PCP model consisted of a systematic four-step process conducted by geriatricians and clinical pharmacists. Relative to the original model, this adapted model entails a protocol for the tools and assessments to be conducted on people identified as being at the EOL. Measurements: After applying the adapted PCP model, the mean change in the number of regular drugs, STOPPFrail (Screening Tool of Older Persons' Prescriptions in Frail adults with limited life expectancy) criteria, drug burden index (DBI), drug-drug interactions, medication regimen complexity index (MRCI) and 28-days medication cost of chronic prescriptions between admission and discharge was analyzed. All patients were followed for 3 months after hospital discharge to measure the intervention's effectiveness over time on pharmacotherapeutic variables and the cost of chronic medical prescriptions. Results: The number of regular prescribed medications at baseline was 9.0 ± 3.2 in the intervention group and 8.2 ± 3.5 in the control group. The mean change in the number of regular prescriptions at discharge was -1.74 in the intervention group and -0.07 in the control group (mean difference = 1.67 ± 0.57; p = 0.007). Applying a PCP model reduced all measured criteria compared with pre-admission (p < 0.05). At discharge, the mean change in 28-days medication cost was significantly lower in the intervention group compared with the control group (-34.91€ vs. -0.36€; p < 0.004). Conclusion: Applying a PCP model improves pharmacotherapeutic indicators and reduces the costs associated with pharmacological treatment in hospitalized geriatric patients at the EOL, continuing for 3 months after hospital discharge. Future studies must investigate continuity in the transition between hospital care and primary care so that these new care models are offered transversally and not in isolation.

The Effect of Combining Transcranial Direct Current Stimulation Treatment and an Exercise Program on Fragility in a Population with Multiple Sclerosis: Cross-Over Design Trial.

BACKGROUND: The relationship between fragility and neurological diseases is extensive and affects many patients with multiple sclerosis (MS), whose risk factors are related to fragility. OBJECTIVE: To study the effects of exercise and transcranial direct current stimulation (tDCS) in MS patients with fatigue from four dimensions: functional mobility, balance, fatigue, and depression. METHODS: A total of 12 patients who belonged to two associations of people with physical disabilities participated. Functional mobility, depression, balance, and fatigue were assessed before and after the intervention. Transcranial direct current stimulation and the exercise program were carried out over a 4-week period with a wash-out period of 5 months. RESULTS: After the application of tDCS, we found significant improvements in balance (p < 0.05, g = 0.632), depression (p < 0.05, g = 0.402), functional mobility (p < 0.05, g = 0.297), and fatigue (p < 0.05, g = 0.526). After the exercise program, significant improvements were shown in balance (p < 0.01, g = 0.418), depression (p < 0.001, g = 0.540), functional mobility (p < 0.01, g = 0.262), and fatigue (p < 0.01, g = 0.742). Two-way mixed-measures ANOVA showed that all variables improved in both groups, with significant differences over time but not between groups. Secondary analysis showed significant correlations between balance and functional mobility (r = 0.671, p = 0.017), depression and fatigue (r = 0.586, p = 0.044) and between intensity of rehabilitation and balance (r = 0.622, p = 0.031). CONCLUSION: Participating in an exercise program and receiving tDCS separately improved the variables of depression, balance, mobility, and fatigue.

Platelet-derived growth factors from a single donor by apheresis and one freeze-thaw cycle for treating medication-related osteonecrosis of the jaw.

Aim: To assess whether the use of allogeneic platelet-derived growth factors could serve as a feasible, effective and safe biological therapy for the treatment of medication-related osteonecrosis of the jaw (MRONJ). Materials & methods: Patients with multiple myeloma and MRONJ were included and treated with allogeneic platelet-rich plasma, continued for between 6 and 18 weeks (mean: 9). Results: We observed a treatment success rate of 87.5% (p < 0.05). Assessing the association between healing and treatment duration, we observed a statistically significant relationship (χ2 = 8.00; p = 0.018; Cramer's V = 1), confirming that healing was very closely related to the duration of the treatment. Conclusion: Allogeneic platelet-rich plasma could be a recommended treatment for MRONJ. Future research with a large sample to validate our findings is required.

Potential Satellite Cell-Linked Biomarkers in Aging Skeletal Muscle Tissue: Proteomics and Proteogenomics to Monitor Sarcopenia.

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.