Mutational Profile and Retinal Phenotypes of PCARE-Related Cone-Rod Dystrophies in a Mexican Cohort.

Purpose: The aim of the study is to describe the genotype and phenotype of a Mexican cohort with PCARE-related retinal disease. Methods: The study included 14 patients from 11 unrelated pedigrees with retinal dystrophies who were demonstrated to carry biallelic pathogenic variants in PCARE. Visual assessment methods included best corrected visual acuity, color fundus photography, Goldmann visual field test, kinetic perimetry, dark/light adapted chromatic perimetry, full-field electroretinography, autofluorescence imaging, and spectral domain-optical coherence tomography imaging. Genetic screening was performed either by gene panel sequencing or by exome sequencing. Results: According to the results of multimodal imaging and functional tests, all 14 patients were diagnosed with cone-rod dystrophy. Six different PCARE pathogenic alleles were identified in our cohort, including three novel mutations: c.3048_3049del (p.Tyr1016∗), c.3314_3315del (p.Ser1105∗), and c.551A > G (p.His184Arg). Notably, alleles p.His184Arg, p.Arg613∗, and p.Arg984∗ were present in 18 of the 22 (82%) PCARE alleles from probands in our cohort. Conclusion: Our work expands the PCARE mutational profile by identifying three novel pathogenic variants causing retinal dystrophy. While phenotypic variations occurred among patients, a cone-rod dystrophy pattern was observed in all affected individuals.

Is developmental plasticity triggered by DNA methylation changes in the invasive cane toad (Rhinella marina)?

Many organisms can adjust their development according to environmental conditions, including the presence of conspecifics. Although this developmental plasticity is common in amphibians, its underlying molecular mechanisms remain largely unknown. Exposure during development to either 'cannibal cues' from older conspecifics, or 'alarm cues' from injured conspecifics, causes reduced growth and survival in cane toad (Rhinella marina) tadpoles. Epigenetic modifications, such as changes in DNA methylation patterns, are a plausible mechanism underlying these developmental plastic responses. Here we tested this hypothesis, and asked whether cannibal cues and alarm cues trigger the same DNA methylation changes in developing cane toads. We found that exposure to both cannibal cues and alarm cues was associated with local changes in DNA methylation patterns. These DNA methylation changes affected genes putatively involved in developmental processes, but in different genomic regions for different conspecific-derived cues. Genetic background explains most of the epigenetic variation among individuals. Overall, the molecular mechanisms triggered by exposure to cannibal cues seem to differ from those triggered by alarm cues. Studies linking epigenetic modifications to transcriptional activity are needed to clarify the proximate mechanisms that regulate developmental plasticity in cane toads.

Exercise Intervention and Hospital-Associated Disability: A Nonrandomized Controlled Clinical Trial.

Importance: Inpatient exercise interventions may prevent, at least partly, hospital-associated disability (HAD) in older adults, but whether they also confer clinical benefits in the months following discharge is unclear. Objective: To examine the association of exercise and health education with HAD incidence in hospitalized older adults receiving acute hospital care at discharge and 3 months later. Design, Setting, and Participants: This single-center open-label, nonrandomized controlled clinical trial included patients aged 75 years or older seen at an acute care for elders unit at a tertiary public hospital in Madrid, Spain, from May 1, 2018, to June 30, 2022. Interventions: Patients were allocated to an intervention or control group. Both groups received usual care, but the intervention group also performed a supervised multicomponent exercise program (daily strength, balance, and walking exercises along with inspiratory muscle training) during hospitalization and received health education on how to exercise at home and telephone counseling during follow-up. Main Outcomes and Measures: The primary outcome was HAD incidence (determined by the Katz Index of Independence in Activities of Daily Living [hereafter, Katz Index]) at discharge and after 3 months compared with baseline (ie, 2 weeks before admission). Secondary outcomes included HAD incidence determined by the Barthel Index for Activities of Daily Living, ambulatory capacity decline at discharge and follow-up, changes in physical performance at discharge, and incidence of falls, readmissions, and mortality during the follow-up period. Results: The study included 260 patients (134 women [51.5%]; mean [SD] age, 87.4 [4.9] years [range, 75-105 years]; median hospital length of stay, 7 days [IQR, 5-10 days]), of whom 130 received the intervention and 130 were in the control group. Differences in HAD incidence did not reach statistical significance at discharge (odds ratio [OR], 0.62; 95% CI, 0.37-1.05; P = .08) or follow-up (OR, 0.65; 95% CI, 0.36-1.17; P = .15) when using the Katz Index. A lower HAD incidence was observed in the intervention group at discharge (OR, 0.47; 95% CI, 0.27-0.81; P = .01) and at follow-up (OR, 0.36; 95% CI, 0.20-0.66; P = .001) when using the Barthel Index for Activities of Daily Living. The intervention was also associated with a lesser decline in ambulatory capacity (OR, 0.55; 95% CI, 0.32-0.96; P = .03) and improved physical performance at discharge (Cohen d, 0.39; 95% CI, 0.12-0.65; P = .004). No significant associations were observed for readmissions, falls, or mortality. Conclusions and Relevance: In this nonrandomized controlled clinical trial, an exercise and health education intervention was not significantly associated with reduced HAD incidence when measured by the Katz Index. However, the benefits found for several secondary outcomes might support the implementation of in-hospital exercise programs for older patients. Trial Registration: ClinicalTrials.gov Identifier: NCT03604640.

Promiscuous CYP87A enzyme activity initiates cardenolide biosynthesis in plants.

Cardenolides are specialized, steroidal metabolites produced in a wide array of plant families1,2. Cardenolides play protective roles in plants, but these molecules, including digoxin from foxglove (Digitalis spp.), are better known for treatment of congenital heart failure, atrial arrhythmia, various cancers and other chronic diseases3-9. However, it is still unknown how plants synthesize 'high-value', complex cardenolide structures from, presumably, a sterol precursor. Here we identify two cytochrome P450, family 87, subfamily A (CYP87A) enzymes that act on both cholesterol and phytosterols (campesterol and ß-sitosterol) to form pregnenolone, the first committed step in cardenolide biosynthesis in the two phylogenetically distant plants Digitalis purpurea and Calotropis procera. Arabidopsis plants overexpressing these CYP87A enzymes ectopically accumulated pregnenolone, whereas silencing of CYP87A in D. purpurea leaves by RNA interference resulted in substantial reduction of pregnenolone and cardenolides. Our work uncovers the key entry point to the cardenolide pathway, and expands the toolbox for sustainable production of high-value plant steroids via synthetic biology.

Enhancing Cognition in Older Adults with Mild Cognitive Impairment through High-Intensity Functional Training: A Single-Blind Randomized Controlled Trial.

Physical exercise is a very promising non-pharmacological approach to prevent or reduce the cognitive decline that occurs in people aged 60 years or older. The objective of this study was to determine the effect of a high-intensity intervallic functional training (HIFT) program on cognitive functions in an elderly Colombian population with mild cognitive impairment. A controlled clinical trial was developed with a sample of 132 men and women aged >65 years, linked to geriatric care institutions, which were systematically blind randomized. The intervention group (IG) received a 3-month HIFT program (n = 64) and the control group (CG) (n = 68) received general physical activity recommendations and practiced manual activities. The outcome variables addressed cognition (MoCA), attention (TMTA), executive functions (TMTB), verbal fluency (VFAT test), processing speed (Digit Symbol Substitution Test-DSST), selective attention and concentration (d2 test). After the analysis, improvement was found in the IG with significant differences with respect to the CG in the level of cognitive impairment (MoCA), attention (TMTA), verbal fluency and concentration (p < 0.001). Executive functions (TMTB) showed differences in both groups, being slightly higher in the IG (p = 0.037). However, no statistically significant results were found for selective attention (p = 0.55) or processing speed (p = 0.24). The multiple analysis of covariance (MANCOVA) showed the influence of the education level on all cognition assessments (p = 0.026); when adjusting for sociodemographic variables, the influence of the intervention remained significant (p < 0.001). This study empirically validates that the implementation of a HIFT program has a positive effect on cognitive functions in elderly people with mild cognitive impairment. Therefore, professionals specialized in the care of this population could consider including functional training programs as an essential part of their therapeutic approaches. The distinctive features of this program, such as its emphasis on functional training and high intensity, appear to be relevant for stimulating cognitive health in the geriatric population.

Residual effects of 12 weeks of power-oriented resistance training plus high-intensity interval training on muscle dysfunction, systemic oxidative damage, and antioxidant capacity after 10 months of training cessation in older people with COPD.

OBJECTIVE: This study aimed to assess the residual effects of a 12-week concurrent training program (power training + high-intensity interval training) in older adults with chronic obstructive pulmonary disease (COPD). METHODS: A total of 21 older adults with COPD [intervention (INT), n = 8; control (CON), n = 13; 76.9 ± 6.8 years] were assessed at baseline and 10 months after the completion of the intervention by the short physical performance battery (SPPB), health-related quality of life (EQ-5D-5L), vastus lateralis muscle thickness (MT), peak pulmonary oxygen uptake (peak VO2 ) and peak work rate (Wpeak ), early and late isometric rate of force development (RFD), leg and chest press maximum muscle power (LPmax and CPmax ), and systemic oxidative damage and antioxidant capacity. RESULTS: Compared to baseline, after 10 months of detraining, the INT group presented increased SPPB (∆ = 1.0 point), health-related quality of life (∆ = 0.07 points), early RFD (∆ = 834 N∙s-1 ), LPmax (∆ = 62.2 W), and CPmax (∆ = 16.0 W) (all p < 0.05). In addition, a positive effect was noted in INT compared to CON regarding MT and Wpeak (both p < 0.05). No between-group differences were reported in peak VO2 , late RFD, systemic oxidative damage, and antioxidant capacity from baseline to 10 months after the completion of the intervention (all p > 0.05). CONCLUSIONS: Twelve weeks of concurrent training were enough to ensure improved physical function, health-related quality of life, early RFD and maximum muscle power and to preserve MT and Wpeak but not peak VO2 , late RFD, systemic oxidative damage and antioxidant capacity in the subsequent 10 months of detraining in older adults with COPD.

Single-cell multi-omics in the medicinal plant Catharanthus roseus.

Advances in omics technologies now permit the generation of highly contiguous genome assemblies, detection of transcripts and metabolites at the level of single cells and high-resolution determination of gene regulatory features. Here, using a complementary, multi-omics approach, we interrogated the monoterpene indole alkaloid (MIA) biosynthetic pathway in Catharanthus roseus, a source of leading anticancer drugs. We identified clusters of genes involved in MIA biosynthesis on the eight C. roseus chromosomes and extensive gene duplication of MIA pathway genes. Clustering was not limited to the linear genome, and through chromatin interaction data, MIA pathway genes were present within the same topologically associated domain, permitting the identification of a secologanin transporter. Single-cell RNA-sequencing revealed sequential cell-type-specific partitioning of the leaf MIA biosynthetic pathway that, when coupled with a single-cell metabolomics approach, permitted the identification of a reductase that yields the bis-indole alkaloid anhydrovinblastine. We also revealed cell-type-specific expression in the root MIA pathway.

Effects of High-Intensity Functional Training (HIFT) on the Functional Capacity, Frailty, and Physical Condition of Older Adults with Mild Cognitive Impairment: A Blind Randomized Controlled Clinical Trial.

Physical exercise has been established as an intervention in the integral approach for the physical, functional, and social health of older adults. The objective of this study was to determine the effects of a high-intensity functional training (HIFT) program on the physical condition and functional capacity of an elderly Colombian population with mild cognitive impairment. This research corresponds to a blind randomized controlled clinical trial. A total of 169 men and women aged over 65 years were evaluated and distributed in two groups: the experimental group that received a 12-week HIFT intervention (n = 82) and the control group (n = 87) that received general recommendations on the benefits of physical exercise. The outcome variables included physical condition, assessed using the Senior Fitness battery (SNB); Fried's frailty phenotype was applied, and gait and balance were assessed using the Tinetti scale. For the functional variables, activities of daily living, instrumental activities of daily living, and advanced activities of daily living were evaluated. All variables were measured pre- and post-intervention. Statistically significant improvements were observed in the IG for gait stability and balance (p < 0.001), as well as for independence in activities of daily living (p = 0.003), and instrumental and advanced activities (p < 0.001). Likewise, greater functionality was found when assessed with the SNB (p < 0.001), except for upper limb strength. The frailty classification did not show changes post-intervention (p = 0.170) nor in the group x time interaction. MANCOVA analysis showed that regardless of gender, health level, age, BMI, cognition, and health level, the HIFT intervention produced better results in functional capacity, balance, and gait (F = 0.173, p < 0.001, Wilks' λ = 88.231).

Integration of discovery and engineering in plant alkaloid research: Recent developments in elucidation, reconstruction, and repurposing biosynthetic pathways.

Plants synthesize tens of thousands of bioactive nitrogen-containing compounds called alkaloids, including some clinically important drugs in modern medicine. The discovery of new alkaloid structures and their metabolism in plants have provided ways to access these rich sources of bioactivities including new-to-nature compounds relevant to therapeutic and industrial applications. This review discusses recent advances in alkaloid biosynthesis discovery, including complete pathway elucidations. Additionally, the latest developments in the production of new and established plant alkaloids based on either biosynthesis or semisynthesis are discussed.

Exercise effects on functional capacity and quality of life in older patients with colorectal cancer: study protocol for the ECOOL randomized controlled trial.

BACKGROUND: Surgery and treatment for colorectal cancer (CRC) in the elderly patient increase the risk of developing post-operative complications, losing functional independence, and worsening health-related quality of life (HRQoL). There is a lack of high-quality randomized controlled trials evaluating the potential benefit of exercise as a countermeasure. The primary aim of this study is to evaluate the effectiveness of a home-based multicomponent exercise program for improving HRQoL and functional capacity in older adults undergoing CRC surgery and treatment. METHODS: This randomized, controlled, observer-blinded, single-center trial aims to randomize 250 patients (>74 years) to either an intervention or a control group (i.e., usual care). The intervention group will perform an individualized home-based multicomponent exercise program with weekly telephone supervision from diagnosis until three months post-surgery. The primary outcomes will be HRQoL (EORTC QLQ-C30; CR29; and ELD14) and functional capacity (Barthel Index and Short Physical Performance Battery), which will be assessed at diagnosis, at discharge, and one, three, and six months after surgery. Secondary outcomes will be frailty, physical fitness, physical activity, inspiratory muscle function, sarcopenia and cachexia, anxiety and depression, ambulation ability, surgical complications, and hospital length of stay, readmission and mortality. DISCUSSION: This study will examine the effects of an exercise program in older patients with CRC across a range of health-related outcomes. Expected findings are improvement in HRQoL and physical functioning. If proven effective, this simple exercise program may be applied in clinical practice to improve CRC care in older patients. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT05448846.

Does an Association among Sarcopenia and Metabolic Risk Factors Exist in People Older Than 65 Years? A Systematic Review and Meta-Analysis of Observational Studies.

Sarcopenia is defined as the generalized and progressive loss of skeletal muscle strength and mass that may be affected by metabolic factors, although this relationship has been poorly studied. The aim of this review and meta-analysis was to analyze the relationship among the different metabolic risk factors and sarcopenia in people older than 65 years. Following the PRISMA 2020 guide, we searched for articles that studied the relationship among sarcopenia and metabolic risk factors in adults over 65 years of age, published between 2012 and 2022 in four databases: PubMed, Web of Science, Cochrane Plus, and CINAHL. A total of 370 articles were identified in the initial search, of which 13 articles were selected for inclusion in this review. It was observed that metabolic risk factors such as Body Mass Index, systolic and diastolic blood pressure, glucose, cholesterol, or triglycerides had a significant association with sarcopenia. There is evidence of the association of different metabolic risk factors with sarcopenia in adults over 65 years of age, so it is necessary to carry out studies that investigate different strategies that reduce the appearance of sarcopenia, and with it, the incidence of metabolic diseases.

Global transcriptome and gene co-expression network analyses reveal regulatory and non-additive effects of drought and heat stress in grapevine.

Despite frequent co-occurrence of drought and heat stress, the molecular mechanisms governing plant responses to these stresses in combination have not often been studied. This is particularly evident in non-model, perennial plants. We conducted large scale physiological and transcriptome analyses to identify genes and pathways associated with grapevine response to drought and/or heat stress during stress progression and recovery. We identified gene clusters with expression correlated to leaf temperature and water stress and five hub genes for the combined stress co-expression network. Several differentially expressed genes were common to the individual and combined stresses, but the majority were unique to the individual or combined stress treatments. These included heat-shock proteins, mitogen-activated kinases, sugar metabolizing enzymes, and transcription factors, while phenylpropanoid biosynthesis and histone modifying genes were unique to the combined stress treatment. Following physiological recovery, differentially expressed genes were found only in plants under heat stress, both alone and combined with drought. Taken collectively, our results suggest that the effect of the combined stress on physiology and gene expression is more severe than that of individual stresses, but not simply additive, and that epigenetic chromatin modifications may play an important role in grapevine responses to combined drought and heat stress.

Effects of Mind-Body Training as a Mental Health Therapy in Adults with Diabetes Mellitus Type II: A Systematic Review.

The increase in the prevalence and disease burden of diabetes has highlighted the need to strengthen a comprehensive care system that includes mental health treatment. A systematic review was carried out to analyze the effectiveness of mind-body training as a therapy for the mental health management of adult patients with type 2 diabetes mellitus (T2DM) following the PRISMA 2020 guidelines. Pubmed, Scopus and Web of Science databases were consulted between November and December 2022. Eight articles were selected according to the inclusion and exclusion criteria. Only randomized controlled trials were included. The interventions focused on mindfulness and yoga with variable durations of between 8 weeks and 6 months. Four of the included studies observed statistically significant changes (p < 0.05) in anxiety. Six articles determined that mind-body training was effective for treating depression. Finally, five articles found favorable effects on stress, while one did not observe changes at 8 weeks of intervention or after 1 year of follow-up. The evidence supports the use of mind-body training to reduce stress, depression, and anxiety levels in the adult population with T2DM, which makes this type of training a valuable intervention to be included in an integral approach to diabetic pathology.

Ten-year longitudinal changes in muscle power, force, and velocity in young, middle-aged, and older adults.

BACKGROUND: Maximum muscle power (Pmax ) is a biomarker of physical performance in all ages. No longitudinal studies have assessed the effects of aging on Pmax obtained from the torque-velocity (T-V) relationship, which should be considered the 'gold standard'. This study evaluated the longitudinal changes in the T-V relationship and Pmax of the knee-extensor muscles in young, middle-aged, and older adults after 10 years of follow-up. METHODS: Four hundred eighty-nine subjects (311 men and 178 women; aged 19-68 years) were tested at baseline and after a 10-year follow-up. Anthropometric data, daily protein intake, physical activity level (PAL), and knee-extension muscle function (isometric, isokinetic, and isotonic) were evaluated. A novel hybrid equation combining a linear and a hyperbolic (Hill-type) region was used to obtain the T-V relationship and Pmax of the participants, who were grouped by sex and age (young: 20-40 years; middle-aged: 40-60 years; and old: ≥60 years). Linear mixed-effect models were used to assess effects of time, sex, and age on T-V parameters, Pmax , and body mass index (BMI). Additional analyses were performed to adjust for changes in daily protein intake and PAL. RESULTS: Pmax decreased in young men (-0.6% per year; P < 0.001), middle-aged men and women (-1.1% to -1.4% per year; P < 0.001), and older men and women (-2.2% to -2.4% per year; P ≤ 0.053). These changes were mainly related to decrements in torque at Pmax at early age and to decrements in both torque and velocity at Pmax at older age. BMI increased among young and middle-aged adults (0.2% to 0.5% per year; P < 0.001), which led to greater declines in relative Pmax in those groups. S/T0 , that is, the linear slope of the T-V relationship relative to maximal torque, exhibited a significant decline over time (-0.10%T0 ·rad·s-1 per year; P < 0.001), which was significant among middle-aged men and old men and women (all P < 0.05). Annual changes in PAL index were significantly associated to annual changes in Pmax (P = 0.017), so the overall decline in Pmax was slightly attenuated in the adjusted model (-5.26 vs. -5.05 W per year; both P < 0.001). CONCLUSIONS: Pmax decreased in young, middle-aged, and older adults after a 10-year follow-up. The early declines in Pmax seemed to coincide with declines in force, whereas the progressive decline at later age was associated with declines in both force and velocity. A progressively blunted ability to produce force, especially at moderate to high movement velocities, should be considered a specific hallmark of aging.

Pelvic Floor Muscle Exercises as a Treatment for Urinary Incontinence in Postmenopausal Women: A Systematic Review of Randomized Controlled Trials.

Women frequently suffer from urinary incontinence due to atrophic changes in the urogenital tract. Recommended conservative treatment includes evaluation of pelvic-floor strength and the functional use of pelvic-floor-muscle (PFM) training. Following the PRISMA 2020 guidelines, a search was conducted in the electronic databases PubMed, Web of Science, and Scopus for articles with at least one group performing PFM exercises in post-menopausal women with urinary incontinence. Eight articles were included, and each study had at least one group of PFM exercise-based intervention alone or combined. The volume or duration, frequency, and number of sessions were heterogeneous. All the studies reported significant differences in favor of PFM exercise in strength, quality of life, and/or severity of urinary incontinence. PFM exercise is a highly recommended intervention to treat urinary incontinence in postmenopausal women. However, more research is needed to establish specific factors such as dose-response relationships and to standardize methods for measuring effects.

Effects of Myofascial Release Using Finding-Oriented Manual Therapy Combined with Foam Roller on Physical Performance in University Athletes. A Randomized Controlled Study.

Sport is a science of constant reinvention that is always searching for strategies to improve performance. Objective: This study seeks to compare the effects of myofascial release with Findings-Oriented Orthopedic Manual Therapy (OMT) combined with Foam Roller (FR), versus FR by itself, on the physical performance of university athletes. A randomized controlled study was conducted with a total of twenty-nine university athletes, measuring Range of Motion (ROM), jump height and flight time, strength and dynamic flexibility using Goniometer pro, CMJ protocol in OptoGait, 1 Repetition Maximum (1RM) and Mean Propulsive Velocity (MPV) and the Sit and Reach (V) test, correspondingly. This study was registered at clinicaltrials.gov prior to the initial measurement of the participants under the code NCT05347303. Through a univariate analysis, together with an analysis of independent groups with ANOVA and an analysis of covariance, it was evidenced that OMT combined with FR generated more and better effects in all the evaluated ROM, jump height and flight time, RM and VMP tests. Finally, it was found that OMT combined with FR is better when it is desired to improve ROM, muscle power, strength and flexibility, while FR alone only improves dynamic flexibility.

Muscle glycogen unavailability and fat oxidation rate during exercise: Insights from McArdle disease.

Carbohydrate availability affects fat metabolism during exercise; however, the effects of complete muscle glycogen unavailability on maximal fat oxidation (MFO) rate remain unknown. Our purpose was to examine the MFO rate in patients with McArdle disease, comprising an inherited condition caused by complete blockade of muscle glycogen metabolism, compared to healthy controls. Nine patients (three women, aged 36 ± 12 years) and 12 healthy controls (four women, aged 40 ± 13 years) were studied. Several molecular markers of lipid transport/metabolism were also determined in skeletal muscle (gastrocnemius) and white adipose tissue of McArdle (Pygm p.50R*/p.50R*) and wild-type male mice. Peak oxygen uptake ( V ̇ O 2 peak ${\dot V_{{{\rm{O}}_{\rm{2}}}{\rm{peak}}}}$ ), MFO rate, the exercise intensity eliciting MFO rate (FATmax) and the MFO rate-associated workload were determined by indirect calorimetry during an incremental cycle-ergometer test. Despite having a much lower V ̇ O 2 peak ${\dot V_{{{\rm{O}}_{\rm{2}}}{\rm{peak}}}}$ (24.7 ± 4 vs. 42.5 ± 11.4 mL kg-1  min-1 , respectively; P < 0.0001), patients showed considerably higher values for the MFO rate (0.53 ± 0.12 vs. 0.33 ± 0.10 g min-1 , P = 0.001), and for the FATmax (94.4 ± 7.2 vs. 41.3 ± 9.1 % of V ̇ O 2 peak ${\dot V_{{{\rm{O}}_{\rm{2}}}{\rm{peak}}}}$ , P < 0.0001) and MFO rate-associated workload (1.33 ± 0.35 vs. 0.81 ± 0.54 W kg-1 , P = 0.020) than controls. No between-group differences were found overall in molecular markers of lipid transport/metabolism in mice. In summary, patients with McArdle disease show an exceptionally high MFO rate, which they attained at near-maximal exercise capacity. Pending more mechanistic explanations, these findings support the influence of glycogen availability on MFO rate and suggest that these patients develop a unique fat oxidation capacity, possibly as an adaptation to compensate for the inherited blockade in glycogen metabolism, and point to MFO rate as a potential limiting factor of exercise tolerance in this disease. KEY POINTS: Physically active McArdle patients show an exceptional fat oxidation capacity. Maximal fat oxidation rate occurs near-maximal exercise capacity in these patients. McArdle patients' exercise tolerance might rely on maximal fat oxidation rate capacity. Hyperpnoea might cloud substrate oxidation measurements in some patients. An animal model revealed overall no higher molecular markers of lipid transport/metabolism.

Clinical Profile, Systemic Association, Treatment and Visual Outcome of Patients with Scleritis in an Eye Care Center in Mexico City.

AIMS: To describe demographic and clinical characteristics as well as etiologies and visual outcomes of patients with scleritis. METHODS: This is a descriptive, observational and retrospective study. We reviewed the electronic health records of patients with diagnosis of scleritis, who presented at the Institute of Ophthalmology Conde de Valenciana from January 2009 to December 2019. RESULTS: The cohort consisted of 162 patients with mean follow-up of 33.7 months. Mean age of scleritis presentation was 53.8 years. The most common type of scleritis was anterior nodular in 67 patients (41.3%). Most cases were idiopathic (52.4%). Visual outcomes were worse in anterior necrotizing scleritis. The most used drugs were oral NSAIDs and corticosteroids. CONCLUSION: The visual outcome in most patients is favorable, however it depends on scleritis type and etiology, with worse prognosis in anterior necrotizing scleritis forms and associated with autoimmune or systemic diseases.

Pathophysiology, Diagnosis and Treatment of Spontaneous Coronary Artery Dissection in Peripartum Women.

Spontaneous coronary artery dissection (SCAD) is an infrequent cause of nonobstructive ischemic heart disease in previously healthy young women and therefore is not usually considered in differential diagnoses. The overall incidence of SCAD in angiographic series is between 0.28 and 1.1%, with a clear predominance in young, healthy women (70%) of whom approximately 30% are in the postpartum period. In the United Kingdom, between 2008 and 2012, SCAD was the cause of 27% of acute myocardial infarctions during pregnancy, with a prevalence of 1.81 per 100,000 pregnancies. Regarding the mechanism of arterial obstruction, this may be due to the appearance of an intramural hematoma or to a tear in the intima of the arteries, both spontaneously. Although multiple diagnostic methods are available, it is suggested to include an appropriate anamnesis, an electrocardiogram in the first 10 min after admission to the service or the onset of symptoms, and subsequently, a CT angiography of the coronary arteries or urgent coronary angiography if the hemodynamic status of the patient allows it. Treatment should be individualized for each case; however, the appropriate approach is generally based on two fundamental pillars: conservative medical treatment with antiplatelet agents, beta-blockers, and nitrates, and invasive treatment with percutaneous coronary intervention for stent implantation or balloon angioplasty, if necessary.

Additive and non-additive epigenetic signatures of natural hybridization between fish species with different mating systems.

Hybridization is a major source of evolutionary innovation. In plants, epigenetic mechanisms can help to stabilize hybrid genomes and contribute to reproductive isolation, but the relationship between genetic and epigenetic changes in animal hybrids is unclear. We analysed the relationship between genetic background and methylation patterns in natural hybrids of two genetically divergent fish species with different mating systems, Kryptolebias hermaphroditus (self-fertilizing) and K. ocellatus (outcrossing). Co-existing parental species displayed highly distinct genetic (SNPs) and methylation patterns (37,000 differentially methylated cytosines). Hybrids had predominantly intermediate methylation patterns (88.5% of the sites) suggesting additive effects, as expected from hybridization between genetically distant species. The large number of differentially methylated cytosines between hybrids and parental species (n = 5,800) suggests that hybridization may play a role in increasing genetic and epigenetic variation. Although most of the observed epigenetic variation was additive and had a strong genetic component, we also found a small percentage of non-additive, potentially stochastic, methylation differences that might act as an evolutionary bet-hedging strategy and increase fitness under environmental instability.