Social cognition in DMD and BMD dystrophinopathies: A cross-sectional preliminary study.

Objective: The dystrophinopathies called Duchenne and Becker muscular dystrophies (DMD/BMD) are rare, progressive, incurable, and life-limiting paediatric-onset neuromuscular diseases. These diseases have long been associated with specific neuropsychological deficits. However, the performance of these patients in the social cognition domain has not been properly investigated. Thus, the main objective of this study was to compare the performance on social cognition between DMD/BMD patients and healthy age-matched boys. Method: This cross-sectional study included 20 DMD/BMD children and adolescents and 20 healthy controls. The protocol included the Social Perception Domain of the NEPSY-II, the Reading the Mind in the Eyes Test - Child and Happé's Strange Stories test. General intelligence was controlled to eliminate the possible influence of covariables. All the assessments were performed remotely. Results: Most social cognition tasks were worse in patients with DMD/BMD than in matched healthy controls. These differences remained even after controlling for the general intelligence variable, with the exception of Total Disgust Errors (F = 1.462, p = .234, η2p= .038) and Verbal task (F = 1.820, p = .185, η2p= .047) scores from the NEPSY-II. Conclusions: This is the first study to demonstrate that the neuropsychological domain of social cognition is impaired in DMD/BMD patients, independent of the level of general intelligence. Screening assessments in DMD/BMD patients should be promoted to allow social cognition difficulties to be detected at an early stage to enhance patients' quality of life and social development.

Relationship of Morphometrics and Symptom Severity in Female Type I Chiari Malformation Patients with Biological Resilience.

In the present study we report the relationship among MRI-based skull and cervical spine morphometric measures as well as symptom severity (disability-as measured by Oswestry Head and Neck Pain Scale and social isolation-as measured by the UCLA Loneliness scale) on biomarkers of allostatic load using estrogen, interleukin-6, C-reactive protein, and cortisol in a sample of 46 CMI patients. Correlational analyses showed that McRae line length was negatively associated with interleukin-6 and C-reactive protein levels, and Analysis of Variance (ANOVA) showed joint effects of morphometric measures (McRae line length, anterior CSF space) and symptom severity (disability and loneliness) on estrogen and intereukin-6 levels. These results are consistent with allostatic load. That is, when the combination of CSF crowding and self-report symptom (disability and loneliness) severity exceed the capacity of biological resilience factors, then biomarkers such as neuroprotective estrogen levels drop, rather than rise, with increasing symptom severity.

Cognition in Chiari Malformation Type I: an Update of a Systematic Review.

Chiari malformation has been classified as a group of posterior cranial fossa disorders characterized by hindbrain herniation. Chiari malformation type I (CM-I) is the most common subtype, ranging from asymptomatic patients to those with severe disorders. Research about clinical manifestations or medical treatments is still growing, but cognitive functioning has been less explored. The aim of this systematic review is to update the literature search about cognitive deficits in CM-I patients. A literature search was performed through the following electronic databases: MEDLINE, PsychINFO, Pubmed, Cochrane Library, Scopus, and Web of Science. The date last searched was February 1, 2023. The inclusion criteria were as follows: (a) include pediatric or adult participants with a CM-I diagnosis, (b) include cognitive or neuropsychological assessment with standardized tests, (c) be published in English or Spanish, and (d) be empirical studies. Articles that did not report empirical data, textbooks and conference abstracts were excluded. After the screening, twenty-eight articles were included in this systematic review. From those, twenty-one articles were focused on adult samples and seven included pediatric patients. There is a great heterogeneity in the recruited samples, followed methodology and administered neurocognitive protocols. Cognitive functioning appears to be affected in CM-I patients, at least some aspects of attention, executive functions, visuospatial abilities, episodic memory, or processing speed. However, these results require careful interpretation due to the methodological limitations of the studies. Although it is difficult to draw a clear profile of cognitive deficits related to CM-I, the literature suggests that cognitive dysfunction may be a symptom of CM-I. This suggest that clinicians should include cognitive assessment in their diagnostic procedures used for CM-I. In summary, further research is needed to determine a well-defined cognitive profile related to CM-I, favoring a multidisciplinary approach of this disorder.

Plant traits poorly predict winner and loser shrub species in a warming tundra biome.

Climate change is leading to species redistributions. In the tundra biome, shrubs are generally expanding, but not all tundra shrub species will benefit from warming. Winner and loser species, and the characteristics that may determine success or failure, have not yet been fully identified. Here, we investigate whether past abundance changes, current range sizes and projected range shifts derived from species distribution models are related to plant trait values and intraspecific trait variation. We combined 17,921 trait records with observed past and modelled future distributions from 62 tundra shrub species across three continents. We found that species with greater variation in seed mass and specific leaf area had larger projected range shifts, and projected winner species had greater seed mass values. However, trait values and variation were not consistently related to current and projected ranges, nor to past abundance change. Overall, our findings indicate that abundance change and range shifts will not lead to directional modifications in shrub trait composition, since winner and loser species share relatively similar trait spaces.

Difficulties in social cognitive functioning among pediatric patients with muscular dystrophies.

Introduction: Pediatric muscular dystrophies (MDs) are a heterogeneous group of rare neuromuscular diseases characterized by progressive muscle degeneration. A neuropsychosocial approach is crucial for these patients due to associated cognitive, behavioral, and psychiatric comorbidities; however, the social cognitive domain has not been adequately addressed. Methods: This study aimed to analyze on social cognition performance in a pediatric MD patient cohort. This cross-sectional study included 32 pediatric patients with MD and 32 matched-healthy controls. The Social Perception Domain of the NEPSY-II, the Reading the Mind in the Eyes Test-Child and Happé's Strange Stories Test were administered. General intelligence and behavioral and emotional symptoms were controlled for to eliminate covariables' possible influence. The assessments were performed remotely. Results: Children with MDs performed significantly worse on most of the social cognition tasks. The differences found between the groups could be explained by the level of general intelligence for some aspects more related to theory of mind (ToM) (TM NEPSY-II: F = 1.703, p = .197; Verbal task: F = 2.411, p = .125; RMET-C: F = 2.899, p = .094), but not for emotion recognition. Furthermore, these differences were also independent of behavioral and emotional symptoms. Discussion: In conclusion, social cognition is apparently impaired in pediatric patients with MD, both for emotion recognition and ToM. Screening assessment in social cognition should be considered to promote early interventions aimed at improving these patient's quality of life.

The Role of Associations in Reducing the Emotional and Financial Impact on Parents Caring for Children with Duchenne Muscular Dystrophy: A Cross-Cultural Study.

Caregivers' emotions and finances are affected by the deterioration of functional capacity of patients with Duchenne muscular dystrophy (DMD), both in Mexico and Spain. Patient associations may reduce this impact on caregivers. This study aims to study the role of two models of associations, inspired by two different cultural models, in how the services they provide can help decrease the emotional and financial impact on the caregivers of children with DMD. The sample consisted of 34 caregivers from Mexico and 40 from Spain recruited from Spanish hospitals and rare disease organizations in Spain and Mexico. The instruments used consisted of a sociodemographic and socioeconomic questionnaire, the CarerQol-7D, the PHQ-15, the Zarit Caregiver's Burden Scale and the SWLS. The results showed that caregivers in Mexico are in better physical and psychological health than caregivers in Spain. They also receive more subsidies than those in Spain. Caregivers in Mexico have a greater well-being and are less affected by the economic impact of the disease due to the associations' day-to-day work and the fact that they generate a network of health services that they make available to the patient free of charge. These differences may also be attributable to cultural issues and to the fact that Mexico has a deeply established culture of support.

Severe type 2 diabetes (T2D) remission using a very low-calorie ketogenic diet (VLCKD).

Summary: There is a close association between obesity and type 2 diabetes (T2D). The value of weight loss in the management of patients with T2D has long been known. Loss of 15% or more of body weight can have a disease-modifying effect in people with diabetes inducing remission in a large proportion of patients. Very low-carbohydrate ketogenic diets (VLCKDs) have been proposed as an appealing nutritional strategy for obesity management. The diet was shown to result in significant weight loss in the short, intermediate, and long terms and improvement in body composition parameters as well as glycemic and lipid profiles. The reported case is a 35-year-old man with obesity, dyslipidemia, and T2D for 5 years. Despite the use of five antidiabetic medications, including insulin, HbA1c was 10.1%. A VLCKD through a commercial multidisciplinary weight loss program (PnK method) was prescribed and all medications were discontinued. The method is based on high-biological-value protein preparations and has 5 steps, the first 3 steps (active stage) consist of a VLCKD (600-800 kcal/d) that is low in carbohydrates (<50 g daily from vegetables) and lipids. The amount of proteins ranged between 0.8 and 1.2 g/kg of ideal body weight. After only 3 months, the patient lost 20 kg with weight normalization and diabetes remission, and after 2 years of follow-up, the patient remained without the pathologies. Due to the rapid and significant weight loss, VLCKD emerges as a useful tool in T2D remission in patients with obesity. Learning points: Obesity and type 2 diabetes (T2D) are conditions that share key pathophysiological mechanisms. Loss of 15% or more of body weight can have a disease-modifying effect in people with T2D inducing remission in a large proportion of patients. Diabetes remission should be defined as a return of HbA1c to <6.5% and which persists for at least 3 months in the absence of usual glucose-lowering pharmacotherapy. The very low-carbohydrate ketogenic diet (VLCKD) is a nutritional approach that has significant beneficial effects on anthropometric and metabolic parameters. Due to the rapid and significant weight loss, VLCKD emerges as a useful tool in T2D remission in patients with obesity.

Drought-exposure history increases complementarity between plant species in response to a subsequent drought.

Growing threats from extreme climatic events and biodiversity loss have raised concerns about their interactive consequences for ecosystem functioning. Evidence suggests biodiversity can buffer ecosystem functioning during such climatic events. However, whether exposure to extreme climatic events will strengthen the biodiversity-dependent buffering effects for future generations remains elusive. We assess such transgenerational effects by exposing experimental grassland communities to eight recurrent summer droughts versus ambient conditions in the field. Seed offspring of 12 species are then subjected to a subsequent drought event in the glasshouse, grown individually, in monocultures or in 2-species mixtures. Comparing productivity between mixtures and monocultures, drought-selected plants show greater between-species complementarity than ambient-selected plants when recovering from the subsequent drought, causing stronger biodiversity effects on productivity and better recovery of drought-selected mixtures after the drought. These findings suggest exposure to recurrent climatic events can improve ecosystem responses to future events through transgenerational reinforcement of species complementarity.

Neuropsychological Profile of Hereditary Ataxias: Study of 38 Patients.

Hereditary ataxias are a heterogeneous group of disorders characterized by degeneration of the cerebellum and its connections. It is known that patients with ataxia can manifest a broad spectrum of motor symptoms; however, current research has emphasized the relevance of cognitive disturbances. The aim of this study is to analyze the presence of cognitive impairment in a heterogeneous cohort of patients with hereditary ataxia (HA). A group of 38 patients with HA of different etiologies and a matched group of 38 healthy controls were recruited and evaluated through a comprehensive battery of neuropsychological tests. The findings show a worse performance in ataxic patients on planning, visuospatial skills, naming, and Theory of Mind tasks, regardless their physical and psychological symptomatology. The influence of clinical status as well as functional ability-related variables on their performance were analyzed, showing that the level of disability and motor disturbances have a significant effect on verbal memory, verbal fluency, and working memory. These findings suggest that patients with HA can manifest cognitive and neuropsychiatric symptoms as part of their clinical features, which demands its inclusion for the diagnosis and management of the disease.

Adult Age Differences in Self-Reported Pain and Anterior CSF Space in Chiari Malformation.

Chiari malformation type I (CMI) is a neural disorder with sensory, cognitive, and motor defects, as well as headaches. Radiologically, the cerebellar tonsils extend below the foramen magnum. To date, the relationships among adult age, brain morphometry, surgical status, and symptom severity in CMI are unknown. The objective of this study was to better understand the relationships among these variables using causal modeling techniques. Adult CMI patients (80% female) who either had (n = 150) or had not (n = 151) undergone posterior fossa decompression surgery were assessed using morphometric measures derived from magnetic resonance images (MRI). MRI-based morphometry showed that the area of the CSF pocket anterior to the cervico-medullary junction (anterior CSF space) correlated with age at the time of MRI (r = - .21). Also, self-reported pain increased with age (r = .11) and decreased with anterior CSF space (r = - .18). Age differences in self-reported pain were mediated by anterior CSF space in the cervical spine area-and this effect was particularly salient for non-decompressed CMI patients. As CMI patients age, the anterior CSF space decreases, and this is associated with increased pain-especially for non-decompressed CMI patients. It is recommended that further consideration of age-related decreases in anterior CSF space in CMI patients be given in future research.

Effectiveness and Safety of a Very Low-Calorie Ketogenic Diet on Weight Regain Following Bariatric Surgery.

PURPOSE: Obesity is one of the major public health problems worldwide and bariatric surgery is considered the gold standard treatment for severe obesity. Although the literature supports the safety and efficacy of the very low-calorie ketogenic diet (VLCKD) in patients with obesity, there is no study analyzing the use in case of failure or weight regain after bariatric surgery. This work has the purpose of assessing the response to a VLCKD (Pnk® method) in this population. METHODS: We have conducted an observational, retrospective, and descriptive study with the analysis of medical charts of private offices where patients were examined between 2014 and 2019, totalizing 11 participants who underwent Roux-en-Y gastric bypass (RYGB) without a reduction of 50% in body weight excess or any weight regain after the surgery. The patients followed the first stage of a commercial weight loss program (Pnk® method) which consists of a VLCKD (600-800 kcal/day), low in carbohydrates and lipids. RESULTS: A significant reduction was observed (p-value < 0.05) in weight, body mass index (BMI), abdominal circumference (AC), and glycated hemoglobin (A1C) post-ketogenic diet. Uric acid, transaminases, urea, and creatinine values did not show differences between pre- and post-ketosis. During the course of the study, no serious adverse events were reported. CONCLUSION: This study has shown that the ketogenic diet can be recommended as an effective and safe treatment for patients who progressed with insufficient weight loss or regain after bariatric surgery.

Diseases Costs and Impact of the Caring Role on Informal Carers of Children with Neuromuscular Disease.

This study aims to evaluate the costs of informal care for children with neuromuscular disease and evaluate how physical and psychological health is associated with socio-demographic variables. A cross sectional design was used with a convenience sample of 110 carers that participated in this study. Participants were recruited from Spanish hospitals and rare diseases organizations. Economic costs and sociodemographic aspects were assessed using the economic costs questionnaire and the sociodemographic questionnaire. Physical and psychological health was evaluated using the CarerQol-7D, PHQ-15, Barthel Index, Zarit Overload Scale and Satisfaction with Life Scale. Carers of children with neuromuscular disease spent a large percentage of their annual income in physical therapy, psychological care and speech therapy. Informal costs differed according to the degree of dependency of the child. These were higher in those caregivers whose child under their care presented low functional independence. The loss of work productivity was related to marital status, use of professional services and the child's dependency. Finally, carers who were female, single or separated and without a job showed worse physical and psychological health. The results highlighted that carers have to face a number of high costs because of the non-existence of social protection and due to the child's diagnosis.

Effects of Teleassistance on the Quality of Life of People With Rare Neuromuscular Diseases According to Their Degree of Disability.

Rare neuromuscular diseases (RNMDs) are a group of pathologies characterized by a progressive loss of muscular strength, atrophy, fatigue, and other muscle-related symptoms, which affect quality of life (QoL) levels. The low prevalence, high geographical dispersion and disability of these individuals involve difficulties in accessing health and social care services. Teleassistance is presented as a useful tool to perform psychosocial interventions in these situations. The main aim of this research is to assess the effects of a teleassistance psychosocial program on the QoL levels of people with RNMDs who have different levels of disability. A sample of 73 participants was divided into an experimental group (n = 40), which participated in the intervention, and a control wait list group (n = 33). QoL was evaluated through the SIP and the SF-36, and disability through the WHO-DAS II. The participants with a moderate to severe level of disability were those who most benefited from the intervention. The results also revealed that the psychosocial teleassistance program was suitable to improve physical and psychosocial aspects of people suffering from a rare neuromuscular disease with a moderate level of disability, but just psychosocial aspects in those with a severe level of disability.

E2F1 and E2F2-Mediated Repression of CPT2 Establishes a Lipid-Rich Tumor-Promoting Environment.

Lipid metabolism rearrangements in nonalcoholic fatty liver disease (NAFLD) contribute to disease progression. NAFLD has emerged as a major risk for hepatocellular carcinoma (HCC), where metabolic reprogramming is a hallmark. Identification of metabolic drivers might reveal therapeutic targets to improve HCC treatment. Here, we investigated the contribution of transcription factors E2F1 and E2F2 to NAFLD-related HCC and their involvement in metabolic rewiring during disease progression. In mice receiving a high-fat diet (HFD) and diethylnitrosamine (DEN) administration, E2f1 and E2f2 expressions were increased in NAFLD-related HCC. In human NAFLD, E2F1 and E2F2 levels were also increased and positively correlated. E2f1 -/- and E2f2 -/- mice were resistant to DEN-HFD-induced hepatocarcinogenesis and associated lipid accumulation. Administration of DEN-HFD in E2f1 -/- and E2f2 -/- mice enhanced fatty acid oxidation (FAO) and increased expression of Cpt2, an enzyme essential for FAO, whose downregulation is linked to NAFLD-related hepatocarcinogenesis. These results were recapitulated following E2f2 knockdown in liver, and overexpression of E2f2 elicited opposing effects. E2F2 binding to the Cpt2 promoter was enhanced in DEN-HFD-administered mouse livers compared with controls, implying a direct role for E2F2 in transcriptional repression. In human HCC, E2F1 and E2F2 expressions inversely correlated with CPT2 expression. Collectively, these results indicate that activation of the E2F1-E2F2-CPT2 axis provides a lipid-rich environment required for hepatocarcinogenesis. SIGNIFICANCE: These findings identify E2F1 and E2F2 transcription factors as metabolic drivers of hepatocellular carcinoma, where deletion of just one is sufficient to prevent disease. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/11/2874/F1.large.jpg.

Randomized Clinical Trial to Evaluate the Morphological Changes in the Adventitial Vasa Vasorum Density and Biological Markers of Endothelial Dysfunction in Subjects with Moderate Obesity Undergoing a Very Low-Calorie Ketogenic Diet.

Weight loss after bariatric surgery decreases the earlier expansion of the adventitial vasa vasorum (VV), a biomarker of early atheromatous disease. However, no data are available regarding weight loss achieved by very low calorie ketogenic diets (VLCKD) on VV and lipid-based atherogenic indices. A randomized clinical trial was performed to examine changes in adventitial VV density in 20 patients with moderate obesity who underwent a 6-month very low calorie ketogenic diet (VLCKD, 600-800 kcal/day), and 10 participants with hypocaloric diet based on the Mediterranean Diet (MedDiet, estimated reduction of 500 kcal on the usual intake). Contrast-enhanced carotid ultrasound was used to assess the VV. Body composition analysis was also used. The atherogenic index of plasma (log (triglycerides to high-density lipoprotein cholesterol ratio)) and the triglyceride-glucose index were calculated. Serum concentrations of soluble intercellular adhesion molecule 1 (sICAM-1), and soluble vascular cell adhesion molecule 1 (sVCAM-1) were measured. The impact of weight on quality of life-lite (IWQOL-Lite) questionnaire was administered. Participants of intervention groups displayed a similar VV values. Significant improvements of BMI (-5.3 [-6.9 to -3.6] kg/m2, p < 0.001), total body fat (-7.0 [-10.7 to -3.3] %, p = 0.003), and IWQOL-Lite score (-41.4 [-75.2 to -7.6], p = 0.027) were observed in VLCKD group in comparison with MedDiet group. Although after a 6-months follow-up period VV density (mean, right and left sides) did not change significantly in any group, participants in the VLCKD exhibited a significantly decrease both in their atherogenic index of plasma and serum concentration of sICAM-1. A 6-month intervention with VLCKD do not impact in the density of the adventitial VV in subjects with moderate obesity, but induces significant changes in markers of endothelial dysfunction and CV risk.

Signal-detection analysis of the WMS faces subtest: Results in amyotrophic lateral sclerosis patients.

About 30% of patients with amyotrophic lateral sclerosis (ALS) suffer from cognitive impairment and 10-15% suffer from frontotemporal dementia (FTD). Due to the patients' reduced motor function, a neuropsychological assessment with a low motor demand can be an advantage when evaluating patients, aiding its application. The present work has studied the usefulness of the Faces subtest of the Wechsler Memory Scale in 42 patients with ALS and 42 healthy volunteers applying Holdnack's Two-High Threshold model. The ALS group performed significantly worse in immediate and delayed discriminability. With respect to the presence of cognitive impairment, it seemed to be independent of the indexes proposed by Holdnack and Delis. On the other hand, motor problems were associated with delayed recognition while behavior alterations were linked to problems with delayed discriminability. ALS patients do not express differences in the bias index, in line with other types of previously studied pathologies.

The role of climate, foliar stoichiometry and plant diversity on ecosystem carbon balance.

Global change is affecting terrestrial carbon (C) balances. The effect of climate on ecosystem C balance has been largely explored, but the roles of other concurrently changing factors, such as diversity and nutrient availability, remain elusive. We used eddy-covariance C-flux measurements from 62 ecosystems from which we compiled information on climate, ecosystem type, stand age, species abundance and foliar concentrations of N and P of the main species, to assess their importance in the ecosystem C balance. Climate and productivity were the main determinants of ecosystem C balance and its stability. In P-rich sites, increasing N was related to increased gross primary production and respiration and vice versa, but reduced net C uptake. Our analyses did not provide evidence for a strong relation between ecosystem diversity and their productivity and stability. Nonetheless, these results suggest that nutrient imbalances and, potentially, diversity loss may alter future global C balance.

Coping with Wolf-Hirschhorn syndrome: quality of life and psychosocial features of family carers.

BACKGROUND: Wolf-Hirschhorn Syndrome (WHS) is a rare, congenital disease characterized by a distinctive facial phenotype, seizures, intellectual disability and developmental delay, and pre and postnatal growth requiring lifelong care. The psychosocial status of the family caregivers of children diagnosed with WHS is unknown. This study aims to characterize the sociodemographic and psychosocial profile of WHS caregivers and analyze how these variables impact their quality of life (QoL) and well-being. RESULTS: The sociodemographic and clinical profile of 22 Spanish caregivers of children with WHS and the characteristics of those affected have been described. Significant relationships were found between sociodemographic and psychosocial characteristics among caregivers. The impact on the parents' QoL and negative relationship with the symptomatology were assessed. The use of engagement strategies such as problem focused coping was associated with improved psychological QoL and social support. CONCLUSIONS: WHS caregivers share similarities in their profile and needs with caregivers of children with other rare diseases. Pychosocial support groups involving parents caring for children with the same disease could improve caregivers' well-being and QoL by strengthening their social support network and using positive coping styles.

Liver osteopontin is required to prevent the progression of age-related nonalcoholic fatty liver disease.

Osteopontin (OPN), a senescence-associated secretory phenotype factor, is increased in patients with nonalcoholic fatty liver disease (NAFLD). Cellular senescence has been associated with age-dependent hepatosteatosis. Thus, we investigated the role of OPN in the age-related hepatosteatosis. For this, human serum samples, animal models of aging, and cell lines in which senescence was induced were used. Metabolic fluxes, lipid, and protein concentration were determined. Among individuals with a normal liver, we observed a positive correlation between serum OPN levels and increasing age. This correlation with age, however, was absent in patients with NAFLD. In wild-type (WT) mice, serum and liver OPN were increased at 10 months old (m) along with liver p53 levels and remained elevated at 20m. Markers of liver senescence increased in association with synthesis and concentration of triglycerides (TG) in 10m OPN-deficient (KO) hepatocytes when compared to WT hepatocytes. These changes in senescence and lipid metabolism in 10m OPN-KO mice liver were associated with the decrease of 78 kDa glucose-regulated protein (GRP78), induction of ER stress, and the increase in fatty acid synthase and CD36 levels. OPN deficiency in senescent cells also diminished GRP78, the accumulation of intracellular TG, and the increase in CD36 levels. In 20m mice, OPN loss led to increased liver fibrosis. Finally, we showed that OPN expression in vitro and in vivo was regulated by p53. In conclusion, OPN deficiency leads to earlier cellular senescence, ER stress, and TG accumulation during aging. The p53-OPN axis is required to inhibit the onset of age-related hepatosteatosis.