ABSTRACT
BACKGROUND: Better living conditions and health care advancements have improved life expectancy worldwide, increasing the number of older patients who require neurosurgery. We would like to report our experience with geriatric neurosurgical patients at our institution. METHODS: This is a retrospective study on geriatric patients (aged ≥ 65 years) who underwent neurosurgery at our center between 2015 and 2022. Data on age, sex, comorbidities, pre-morbid status, type of admission, diagnosis, operation, complications, short-term outcome, hospital length of stay (LOS), and 30-day readmission were collected. Descriptive statistics and multiple regression analysis were used. RESULTS: A total of 327 patients were included. The mean age was 70.4 years and 51.3 % were female. Majority (70.6 %) had at least one comorbid condition, most commonly hypertension. Most patients were admitted through emergency systems (80.1 %), with 40.4 % consulting for traumatic brain injury. The top diagnoses were chronic subdural hematoma (35.2 %), ruptured intracerebral aneurysm (15.6 %), and meningioma (10.1 %). The most common procedures were burrhole drainage of hematoma (34.8 %), brain tumor excision (16.7 %), and aneurysm clipping (14.6 %). The post-operative complication rate was 15.2 %, and mean LOS was 16.7 days. Majority of patients (86.9 %) were discharged home, and 2.8 % were readmitted within 30 days. The 30-day mortality rate was 13.1 %. Lower pre-operative GCS, certain comorbidities, and intra- and post-operative complications were significantly associated with mortality and LOS. CONCLUSION: Advanced age alone should not be a contraindication to surgery; other factors such as frailty and comorbid conditions should also be considered. Proper patient selection and preoperative preparation are key to achieving good outcomes.
ABSTRACT
Organic acids (OAs) are employed in animal feed to regulate gastrointestinal disorders and diarrhoea thanks to their ability to modulate the gastrointestinal environment and their antimicrobial capacity. However, there is not enough evidence regarding the most adequate OA and its effectiveness in rabbit farming. Therefore, the aim of this study was to screen and evaluate the response of young rabbits to six OAs, administered via drinking water, at three different concentrations (pH levels). Organic acids (acetic, ACET; formic, FOR; propionic, PROP; lactic, LAC; citric, CIT; and butyric, BUT) were tested at three concentrations (pH 3, 4, and 5). A negative control (CON; non-acidified water) was also included. We used 240 weaned rabbits (28 days old) divided into 2 batches. In each batch, animals were randomly allocated to 1 of the 19 experimental treatments and were housed in group cages of 6 animals per cage, treatment, and batch. Among the 240 rabbits, an additional cage with 6 animals was included to determine the initial physiological state of the animals. All animals were fed with commercial pelleted feed throughout the whole experiment. The duration of the study was 7 days, until 35 days of age. At 31 and 35 days of age, in each batch, three animals per day and treatment were slaughtered. The pH of the digestive contents in the fundus, antrum, duodenum, jejunum, ileum, and cecum, as well as the gastric pepsin enzyme activity, was measured. Water and feed consumption per cage and individual body weight (BW) were recorded daily. The type and dosage of OAs affected water intake. ACET 3, PROP 3, and BUT 3 reduced water intake compared to CON, negatively impacting feed intake and weight gain. FOR and CIT acids led to the highest BW and weight gain at 35 days, compared to PROP, LAC, and BUT (p < 0.05); showing ACET intermediate values. While OAs had limited effects on gastric and small intestine pH, acidified water at pH 4 and 5 lowered ileum and caecum pH (p < 0.05) compared to pH 3. Acidified water at pH 4 showed the highest (p < 0.05) pepsin activity compared to pH 3 and pH 5. Considering the limited sample size and short-term assessment period of our screening test, the OAs with the highest potential for use in post-weaning rabbits were FOR, ACET, and CIT at pH 4. The selected combinations did not exhibit any early adverse effects in young rabbits. These results should be further confirmed in a broader population of animals. It would also be advisable to extend the application of OAs over longer periods to evaluate their effects throughout the entire growing period of rabbits.
ABSTRACT
Magnetic resonance-guided focused ultrasound (MRgFUS) is a non-invasive lesioning technique used to treat movement disorders such as essential tremor (ET), Parkinson's disease (PD), and X-linked dystonia-parkinsonism (XDP). We would like to report our experience in establishing and developing our MRgFUS program and preliminary results. Adult patients with tremor-dominant PD (TDPD), ET, and XDP were considered for initial screening (neurologic evaluation, skull density ratio [SDR] determination). Eligible patients underwent secondary screening (neurosurgical and neuropsychological evaluation, psychiatric and medical clearance). During the procedure, a neuro-anesthesiologist and neurologist were also present to monitor the patient and perform neurologic evaluation, respectively. Clinical follow-up was scheduled at 2 weeks post-treatment, then at every 3 months. A total of 30 patients underwent MRgFUS treatment: 22 TDPD, 6 XDP, and 2 ET. The mean age was 55.7 years, and majority were male (86.7%). Mean disease duration was 8.6 years. Mean SDR was 0.46. The targets for TDPD and ET were the contralateral ventral intermediate nucleus of the thalamus; for XDP, it was the pallidothalamic tract. The mean maximum temperature was 59.8oC; number of sonocations, 7.3; and treatment time, 64.6 min. Majority of patients improved after the procedure. Transient intraprocedural adverse events (headache, dizziness) were reported in 20% of patients while post-procedural events (mild weakness, numbness) were seen in 16.7%. Only 26.7% of patients had follow-up data. Despite the unique challenges encountered, MRgFUS treatment is feasible in resource-limited settings. Additional steps would have to be made to develop and improve the program.
Subject(s)
Essential Tremor , Magnetic Resonance Imaging , Humans , Male , Female , Middle Aged , Essential Tremor/therapy , Aged , Adult , Philippines , Parkinson Disease/therapy , Treatment Outcome , Resource-Limited SettingsABSTRACT
BACKGROUND: Low-income countries (LICs) and lower-middle-income countries (LMICs) are presented with unique challenges and opportunities when performing awake craniotomy (AC) for brain tumors. These circumstances arise from factors that are financial, infrastructural, educational, personnel, and sociocultural in nature. METHODS: We performed a systematic narrative review of series on AC for intra-axial brain tumors in LICs/LMICs using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, focusing on the challenges and opportunities in these settings. The PubMed, Scopus, and Web of Science databases were searched. RESULTS: After initially identifying 74 studies, inclusion-exclusion criteria were applied, leaving a total of 14 studies included in the review. These involved 409 patients who underwent AC in LICs/LMICs. These series were from India, Ghana, Nigeria, Iran, Pakistan, Morocco, the Philippines, and Egypt. The most common pathology encountered were gliomas (10-70%). Most studies (11/14, 78.5%) reported on their technique of cortical-subcortical mapping. All reported on motor mapping and 8 of these performed language mapping. The most common outcomes reported were seizure and neurologic deficits, and longest follow-up was at 1 year. Challenges noted were lack of equipment and trained personnel, need for validated tests for the local setting, and sociocultural factors. Opportunities identified were volume for training, technique innovation, and international collaboration. CONCLUSIONS: There are numerous challenges and opportunities that arise when performing AC in LICs/LMICs. A collaborative approach toward harnessing the opportunities, and seeking creative solutions to address the challenges, would provide an ideal mechanism toward advancing neurosurgical care and specialty worldwide.
ABSTRACT
With the main aim of identifying biomarkers that contribute to defining the concept of ideal protein in growing rabbits under the most diverse conditions possible this work describes two different experiments. Experiment 1: 24 growing rabbits are included at 56 days of age. The rabbits are fed ad libitum one of the two experimental diets only differing in lysine levels. Experiment 2: 53 growing rabbits are included at 46 days of age, under a fasting and eating one of the five experimental diets, with identical chemical composition except for the three typically limiting amino acids (being fed commercial diets ad libitum in both experiments). Blood samples are taken for targeted and untargeted metabolomics analysis. Here we show that the metabolic phenotype undergoes alterations when animals experience a rapid dietary shift in the amino acid levels. While some of the differential metabolites can be attributed directly to changes in specific amino acids, creatinine, urea, hydroxypropionic acid and hydroxyoctadecadienoic acid are suggested as a biomarker of amino acid imbalances in growing rabbits' diets, since its changes are not attributable to a single amino acid. The fluctuations in their levels suggest intricate amino acid interactions. Consequently, we propose these metabolites as promising biomarkers for further research into the concept of the ideal protein using rabbit as a model.
Subject(s)
Amino Acids , Animal Feed , Biomarkers , Metabolomics , Animals , Rabbits , Biomarkers/blood , Biomarkers/metabolism , Metabolomics/methods , Amino Acids/metabolism , Amino Acids/blood , Animal Feed/analysis , Dietary Proteins/metabolism , Diet , MaleABSTRACT
Although the clinical symptoms of borderline personality disorder (BPD) tend to remit over time, a substantial proportion continues to present "long-lasting symptoms" (LLS). This term refers to individuals who present some degree of clinical improvement, but low mood, feelings of emptiness, and poor psychosocial adjustment typically persist. The aim of this study was to compare the sociodemographic, clinical, and therapeutic variables in individuals with BPD with and without LLS. A total of 620 participants with BPD were included and subdivided into two groups: non-LLS group (n = 549, mean age = 28.02 [6.1] and range, 18-40 years) and LLS group (n = 71, mean age = 44.69 [3.6] and range, 41-56 years). The groups were compared in sociodemographic, clinical, and drug treatment characteristics. We also evaluated the impact of dialectical behavioral therapy-skills training (DBT-ST) on polypharmacy. The prevalence of individuals with long-lasting BPD symptoms increased significantly over a 20-year period (from <1% to 16%). The LLS group was characterized by less clinical severity, higher comorbidity with affective disorders but lower comorbidity with eating disorders, more disability, and more medication taking. Patients with LLS who received DBT-ST experienced a significant decrease in the use of benzodiazepines and the number of medications prescribed compared with those who did not receive DBT-ST. Clinicians should be aware of the specific features of older patients with BPD in order to better identify and address their specific therapeutic needs.
Subject(s)
Borderline Personality Disorder , Dialectical Behavior Therapy , Humans , Borderline Personality Disorder/therapy , Borderline Personality Disorder/epidemiology , Adult , Female , Male , Adolescent , Young Adult , Middle Aged , Comorbidity , PolypharmacyABSTRACT
BACKGROUND: Carotid occlusion often leads to the formation of a collateral network. On rare occasions, due to hemodynamic influence, aneurysms can occur. Here, the authors describe a 69-year-old male presenting with intracerebral hemorrhage secondary to a ruptured aneurysm within such a network. OBSERVATIONS: The patient presented to the emergency department with an altered level of consciousness. Imaging showed a left temporal lobe hemorrhage extending into the ventricle, subdural hematoma, and evidence of contrast extravasation. Digital subtraction angiography revealed an occluded left internal carotid artery with the left middle cerebral artery territory reconstituted by flow through an external carotid artery-internal carotid artery anastomosis. The latter was formed by the superficial temporal artery-superior orbital artery, as well as pial-pial collaterals from the posterior temporal artery. Notably, a 4-mm aneurysm arising from the pial-pial collateral network was identified. Surgical intervention involved a left temporal craniectomy and aneurysm excision, with special attention paid to preserving the anastomotic flow through the superficial temporal artery. LESSONS: This case underscores the importance of recognizing and preserving collateral vascular pathways in cases of carotid occlusion with an associated aneurysm. It emphasizes the necessary balance between managing aneurysm risk and maintaining cerebral perfusion, highlighting the need for careful preoperative planning and intraoperative caution.
ABSTRACT
Non-Suicidal Self-Injury (NSSI) is associated with a heightened overall risk of future psychopathological problems. However, elucidating specific characteristics that determine an increased risk for certain individuals remains an area requiring further exploration. This study aimed to identify latent subgroups in a sample of college students with NSSI. Additionally, it sought to explore the differential associations of these subgroups with their psychopathological status (e.g., borderline symptoms and suicidal tendencies) both at baseline and after two years. The sample comprised 259 participants (89% females, Mage = 20.39, SD = 1.90) who reported engaging in NSSI in the last year. Three latent groups were found. The group exhibiting severe NSSI-features, high emotion dysregulation, and low perceived social support was the profile with high-risk of psychopathology both at baseline and follow-up. The findings enhance our understanding of the complex association between NSSI and future mental health issues, aiding in the early identification of at-risk individuals.
Subject(s)
Self-Injurious Behavior , Students , Humans , Female , Self-Injurious Behavior/psychology , Students/psychology , Students/statistics & numerical data , Male , Young Adult , Follow-Up Studies , Universities , Suicidal Ideation , Social Support , Risk Factors , Adolescent , Emotional Regulation , Adult , Borderline Personality Disorder/psychologyABSTRACT
Antecedentes y objetivo: El propósito de una adaptación protésica no es únicamente mejorar el entendimiento del lenguaje, sino mejorar la calidad de vida. El objetivo de esta investigación es medir la calidad de vida de los pacientes con prótesis auditivas e indagar qué variables sociodemográficas, audiológicas y audioprotésicas la afectan. Material y métodos: Estudio descriptivo transversal multicéntrico en la Comunidad de Madrid (España). Muestra formada por 54 pacientes. Se usó la escala Effectiveness of auditory rehabilitation (EAR). Resultados: Edad media de 66.4 años; el 55.6% eran hombres. La puntuación media de 10 ítems de la escala EAR audiológica fue 64.54 (DE 16.43). La puntuación media de 10 ítems de la EAR audioprotésica fue 71.84 (DE 13.49). La edad, sexo, actividad laboral, nivel de estudios, grado de pérdida auditiva, resultados de logoaudiometría, campo libre, número y formato de prótesis auditivas, prescriptor de las prótesis y año de fabricación de las prótesis se asocian con diferentes ítems de la escala EAR (p<.05). Conclusiones: La calidad de vida audiológica oscila entre regular y buena, y la audioprotésica se acerca a buena. Tener menor edad, ser de sexo femenino y tener actividad laboral se asocian con mejor calidad de vida. Las personas con buenos resultados logoaudiométricos se asocian con mejor calidad de vida. Las adaptaciones monoaurales, los audífonos retroauriculares, los audífonos más modernos y que el paciente no se autoprescriba prótesis auditivas se asocian con mejor calidad de vida. Las prótesis auditivas mejoran la calidad de vida de los pacientes siempre que se tengan en cuenta las características sociodemográficas, audiológicas y audioprotésicas específicas de cada paciente para realizar un ajuste audioprotésico personalizado y óptimo.(AU)
Background and objective: The purpose of a prosthetic adaptation is not only to improve language understanding and sound recognition, but to improve the patient's quality of life. The purpose of this investigation is to measure quality of life of patients with hearing aids, and investigate which sociodemographic, audiological and audioprosthetic variables affect it. Material and methods: Multicenter cross-sectional descriptive study in the Community of Madrid (España). Sample 54 patients and Effectiveness of Auditory Rehabilitation (EAR) scale was used. Results: Mean age 66.4 years; 55.6% men. The mean score of 10 audiological EAR items was 64.54 (SD 16.43). The mean score of 10 ear audioprosthetic items was 71.84 (SD 13.49). Age, sex, work activity, level of education, degree of hearing loss, logoaudiometry results, free field, number and format of hearing aids, prescriber of the prostheses and year of manufacture of the prostheses, are associated with different items of the EAR scale (P<.05). Conclusions: The audiological quality of life ranges from regular to good, and audioprosthetics is close to good.Younger age, female sex and work activity are associated with better quality of life. People with good logoaudiometric results are associated with better quality of life. Monaural adaptations, retroauricular hearing aids, more modern hearing aids and that the patient does not self-describe hearing aids, are associated with better quality of life. Hearing aids improve the quality of life of patients, provided that sociodemographic, audiological and audioprosthetic characteristics, specific to each patient are taken into account to make a personalized and optimal audioprosthetic adjustment.(AU)
Subject(s)
Humans , Male , Female , Middle Aged , Aged , Quality of Life , Hearing Aids , Cochlear Implants , Audiology , Spain , Epidemiology, Descriptive , Cross-Sectional Studies , Speech, Language and Hearing SciencesABSTRACT
OBJECTIVE: We aimed to study physical health and primary care utilization in the long-term course of borderline personality disorder (BPD) and their impact on quality of life (QOL) in a Spanish clinical sample. METHODS: This study is part of a longitudinal study following a clinical cohort with BPD. A total of 41 participants were re-evaluated at 10-year follow-up, when current medical conditions, primary care utilization, and quality of life were assessed. Comparative population data were extracted from the Catalan Health Survey ESCA. RESULTS: 68% of BPD patients reported physical health problems, and 32% informed of multiple medical illnesses at follow-up. Higher rates of musculoskeletal disorders and frequent use of general practitioner (GP) consultations were reported by BPD patients compared to the general population. Differences in physical health and use of primary care services between remitted and non-remitted BPD patients were not significant. BPD remission was independently associated with better long-term QOL. Comorbid somatic diseases worsened the long-term QOL of non-remitted BPD patients. CONCLUSION: Chronic somatic conditions are prevalent in people with BPD and interact negatively with persistent BPD pathology, worsening their QOL in the long-term. Health care strategies in the assistance of long-lasting BPD patients are recommended.
Subject(s)
Borderline Personality Disorder , Humans , Borderline Personality Disorder/therapy , Follow-Up Studies , Quality of Life , Longitudinal Studies , Chronic Disease , Primary Health CareABSTRACT
Evolution depends upon genetic variations that influence physiology. As defined in a genetic screen, phenotypic performance may be enhanced or degraded by such mutations. We set out to detect mutations that influence motor function, including motor learning. Thus, we tested the motor effects of 36,444 non-synonymous coding/splicing mutations induced in the germline of C57BL/6J mice with N-ethyl-N-nitrosourea by measuring changes in the performance of repetitive rotarod trials while blinded to genotype. Automated meiotic mapping was used to implicate individual mutations in causation. In total, 32,726 mice bearing all the variant alleles were screened. This was complemented with the simultaneous testing of 1408 normal mice for reference. In total, 16.3% of autosomal genes were thus rendered detectably hypomorphic or nullified by mutations in homozygosity and motor tested in at least three mice. This approach allowed us to identify superperformance mutations in Rif1, Tk1, Fan1 and Mn1. These genes are primarily related, among other less well-characterized functions, to nucleic acid biology. We also associated distinct motor learning patterns with groups of functionally related genes. These functional sets included, preferentially, histone H3 methyltransferase activity for mice that learnt at an accelerated rate relative to the remaining mutant mice. The results allow for an estimation of the fraction of mutations that can modify a behaviour influential for evolution such as locomotion. They may also enable, once the loci are further validated and the mechanisms elucidated, the harnessing of the activity of the newly identified genes to enhance motor ability or to counterbalance disability or disease. KEY POINTS: We studied the effect of chemically induced random mutations on mouse motor performance. An array of mutations influenced the rate of motor learning. DNA regulation genes predominated among these mutant loci. Several mutations in unsuspected genes led to superperformance. Assuming little-biased mutagenicity, the results allow for an estimation of the probability for any spontaneous mutation to influence a behaviour such as motor learning and ultimate performance.
Subject(s)
Mice, Inbred C57BL , Mutation , Animals , Mice , Male , Learning/physiology , Genome , Motor Activity/physiology , Motor Activity/genetics , FemaleABSTRACT
PURPOSE: To identify the effects of mirror neuron activation (MNAT) combined or not with physical exercise (PE) in healthy older adults, on functionality, balance, gait velocity and risk of falls. METHODS: A systematic electronic search was performed in PubMed/MEDLINE, Cochrane, and Embase databases. RESULTS: Thirteen randomized controlled trials were included in the qualitative analysis, and eleven in the quantitative analysis. All studies showed fair to high quality and the most frequent high-risk bias was "Blinding of participants and personnel". Compared to the control condition, higher improvement was shown in older people who received MNAT, on functionality (1.57 [0.57, 2.62], balance (1.95 [1.32, 2.572]), and gait velocity (1.20 [0.30, 2.11]). Compared to PE, MNAT combined with PE does not improve functionality. More studies are needed to assess MNAT effectiveness in the rest of the outcomes. CONCLUSIONS: Neuron system activation through MNAT improves relevant abilities in older adults, with better results when including functional activities. However, the beneficial effects on these variables of adding MNAT to a PE program are controversial.
Subject(s)
Accidental Falls , Mirror Neurons , Postural Balance , Humans , Accidental Falls/prevention & control , Aged , Mirror Neurons/physiology , Exercise Therapy/methods , Randomized Controlled Trials as Topic , ExerciseABSTRACT
BACKGROUND: Severe mental disorders like Schizophrenia and related psychotic disorders (SRD) or Bipolar Disorder (BD) require pharmacological treatment for relapse prevention and quality of life improvement. Yet, treatment adherence is a challenge, partly due to patients' attitudes and beliefs towards their medication. Social media listening offers insights into patient experiences and preferences, particularly in severe mental disorders. METHODS: All tweets posted between 2008 and 2022 mentioning the names of the main drugs used in SRD and BD were analyzed using advanced artificial intelligence techniques such as machine learning, and deep learning, along with natural language processing. RESULTS: In this 15-year study analyzing 893,289 tweets, second generation antipsychotics received more mentions in English tweets, whereas mood stabilizers received more tweets in Spanish. English tweets about economic and legal aspects displayed negative emotions, while Spanish tweets seeking advice showed surprise. Moreover, a recurring theme in Spanish tweets was the shortage of medications, evoking feelings of anger among users. LIMITATIONS: This study's analysis of Twitter data, while insightful, may not fully capture the nuances of discussions due to the platform's brevity. Additionally, the wide therapeutic use of the studied drugs, complicates the isolation of disorder-specific discourse. Only English and Spanish tweets were examined, limiting the cultural breadth of the findings. CONCLUSION: This study emphasizes the importance of social media research in understanding user perceptions of SRD and BD treatments. The results provide valuable insights for clinicians when considering how patients and the general public view and communicate about these treatments in the digital environment.
Subject(s)
Antipsychotic Agents , Social Media , Humans , Lithium/therapeutic use , Sentiment Analysis , Anticonvulsants , Antipsychotic Agents/therapeutic use , Artificial Intelligence , Quality of LifeABSTRACT
Prior studies have identified that mentally healthy people tend to share common characteristics and common ways of coping with stressful life events; they show similar patterns of behavior and more flexible and adaptive social roles. The objectives of the study are to assess the influence of personality factors on gender roles and mental health, to identify personality patterns along with gender roles, and to assess the influence of the patterns identified on mental health. Data collection from a sample of 795 university students was carried out during 2019. Multilevel analyses tested the associations between gender (BSRI) and personality (TIPI) and between personality and health -mental health (GHQ12) and wellbeing (MHC-SF). Cluster analysis explored tendencies of gender and personality, and each cluster showed different health patterns. Individuals with high scores in extraversion, conscientiousness, emotional stability, openness to experience, and very high agreeableness score, as well as high femininity and masculinity scores, presented a decreased psychological morbidity (ß= -3.62, 0.57 (SE), p<0.001) and an increased well-being (ß=7.68, 1.15 (SE), p<0.001). The most relevant indicators of mental health were identified in androgynous individuals, those individuals with high scores in masculinity and femininity, as well as high scores in extraversion, openness to experience, emotional stability, agreeableness, and conscientiousness.
Subject(s)
Gender Identity , Personality , Male , Female , Humans , Personality Disorders , Personality InventoryABSTRACT
PURPOSE: In the field of health sciences gender is often confused with biological sex (male/female) or reduced to a dichotomous classification (masculinity/femininity). The concepts of sex and gender interact with each other, but they are not equivalent. According to Sandra Bem four gender typologies can be established (androgynous, masculine, feminine and undifferentiated). A relationship has been shown to exist between gender and health. Yet, there is little evidence as to the relationship between gender typologies and adherence to the Mediterranean diet. The aim of this research is to evaluate the association between Bem's gender typologies and adherence to the Mediterranean diet. METHODS: Mediterranean Diet Adherence Screener (MEDAS) and Bem's gender typologies were the main variables. Sex, age, socioeconomic status (SES), body mass index (BMI) and obesity were analyzed as covariates. RESULTS: Multilevel multivariate analysis showed that androgynous typology was associated with increased adherence to Mediterranean diet (ß = 0.46 (SE 0.21), p = 0.033), adjusting by covariates, in a university population in Spain. Moreover, this was not the case with masculinity or femininity typologies. CONCLUSION: Thus, the results of this study suggest (1) that androgynous typology is not only associated with better mental health but also with healthy/healthier lifestyles, and (2) the complexity of the relationship between sex-gender and health would advise researchers avoid dichotomies such as male/female or masculinity/femininity.
Subject(s)
Femininity , Masculinity , Female , Male , Humans , Adult , Diet, Healthy , Obesity , Healthy LifestyleABSTRACT
Cerebellar dysfunction has been linked to autism spectrum disorders (ASDs). Although cerebellar pathology has been observed in individuals with fragile X syndrome (FXS) and in mouse models of the disorder, a cerebellar functional contribution to ASD-relevant behaviors in FXS has yet to be fully characterized. In this study, we demonstrate a critical cerebellar role for Fmr1 (fragile X messenger ribonucleoprotein 1) in ASD-relevant behaviors. First, we identify reduced social behaviors, sensory hypersensitivity, and cerebellar dysfunction, with loss of cerebellar Fmr1. We then demonstrate that cerebellar-specific expression of Fmr1 is sufficient to impact social, sensory, cerebellar dysfunction, and cerebro-cortical hyperexcitability phenotypes observed in global Fmr1 mutants. Moreover, we demonstrate that targeting the ASD-implicated cerebellar region Crus1 ameliorates behaviors in both cerebellar-specific and global Fmr1 mutants. Together, these results demonstrate a critical role for the cerebellar contribution to FXS-related behaviors, with implications for future therapeutic strategies.
Subject(s)
Autism Spectrum Disorder , Autistic Disorder , Cerebellar Diseases , Fragile X Syndrome , Animals , Mice , Fragile X Syndrome/metabolism , Autistic Disorder/genetics , Fragile X Mental Retardation Protein/genetics , Fragile X Mental Retardation Protein/metabolism , Disease Models, Animal , Mice, KnockoutABSTRACT
A total of 338 weaned rabbits (from the R line, selected for post-weaning growth rate) were used to evaluate the response to 18 generations of selection for increased growth rate on rabbit performance. Animals were obtained from two vitrified populations of the R line: R19V, belonging to the 18th generation (n = 165), and R37V, belonging to the 36th generation (n = 173), were allocated in individual and collective pens (178 and 160, respectively). A fattening trial was conducted from weaning (28 d of age until 63 d of age). During the trial, the body weight (BW), daily feed intake (DFI), average daily gain (ADG) and feed conversion ratio (FCR) were weekly monitored. Additionally, mortality and morbidity were daily registered. On days 49 to 53, an apparent faecal digestibility trial was also performed (12 animals per generation). Our results indicate that the generation of selection for growth rate did not affect mortality and morbidity. There were no differences in the diet digestibility according to the generation of selection. Regarding performance traits, R37V animals showed higher global BW (+6.7%; p = 0.0011) than R19V animals. R37V animals showed the same BW at weaning; however, R37V animals showed higher BW values in the last three weeks compared with R19V animals. Animals from the R37V generation also showed a higher DFI from 56 to 63 d of age (+12%; p = 0.0152) than R19V animals. However, there were no differences in global ADG and FCR between generations. These results indicate that the selection for growth rate in growing rabbits has slowed down, suggesting a lack of effectiveness in the genetic progress.
ABSTRACT
La Autolesión No Suicida (ANS) se define como un dolor auto-infligido que se utiliza como un mecanismo para aliviar la angustia psicoló-gica. Aunque ANS es común en el trastorno límite de la personalidad (TLP), también es un problema creciente en estudiantes universitarios. Si bien la desregulación emocional y la urgencia negativa están asociadas con ANS, poco se sabe sobre las dimensiones específicas que predicen la moti-vación (funciones) y la frecuencia de las autolesiones. Se exploró la relación entre la desregulación emocional, la urgencia negativa, y ANS en 86 adultos jóvenes, divididos en tres grupos: estudiantes universitarios con ANS, pa-cientes TLP con ANS y un grupo de control sano sin ANS. Realizamos análisis de regresión múltiple para predecir las funciones y frecuencia de ANS. La no aceptación de las emociones, una dimensión especifica de la desregulación emocional, predijo de manera única las funciones intraperso-nales de ANS, pero no las funciones interpersonales. Por último, la falta de estrategias de regulación emocional predijo la frecuencia de ANS solo en individuos con una alta urgencia negativa, es decir, individuos que tienden a actuar impulsivamente cuando experimentan emociones negativas, pero no en aquellos con una baja urgencia negativa. Los hallazgos resaltan las moti-vaciones subyacentes a la autolesión y revelan facetas de la desregulación emocional relevantes para el tratamiento de ANS.(AU)
Non-suicidal self-injury (NSSI) is defined as self-inflicted pain, and it is used as a mechanism to alleviate psychological distress. Although NSSI is prevalent in Borderline Personality Disorder (BPD), it is also an increasing concern among college student populations. While emotion dysregulation and negative urgency are associated with NSSI, little is known about which dimensions specifically predict the motivations (NSSI-functions) and frequency of self-harm. The current study explored the rela-tionship between emotion dysregulation, negative urgency, and NSSI in 86 young adults, divided into three groups: college students with NSSI, BPD patients with NSSI, and a healthy control group without NSSI. We con-ducted multiple regression analyses to predicted NSSI-functions and NSSI-frequency. Non-acceptance of emotions, a specific dimension of emotion dysregulation, uniquely predicted intrapersonal NSSI-functions (e.g., regu-lating distressing emotions), but not interpersonal NSSI-functions (e.g., communicating distress). Lastly, poor emotion regulation strategies pre-dicted NSSI-frequency only in individuals with high negative urgency, that is, individuals who tend to act impulsively when experiencing negative emotions, but not in those with low negative urgency. Findings shed light on the underlying motivations for engaging in self-injury, and they reveal facets of emotion dysregulation relevant for NSSI treatment.(AU)
Subject(s)
Humans , Male , Female , Young Adult , Self-Injurious Behavior/psychology , Borderline Personality Disorder , Adolescent Behavior , Self-Injurious Behavior , Self-Control , Disruptive, Impulse Control, and Conduct Disorders , Mental Health , Psychology, Social , Psychology , Case-Control Studies , PsychiatryABSTRACT
Glucose represents the principal brain energy source. Thus, not unexpectedly, genetic glucose transporter 1 (Glut1) deficiency (G1D) manifests with encephalopathy. G1D seizures, which constitute a prominent disease manifestation, often prove refractory to medications but may respond to therapeutic diets. These seizures are associated with aberrant thalamocortical oscillations as inferred from human electroencephalography and functional imaging. Mouse electrophysiological recordings indicate that inhibitory neuron failure in thalamus and cortex underlies these abnormalities. This provides the motivation to develop a neural circuit testbed to characterize the mechanisms of thalamocortical synchronization and the effects of known or novel interventions. To this end, we used mouse thalamocortical slices on multielectrode arrays and characterized spontaneous low frequency oscillations and less frequent 30-50 Hz or gamma oscillations under near-physiological bath glucose concentration. Using the cortical recordings from layer IV among other regions recorded, we quantified oscillation epochs via an automated wavelet-based algorithm. This method proved analytically superior to power spectral density, short-time Fourier transform or amplitude-threshold detection. As expected from human observations, increased bath glucose reduced the lower frequency oscillations while augmenting the gamma oscillations, likely reflecting strengthened inhibitory neuron activity, and thus decreasing the low:high frequency ratio (LHR). This approach provides an ex vivo method for the evaluation of mechanisms, fuels, and pharmacological agents in a crucial G1D epileptogenic circuit.