The Effect of Regular Resistance Exercise, Vitamin D, and Calcium Supplements on the Gastrocnemius Muscle in Rats in the Post-menopausal Period: an Experimental Study

Background: Menopause is the natural termination of menstruation which affects the quality and important aspects of women's life. Objective: To evaluate the effect of regular resistance training (Ex) with vitamin D (Vit. D) and calcium (Ca) supplements in the postmenopausal period on muscle tissue in rats. Materials and Methods: In this experimental study, 72 female Wistar rats (8-10-wk old) were randomly divided into control, placebo, Vit. D, Ca, Ex, Ca + Vit. D, Ex + Ca, Ex + Vit. D, and Ex + Ca + Vit. D groups. Control and placebo groups were fed with a standard diet and sesame oil, respectively. Two months after the ovariectomy, Ex, Ca (35 mg/kg), and Vit. D (10000 IU) were administered in all groups except the control. The number of muscle and inflammatory cells, fiber diameter, endomysium thickness, and degenerative collagen fiber area were assessed through hematoxylin-eosin staining. Results: Muscle cell number was increased in the Ex + Vit. D + Ca, Vit. D + Ex, and Vit. D groups compared to the control group; also, inflammatory cell number showed significant increase in the Ex + Vit. D + Ca (12 ± 5.46), Vit. D + Ex (14 ± 3.25), Ex (13 ± 4.08), Vit. D (11 ± 3.26), Ca + Vit. D (10 ± 1.01), and Ca + Ex (9 ± 2.87) groups. Muscle fiber diameter in the Ex + Vit. D + Ca and Vit. D + Ex groups was higher than the other groups. Endomysium thickness was significantly decreased in the Ex + Vit. D + Ca and Vit. D + Ex groups compared to the control and placebo groups (p < 0.001). Degenerative collagen fiber area showed a significant increase in the Ex + Vit. D + Ca and Vit. D + Ex groups (p ≤ 0.001) comparison with the control group. Conclusion: Regular resistance exercise, Vit. D, and Ca supplements can improve muscle morphological features in the postmenopausal period. Key words: Menopause, Muscle, Vitamin D, Calcium, Exercise

Clinical efficacy of endovascular treatment approach in patients with carotid cavernous fistula: A systematic review and meta-analysis

Background and objectives: Carotid-cavernous fistulas (CCFs) represent a group of rare, abnormal arteriovenous communications between the carotid arterial system and the cavernous sinuses (CS). CCFs often produce ophthalmologic symptoms related to increased CS pressures and retrograde venous drainage of the eye. Although endovascular occlusion remains the preferred treatment for symptomatic or high-risk CCFs, most of the data for these lesions is limited to small, single-center series. As such, we performed a systematic review and meta-analysis evaluating endovascular occlusions of CCFs to determine any differences in clinical outcomes based on presentation, fistula type, and treatment paradigm. Method: A retrospective review of all studies discussing the endovascular treatment of CCFs published through March 2023 was conducted using PubMed, Scopus, Web of Science, and Embase databases. A total of 36 studies were included in the meta-analysis. Data from the selected articles were extracted and analyzed using Stata software version 14. Results: 1494 patients were included. 55.08% were female and the mean age of the cohort was 48.10 years. A total number of 1516 fistulas underwent endovascular treatment, 48.05% of which were direct and 51.95% of which were indirect. 87.17% of CCFs were secondary to a known trauma while 10.18% were spontaneous. The most common presenting symptoms were 89% exophthalmos (95% CI: 78.0–100.0; I2 = 75.7%), 84% chemosis (95% CI: 79.0–88.0; I2 = 91.6%), 79% proptosis (95% CI: 72.0–86.0; I2 = 91.8%), 75.0% bruits (95% CI: 67.0–82.0; I2 = 90.7%), 56% diplopia (95% CI: 42.0–71.0; I2 = 92.3%), 49% cranial nerve palsy (95% CI: 32.0–66.0; I2 = 95.1%), 39% visual decline (95% CI: 32.0–45.0; I2 = 71.4%), 32% tinnitus (95% CI: 6.0–58.0; I2 = 96.7%), 29% elevated intraocular pain (95% CI: 22.0–36.0; I2 = 0.0%), 31% orbital or pre-orbital pain (95% CI: 14.0–48.0; I2 = 89.9%) and 24% headache (95% CI: 13.0–34.0; I2 = 74.98%). Coils, balloons, and stents were the three most used embolization methods respectively. Immediate complete occlusion of the fistula was seen in 68% of cases and complete remission was seen in 82%. Recurrence of CCF occurred in only 35% of the patients. Cranial nerve paralysis after treatment was observed in 7% of the cases. Conclusions: Exophthalmos, Chemosis, proptosis, bruits, cranial nerve palsy, diplopia, orbital and periorbital pain, tinnitus, elevated intraocular pressure, visual decline and headache are the most common clinical manifestations of CCFs. The majority of endovascular treatments involved coiling, balloons and onyx and a high percentage of CCF patients experienced complete remission with the improvement of their clinical symptoms

video_NEUROLOGY ID# 2018_879940

VIDE

Data from: Biallelic SQSTM1 mutations in early-onset, variably progressive neurodegeneration

Objective: To characterize clinically and molecularly an early-onset, variably progressive neurodegenerative disorder characterized by a cerebellar syndrome with severe ataxia, gaze palsy, dyskinesia, dystonia, and cognitive decline affecting 11 individuals from 3 consanguineous families. Methods: We used whole-exome sequencing (WES) (families 1 and 2) and a combined approach based on homozygosity mapping and WES (family 3). We performed in vitro studies to explore the effect of the nontruncating SQSTM1 mutation on protein function and the effect of impaired SQSTM1 function on autophagy. We analyzed the consequences of sqstm1 down-modulation on the structural integrity of the cerebellum in vivo using zebrafish as a model. Results: We identified 3 homozygous inactivating variants, including a splice site substitution (c.301+2T>A) causing aberrant transcript processing and accelerated degradation of a resulting protein lacking exon 2, as well as 2 truncating changes (c.875_876insT and c.934_936delinsTGA). We show that loss of SQSTM1 causes impaired production of ubiquitin-positive protein aggregates in response to misfolded protein stress and decelerated autophagic flux. The consequences of sqstm1 down-modulation on the structural integrity of the cerebellum in zebrafish documented a variable but reproducible phenotype characterized by cerebellum anomalies ranging from depletion of axonal connections to complete atrophy. We provide a detailed clinical characterization of the disorder; the natural history is reported for 2 siblings who have been followed up for >20 years. Conclusions: This study offers an accurate clinical characterization of this recently recognized neurodegenerative disorder caused by biallelic inactivating mutations in SQSTM1 and links this phenotype to defective selective autophagy

A 12-week double-blind randomized clinical trial of vitamin D₃ supplementation on body fat mass in healthy overweight and obese women

<p>Abstract</p> <p>Background</p> <p>Vitamin D concentrations are linked to body composition indices, particularly body fat mass. Relationships between hypovitaminosis D and obesity, described by both BMI and waist circumference, have been mentioned. We have investigated the effect of a 12-week vitamin D3 supplementation on anthropometric indices in healthy overweight and obese women.</p> <p>Methods</p> <p>In a double-blind, randomized, placebo-controlled, parallel-group trial, seventy-seven participants (age 38±8.1 years, BMI 29.8±4.1 kg/m²) were randomly allocated into two groups: vitamin D (25 μg per day as cholecalciferol) and placebo (25 μg per day as lactose) for 12 weeks. Body weight, height, waist, hip, fat mass, 25(OH) D, iPTH, and dietary intakes were measured before and after the intervention.</p> <p>Results</p> <p>Serum 25(OH)D significantly increased in the vitamin D group compared to the placebo group (38.2±32.7 nmol/L vs. 4.6±14.8 nmol/L; P<0.001) and serum iPTH concentrations were decreased by vitamin D3 supplementation (-0.26±0.57 pmol/L vs. 0.27±0.56 pmol/L; P<0.001). Supplementation with vitamin D3 caused a statistically significant decrease in body fat mass in the vitamin D group compared to the placebo group (-2.7±2.1 kg vs. -0.47±2.1 kg; P<0.001). However, body weight and waist circumference did not change significantly in both groups. A significant reverse correlation between changes in serum 25(OH) D concentrations and body fat mass was observed (r = -0.319, P = 0.005).</p> <p>Conclusion</p> <p>Among healthy overweight and obese women, increasing 25(OH) D concentrations by vitamin D3 supplementation led to body fat mass reduction.</p> <p>This trial is registered at clinicaltrials.gov as NCT01344161.</p

Biallelic PRMT7 pathogenic variants are associated with a recognizable syndromic neurodevelopmental disorder with short stature, obesity, and craniofacial and digital abnormalities

PURPOSE: Protein arginine methyltransferase 7 (PRMT7) is a member of a family of enzymes that catalyzes the methylation of arginine residues on several protein substrates. Biallelic pathogenic PRMT7 variants have previously been associated with a syndromic neurodevelopmental disorder characterized by short stature, brachydactyly, intellectual developmental disability, and seizures. To our knowledge, no comprehensive study describes the detailed clinical characteristics of this syndrome. Thus, we aim to delineate the phenotypic spectrum of PRMT7-related disorder. METHODS: We assembled a cohort of 51 affected individuals from 39 different families, gathering clinical information from 36 newly described affected individuals and reviewing data of 15 individuals from the literature. RESULTS: The main clinical characteristics of the PRMT7-related syndrome are short stature, mild to severe developmental delay/intellectual disability, hypotonia, brachydactyly, and distinct facial morphology, including bifrontal narrowing, prominent supraorbital ridges, sparse eyebrows, short nose with full/broad nasal tip, thin upper lip, full and everted lower lip, and a prominent or squared-off jaw. Additional variable findings include seizures, obesity, nonspecific magnetic resonance imaging abnormalities, eye abnormalities (i.e., strabismus or nystagmus), and hearing loss. CONCLUSION: This study further delineates and expands the molecular, phenotypic spectrum and natural history of PRMT7-related syndrome characterized by a neurodevelopmental disorder with skeletal, growth, and endocrine abnormalities

Biallelic variants in ZNF142 lead to a syndromic neurodevelopmental disorder

Biallelic variants of the gene encoding for the zinc‐finger protein 142 (ZNF142) have recently been associated with intellectual disability (ID), speech impairment, seizures, and movement disorders in nine individuals from five families. In this study, we obtained phenotype and genotype information of 26 further individuals from 16 families. Among the 27 different ZNF142 variants identified in the total of 35 individuals only four were missense. Missense variants may give a milder phenotype by changing the local structure of ZF motifs as suggested by protein modeling; but this correlation should be validated in larger cohorts and pathogenicity of the missense variants should be investigated with functional studies. Clinical features of the 35 individuals suggest that biallelic ZNF142 variants lead to a syndromic neurodevelopmental disorder with mild to moderate ID, varying degrees of delay in language and gross motor development, early onset seizures, hypotonia, behavioral features, movement disorders, and facial dysmorphism. The differences in symptom frequencies observed in the unpublished individuals compared to those of published, and recognition of previously underemphasized facial features are likely to be due to the small sizes of the previous cohorts, which underlines the importance of larger cohorts for the phenotype descriptions of rare genetic disorders