MRM2 variants in families with complex dystonic syndromes: evidence for phenotypic heterogeneity.

BACKGROUND: Dystonia involves repetitive movements and muscle contractions leading to abnormal postures. We investigated patients in two families, DYAF11 and M, exhibiting dystonic or involuntary movement disorders. METHODS: Clinical investigations were performed for all patients. Genetic analyses included genome-wide linkage analysis and exome sequencing followed by Sanger sequencing validation. MRM2-specific transcripts were analysed from participants' blood samples in Family DYAF11 after cloning of gene-specific cDNA. RESULTS: Four affected siblings in Family DYAF11 had progressive dystonic features. Two patients in Family M exhibited a neurodevelopmental disorder accompanied by involuntary movements. In Family DYAF11, linkage was detected to the telomere at chromosome 7p22.3, spanning <2 Mb. Exome sequencing identified a donor splice-site variant, c.8+1G>T in MRM2, which segregated with the phenotype, corresponding to the linkage data since all affected individuals were homozygous while the obligate unaffected carriers were heterozygous for the variant. In the MRM2 c.8+1G>T allele, an aberrant alternative acceptor splice-site located within exon 2 was used in a subset of the transcripts, creating a frameshift in the open reading frame. Exome sequencing in Family M revealed a rare missense variant c.242C>T, p.(Ala81Val), which affected a conserved amino acid. CONCLUSIONS: Our results expand the clinical and allelic spectrum of MRM2 variants. Previously, these descriptions were based on observations in a single patient, diagnosed with mitochondrial DNA depletion syndrome 17, in whom movement disorder was accompanied by recurrent strokes and epilepsy. We also demonstrate a subset of correctly spliced tt-ag MRM2 transcripts, raising the possibility to develop treatment by understanding the disease mechanism.

Environmental Drivers of Antimicrobial Resistance in Low and Middle-Income Countries: The Impacts of a Changing World.

This letter highlights the impact of environmental drivers on antimicrobial resistance (AMR) in low and middle-income countries (LMICs) and highlights the need for a comprehensive approach to address this global health threat. Key factors, such as agricultural practices, wastewater treatment, and pollution, contribute to the development and spread of resistant pathogens. Utilizing the One Health approach, the paper emphasizes the importance of promoting responsible antimicrobial use, strengthening public health systems, investing in innovative research, and raising public awareness. By understanding and addressing these environmental drivers, we can work toward safeguarding global health and ensuring a sustainable future.

Cardiac sarcoidosis: a comprehensive review of risk factors, pathogenesis, diagnosis, clinical manifestations, and treatment strategies.

Cardiac Sarcoidosis (CS) is a deadly consequence of systemic sarcoidosis that inflames all three layers of the heart, especially the myocardium-clinical signs of CS range from asymptomatic disease to abrupt cardiac death. CS generally remains undiagnosed secondary to a lack of definitive diagnostic criteria, a high percentage of false negative results on endomyocardial biopsy, and ill-defining clinical manifestations of the disease. Consequently, there is a lack of evidence-based recommendations for CS, and the present diagnostic and therapeutic management depend on expert opinion. The aetiology, risk factors, clinical symptoms, diagnosis, and therapy of CS will be covered in this review. A particular emphasis will be placed on enhanced cardiovascular imaging and early identification of CS. We review the emerging evidence regarding the use of Electrocardiograms (ECGs), Magnetic Resonance Imaging (MRI), and Positron Emission Tomography (PET) imaging of the heart to identify and quantify the extent of myocardial inflammation, as well as to guide the use of immunotherapy and other treatment regimens, such as ablation therapy, device therapy, and heart transplantation, to improve patient outcomes.

Isolation of secondary metabolites from Syzygium aromaticum (L.) Merr. & L.M.Perry. (cloves), and evaluation of their biological activities.

Phytochemical investigation of dried flower buds of Syzygium aromaticum (L.) Merr. & L.M.Perry. (clove) led to the isolation and identification of fourteen known compounds, oleanolic acid (1), betulinic acid (2), para methyl benzoic acid (3), sabrinic acid (4) eucalyptolic acid (5), nigricin (6), 3-O-trans-para-coumaroylmaslinic acid (7), methyl maslinate (8), maslinic acid (9), 3, 4, 5-trimethoxy-3',4'-O,O-methylideneflavellagic acid (10), lantanone (11) 3,4,3'-trimethoxyellagic acid (12), 11-oxo-oleanolic acid (13), and ß-sitosterol-3-O-ß-D-glucopyranoside (14). Their structures were identified by 1H NMR, 13C NMR, Mass spectroscopic techniques, and comparison with the literature data. Compounds 3, and 7-9 showed a strong mortality against root knot nematode, Meloidogyne incognita at 0.125% concentration after 72 hours (88-92% inhibition). Compound 4 showed a good anti-glycation activity with IC50 = 142.0 ± 1.8 µM when compared with standard, i.e. rutin (IC50 = 54.59 ± 2.20 µM). Compound 10 showed a comparable urease inhibitory activity (IC50 = 26.1 ± 0.19 µM) with the positive control thiourea (IC50 = 24.5 ± 0.34 µM).

Nationwide Assessment of Knowledge and Perception in Reinforcing Telemedicine in the Age of COVID-19 Among Medical Students From Pakistan.

The urgency for telemedicine is felt during the COVID-19 pandemic which has rendered the world shut by enforcing quarantines and lockdowns. Many developing countries including Pakistan have inadequate telehealth care services that limited access to rural and remote areas. A cross-sectional survey was carried out among medical students i.e., both preclinical and clinical enrolled in various medical colleges from all provinces of Pakistan to determine their Knowledge, Attitude and Perception regarding the use of Telemedicine during the COVID-19 Pandemic. A total of 398 respondents were included in this preliminary survey. Knowledgeable scores were calculated, from a maximum obtainable score of 7. The mean knowledge was found to be significantly associated with age, province, and year of study (p-value < 0.05). Attitude scores were calculated from a maximum obtainable score of 10. All the independent variables failed to reach a significant (p < 0.05) association with the mean attitude of respondents about telemedicine. Perception scores were calculated from a maximum obtainable score of 8. Residents of Khyber Pakhtunkhwa are more likely to know about telemedicine than Balochistan (p = 0.022) on univariate regression. We identified, lack of knowledge and training for telemedicine in medical institutes. It is crucial to assess the knowledge of medical students regarding telemedicine to comprehend, and evaluate their attitude as future doctors who can play a significant role in establishing telemedicine services in the health care system.

Functional Outcomes of Cementless Total Hip Arthroplasty in Avascular Necrosis of the Hip: A Prospective Study.

Introduction Avascular necrosis occurs due to impaired blood supply to the bone. It can be caused by fractures, dislocations, chronic steroid use, chronic alcohol use, coagulopathy, congenital source, and many other factors. It mostly affects the femoral head (hip joint). Its management can be conservative or invasive. Total hip arthroplasty is the treatment of choice for third and fourth stage avascular necrosis that can be cemented or uncemented. The purpose of this study is to access the functional outcomes of cementless total hip arthroplasty in patients with avascular necrosis of the hip. Materials and methods This prospective study was conducted at a major metropolitan hospital in Karachi, Pakistan over a period of six months. A total of 30 patients of age <60 years, either gender, and a confirmed diagnosis of avascular necrosis of hip with no other associated hip pathologies were included in this study. Demographic features, comorbidities, level of activity, range of movement before the development of avascular necrosis, Charnley's class, and laterality were noted. Cementless press-fit extensively porous-coated acetabular cup with or without cancellous screws and cementless press-fit extensively hydroxyapatite coated femoral stem were used through modified Gibson's posterior approach. The patients were checked for early and late complications, the position of acetabular and femoral components by radiography, and overall performance by Harris Hip Score (HHS) and modified HHS over a period of 12 months. All statistical analyses were performed using Statistical Package for Social Sciences (SPSS) version 19.0 (IBM Corp, Armonk, NY). Results The mean age was 43.9±6.7 years with 21 (70%) patients ranging from 40 to 60 years of age. There were 22 (73%) male and 8 (27%) female patients. Nine (30%) patients had diabetes mellitus, eight (27%) had hypertension, two (7%) had other comorbidities, and eleven (37%) had no comorbidities. A total of 11 (37%) patients were highly active, 18 (60%) were moderately active, and 1 (3%) was non-active before developing avascular necrosis. There were 4 (13%) patients in Charnley's class I, 15 (50%) in Charnley's class II, and 11 (37%) in Charnley's class III. Fifteen (50%) patients were operated on the left side, seven (23%) on the right side, and eight (27%) bilaterally. No significant early or late complications were noted. Acetabular component was found to be anteverted in 22 (73%), retroverted in zero (0%), neutral in 8 (27%), <35o inclined in 0 (0%), 35o-50o inclined in 23 (77%), and >50o inclined in 7 (23%) patients, while femoral component was found neutral in 28 (93%), valgus in 2 (7%), and varus in zero (0%) patients on radiography at follow-up. On functional assessment, the HHS was 100% in 27 (90%) patients, 96% in 2 (7%) patients, and 83% in 1 (3%) patient with an average of 99.2%, while 29 (97%) patients had excellent and only 1 (3%) patient had a good outcome on modified HHS. Conclusions Cementless total hip arthroplasty, performed in patients <60 years of age and avascular necrosis of the hip with no other associated hip pathologies, has excellent functional outcomes with no pain, limping, physical deformity, difficulty in walking, difficulty in climbing stairs, difficulty using public transport, difficulty in sitting, or difficulty in wearing shoes and socks. They usually attain normal limb length and range of movement.

Clinical Spectrum of Hyponatremia in Patients with Stroke.

Introduction Hyponatremia is a common electrolyte imbalance, which is readily observed in patients with ischemic as well as hemorrhagic stroke. It is mostly hypoosmolal and may be due to syndrome of inappropriate anti-diuretic hormone (SIADH) or cerebral salt wasting syndrome (CSWS). The aim of this study was to evaluate the clinical spectrum of hyponatremia in patients of both hemorrhagic and ischemic strokes. Methods In this prospective observational study, all patients admitted with stroke were screened for serum sodium levels right after hospital admission. Patients with serum sodium levels <135 mEq/L were included. Their demographic characteristics, type of stroke, etiology of hyponatremia, and site of hemorrhage/vascular territory ischemia was included. Results Hyponatremia was diagnosed in 34.2% of patients. Their mean serum sodium level was 130.4 ± 3.5 (mEq/L). Ischemic stroke was more common in the hyponatremia group (67.7%), and SIADH was a more common cause of hyponatremia (71.1%). In hyponatremic patients with hemorrhagic stroke, right putamen hemorrhage was seen in 50% of patients with SIADH, and right thalamus was seen in 73.3% patients with CSWS. In hyponatremic patients with ischemic stroke, left middle cerebral artery ischemia was seen in 47% patients with SIADH and right middle cerebral artery ischemia was seen in 55% patients with CSWS. Conclusion In patients with hyponatremia secondary to stroke, ischemic stroke is a common entity. SIADH remains a more frequently witnessed underlying pathology in hyponatremic stroke patients.