Spinocerebellar ataxia type 12 (SCA12), a progressive neurological disorder, is the second-most common autosomal dominant ataxia in India. The disease is clinically heterogeneous with a variable age-of-onset. A CAG repeat expansion mutation upstream of PPP2R2B gene is causal to SCA12 motor and non-motor symptoms but its pathophysiological significance remains unknown. PPP2R2B encodes for the regulatory subunit B of the protein phosphatase 2 A (PP2A), a major regulator of amyloid beta (Aβ) and tau proteins. We aimed to determine whether PPP2R2B mutation leads to Aβ and tau dysregulation in SCA12. Plasma Aβ42/Aβ40 ratio, a core biomarker for Aβ toxicity and cognitive impairment was further investigated. This cross-sectional study included 27 genetically confirmed SCA12 patients and 24 healthy controls. The patients were subjected to ICARS and MoCA clinical scales for disease severity and cognition respectively. Plasma levels for Aβ42, Aβ40, total tau (t-tau) and phosphorylated tau (p-tau) levels were estimated spectrophotometrically using validated ELISA kits. A significant decrease in the plasma Aβ40 level (p = 0.014) and an increase in the Aβ42/Aβ40 ratio (p = 0.007) was observed in SCA12. Total tau and p-tau levels were unchanged. No significant correlation of the plasma Aβ and tau proteins with clinical parameters was obtained. In SCA12, we identified an altered plasma Aβ profile indicative of abnormal peripheral amyloidogenesis. Plasma Aβ and tau concentrations were not correlated with the patients’ cognitive status. The dynamic ratiometric Aβ42/Aβ40 shift in plasma is a forerunner of Aβ neurotoxicity and opens novel avenues for Aβ-targeted therapy in SCA12.
Breast cancer is associated mostly with women; however, breast cancer also appears in men, which dictates the need to know about gender-specific differences in the pathology and treatment. Male breast cancer constitutes less than 1 % of all cases and is usually diagnosed when the patient is older, with bigger tumors and at later stages than breast cancer in women. The most widespread subtype in both genders is invasive ductal carcinoma. The effect of hormone receptor positivity is very prominent in the treatment of men, and the risk factors include the BRCA2 mutations and the hormonal imbalance. The management approach, such as surgery, chemotherapy, radiotherapy, and hormonal therapy, is like that of women, and it may vary in treatment effectiveness because of hormonal and biological differences. The prognostic data in males are scarce, with generally worse outcomes, most likely because of delayed diagnosis and low rates of clinical trial representation. Men with breast cancer also face special psychosocial obstacles with regard to stigma and support. The use of artificial intelligence (AI) and machine learning are emerging options that have the potential to improve detectability and personalized treatment in both genders. The current review draws similarities between breast cancer in males and females to promote gender-specific interventions and better outcomes.
Epilepsy remains a debilitating neurological disorder affecting approximately 50 million individuals worldwide. Current Anti-seizure medications (ASM) targeting Synaptic Vesicle Protein 2A (SV2A), such as levetiracetam, exhibit variable efficacy and adverse effect profiles, necessitating exploration of novel therapeutic approaches. This study investigates Bacopa monnieri-derived compounds as potential dual inhibitors of SV2A and Carbonic Anhydrase II (CA-II), two mechanistically distinct targets implicated in seizure pathophysiology. An integrated computational workflow comprising ADMET profiling, molecular docking, molecular dynamics (MD) simulations, and MM-GBSA binding free energy calculations was implemented to evaluate selected phytoconstituents. ADMET analysis revealed favourable pharmacokinetic parameters for several compounds, particularly Ebelin Lactone and Jujubogenin, with superior blood-brain barrier permeability (BBB >0.9) and human intestinal absorption (>95 %) compared to reference drugs. Molecular docking identified compelling binding affinities, with Ebelin Lactone (-11.2 kcal/mol) and Jujubogenin (-10.9 kcal/mol) exhibiting stronger interactions with SV2A than brivaracetam (-6.8 kcal/mol). Similarly, these compounds demonstrated robust binding to CA-II (-8.4 and -8.7 kcal/mol, respectively). Protein-ligand interaction profiler analysis elucidated key stabilizing interactions, including hydrogen bonds with Thr199 and His64 in CA-II and hydrophobic contacts within the SV2A binding pocket. MD simulations confirmed structural stability of the protein-ligand complexes, evidenced by equilibrated RMSD trajectories (0.2-0.3 nm). MM-GBSA calculations substantiated the thermodynamic favourability of these interactions, with binding free energies for top candidates significantly exceeding reference compounds. These findings establish an in silico framework for prioritizing Bacopa monnieri phytoconstituents as computationally predicted dual-target candidates, highlighting their potential relevance for seizure management, with the possibility of improved efficacy through simultaneous modulation of distinct pathophysiological mechanisms. All findings are based solely on in silico analyses and require experimental validation.
BACKGROUND:Progressive supranuclear palsy (PSP) is a rare and devastating tauopathy with limited global data. Given India's large population, genetic diversity, and clinical heterogeneity, large multicenter datasets are crucial to enrich global understanding of PSP. OBJECTIVE:To characterize the demographic, clinical, and phenotypic profiles of a large multicenter Indian PSP cohort. METHODS:Subjects fulfilling MDS-PSP criteria were prospectively recruited across movement disorders centers (2021-2025). Standardized demographic and clinical data were collected. RESULTS:A total of 1035 subjects were enrolled (M:F = 709:326), with a median age of 65 years and a mean onset age of 62.2 ± 7.9 years. Regional distribution reflected pan-Indian recruitment (South 35%, North 26%, West 21%, East 18%). PSP-Richardson's syndrome was most common (41%), followed by PSP-Parkinsonism (18%) and PSP-CBS (11%); rarer phenotypes included PSP-PI (7%), PSP-F (7%), PSP-PGF (5%), PSP-OM (2%), PSP-SL (1%), and PSP-C (1%). Falls occurred earliest in PSP-PGF (13.7 months) and PSP-SL (16.3 months), while PSP-P showed delayed disability (falls at 31 months) indicating progression patterns. Cognitive onset was prominent in PSP-F (21%) and PSP-SL (57%). Levodopa was prescribed to 893 patients; 186 (21%) reported >25% subjective benefit, and 358 (40%) reported ≤25% benefit. Amantadine was used in 351 (34%) patients, with improvement in 177. CONCLUSION:This largest systematically profiled PSP cohort highlights both shared and distinctive features: high frequency of non-RS variants, aggressive course in PSP-RS/SL, better survival in PSP-P, and limited pharmacological benefit. These findings establish a foundation for longitudinal and genetic studies in diverse populations.
BACKGROUND:Groin flap surgery carries a risk of iatrogenic nerve injury, most commonly involving the lateral femoral cutaneous nerve and presenting as meralgia paresthetica. In contrast, femoral nerve injury is rare and typically associated with motor deficits. Pure sensory femoral neuropathy is exceptionally uncommon and may closely mimic meralgia paresthetica, creating a diagnostic challenge. CASE REPORT:We report a 24-year-old man who developed severe neuropathic pain over the anterolateral thigh following groin flap donor-site closure. Initial clinical suspicion was meralgia paresthetica. However, motor examination and electrodiagnostic studies were normal. High-resolution ultrasound revealed femoral nerve displacement and edema, and ultrasound-guided transcutaneous nerve stimulation reproduced the patient's symptoms, confirming a diagnosis of pure sensory iatrogenic femoral neuropathy. The patient was successfully treated with ultrasound-guided femoral nerve hydrodissection, resulting in sustained pain relief at the 6-month follow-up visit. CONCLUSIONS:Pure sensory femoral neuropathy can mimic meralgia paresthetica after groin surgery. High-resolution ultrasound is critical for accurate diagnosis, and ultrasound-guided hydrodissection may be an effective therapeutic option when conservative management fails, though further studies are needed.
