Understanding the Pathophysiology of Spinocerebellar Ataxias through genetics, neurophysiology, structural and functional neuroimaging

Over the past 10 years a large cohort of 656 index patients with clinically suspected degenerative ataxias were clinically evaluated under various research projects. Of these, 625 index patients underwent genetic tests for the clinically suspected most probable diagnosis. A diagnosis could be achieved in 218 patients (34.9%). Among these 218 index patients, 82 each were SCA1 and SCA2, 32 were SCA3, 4 were SCA12, and 18 were Friedreich's Ataxia. Thus among the Autosomal Dominant Ataxias (SCAs) there was equal prevalence of SCA1 and SCA2 (41% each) followed by SCA3 (16%) and SCA12 (2%). This high prevalence of SCA1 is in contrast to the available National and International literature. The rate of clinical disease progression, especially in SCA2, was dependent on the CAG repeat size, and may commence linearly from birth.Apart from cerebellar involvement, a comprehensive evaluation of the neuroaxis in various subsets of this genetically proved cohort showedsubclinicalinvolvement of the cerebral cortex, central motor and sensory pathways, peripheral nervous system and autonomic nervous system. Important findings include: (a)Amixedsensorimotor and pure sensory neuropathy was seen in all the three subtypes of SCAs, while pure motor neuropathy was uncommon; (b) There was reduced cortical excitability and prolonged central motor conduction time, most evident in SCA1 and least in SCA2; (c) Cardiac autonomic dysfunction, predominantly parasympathetic, was seen in SCA, and the severity correlated with the duration of illness in SCA1; (d) In SCA1 there was a global impairment of balance, with greater instability in anterior–posterior than medio–lateral directions; (e) In all the three SCAs there was a significant loss of gray matter in both cerebellar hemispheres and vermis. Vermian atrophy was more pronounced in SCA3, while SCA1 and SCA2 had significant white matter atrophy. Pontine white matter atrophy was more pronounced in SCA2; (f) Cerebellar activity was largely absent with additional activity in contralateral cortices and in thalami in patients with SCA1; increased thalamic function could be one of the causes for disinhibition of the motor cortex contributing to uncoordinated movements.Studies on larger cohort of each subtype of SCAs to validate the above findings, follow-up studies to determine the rate and nature of progression of neurodegeneration and evaluation of pre-symptomatic genetically confirmed SCAs will help understand the pathophysiology of the SCAs

Study of Gentian Violet Toxicity in Labeo rohita: Behavioral Modifications, and Sub-lethal Impacts

This study explores the acute and sub-lethal toxicological effects of Gentian Violet (GV), a synthetic triphenylmethane dye, on Labeo rohita, a prevalent freshwater aquaculture species. GV, utilized extensively in industrial applications, including aquaculture for antifungal treatment, poses potential ecological risks to aquatic organisms. Acute toxicity was evaluated by determining the 96-hour lethal concentration (LC50) via Probit analysis, with an LC50 value of 1.8 mg/L identified, indicating substantial toxicity. For sub-lethal exposure, concentrations corresponding to 1/5th and 1/20th of the LC50 (0.36 mg/L and 0.09 mg/L) were assessed over 7, 14, and 28 days. Behavioral alterations, including reduced feeding, erratic swimming, and gill irritation, were observed, particularly at the higher concentration, though recovery was noted over time, suggesting adaptive physiological responses. Physiological stress markers, including oxygen uptake and hematological parameters, exhibited significant perturbations at 0.36 mg/L, with partial recovery by the 28th day. These results underscore the dose-dependent toxicity of GV, with pronounced acute effects and sub-lethal stress responses manifesting through behavioral and biochemical alterations. The study further emphasizes the need for stringent regulatory frameworks to mitigate GV contamination in aquatic ecosystems, alongside the pursuit of eco-friendly alternatives to mitigate the long-term environmental impact of synthetic dyes. The findings also advocate for further research to elucidate chronic toxicity and reproductive effects to inform sustainable aquaculture practices and environmental conservation strategies

Study of Hematological Alterations and Oxidative Stress in Labeo rohita Exposed to Sub-lethal Methylene Blue

Methylene Blue (MB), a synthetic dye widely used in aquaculture for its antifungal properties, poses significant ecological risks due to its sub-lethal toxicity in aquatic organisms. This study investigates the hematological and oxidative stress responses in Labeo rohita (rohu) exposed to sub-lethal concentrations of MB (1/5th and 1/20th of the 96-hour LC50 of 8.5 mg/L) over 7, 14, and 28 days. Hematological parameters, including red blood cell (RBC) morphology, hemoglobin (Hb%) levels, total leukocyte count (TLC), and differential leukocyte profiles, were analyzed alongside lipid peroxidation (LPO) to assess oxidative damage. Results revealed significant dose- and time-dependent disruptions: RBCs exhibited crenation and membrane shrinkage, Hb% declined by 51% (4.8 ± 0.3%) in the 1/5th LC50 group by day 28, and TLC increased by 116% (15.8 ± 0.7 ×10⁴ cells/mm³), accompanied by neutrophilia (37.5 ± 1.8%) and lymphocytopenia (58.0 ± 1.8%). Oxidative stress markers, quantified as malondialdehyde (MDA), surged to 7.8 ± 0.6 nmol/g in high-dose groups, correlating strongly with Hb% reduction (r = -0.89, p < 0.01), underscoring ROS-mediated erythrocyte damage. Statistical analysis (ANOVA, p < 0.001) confirmed the significance of these alterations. The study identifies MB-induced anemia, immunosuppression, and oxidative stress as critical threats to fish health, validating hematological biomarkers as reliable indicators of sub-lethal toxicity. These findings emphasize the need for regulatory limits on MB discharge and advocate for eco-friendly alternatives in aquaculture. Future research should explore molecular mechanisms of MB toxicity and long- term ecological impacts to inform sustainable practices and mitigate risks to aquatic biodiversity

Total Ionization Cross Sections due to Electron Impact of Ammonia from Threshold to 10 MeV

In the present paper, we have employed modified Khare-BEB method [Atoms, (2019)] to evaluate total ionization cross sections by the electron impact for ammonia in energy range from the ionization threshold to 10 MeV.  The theoretical ionization cross sections have been compared to the available previous theoretical and experimental results. The collision parameters dipole matrix squared  and CRP  also have been calculated. The present calculations were found in remarkable agreement with the available experimental results

Re-emergent Tongue Tremor in Neuroleptic Induced Parkinsonism

Background: A re-emergent tremor is suggested to be specific to Parkinson’s disease and although a tongue tremor has been reported in levosulpiride-induced parkinsonism (LIP), re-emergence has never been reported. Case Report: A 59-year-old female presented with a 3-month history of bradykinesia, 2-week history of right-leg tremor, and 10-day history of lip and tongue tremor. A review of the medication revealed a 15-month history of levosulpiride consumption. On examination, asymmetric bradykinesia, rigidity, rest tremor of the right leg, and re-emergent tongue tremor were observed. The parkinsonism subsided after levosulpiride was stopped. Discussion: This is the first report of re-emergent tongue tremor in LIP

Luminescent quantum clusters of gold in transferrin family protein, lactoferrin exhibiting FRET

We report the synthesis of highly luminescent, water soluble quantum clusters (QCs) of gold, which are stabilized by an iron binding transferrin family protein, lactoferrin (Lf). The synthesized AuQC@Lf clusters were characterized using UV-Visible spectroscopy, X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), photoluminescence (PL), matrix assisted laser desorption ionization mass spectrometry (MALDI-MS), FTIR spectroscopy and circular dichroism (CD) spectroscopy along with picosecond-resolved lifetime measurements. Detailed investigations with FTIR and CD spectroscopy have revealed changes in the secondary structure of the protein in the cluster. We have also studied Forster resonance energy transfer (FRET) occurring between the protein and the cluster. The ability of the clusters to sense cupric ions selectively at ppm concentrations was tested. The stability of clusters in widely varying pH conditions and their continued luminescence make it feasible for them to be used for intracellular imaging and molecular delivery, particularly in view of Lf protection

Total Total Ionization Cross Sections due to Electron Impact of Carbon Tetrafluoride from Ionization Threshold to 10 MeV

Modified Khare-BEB model has been used to calculate the electron impact ionization cross section for carbon tetrafluoride (CF4) from ionization threshold to 10 MeV. The collisional parameters CRP and also has been  calculated. The calculations are compared with available experimental data . A good agreement is found among the present results, other previous calculations, and experimental data

Status Dystonicus as an Acute Sequelae Following Anoxic Cerebral Damage

Background: Status dystonicus (SD) is the term used for extreme, continuous, generalized muscle contractions that are poorly responsive to treatment. Here, we report a rare case of acute hypoxic ischemic encephalopathy presenting with SD. Case Report: A young male sustained cerebral hypoxia following a cardiac event and presented with opisthotonic posturing and dystonia refractory to medical therapy. His serum creatine phosphokinase was high and his urine tested positive for myoglobin. Discussion: SD as an acute sequelae following acute brain hypoxia is rare. Management of brain anoxia is challenging, even more so when the presentation is compounded by refractory SD. Keywords: Dystonia, emergency, hypoxia, status, anoxia Citation: Ray S, Sidhu RJS, Pal PK, Yadav R. Status dystonicus as an acute sequelae following anoxic cerebral damage. Tremor Other Hyperkinet Mov. 2019; 9. doi: 10.7916/98r0-743

Chemical potential shift and gap-state formation in SrTiO3−δ_{3-\delta} revealed by photoemission spectroscopy

In this study, we report on investigations of the electronic structure of SrTiO$_3$ annealed at temperature ranging between 550 and 840$^\circ$C in an ultrahigh vacuum. Annealing induced oxygen vacancies (O$_{vac}$) impart considerable changes in the electronic structure of SrTiO$_3$. Using core-level photoemission spectroscopy, we have studied the chemical potential shift ($\Delta\mu$) as a function of annealing temperature. The result shows that the chemical potential monotonously increases with electron doping in SrTiO$_{3-\delta}$. The monotonous increase of the chemical potential rules out the existence of electronic phase separation in the sample. Using valence band photoemission, we have demonstrated the formation of a low density of states at the near Fermi level electronic spectrum of SrTiO$_{3-\delta}$. The gap-states were observed by spectral weight transfer over a large energy scale of the stoichiometric band gap of SrTiO$_3$ system leading finally to an insulator - metal transition. We have interpreted our results from the point of structural distortions induced by oxygen vacancies.Comment: 7 pages, 6 figures, 1 tabl