Xiang pig is a native inbred line originating from a warm and humid mountainous region and is prone to infections by pathogens causing lung lesions. However, the underlying genetic factors still remain unclear. Our previous genomic resequencing comparisons found a deletion type of structural variation (SV) within the intron of gene cerebellar degeneration related protein 2 (CDR2) with a higher frequency in Xiang pigs compared with European pig breeds. This study is aimed to explore the relationship between the SV and the lung injury in Xiang pig populations. It demonstrated that the deletion genotype (MM) was dominant in Xiang pig herds and with a higher percentage of allele M than that in Xiang pig with pulmonary lesions and Large White breeds. By Sanger sequencing and RepeatMasker analysis, a SINE in 277bp (namely SINE-277) was detected and located in the opposite orientation of CDR2 gene. The inhibit effects of SINE-277 on transcription was confirmed by EGFP reporter gene after transfected into HEK-293T cells. And the expression levels of CDR2 was increased in the lungs with MM types (P < 0.05) via both RT-qPCR and Western blotting assays. Moreover, significant differences were estimated between the SV genotypes and the lung lesion severity scores, the antibody concentrations against pathogens, and expressions of nine inflammation factor genes including NFκB. It reinforced the effects of SINE on gene CDR2 expression and might be taken as a DNA marker for the resistance/susceptibility to lung diseases in pigs.

Spinocerebellar ataxias (SCAs) are a group of progressive neurodegenerative disorders caused by pathogenic variants in more than 40 genes with diverse cellular functions. In this study, we identified the c.247C > T p.(Arg83Trp) variant in RAB3A, encoding a small GTPase involved in membrane-associated regulated exocytosis, in two families with cerebellar ataxia. Affected individuals presented with adult-onset, gradually progressive cerebellar symptoms, often accompanied by mild gait spasticity and tremors. Variable features of neurodevelopmental disorders were also observed. Brain MRI consistently revealed cerebellar atrophy, often accentuated in the vermis, and neuropathological examinations demonstrated diffuse cerebellar cortical degeneration. Functionally, the R83W mutation lies within the conserved switch II region of Rab3A, a domain critical for effector interaction. Although the mutant Rab3A R83W retained GTP-binding affinity, it failed to bind the key effector proteins RIM1 and Rabphilin-3A, highlighting the functional importance of R83 in effector complex formation, as supported by structural analysis. In PC12 cells, the R83W mutant exhibited diffuse cytoplasmic localization, in contrast to the vesicle- and neurite-tip localization of the wild-type and GTP-bound Rab3A mutant. The concordant localization pattern of R83W and GDP-bound Rab3A mutants suggests that R83W-induced mislocalization results from a failure to engage downstream effector proteins. In the cerebellum, Rab3A was predominantly localized to parallel fiber terminals and was absent from postsynaptic Purkinje cells. These findings suggest that disruption of the interaction between Rab3A and its effector proteins may underlie disease pathogenesis, possibly involving presynaptic dysfunction at parallel fiber-Purkinje cell synapses mediated by the Rab3A-RIM1 complex.

Multidimensional abnormal gait analysis and biomarker identification for patients with spinocerebellar ataxia type 3 using an Azure Kinect-based motion capture system.

Anti-Yo–associated paraneoplastic cerebellar degeneration revealing appendiceal adenocarcinoma: a case report with complete neurological recovery

Paraneoplastic syndromes are secondary conditions to the systemic effects of cancer. Among these, paraneoplastic cerebellar degeneration (PCD) is one of the most common neurological forms. PCD is characterized by immune-mediated damage to Purkinje cells and progressive cerebellar atrophy. Exercise has already been suggested as a non-pharmacological strategy to counteract cachexia, one of the most prevalent paraneoplastic syndromes. However, the impact of physical training on PCD has not yet been investigated. In this study, male BALB/c mice were assigned to four experimental groups. Two groups (T+) were inoculated with C26 tumor fragments and either underwent a 4-week endurance training protocol (TR) or remained sedentary (SED). The remaining two groups (T−) were subjected to the same training or sedentary conditions. Tumor groups were sacrificed at the onset of cachexia to assess the impact of proactive endurance training. Cachexia onset was confirmed during the third week through body weight loss and reduced grip strength analyses. Preliminary histological analysis revealed that the overall cerebellar area was comparable across groups. Interestingly, the Purkinje cell body circularity index and layer thickness were significantly reduced in SED T+ mice and restored in TR T+ animals. Among cerebellar regions, the flocculonodular lobe -crucial for postural and oculomotor regulation- was the most impacted, yet also the one where training provided the strongest effect in preserving Purkinje cell soma size. Since ZIC4 is one of the transcription factors targeted by the autoimmune response in PCD, we evaluated its expression and localization using both immunohistochemistry and immunofluorescence. ZIC4 expression was reduced in the Purkinje cells of SED T+ mice, but training was able to protect Purkinje cells from any autoimmune attack during tumour development. We also assessed the expression of PSD95, a common marker used for the immunolabeling of the post-synaptic side of excitatory synapses. The very low expression of the PSD95 protein in SED T+ mice suggested that the tumour mass affected the synaptic plasticity, while endurance training again preserved synaptic integrity. Altogether, these results suggest an important role of training in the protection of cerebellum damage. Further studies are needed to clarify the role of exercise in protecting the stimulating synapses of the efferent fibers of the cerebellar cortex.

ObjectiveThis study primarily aimed to comprehensively characterize the neurological, neuroradiological and neurocognitive profiles, as well psychiatric features of individuals with Spinocerebellar Ataxia Type 34 (SCA34) associated with pathogenic variants in the ELOVL4 gene. Secondarily, we investigated the relationship between neurocognitive functions and cerebellar morphology in individuals with SCA34 by correlating structural changes to cognitive performance. Given involvement of the cerebellum in SCA34, our findings will contribute to a broader understanding of the role of the cerebellum in cognition.MethodsFour individuals (52 f, 72 m, 76 m, 76 f) underwent DNA testing using Next-Generation Sequencing and detailed assessment of neurocognitive functions. The test battery evaluated all six cognitive domains: verbal functions, executive functions, attention and processing speed, learning and memory, visuospatial perception and abilities, and social cognition. In addition, cerebellar and motor functions were evaluated using Finger Tapping, Prism Adaptation, and the Motor Speed subtest of the Delis-Kaplan executive function system (D-KEFS). Test results were compared with each individual’s estimated premorbid cognitive level, determined from their highest educational attainment or occupational status prior to disease onset. Psychiatric symptoms related to anxiety, depression, and sleep were reported using clinical scales. The Scale for the Assessment and Rating of Ataxia (SARA) was used to assess ataxia severity. Two individuals and one matched control underwent high-resolution 7T MRI to characterize cerebellar morphology.ResultsNeurocognitive assessments identified cognitive and motor dysfunction across all individuals, including distinct neurocognitive impairments consistent with cerebellar cognitive-affective syndrome (CCAS), along with additional deficits in learning, visual and verbal episodic memory, emotion recognition—a component of social cognition. Anxiety and sleep disturbance, but not depression, were observed in both female participants. High-resolution 7 T MRI revealed structural cerebellar alterations, with moderate to severe bilateral cerebellar atrophy, including the vermis and multiple lobules (Crus II, VIIb, VIIIa, VIIIb, IX), as well as atrophy of the middle and superior cerebellar peduncles, accompanied by mild pontine atrophy. Genetic analyses confirmed the involvement of ELOVL4-related disruptions in long-chain fatty acid biosynthesis, offering insight into the molecular underpinnings of cerebellar degeneration in SCA34.ConclusionIndividuals with SCA34 show cerebellar degeneration accompanied by cognitive, motor, and social-affective impairments consistent with CCAS. Atrophy of the vermis, multiple lobules, and cerebellar peduncles align with these deficits, highlighting the cerebellum’s key role in cognition. ELOVL4-related disruptions in fatty acid biosynthesis provides insight into the molecular basis of SCA34. Together, these findings advance our understanding of how cerebellar pathology contributes to complex neurocognitive and psychiatric symptoms in genetic ataxias.

BackgroundSocial cognitive dysfunction manifests early in behavioral variant frontotemporal dementia (bvFTD), causing significant distress and burden for caregivers. Research on impaired social cognition in bvFTD has traditionally focused on cortical networks. Emerging evidence highlights cerebellar changes associated with cognitive and neuropsychiatric symptoms in bvFTD. Notable, these changes occur at early disease stages and are accompanied by social cognitive deficits. However, the impact of cerebellar degeneration on social cognition and its relation to cortical networks in bvFTD remains unknown.MethodA total of 109 individuals with bvFTD and 100 healthy controls were evaluated across three social domains: Theory of Mind (ToM) (The Awareness of Social Inference test—Social Inference–Enriched, Cognitive Emotional Perspective Taking Test), emotion reading (Dynamic Affect Recognition Test, Comprehensive Affect Testing System), and real‐life empathy (Revised Self‐Monitoring Scale, Interpersonal Reactivity Index). Cerebellar subregion volumes associated with social‐linguistic and executive‐control functions, as defined by a precision cerebellar mapping atlas, were extracted from participants’ earliest structural MRIs. Region‐of‐interest‐based partial least squares correlation and voxel‐wise structural covariance network analyses were conducted to examine the contributions of cerebellar subregion volumes to social cognition and their relationship with cortical integrity.ResultIndividuals with early‐stage bvFTD (Global Clinical Dementia Rating=1.1±0.6) performed worse on all assessments than healthy controls (p < 0.05). Significant volume loss was observed in cerebellar subregions (p < 0.05), including bilateral Crus I, Crus II, and lobules VIIb, which contributed to all social domains, particularly ToM and emotion reading. The most influential cerebellar subregions, the left Crus I and II, exhibited increased morphological covariance with cortical regions implicated in social cognition, including the right salience network, compared to controls (pFWE < 0.005). Incorporating cerebellar measures alongside cortical network volumes (salience, semantic appraisal, and default mode networks) significantly improved the predictive power of brain‐behavior models.ConclusionThese results demonstrate that in early‐stage bvFTD, cerebellar involvement and its interaction with cerebral network regions may play a more important role in social cognition than previously appreciated. Specifically, posterior cerebellar subregions significantly contribute to social cognitive dysfunction in bvFTD. The observed morphological covariance between cerebellar subregions and cortical social network regions underscores the cerebellum's integrative role within larger brain networks.

BackgroundSocial cognitive dysfunction manifests early in behavioral variant frontotemporal dementia (bvFTD), causing significant distress and burden for caregivers. Research on impaired social cognition in bvFTD has traditionally focused on cortical networks. Emerging evidence highlights cerebellar changes associated with cognitive and neuropsychiatric symptoms in bvFTD. Notable, these changes occur at early disease stages and are accompanied by social cognitive deficits. However, the impact of cerebellar degeneration on social cognition and its relation to cortical networks in bvFTD remains unknown.MethodA total of 109 individuals with bvFTD and 100 healthy controls were evaluated across three social domains: Theory of Mind (ToM) (The Awareness of Social Inference test—Social Inference–Enriched, Cognitive Emotional Perspective Taking Test), emotion reading (Dynamic Affect Recognition Test, Comprehensive Affect Testing System), and real‐life empathy (Revised Self‐Monitoring Scale, Interpersonal Reactivity Index). Cerebellar subregion volumes associated with social‐linguistic and executive‐control functions, as defined by a precision cerebellar mapping atlas, were extracted from participants’ earliest structural MRIs. Region‐of‐interest‐based partial least squares correlation and voxel‐wise structural covariance network analyses were conducted to examine the contributions of cerebellar subregion volumes to social cognition and their relationship with cortical integrity.ResultIndividuals with early‐stage bvFTD (Global Clinical Dementia Rating=1.1±0.6) performed worse on all assessments than healthy controls (p<0.05). Significant volume loss was observed in cerebellar subregions (p<0.05), including bilateral Crus I, Crus II, and lobules VIIb, which contributed to all social domains, particularly ToM and emotion reading. The most influential cerebellar subregions, the left Crus I and II, exhibited increased morphological covariance with cortical regions implicated in social cognition, including the right salience network, compared to controls (pFWE<0.005). Incorporating cerebellar measures alongside cortical network volumes (salience, semantic appraisal, and default mode networks) significantly improved the predictive power of brain‐behavior models.ConclusionThese results demonstrate that in early‐stage bvFTD, cerebellar involvement and its interaction with cerebral network regions may play a more important role in social cognition than previously appreciated. Specifically, posterior cerebellar subregions significantly contribute to social cognitive dysfunction in bvFTD. The observed morphological covariance between cerebellar subregions and cortical social network regions underscores the cerebellum's integrative role within larger brain networks.

BackgroundWe present a 66‐year‐old female with persistent subacute vertigo lasting 3 weeks, along with a 15 kg weight loss. Her medical history included rheumatoid arthritis, type 2 diabetes, gastroesophageal reflux disease, hypertension, anxiety, and depression. Initially, she was discharged from the emergency department and referred to a neurology outpatient clinic. Six months later, during a follow‐up examination, she exhibited opsoclonus, tongue fasciculations, dysmetria with bilateral intentional tremor, tactile hypoesthesia in the limbs, and significant ataxia.MethodHospitalized for further evaluation, she underwent extensive testing. Magnetic Resonance Imaging (MRI) revealed cerebellar atrophy. Cerebrospinal fluid (CSF) analysis showed oligoclonal bands and an IgG index of 6.2, while other results were normal. Pulse therapy with methylprednisolone failed to improve her symptoms. A chest CT scan revealed a left axillary lymph node (1.4 cm x 1.4 cm), and breast MRI was classified as BI‐RADS 5. A wholebody PET‐CT scan showed hypermetabolic activity in the lymph node, suggesting malignancy.ResultThe patient underwent a left lymph node biopsy, and immunohistochemical analysis revealed: positive CK 7 (SP 52), negative CK 20 (Ks 20.8), positive GATA‐3 (L50‐823), weakly positive estrogen receptor (ER) in 2% of cells, negative progesterone receptor (PR), indeterminate C‐erbB‐2, and a Ki‐67 proliferative index of 50%. These findings confirmed metastasis from primary breast carcinoma.ConclusionThe diagnosis of paraneoplastic syndrome with cerebellar degeneration secondary to breast cancer was established. Paraneoplastic neurological syndromes, triggered by autoimmune responses to tumors or metastases, may present months or even years before or after cancer diagnosis. Early recognition and treatment are essential not only to manage neurological symptoms but also to identify and treat the underlying malignancy. This case underscores the importance of comprehensive clinical evaluation for differential diagnosis of neurological syndromes.

BackgroundAlzheimer's disease (AD) and diabetes mellitus (DM) are associated with neurodegeneration, yet their combined effects on the cerebellum remain unclear. While prior studies highlight cortical and hippocampal atrophy in AD, the cerebellum's role has been largely overlooked. This study examines DM's impact on cerebellar volume across AD stages, including normal cognition, preclinical AD, and amyloid‐positive mild cognitive impairment (MCI).MethodA total of 134 patients with AD pathology and 66 normal controls were classified into normal cognition (66), preclinical AD (22), amyloid‐positive MCI (37), and AD dementia (75), stratified by DM status. Cerebellar volumes of the anterior, posterior, and flocculonodular lobes were analyzed. Cognitive grouping was based on the Consortium to Establish a Registry for Alzheimer's Disease‐Korean version (CERAD‐K) assessments, and amyloid positivity was determined via [^18F] flutemetamol PET imaging. MRI data were processed using voxel‐based morphometry (VBM) with the CAT12 toolbox, and cerebellar segmentation was performed using the Spatially Unbiased Infratentorial Template (SUIT) atlas. ANCOVA, adjusted for age, sex, and total cranial volume, assessed cerebellar volume differences across groups.ResultsDM was associated with reduced anterior lobe volume in normal cognition (p = 0.042) and exacerbated posterior lobe atrophy in amyloid‐positive MCI (p = 0.045, Bonferroni‐corrected). No significant changes were observed in preclinical AD.ConclusionDM influences cerebellar volume differently across the AD spectrum. Anterior lobe atrophy in normal cognition suggests early cerebellar vulnerability to DM, while posterior lobe atrophy in amyloid‐positive MCI indicates accelerated degeneration in advanced amyloid pathology. The absence of significant changes in preclinical AD may reflect compensatory mechanisms. These findings highlight the complex interaction between DM and AD, with DM potentially exacerbating cerebellar degeneration in later disease stages.

Amyotrophic lateral sclerosis (ALS) has a very specific neuroimaging signature, but the molecular underpinnings of the strikingly selective anatomic involvement have not elucidated to date. Accordingly, a large neuroimaging study was conducted with 258 participants to evaluate associations between patterns of neurodegeneration and focal metabolic metrics. Structural and diffusivity alterations were systematically evaluated in a genetically stratified cohort. Voxelwise associations between neurodegeneration and physiological mitochondrial indices were systematically evaluated over the entire brain and also examined in specific regions. Significant topological associations were identified between physiological mitochondria tissue density, nicotinamide adenine dinucleotide (NADH)-ubiquinone oxidoreductase, succinate dehydrogenase, cytochrome c oxidase (COX), mitochondrial respiratory capacity (MRC), tissue respiratory capacity (TRC), and propensity to focal atrophy in ALS. Anatomic correlations between mitochondrial metrics and morphometric change were particularly strong in GGGGCC hexanucleotide repeat carriers in C9orf72. Diffusivity analyses also confirmed associations between brain metabolism and microstructural degeneration. Higher focal mitochondria tissue density was associated with higher likelihood of frontal, temporal, cerebellar, opercular, thalamic, cingulum, putamen, corpus callosum, and corona radiata degeneration. Uncinate fasciculus degeneration was associated with higher Complex I, II, COX, and TRC activity. Topological associations were readily replicated in an external validation cohort. Our data indicate that brain regions with high metabolic activity are particularly vulnerable to neurodegeneration in ALS. Anatomic associations between physiological cerebral metabolism and patterns of neurodegeneration implicate mitochondrial dysfunction in the pathophysiology of ALS. Although mitochondrial dysfunction may not be the primary etiological factor, it may represent a shared bottleneck of multiple converging molecular and genetic pathways, offering a potential opportunity formeaningful pharmacological intervention. ANN NEUROL 2025.

Anti-Tr/DNER antibody-associated rapidly progressive cerebellar degeneration in anaplastic large cell lymphoma: A case report with literature review.

Abstract BACKGROUND Paraneoplastic cerebellar degeneration (PCD) is a rare but debilitating autoimmune neurological syndrome often associated with gynecological malignancies, particularly ovarian cancer. PCD may precede the diagnosis of the underlying tumor, and its early recognition is crucial to improving patient outcomes. METHODS We present a case of a 61-year-old woman from Nepal who developed progressive slurred speech and unsteady gait. Initial neurological work-up, cerebrospinal fluid analysis, and serum biomarkers were inconclusive for metastasis or infection. Further investigations, including imaging, histopathology, and immunohistochemistry, were conducted. RESULTS The patient was found to have elevated CA-125 and a strongly positive anti-Yo antibody. Imaging revealed recurrent pelvic masses with metastases. Biopsy confirmed metastatic ovarian adenocarcinoma. Brain MRI later showed cerebellar atrophy and T2/FLAIR hyperintensities. The patient was diagnosed with paraneoplastic cerebellar degeneration secondary to metastatic ovarian carcinoma. CONCLUSION This case underscores the significance of considering paraneoplastic syndromes in patients with unexplained cerebellar symptoms. Timely evaluation and recognition of PCD can facilitate early cancer detection, allowing for earlier intervention and potentially limiting irreversible neurological damage.

Abstract Paraneoplastic syndromes (PNS) are effects of cancer associated with pathogenic immune-mediated antibodies expressed by tumor cells. We present a case of a 74-year-old male with Merkel cell carcinoma on lenvatinib plus pembrolizumab who presented with gait instability and frequent falls. MRI brain and total spine unremarkable. CSF revealed elevated nucleated cells (13), protein (61 mg/dL), and myelin basic protein (6). Serum neurofilament light chains (NfL) were markedly elevated at 141 pg/mL. After treatment with five days of high dose IVMP followed by two days of IVIG for presumed ICI-induced cerebellitis, the patient’s truncal ataxia resolved. One month later, while tapering oral prednisone, symptoms recurred with severe orthostatic hypotension, prompting an additional dose of IVIG. Due to limited improvement, rituximab (375 mg/m2) was administered, leading to the resolution of symptoms. Paraneoplastic evaluation showed significantly elevated anti-Hu antibodies in the CSF (titers &amp;gt;1:1024) and serum (titers 1:30720) resulting in a diagnosis of anti-Hu associated paraneoplastic cerebellar degeneration (PCD) and dysautonomia. A severe sensorimotor axonal polyneuropathy with a proximal to distal gradient of involvement was identified on EMG. Despite aggressive immunosuppression and physical therapy, symptoms returned with progressive dysarthria, dysphagia, and pronounced functional deterioration. Repeat MRI brain/spine stable. NfL (26 pg/mL) and anti-Hu antibodies (titers 1:15360) in the serum had improved. Although reduced, inflammatory markers persisted in the CSF. In the context of clinical instability and ongoing inflammation, three subsequent doses of rituximab were administered, without response. A recent PET scan showed cancer remission. He started cyclophosphamide (750 mg/m2) and aggressive rehabilitation with the Curren Foundation. This case is rare and illustrates a prolonged recovery in a patient with anti-Hu PNS and Merkel cell carcinoma. We shed light on the importance of suspecting PNS to avoid misdiagnosis. Our case opens discussion regarding the perceived risk of PNS in patients being treated with ICI.

Background/Objectives: Fragile X-associated tremor/ataxia syndrome (FXTAS) is characterized by tremor, gait ataxia, and cerebellar white matter degeneration, along with possible cognitive and cerebral changes. Although diagnostic criteria were originally developed in males, emerging evidence suggests that FXTAS may present differently in females. The present study examined sensorimotor and memory features of aging in female premutation carriers with (FXTAS+) and without FXTAS (FXTAS−). Methods: We studied 51 female premutation carriers (FXTAS+ = 16, FXTAS− = 35) and 24 age-matched female controls. Participants ranged in age from 47–80 years. All participants completed genetic testing, clinical evaluations, T2-weighted MRIs, and quantitative assessments of sensorimotor (precision grip force task) and memory (reading span; visual paired associates task) functions. Results: During precision grip testing, FXTAS+ carriers showed higher sustained force regularity than FXTAS− carriers (p = 0.03, d = 1.0) and controls (p = 0.004, d = 1.1) at low gain levels only. FXTAS+ participants were slower than controls on motor reaction time (p = 0.009, d = 0.82). Initial force output was higher in FXTAS+ than FXTAS− carriers (p = 0.03, d = 1.0) and controls (p = 0.03, d = 1.0) but at low gain only. FXTAS+ carriers exhibited poorer working memory than FXTAS− carriers (p = 0.03, d = 0.91) and controls (p = 0.02, d = 1.0). During a long-term memory task, FXTAS+ participants were less accurate than FXTAS− carriers (p = 0.04, d = 0.86) and controls (p = 0.004, d = 1.1) and showed increased reaction times relative to FXTAS− carriers (p = 0.03, d = −0.82) and controls (p = 0.01, d = −1.2). Conclusions: Together, these findings indicate that FXTAS+ females exhibit distinct motor and cognitive impairments, underscoring the value of quantitative behavioral measures for detecting and tracking neurodegenerative progression in female premutation carriers.

BackgroundAlcohol use disorder (AUD) marked by heavy chronic or binge alcohol consumption, causes cerebellar and white matter (WM) atrophy with cognitive-motor impairments. Major pathological features of alcohol-related brain damage (ARBD) include alterations in WM integrity with myelin loss, and cerebellar degeneration with neuronal loss.PurposeThis study characterizes molecular and biochemical oligodendrocyte-related pathology in cerebellar tissue from donors with AUD to better understand the mechanisms of ARBD in humans.MethodsCores of cerebellar vermis, including cortex and underlying WM from adult human postmortem AUD and control brains, were processed for RNA and protein analyses using duplex and multiplex panels.ResultsAUD cerebellar WM had significant alterations in immature and mature oligodendrocyte protein and mRNA expression, and reduced expression of hepatocyte growth factor, Akt and GSK-3β signaling molecules, and Notch pathway activation. Moreover, the only significant AUD-related alteration in cerebellar cytokine/chemokine expression was reduced IL-16 immunoreactivity.ConclusionHuman AUD WM degeneration is associated with oligodendrocyte dysfunction, which mechanistically could be mediated by impairments in insulin/IGF signaling through Akt/GSK-3β or Notch pathway activation. Future studies should focus on the non-invasive detection and monitoring of AUD-related oligodendrocyte pathology through the analysis of cell-type-specific exosomes isolated from peripheral blood.

The maintenance of metabolic homeostasis relies on the ability to flexibly transit between catabolic and anabolic states in response to insulin signaling. Here we show insulin-activated ATM is a critical mediator of this process, facilitating the swift transition between catabolic-and-anabolic fates of glucose by regulating the functional status of PKM2 and HIF1α. In Ataxia-Telangiectasia (A-T), these mechanisms are disrupted, resulting in intrinsic insulin resistance and glucose intolerance. Consequently, cells exhibit a compensatory dependence on glutamine as an alternative metabolite for energy metabolism. Cerebellar degeneration, a hallmark of A-T, is characterized by the pronounced vulnerability of Purkinje cells, attributed to their unexpected sensitivity to insulin. Supplementation with α-ketoglutarate, the α-keto acid backbone of glutamine, has demonstrated potentials in alleviating glutamine dependence and attenuating Purkinje cell degeneration. These findings suggest that peripheral metabolic deficiencies may contribute to sustained neurodegenerative changes in A-T, underscoring the importance of screening, monitoring and addressing these metabolic disruptions in patients.

The practice of burning waste tyres by the locals to obtain steel and rod is usually accompanied with the release of toxic fumes directly into the atmosphere or transport of leachate of particulate matters by the surface run-off into the aquatic environments where they impact serious ecotoxicological damage. This study was conducted to investigate the histomorphological changes in the visceral organs of Clarias gariepinus juveniles exposed to sub-lethal concentrations (SLCs) of water soluble fractions (WSFs) of waste burnt tyres (WBTRs). The SLCs of WBTRs were obtained by dividing LC50 of 11.22g/L by 1/3th, 1/6 th, 1/9 th , 1/12 th , 1/24 th and 1/48 th respectively. C. gariepinus juveniles of mixed sexes (Average weight: Male (M) - 46.9±0.3.44g; Female (F) - 26.69 ± 3.46g; Average length: M - 14.08±0.54cm; F -16.29±0.51cm) were exposed to SLCs (0.00, 0.23, 0.47, 0.94, 1.87 and 3.74g/L) of WBTRs for 58 days in duplicate. Sequel to the completion of the experiment, catfish were sacrificed using cervical dislocation method. The gills, liver, kidneys, testes, ovaries, brain and intestine were excised and routinely processed for histological studies. The sub lethal grades of WBTRs distinctly induced dose-dependant histo-architectural damages in the different organs including moderate to severe gill epithelial cell hypertrophy and lamellar venous congestion, hepatocellular degeneration and sinusoidal congestion, moderate cellular infiltration into the renal interstitium, reduced seminiferous tubular luminal contents, cerebellar Purkinje cell degeneration and gliosis. Waste burnt tyres demonstrated to be very toxic to fish and therefore, preventive measures should be taken to avoid the burning of waste tyres near riparian vegetation and aquatic ecosystems.

Visuospatial impairment and resting-state network correlations in Alzheimer's disease: A systematic review.

Paraneoplastic syndromes encompass an enigmatic spectrum of clinical manifestations precipitated by various malignancies but not attributable to direct tumor invasion, metastatic dissemination, or hormone secretion from the affected organ. In ovarian cancer, a notably heterogeneous malignancy with a predilection for presentation at the advanced stage, paraneoplastic manifestations may arise from multiple organ systems, thereby complicating diagnosis, altering clinical trajectories, and exerting profound impact on both short- and long-term patient outcomes. These phenomena, observed across both epithelial and nonepithelial ovarian tumors, are often mediated through immune cross-reactivity, ectopic hormone secretion, or cytokine dysregulation. Notable manifestations include neurological syndromes, such as cerebellar degeneration, anti-N-methyl-D-aspartate receptor encephalitis, and metabolic disturbances like hypercalcemia, Cushing's syndrome, and thromboembolic states. Despite significant advancements, the diverse clinical presentations of paraneoplastic syndromes continue to pose substantial diagnostic ambiguities, with challenges in surgical planning and operative intricacies. This narrative review aims to elucidate an expansive analysis of the extant data on epidemiological patterns of ovarian cancer-associated paraneoplastic syndromes, their underlying molecular and immunological drivers, and management strategies. The review utilized extensive search across PubMed, EMBASE, Medline, Scopus, and Cochrane Library databases from January 2000 to March 2024. Inclusion criteria included peer-reviewed studies reporting ovarian cancer patients with clinically confirmed paraneoplastic syndromes, definite investigations, and clinical outcomes. Furthermore, it emphasizes the critical importance of multidisciplinary approaches to deliver holistic perioperative care, while addressing the systemic perturbations induced by paraneoplastic processes.