Medicine and Pharmacology

Abstract: Flavonoids represent a varied collection of polyphenolic compounds derived from plants, present in numerous food sources, including fruits, vegetables, tea, coffee, honey, and various medicinal plants. Historically, these compounds have garnered attention regarding their potential effects on brain health, a focus that has grown particularly urgent due to the escalating global prevalence of neurodegenerative disorders. Diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and other forms of cognitive decline associated with ageing now impact millions, highlighting the pressing demand for therapeutic approaches that are both safe and biologically relevant. A substantial body of empirical research indicates that flavonoids may interact with multiple pathways that influence neuronal sensitivity. Various subclasses of flavonoids appear to modulate oxidative homeostasis, inflammatory signaling, mitochondrial function, and synaptic communication. In a range of in vitro and in vivo investigations, these compounds have demonstrated the capacity to neutralize reactive oxygen species, regulate apoptotic and inflammatory pathways, and facilitate processes integral to neurogenesis and synaptic plasticity. Certain metabolites possess the ability to traverse the blood–brain barrier, suggesting a more profound interaction with neural tissue than initially believed. This chapter synthesizes preclinical and clinical data on prominent flavonoid subclasses, including flavanones, flavanols, flavones, flavonols, anthocyanins, and isoflavones, and explores how their structural characteristics may correlate with neuroprotective effects. The discussion extends to the principal barriers that hinder the transition of these compounds into clinical applications, including limited bioavailability, metabolic differences among individuals, dose-dependent effects, and the challenge of translating experimental outcomes to human contexts. Potential strategies aimed at enhancing their therapeutic profiles are also considered.

Abstract: This review examines the evolving role of muscle biopsy in the diagnosis of neuromuscular disorders in the era of modern genomic medicine. Historically the cornerstone of myopathy diagnosis, muscle biopsy enabled structural, histochemical, and ultrastructural characterization of muscle diseases. However, the introduction of next-generation sequencing and other genomic technologies has shifted the diagnostic paradigm, with genetic testing now serving as the preferred first-line approach for many hereditary myopathies due to its non-invasive nature and high diagnostic yield. However, muscle biopsy remains indispensable in the evaluation of inflammatory, toxic, metabolic, mitochondrial, and certain rare acquired myopathies. Biopsy is also valuable when genetic testing is inconclusive, particularly for interpreting variants of uncertain significance, through histopathological, immunohistochemical, and biochemical analyses. In certain disorders diagnosis may rely primarily on biopsy findings. Emerging technologies, including RNA sequencing, transcriptomics, proteomics, spatial transcriptomics, and artificial intelligence–assisted pathology, are expanding the diagnostic value of muscle tissue beyond traditional morphological assessment. Rather than being replaced by genomic medicine, muscle biopsy is evolving into a complementary component of an integrated diagnostic strategy that combines clinical, pathological, and molecular data to improve diagnostic accuracy and guide precision medicine in neuromuscular disorders.

Abstract: It is hypothesized that in most cases of sporadic late-onset Alzheimer’s disease (LOAD), the abnormally elevated cholesterol level in brain neurons represents a critical caus­ative factor that drives the pathogenic processes of LOAD. Specifically, it is hypothesized that the abnormally elevated neuronal cholesterol will disrupt mitochondrial structure and metabolic activity, resulting in ATP deficiency as well as reduced formation of neuroactive metabolic intermediates (such as mevalonate and geranylgeraniol) along the cholesterol synthesis pathway in brain neurons. In addition, the abnormally elevated neuronal cholesterol will cause direct neuronal damage as well as other pathogenic changes in the brain, including increased formation and deposition of amyloid β (Aβ) plaques. It is speculated that Aβ accumulation and plaque formation in most LOAD cases only represent characteristic secondary pathological changes and are usually not the main force driving the pathogenesis of LOAD. As discussed in detail in this paper, abnormally elevated neuronal cholesterol in conjunction with ATP deficiency and lack of neuroactive metabolic intermediates will not only cause learning and memory impairment, but will also induce tauopathy and reduce the formation of cholinergic vesicles. It is expected that these pathogenic changes are more readily seen initially in ischemia-sensitive neurons in hippocampus and posterior parietal cortex, which are then followed by neurodegenerative and atrophic changes in other brain regions along with progressive cognitive decline. As explained in this paper, ApoE4 is a major risk factor in LOAD because it has a drastically reduced ability than ApoE2 and ApoE3 to efflux excess cholesterol out of neurons. Overall, there is a large body of direct, indirect and circumstantial clinical and experimental evidence which jointly offers strong support for the cholesterol-centered hypothesis on the etiology and pathogenesis of LOAD. Considerable efforts are made to apply the proposed hypothesis to offer a better mechanistic explanation for many of the poorly understood experimental and/or clinical observations related to AD (mostly LOAD).

Abstract: Ergothioneine (ET) is a chemically-stable, tasteless, odourless, highly water-soluble diet-derived compound that is avidly absorbed and retained by the human body using a selective transporter, organic cation transporter novel 1, OCTN1 (often called the ET transporter, ETT). A substantial and growing body of evidence supports a role for ET in maintaining human health and protecting against age-related diseases, especially neurodegenerative diseases, and multiple studies indicate that low blood/plasma/serum ET levels increase the risk of developing age-related diseases. Despite the growing interest in ET, much fundamental work remains to be done to investigate its metabolism, actions (if any) on the genome, lipidome, metabolome and proteome, intracellular and intercellular transport (especially in the brain), precise mechanisms of cytoprotection, interactions with the microbiome, mycobiome and human pathogens, and identifying the factors that control body ET levels. This narrative review explores these issues and suggests what research needs to be done to improve our understanding of ET biology.

Abstract:

Background: Parkinson's disease (PD) and gout are common chronic disorders with potentially shared biological mechanisms involving urate metabolism, inflammation, and oxidative stress. However, epidemiological findings remain inconsistent. This systematic review and meta-analysis evaluated the bidirectional association between gout and PD. Methods: A systematic search of PubMed/Medline, Embase, and the Cochrane Library was conducted from database inception to January 2026. Observational studies evaluating the association between gout and PD were included. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using random-effects models. Statistical significance was defined as p<0.05. The review was prospectively registered in PROSPERO (CRD420261439697). Results: Six cohort studies were included. In pooled analyses, gout was not associated with subsequent PD risk (HR=1.02, 95% CI 0.93–1.12; p=0.70). Sex-stratified analyses also demonstrated no significant associations among women (HR=1.10, 95% CI 0.93–1.30; p=0.27) or men (HR=0.99, 95% CI 0.92–1.07; p=0.79). Evidence regarding the reverse association was limited to a single nationwide cohort study, which reported a lower subsequent risk of gout among individuals with PD (HR=0.51, 95% CI 0.43–0.60; p<0.00001). Similar findings were observed among women (HR=0.56, 95% CI 0.43–0.72) and men (HR=0.47, 95% CI 0.39–0.57). Conclusion: Gout was not associated with subsequent PD risk. Evidence from a single nationwide cohort suggests that PD may be associated with a reduced risk of subsequent gout. Further large-scale prospective studies are needed to clarify the relationship between PD, gout, and urate metabolism.

Abstract: Sleep architecture alterations are consistently reported across major psychiatric disorders, but the contribution of demographic factors to between-study heterogeneity remains insufficiently characterized. Age and sex have not been systematically examined as study-level moderators across harmonized case-control polysomnographic evidence spanning psychotic and mood disorders. A transdiagnostic systematic review and meta-regression of case-control polysomnographic studies compared schizophrenia, bipolar disorder and unipolar depression with healthy controls. Eligible studies reported diagnostic criteria, treatment status, age and sex. Standardized mean differences were synthesized using random-effects models with REML estimation. Univariable mixed-effects meta-regressions assessed age and sex as moderators within each diagnostic group. Age and sex moderated delta sleep-related effect sizes in schizophrenia and unipolar depression. Age also moderated sleep continuity and sleep duration effect sizes in unipolar depression and REM sleep-related effect sizes across all disorders. Sex moderated delta sleep duration and REM density in bipolar mania. No significant effects were observed in bipolar depression. These effects were heterogeneous and not consistently observed across disorders or sleep parameters. Overall, demographic composition explains only a modest proportion of heterogeneity. Interpretation is limited by the ecological nature of study-level meta-regression and residual between-study heterogeneity.

Abstract: Impulsivity is a common trait of various mental disorders having a high worldwide prevalence in childhood and adolescence, such as ADHD and conduct disorders. We propose the ImpulsivityBank protocol, a standardized discourse protocol and a battery of linguistic assessments. Our research aims to provide standardized procedures for retrieving speech samples that enable the determination of the speech features related to impulsivity trait in children and adolescents. We also report on the Impulsivity corpus, a new corpus that consists of speech samples collected using our protocol. Our protocol and corpus are resources that facilitate the investigation of speech in relation to impulsivity trait in children and adolescents. Our protocol is different from current studies because we use different elicitation methods (recall task, storyboard, and picture description) in the same participants to recollect diverse speech samples. Thus, we incorporated traditional elicitation methods that are present in similar studies and existing clinical language banks, in order to promote comparisons between our findings and other research.

Abstract: Background: Subjective experience is increasingly recognised as an important component of brain–computer interface (BCI) performance in extended reality (XR) environments. Although embodiment and simulator sickness are known to influence user experience, their relationships with cortical activity during XR–BCI operation remain poorly understood. Building upon our previous investigations of embodiment and simulator sickness in XR–BCIs, the present study examined whether these subjective dimensions are associated with distinct neurophysiological patterns during repeated XR–BCI use in a participant with chronic spinal cord injury (SCI). Methods: Seventeen XR–BCI sessions performed by a participant with chronic complete SCI were analysed. Bayesian correlation analyses examined associations among embodiment, simulator sickness, BCI performance, and EEG activity. Multiple linear regression was used to identify variables independently associated with sensorimotor beta activity, and the robustness of the regression findings was evaluated using bootstrap estimation and leave-one-out sensitivity analyses. Results: Bayesian analyses identified two principal patterns of association. Sense of embodiment was positively associated with frontal theta activity (F3), whereas simulator sickness showed a negative association with sensorimotor beta activity (C3–C4). As expected, classifier acquisition accuracy was strongly associated with subsequent BCI performance. Multiple regression demonstrated that simulator sickness was the only variable independently associated with C3–C4 beta activity after accounting for embodiment and BCI performance. This association remained robust following bootstrap estimation and leave-one-out sensitivity analyses. Conclusions: Although limited to a single participant, these findings suggest that different dimensions of subjective experience during XR–BCI operation are associated with partially distinct neurophysiological correlates. In particular, simulator sickness was the variable most consistently associated with sensorimotor beta activity across all analyses. These findings provide a foundation for future longitudinal investigations of the neural mechanisms linking subjective experience and cortical dynamics during XR–BCI use.

Abstract: Thoracoabdominal aortic aneurysm (TAAA) is a complex vascular disorder involving both thoracic and abdominal segments of the aorta and remains associated with substantial morbidity and mortality. One of the most serious complications after thoracoabdominal aortic aneurysm (TAAA) repair is spinal cord ischemia (SCI), which may progress to spinal cord infarction and result in irreversible neurologic deficits including paraplegia, neurogenic bladder dysfunction, and bowel dysfunction. The incidence of SCI after TAAA repair varies with the extent of aneurysmal involvement, operative duration, and patient comorbidities. The primary pathophysiologic mechanism involves interruption of radiculomedullary arterial flow, compounded by systemic hypotension, and limited collateral circulation. Because SCI profoundly affects functional recovery and long-term quality of life, prevention and early recognition are central to perioperative management. Established neuroprotective strategies emphasize maintenance of spinal cord perfusion through meticulous hemodynamic optimization, cerebrospinal fluid (CSF) drainage, and temperature modulation. Intraoperative neuromonitoring using motor- and somatosensory-evoked potentials facilitate early detection, while newer modalities such as near-infrared spectroscopy and CSF lactate monitoring may offer additional insight. When SCI occurs despite prophylaxis, rapid initiation of rescue measures including CSF drainage, hemodynamic augmentation, and other discussed treatments may improve neurologic outcomes. Long-term care focuses on rehabilitation, symptom management, and psychological support. Therefore, this review aims to consolidate medical evidence to improve the prevention, detection, and treatment of spinal cord infarction associated with thoracoabdominal aortic aneurysm repair.

Abstract: Skull base pneumatization is anatomically variable and clinically relevant for temporal bone and transsphenoidal surgical corridors, but manual volumetric segmentation is time-consuming. This retrospective pilot study evaluated a clinician-guided deep learning workflow for computed tomography segmentation of temporal bone/mastoid and sphenoid sinus pneumatization. Bone-window computed tomography (CT) datasets were curated, converted to NIfTI format, and segmented using 3D Slicer, MONAI Label, and a three-dimensional SegResNet-based model. The mastoid workflow used side-specific temporal bone crops, while the sphenoid workflow used full-head CT volumes. The final mastoid development dataset included 122 side-cases, with an independent 28 side-case expert-validation cohort. The sphenoid arm included 117 expert-submitted development labels and a separate 17-case expert-validation cohort. The mastoid model achieved strong expert agreement, with mean Dice 0.9691 and median Dice 0.9794 on the independent validation set. The sphenoid workflow achieved a best internal validation Dice of 0.8750, while expert comparison of saved automatic masks showed mean Dice 0.9426 and median Dice 0.9408. Exploratory mask analysis enabled volumetric, densitometric, and extension-pattern assessment of pneumatized skull base compartments. This research supports clinician-guided deep learning as a feasible approach for reproducible CT-based skull base pneumatization segmentation and radiomic analysis.

Abstract: Background/Objectives. Human voices convey critical socio-affective information, including emotional states. Although autistic individuals are often reported to show difficulties in processing vocal emotional cues, behavioral findings remain inconsistent. This study aimed to assess neural and behavioral sensitivity to vocal emotion expressions in autistic adults using a sensitive, individual-level EEG approach. Methods. We compared autistic adult men (N = 25) with a non-autistic control group (N = 25), matched for age, sex, and IQ. Neural responses were measured using an auditory frequency-tagging EEG paradigm, in which streams of neutral vocal utterances were presented at 4 Hz, interspersed with emotional utterances (fear, anger, sadness, happiness) every third stimulus, yielding an oddball frequency of 1.333 Hz. Participants also completed a multimodal behavioral emotion recognition task. Results. No significant group differences were observed in either behavioral performance or EEG responses. Both groups showed greater difficulty in auditory emotion recognition compared to visual and audiovisual modalities. Robust oddball EEG responses were found in both groups, indicating automatic neural discrimination of vocal emotions. Higher response amplitudes were observed for fear and anger across groups. Conclusions. These findings indicate intact neural and behavioral processing of vocal emotions in autistic adult men, supporting the notion of developmental delay rather than persistent deficit in socio-affective auditory processing.

Abstract: Background: Identifying biomarkers in prodromal Parkinson's disease (PD) remains critical for early therapeutic interventions. In addition to genetic predisposition, non-motor symptoms, such as REM sleep behavior disorder (RBD) and anosmia, have been associated with an increased risk for developing PD. This systematic review focuses on assessing gait abnormalities through kinematic assessments in individuals at increased PD risk.Methods: A Boolean phrase was applied to search for gait kinematic studies in cohorts with preclinical PD state. Thirty-seven studies were extracted from PubMed: 13 were deemed relevant by abstract screening, 9 met the inclusion criteria while 4 were excluded due to established PD diagnosis in participants.Results: In individuals with RBD, reduced gait velocity and cadence, increased stride and double-support times, impaired trunk kinematics, and greater gait variability under dual-task conditions were observed. Genetic carriers of PD-related mutations (GCPDM) demonstrated increased arm swing asymmetry and variability, increased stride time variability, and reduced lower-limb excursion. Longitudinal assessments of individuals with idiopathic hyposmia (IH) showed progressive motor deterioration which later turned into overt PD using dopaminergic challenge tests and imaging. When machine learning was applied to sensor assessments, it was capable of distinguishing healthy individuals from those with risk factors for PD or overt PD.Conclusion: Sensor-based gait analysis is a promising tool for detecting early subclinical gait abnormalities in individuals at increased risk for developing PD. Kinematic assessments not only can assist in identifying at-risk individuals for PD but potentially support disease modifying clinical trials.

Abstract: Induced pluripotent stem cells (iPSCs) have revolutionized the research landscape for Alzheimer's disease (AD) and related dementias by providing human, patient-specific neuronal models for studying the genetic and phenotypic diversity of these disorders. This review aims to integrate the latest advances in iPSC-based modeling of AD and dementia across multiple levels of biological organization. After describing the principles of pluripotency, iPSC generation, and quality control (genetic integrity, pluripotency assessment, long-term stability) the review will compare 2D monolayer culture with 3D organoid-based systems regarding their ability to model amyloid-beta, tau, and neuroinflammatory aspects of AD and dementia. The development of global stem cell biobanks and large iPSC collections with genetic diversity will be highlighted as an essential tool for dissecting the complex interplay of multiple genetic risk factors, ethnicity-based differences, and genotype-phenotype correlations. The review will discuss the use of genome editing technology, such as CRISPR/Cas9, for studying the effect of specific AD risk and protective variants in neurons and glial cells, and their implications for cell type-specific roles in neurodegeneration and neuroinflammation. We will highlight the challenges and limitations of iPSCs, such as cellular immaturity, loss of aging signatures, limited vascularization, and batch-to-batch differences, while noting the latest advances in partial/direct reprogramming, biomaterials science, and AI-based phenotypic analysis. Finally, the review will cover the expanding use of iPSC-based systems for high-content screening, functional therapeutic target validation, biomarker discovery, and development, and provide an overview of the future prospects for “clinical-trials-in-a-dish” and precision medicine for AD and other dementia disorders.

Abstract: Ehlers–Danlos syndromes (EDS) are heritable connective tissue disorders caused by defects in collagen and related extracellular-matrix proteins. Because the vocal fold (VF) lamina propria is a collagen-dependent structure, the voice might be expected to be affected, yet laryngeal involvement has received comparatively little attention. This scoping review, conducted according to the Joanna Briggs Institute framework and reported following the PRISMA extension for Scoping Reviews (PRISMA-ScR), mapped the available evidence on voice and laryngeal manifestations in adults with EDS. PubMed, Scopus and Web of Science were searched to 11 March 2026, and thirteen studies were included: four questionnaire-based and nine clinical or instrumental. Self-reported voice problems were common across EDS and hypermobility spectrum disorder populations, ranging from mild-to-moderate handicap in large cohorts to frequent, fluctuating difficulties in professional singers, although their prevalence varied with population and assessment method. Direct laryngeal examination revealed a recurring substrate of cricoarytenoid joint subluxation or fixation, arytenoid prolapse and hyolaryngeal instability, together with microvascular and mucosal fragility, characteristically accompanied by preserved VF mobility. Muscle tension dysphonia was the most frequent diagnosis in high-vocal-demand cohorts. Reflux, vocal load and autonomic comorbidities such as postural orthostatic tachycardia syndrome were frequently reported and may modulate the clinical picture. Taken together, the evidence indicates that voice and laryngeal involvement is a genuine, multi-level manifestation of EDS that remains under-recognised. The current literature is limited by small, heterogeneous and largely uncontrolled studies; prospective research using standardised multimodal assessment is needed to clarify its prevalence, mechanisms and management.

Abstract: In brain nanomedicine, large libraries of barcoded nanoparticles (NP) have, mirroring similar trends in viral vector research, have created an alternative to the traditional, low-throughput way of rationally designing NPs for blood-brain barrier (BBB) transport. Testing sizable pools of NPs administered simultaneously can, aside from the straightforward benefit of reducing animal use, transform the screening funnel itself to reflect which steps are best performed in vitro vs in vivo. Advances in barcoding technology have also allowed distinguishing between NP biodistribution and functional delivery of the payload. Despite some intrinsic limitations such as the low dose of individual NPs in a pool or possible NP-NP interactions, barcoded library screening may also dissect NP passage across the BBB and within brain parenchyma, to identify combinations of NP properties that enable each step of this passage and use this data to build predictive models. Iterative screens of large NP libraries, refined at each stage by this modeling, informed by mechanistic insights into BBB transport and, possibly, leveraging targets known to mediate this transport in human BBB, can maximize the efficiency of NP BBB transport and unlock the full potential of brain nanomedicine.

Abstract: Background/ Aim: Stroke continues to be a leading cause of death and disability worldwide. Although stroke care has advanced considerably, there are still unmet needs in the medical management of large hemispheric strokes. Glyburide has been researched in stroke due to its potential to reduce cerebral edema and improve patient outcomes through its neuroprotective abilities. This literature review aims to synthesize current knowledge of glyburide use in stroke care and provide recommendations for future directions. Methodology: We conducted a literature review by searching PubMed and included studies exploring the therapeutic benefits, risks, and synergistic combinations of using glyburide in stroke. We also explored circumstances that led to the discontinuation of potentially landmark trials such as the GAMES-RP. Results: Glyburide use in patients with large hemispheric infarct has overall favorable outcomes, with most trials reporting benefit or neutrality. We found that a large number of animal studies and clinical trials conducted so far support its use with tolerable adverse effects limited to hypoglycemia. Conclusion: Glyburide can potentially improve patient outcomes in patients with large hemispheric infarcts and can be used along with the standard of care. Further large-scale clinical trials are warranted to explore its therapeutic benefits, its use in other conditions causing cerebral edema, and risk-mitigating efforts.

Abstract: Background: Chronic Multi-symptom Illness (CMI) is an idiopathic condition that can cause severe disability in U.S. Veterans. Objectives: 1. The collection of data to assist in the development of a hypothesis that describes the pathophysiology of CMI and related conditions including Gulf War Illness and Chronic Fatigue Syndrome. 2. Development of a better understanding of the consequences of this syndrome on the study subjects impaired level of functioning. Design: This is an observational VA Pilot study of a cohort of 40 US Veterans with Chronic Multi-symptom illness studied between 2019 and 2025. Methods: The study population was drawn from U.S. veterans who receive medical care from the W.G. Hefner VA Health Care System in Salisbury, N.C. U.S. veterans were initially referred to the Rehabilitation Medicine Service (RMS) for various diagnoses associated with chronic or persistent pain. From this pool of RMS patients, 36 males and 4 females who were diagnosed with Chronic Multi-symptom Illness and who met the study inclusion criteria were selected to participate in the study. Data collected from this study group included: demographic, medical history, and physical symptom information, psychological and cognitive evaluation and testing data, physical exam results, and serum lab test data. Lab tests were performed twice on the study subjects. Lab tests included serum active vitamin D precursor, 25(OH)D3, levels, calcium levels, and human IgM and IgG antibody levels to dUTPase enzymes from three latent herpetic viruses, Varicella Zoster virus (VZV), Human Herpes 6 virus (HH6V), and Epstein Barr virus (EBV). Serum active vitamin D precursor levels were examined because active vitamin D has a role in immune system function including the suppression of latent viruses and the modulation (attenuation) of the immune system’s inflammatory response to microbials including latent viruses. The herpesvirus dUTPases from EBV, HH6V, and VZV are proteins/enzymes in viral DNA replication but not structural components of the mature virion. In this pilot study, antibodies against these proteins were used as biomarkers for abortive lytic replication, a process that can stimulate an inflammatory immune process. This abortive lytic inflammatory process is hypothesized to be distinct from the inflammatory response associated with full lytic viral reactivation, which results in the production of complete virions. Results: Demographic Data – 75% of study subject men and 50 % of women served in combat. Comparison of our pilot study population to the general VA population revealed differences: US Marines made up 25% of our study population versus 9.9% in the general VA population, and African American/Black study subjects made up 30% or our study population verses 15% in the VA general population. Our study subjects had high service connected, disability/ compensation ratings: 55% or 22/40 had a rating of greater than or equal to 80%, and 22.5% or 9/40 had a rating of greater than or equal to 100%. Neurological findings in study subjects included hyperalgesia to pin prick over the skin, which was present in 95% of study subjects, tinnitus (ringing in the ears) in 82% of study subjects, decreased balance on heel to toe walking which was normal in only 28.9% of study subjects with their eyes open and in only 2.7% with eyes closed. This test could not be performed in 18.4% with eyes open and in 40.5% with their eyes closed. Two study subjects developed severe quadriparesis and idiopathic neurocognitive disorders later in the study after their initial interview, physical exam, cognitive testing and blood tests were performed. Serum Lab Tests: Vitamin D, 25(OH)D3 Levels: in Trial 1 – Deficient range 11/40 (27.5%), Insufficient range 17/40 (42.5%) in Trial 2 – Deficient range 8/36 (22.2%), Insufficient range 11/36 (30.6%) Note: Only two study subjects were deficient for both seasonally adjusted 25(OH)D3 levels checked in Trials 1&2 Human IgG antibody levels to Herpesvirus dUTPase proteins: Trial 1 serum test results for human IgG serum antibody levels to herpes virus dUTPase proteins were negative for all three viruses tested in 10/40 (25%) of study subjects and positive for all three viruses examined in 7/40 (17.5%) of study subjects. Trial 2 serum test results for human IgG antibody levels to herpes virus dUTPase enzymes were negative for all three viruses tested in only 1/36 (2.8%) study subjects. Human IgG dUTPase antibodies were positive for all three viruses in 17/36 (47%) study subjects. In Trial 1 – Human VZV IgG was Pos. (elevated) for VZV dUTPase in 11/40 (12.5%) of study subjects, In Trial 2 – Human VZV IgG was Pos. (elevated) for VZV dUTPases in 23/36 (64%) of study subjects.

Abstract: Neurodegenerative diseases represent a major and growing global health burden characterized by progressive neuronal dysfunction, axonal degeneration, and irreversible neural tissue loss. Increasing evidence identifies oxidative stress as a central pathogenic mechanism in Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and several optic neuropathies. Interest has increasingly focused on the brain-retina axis, as the retina and optic nerve share structural, metabolic, and molecular features with the central nervous system and may provide accessible insights into neurodegeneration.This scoping review mapped current evidence on oxidative stress in neurodegeneration, emphasizing cranial nerve involvement, optic nerve vulnerability, retinal ganglion cell degeneration, visual dysfunction, oxidative biomarkers, and emerging therapeutic strategies. The review followed established methodological frameworks and PRISMA-ScR recommendations.The literature shows that oxidative stress interacts with mitochondrial dysfunction, neuroinflammation, impaired mitophagy, ferroptosis, and altered bioenergetics, contributing to neuronal injury in cerebral and retinal disorders. Retinal ganglion cells appear particularly vulnerable because of their high metabolic demands and reliance on oxidative phosphorylation. Glaucoma and other optic neuropathies share molecular signatures with central neurodegenerative diseases. Retinal imaging and oxidative biomarkers show promise for diagnosis, monitoring, and stratification. Overall, oxidative stress emerges as a convergent mechanism across the brain-retina continuum, supporting biomarker-driven neuroprotection and precision medicine.

Abstract:

Bryostatin is a marine natural marine product that was originally extracted from the sessile invertebrate Bugula nerintina. There is a marine bacterium, (Candidatus Endobugula sertula) that has a symbiotic relationship with Bugula that produces bryostatin. In the first large scale collection of Bugula, it took 14 tons of the obscure bryozoan to isolate 18 grams of the drug. This study focuses on isolating bryostatin from a material designed to attract and grow bacterium in the marine environment. Fourier transform Ion Cyclotron Resonance Spectrometer (FT-ICR) is used to identify bryostatins, bryostatin, fragments, and adducts that are present in the matrix. Data is divided into two groups; 1. Calculated exact molar masses, using the NIST Isotope Tables, for the bryostatins 0-21, adducts, fragments and dimers of bryrostatins. These values are correlated with the data from the FT-ICR with possible structure identification. 2. The FT-ICR data acquired from the extracts of the samples. This data is matched with the calculated values to identify specific empirical formulas. For bryostatin-1, the five most common isotopic variations and their natural abundance); would be: M; C₄₇H₆₈O₁₇Na, 927.43487 (2) M+1 (+1 × ¹³C) 928.43823 (3) M+2 (+2 ¹³C) 929.44158 (4) M+3 × ¹³C (930.44494) (5) M + 4 (+2 × ¹³C + ¹⁸O, 931.44583.

Abstract: The intersection of COVID-19 and neurological complications has highlighted post-COVID anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, a severe autoimmune disorder mediated by antibodies targeting NMDA receptors. This systematic review and institutional case series aimed to synthesize existing literature and present eight new cases from Tehran, Iran, to clarify the pathophysiology, prevalence, clinical manifestations, diagnostic challenges, and therapeutic strategies of this emerging condition. A total of 23 adult patients were analyzed, including 15 cases from the literature and 8 new institutional cases. The mean age was 35.6 years, with a female predominance (60.9%). SARS-CoV-2 infection was confirmed in 91.3% of patients by RT-PCR. The median latency from COVID-19 diagnosis to encephalitis onset was 10 days, with 91.3% occurring within the first month. Neuropsychiatric manifestations were nearly universal (91.3%), including psychosis/hallucinations (56.5%), behavioral or cognitive disturbances (52.2%), seizures (52.2%), movement disorders (34.8%), and altered consciousness (43.5%). MRI revealed abnormalities in 59.1% (most frequently hippocampal involvement), and EEG abnormalities were present in 76.2%, with diffuse slowing, epileptiform activity, and delta brush patterns. Anti-NMDAR antibodies were detected in CSF or serum in 60.9% of cases, with pleocytosis in 34.8%. First-line immunotherapies included intravenous methylprednisolone (87.0%), intravenous immunoglobulin (56.5%), and plasmapheresis (34.8%), while rituximab was used in 30.4% as second-line therapy. At a median 3-month follow-up, 52.2% achieved full recovery, 39.1% partial recovery, and 8.7% died. This study underscores the temporal association between COVID-19 and anti-NMDAR encephalitis, with a consistent clinical phenotype and treatment response resembling classical cases. Early recognition, timely antibody testing, and initiation of immunotherapy are critical to improving outcomes. Larger, prospective studies are warranted to confirm causality, refine diagnostic algorithms, and optimize management strategies.