The jugular–nodose ganglion (JNG) complex of the vagus nerve is a key autonomic relay. However, how aging and hypertension affect its neuropeptide expression remains unclear. This study examined age-, strain-, and side-dependent expression of CGRP, nNOS, and TTN3 in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats.

Methods:
Male SHR and WKY rats were grouped as young (4–9 weeks), middle-aged (39–42 weeks), or old (60–63 weeks). JNG tissues were processed for immunohistochemistry with antibodies against CGRP, nNOS, and TTN3. Neuronal expression was quantified bilaterally and compared using unpaired and paired t-tests.

Results:
In young rats, CGRP-positive neurons accounted for 11.05% in SHR and 0.98% in WKY (p = 0.0007); in middle-aged rats – 6.79% vs. 0.32% (p < 0.0001); no significant difference in old rats (28.36% vs. 34.45%, p = 0.11). nNOS expression was lower in young SHR (3.35%) than WKY (37.07%, p = 0.01) but similar in middle-aged (31.64% vs. 29.78%) and old rats (40.27% vs. 38.53%). TTN3-positive neurons were more frequent in SHR across all ages: young (70.13% vs. 47.23%, p < 0.0001), middle-aged (42.56% vs. 78.30%, p = 0.0025), and old (70.11% vs. 44.22%, p = 0.0086). Neuron size in SHR increased with age (Me = 23.23→24.97 µm²), whereas WKY showed no significant change. Neuron density was higher in young SHR (762/mm²) vs. WKY (608/mm²) and declined with age. Ganglion area correlated positively with neuron number in young and middle-aged but not old animals.

Discussion:
Hypertension induces dynamic, age-dependent neurochemical and morphological remodeling of the JNG. Elevated CGRP, reduced nNOS, and persistent TTN3 upregulation suggest adaptive–maladaptive interplay in baroreceptor pathways. Although these results were obtained in rats, the JNG shares key molecular features with the human vagus nerve. Direct evidence of age- or hypertension-related morphological changes in human vagal ganglia is still lacking, but many mammalian species exhibit comparable autonomic aging, supporting the translational relevance of these findings.

The occupational hazards and multiple sclerosis (MS) during the COVID-19 pandemic reveal a multifaceted interplay between mental health, work-related challenges, and the unique experiences of individuals with MS. The initial research highlights the significant work-related outcomes of healthcare workers with multiple sclerosis. A secondary meta-analysis study was conducted to provide a comprehensive examination of the current state of research regarding the occupational outcomes for individuals with multiple sclerosis. The study found that only 23% of participants experienced a relapse during the pandemic, yet more than half reported an increase in the frequency or severity of adverse MS symptoms, which were exacerbated by the occupational hazards during the COVID-19 pandemic's stressors. The correlation between increased chronic symptoms and higher perceived stress levels further emphasizes the psychological dimensions of living with MS during such a stressful period. This highlight the significant gaps in the literature, specifically noting the scarcity of longitudinal and interventional studies that could offer deeper insights into how occupational outcomes for MS have evolved and may have been exacerbated for this vulnerable population. The existing literature is limited in scope and lacks clear definitions regarding occupational outcomes, complicating the interpretation of findings. This study emphasizes the economic burden of MS on public health and the necessity for further research into the bio-psychosocial factors influencing work disability and potential protective elements that could enhance occupational outcomes. The findings point to the necessity of organizational interventions, such as the provision to mitigate these adverse effects, and underscore the significance of workplace policies in promoting mental well-being during crises. The evolving landscape of work-related issues in the context of chronic illness necessitates a nuanced understanding of how external factors, such as a global health crisis, can shape the experiences of affected individuals. There is a clear need for targeted interventions and further research.

Spinal cord injury is a neurological and pathological state that causes motor, sensory and autonomic dysfunction. The corticospinal tract (CST) is one of the main motor tracts in the spinal cord, so damaging it causes a loss of fine motor movements and dexterity. The mouse model of unilateral pyramidotomy allows the study of compensatory sprouting in the CST axons. However, to date, surgery confirmation can only be performed postmortem using immunofluorescent staining. Prognosis biomarkers can help optimize animal care and minimize pain and suffering. In this context, magnetic resonance imaging (MRI) is an effective tool that allows for the comprehensive and non-invasive assessment of the progression of different types of CNS lesions. Moreover, in vivo preclinical CNS models can be used as their own control in longitudinal studies.

In this preclinical study, we proposed the use of MRI to assess the outcome of pyramidotomy surgery in C57BL/6 mice (n = 21). We examined the volume and T2-signal in the area occupied by the dorsal column (DC). We found non-significant changes, with none in the volume nor the T2-signal at any post-injury week. Then, knowing that the CST is a small tract in the DC, we measured the area occupied by the CST within the DC. Interestingly, we observed a general reduction in volumes, which was statistically significant at 7 days post-injury. On the other hand, we observed a decrease in the T2-signal following injury that was statistically significant from 14 days post-injury onward.

In conclusion, these results indicate that MRI could be a suitable tool to detect slight changes in the T2-signal in small regions in an earlier way to predict the efficacy of the surgery.

Introduction: Alzheimer’s disease (AD) and mild cognitive impairment (MCI) are widely recognized for their hallmark cognitive deficits, typically characterized by progressive cognitive deterioration. However, neuropsychiatric symptoms (NPS) including depression, apathy, anxiety, irritability, and sleep disturbances are increasingly prevalent in early stages of these conditions and significantly influence disease trajectory and patient outcomes. Importantly, neuropsychiatric symptoms often precede overt memory loss by several years, with subtle mood and behavioral disturbances serving as early pre-diagnostic markers of underlying Alzheimer’s pathology. Their presence complicates diagnosis, accelerates disease progression, and intensifies caregiver burden. However, distinguishing NPS arising from neurodegeneration from primary psychiatric disorders remain a profound diagnostic challenge, delaying timely intervention and obscuring early disease recognition.

Methods: A structured narrative review of peer-reviewed studies published between 2012 and 2025 was conducted using PubMed, MEDLINE, Scopus, PsycINFO, Google Scholar, and CINAHL to examine the diagnostic complexities, clinical impact, and current management of NPS in early-stage AD and MCI. We argue that understanding and managing NPS is essential to improving clinical outcomes and guiding therapeutic innovation.

Findings: NPS affects up to 80% of individuals with early AD or MCI, often preceding cognitive decline. Current management strategies rely heavily on non-pharmacological interventions such as caregiver support, behavioral activation, and structured routines, while pharmacological options remain limited by modest efficacy and safety concerns. Advancing knowledge of neuropsychiatric symptoms (NPS) and their association with cognitive decline is critical for establishing more precise diagnostic criteria and for informing personalized therapeutic approaches.

Conclusions: Not understanding the role and impact of neuropsychiatric symptoms in early-stage AD and MCI may have serious clinical, personal, and societal consequences. It may lead to delayed diagnosis, poor patient care, and increased caregiver stress and hampers both research and innovation. Recognizing NPS as early and integral features of disease progression is essential for transforming the diagnosis, care, and treatment of dementia-related disorders.

Introducion: Multiple Sclerosis (MS) is a chronic, inflammatory disease affecting the central nervous system. Although primarily managed in outpatient settings, MS may lead to costly hospitalizations. While hospital mortality associated with MS is uncommon in high-income countries, its impact within developing healthcare systems remains insufficiently studied. This study aims to describe the clinical and economic implications of MS-related hospitalizations in Brazil.

Methods: A descriptive ecological study was conducted using data from the Brazilian Unified Health System Hospital Information System (SIH/SUS). All hospital admissions registered under ICD-10 code G35 (MS) between July 2015 and July 2025 were included. The variables analyzed comprised the number of hospitalizations, in-hospital deaths, length of stay, associated costs, and regional distribution across the country.

Results: A total of 9,482 hospitalizations for Multiple Sclerosis were recorded, amounting to 92,415 hospital days. There were 245 in-hospital deaths, resulting in a mean case fatality rate of 2.6% (ranging from 1.7% to 3.2%). The average length of stay was 9.7 days. Cumulative hospital expenditures reached R$ 24.8 million (approximately USD 5 million), with an average cost of R$ 2,600 per admission—exceeding R$ 3,000 in certain years. Regionally, the Southeast accounted for 43% of all hospitalizations and the South for 25%, whereas the North and Northeast regions showed proportionally higher mortality rates (>3%).

Conclusion: From 2015 to 2025, MS led to nearly 10,000 hospital admissions in Brazil, with hospital mortality rates two to three times higher than those reported in high-income countries. The economic impact of almost R$ 25 million reinforces the significance of MS within the framework of a universal public healthcare system. Regional disparities emphasize the urgent need for public health policies to improve equitable access to specialized care and to reduce preventable hospitalizations.

Background The ubiquitin–proteasome system modulates immune signalling; under inflammatory stimuli, standard 20S proteasomes switch to immunoproteasomes incorporating PSMB8 (LMP7) and PSMB9 (LMP2). Proteasome dysfunction is implicated in multiple sclerosis (MS) and may influence the response to disease-modifying therapies (DMTs).

Aim To test whether PSMB8 and PSMB9 single-nucleotide polymorphisms (SNPs) associate with two-year clinical outcomes in Latvian MS patients.

Methods We analysed rs2071543, rs9357155 (PSMB8) and rs17587 (PSMB9) genotypes, previously generated by PCR-RFLP, in 230 patients (342 DMT courses) from a national MS registry. Therapy response was defined as the annual change in Expanded Disability Status Scale (EDSS) and the attainment of “no evidence of disease activity” (NEDA) over 24 months. Associations with glatiramer acetate (GA) and other DMTs were evaluated using χ² and logistic regression (α = 0.05).

Results and Discussion GA-treated patients carrying rare-allele genotypes CT+TT of PSMB8 rs2071543, common-allele homozygote CC of PSMB8 rs9357155, or common-allele homozygote GG of PSMB9 rs17587 exhibited significantly greater EDSS worsening during the first treatment year (p ≤ 0.037). In year 2, the risk pattern shifted: carriers of rare alleles (AA+GA) of PSMB9 rs17587 showed poorer EDSS outcomes (p = 0.028) than GG homozygotes, suggesting time-dependent genotype effects. No significant associations were observed for other DMT classes, underscoring a GA-specific interaction. This data suggests that genetic variation in immunoproteasome genes may influence GA treatment response in a time-dependent manner, possibly due to shifting immune mechanisms over the course of therapy.

Conclusion Polymorphisms in PSMB8 and PSMB9 modulate the clinical response to glatiramer acetate in Latvian MS patients and merit validation as pharmacogenetic markers for personalised DMT selection.

Funding UL project 1.1.1.2/VIAA/4/20/718; ERDF 1.1.1.1/16/A/016; UL Foundation (MikroTik) 40021.

Background Vitamin D-binding protein (VDBP), encoded by the GC gene, governs vitamin D transport and bioavailability. Two common GC SNPs, rs7041 and rs4588, influence serum vitamin D and may modify multiple sclerosis (MS) course and response to disease-modifying therapies (DMTs).

Aim To determine whether rs7041 and rs4588 predict two-year treatment outcomes in Latvian MS patients.

Methods We genotyped rs7041/rs4588 (restriction analysis) in 296 MS patients; 230 received 342 DMT courses. Clinical response was defined as a change in Expanded Disability Status Scale (EDSS) and the attainment of “no evidence of disease activity” (NEDA) over 24 months. Associations were analysed with χ²/Fisher tests and multivariate logistic regression.

Results and Discussion

Our analysis revealed associations between GC gene variants and treatment outcomes in Latvian MS patients. The rs7041 GG genotype was linked to reduced mitoxantrone efficacy (OR 2.3, p = 0.02) and a lower chance of achieving NEDA in the first year (OR 1.9, p = 0.04). Conversely, rs4588 CC homozygotes showed a higher likelihood of sustained NEDA by year two (OR 2.1, p = 0.03). Neither SNP significantly influenced EDSS progression, and no relevant associations were found with other DMTs. These results indicate that GC polymorphisms may act as markers of therapeutic response, particularly regarding mitoxantrone and NEDA. Further studies are needed to explore the underlying biological mechanisms.

Conclusions
GC variants rs7041 and rs4588 affect MS treatment outcomes in Latvians. rs7041 GG is associated with a reduced benefit from mitoxantrone, while rs4588 CC correlates with more favorable NEDA results. These findings support the potential for genotype-guided therapy, pending further validation.

Funding UL project 1.1.1.2/VIAA/4/20/718; ERDF 1.1.1.1/16/A/016; UL Foundation (MikroTik) 40021.

Background Vitamin D receptor (VDR) polymorphisms can modulate immune pathways and may influence the efficacy of disease-modifying therapies (DMTs) in multiple sclerosis (MS).
Aim To determine whether four common VDR single-nucleotide polymorphisms (SNPs) affect two-year therapeutic outcomes in Latvian MS patients.
Methods We genotyped rs2228570, rs1544410, rs7975232 and rs731236 by RFLP in 230 patients (342 DMT courses). Clinical response was defined as a change in the Expanded Disability Status Scale (EDSS) and the maintenance of “no evidence of disease activity” (NEDA) within two years after therapy initiation.
Results and Discussion
Homozygous CC (rs2228570) and TT (rs731236) and heterozygous GA (rs1544410) genotypes were linked to greater EDSS worsening under glatiramer acetate (p < 0.05). The GA genotype of rs1544410 also predicted a higher EDSS in year 2 among interferon-treated patients (p < 0.05). No significant genotype effect was observed for rs7975232.
These data indicate genotype-dependent variability in DMT response, suggesting that VDR polymorphisms modulate the clinical efficacy of glatiramer acetate and interferon in MS.
Conclusions Variants rs2228570, rs731236 and rs1544410 of the VDR gene may serve as pharmacogenetic markers to guide personalised DMT selection in Latvian MS patients.
Funding UL project 1.1.1.2/VIAA/4/20/718; ERDF 1.1.1.1/16/A/016; UL Foundation (MikroTik) 40021. (228 words)

Background. SNP rs9275596, situated between HLA-DQB1 and HLA-DQA2, is linked to MS risk in Latvians. Its effect on disease-modifying therapy (DMT) outcomes is unexplored.
Aim. Assess the impact of rs9275596 on two-year clinical response to DMTs.
Methods. Among 296 registry patients, 230 received 342 treatment courses. Annual change in Expanded Disability Status Scale (ΔEDSS) and “no evidence of disease activity” (NEDA) status were analysed by genotype (α = 0.05).
Results and Discussion. In patients on less frequently used therapies (e.g., mitoxantrone, azathioprine), rare-allele homozygotes TT showed an average first-year ΔEDSS of –0.30 ± 0.75, which was significantly better than common homozygotes CC (0.20 ± 0.26; p = 0.038), suggesting a protective TT effect with these drugs.
In contrast, patients carrying the TT genotype who were treated with glatiramer acetate (GA) had worse outcomes, showing an average EDSS increase of 0.41 ± 0.80 during the first year, which was significantly higher than those receiving other treatments (p = 0.024; η = 0.36). This indicates a genotype-specific adverse response to GA. No significant differences between genotypes were observed in the second year of therapy or in NEDA status, suggesting that the influence of rs9275596 is limited to early treatment response and may depend on the specific therapy used.
Conclusions. The HLA variant rs9275596 appears to influence short-term treatment response in Latvian MS patients. TT genotype carriers show better outcomes with less commonly used therapies but respond poorly to glatiramer acetate (GA), while CC carriers tend to benefit more from GA. These findings suggest that rs9275596 may serve as a pharmacogenetic marker to guide therapy selection, warranting further validation.
Funding. UL 1.1.1.2/VIAA/4/20/718; ERDF 1.1.1.1/16/A/016; UL Foundation (MikroTik) 40021.

Metabolic changes and rearrangements of inhibitory/excitatory neurotransmitters identified since the early stages of multiple sclerosis (MS) [1] are associated with axonal loss and synaptic dysfunction at advanced stages [2]. The aim of this study was to identify a combination of biomarkers that would help to monitor MS progression at more advanced stages [3].

CSF levels of some neurotransmitters (glutamate-Glu, aspartate-Asp, glycine-Gly, GABA) in combination with markers of lipid peroxidation (MDA, 8-iso-PGF2α), the total antioxidant capacity (TAS), and specific neuronal damage (NSE) were determined in patients with MS (n=85; of which 76 had RR-MS, 9 had SP-MS), non-neurological controls (CG; n=26) and other neurological diagnoses (ONDs; n=31). The RP-HPLC method was used for the determination of neurotransmitters [4] and MDA [5]; F2-isoprostanes and NSE were determined by ELISA; TAS was determined colorimetrically [6].

Significantly higher concentrations of Gly (1.60 µmol/l vs 0.96 µmol/l p=0.0104) and Asp (0.16 µmol/l vs 0.026 µmol/l p=0.0333) in the whole cohort of MS and RR-MS patients compared to the CG and ONDs were found. Glu levels were higher in the total MS and RR subtype than in the CG (0.089 µmol/l vs 0.038 µmol/l p=0.0689; p=0.0616). Asp levels were significantly increased in EDSS≤3 compared to EDSS>3. Furthermore, Gly negatively correlated with NSE in MS and RR-MS, and positively correlated with TAS in CG. Glu levels positively correlated with 8-iso-PGF2α in MS and RR-MS.

Our results show that CSF levels of some of the studied neurotransmitters have the potential to be used as biomarkers monitoring the course of a specific pathological process in MS - Asp as an indicator of oxidative stress-induced metabolic changes in glutamatergic synapses of demyelinating lesions; Gly has potential as a cytoprotectant and immunosuppressant in the processes of remyelination [7,8].