Can Glatiramer Acetate Prevent Cognitive Impairment by Modulating Oxidative Stress in Patients with Multiple Sclerosis?

Multiple sclerosis (MS) is an autoimmune disease characterized by demyelination and neuroinflammation, often accompanied by cognitive impairment. This study aims (1) to investigate the potential of glatiramer acetate (GA) as a therapy for preventing cognitive decline in patients with MS (pwMS) by modulating oxidative stress (OS) and (2) to seek out the differences in cognition between pwMS in a cohort exhibiting good clinical evolution and control subjects (CS). An exploratory, prospective, multicentre, cross-sectional case-control study was conducted, involving three groups at a 1:1:1 ratio-41 GA-treated pwMS, 42 untreated pwMS, and 42 CS. The participants performed a neuropsychological battery and underwent venepuncture for blood sampling. The inclusion criteria required an Expanded Disability Status Scale score of ≤3.0 and a minimum of 5 years of MS disease. Concerning cognition, the CS had a better performance than the pwMS (p = <0.0001), and between those treated and untreated with GA, no statistically significant differences were found. Regarding oxidation, no statistically significant differences were detected. Upon categorizing the pwMS into cognitively impaired and cognitively preserved groups, the lactate was elevated in the pwMS with cognitive preservation (p = 0.038). The pwMS exhibited a worse cognitive performance than the CS. The pwMS treated with GA did not show an improvement in oxidation. Lactate emerged as a potential biomarker for cognitive preservation.

Be a Champion! An Approach to Medical Emergency Response In Situ Simulations in the Outpatient Setting.

Results from a needs assessment conducted by nursing professional development practitioners across several clinics in the Midwest showed current educational methods to prepare for medical emergencies were insufficient. A champion model was used to complete in situ medical emergency response simulations. This proved to be an effective method for staff preparation when resources were limited and identified opportunities for practice improvement.

Use of hypothermically stored amniotic membrane on diabetic foot ulcers: a multicentre retrospective case series.

OBJECTIVE: The aim of this retrospective case series was to report on the outcomes of diabetic foot ulcers (DFUs) managed with hypothermically stored amniotic membrane (HSAM). METHOD: Deidentified case data of patients who received HSAM were obtained from wound care sites across the US. Data were collected, beginning at the first patient visit to the wound care site (first presentation), at the visit in which the first HSAM application occurred (baseline), and at each subsequent visit over 12 weeks of treatment (follow-up). All patients received standard of care (SoC) between first presentation and baseline. RESULTS: Of the 50 patients in the study, 68% were male. Mean age of the entire cohort was 66.7 years. Of the DFUs, 88% were present for <6 months at first presentation. Mean wound area was 3.5cm2, and mean percentage area reduction was -68.3% from first presentation to baseline. The mean number of HSAM applications was 5.5, and mean number of days between applications was 7.5. A >60% area reduction was attained in 96.0% of DFUs, and 78% attained complete wound closure (CWC) by week 12. The median time to CWC was 55 days. CONCLUSION: The results of this retrospective case series suggest positive outcomes for DFUs managed with HSAM. A reduction in time to CWC may lead to lesser financial burden and improved quality of life for DFU patients. DECLARATION OF INTEREST: The authors have no conflicts of interest.

Predictive Model for Estimating the Risk of Epilepsy After Aneurysmal Subarachnoid Hemorrhage: The RISE Score.

BACKGROUND AND OBJECTIVES: The occurrence of seizures after aneurysmal subarachnoid hemorrhage (aSAH) is associated with a poorer functional and cognitive prognosis and less favorable quality of life. It would be of value to promptly identify patients at risk of epilepsy to optimize follow-up protocols and design preventive strategies. Our aim was to develop a predictive score to help stratify epilepsy risk in patients with aSAH. METHODS: This is a retrospective, longitudinal study of all adults with aSAH admitted to our center (2012-2021). We collected demographic data, clinical and radiologic variables, data on early-onset seizures (EOSs), and data on development of epilepsy. Exclusion criteria were previous structural brain lesion, epilepsy, and ≤7 days' follow-up. Multiple Cox regression was used to evaluate factors independently associated with unprovoked remote seizures (i.e., epilepsy). The best fitting regression model was used to develop a predictive score. Performance was evaluated in an external validation cohort of 308 patients using receiver-operating characteristic curve analysis. RESULTS: From an initial database of 743 patients, 419 met the inclusion criteria and were included in the analysis. The mean age was 60 ± 14 years, 269 patients (64%) were women, and 50 (11.9%) developed epilepsy within a median follow-up of 4.2 years. Premorbid modified Rankin Score (mRS) (hazard ratio [HR] 4.74 [1.8-12.4], p = 0.001), VASOGRADE score (HR 2.45 [1.4-4.2], p = 0.001), surgical treatment (HR 2.77 [1.6-4.9], p = 0.001), and presence of EOSs (HR 1.84 [1.0-3.4], p = 0.05) were independently associated with epilepsy. The proposed scale, designated RISE, scores 1 point for premorbid mRS ≥ 2 (R), VASOGRADE-Yellow (I, Ischemia), surgical intervention (S), and history of EOSs (E) and 2 points for VASOGRADE-Red. RISE stratifies patients into 3 groups: low (0-1), moderate (2-3), and high (4-5) risk (2.9%, 20.8%, and 75.7% developed epilepsy, respectively). On validation in a cohort from a different tertiary care center (N = 308), the new scale yielded a similar risk distribution and good predictive power for epilepsy within 5 years after aSAH (area under the curve [AUC] 0.82; 95% CI 0.74-0.90). DISCUSSION: The RISE scale is a robust predictor of post-SAH epilepsy with immediate clinical applicability. In addition to facilitating personalized diagnosis and treatment, RISE may be of value for exploring future antiepileptogenesis strategies.

Current Status and Challenges in Dementia Care in the Philippines: A Scoping Review.

Background: Dementia prevalence is increasing in low- and middle-income countries such as the Philippines. Objective: This study aimed to give an overview of dementia care in the Philippines and to identify gaps in terms of local epidemiology, research, financial coverage, diagnostics, pharmacotherapy, manpower, and caregiver support. Methods: This scoping review was conducted using the Preferred Reporting Items for Systematic reviews and Meta-analysis guidelines extension for scoping reviews. Six international and two local databases, and government and non-government websites were searched. Data published in the English or Filipino language on dementia epidemiology, research, diagnostics, management, manpower, and training were extracted from the earliest indexed record until June 2022. Results: The prevalence of dementia in the Philippines is high and research output on all aspects of dementia is low. Cost is a major barrier as health care coverage is limited, with reliance mainly on out-of-pocket payments, leading to challenges in the proper diagnosis and treatment of dementia. There is a low specialist-to-population ratio, with shortages beyond manpower and training. Conclusions: Gaps in dementia care include limited published local data, high healthcare costs, inadequate health financing, and limited manpower.

Effects of Vortioxetine on Cognition and Fatigue in Patients with Multiple Sclerosis and Depression: A Case Series Study.

INTRODUCTION: Vortioxetine is a multimodal antidepressant drug that has been reported to have a positive impact on cognition, social function, and fatigue. Nevertheless, it has not been widely studied. Our objective was to explore the effects of vortioxetine on these and other parameters in patients with multiple sclerosis (MS) and depression. PATIENTS AND METHODOLOGY: This observational case series study included patients with MS and depression who received treatment with vortioxetine for at least 6 months. The patient history of depression and depressive symptoms was assessed. A neuropsychiatric evaluation was carried out using different scales, both before and after treatment. RESULTS: Of the 25 patients who enrolled in the study, 17 completed the treatment. Significant improvements were observed in health status (EQ-5D; p = 0.002), mood (Beck's Depression Inventory, BDI-II; p = 0.006), anxiety (State-Trait Anxiety Inventory, STAI-State; p = 0.021, and STAI-Trait; p = 0.011), and in the general health test (Short Form Health Survey, SF-36) for the vitality (p = 0.028) and mental health (p = 0.025) domains of the patients who completed the treatment. However, no statistically significant differences were observed in the cognitive tests related to attention, information processing speed, or fatigue. CONCLUSION: In this population, vortioxetine treatment was effective in reducing the symptoms of depression and improving anxiety, vitality, and mental health. In contrast, it did not produce any improvement in cognition or fatigue but an increase in sample size would be necessary to confirm these results.

Seroprevalence of SARS-CoV-2 in Patients with Multiple Sclerosis under Disease-Modifying Therapies: A Multi-Centre Study.

BACKGROUND: The EMCOVID project conducted a multi-centre cohort study to investigate the impact of COVID-19 on patients with Multiple Sclerosis (pwMS) receiving disease-modifying therapies (DMTs). The study aimed to evaluate the seroprevalence and persistence of SARS-CoV-2 antibodies in MS patients enrolled in the EMCOVID database. The DMTs were used to manage MS by reducing relapses, lesion accumulation, and disability progression. However, concerns arose regarding the susceptibility of pwMS to COVID-19 due to potential interactions between SARS-CoV-2 and the immune system, as well as the immunomodulatory effects of DMTs. METHODS: This prospective observational study utilized data from a Multiple Sclerosis and COVID-19 (EMCOVID-19) study. Demographic characteristics, MS history, laboratory data, SARS-CoV-2 serology, and symptoms of COVID-19 were extracted for pwMS receiving any type of DMT. The relationship between demographics, MS phenotype, DMTs, and COVID-19 was evaluated. The evolution of SARS-CoV-2 antibodies over a 6-month period was also assessed. RESULTS: The study included 709 pwMS, with 376 patients providing samples at the 6-month follow-up visit. The seroprevalence of SARS-CoV-2 antibodies was higher among pwMS than the general population, with Interferon treatment being significantly associated with greater seroprevalence (16.9% vs. 8.4%; p 0.003). However, no other specific DMT showed a significant association with antibody presence. A total of 32 patients (8.5%) tested positive for IgG, IgM, or IgA antibodies against SARS-CoV-2 at baseline, but then tested negative at 6 months. Most of the pwMS in the cohort were asymptomatic for COVID-19 and, even among symptomatic cases, the prognosis was generally favourable. CONCLUSION: pwMS undergoing DMTs exhibited a higher seroprevalence of COVID-19 than the general population. Interferon treatment was associated with a higher seroprevalence, suggesting a more robust humoral response. This study provides valuable insights into the seroprevalence and persistence of SARS-CoV-2 antibodies in pwMS and contributes to our understanding of the impact of COVID-19 amongst this population.

Reliability, validity and distribution of the Spanish female sexual function index in women with relapsing multiple sclerosis.

BACKGROUND: The Female Sexual Function Index (FSFI) is a widely recognized tool for assessing sexual dysfunction (SD). However, its validation for Spanish women suffering from multiple sclerosis (MS) has not yet been conducted. AIM: The study aimed to examine the psychometric properties of the 19-item Spanish version of the FSFI (svFSFI) in women with relapsing MS. METHOD: A total of 137 women with relapsing MS from three Spanish centers participated in the study and completed the svFSFI. The psychometric properties of the questionnaire were evaluated. The prevalence of SD in the study cohort was determined, and its association with clinical and sociodemographic variables was analyzed using bi- and multivariate regression analyses. RESULTS: The svFSFI demonstrated excellent test-retest reliability and substantial-to-excellent internal consistency in the context of relapsing MS. There was significant convergent validity in the intercorrelations of domains. Discriminant validity showed differences in SD between women with high and low neurological disability, as measured by the Expanded Disability Status Scale (EDSS) scores. An exploratory factor analysis indicated a five-factor structure for the svFSFI. The prevalence of SD in the MS cohort was found to be 42.6%, with the 'desire' and 'arousal' domains being the most affected. Factors such as EDSS score, fatigue, depression, and having a stable partner were found to influence the total svFSFI score. CONCLUSION: The study validates the svFSFI as a reliable and valid instrument for evaluating sexual dysfunction in Spanish women with MS.

Prophylactic treatment can modify vascular risk biomarkers in high-frequency episodic and chronic migraine patients: a pilot study.

To evaluate whether preventive treatment can modify endothelial and oxidative biomarkers of vascular disease risk in patients with high-frequency episodic and chronic migraine. In this observational, prospective pilot study, 88 prophylactic treatment-naïve patients with episodic and chronic migraine and 56 healthy sex/age matched controls underwent ultrasonography exams and blood tests at baseline, and again in the migraine patients after 3 months' treatment with metoprolol or topiramate. Biomarkers for endothelial function and oxidative stress were analyzed. At baseline, patients with migraine in the low-frequency episodic group had differences exclusively in nitrates 17.6 versus 27.33 µM; p = 0.046 compared to the controls. However, when comparing the group comprised of patients with high-frequency episodic migraine and chronic migraine versus controls, statistically significant differences appeared in hsCRP 2.68 versus 1.64 mg/dL; p = 0.049, vWF antigen (133% vs. 110%; p = 0.020, vWF activity (111% vs. 90%; p = 0.010) and isoprostane levels (181 vs. 238 µM; p = 0.05). Only in the chronic migraine subgroup did we found statistically significant differences in CIMT (0.60 vs. 0.54 mm; p = 0.042) which were significantly greater than in the controls. After treatment, patients who respond to preventive treatment exhibited significantly higher levels of nitrates (24.2-13.8 µM; p = 0.022) and nitrites (10.4-3.43 µM; p = 0.002) compared than non-responders. Moreover, biomarker levels improved in treatment-responsive patients with migraine; hsCRP levels decreased from 2.54 to 1.69 mg/dL (p < 0.05), vWF activity levels decreased from 124 to 103 IU/dL (p = 0.003) and prothrombin activity decreased from 1.01 to 0.93 (p = 0.01). These differences were also observed in the high-frequency and chronic migraine subgroup and reach statistical significance in the case of hsCRP, which decreased from 2.12 to 0.83 mg/dL (p = 0.048). Patients with migraines have differences in biomarker levels compared to controls, suggesting endothelial and oxidative dysfunction. The greatest differences in biomarker levels compared to controls are observed in migraine patients in the high-frequency and chronic migraine subgroups. Based on our results, preventive treatment is capable of modifying markers of endothelial dysfunction and oxidative stress in migraine patients, even in cases of chronic and high-frequency migraine.

Surgical treatment of retrorectal tumors: a plea for a laparoscopic approach.

INTRODUCTION: Retrorectal tumors (RRTs) are rare and often surgically excised due to the risk of malignant degeneration and compressive or obstructive symptoms. The approach for excision has traditionally been based on tumor location and performed using either a transabdominal or perineal approach depending on the position of the tumor. The advent of minimally invasive surgery, however, has challenged this paradigm. Here, we determined the applicability and potential advantages of a laparoscopic transabdominal approach in a series of 23 patients with RRTs. MATERIAL AND METHODS: We included 23 patients presenting with RRTs treated at the Surgical Gastrointestinal Unit at Hospital de Sant Pau that were registered prospectively since 1998. The preoperative evaluation consisted of colonoscopy, CT scan and/or MRI, mechanical bowel lavage, and antibiotic therapy. Signed consent was obtained from all patients for a laparoscopic transabdominal approach unless the tumor was easily accessible via a perineal approach. In case of recurrence, a transanal endoscopic microsurgery (TEM) approach was considered. Surgical details, immediate morbidity, and short- and long-term outcomes were recorded. RESULTS: Of the 23 RRT cases evaluated, 16 patients underwent a laparoscopic transabdominal approach and 6 underwent a perineal approach. No patients required conversion to open surgery. In the laparoscopic transabdominal group, the mean operating time was 158 min, the average postoperative hospital stay was 5 days, and postoperative morbidity was 18%. Three patients had recurrent RRTs, two of the three underwent surgical reintervention. The third patient was radiologically stable and close follow-up was decided. CONCLUSION: Our results show that laparoscopic transabdominal excision of RRT is a safe and effective technique, offering the potential advantages of less invasive access and reduced morbidity. This approach challenges the traditional paradigm of excision of these infrequent tumors based solely on tumor location and offers a viable alternative for the treatment of these infrequent tumors.

Barreras y facilitadores en la implementación de una investigación observacional sobre SARS-CoV-2 en una red de escuelas centinela de Cataluña / Barriers and facilitators in the implementation of an observational research on SARS-CoV-2 in a Sentinel School Network in Catalonia

El presente artículo describe las barreras y facilitadores identificadas durante laplementación en campo de un proyecto de investigación observacional sobre SARS-CoV-2 realizado en una red de escuelas centinela de Cataluña durante los cursos escolares 2020-21 y 2021-22. Los objetivos del proyecto Escoles Sentinella aquí descritos son monitorizar la dinámica de la infección y sus determinantes a través de recogida de muestras biológicas, así como describir los conocimientos, actitudes y conductas del alumnado, personal docente y no docente sobre la infección por SARS-CoV-2 a través de cuestionarios bioconductuales. La experiencia desarrollada demostró que, a pesar de las dificultades operativas ante un contexto pandémico cambiante y con presión social y mediática, el estudio fue viable y contó con la aceptabilidad de gran parte de la comunidad educativa. Las lecciones aprendidas de esta experiencia en campo podrían ser útiles y aplicables en la implementación de otros estudios de investigación en situaciones epidemiológicas similares. (AU)

This article describes the barriers and facilitators identified during the implementation in the field of an observational research project about SARS-CoV-2 and carried out in different schools in Catalonia during 2020-21 and 2021-22 school years. The objectives of Escoles Sentinella project here described are to monitor the dynamics of the infection and its determinants through collection of biological samples, and to describe the knowledge, attitudes, and behaviours of students, teaching, and non-teaching staff about the infection by SARS-CoV-2 through biobehavioral questionnaires. The experience developed showed that, despite the operational difficulties due to the changing pandemic context and the social and media pressure, the study was viable and had the acceptability of a large part of the educational community. Lessons learned from this field experience could be useful and applicable in the implementation of other research studies in similar epidemiological situations. (AU)

Mitochondrial Aconitase Enzymatic Activity: A Potential Long-Term Survival Biomarker in the Blood of ALS Patients.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a multisystemic, progressive, neurodegenerative disorder. Despite it being generally fatal within a period of 2-4 years, it is highly heterogeneous; as a result, survival periods may vary greatly among individual patients. Biomarkers can serve as tools for diagnosis, prognosis, indicators of therapeutic response, and future therapeutics. Free-radical-dependent mitochondrial damage is believed to play a crucial role in neurodegeneration in ALS. Mitochondrial aconitase, which is also known as aconitase 2 (Aco2), is a key Krebs cycle enzyme and is involved in the regulation of cellular metabolism and iron homeostasis. Aco2 is very sensitive to oxidative inactivation and can aggregate and accumulate in the mitochondrial matrix, causing mitochondrial dysfunction. Loss of Aco2 activity may therefore reflect increased levels of mitochondrial dysfunction due to oxidative damage and could be relevant to ALS pathogenesis. The aim of our study was to confirm changes in mitochondrial aconitase activity in peripheral blood and to determine whether such changes are dependent on, or independent of, the patient's condition and to propose the feasibility of using them as possible valid biomarkers to quantify the progression of the disease and as a predictor of individual prognosis in ALS. METHODS: We measured the Aco2 enzymatic activity in the platelets of blood samples taken from 22 controls and 26 ALS patients at different stages of disease development. We then correlated antioxidant activity with clinical and prognostic variables. RESULTS: Aco2 activity was significantly lower in the 26 ALS patients than in the 22 controls (p < 0.05). Patients with higher levels of Aco2 activity survived longer than those with lower levels (p < 0.05). Aco2 activity was also higher in patients with earlier onset (p < 0.05) and in those with predominantly upper motor neuron signs. CONCLUSIONS: Aco2 activity seems to be an independent factor that could be used in the long-term survival prognosis of ALS. Our findings suggest that blood Aco2 could be a leading candidate for use as a biomarker to improve prognosis. More studies are needed to confirm these results.

A prospective study of cellular immune response to booster COVID-19 vaccination in multiple sclerosis patients treated with a broad spectrum of disease-modifying therapies.

BACKGROUND: Most people with Multiple Sclerosis (pwMS) are subjected to immunomodulatory disease-modifying treatments (DMTs). As a result, immune responses to COVID-19 vaccinations could be compromised. There are few data on cellular immune responses to the use of COVID-19 vaccine boosters in pwMS under a broad spectrum of DMTs. METHODS: In this prospective study, we analysed cellular immune responses to SARS-CoV-2 mRNA booster vaccinations in 159 pwMS with DMT, including: ocrelizumab, rituximab, fingolimod, alemtuzumab, dimethyl fumarate, glatiramer acetate, teriflunomide, natalizumab and cladribine. RESULTS: DMTs, and particularly fingolimod, interact with cellular responses to COVID-19 vaccination. One booster dose does not increase cellular immunity any more than two doses, except in the cases of natalizumab and cladribine. SARS-CoV-2 infection combined with two doses of vaccine resulted in a greater cellular immune response, but this was not observed after supplementary booster jabs. Ocrelizumab-treated pwMS who had previously received fingolimod did not develop cellular immunity, even after receiving a booster. The time after MS diagnosis and disability status negatively correlated with cellular immunity in ocrelizumab-treated pwMS in a booster dose cohort. CONCLUSIONS: After two doses of SARS-CoV-2 vaccination, a high response yield was achieved, except in patients who had received fingolimod. The effects of fingolimod on cellular immunity persisted for more than 2 years after a change to ocrelizumab (which, in contrast, conserved cellular immunity). Our results confirmed the need to find alternative protective measures for fingolimod-treated people and to consider the possible failure to provide protection against SARS-CoV-2 when switching from fingolimod to ocrelizumab.

A Bibliometric Analysis on Viral Central Nervous System Infection Research Productivity in Southeast Asia.

Research productivity on viral infections of the nervous system in Southeast Asia (SEA) is unknown. We aimed to determine the research productivity of SEA in terms of bibliometric indices and PlumX metrics and their correlation with socioeconomic factors. A comprehensive search of major electronic databases was done to identify studies on viral infections of the nervous system with at least one author from SEA. Socioeconomic factors and collaborations outside SEA were determined. Correlational analysis was done on bibliometric indices and socioeconomic factors. A total of 542 articles were analyzed. The majority came from Thailand (n = 164, 30.2%). Most articles used a descriptive study design (n = 175, 32.2%). The most common topic was Japanese encephalitis (n = 170, 31.3%). The % gross domestic product allotted for research, number of neurologists, and number of collaborations outside SEA correlated with the bibliometric indices and PlumX metrics. In conclusion, the number of research from SEA was low but the quality was comparable to the global benchmark. Improving resource allocation and collaboration between SEA nations and other countries may support this endeavor.

Preventive treatment can reverse cognitive impairment in chronic migraine.

OBJECTIVE: To study the impact of chronic migraine (CM) on the cognition and quality of life (QoL) of patients in the interictal period, and to analyse the degree of reversibility of any observed alterations following the use of preventive treatment. BACKGROUND: CM is a highly disabling disease, and migraineurs often have associated comorbidities, such as subjective memory problems, that are involved in the development of cognitive impairment. Our hypotheses are that patients suffering from chronic migraine experience objective cognitive alterations that are not only due to the pain that they suffer or their current emotional state. Furthermore, preventive treatment should be capable of reversing, or at least reducing, the impact of CM on the cognition and QoL of migraineurs. METHODS: The cognition and QoL of 50 control subjects and 46 patients with CM were assessed using a battery of tests, prior to the use of preventive treatment based on botulinum toxin or oral drugs and after 3 months of this treatment. RESULTS: Compared with controls, patients with CM had lower scores on the assessment of cognitive performance (Rey-Osterrieth Complex Figure test [ROCF] (p<0.05), Trail Making Test [TMT] B) (p < 0.05) and QoL (p < 0.05). Three months after the use of preventive treatment, improvement was observed in all cognitive parameters (p < 0.05) and QoL (p < 0.05), except the ROCF copy task (p = 0.79). No statistically significant differences were observed when these outcomes were compared based on treatment. CONCLUSIONS: This study confirms poor cognitive performance that is not explained by migraine pain itself, as it occurs in the interictal period, irrespective of the patient's emotional status. Our findings show that these effects are reversible in some cases with preventive treatment of CM, reaffirming the important impact of this condition on the QoL of these patients, and the need to establish preventive treatment guidelines.

Seroprevalence of SARS-CoV-2 in a Cohort of Patients with Multiple Sclerosis under Disease-Modifying Therapies.

Background: Disease-modifying therapies (DMTs) used to treat multiple sclerosis (MS) alter the immune system and therefore increase the risk of infection. There is growing concern about the impact of COVID-19 on patients with MS (pwMS), especially those treated with DMTs. Methods: This is a single-center prospective observational study based on data from the Esclerosis Múltiple y COVID-19 (EMCOVID-19) study. Demographic characteristics, MS history, laboratory data and SARS-CoV-2 serology, and symptoms of COVID-19 in pwMS treated with any DTM were extracted. The relationship among demographics, MS status, DMT, and COVID-19 was evaluated. Results: A total of 259 pwMS were included. The administration of interferon was significantly associated with the presence of SARS-CoV-2 antibodies (26.4% vs. 10.7%, p = 0.006). Although patients taking interferon were significantly older (49.1 vs. 43.5, p = 0.003), the association of interferon with the presence of SARS-CoV-2 antibodies was still significant in the multivariate analysis (OR 2.99 (1.38; 6.36), p = 0.006). Conclusions: According to our data, pwMS present a higher risk of COVID-19 infection compared with results obtained from the general population. There is no evidence of a worse COVID-19 outcome in pwMS. DMTs did not significantly change the frequency of COVID-19, except for interferon; however, these findings must be interpreted with caution given the small sample of pwMS taking each DMT.

Effects of GSK-J4 on JMJD3 Histone Demethylase in Mouse Prostate Cancer Xenografts.

BACKGROUND/AIM: Histone methylation status is required to control gene expression. H3K27me3 is an epigenetic tri-methylation modification to histone H3 controlled by the demethylase JMJD3. JMJD3 is dysregulated in a wide range of cancers and has been shown to control the expression of a specific growth-modulatory gene signature, making it an interesting candidate to better understand prostate tumor progression in vivo. This study aimed to identify the impact of JMJD3 inhibition by its inhibitor, GSK4, on prostate tumor growth in vivo. MATERIALS AND METHODS: Prostate cancer cell lines were implanted into Balb/c nude male mice. The effects of the selective JMJD3 inhibitor GSK-J4 on tumor growth were analyzed by bioluminescence assays and H3K27me3-regulated changes in gene expression were analyzed by ChIP-qPCR and RT-qPCR. RESULTS: JMJD3 inhibition contributed to an increase in tumor growth in androgen-independent (AR-) xenografts and a decrease in androgen-dependent (AR+). GSK-J4 treatment modulated H3K27me3 enrichment on the gene panel in DU-145-luc xenografts while it had little effect on PC3-luc and no effect on LNCaP-luc. Effects of JMJD3 inhibition affected the panel gene expression. CONCLUSION: JMJD3 has a differential effect in prostate tumor progression according to AR status. Our results suggest that JMJD3 is able to play a role independently of its demethylase function in androgen-independent prostate cancer. The effects of GSK-J4 on AR+ prostate xenografts led to a decrease in tumor growth.

Cytomegalovirus Meningoencephalitis in a Critically Ill Elderly Female: A Case Report.

Cytomegalovirus (CMV) disease is usually a mild and self-limiting disease in immunocompetent patients. Recent evidence shows that CMV infection may also develop in the setting of critical illness, burn and sepsis and is usually associated with increased mortality rate and prolonged ICU stay. This paper describes an 83-year-old female who was initially admitted as a case of community-acquired pneumonia-high risk but remained febrile with paucity of verbal output despite correction of pneumonia and other electrolyte derangements. MRI showed the presence of peculiar-appearing signal abnormalities in the interhemispheric region and the anterior frontal convexities which were suspected to represent secondarily infected fluid collections. On lumbar tap, viral cerebrospinal fluid (CSF) panel showed a positive result for CMV infection. The patient was then given ganciclovir for 14 days followed by valganciclovir for three months. The most notable improvement was noted with the lysis of fever several days after starting anti-viral treatment. Verbal output remained limited, yet, on repeat tap after completion of treatment, CMV viral panel is now negative.

Comparative of meibomian gland morphology in patients with evaporative dry eye disease versus non-dry eye disease.

Many recent studies have showed that morphological changes are one of the key signs of meibomian gland disease (MGD). These changes can be seen even before symptom onset, potentially underestimating the prevalence of MGD; however, until now, there is no conclusive information about the impact of meibomian gland (MG) morphology in tear film physiology and disease. This study aimed to investigate the prevalence of anatomical and morphological MG alterations between patients with evaporative dry eye disease (DED) and healthy controls. Retrospective chart review of seventy-five patients with evaporative DED and healthy individuals who had dry eye assessments included Ocular Surface Disease Index questionnaire, meibum quality, meibum expressibility, lid margin abnormality, ocular staining, non-invasive tear film break-up time, and meibography. We did not find significant differences in MG alterations in the upper lid between healthy and DED subjects. Patients with evaporative DED presented MG alterations in the lower lid more frequently than healthy subjects (54.8 vs. 30.3%; p = 0.03). The presence of shortened glands was the only MG alteration that was more prevalent in the lower lid in dry-eye patients than in healthy subjects (p < 0.05). Subjects with evaporative DED presented more alterations in the lower lid than healthy subjects.