Spanish Multiple Sclerosis Network

The area of institutional delivery is the core of the reduction of maternal and neonatal mortality, and the coverage in remote provinces of Nepal is not the same. This study evaluates the institutional delivery determinants in the Karnali Province based on nationally representative data. The data were using Nepal Demographic and Health Survey (NDHS) 2021 Karnali subsample of women who have had a recent live birth (15 49 years). The survey logistic regression was adjusted by age, birth order, education, caste/ethnicity, religion, residence and wealth to institutional delivery (facility vs. home). Sampling weight was used (two strata; 60 PSUs; df=58). The results will be provided as adjusted odds ratios (AOR) with 95 percent confidence intervals (CI). Older maternal age and schooling was positively correlated with institutional delivery, whereas higher parity was negatively correlated with institutional delivery. Age 30 -49 was significantly increased in odds compared to 20 years (AOR = 7.71; 95% CI: 2.1730.38). In comparison with lack of schooling, basic and high education (AOR = 3.23; 1.39-7.50 and 7.31; 2.60- 20.59) augmented utilization. AOR decreased with second (AOR = 0.33; 0.16–0.66) and third/higher births (AOR = 0.25; 0.11-0.55). The odds in the poorer quintile were greater than the poorest (AOR = 2.42; 1.13- 5.22). Religion, caste/ethnicity and rural residence were not big. The model was significant (F (15, 44) =3.41; p=0.0008). Parity, age, economic position, and education determine the facility delivery in Karnali. Girls' education, transport/financial support and increased facility preparedness are the most critical strategies that should be incorporated to increase safe and respectful childbirth in geographically disadvantaged conditions.

Balidaan is a highly acclaimed film that redefines gender boundaries within a historical context. This paper examines the portrayal of subaltern consciousness, manifested through revolutionary songs, inclusive representations of ordinary people, underground resistance movements, and their collective struggle against autocratic rule. The film critiques the cruelty and domination of the Panchayat regime, highlighting the suffering of ordinary Nepalese citizens and their resistance against systemic oppression. Central to this analysis is exploring the subaltern voice and agency, which emerges through the active participation of marginalized individuals and rebel groups in dismantling autocratic hierarchies. The paper also investigates the redefinition of gender boundaries within these revolutionary dynamics, underscoring how collective resistance challenges oppressive norms. These issues are analyzed through the theoretical frameworks of liminal performance pedagogy and subaltern consciousness, offering insights into the intersection of marginality, resistance, and transformative action.

The combined use of serum and CSF biomarkers for prognostic stratification in multiple sclerosis (MS) remains underexplored. This multicenter observational study investigated associations between serum neurofilament light chain (sNfL), glial fibrillary acidic protein (sGFAP), and CSF lipid-specific IgM oligoclonal bands (LS-OCMB) with different forms of disability worsening, such as relapse-associated worsening (RAW), active progression independent of relapse activity (aPIRA), and non-active PIRA (naPIRA). A total of 535 patients with MS were included, all sampled within one year of disease onset. Biomarkers were quantified using single-molecule array and immunoblotting techniques, and CSF cell subsets were analyzed by flow cytometry. High sNfL z-scores and LS-OCMB positivity were independently associated with increased risk of RAW and aPIRA, collectively termed inflammatory-associated worsening (IAW), while elevated sGFAP levels predicted naPIRA. Patients with both high sNfL and LS-OCMB positivity had the highest risk of IAW. Among LS-OCMB-positive patients, higher regulatory T cell percentages were associated with lower sNfL levels, suggesting a protective role. Conversely, in LS-OCMB-negative patients, sNfL levels correlated with CSF C3 concentrations. These findings support the complementary role of sNfL, sGFAP, and LS-OCMB in identifying distinct mechanisms of disease worsening and may inform early personalized management strategies in MS.

Multiple sclerosis (MS) is associated with complex needs and demands, which require patient-centered care. Expert patient (EP) programs foster knowledge transfer through peer learning, facilitating patients' empowerment to self-manage their disease. Based on a previous focus group study, we designed an EP program for MS coordinated by nursing professionals for implementation in the different MS reference units of Catalonia (Southwestern Europe). This study aimed to deploy a nurse-led Expert Patient Program of Catalonia™ (EPPC) for people with MS and evaluate its impact on disease-related knowledge, empowerment, and health indicators. Pre-test, post-test interventional, multicenter study conducted between January 2021 and December 2023 (NCT NCT04988880). Six MS teams recruited 12 groups of people with relapsing and progressive MS. Participants attended nine virtual sessions led by an EP, trained and supported by a nurse. Questionnaires were delivered after certain sessions and at 6 and 12 months. Fifty-five participants with relapsing disease and 57 with progressive disease received the intervention. Nine of 18 knowledge questions showed significantly higher post-test vs. pre-test correct answers. Hospital Anxiety and Depression Scale remained unchanged for anxiety and transiently increased for depression, whereas the Patient Activation Measure-13 increased at 12 months, by mean (SD) 2.04 [5.88] points (p = 0.0001) in patients with relapsing MS and by 3.28 (5.24) points (p = 0.0004) in those with progressive MS. Lifestyle habits remained mostly unchanged, except for medication self-management and diet, whereas visits to nurses and other professionals in MS units significantly decreased. Physical health composite scores in the MS quality of life-54 questionnaire decreased, while the mental health composite scores remained unchanged. Fatigue Severity Scale scores remained unchanged and Expanded Disability Status Scale scores increased in participants with progressive disease. In conclusion, the nurse-led program was successfully implemented across Catalonia and resulted in increased MS knowledge and patient activation, impacting medication self-management, diet, and visits to certain professionals in MS units, despite decreased quality of life and disability in participants with progressive disease.

BackgroundCD19-directed cancer immunotherapies, based on engineered T cells bearing chimeric antigen receptors (CARs, CAR-T cells) or the systemic administration of bispecific T cell-engaging (TCE) antibodies, have shown impressive clinical responses in relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). However, more than half of patients relapse after CAR-T or TCE therapy, with antigen escape or lineage switching accounting for one-third of disease recurrences. To minimize tumor escape, dual-targeting CAR-T cell therapies simultaneously targeting CD19 and CD22 have been developed and validated both preclinically and clinically.MethodsWe have generated the first dual-targeting strategy for B-cell malignancies based on CD22 CAR-T cells secreting an anti-CD19 TCE antibody (CAR-STAb-T) and conducted a comprehensive preclinical characterization comparing its therapeutic potential in B-ALL with that of previously validated dual-targeting CD19/CD22 tandem CAR cells (TanCAR-T cells) and co-administration of two single-targeting CD19 and CD22 CAR-T cells (pooled CAR-T cells).ResultsWe demonstrate that CAR-STAb-T cells efficiently redirect bystander T cells, resulting in higher cytotoxicity of B-ALL cells than dual-targeting CAR-T cells at limiting effector:target ratios. Furthermore, when antigen loss was replicated in a heterogeneous B-ALL cell model, CAR-STAb T cells induced more potent and effective cytotoxic responses than dual-targeting CAR-T cells in both short- and long-term co-culture assays, reducing the risk of CD19-positive leukemia escape. In vivo, CAR-STAb-T cells also controlled leukemia progression more efficiently than dual-targeting CAR-T cells in patient-derived xenograft mouse models under T cell-limiting conditions.ConclusionsCD22 CAR-T cells secreting CD19 T-cell engagers show an enhanced control of B-ALL progression compared with CD19/CD22 dual CAR-based therapies, supporting their potential for clinical testing.

A esclerose múltipla trata-se de uma doença neurológica desmielinizante autoimune crônica provocada por mecanismos inflamatórios e degenerativos que comprometem a bainha de mielina que reveste os neurônios das substâncias branca e cinzenta do sistema nervoso central.

Natalizumab is a highly effective therapy for multiple sclerosis (MS). The aim of this study was to evaluate serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) in patients with relapsing–remitting MS treated with Natalizumab. sNfL and sGFAP were analyzed at baseline, 6 and 12 months post treatment using the single-molecule array (SiMoA) technique. We recruited matched healthy controls for comparison. The study included 54 patients, with a median age of 33 years (Interquartile range (IQR), 29–41), with 32 women (60%) and 76 healthy controls. A decrease in sNfL was observed at 6 (67%, p = 0.005) and 12 (72%, p < 0.0001) months compared to baseline. After two years, six patients experienced evidence of disease activity (EDA-3). The remaining ones had no evidence of disease activity (NEDA-3). NEDA-3 presented a remarkable reduction in sNfL (p < 0.0001) and sGFAP (p = 0.01) after 6 months of treatment that continued to be observed after 12 months compared to baseline. EDA-3 only reached a significant decrease in sNfL after 12 months; there were no significant changes in sGFAP values. Natalizumab leads to a decrease in sNfL, which is higher and occurs earlier in NEDA-3 patients. Patients also showed a significant reduction in sGFAP levels, which was not observed in the EDA-3 group.

This study aimed to describe the use of pressurized metered-dose inhalers (pMDIs) and dry powder inhalers (DPIs) in Spanish subjects in terms of sociodemographic, clinical, and functional characteristics in subjects with asthma or COPD on maintenance treatment with inhaled therapy. This was a retrospective, descriptive, national, multi-center, and observational study using a database with 1.8 million patients from hospitals and primary care centers as a secondary information source. The sample included 24,102 subjects with asthma on maintenance therapy (26.0% with pMDI, 55% with DPI, and 19.0% with a combination of DPI + pMDI inhalers) and 12,858 subjects with COPD on maintenance therapy (26% with pMDI; 39% with DPI; and 35% with a combination of pMDI + DPI inhalers, mostly extemporary triple therapy). In proportion, subjects ≥ 75 y old used more pMDI than DPI, while younger subjects (40-64 y old) used more DPI. An inhalation chamber was prescribed in 51.0% of subjects with asthma and 47.2% of subjects with COPD treated with pMDI. The use of an inhalation chamber increases with the degree of air-flow limitation by disease and age. In subjects with comorbidities, pMDI inhaler use increased in those ≥ 75 y old for subjects with asthma and subjects with COPD. Switching from pMDI to DPI and vice versa was relatively common: 25% of subjects with asthma and 21.6% of subjects with COPD treated with pMDI had switched from DPI in the previous year. On the contrary, 14.1% and 11.4% of subjects with asthma and subjects with COPD, respectively, treated with DPI had switched from pMDI the last year. The use of pMDI or DPI can vary according to age, both in asthma and COPD. Switching from pMDI to DPI and vice versa is relatively common. Despite the availability of dual- and triple-therapy inhalers on the market, a considerable number of subjects were treated with multiple devices.

Men tend to eat more meat than women, but it is not clear why. We tested three hypotheses in a cross-cultural design (20,802 individuals in 23 countries across four continents): that gender differences are (a) universal, (b) related to gender roles and thus weaker in countries with higher gender equality and human development, or (c) related to opportunities to express gender roles and thus stronger in countries with higher gender equality and human development. Across all countries, men tended to consume more meat than women. However, this difference increased significantly in countries with greater human development and gender equality. The paradoxical gender gap in meat consumption aligns with previous research that suggests greater differences in behavior across genders in contexts that are more developed and gender equal. We discuss implications for theories of culture and gender as well as practical implications for global meat reduction.