Search

ObjectiveTo ascertain the changes of serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) values in relapsing–remitting multiple sclerosis (RRMS) patients treated with ocrelizumab and their association with treatment response.MethodsMulticenter prospective study including 115 RRMS patients initiating ocrelizumab treatment between February 2020 and March 2022 followed during a year. Serum samples were collected at baseline and every 3 months to measure sNfL and sGFAP levels using single-molecule array (SIMOA) technology. Based on age and body mass index, sNfL values were standardized using z-score. NEDA (non-evidence of disease activity)-3 status was defined for patients free of disease activity after a year of follow-up. Inflammation (INFL) was considered when new relapses occurred during follow-up or new MRI lesions were found at 1-year exploration. PIRA (progression independent of relapse activity) was defined as disability progression occurring in the absence of relapses or new MRI activity.ResultsAfter a year on ocrelizumab, 85 patients (73.9%) achieved NEDA-3. Thirty patients did not achieve NEDA: 20 (17.4%) because of INFL and 10 (8.7%) because of PIRA. Of INFL patients, 6 (30.0%) had relapses, and 17 (85.0%) had at least one new MRI lesion at the 12-month examination. At baseline, INFL patients had higher sNfL (p = 0.0003) and sGFAP (p = 0.03) than the NEDA-3 group. PIRA patients mostly exhibited low sNfL and heterogeneous sGFAP levels. After a year, NEDA-3 and INFL patients showed similar decreases in sNfL (p < 0.0001) and sGFAP (p < 0.0001 for NEDA-3 and p = 0.001 for INFL ones). However, the decrease occurred earlier in NEDA-3 patients. Accordingly, sNfL > 1.5 z-score 3 months after ocrelizumab initiation indicated a higher risk of inflammation (OR = 13.6; p < 0.0001). Decrease in sGFAP values occurred later in both groups, with significant reductions observed at 12 months for INFL and 6 and 12 months for NEDA-3. No significant changes in sNfL or sGFAP were observed in PIRA patients.ConclusionOcrelizumab induced normalization of sNfL and sGFAP in the majority of NEDA-3 and inflammatory patients but did not cause changes in the PIRA group. Our data suggest that normalization of sNfL and sGFAP is associated with the lack of inflammatory-associated disease progression but it may not affect non-inflammatory PIRA.

The purpose of this research was to study the impact of human factor management on company productivity, with digitalization as a moderating variable, with emphasis on medium and large companies in the services sector, in Lima, Peru. This research has a quantitative approach and cross-sectional design. The technique used was structural equation modeling with the maximum likelihood estimation method. The study was carried out with a sample of 330 people from the banking sector in the city of Lima, in Peru. For statistical analysis, Confirmatory Factorial Analysis, and hypothesis testings, the SPPS AMOS tool was used. A conceptual model based on Dynamic Capability View theory was developed that allows us to better understand the phenomenon of the impact of human factor management on the productivity of companies, under the moderating effect of digitalization. As the main conclusions of this research, it was found that there is a positive relationship between the human factor management and the company productivity; likewise, it was found that digitalization has a moderating effect in the relationship between human factor management and productivity, with the exception of the human factor performance appraisal. These findings contribute to the existing literature and debate, as well as, allow to determine which dimensions of human factor management can be enhanced under the impact of a digital environment, thus contributing better to business performance.

ObjectiveTo evaluate the safety of COVID-19 vaccines in patients with multiple sclerosis (MS) by assessing their impact on serum neurofilament light chain (sNfL) levels as a marker of neuroaxonal damage.MethodsSingle-center observational longitudinal study including patients with MS who consecutively received their initial vaccination against SARS-CoV-2 at Hospital Universitario Ramón y Cajal, following the first national immunization program in Spain. Serum samples were collected at baseline and after receiving the second dose of the vaccine. sNfL levels were quantified using the single molecule array (SIMOA) technique. Adverse events, including clinical or radiological reactivation of the disease, were recorded.ResultsFifty-two patients were included (median age, 39.7 years [range, 22.5-63.3]; 71.2% female). After SARS-CoV-2 vaccination, no increased inflammatory activity, either determined by the presence of relapses and/or new MRI lesions and/or high sNfL levels, was detected. Accordingly, there was no difference between median sNfL levels before and after vaccination (5.39 vs. 5.76 pg/ml, p=0.6). Despite this, when looking at baseline patient characteristics before vaccination, younger age associated with disease activity after vaccination (OR 0.87, 95% CI: 0.77–0.98, p=0.022). Larger studies are needed to validate these results.ConclusionCOVID-19 vaccines did not cause reactivation of disease at a clinical, radiological or molecular level, thus suggesting that they are safe in MS patients.

IntroductionAlemtuzumab is a highly effective pulsed immune reconstitution therapy for multiple sclerosis (MS).AimTo evaluate serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) in patients with relapsing-remitting MS who have been treated with Alemtuzumab over the course of 2 years.MethodsThis prospective study involved MS patients treated with Alemtuzumab at a referral MS center. Both sNfL and sGFAP were analyzed at baseline and then again at 6, 12, and 24 months post-treatment using the single molecule array (SiMoA) technique. We also recruited matched healthy controls (HCs) for comparison.ResultsThe study included 46 patients (with a median age of 34.2 [Interquartile range (IQR), 28.7–42.3] years, 27 of which were women [58%]) and 76 HCs. No differences in demographic characteristics were observed between patients and HC. The median disease duration was 6.22 (IQR, 1.56–10.13) years. The median annualized relapse rate before treatment was 2 (IQR, 1–3). At baseline, sNfL and sGFAP levels were higher in MS patients (median of 18.8 [IQR, 10.7–52.7] pg/ml and 158.9 [IQR, 126.9–255.5] pg/ml, respectively) when compared to HC (6.11 [IQR, 2.03–8.54] pg/ml and 91.0 [72.6–109] pg/ml, respectively) (p

Multiple studies have shown the importance of blood-based biomarkers indicating axonal damage (serum neurofilament light chains [sNfL]) or astroglia activation (serum glial fibrillary acidic protein [sGFAP]) for monitoring different neurological diseases. However, normal values of these variables remain to be clearly defined, partly due to the influence of different demographic factors. We investigated demographic differences in a cohort of healthy volunteers. A cross-sectional study was conducted including 116 healthy controls with ages between 18 and 69 years (67.5% females; n = 79). sNfL and sGFAP concentrations were measured using single-molecule arrays. Age and body mass index affected sNfL values, and age was found to be the most important factor. The normal values changed with age, and we established normal values for individuals younger than 45 years as

The design of walking-assistance exosuits is becoming increasingly popular among those who aim at developing a light, affordable and wearable system. They are indeed an alternative to traditional exoskeletons, which tend to be bulkier and more expensive. The main advantages of exosuits, as opposed to exoskeletons, are their lower weight and price, as well as their increased wearability and kinematic compatibility with the user. Thus, it is key to optimize their design and, particularly, the number of actuators and the actuation scheme. One of the current, common ways to achieve better designs, is to conduct a Principal Component Analysis (PCA) on some of the involved variables to reduce their dimensionality and thus, simplify the actuation system. The goal of this paper is to analyze the different variables upon which PCA can be conducted and propose the resulting actuation schemes, comparing the results and determining the best design approach for the design of a synergy-based, gait-assistance exosuit. The study focuses on both postural and dynamic synergies to optimize their design. Here, both synergy types are reviewed from a design perspective, yielding different design criteria following a PCA-based study, each with their own set of advantages and disadvantages. Thus, the design of cable-driven exosuits is optimized via analysis of gait parameters related with its actuation, such as joint torque or cable extensions. Kinematics or postural synergies lead to a higher cumulative variance of the first principal component and the transmission system is simpler than the ones obtained through dynamic synergies.

Las aguas residuales de la industria azucarera y sus derivados constituyen una fuente de contaminantes de Cuba, por su alta demanda química de oxígeno (DQO) y los volúmenes de residuales que se emiten al medioambiente, por lo que es de vital importancia tratarlos. Una de las alternativas para disminuir la con- taminación es la inclusión de microorganismos eficientes en dichas aguas. La aplicación de un tratamiento adecuado, en función de las características específicas de los efluentes y velar por los requerimientos de depuración apropiados, permiten que el agua pueda cumplir con los requisitos exigidos por la normativa ambiental y ser aprovechada para otros usos. Los microorganismos eficientes han sido informados en la literatura como una alternativa para solucionar los problemas de contaminación hídrica. Se trata de un con- junto probiótico natural que incluye, únicamente, microorganismos que existen en la naturaleza, que no son manipulados genéticamente. Pueden utilizar los compuestos contaminantes presentes en las aguas como fuente de carbono y energía, para su metabolismo y desarrollo.

Introduction: Spinal cord infarction is a rare disease with a high rate of morbidity. Its diagnosis can be challenging and controversy remains regarding the best treatment. Few case series have been published. Methods: We conducted a retrospective review of cases of spinal cord infarction attended in a tertiary hospital from 1999 to 2020. Aetiology and clinical, imaging, and prognostic features were assessed. Results: Forty-one patients (58.5% men, mean [standard deviation] age 61 [17] years) were included in the study. Thirty-one patients (75.6%) presented vascular risk factors. Motor deficits were recorded in 39 (95.1%), pain in 20 (48.8%), sensory deficits in 33 (80.4%), and autonomic dysfunction in 24 (58.5%). MRI was performed in 37 (90.2%) patients. Diffusion-weighted images were available for 12 patients, with 10 showing diffusion restriction. The thoracic region was the most frequently affected (68.2%). Vascular imaging studies were performed in 33 patients (80.4%). The most frequent aetiologies were aortic dissection (6 cases), atherosclerosis demonstrated by vascular imaging (6 cases), fibrocartilaginous embolism (6 cases), surgery (5 cases), and hypotension (4 cases). Aetiology was undetermined in 12 patients (29.3%), although 9 of these presented vascular risk factors. At the end of the follow-up period (median, 24 months; interquartile range, 3–70), 12 patients (29.2%) were able to walk without assistance. Vascular risk factors and paraparesis were significantly associated with poorer prognosis (P

Resumen: Introducción: El infarto medular es una entidad infrecuente y con elevada morbilidad. El diagnóstico puede resultar difícil y el tratamiento óptimo sigue siendo controvertido. Existen pocas series de casos publicadas. Métodos: Estudio retrospectivo de infarto medular en un hospital terciario desde 1999 a 2020. Se evaluaron la etiología, las características clínicas, radiológicas, terapéuticas y pronósticas. Resultados: Se incluyeron 41 pacientes (58,5% varones, edad media 61 ±17 años). Treinta y un pacientes (75,6%) presentaban factores de riesgo vascular (FRV). Presentaron déficit motor (39, 95,1%), dolor (20, 48,8%), déficit sensitivo (33, 80,4%) y alteración autonómica (24, 58,5%). Se realizó resonancia magnética (RM) en 37 pacientes (90,2%). En los 12 pacientes con secuencias de difusión, esta estaba alterada en 10. La localización más afectada fue la dorsal (68,2%). Se realizó estudio vascular en 33 pacientes (80,4%). Las etiologías más frecuentes fueron disección aórtica en 6, ateroesclerosis demostrada en estudio vascular en 6, embolia fibrocartilaginosa en 6, posquirúrgico en 5 e hipotensión en 4. El mecanismo etiológico quedó sin filiar en 12 pacientes (29,3%), 9 presentaban FRV. Al final del periodo de seguimiento (mediana 24 meses, rango intercuartílico 3-70), 12 pacientes (29,2%) presentaban deambulación autónoma. La presencia de FRV y la paraparesia se asociaron significativamente a peor pronóstico (p

IntroductionThe immunoglobulin kappa free light chain (KFLC) index has been proposed as a potentially suitable alternative to oligoclonal IgG bands (OCGB) for diagnosing multiple sclerosis (MS), offering automation and reduced processing time. However, there is no consensus on the preferred approach or how to combine both techniques.MethodsThis prospective cohort study aimed to determine the best utilization of OCGB and KFLC index in patients with a clinically isolated syndrome (CIS) followed for at least two years. OCGB and KFLC were assessed using isoelectric focusing and immunoblotting and turbidimetry, respectively. Sensitivity, specificity, and accuracy for diagnosing MS were calculated for each method.ResultsThe study included 371 patients, with 260 (70.1 %) being women, and a median age of 34.9 (27.8 – 43.9) years. Using a cut-off value of 6.1, the KFLC index demonstrated a sensitivity and specificity of 86.3% and 93.9%, respectively. The sensitivity of OCGB (95.3%) was higher (p < 0.001 vs. KFLC index) and the specificity (100%) was comparable to that of the KFLC index (p = 0.5). The concordance between the methods was not uniform across all patients, with 97.8% agreement in patients with KFLC index ≥ 6.1 and 56.0 % in patients with KFLC index < 6.1. In patients with a KFLC index < 6.1, OCGB still identified 75.0 % of MS patients due to its higher sensitivity. An algorithm using the KFLC index as a screening tool and OCGB as an alternative for patients with a negative KFLC index result achieved an accuracy of 96.3 %.DiscussionCombining the KFLC index and OCGB can provide an easily reproducible and accurate method for diagnosing MS, with OCGB primarily reserved for patients with a KFLC index < 6.1.

The subsoil of Mexico City (SMC) is highly compressible when loads are applied. This feature is associated with many uncertainties and complex issues during foundation design processes. The compressibility of the SMC has been investigated since the 40s by using oedometer tests in most cases. However, the importance of the results in interpreting compression test data requires a systematic method of determining the end of consolidation (EOC) under a load increment. This paper offers an alternative view to analyze a one-dimensional compression test, decomposing the time-compression curve into two curves, one due to consolidation and another due to volumetric creep, using numerical processing. This approach has several advantages: (1) Data reduction allows us to know the contribution of consolidation and volumetric creep at any time and for each load increment. (2) a systematic method of determining the end-of-consolidation (EOC) under a load increment, and (3) long-term strains (settlements) can be estimated at any time. Finally, an example of the results obtained using the suggested method is presented.

Introduction: The confrontation to the epidemic of COVID-19 had a negative economic impact in the world, what generated an increment of the expenses and costs in the health sector of Santiago de Cuba province. Objective: To describe the economic impact of the COVID-19 in the sanitary sector of Santiago de Cuba during a year. Methods: A descriptive and prospective study was carried out in Santiago de Cuba province in the year 2021, for which the day-patient, budgetary expenses, average salary, total costs of a day-patient and unitary costs of a day-patient variables were analyzed. Results: The investigation revealed an increment in the expenses and its effect in the economy of the sanitary sector in 2021. When analyzing the expenses for departures, a higher significance was determined in those of medications, with 59.0 % of the total, what represented a growth of the unitary costs in comparison with the published standards. Conclusions: The expenses of the sanitary sector in this province contributed to control the propagation of COVID-19, to avoid the over expense for the introduction of vaccines, and allowed the decrease of the infection indexes. Also, the increment of the costs was evidenced in the different activity levels between 3 and 29 times more than the standardized costs of the country.

This single-center study included 68 multiple sclerosis (MS) patients who received the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination from one of several approved vaccine preparations in Spain. Blood samples were collected one to three months after the second dose of the vaccine had been administered. Cellular immune responses to the vaccine were assessed using QuantiFERON analysis, and peripheral blood mononuclear cell subsets were assayed using flow cytometry. Response associated with higher percentages of total lymphocytes, naïve CD4+ T-cells (p = 0.028), CD8+ T-cells (p = 0.013), and, mostly, naïve CD8+ T-cells (p = 0.0003). These results were confirmed by analyzing absolute numbers (p = 0.019; p = 0.002, and p = 0.0003, respectively). Naïve CD8 T-cell numbers higher than 17 cells/μL were closely associated with an optimal cellular response to SARS-CoV-2 vaccination (odds ratio: 24.0, confidence interval: 4.8–460.3; p = 0.0001). This finding clearly shows that independent of the treatment received, higher numbers of naïve CD8+ T-cells yield a strong cellular response to SARS-CoV-2 vaccines in MS patients. If this finding is validated with other viruses/vaccines, it could provide a good tool for identifying MS patients undergoing treatment who will develop strong cellular responses to anti-virus vaccines.

With ever-rising population comes a corresponding rise in people with mobility issues who have difficulty handling tasks in their daily lives. Such persons could benefit significantly from an active movement assistance device. This paper presents the design of a lower-limb exosuit designed to provide the wearer with useful gait assistance. While exoskeletons have existed for a while, soft exoskeletons or exosuits are relatively new. One challenge in the design of a gait-assistance device is the reduction of device weight. In order to facilitate this, the concept of kinematic synergies is implemented to reduce the number of actuators. In this prototype, the exosuit can actuate the hip, ankle, and knee of both legs using just one single motor, and a transmission system consisting of gears and clutches. The implementation of these synergies and their advantages are detailed in this paper, as well as preliminary tests to assess performance. This was performed by testing the exosuit worn by a subject on a treadmill while taking EMG readings and measuring cable tension produced. Significant reductions by up to 35% in certain muscle activations were observed, demonstrating the validity of this prototype for gait assistance.

CD8+ T lymphocytes are one of the main effector cells of the immune system, they protect the organism against intracellular threats such as viruses and bacteria, as well as neoplasms. It is currently well established that CD8+ T cells have distinct immune responses, given by their phenotypes Tc1, Tc2, Tc17, and TcReg. The cellular plasticity of such phenotypes depends on the presence of different combinations of cytokines in the extracellular medium. It is known that metabolic imbalances play an important role in immune response, but the precise role of metabolic disturbances on the differentiation and function of CD8+ T cells, however, has not been explored. In this work, we used a computational model to explore the potential effect of metabolic alterations such as hyperglycemia, high alcohol consumption, dyslipidemia, and diabetes on CD8+ T cell differentiation. Our model predicts that metabolic alterations preclude the effector function of all CD8+ T cell phenotypes except for TcReg cells. It also suggests that such inhibition originates from the increase of reactive oxygen species in response to metabolic stressors. Finally, we simulated the outcome of treating metabolic-inhibited CD8+ T cells with drugs targeting key molecules such as mTORC1, mTORC2, Akt, and others. We found that overstimulation of mTORC2 may restore cell differentiation and functions of all effector phenotypes, even in diabetic patients. These findings highlight the importance of our predictive model to find potential targets to strengthen immunosuppressed patients in chronic diseases, like diabetes.

Background: clinical studies in patients with sickle cell disease have shown that the use of hydroxyurea is associated with a reduction in acute and chronic complications, including those related to the nutritional status of these patients. Objective: to evaluate the nutritional status in patients with sickle cell disease treated with hydroxyurea at the Paquito González Cueto University Pediatric Hospital in Cienfuegos. Methods: a descriptive, analytical and prospective study was carried out of all the patients with sickle cell disease treated with hydroxyurea, treated at the Hematology Service of the Pediatric Hospital of Cienfuegos in the period from January 2012 to December 2018. The study variables were: age, sex, hemoglobin variant, clinical manifestations and nutritional evaluation, hematological parameters, hospitalizations and transfusion requirements. The information was obtained from the clinical records. Results: 15 patients were studied, there was a predominance of females (60 %) and adolescents represented 80 % of the patients in the study. 10 patients (66.7 %) presented the homozygous form; the Sβ thalassemia and SC variant were represented with 2 and 3 patients, respectively. There were no significant differences when comparing hematological values before and after treatment. A decrease was observed in the frequency and severity of the seizures, in the number of hospitalizations and transfusion requirements in all the patients. Malnutrition was present in only 4 patients out of the total. Conclusions: treatment with hydroxyurea for the study patients resulted in clinical improvement, reduction in the number of admissions and decrease in transfusion requirements, which favorably affected their nutritional status.

Ageing results in the eventual loss of muscle mass and strength, joint problems, and overall slowing of movements, with a greater risk of suffering falls or other such accidents. The use of gait assistance exoskeletons can help in the active aging of this segment of the population. Given the user specificity of the mechanics and control these devices need, the facility used to test different design parameters is indispensable. This work deals with the modeling and construction of a modular test bench and prototype exosuit to test different mounting and control schemes for a cable-driven exoskeleton or exosuit. The test bench allows the experimental implementation of postural or kinematic synergies to assist multiple joints by using only one actuator and the optimization of the control scheme to better adapt to the characteristics of the specific patient. The design is open to the research community and it is expected to improve the design of cable-driven systems for exosuits.

Background: This study aimed to evaluate short- and long-term humoral and T-cell-specific immune responses to SARS-CoV-2 vaccines in patients with multiple sclerosis (MS) treated with different disease-modifying therapies (DMTs). Methods: Single-center observational longitudinal study including 102 patients with MS who consecutively received vaccination against SARS-CoV-2. Serum samples were collected at baseline and after receiving the second dose of the vaccine. Specific Th1 responses following in vitro stimulation with spike and nucleocapsid peptides were analyzed by quantifying levels of IFN-γ. Serum IgG-type antibodies against the spike region of SARS-CoV-2 were studied by chemiluminescent microparticle immunoassay. Results: Patients undergoing fingolimod and anti-CD20 therapies had a markedly lower humoral response than those treated with other DMTs and untreated patients. Robust antigen-specific T-cell responses were detected in all patients except those treated with fingolimod, who had lower IFN-γ levels than those treated with other DMTs (25.8 pg/mL vs. 868.7 pg/mL, p = 0.011). At mid-term follow-up, a decrease in vaccine-induced anti-SARS-CoV-2 IgG antibodies was observed in all subgroups of patients receiving DMTs, although most patients receiving induction DMTs or natalizumab and non-treated patients remained protected. Cellular immunity was maintained above protective levels in all DMT subgroups except the fingolimod subgroup. Conclusions: SARS-CoV-2 vaccines induce robust and long-lasting humoral and cell-mediated specific immune responses in most patients with MS.

Copyright of Revista de la Academia Colombiana de Ciencias Exactas, Físicas y Naturales is the property of Academia Colombiana de Ciencias Exactas, Fisicas y Naturales and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)