Increased plasma neurofilament light chain levels in patients with type-1 diabetes with impaired awareness of hypoglycemia

Altres ajuts: This work was financially supported by a grant from the SPANISH DIABETES SOCIETY.Impaired awareness of hypoglycemia (IAH) is a common complication in patients with type-1 diabetes (T1D). IAH is a major risk factor for severe hypoglycemic events, leading to adverse clinical consequences and cerebral damage. Non-invasive, cost-effective, and logistically efficient biomarkers for this condition have not been validated. Here, we propose plasma neurofilament light chain (NfL) levels as a biomarker of neuroaxonal damage in patients with T1D-IAH. 54 patients were included into the study (18 T1D-IAH, 18 T1D with normal awareness of hypoglycemia (NAH) and 18 healthy controls). We measured plasma NfL levels and studied cerebral gray matter alterations on MRI. We found that NfL levels were increased in patients with T1D-IAH compared with patients with T1D-NAH and healthy controls. Importantly, increased NfL levels correlated with reduced cerebral gray matter volume and increased IAH severity in patients with T1D-IAH. Overall, our findings identify plasma NfL levels as a potential biomarker of cerebral damage in this population, motivating further confirmatory studies with potential implications in clinical trials

Novel liposome-based and in situ gelling artificial tear formulation for dry eye disease treatment

Purpose. Artificial tears are widely used in the treatment of dry eye disease, although current formulations do not closely resemble natural tears. The purpose of this study was the design and characterization of a novel in situ gelling artificial tear formulation, containing both lipid and aqueous components, in order to resemble natural tears and replenish the tear film. Methods. Liposomes, containing phosphatidylcholine, cholesterol, vitamins A and E, were prepared by the thin-film hydration method. The aqueous phase of the formulation was comprised of gellan gum, hydroxypropyl methylcellulose, levocarnitine, electrolytes (sodium chloride and potassium chloride), trehalose, and borates. The artificial tear was characterized in terms of liposome size, pH, surface tension, and viscosity. In vitro tolerance studies were performed in a human epithelial carcinoma cell line (HeLa) and a murine macrophage cell line (J774). In vivo tolerance was assessed in rabbits. Results. Liposomes presented a unimodal distribution with a mean size of 200.1 ± 4.4 nm. The resulting surface tension was 53.4 ± 1.1 mN/m (at 33°C) and the pH was 7.6 ± 0.1. The viscosity of the formulation presented a mean value of 4.0 ± 0.1 mPa.s within the shear rate interval of 200-1000 s-1 at 33°C. Cell viability remained higher than 90% in both cell lines. No discomfort or clinical signs were observed in rabbits. Conclusions. The liposome-based and in situ gelling artificial tear formulation presented good tolerance and suitable properties for topical ophthalmic administration. It may be beneficial in the treatment of dry eye disease

Quantifying the patient´s perspective in neuromyelitis optica spectrum disorder: Psychometric properties of the SymptoMScreen questionnaire

Background: The assessment of self-reported outcomes in neuromyelitis optica spectrum disorder (NMOSD) is limited by the lack of validated disease-specific measures. The SymptoMScreen (SyMS) is a patient-reported questionnaire for measuring symptom severity in different domains affected by multiple sclerosis (MS), but has not been thoroughly evaluated in NMOSD. The aim of this study was to assess the psychometric properties of the SyMS in a sample of patients with NMOSD. Methods: A non-interventional, cross-sectional study in adult subjects with NMOSD (Wingerchuk 2015 criteria) was conducted at 13 neuroimmunology clinics applying the SyMS. A non-parametric item response theory procedure, Mokken analysis, was performed to assess the underlying dimensional structure and scalability of items and overall questionnaire. All analyses were performed with R (v4.0.3) using the mokken library. Results: A total of 70 patients were studied (mean age: 47.5 ± 15 years, 80% female, mean Expanded Disability Status Scale score: 3.0 [interquartile range 1.5, 4.5]). Symptom severity was low (median SyMS score: 19.0 [interquartile range 10.0, 32.0]). The SyMS showed a robust internal reliability (Cronbach's alpha: 0.90 [95% confidence interval 0.86, 0.93]) and behaved as a unidimensional scale with all items showing scalability coefficients > 0.30. The overall SyMS scalability was 0.45 conforming to a medium scale according to Mokken's criteria. Fatigue and body pain were the domains with the highest scalability coefficients. The SyMS was associated with disability (rho: 0.586), and physical and psychological quality of life (rho: 0.856 and 0.696, respectively). Conclusions: The SyMS shows appropriate psychometric characteristics and may constitute a valuable and easy-to-implement option to measure symptom severity in patients with NMOSD

Impact of Neuromyelitis Optica Spectrum Disorder on Quality of Life from the Patients' Perspective : An Observational Cross-Sectional Study

Altres ajuts: Medical Department of Roche Farma, Spain (ML41397).Introduction: Neuromyelitis optica spectrum disorder (NMOSD) is associated with a reduced health-related quality of life (HRQoL). The purpose of this study was to describe the impact of NMOSD on HRQoL from the patients' perspective and its relationship with other disease factors. Methods: An observational, cross-sectional study was conducted at 13 neuroimmunology clinics in Spain. Patients with NMOSD diagnosis (2015 Wingerchuk criteria) were included. The 29-item Multiple Sclerosis Impact Scale (MSIS-29) was used to assess the HRQoL. Different questionnaires were used to measure symptom severity, stigma, mood disorders, pain, fatigue, and difficulties in the workplace. Factors that impact HRQoL were identified by Spearman's correlation and multivariate linear regression analysis. Results: Seventy-one patients were included (mean age 47.4 ± 14.9 years, 80.3% female, mean time since disease onset 9.9 ± 8.1 years). The median Expanded Disability Status Scale score was 3.0 (1.5-4.5). The mean (± SD) physical and psychological MSIS-29 sub-scores were 41.9 ± 16.8 and 20.9 ± 8.3, respectively. Fatigue and body pain were the most prevalent symptoms. Depressive symptoms were found in 44.3% (n = 31) of patients. The physical MSIS-29 dimension showed the highest correlation with symptom severity (ρ = 0.85584, p < 0.0001), whereas the highest correlations for psychological MSIS-29 dimension were pain, MSIS-29 physical dimension, and depression (ρ = 0.76487, 0.72779, 0.71380; p < 0.0001, respectively). Pain was a predictor of both dimensions of MSIS-29. Conclusion: Fatigue, pain, and depressive symptoms are frequent problems among patients with NMOSD, impacting on their quality of life. Assessment of patient-oriented outcomes may be useful to achieve a holistic approach, allowing early specific interventions

Temas Socio-Jurídicos. Volumen 26 No. 54 Junio de 2008

La revista Temas Socio-jurídicos llega a su edición número 54, en el vigésimo sexto año de publicación continuada con periodicidad semestral; ella es el resultado de la producción intelectual de la comunidad académica Universidad Autónoma de Bucaramanga.The magazine Temas Socio-jurídicos reaches its 54th edition, in its twenty-sixth year of continuous publication on a semi-annual basis; it is the result of the intellectual production of the academic community of the Autonomous University of Bucaramanga

Amphiphilic Acrylic Nanoparticles Containing the Poloxamer Star Bayfit® 10WF15 as Ophthalmic Drug Carriers

Topical application of drops containing ocular drugs is the preferred non-invasive route to treat diseases that a_ect the anterior segment of the eye. However, the formulation of eye drops is a major challenge for pharmacists since the access of drugs to ocular tissues is restricted by several barriers. Acetazolamide (ACZ) is a carbonic anhydrase inhibitor used orally for the treatment of ocular hypertension in glaucoma. However, large ACZ doses are needed which results in systemic side e_ects. Recently, we synthesized copolymers based on 2-hydroxyethyl methacrylate (HEMA) and a functionalized three-arm poloxamer star (Bayfit-MA). The new material (HEMA/Bayfit-MA) was engineered to be transformed into nanoparticles without the use of surfactants, which represents a significant step forward in developing new ophthalmic drug delivery platforms. Acetazolamide-loaded nanocarriers (ACZ-NPs) were prepared via dialysis (224 +/- 19 nm, ̶ 17.2 +/- 0.4 mV). The in vitro release rate of ACZ was constant over 24 h (cumulative delivery of ACZ: 83.3 +/- 8.4%). Following standard specifications, ACZ-NPs were not cytotoxic in vitro in cornea, conjunctiva, and macrophages. In normotensive rabbits, ACZ-NPs generated a significant intraocular pressure reduction compared to a conventional solution of ACZ (16.4% versus 9.6%) with the same dose of the hypotensive drug (20 μg). In comparison to previously reported studies, this formulation reduced intraocular pressure with a lower dose of ACZ. In summary, HEMA:Bayfit-MA nanoparticles may be a promising system for ocular topical treatments, showing an enhanced ocular bioavailability of ACZ after a single instillation on the ocular surface

Therapeutic inertia in the management of neuromyelitis optica spectrum disorder

Introduction and objectiveLimited information is available on how neurologists make therapeutic decisions in neuromyelitis optica spectrum disorder (NMOSD), especially when new treatments with different mechanisms of action, administration, and safety profile are being approved. Decision-making can be complex under this uncertainty and may lead to therapeutic inertia (TI), which refers to lack of treatment initiation or intensification when therapeutic goals are not met. The study aim was to assess neurologists’ TI in NMOSD.MethodsAn online, cross-sectional study was conducted in collaboration with the Spanish Society of Neurology. Neurologists answered a survey composed of demographic characteristics, professional background, and behavioral traits. TI was defined as the lack of initiation or intensification with high-efficacy treatments when there is evidence of disease activity and was assessed through five NMOSD aquaporin-4 positive (AQP4+) simulated case scenarios. A multivariate logistic regression analysis was used to determine the association between neurologists’ characteristics and TI.ResultsA total of 78 neurologists were included (median interquartile range [IQR] age: 36.0 [29.0–46.0] years, 55.1% male, median [IQR] experience managing demyelinating conditions was 5.2 [3.0–11.1] years). The majority of participants were general neurologists (59.0%) attending a median (IQR) of 5.0 NMOSD patients (3.0–12.0) annually. Thirty participants (38.5%) were classified as having TI. Working in a low complexity hospital and giving high importance to patient’s tolerability/safety when choosing a treatment were predictors of TI.ConclusionTI is a common phenomenon among neurologists managing NMOSD AQP4+. Identifying TI and implementing specific intervention strategies may be critical to improving therapeutic decisions and patient care

Temas Socio-Jurídicos. Volumen 23 No. 49 Diciembre 2005

El texto que se ofrece a continuación se ha estructurado en función del estudio de dos momentos claves en la configuración del institucionalismo. En un primer momento se retoman las iniciales ideas de Veblen, Commons y Mitchell, buscando identificar en ellas el tópico que las conecta con el proceso de construcción de este marco analítico. En un segundo momento, se examina cómo la ideas de los protoinstitucionalistas mencionados, son retomadas por Coase, Williamson y North en tiempos y contextos relativamente lejanos a los que se plantearon los primeros enfoques, dándole forma a un enfoque analítico concebido para afianzar el rol de las organizaciones y promover la eficiencia en las transacciones sobre las que descansan el bienestar social, la transparencia política y el desarrollo económico.The text offered below has been structured based on the study of two key moments in the configuration of institutionalism. At first, the initial ideas of Veblen, Commons and Mitchell are taken up, seeking to identify in them the topic that connects them with the construction process of this analytical framework. In a second moment, it is examined how the ideas of the aforementioned proto-institutionalists are taken up by Coase, Williamson and North in times and contexts relatively distant from those of the first approaches, giving shape to an analytical approach designed to strengthen the role of organizations and promote efficiency in the transactions on which social welfare, political transparency rest and economic development

Cognitive Performance and Health-Related Quality of Life in Patients with Neuromyelitis Optica Spectrum Disorder

Background: The frequency of cognitive impairment (CI) reported in neuromyelitis optica spectrum disorder (NMOSD) is highly variable, and its relationship with demographic and clinical characteristics is poorly understood. We aimed to describe the cognitive profile of NMOSD patients, and to analyse the cognitive differences according to their serostatus; furthermore, we aimed to assess the relationship between cognition, demographic and clinical characteristics, and other aspects linked to health-related quality of life (HRQoL). Methods: This cross-sectional study included 41 patients (median age, 44 years; 85% women) from 13 Spanish centres. Demographic and clinical characteristics were collected along with a cognitive z-score (Rao's Battery) and HRQoL patient-centred measures, and their relationship was explored using linear regression. We used the Akaike information criterion to model which characteristics were associated with cognition. Results: Fourteen patients (34%) had CI, and the most affected cognitive domain was visual memory. Cognition was similar in AQP4-IgG-positive and -negative patients. Gender, mood, fatigue, satisfaction with life, and perception of stigma were associated with cognitive performance (adjusted R-2 = 0.396, p < 0.001). Conclusions: The results highlight the presence of CI and its impact on HRQoL in NMOSD patients. Cognitive and psychological assessments may be crucial to achieve a holistic approach in patient care

Temas Socio-Jurídicos. Volumen 22 No. 46 Julio de 2004

Presentamos a la comunidad académica la edición número 46 de la revista Temas Socio-Jurídicos de la Facultad de Derecho de la Universidad Autónoma de Bucaramanga, que se inserta como muestra del análisis académico en el marco de las preocupantes modificaciones estructurales que dentro del desarrollo jurídico de país, adelanta el Estado Colombiano.We present to the academic community the 46th edition of the Temas Socio-Jurídicos magazine of the Faculty of Law of the Autonomous University of Bucaramanga, which is inserted as a sample of academic analysis within the framework of the worrying structural modifications that within the legal development of country, advances the Colombian State