[Comorbidities in multiple sclerosis and their influence on the choice of treatment]. / Comorbilidades en la esclerosis múltiple y su influencia en la elección del tratamiento.

Clinical trials of disease-modifying therapies (DMTs) for people with multiple sclerosis (pMS) are conducted in selected populations, excluding patients with comorbidities or concomitant medications. However, a large percentage of pMS have some additional disease, which could affect the response and choice of the DMT. The objective of this review is to assess how concurrent pathologies can impact the choice of DMTs. Relevant articles were selected through a systematic search in PubMed. Comorbidities were grouped for better classification into autoimmune, chronic infections, cardiovascular and metabolic, oncological and neuropsychiatric. In autoimmune pathologies, it is key to take into account the effects of TME on them and the possibility of interaction with their specific treatments. Immunomodulatory therapies are safe for people with chronic infections. Immunosuppressive treatments are generally contraindicated in people with active infections. In cardiovascular and metabolic comorbidities, infusion reactions associated with monoclonal antibodies, and the phenomena of starting treatment with S1P modulators, must be taken into account. DMTs with an immunosuppressive effect are contraindicated in people with active malignancies. Although psychiatric pathology per se does not preclude the use of DMTs, caution should be exercised when new psychiatric symptoms appear. For these reasons, among the multiple factors that must be considered when starting or changing a DMT in pMS, comorbidities constitute a decisive element.

TITLE: Comorbilidades en la esclerosis múltiple y su influencia en la elección del tratamiento.Los estudios clínicos de tratamientos para personas con esclerosis múltiple (pEM) se realizan en poblaciones seleccionadas, que excluyen a pacientes que presenten comorbilidades o medicaciones concomitantes. Sin embargo, un gran porcentaje de las pEM tiene alguna enfermedad adicional, que podría afectar a la respuesta y la elección del tratamiento. El objetivo de esta revisión es valorar cómo pueden las diferentes patologías concurrentes impactar en la elección de las terapias modificadoras de la enfermedad (TME) en las pEM. Se seleccionaron artículos relevantes mediante búsqueda en PubMed. Las comorbilidades se agruparon, a los fines de mejor ordenamiento de los artículos encontrados, en patologías diversas: autoinmunes, infecciones crónicas, cardiovasculares, respiratorias, metabólicas, oncológicas, neuropsiquiátricas y epilepsia. En cuanto a las patologías autoinmunes, es clave tener en cuenta los efectos de las TME sobre ellas y la posibilidad de interacción con sus tratamientos específicos. Las terapias inmunomoduladoras son seguras para personas con infecciones crónicas. Los tratamientos inmunosupresores, en general, están contraindicados en personas con infecciones activas. En las comorbilidades cardiovasculares y metabólicas deben tenerse en cuenta las potenciales reacciones de infusión asociadas a anticuerpos monoclonales, y los fenómenos asociados al inicio de tratamiento con moduladores del receptor de la esfingosina-1-fosfato. Las TME con efecto inmunosupresor están contraindicadas en personas con malignidades activas. Aunque la patología psiquiátrica de por sí no impide el uso de TME, debería tenerse precaución cuando aparecen nuevos síntomas psiquiátricos, y siempre tenerse en cuenta su monitorización y tratamiento. Por este motivo, entre los múltiples factores que deben considerarse a la hora de iniciar o cambiar una TME en pEM, las comorbilidades constituyen un elemento muchas veces decisivo.

Effect of vascular geometry on haemodynamic changes in a carotid artery bifurcation using numerical simulation.

OBJECTIVES: The geometry of carotid bifurcation is a crucial contributing factor to the localization of atherosclerotic lesions. Currently, studies on carotid bifurcation geometry are limited to the region near to bifurcation. This study aimed to determine the influence of carotid bifurcation geometry on the blood flow using numerical simulations considering magnitude of haemodynamic parameters in the extended regions of carotid artery. METHODS: In the present study, haemodynamic analysis is carried out using the non-Newtonian viscosity model for patient-specific geometries consisting of both Left and Right carotid arteries. A 3D patient-specific geometric model is generated using MIMICS, and a numerical model is created using ANSYS. RESULTS: The results obtained from patient-specific cases are compared. The influence of geometric features such as lumen diameter, bifurcation angle, and tortuosity on the haemodynamics parameters such as velocity, WSS, pressure, Oscillatory Shear Index (OSI), and Time-Averaged Wall Shear Stress (TAWSS) are compared. CONCLUSION: The results demonstrate significant changes in the flow regime due to the geometric shape of the carotid artery. It is observed that the lower value of TAWSS occurs near the bifurcation region and carotid bulb region. In addition, the higher value of the (OSI) is observed in the Internal Carotid Artery (ICA) and the tortuous carotid artery region. However, it is also observed that apart from the bifurcation angle, other factors, such as tortuosity and area ratio, play a significant role in the flow dynamics of the carotid artery.

[Argentinean consensus guidelines on the identification and clinical care of secondary progressive multiple sclerosis]. / Consenso sobre la identificación y seguimiento de la esclerosis múltiple secundaria progresiva en Argentina.

INTRODUCTION: The identification, diagnosis, follow-up, and treatment of patients with secondary progressive multiple sclerosis (SPMS) show significant differences between health care professionals in Argentina. AIM: To provide consensus recommendations on the management of patients with SPMS in Argentina to optimize patient care. DEVELOPMENT: A panel of expert neurologists from Argentina dedicated to the diagnosis and care of multiple sclerosis patients gathered during 2019 and 2020 to carry out a consensus recommendation on the diagnosis and treatment of SPMS patients in Argentina. To achieve consensus, the methodology of 'formal consensus-RAND/UCLA method' was used. Recommendations were established based on published evidence and the expert opinion. Recommendations focused on how to define SPMS and how to follow SPMS patients. CONCLUSION: The recommendations of this consensus guidelines attempt to optimize the care of SPMS patients in Argentina.

TITLE: Consenso sobre la identificación y seguimiento de la esclerosis múltiple secundaria progresiva en Argentina.Introducción. Existen diferencias significativas en el diagnóstico, la identificación y el seguimiento de pacientes con esclerosis múltiple secundaria progresiva (EMSP) entre los profesionales de la salud a cargo de su tratamiento. Objetivo. Proveer recomendaciones sobre el tratamiento de los pacientes con EMSP en Argentina con el fin de optimizar su cuidado. Desarrollo. Un grupo de neurólogos expertos en esclerosis múltiple de Argentina elaboró un consenso para el tratamiento de pacientes con EMSP en la región mediante metodología de ronda de encuestas a distancia y reuniones presenciales. Se establecieron 33 recomendaciones basadas en la evidencia publicada y en el criterio de los expertos que participaron. Las recomendaciones se enfocaron en el diagnóstico y el seguimiento de los pacientes con EMSP. Conclusión. Las recomendaciones establecidas en el presente consenso permitirían optimizar el cuidado y el seguimiento de los pacientes con EMSP en Argentina.

Evening chronotype, disordered eating behavior, and poor dietary habits in bipolar disorder.

OBJECTIVE: Our aim was to evaluate the relationship between evening chronotype, a proxy marker of circadian system dysfunction, and disordered eating behavior and poor dietary habits in individuals with bipolar disorder (BD). METHODS: In this cross-sectional study, we evaluated 783 adults with BD. Chronotype was determined using item 5 from the reduced Morningness-Eveningness Questionnaire. The Eating Disorder Diagnostic Scale (EDDS) and the Rapid Eating Assessment for Participants-Shortened Version (REAP-S) were used to assess disordered eating behavior and dietary habits respectively. General linear models and logistic regression models were utilized to evaluate differences between chronotype groups. RESULTS: Two hundred and eight (27%) BD participants self-identified as having evening chronotypes. Compared to non-evening types, evening types were younger (P < 0.01) and, after controlling for age, had higher mean EDDS composite z-scores (P < 0.01); higher rates of binge-eating (BE) behavior (P = 0.04), bulimia nervosa (P < 0.01), and nocturnal eating binges (P < 0.01); and a higher body mass index (P = 0.04). Compared to non-evening types, evening chronotypes had a lower REAP-S overall score (P < 0.01) and scored lower on the 'healthy foods' and 'avoidance of unhealthy food' factors. Evening types also skipped breakfast more often (P < 0.01), ate less fruit (P = 0.02) and vegetables (P = 0.04), and consumed more fried foods (P < 0.01), unhealthy snacks (P = 0.02), and soft drinks (P = 0.01). CONCLUSIONS: Our findings suggest that the circadian system plays a role in the disordered eating and unhealthy dietary behaviors observed in BD patients. The circadian system may therefore represent a therapeutic target in BD-associated morbidity that warrants further investigation.

A Practical Approach to the Diagnosis and Treatment of Adult Erythroderma. / Eritrodermia en el adulto: un enfoque práctico para el diagnóstico y tratamiento.

Erythroderma is an inflammatory skin syndrome that involves desquamation and erythema of more than 90% of the body surface area. It represents a final clinical endpoint for many adult dermatological conditions. The most frequent cause of erythroderma is psoriasis followed by eczematous conditions, drug-induced reactions, pityriasis rubra pilaris and cutaneous T-cell lymphomas. Diagnostic approach must include a thorough history and clinical examination. If the etiology of erythroderma is uncertain multiple skin biopsies may enhance diagnostic accuracy. The initial management of erythroderma must include a nutrition expert evaluation, fluid imbalance assessment, maintaining skin barrier function, sedative antihistamines and exclusion of secondary bacterial infection. We present a practical review of the etiology, diagnosis, and treatment of this entity.

Leveraging electronic health records to study pleiotropic effects on bipolar disorder and medical comorbidities.

Patients with bipolar disorder (BD) have a high prevalence of comorbid medical illness. However, the mechanisms underlying these comorbidities with BD are not well known. Certain genetic variants may have pleiotropic effects, increasing the risk of BD and other medical illnesses simultaneously. In this study, we evaluated the association of BD-susceptibility genetic variants with various medical conditions that tend to co-exist with BD, using electronic health records (EHR) data linked to genome-wide single-nucleotide polymorphism (SNP) data. Data from 7316 Caucasian subjects were used to test the association of 19 EHR-derived phenotypes with 34 SNPs that were previously reported to be associated with BD. After Bonferroni multiple testing correction, P<7.7 × 10(-5) was considered statistically significant. The top association findings suggested that the BD risk alleles at SNP rs4765913 in CACNA1C gene and rs7042161 in SVEP1 may be associated with increased risk of 'cardiac dysrhythmias' (odds ratio (OR)=1.1, P=3.4 × 10(-3)) and 'essential hypertension' (OR=1.1, P=3.5 × 10(-3)), respectively. Although these associations are not statistically significant after multiple testing correction, both genes have been previously implicated with cardiovascular phenotypes. Moreover, we present additional evidence supporting these associations, particularly the association of the SVEP1 SNP with hypertension. This study shows the potential for EHR-based analyses of large cohorts to discover pleiotropic effects contributing to complex psychiatric traits and commonly co-occurring medical conditions.

Complete genome sequence of bean rugose mosaic virus, genus Comovirus.

Since the first report in Costa Rica in 1971, bean rugose mosaic virus (BRMV) has been found in Colombia, El Salvador, Guatemala and Brazil. In this study, the complete genome sequence of a soybean isolate of BRMV from Paraná State, Brazil, was determined. The BRMV genome consists of two polyadenylated RNAs. RNA1 is 5909 nucleotides long and encodes a single polypeptide of 1856 amino acids (aa), with an estimated molecular weight of 210 kDa. The RNA1 polyprotein contains the polypeptides for viral replication and proteolytic processing. RNA2 is 3644 nucleotides long and codes for a single polypeptide of 1097 aa, containing the movement and coat proteins. This is the first complete genome sequence of BRMV. When compared with available aa sequences of comoviruses, the highest identities of BRMV coat proteins and proteinase polymerase were 57.5 and 58 %, respectively. These were below the 75 and 80 % identity limits, respectively, established for species demarcation in the genus. This confirms that BRMV is a member of a distinct species in the genus Comovirus.

Risk of myocardial infarction and stroke in bipolar disorder: a systematic review and exploratory meta-analysis.

OBJECTIVE: To review the evidence on and estimate the risk of myocardial infarction and stroke in bipolar disorder. METHOD: A systematic search using MEDLINE, EMBASE, PsycINFO, Web of Science, Scopus, Cochrane Database of Systematic Reviews, and bibliographies (1946 - May, 2013) was conducted. Case-control and cohort studies of bipolar disorder patients age 15 or older with myocardial infarction or stroke as outcomes were included. Two independent reviewers extracted data and assessed quality. Estimates of effect were summarized using random-effects meta-analysis. RESULTS: Five cohort studies including 13 115 911 participants (27 092 bipolar) were included. Due to the use of registers, different statistical methods, and inconsistent adjustment for confounders, there was significant methodological heterogeneity among studies. The exploratory meta-analysis yielded no evidence for a significant increase in the risk of myocardial infarction: [relative risk (RR): 1.09, 95% CI 0.96-1.24, P = 0.20; I(2)  = 6%]. While there was evidence of significant study heterogeneity, the risk of stroke in bipolar disorder was significantly increased (RR 1.74, 95% CI 1.29-2.35; P = 0.0003; I(2)  = 83%). CONCLUSION: There may be a differential risk of myocardial infarction and stroke in patients with bipolar disorder. Confidence in these pooled estimates was limited by the small number of studies, significant heterogeneity and dissimilar methodological features.

Genome-wide association study of bipolar disorder accounting for effect of body mass index identifies a new risk allele in TCF7L2.

Bipolar disorder (BD) is associated with higher body mass index (BMI) and increased metabolic comorbidity. Considering the associated phenotypic traits in genetic studies of complex diseases, either by adjusting for covariates or by investigating interactions between genetic variants and covariates, may help to uncover the missing heritability. However, obesity-related traits have not been incorporated in prior genome-wide analyses of BD as covariates or potential interacting factors. To investigate the genetic factors underlying BD while considering BMI, we conducted genome-wide analyses using data from the Genetic Association Information Network BD study. We analyzed 729,454 genotyped single-nucleotide polymorphism (SNP) markers on 388 European-American BD cases and 1020 healthy controls with available data for maximum BMI. We performed genome-wide association analyses of the genetic effects while accounting for the effect of maximum BMI, and also evaluated SNP-BMI interactions. A joint test of main and interaction effects demonstrated significant evidence of association at the genome-wide level with rs12772424 in an intron of TCF7L2 (P=2.85E-8). This SNP exhibited interaction effects, indicating that the bipolar susceptibility risk of this SNP is dependent on BMI. TCF7L2 codes for the transcription factor TCF/LF, part of the Wnt canonical pathway, and is one of the strongest genetic risk variants for type 2 diabetes (T2D). This is consistent with BD pathophysiology, as the Wnt pathway has crucial implications in neurodevelopment, neurogenesis and neuroplasticity, and is involved in the mechanisms of action of BD and depression treatments. We hypothesize that genetic risk for BD is BMI dependent, possibly related to common genetic risk with T2D.

The use of a Ga+ focused ion beam to modify graphene for device applications.

In this work, we clarify the features of the lateral damage of line defects in single layer graphene. The line defects were produced through well-controlled etching of graphene using a Ga(+) focused ion beam. The lateral damage length was obtained from both the integrated intensity of the disorder induced Raman D band and the minimum ion fluence. Also, the line defects were characterized by polarized Raman spectroscopy. It was found that graphene is resilient under the etching conditions since the intensity of the defect induced Raman D peak exhibits a dependence on the direction of the lines relative to the crystalline lattice and also on the direction of the laser polarization relative to the lines. In addition, electrical measurements of the modified graphene were performed. Different ion fluences were used in order to obtain a completely insulating defect line in graphene, which was determined experimentally by means of charge injection and electric force microscopy measurements. These studies demonstrate that a Ga+ ion column combined with Raman spectroscopy is a powerful technique to produce and understand well-defined periodic arrays of defects in graphene, opening possibilities for better control of nanocarbon devices.

Cancer survival in Costa Rica, 1995-2000.

The Costa Rica national tumour registry was founded in 1976 and nationwide data collection commenced in 1980. Cancer registration is predominantly done by passive methods. The registry contributed data on survival for invasive cancers of breast and cervix and in situ cancer of the cervix registered during 1995-2000. Followup has been carried out predominantly by passive methods, with median follow-up ranging from 31-47 months. The proportion of cases with histological confirmation of cancer diagnosis was 92% for invasive cancers and almost 100% for in-situ cancer of the cervix; death certificates only (DCOs) comprised 3%, and 78-86% of total cases registered were included for survival analysis. The one-, three- and five-year relative survival were 93%, 77% and 68%, respectively for breast cancer; the corresponding figures for invasive cervix cancer were 83%, 61% and 54%, respectively. The five-year relative survival for in-situ cervix cancer was 99%. A decreasing survival with increasing age group at diagnosis was noted for in-situ cancer of the cervix, while it fluctuated for invasive breast and cervix cancers. A decreasing survival with increasing clinical extent of disease was noted for invasive breast and cervix cancers.

Persistence of the efficacy of copper oxide wire particles against Haemonchus contortus in sheep.

The aim was to determine the persistent efficacy of copper oxide wire particles (COWP) against Haemonchus contortus in sheep, using the harmonization guidelines protocol. Thirty-six male lambs (2 months old) reared free of gastrointestinal nematodes were used (average body weight of 10.8±3.8kg). Before and for the duration of the study, lambs were kept in raised cages with slatted floors and were offered ad libitum a complete mixed diet. Animals were divided into six groups (n=6): one non-treated control group (G0) and five groups treated with one COWP capsule (1.7g of copper oxide; Copinox(®)). Animals in each group were treated on pre-defined dates before the artificial infection was applied: days -35 (G1), -28 (G2), -21 (G3), -14 (G4) and -7 (G5). On day 0 animals were infected with 3700 H. contortus infective larvae per animal. Animals were humanely slaughtered between days 22 and 23 post-infection. The abomasums were individually washed to obtain the contents. These organs were subjected to separate artificial digestions. Adult parasites were counted from the abomasum contents and the larvae from the digested material. Worm burden geometric means were calculated for each group. A significant worm burden reduction in either of the treated groups (G1, G2, G3, G4, and G5) compared to the control (G0) was considered as persistence of the anthelmintic effect. Copper levels were determined from individual liver samples of each animal. The geometric mean worm burden of the control group (G0) was 1959. Compared to the control, worm burdens geometric means were significantly reduced in groups G1 (1108), G4 (528) and G5 (1063) (P<0.03). Efficacies in G1, G4 and G5 were 43.4%, 73.0% and 45.7% respectively. No significant reduction was found for G2 (1342) and G3 (1430). A larger quantity of Cu was found in the livers of treated animals compared to the control group (P<0.05) except for G3 (P=0.06). A negative association between Cu liver content and worm burdens was found (r=-0.42, P<0.05). Live weight gain was similar in all groups and no clinical or post-mortem manifestations of Cu toxicity were recorded in treated animals.

Métodos diagnósticos para os patógenos alimentares: Campylobacter sp., Salmonella sp. e Listeria monocytogenes / Diagnostic methods for the food pathogens Campylobacter sp., Salmonella sp. and Listeria monocytogenes

Os métodos moleculares de detecção rápida e eficaz de lotes de aves infectados por bactérias como Salmonella sp. Campylobacter sp. e Listeria monocytogenes são importantes para reduzir a frequência da transmissão destes patógenos entre os lotes de aves e aos consumidores de produtos de origem animal. Recentemente, as técnicas de biologia molecular, em especial a reação em cadeia polimerase, que permite a amplificação específica de segmentos de DNA, têm possibilitado novos rumos na identificação de bactérias supracitadas, reduzindo o tempo de cultivo e ampliando a confiabilidade das provas diagnósticas. A utilização da biologia molecular por laboratórios de diagnóstico humano e animal, assim como em programas de controle de qualidade de alimentos e produtos de origem animal, já é realidade e tende a se expandir rapidamente. O objetivo deste artigo é fazer uma breve revisão dos testes diagnósticos convencionais e moleculares para identificar Campylobacter sp., Salmonella sp. e Listeria monocytogenes. Concluindo, o diagnóstico molecular é um campo em avanço científico e tecnológico, no qual novas técnicas moleculares estão em desenvolvimento para o diagnóstico de bactérias em alimentos.

The molecular methods for quick and efficient detection of chicken lots infected by bacteria such as Salmonella sp. Campylobacter sp. and Listeria monoytogenes is basic for the effort to reduce the frequency of the transmission between chicken lots and to the consumers of poultry products. Recently, the development of techniques involving molecular biology, especially polymerase chain reaction, which allows the specific enlargement of segments of DNA, has been making new procedures possible for the identification of the abovementioned bacteria, reducing the time necessary for the tests and enhancing the reliability of the resulting diagnoses. The use of molecular biology in laboratories for human and animal diagnosis, as well as in quality control programs for foods and products of animal origin is already a reality and has tended to expand quickly. The objective of this article is to present a brief review of the conventional diagnostic and molecular tests for the identification of Campylobacter sp., Salmonella sp. and Listeria monocytogenes. In conclusion, molecular diagnosis is a field undergoing scientific and technological advancement, in which new molecular techniques are under development for the diagnosis of bacteria in foods.

Comportamiento epidemiológico de la rabia humana en el estado Zulia Venezuela: durante el período de vigilancia enero 1993 junio 2009 / Epidemiological Behavior of human rabies in the state of Zulia Venezuela: during the surveillance period january 1993 june 2009

La rabia representa un importante problema de salud pública en el estado Zulia, constituyendo en Venezuela la entidad con mayor incidencia de casos en animales y humanos, registrándose 25 muertes humanas por rabia durante el período enero 1993 - junio 2009. Describir su comportamiento epidemiológico durante este período constituye nuestro objetivo. Estudio epidemiológico realizado: observacional, descriptivo. La muestra incluyó todos los casos confirmados como rabia humana en la entidad durante este lapso (n = 25), con edades entre 2-57 años, de ambos sexos y procedentes de 7 municipios con incidencia. Datos tomados de los informes de casos de rabia de la Dirección Regional de Epidemiología. Los resultados están expresados en porcentajes, promedios, intervalos de confianza, tasa de letalidad y distribuciones según edad, sexo y municipio de ocurrencia. La mayor incidencia ocurrió en varones (68%). El grupo entre 2-10 años resultó mayormente afectado (60%). El 80% casos no efectuó consulta post exposición no recibiendo inmunoprofilaxia oportuna. La Inmunofluorescencia directa fue utilizada para confirmación diagnóstica. El conocimiento sobre las formas de transmisión de rabia es crucial para prevenirla; el tiempo entre la inoculación viral y la invasión neural es quizá el único período para una inmunoprofilaxia efectiva

Rabies represents a major public health problem in the State of Zulia, constituting the entitywith the highest incidence of animal and human cases in Venezuela, registering 25 human deathsby rabies from January, 1993 – June, 2009. The objective of this study is to describe its epidemiologicalbehavior during this period; the epidemiological study was observational and descriptive.The sample included all cases confirmed as human rabies in the entity during this period (n = 25);they were between 2 and 57 years of age, from both sexes and 7 municipalities. Data was takenfrom the reports of rabies cases in the Regional Epidemiology Direction. The results are expressedin percentages, means, confidence intervals, mortality rate and distributions according to age, sexand municipality of occurrence. The highest incidence was in males (68%).The group between2-10 years was principally affected (60%). Eighty per cent of the cases did not seek post-exposureconsultation and did not receive timely prophylaxis. The direct fluorescent antibody test was usedfor diagnostic confirmation. Knowledge about forms of rabies transmission is crucial for its prevention;the time between viral inoculation and neural invasion is perhaps the only period for aneffective prophylaxis

Universal response of single-wall carbon nanotubes to radial compression.

The mechanical response of single-wall carbon nanotubes to radial compression is investigated via atomic force microscopy (AFM). We find that the force F applied by an AFM tip (with radius R) onto a nanotube (with diameter d), rescaled through the quantity Fd;{3/2}(2R);{-1/2}, falls into a universal curve as a function of the compressive strain. Such universality is reproduced analytically in a model where the graphene bending modulus is the only fitting parameter. The application of this model to the radial Young's modulus E_{r} leads to a further universal-type behavior which explains the large variations of nanotube E_{r} reported in the literature.