Novel nanostructured lipid carriers loading Apigenin for anterior segment ocular pathologies.

Dry eye disease (DED) is a chronic multifactorial disorder of the ocular surface caused by tear film dysfunction and constitutes one of the most common ocular conditions worldwide. However, its treatment remains unsatisfactory. While artificial tears are commonly used to moisturize the ocular surface, they do not address the underlying causes of DED. Apigenin (APG) is a natural product with anti-inflammatory properties, but its low solubility and bioavailability limit its efficacy. Therefore, a novel formulation of APG loaded into biodegradable and biocompatible nanoparticles (APG-NLC) was developed to overcome the restricted APG stability, improve its therapeutic efficacy, and prolong its retention time on the ocular surface by extending its release. APG-NLC optimization, characterization, biopharmaceutical properties and therapeutic efficacy were evaluated. The optimized APG-NLC exhibited an average particle size below 200 nm, a positive surface charge, and an encapsulation efficiency over 99 %. APG-NLC exhibited sustained release of APG, and stability studies demonstrated that the formulation retained its integrity for over 25 months. In vitro and in vivo ocular tolerance studies indicated that APG-NLC did not cause any irritation, rendering them suitable for ocular topical administration. Furthermore, APG-NLC showed non-toxicity in an epithelial corneal cell line and exhibited fast cell internalization. Therapeutic benefits were demonstrated using an in vivo model of DED, where APG-NLC effectively reversed DED by reducing ocular surface cellular damage and increasing tear volume. Anti-inflammatory assays in vivo also showcased its potential to treat and prevent ocular inflammation, particularly relevant in DED patients. Hence, APG-NLC represent a promising system for the treatment and prevention of DED and its associated inflammation.

Optimizing cellulose fraction for enhanced utility: Comparative pre-treatment of Agave tequilana Weber var. blue bagasse fiber for sustainable applications.

In recent decades, natural fibers have emerged as an alternative to synthetic fibers due to their renewable nature, lower environmental impact, and comparable strength properties. Agave bagasse, a byproduct of agave juice extraction in Mexico, stands out for its potential in various industrial applications, notably biocomposite production. Bagasse is rich in cellulose, along with hemicellulose and lignin. Cellulose is the most suitable to be converted into valuable products, and it is versatile, renewable, and biodegradable. An effective pre-treatment is crucial to enrich its fraction. This study aims to determine the optimal pre-treatment conditions for the agave bagasse. Three different pre-treatments were tested, acid (H2SO4), enzymatic (Cellic® HTec2 enzymatic preparation), and sequence of acid-enzymatic (sulfuric acid and Cellic® HTec2), to determine which pre-treatment got the optimal cellulose fraction increase. The acid pre-treatment was conducted over three time ranges (5, 10, and 15 min) at different acid concentrations (1%, 1.5%, and 2%). Enzymatic reactions were conducted over 24 h, testing three different enzyme concentrations (1.5%, 3%, 4.5%). The sequential pre-treatment utilized the optimal conditions derived from the acid experiments (1.5% H2SO4 for 10 min), followed by enzymatic reactions carried out over three different durations (6, 12, and 24 h). The findings revealed that a 1.5% acid concentration applied for 10 min was the most efficient pre-treatment method. This pre-treatment resulted in a 1.9-fold increase in the cellulose fraction while reducing hemicellulose content by 30%. The hemicellulose reduction was confirmed through Fourier Transform IR spectroscopy (FTIR) analysis, complemented by scanning electron microscopy (SEM) observations highlighting physical alterations in the fiber structure. Furthermore, thermogravimetric analysis (TGA) demonstrated improved thermal stability, suggesting potential use in biocomposites. Future research should evaluate the environmental impact of optimized pre-treatment methods for agave bagasse.

Stress response and adaptation mechanisms in Kluyveromyces marxianus.

Kluyveromyces marxianus is a non-Saccharomyces yeast that has gained importance due to its great potential to be used in the food and biotechnology industries. In general, K. marxianus is a known yeast for its ability to assimilate hexoses and pentoses; even this yeast can grow in disaccharides such as sucrose and lactose and polysaccharides such as agave fructans. Otherwise, K. marxianus is an excellent microorganism to produce metabolites of biotechnological interest, such as enzymes, ethanol, aroma compounds, organic acids, and single-cell proteins. However, several studies highlighted the metabolic trait variations among the K. marxianus strains, suggesting genetic diversity within the species that determines its metabolic functions; this diversity can be attributed to its high adaptation capacity against stressful environments. The outstanding metabolic characteristics of K. marxianus have motivated this yeast to be a study model to evaluate its easy adaptability to several environments. This chapter will discuss overview characteristics and applications of K. marxianus and recent insights into the stress response and adaptation mechanisms used by this non-Saccharomyces yeast.

Heterogeneity of sensitization profiles and clinical phenotypes among patients with seasonal allergic rhinitis in Southern European countries-The @IT.2020 multicenter study.

BACKGROUND: Pollen allergy poses a significant health and economic burden in Europe. Disease patterns are relatively homogeneous within Central and Northern European countries. However, no study broadly assessed the features of seasonal allergic rhinitis (SAR) across different Southern European countries with a standardized approach. OBJECTIVE: To describe sensitization profiles and clinical phenotypes of pollen allergic patients in nine Southern European cities with a uniform methodological approach. METHODS: Within the @IT.2020 multicenter observational study, pediatric and adult patients suffering from SAR were recruited in nine urban study centers located in seven countries. Clinical questionnaires, skin prick tests (SPT) and specific IgE (sIgE) tests with a customized multiplex assay (Euroimmun Labordiagnostika, Lübeck, Germany) were performed. RESULTS: Three hundred forty-eight children (mean age 13.1 years, SD: 2.4 years) and 467 adults (mean age 35.7 years SD: 10.0 years) with a predominantly moderate to severe, persistent phenotype of SAR were recruited. Grass pollen major allergenic molecules (Phl p 1 and/or Phl p 5) ranged among the top three sensitizers in all study centers. Sensitization profiles were very heterogeneous, considering that patients in Rome were highly poly-sensitized (sIgE to 3.8 major allergenic molecules per patient), while mono-sensitization was prominent and heterogeneous in other cities, such as Marseille (sIgE to Cup a 1: n = 55/80, 68.8%) and Messina (sIgE to Par j 2: n = 47/82, 57.3%). Co-sensitization to perennial allergens, as well as allergic comorbidities also broadly varied between study centers. CONCLUSIONS: In Southern European countries, pollen allergy is heterogeneous in terms of sensitization profiles and clinical manifestations. Despite the complexity, a unique molecular, multiplex, and customized in-vitro IgE test detected relevant sensitization in all study centers. Nevertheless, this geographical diversity in pollen allergic patients imposes localized clinical guidelines and study protocols for clinical trials of SAR in this climatically complex region.

Chronic Degradation of Seasonally Dry Tropical Forests Increases the Incidence of Genotoxicity in Birds.

Multiple studies have shown that exposure to pollutants can increase genotoxic damage in different taxa. However, to our knowledge, the effects of environmental stress have been explored little. In certain stressful ecosystems, such as seasonally dry tropical forests, the combined effects of anthropogenic activities and ongoing global changes can cause an increase in environmental stresses, in turn, may trigger physiological and genetic effects on biodiversity. The present aims to assess changes in the prevalence of genotoxic damage in birds within three states of forest degradation in the Tumbesian Region of Western Ecuador. We used blood samples from 50 bird species to determine the frequency of micronucleus and nuclear abnormalities in erythrocytes. Our results revealed a significant impact of forest degradation on the occurrence probability of micronucleus and nuclear abnormalities at the community level. Localities with higher levels of degradation exhibited higher levels of abnormalities. However, when analyzing the dominant species, we found contrasting responses. While Lepidocolaptes souleyetii showed a reduction in the proportion of nuclear abnormalities from the natural to shrub-dominated localities Troglodytes aedon and Polioptila plumbea showed an increase for semi-natural and shrub-dominated respectively. We concluded that the degradation process of these tropical forests increases the stress of bird community generating genotoxic damage. Bird responses seem to be species-specific, which could explain the differences in changes in bird composition reported in other studies.

Diet quality, asthma and airway inflammation in school-aged children.

Summary: Background. Asthma is a major public health problem, with increasing prevalence in most countries, particularly among children. Poor dietary quality is also increasing in children, and evidence of the overall quality of children's food patterns effects on asthma is scarce. Methods. This cross-sectional analysis (660 children: 49.1% females, aged 7-12years) evaluated the association between diet quality and asthma (n = 56) and airway inflammation among school-aged children according to body mass index (BMI). Diet quality was assessed through the Healthy Eating Index (HEI)-2015, and categorized by tertiles. Higher scores represent a healthier diet. A questionnaire was used to enquire about self-reported medical diagnosis of asthma and asthma under medication. Lung function and airway reversibility were measured, and airway inflammation assessed measuring exhaled fractional nitric oxide (eNO). Two categories of BMI were considered: non-overweight/obese (p less than 85th), (n = 491), and overweight/obese (p ≥ than 85th), (n = 169). The associations between diet quality and asthma and airway inflammation were estimated using logistic regression models. Results. Non-overweight/obese children in 2nd tertile of HEI-2015 score had decreased odds of having eNO ≥ 35ppb (OR 0.43, 95%CI 0.19-0.98), medical diagnosis of asthma (OR 0.18; 95%CI 0.04-0.84), and asthma treatment (OR 0.12; 95%CI 0.01-0.95), compared to children in the 1st tertile. Conclusions. Our findings suggest that a higher diet quality associates with lower levels of airway inflammation and reduced prevalence of asthma among non-overweight/obese school-aged children.

Biologicals in severe chronic rhinosinusitis with nasal polyps: translation to clinical practice while waiting for head-to-head studies.

Chronic rhinosinusitis with nasal polyps (CRSwNP) affects 1.0-2.6% of the population (1) and results in relevant direct and indirect costs. Recently, several randomized controlled trials (RCTs) with Type 2-targeting biologicals (anti-IL4Rα, anti-IL5R, anti-IL5 and anti-IgE) opened a new treatment field for patients refractory to first-line treatments (2,3).

Distinct TNF-alpha and HLA polymorphisms associate with fibrotic and non-fibrotic subtypes of hypersensitivity pneumonitis.

INTRODUCTION: Since Hypersensitivity Pneumonitis (HP) categorization in fibrotic and nonfibrotic/inflammatory types seems to be more consistent with the distinctive clinical course and outcomes, recent international guidelines recommended the use of this classification. Moreover, fibrotic subtype may share immunogenetic and pathophysiological mechanisms with other fibrotic lung diseases. AIM: To investigate HLA -A, -B, -DRB1 and TNF-α -308 gene polymorphisms among fibrotic and nonfibrotic HP patients due to avian exposure, also in comparison with asymptomatic exposed controls. METHODS: We prospectively enrolled 40 HP patients, classified as fibrotic or nonfibrotic/inflammatory, and 70 exposed controls. HLA and TNF-α polymorphisms were determined by polymerase chain reaction-sequence specific primer amplification. RESULTS: While HLA alleles were not associated to HP susceptibility, fibrotic HP patients showed increased frequencies of HLA A*02 (46.7% vs 25.7%; OR=2.53, p = 0.02) and HLA DRB1*14 (10.0% vs 0.7%; OR=15.44, p=0.02) alleles when compared with exposed controls, although not statistically significant after correction for multiple comparisons. TNF-α G/G genotype (associated with low TNF-α production) frequencies were significantly increased among the non-fibrotic/inflammatory HP patients comparatively to fibrotic presentations (88% vs 60%; RR=0.44; p=0.04) and controls (88% vs 63%, OR 4.33, p=0.037). Also, these patients had a significantly increased frequency of the G allele (94.0% vs 73.3%, RR=0.44, p=0.01), while fibrotic HP patients predominantly presented the A allele (26.7% vs 6.0%, RR=2.28, p=0.01). CONCLUSIONS: Our results support the hypothesis that fibrotic and non-fibrotic HP subtypes exhibit a distinct profile of TNF-α and HLA polymorphisms, which may be relevant to predict disease course and better define treatment strategies.

Cost-effectiveness analysis of grass pollen specific immunotherapy in children with allergic rhinitis compared to the standard of care symptomatic treatment in Portugal.

Summary: Background. Cost-effectiveness studies evaluating allergen immunotherapy (AIT) in children are scarce. We aim to compare the cost-effectiveness of subcutaneous (SCIT) and sublingual immunotherapy (SLIT) against standard-of-care (SOC) treatment in children with grass pollen allergic rhinitis. Methods. We created a Markov model to compare the three strategies over a 10-year horizon. SOC was the reference to calculate the incremental cost-effectiveness ratio (ICER). Deterministic and probabilistic sensitivity analysis were used to assess models' uncertainty. Results. We obtained an ICER of € 12,605 and € 6,318 for SLIT and SCIT, respectively. In sensitivity analysis, SCIT was more cost-effective than SLIT. Conclusions. AIT is cost-effective in children with grass pollen allergic rhinitis, especially for the subcutaneous route.

Tratamiento con inhibidores de la bomba de protones. ¿Realmente lo necesita el paciente? / Proton-pump inhibitors treatment. Does your patient really need it?

Introducción: Los inhibidores de la bomba de protones (IBP) son fármacos utilizados frecuentemente para el manejo de diferentes enfermedades gastrointestinales. Aunque sus indicaciones y dosis están bien establecidas, se han comunicado elevadas tasas de maluso. Métodos: Estudio observacional transversal realizado en un servicio de urgencias de un hospital terciario. Pacientes adultos que acudían por distintas patologías fueron invitados a participar. Se evaluó la correcta indicación del IBP, además de su dosis, duración del tratamiento y facultativo prescriptor. Resultados: Se incluyeron 300 pacientes. La indicación se consideró correcta en 142 pacientes (47,3%), siendo la indicación más frecuente la profilaxis de enteropatía inducida por AINE/AAS (n=95; 31,7%). La «gastroprotección» en paciente polimedicados, sin fármacos gastroerosivos fue la principal indicación inadecuada (n=82; 27,3%) seguida de la profilaxis innecesaria en pacientes menores de 60 años tratados en monoterapia con un fármaco gastroerosivo. La mediana del tiempo de prescripción fue de 31 meses (RIC: 9-72) con un intervalo de 1-360 meses. El tiempo de prescripción era inferior en aquellos con indicación correcta (42,3 vs. 59,6 meses, p=0,02). El médico de atención primaria era el prescriptor más frecuente (n=165; 55%), seguido del gastroenterólogo (n=38; 12,7%), sin encontrar diferencias significativas en cuanto a la adecuación de la prescripción. Conclusiones: Estudios como el presente alertan de la persistencia de unas elevadas sobreutilización y maluso de los IBP. La desprescripción, cuando el IBP no está indicado, puede ayudar a controlar el gasto sanitario innecesario y a evitar iatrogenia (AU)

Introduction: Proton-pump inhibitors (PPI) are frequently prescribed for wide gastrointestinal disorders. The indications are well established, although a high rate of misuse has been reported. Methods: Observation cross-sectional study conducted a tertiary hospital. Adult patients who attended the emergency department were eligible. The appropriate indication was evaluated. Also, the prescription period, dosage and the prescribing clinician were reviewed. Results: 300 patients were included. The indication was adequate in 142 patients (47.3%). The main indication was the primary prophylaxis for NSAIDs/ASA-induced enteropathy (n=95 patients, 31.7%). Polypharmacy was the main misuse indication (n=82 patients, 27.3%). The median prescription duration was 31 months (IQR 9-72), ranging from one month to 360 months. The duration was lower in those with correct indication (42.3 vs 59.6 months, P=.02). The primary care physician was the main responsible for prescription (n=165 patients, 55%), followed by gastroenterologist (n=38 patients, 12.7%) without significant differences in appropriateness by speciality. Conclusions: Studies like this raise awareness about the PPI overuse and misuse. Deprescribing should be considered as essential to reduce iatrogenic risk and redundant health expenditure (AU)

[Proton-pump inhibitors treatment. Does your patient really need it?] / Tratamiento con inhibidores de la bomba de protones. ¿Realmente lo necesita el paciente?

INTRODUCTION: Proton-pump inhibitors (PPI) are frequently prescribed for wide gastrointestinal disorders. The indications are well established, although a high rate of misuse has been reported. METHODS: Observation cross-sectional study conducted a tertiary hospital. Adult patients who attended the emergency department were eligible. The appropriate indication was evaluated. Also, the prescription period, dosage and the prescribing clinician were reviewed. RESULTS: 300 patients were included. The indication was adequate in 142 patients (47.3%). The main indication was the primary prophylaxis for NSAIDs/ASA-induced enteropathy (n=95 patients, 31.7%). Polypharmacy was the main misuse indication (n=82 patients, 27.3%). The median prescription duration was 31 months (IQR 9-72), ranging from one month to 360 months. The duration was lower in those with correct indication (42.3 vs 59.6 months, P=.02). The primary care physician was the main responsible for prescription (n=165 patients, 55%), followed by gastroenterologist (n=38 patients, 12.7%) without significant differences in appropriateness by speciality. CONCLUSIONS: Studies like this raise awareness about the PPI overuse and misuse. Deprescribing should be considered as essential to reduce iatrogenic risk and redundant health expenditure.

Anaphylaxis: A Decade of a Nationwide Allergy Society Registry

Background: Anaphylaxis is an acute, life-threatening, multiorgan hypersensitivity reaction.Objective: The aim of this study was to identify the causes of anaphylaxis in Portugal in order to improve our knowledge of epidemiology and management.Methods: We implemented a nationwide notification system for anaphylaxis over a 10-year period, with voluntary reporting by allergists. Data on 1783 patients with anaphylaxis were included. Etiopathogenesis, manifestations, and clinical management were characterized in detail for both children and adults.Results: The mean age was 32.7 (20.3) years, and 30% were under 18 years of age; 58% were female. The mean age at the first anaphylaxis episode was 27.5 (20.4) years (ranging from 1 month to 88 years). The main culprits of anaphylaxis were foods (48%), drugs (37%) (main trigger in adults, 48%), and hymenoptera venom (7%). The main culprit foods were shellfish (27%), fresh fruit (17%), cow’s milk (16%), tree nuts (15%), fish (8%), egg (7%), and peanut (7%). The main drugs were nonsteroidal anti-inflammatory drugs (43%), antibiotics (39%), and anesthetic agents (6%). Other causes included exercise (3%), latex (2%), cold-induced anaphylaxis (2%), and idiopathic anaphylaxis (2%). Most patients (80%) were admitted to the emergency department; only 43% received adrenaline. Anaphylaxis recurred in 41% of patients (21% with ≥3 anaphylactic episodes); 7% used an adrenaline autoinjector device.Conclusions: Food is the leading cause of anaphylaxis in Portugal, while drugs were the main elicitors in adults. We emphasize undertreatment with adrenaline and recurrent episodes, highlighting the need to improve diagnostic and therapeutic approaches to anaphylaxis (AU)

Antecedentes: La anafilaxia es una reacción de hipersensibilidad sistémica potencialmente mortal.Objetivo: El objetivo de este estudio fue el identificar las causas de la anafilaxia en Portugal para mejorar el conocimiento de la epidemiologíay del manejo de la enfermedad.Métodos: Durante un período de 10 años, se implementó un sistema nacional de notificación de anafilaxia, por parte de los alergólogos,mediante la emisión de informes voluntarios. Se recogieron datos de 1.783 pacientes con anafilaxia, pediátricos y adultos, relativos a laetiopatogenia, las manifestaciones clínicas y el manejo clínico de la misma.Resultados: La edad media fue de 32,7 ± 20,3 años, siendo el 30% de los pacientes menores de 18 años. El 58% fueron mujeres. Laedad media del primer episodio de anafilaxia fue de 27,5 ± 20,4 años (desde 1 mes hasta 88 años). Los principales agentes responsablesde anafilaxia fueron los alimentos (48%), los medicamentos (37%), que fue el principal desencadenante en los pacientes adultos, y losvenenos de himenópteros (7%). Los principales alimentos responsables fueron: mariscos (27%), frutas frescas (17%), leche de vaca (16%),nueces (15%), pescado (8%), huevo (7%) y cacahuete (7%). Los principales fármacos, fueron los antiinflamatorios no esteroideos (43%),antibióticos (39%) y anestésicos (6%). Entre otras causas implicadas se incluyó: ejercicio físico (3%), látex (2%), frío (2%) e idiopática (2%). La mayoría de los pacientes fueron atendidos en el servicio de urgencias (80%), y solo el 43% recibió tratamiento con adrenalina.La recurrencia de la anafilaxia ocurrió en el 41% de los pacientes (21% con ≥3 episodios anafilácticos). El 7% utilizó un dispositivoautoinyector de adrenalina.Conclusiones: Los alimentos son la principal causa de anafilaxia en Portugal y en el subgrupo de pacientes adultos, lo son los medicamentos

Expression of spindle assembly checkpoint proteins BubR1 and Mad2 expression as potential biomarkers of malignant transformation of oral leukoplakia: an observational cohort study.

BACKGROUND: The Spindle Assembly Checkpoint (SAC) is a surveillance mechanism essential to ensure the accuracy of chromosome segregation during mitosis. Our aim was to evaluate the expression of SAC proteins in oral carcinogenesis, and to assess their potential in predicting malignant transformation of oral leukoplakia. MATERIAL AND METHODS: We analysed the immunoexpression of BubR1, Mad2, Bub3, and Spindly proteins in 64 oral biopsies from 52 oral leukoplakias and 12 normal tissues. Univariate and multivariate analysis were performed to evaluate predictive factors for malignant transformation (MT). RESULTS: We observed that BubR1 and Mad2 were more highly expressed in high dysplasia grade lesions than in low grade or normal tissues (P<0.05). High expression of Spindly was significantly correlated with a high Ki-67 score (P=0.004). Six (11.5%) oral leukoplakias underwent malignant transformation. In univariate analysis, the binary dysplasia grade (high grade) (P<0.001) was associated with a higher risk of malignant transformation as well as high BubR1 (P<0.001) and high Mad2 (P=0.013) expression. In multivariate analysis, high expression of BubR1 and Mad2 when combined showed an increased risk for malignant transformation (P=0.013; HR of 4.6, 95% CI of 1.4-15.1). CONCLUSIONS: Our findings reveal that BubR1 and Mad2 were associated with an increased risk for malignant transformation independently of histological grade and could be potential and useful predictive risk markers of malignant transformation in oral leukoplakias.

Airborne Food Allergen and Aeroallergen Levels in Health Care Settings: An Unaccounted for but Potentially Relevant Source of Exposure?

BACKGROUND AND OBJECTIVE: Exposure to airborne allergens of biological origin is associated with the development and exacerbation of allergic asthma and rhinitis. Assessment of allergen exposure in health care facilities may improve monitoring of hygiene and surveillance of specific allergens that can cause symptoms in sensitized persons. Objective: To assess concentrations of airborne food and aeroallergens in various health care settings in Portugal. METHODS: Dust was vacuumed from primary health care centers in Lisbon and from the emergency department, day hospital, internal medicine ward, operating room, and outpatient clinic of a university central hospital in Porto. Samples were sieved, weighed, and extracted, and concentrations of Nbos d 5, Cor a 9, Gal d 2, Ara h 3, Ara h 6, Der p 1, Fel d 1, Can f 1, Bla g 2, Alt a 1, and Phl p 5 were determined using a multiplex array for allergens (MARIA). RESULTS: All airborne food and aeroallergens were found in at least 1 sampled area, except for Alt a 1. Levels of Der p 1 and Fel d 1 ranged from 13.0 µg/g to 971.0 µg/g and from 7.0 µg/g to 4618.8 µg/g, respectively. Higher levels of food allergens were found in the emergency department (Nbos d 5, 16 034.0 µg/g; and Cor a 9, 10 649.5 µg/g). CONCLUSIONS: Except for the operating room, exposure levels for dust mite and cat and dog dander in health care facilities were above the values associated with sensitization and allergic asthma or rhinitis symptoms in sensitized persons.

Brachial plexus tumors extending into the cervicothoracic spine: a review with operative nuances and outcomes

Background The rarity and anatomical complexity of brachial plexus tumors (BPTs) impose many challenges onto surgeons performing surgical resections, especially when these tumors invade the cervicothoracic spine. Treatment choices and surgery outcomes heavily depend on anatomical location and tumor type. Methods The authors performed an extensive review of the published literature (PubMed) focusing on “brachial plexus tumors” that identified invasion of the cervicothoracic spine. Result The search yielded 2774 articles pertaining to “brachial plexus tumors”. Articles not in the English language or involving cervicothoracic spinal invasion were excluded. Conclusions Recent research has shown that the most common method used to resect tumors of the proximal roots is the dorsal subscapular approach. Despite its association with high morbidity rate, this technique offers excellent exposure to the spinal roots and intraforaminal portion of the spinal nerve. The dorsal approach is used to resect recurrent lower trunk tumors and dumbbell-shaped neurofibromas, yet it is also the least common overall approach used in brachial plexus tumor resections. The ventral or anterior technique is commonly used to resect tumors at the cord to division level, and root to trunk level. Motor complications, transient nerve palsy, and bleeding are among the most common complications of the anterior supraclavicular approach. Further controlled studies are needed to fully determine the optimal surgical approach used to obtain the best outcomes and least complications for each type of brachial plexus tumor (AU)

The immune response to SARS-CoV-2 and COVID-19 immunopathology - Current perspectives.

SARS-CoV-2 is a new beta coronavirus, similar to SARS-CoV-1, that emerged at the end of 2019 in the Hubei province of China. It is responsible for coronavirus disease 2019 (COVID-19), which was declared a pandemic by the World Health Organization on March 11, 2020. The ability to gain quick control of the pandemic has been hampered by a lack of detailed knowledge about SARS-CoV-2-host interactions, mainly in relation to viral biology and host immune response. The rapid clinical course seen in COVID-19 indicates that infection control in asymptomatic patients or patients with mild disease is probably due to the innate immune response, as, considering that SARS-CoV-2 is new to humans, an effective adaptive response would not be expected to occur until approximately 2-3 weeks after contact with the virus. Antiviral innate immunity has humoral components (complement and coagulation-fibrinolysis systems, soluble proteins that recognize glycans on cell surface, interferons, chemokines, and naturally occurring antibodies) and cellular components (natural killer cells and other innate lymphocytes). Failure of this system would pave the way for uncontrolled viral replication in the airways and the mounting of an adaptive immune response, potentially amplified by an inflammatory cascade. Severe COVID-19 appears to be due not only to viral infection but also to a dysregulated immune and inflammatory response. In this paper, the authors review the most recent publications on the immunobiology of SARS-CoV-2, virus interactions with target cells, and host immune responses, and highlight possible associations between deficient innate and acquired immune responses and disease progression and mortality. Immunotherapeutic strategies targeting both the virus and dysfunctional immune responses are also addressed.

Comparación de biomarcadores de primer trimestre en gestantes normotensas según su grado de obesidad en el tercer trimestre / Comparison of first trimester biomarkers in normotensive pregnancies according to their level of obesity in the third trimester

INTRODUCCIÓN: Nuestro trabajo tiene como objetivo aumentar la eficiencia del cribado de aneuploidías del primer trimestre de la gestación mediante la creación de modelos predictivos que sirvan para identificar gestantes en riesgo de desarrollar sobrepeso u obesidad en el tercer trimestre e instaurar medidas preventivas de obesidad a partir de ellos. MÉTODOS: Estudio observacional de tipo ambispectivo realizado en atención primaria, en el que se han recogido un total de 380 registros correspondientes a otros tantos embarazos. Se han muestreado 6 centros de salud con las variables siguientes: edad en la gestación, proteína A placentaria asociada al embarazo (PAPP-A) (mU/ml), gonadotropina coriónica humana (b-HCG) (ng/ml), semana de recogida de la muestra para el cribado de primer trimestre, índice de masa corporal (IMC) a las 12 y a las 28 semanas de gestación, TSH a las 12 semanas de gestación, presión arterial sistólica (PAS), presión arterial diastólica (PAD) y presión arterial media (PAM) a las 12 y a las 28 semanas de gestación. Se recodificó la variable IMC a las 28 semanas, clasificando a las embarazadas en peso normal (IMC<25), sobrepeso (IMC 25-29,99) y obesas (IMC≥30). El IMC a las 28 semanas recodificada fue la variable resultado del modelo de regresión logística ordinal. Utilizamos el estudio ANOVA de varios factores para discernir diferencias entre las presiones arteriales. Se aceptó un error alfa del 5%. RESULTADOS: Las medianas de la PAPP-A y de b-HCG medidas en el primer trimestre son menores de manera progresiva en los grupos de gestantes con normopeso, sobrepeso y obesidad observadas en el tercer trimestre. Estos valores son predictores del peso en el tercer trimestre (regresión logística ordinal) (PAPP-A: p = 0,022; b-HCG: p = 0,002). Ninguna gestante desarrolló preeclampsia. Las PAS, PAD y PAM en el tercer trimestre fueron significativamente diferentes (ANOVA de varios factores; p < 0,05). DISCUSIÓN: La regresión logística ordinal demuestra que la disminución de los valores observada de PAPP-A y de b-HCG en el primer trimestre es predictora del grado de obesidad de forma significativa y gradual en una muestra de gestantes normotensas. No hemos querido confeccionar un modelo de regresión ordinal incluyendo el IMC de las 12 semanas por la colinealidad interna que aportaría al estar basada la variable resultado en él. El efecto predictor de la b-HCG es más homogéneo que el de la PAPP-A para el estado de sobrepeso y obesidad

INTRODUCTION: This study aims to improve the efficiency of aneuploidy screening in the first trimester of pregnancy by creating predictive models that serve to identify pregnant women at risk of becoming overweight or obese in the third trimester and to using them to implement preventive measures of obesity. METHODS: An ambispective, observational, primary care study was conducted in which a total of 380 records corresponding to as many pregnancies were collected. Samples were collected from patients of 6 health centres, in order to determine the following variables: age at gestation, pregnancy-associated plasma protein A (PAPP-A) (mU/ml), human chorionic gonadotropin (b-HCG) (ng/ml), sample collection week for first trimester screening, body mass index at 12 and 28 weeks gestation (BMI), TSH at 12 weeks gestation, and systolic, diastolic, and mean arterial blood pressure (SBP, DBP, and MBP, respectively) at 12 and 28 weeks gestation. The BMI variable was recoded at 28 weeks, classifying pregnant women as normal weight (BMI<25), overweight (BMI 25-29.99), or obese (BMI≥30). The recoded BMI at 28 weeks was the variable resulting from the ordinal logistic regression model. An ANOVA study of several factors was used to discern differences between arterial pressures. A 5% alpha error was accepted. RESULTS: The PAPP-A and b-HCG medians measured in the first trimester are progressively lower in the groups of pregnant women with normal weight, overweight, and obesity observed in the third trimester. These values are predictors of the weight in the third trimester (ordinal logistic regression) (PAPP-A: P=.022; b-HCG: P=.002). No pregnant woman developed pre-eclampsia. The SBP, DBP, and MBP in the third trimester were significantly different (ANOVA in several factors; P<.05). DISCUSSION: The ordinal logistic regression demonstrates that the decrease in the observed values of PAPP-A and b-HCG in the first trimester is a predictor of the level of significant and gradual obesity in a sample of normotensive pregnant women. An ordinal regression model including the 12-week BMI was not made due to the internal collinearity that it would provide if the result variable was based on it. The predictive effect of b-HCG is more homogeneous than that of PAPP-A for the level of overweight and obesity

Brachial plexus tumors extending into the cervicothoracic spine: a review with operative nuances and outcomes.

BACKGROUND: The rarity and anatomical complexity of brachial plexus tumors (BPTs) impose many challenges onto surgeons performing surgical resections, especially when these tumors invade the cervicothoracic spine. Treatment choices and surgery outcomes heavily depend on anatomical location and tumor type. METHODS: The authors performed an extensive review of the published literature (PubMed) focusing on "brachial plexus tumors" that identified invasion of the cervicothoracic spine. RESULTS: The search yielded 2774 articles pertaining to "brachial plexus tumors". Articles not in the English language or involving cervicothoracic spinal invasion were excluded. CONCLUSIONS: Recent research has shown that the most common method used to resect tumors of the proximal roots is the dorsal subscapular approach. Despite its association with high morbidity rate, this technique offers excellent exposure to the spinal roots and intraforaminal portion of the spinal nerve. The dorsal approach is used to resect recurrent lower trunk tumors and dumbbell-shaped neurofibromas, yet it is also the least common overall approach used in brachial plexus tumor resections. The ventral or anterior technique is commonly used to resect tumors at the cord to division level, and root to trunk level. Motor complications, transient nerve palsy, and bleeding are among the most common complications of the anterior supraclavicular approach. Further controlled studies are needed to fully determine the optimal surgical approach used to obtain the best outcomes and least complications for each type of brachial plexus tumor.

Integrating genetic and clinical data to predict impulse control disorders in Parkinson's disease.

BACKGROUND AND PURPOSE: Impulse control disorders (ICDs) are frequent in Parkinson's disease (PD), with associated clinical and genetic risk factors. This study was aimed at analyzing the clinical features and the genetic background that underlie ICDs in PD. METHODS: We included 353 patients with PD in this study (58.9% men, mean age 62.4 ± 10.58 years, mean age at disease onset 52.71 ± 11.94 years). We used the validated Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease for ICDs screening. Motor, nonmotor, and treatment-related features were evaluated according to the presence of ICDs. Twenty-one variants related to dopaminergic, serotonergic, glutamatergic, and opioid neurotransmitter systems were assessed. Association studies between polymorphisms and ICDs were performed. The combination of clinical and genetic variables was analyzed with receiver operating characteristic curves to assess the predictability of experiencing ICDs. RESULTS: Impulse control disorders appeared in 25.1% of the cases. Patients with ICDs were younger and presented a higher rate of anxiety. Treatment with dopamine agonists increased the risk of ICDs and it was dose dependent (P < 0.05). Genetic association studies showed that the DOPA decarboxylase gene (DDC), rs1451375, might modulate the risk of ICDs. Plotting the clinical-genetic model, the predictability of ICDs increased 11% (area under curve = 0.80; z = 3.22, P = 0.001) when adding the genotype data for single nucleotide polymorphisms. CONCLUSIONS: Polymorphisms in DDC might act as risk markers for ICDs in PD. The predictability of experiencing ICDs increased by adding genetic factors to clinical features. It is therefore important to assess the patient's genetic background to identify individuals at risk for ICDs.

Brain event-related potentials predict individual differences in inhibitory control.

Stop-signal reaction time (SSRT), the time needed to cancel an already-initiated motor response, quantifies individual differences in inhibitory control. Electrophysiological correlates of SSRT have primarily focused on late event-related potential (ERP) components over midline scalp regions from successfully inhibited stop trials. SSRT is robustly associated with the P300, there is mixed evidence for N200 involvement, and there is little information on the role of early ERP components. Here, machine learning was first used to interrogate ERPs during both successful and failed stop trials from 64 scalp electrodes at 4 ms resolution (n = 148). The most predictive model included data from both successful and failed stop trials, with a cross-validated Pearson's r of 0.32 between measured and predicted SSRT, significantly higher than null models. From successful stop trials, spatio-temporal features overlapping the N200 in right frontal areas and the P300 in frontocentral areas predicted SSRT, as did early ERP activity (<200 ms). As a demonstration of the reproducibility of these findings, the application of this model to a separate dataset of 97 participants was also significant (r = 0.29). These results show that ERPs during failed stops are relevant to SSRT, and that both early and late ERP activity contribute to individual differences in SSRT. Notably, the right lateralized N200, which predicted SSRT here, is not often observed in neurotypical adults. Both the ascending slope and peak of the P300 component predicted SSRT. These results were replicable, both within the training sample and when applied to ERPs from a separate dataset.