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In recent years, some new concepts have been added to asthma treatment such as "anti-inflammatory reliever" (β2-agonist use associated to an inhaled corticosteroid (ICS) as a reliever treatment) that combines the benefits of both therapies and provides short- and long-term benefits for treatment in asthma patients. Robust evidence has been presented in patients over 12 years, and the main changes in the international guidelines for asthma treatment were originally made in this age group. However, a few suggestions have been added to treatments in younger patients, in part because of the scarce evidence that exists in this group. We aim to analyze the information regarding the utilization of ICS + fast-acting beta-agonist (FABA) combination in children between 6 and 11 years. Although up until today only three published trials exist (two studies use beclomethasone + albuterol and one study uses budesonide + formoterol), they provide significant information on the benefits of ICS + FABA use in this population. [ABSTRACT FROM AUTHOR]

Resumen Introducción La piedra angular del tratamiento de alergia alimentaria es la eliminación de los alimentos causantes. Sin embargo, los niños que restringen el consumo de alimentos básicos tienen un mayor riesgo de desnutrición. El objetivo del estudio fue identificar el estado nutricional de pacientes con dieta de eliminación e identificar la proporción de pacientes del grupo con verdadera alergia alimentaria. Métodos Se realizó un estudio transversal de enero a octubre de 2014 en el Hospital Infantil de México Federico Gómez. Se incluyeron pacientes de 1 a 11 años con historia de eliminación de, al menos, uno de cinco alimentos (huevo, leche, trigo, maíz, soya) por un mínimo de 6 meses. Se realizó la valoración nutricional completa y se compararon los índices antropométricos con tablas de Z score para la edad. Se analizaron los datos por medio de estadística descriptiva, y posteriormente con prueba de Kruskal-Wallis y correlación de Spearman. Resultados Los alimentos más frecuentemente eliminados fueron leche, soya, huevo, maíz y trigo. Al comparar el número de alimentos eliminados de la dieta con los distintos índices antropométricos evaluados, se encontró que entre mayor cantidad de alimentos eliminados, el score Z de peso para la edad (PE) y talla para la edad (TE), así como peso para la talla (PT) fueron menores, y el más afectado fue la reserva grasa. Solamente en el 5% de los niños se corroboró alergia alimentaria. Conclusiones Nuestro estudio confirma la necesidad de una correcta asesoría nutricional en aquellos pacientes que cuenten con dietas de eliminación, así como el sobrediagnóstico que existe de alergia alimentaria. Background The backbone of food allergy treatment is the restriction of causative foods. These interventions have shown that children who restrict the consumption of basic foods have a higher risk of malnutrition. The aim of the study was to identify the nutritional status of patients with elimination diet, characterizing their anthropometric indexes and identifying the percentage of patients in the group with true food allergies. Methods A cross-sectional study was carried out from January to October 2014 at the Hospital Infantil de Mexico Federico Gomez. Patients 1 to 11 years of age with a history of elimination of at least one of five foods (eggs, milk, wheat, corn, soybeans) for a minimum of 6 months were included. Full nutritional assessment was performed by comparing the anthropometric indexes to z score for age. Data analysis used descriptive statistics. Kruskal-Wallis and Spearman correlation were performed. Results The most frequent eliminated foods were milk, soy, eggs, corn, and wheat. Comparing the number of foods eliminated with different anthropometric indexes, with a greater amount of eliminated food, the z-score of weight/age (W/A), height/age (H/A) and weight/height (W/H) were lower and the most affected index was fat reserve. Only in 5% of children was food allergy confirmed. Conclusions The study confirms the need for nutrition counseling for patients who have elimination diets and overdiagnosis of food allergy. [ABSTRACT FROM AUTHOR]

Introduction: Thrombocytopenia is often associated with diseases like dengue, Idiopathic Thrombocytopenic Purpura (ITP), malignancy, aplastic anaemia, drug induced thrombocytopenic purpura and haemolytic uremic syndrome. There are no effective methods to treat thrombocytopenia. Carica papaya (C. papaya) fruit pulp juice contains many constituents that can act on the bone marrow and enhance its ability to produce platelets. Aim: To evaluate the effects of fresh Carica papaya unripe and ripe fruit pulp juice on platelet count in cyclophosphamide induced thrombocytopenic rat model. Materials and Methods: A total of 24 male Albino Wistar rats were grouped into 'Control' (A), 'Drug control' (B), 'Papaya unripe fruit pulp' (C) and 'Papaya ripe fruit pulp' (D) groups. Thrombocytopenia was induced by three doses of cyclophosphamide (50 mg/kg body weight) given subcutaneously to Groups B, C and D from day 1 to 3. Groups C and D received Carica papaya unripe and ripe fruit pulp juice orally from day 11 to 14 respectively. Platelet count, Packed Cell Volume (PCV), Red Blood Cell (RBC) count, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and serum creatinine levels was measured on day 1, 10, 14 and 21. For comparison between groups, 'unpaired t-test' and within the group, paired t-test were used. A p-value ≤0.05 was considered significant. Results: There was significant increase in platelet count in Group C (6.27x105/µL) and D (20.5x105/µL) compared to drug control B (3.94x105/µL) on day 14. Within the group, there was significant increase in platelet count in Group C and D on day 14 compared to day 10. Between the groups, Group D showed higher platelet increasing effect on thrombocytopenic rats. Conclusion: Carica papaya ripe and unripe fruit pulp juice has platelet enhancing effect. Further preclinical studies are required to identify those chemicals of C. papaya fruit responsible for boosting thrombopoiesis. [ABSTRACT FROM AUTHOR]

Asparagine (N)-linked glycosylation regulates numerous cellular activities, such as glycoprotein quality control, intracellu-lar trafficking, and cell-cell communications. In eukaryotes, the glycosylation reaction is catalyzed by oligosaccharyltransferase (OST), a multimembrane protein complex that is localized in the endoplasmic reticulum (ER). During N-glycosylation in the ER, the protein-unbound form of oligosaccharides (free oligosaccharides; fOSs), which is structurally related to N-glycan, is released into the ER lumen. However, the enzyme responsible for this process remains unidentified. Here, we demonstrate that eukaryotic OST generates fOSs. Biochemical and genetic analyses using mutant strains of Saccharomyces cerevisiae revealed that the generation of fOSs is tightly correlated with the N-glycosylation activity of OST. Furthermore, we present evidence that the purified OST complex can generate fOSs by hydrolyzing dolichol-linked oligosaccharide, the glycan donor substrate for N-glycosylation. The heterologous expression of a single subunit of OST from the protozoan Leishmania major in S. cerevisiae demonstrated that this enzyme functions both in N-glycosylation and generation of fOSs. This study provides insight into the mechanism of PNGase-independent formation of fOSs. [ABSTRACT FROM AUTHOR]

We developed a diabetes risk score using a novel analytical approach and tested its diagnostic performance to detect individuals at high risk of diabetes, by applying it to the Qatari population. A representative random sample of 5,000 Qataris selected at different time points was simulated using a diabetes mathematical model. Logistic regression was used to derive the score using age, sex, obesity, smoking, and physical inactivity as predictive variables. Performance diagnostics, validity, and potential yields of a diabetes testing program were evaluated. In 2020, the area under the curve (AUC) was 0.79 and sensitivity and specificity were 79.0% and 66.8%, respectively. Positive and negative predictive values (PPV and NPV) were 36.1% and 93.0%, with 42.0% of Qataris being at high diabetes risk. In 2030, projected AUC was 0.78 and sensitivity and specificity were 77.5% and 65.8%. PPV and NPV were 36.8% and 92.0%, with 43.0% of Qataris being at high diabetes risk. In 2050, AUC was 0.76 and sensitivity and specificity were 74.4% and 64.5%. PPV and NPV were 40.4% and 88.7%, with 45.0% of Qataris being at high diabetes risk. This model-based score demonstrated comparable performance to a data-derived score. The derived self-complete risk score provides an effective tool for initial diabetes screening, and for targeted lifestyle counselling and prevention programs. [ABSTRACT FROM AUTHOR]

Oligosaccharyltransferase (OST) is an essential membrane protein complex in the endoplasmic reticulum, where it transfers an oligosaccharide from a dolicholpyrophosphate– activated donor to glycosylation sites of secretory proteins. Here we describe the atomic structure of yeast OST determined by cryo–electron microscopy, revealing a conserved subunit arrangement. The active site of the catalytic STT3 subunit points away from the center of the complex, allowing unhindered access to substrates. The dolichol-pyrophosphate moiety binds to a lipid-exposed groove of STT3, whereas two noncatalytic subunits and an ordered N-glycan form a membrane-proximal pocket for the oligosaccharide. The acceptor polypeptide site faces an oxidoreductase domain in stand-alone OST complexes or is immediately adjacent to the translocon, suggesting how eukaryotic OSTs efficiently glycosylate a large number of polypeptides before their folding. [ABSTRACT FROM AUTHOR]

The process of pyroptosis is mediated by inflammasomes and a downstream effector known as gasdermin D (GSDMD). Upon cleavage by inflammasome-associated caspases, the N-terminal domain of GSDMD forms membrane pores that promote cytolysis. Numerous proteins promote GSDMD cleavage, but none are known to be required for pore formation after GSDMD cleavage. Herein, we report a forward genetic screen that identified the Ragulator-Rag complex as being necessary for GSDMD pore formation and pyroptosis in macrophages. Mechanistic analysis revealed that Ragulator-Rag is not required for GSDMD cleavage upon inflammasome activation but rather promotes GSDMD oligomerization in the plasma membrane. Defects in GSDMD oligomerization and pore formation can be rescued by mitochondrial poisons that stimulate reactive oxygen species (ROS) production, and ROS modulation impacts the ability of inflammasome pathways to promote pore formation downstream of GSDMD cleavage. These findings reveal an unexpected link between key regulators of immunity (inflammasome-GSDMD) and metabolism (Ragulator-Rag). [Display omitted] • The Ragulator-Rag-mTORC1 pathway is required for pyroptosis induced by gasdermin D • Ragulator-Rag promotes gasdermin D oligomerization but not membrane localization • Ragulator-Rag promotes reactive oxygen species (ROS) production in macrophages • ROS promotes gasdermin D oligomerization, pore formation, and pyroptosis The Ragulator-Rag complex is required for the oligomerization of gasdermin D at the plasma membrane and for pore formation and pyroptosis in macrophages. [ABSTRACT FROM AUTHOR]