Integration of IgA and IgG Autoantigens Improves Performance of Biomarker Panels for Early Diagnosis of Lung Cancer.

Lung cancer (LC) remains the leading cause of mortality from malignant tumors worldwide. In our previous study, we surveyed both IgG and IgM-bound serological biomarkers and validated a panel of IgG-bound autoantigens for early LC diagnosis with 50% sensitivity at 90% specificity. To further improve the performance of these serological biomarkers, we surveyed HuProt arrays, comprised of 20,240 human proteins, for IgA-bound autoantigens because IgAs are a major immunoglobulin isotype in the lung. Integrating with IgG-bound autoantigens, we discovered and validated a combined biomarker panel using ELISA-format tests. Specifically, in Phase I, we obtained IgA-based autoimmune profiles of 69 early stage LC patients, 30 healthy subjects and 25 patients with lung benign lesions (LBL) on HuProt arrays and identified 28 proteins as candidate autoantigens that were significantly associated with early stage LC. In Phase II, we re-purified the autoantigens and converted them into an ELISA-format testing to profile an additional large cohort, comprised of 136 early stage LC patients, 58 healthy individuals, and 29 LBL patients. Integration of IgG autoimmune profiles allowed us to identify and validate a biomarker panel of three IgA autoantigens (i.e. BCL7A, and TRIM33 and MTERF4) and three IgG autoantigens (i.e. CTAG1A, DDX4 and MAGEC2) for diagnosis of early stage LC with 73.5% sensitivity at >85% specificity. In Phase III, the performance of this biomarker panel was confirmed with an independent cohort, comprised of 88 early stage LC patients, 18 LBL patients, and 36 healthy subjects. Finally, a blind test on 178 serum samples was conducted to confirm the performance of the biomarker panel. In summary, this study demonstrates for the first time that an integrated panel of IgA/IgG autoantigens can serve as valuable biomarkers to further improve the performance of early diagnosis of LC.

Factores socioculturales de la vulnerabilidad al sobrepeso durante los primeros años de vida en México.

OBJETIVO: Analizar el rol de los factores socioeconómicos y culturales en la vulnerabilidad a la obesidad en madres y sus hijos menores de dos años, en localidades del Sur de Morelos, México. Material y métodos. Se realizó trabajo de campo y observación no participativa. Durante 2019, se aplicaron 17 entrevistas semiestructuradas a una submuestra de una cohorte. Los datos fueron ordenados y analizados con apoyo del software Atlas-Ti v. 7, usando 18 códigos libres. RESULTADOS: Factores sociales como los ingresos del hogar y los roles de género, combinados con la influencia de la parentela y las creencias sobre la preferencia de la niñez por productos ultraprocesados, predisponen la disponibilidad de bebidas y alimentos calóricos que generan vulnerabilidad a la obesidad durante la infancia temprana. La actividad eco-nómica de las madres, la participación de los padres y evitar influencia de parientes puede predisponer una mejor calidad de los alimentos y mayor actividad física. CONCLUSIONES: La baja disponibilidad de alimentos saludables, los riesgos de inseguridad alimentaria y los factores familiares y culturales, que se presentan en contextos de vulnerabilidad económica y social, incrementan la vulnerabilidad del binomio madre-hijo a la obesidad.

A toolbox of immunoprecipitation-grade monoclonal antibodies to human transcription factors.

A key component of efforts to address the reproducibility crisis in biomedical research is the development of rigorously validated and renewable protein-affinity reagents. As part of the US National Institutes of Health (NIH) Protein Capture Reagents Program (PCRP), we have generated a collection of 1,406 highly validated immunoprecipitation- and/or immunoblotting-grade mouse monoclonal antibodies (mAbs) to 737 human transcription factors, using an integrated production and validation pipeline. We used HuProt human protein microarrays as a primary validation tool to identify mAbs with high specificity for their cognate targets. We further validated PCRP mAbs by means of multiple experimental applications, including immunoprecipitation, immunoblotting, chromatin immunoprecipitation followed by sequencing (ChIP-seq), and immunohistochemistry. We also conducted a meta-analysis that identified critical variables that contribute to the generation of high-quality mAbs. All validation data, protocols, and links to PCRP mAb suppliers are available at http://proteincapture.org.

Stakeholder analysis of the deliberation of an increase to the excise tax on sweetened beverages in Mexico.

OBJECTIVE: To present the results of a stakeholder analysis used to construct a map of the actors involved in the delib-eration of a proposal to increase the tax on sugar-sweetened beverages (SSB) in Mexico from 10 to 20 percent per liter. MATERIALS AND METHODS: A literature review and in-terviews to key actors were implemented. The analysis of the actors' power and position was made using Policymaker. RESULTS: There was concern for the obesity epidemic among all stakeholders, but little consensus on the way to solve it. Researchers and non-governmental organizations (NGO) support an increase in the tax on SSB, while government officials and industry representatives oppose this measure. CONCLUSION: Supporters of an increase to the tax on SSB need to build a coalition in order to force government officials to support this policy and successfully confront the soda industry, which has a solid opposing strategy and enormous financial resources to influence public opinion and congressmen.

Identification of Serological Biomarkers for Early Diagnosis of Lung Cancer Using a Protein Array-Based Approach.

Lung cancer (LC) remains the leading cause of mortality from malignant tumors worldwide. Currently, a lack of serological biomarkers for early LC diagnosis is a major roadblock for early intervention and prevention of LC. To undertake this challenge, we employed a two-phase strategy to discover and validate a biomarker panel using a protein array-based approach. In Phase I, we obtained serological autoimmune profiles of 80 LC patients and 20 healthy subjects on HuProt arrays, and identified 170 candidate proteins significantly associated with LC. In Phase II, we constructed a LC focused array with the 170 proteins, and profiled a large cohort, comprised of 352 LC patients, 93 healthy individuals, and 101 patients with lung benign lesions (LBL). The comparison of autoimmune profiles between the early stage LC and the combined group of healthy and LBL allowed us to identify and validate a biomarker panel of p53, HRas, and ETHE1 for diagnosis of early stage LC with 50% sensitivity at >90% specificity. Finally, the performance of this biomarker panel was confirmed in ELISA tests. In summary, this study represents one of the most comprehensive proteome-wide surveys with one of the largest (i.e. 1,101 unique samples) and most diverse (i.e. nine disease groups) cohorts, resulting in a biomarker panel with good performance.

Challenges to the development of taxation policies for sugar-sweetened beverages in Colombia.

Frequent consumption of sugar sweetened beverages (SSB) is related to the risks of developing overweight, obesity, cavities, diabetes and other diseases. Policies to significantly increase taxes on SSB have proven to be effective in reducing their consumption. The political debate on implementing these taxes in Colombia shows a series of barriers to placing this policy on the political agenda, and therefore, to its approval. This work analyses the political process involved in the struggle for the approval of an SBB tax in Colombia, as well as barriers and opportunities to putting it on the political agenda. This is done through a policy analysis with three research methods: a documentary analysis, political mapping of actors and semistructured interviews with key actors. Among the main findings, we have that actors who are in favour of the SSB tax stated that it is needed due to the health problems caused by SSB consumption, while those who opposed it argue that Colombia regulations are sufficient and already inform and educate consumers on excessive sugar consumption and its health implications. The Colombian political context is a barrier to SSB taxation, as the government favours and has a close connection with the food and SSB industry. In short, the policy issue has been reaching the agenda intermittently throughout the years. Nevertheless, new opportunities are arising after the COVID-19 pandemic and the 2022 administrative changes and further efforts from policy entrepreneurs are required to make this initiative progress in the political agenda.

Medioapical contractile pulses coordinated between cells regulate Drosophila eye morphogenesis.

Lattice cells (LCs) in the developing Drosophila retina constantly move and change shape before attaining final forms. Previously we showed that repeated contraction and expansion of apical cell contacts affect these dynamics. Here we describe a second contributing factor, the assembly of a medioapical actomyosin ring composed of nodes linked by filaments that attract each other, fuse, and contract the LCs' apical area. This medioapical actomyosin network is dependent on Rho1 and its known effectors. Apical cell area contraction alternates with relaxation, generating pulsatile changes in apical cell area. Strikingly, cycles of contraction and relaxation of cell area are reciprocally synchronized between adjacent LCs. Further, in a genetic screen, we identified RhoGEF2 as an activator of these Rho1 functions and RhoGAP71E/C-GAP as an inhibitor. Thus, Rho1 signaling regulates pulsatile medioapical actomyosin contraction exerting force on neighboring cells, coordinating cell behavior across the epithelium. This ultimately serves to control cell shape and maintain tissue integrity during epithelial morphogenesis of the retina.

Pink Pigmented Facultative Methylotrophic Bacteria Isolated from Fermented Philippine Shrimp Paste.

Pink pigmented facultative methylotrophic (PPFM) bacteria are ecologically distributed microorganisms. They have been isolated in many types of ecosystems like soil, water, air, in association with plants and even as pathogens in humans. However, a yet unexplored area for PPFM bacteria research is in food. Hence, the objective of this study was to establish the presence of PPFM bacteria in Philippine fermented food, in particular shrimp paste, and characterise them phenotypically and genotypically. A total of 13 PPFM bacteria were obtained from Philippine shrimp paste. Sequencing of the 16S rRNA gene revealed that the PPFM bacterial isolates belong to the genus Methylobacterium. A total of 35 phenotypic characterisations were performed that included morphological, biochemical and physiological tests. Phylogenetic tree was constructed to establish the genetic relatedness of the isolates. Morphological test results showed that all 13 isolates were consistent with the established phenotypic characters of the genus such as pink colony colour, Gram negative and rod-shaped. Biochemically, the use of API® 20 NE tests showed heterogeneity of results and physiological tests exhibited that the isolates are primarily mesophilic and halotolerant, being able to grow at 2% salt. Phylogenetic analysis showed that the isolates are Methylobacterium populi, M. dankookense, M. lusitanum, M. radiotolerans and M. zatmanii. This study confirmed the presence and diversity of PPFM bacteria in Philippine shrimp paste. Further studies are needed to show the functional activity of Methylobacterium in Philippine shrimp paste production.

Stakeholder analysis of the deliberation of an increase to the excise tax on sweetened beverages in Mexico / Análisis de grupos de interés sobre la deliberación del incremento al impuesto a bebidas azucaradas en México

Abstract Objective: To present the results of a stakeholder analysis used to construct a map of the actors involved in the delib- eration of a proposal to increase the tax on sugar-sweetened beverages (SSB) in Mexico from 10 to 20 percent per liter. Materials and methods: A literature review and in- terviews to key actors were implemented. The analysis of the actors' power and position was made using Policymaker. Results: There was concern for the obesity epidemic among all stakeholders, but little consensus on the way to solve it. Researchers and non-governmental organizations (NGO) support an increase in the tax on SSB, while government officials and industry representatives oppose this measure. Conclusión: Supporters of an increase to the tax on SSB need to build a coalition in order to force government officials to support this policy and successfully confront the soda industry, which has a solid opposing strategy and enormous financial resources to influence public opinion and congressmen.

Resumen Objetivo: Presentar los resultados de un análisis de grupos de interés para definir un mapa de los actores involucrados en la deliberación de una propuesta para incrementar el impuesto a bebidas azucaradas (BA) en México del 10 al 20% por litro. Material y métodos: Se revisó la literatura y se entrevistó a actores clave. El análisis del poder y posición de los actores se realizó con el programa Policymaker. Resultados: Se identificó una amplia preocupación por la epidemia de obesidad, pero poco consenso sobre cómo resolverla. Los investigadores y las Organizaciones No Gubernamentales (ONG) apoyan un incremento en el impuesto a las BA, mientras que los funcionarios gubernamentales y los representantes de la industria se oponen a dicha medida. Conclusión: Quienes apoyan un incremento al impuesto deben crear una coalición que fuerce a los funcionarios gubernamentales a apoyar el aumento y confrontar exitosa- mente a la industria, la cual cuenta con una estrategia sólida y recursos financieros abundantes para influir en la opinión pública y en los legisladores.

Breastfeeding and feeding practices in the first year of life and its association with overweight and obesity of children in Mexico / Prácticas de lactancia y alimentación en el primer año de vida y su asociación con sobrepeso y obesidad de niños en México

Abstract Objectives: to evaluate feeding practices in the first year of life and their association with the development of overweight and obesity in children in Mexico. Methods: the association between overweight and obesity with different feeding practices were evaluated. The data was processed using the statistical package Stata version 14 using logistic regression models. Results: 396 children were evaluated; the prevalence of overweight and obesity was 6% and 7.7% presented a possible risk of overweight. 6.9% had exclusive breastfeeding in the first 6 months of life and 71.7% were fed infant formula. The variables significantly associated with the development of overweight and obesity in the first year of life were the age of the child (p =0.043, RR=0.57), the introduction of fluids in the first three days of life (p=0.02, RR=2.90), consumption of foods with a high sugar content (p =0.01, RR=0.25), consumption of milk other than breast (p =0.02, RR3.25) and egg consumption (p =0.05; RR=0.28). Conclusions: our results show that it is essential to attend complementary feeding practices and reinforce exclusive breastfeeding in the first year of life, as measures to prevent overweight and obesity to improve health in childhood.

Resumen Objetivos: evaluar las prácticas de lactancia y alimentación en el primer año de vida y su asociación con desarrollo del sobrepeso y obesidad de niños en México. Métodos: estudio transversal, analítico, y explicativo, se evaluó la asociación entre sobrepeso y obesidad con las distintas prácticas de alimentación en menores de un año de edad. Resultados: se evaluaron 396 menores, la prevalencia de sobrepeso y obesidad fue de 6% y 7.7% presentaba posible riesgo de sobrepeso. El 6.9% tuvo lactancia materna exclusiva en los primeros 6 meses de vida; 71.7% fueron alimentados con fórmula infantil. Las variables asociadas significativamente con el desarrollo de sobrepeso y obesidad en el primer año de vida fueron: la edad del menor (p =0.043; RR=0.57), introducción de líquidos en los tres primeros días de vida (p=0.02; RR=2.90), consumo de alimentos con alto contenido de azúcar (p = 0.01; RR=0.25), consumo de leches distintas al pecho (p = 0.02; RR=3.25) y consumo de huevo (p =0.05; RR=0.28). Conclusiones: nuestros resultados muestran que es fundamental atender las prácticas de alimentación complementaria y reforzar la lactancia materna exclusiva en el primer año de vida, como medidas de prevención del sobrepeso y obesidad para mejorar la salud en la infancia.

Pharmacogenetic studies in children with acute lymphoblastic leukemia in Argentina.

The aim of this study was to evaluate the influence of the most common genetic variants in methylenetetrahydrofolate reductase (MTHFR), thiopurine methyltransferase (TPMT) and glutathione-S-transferases (GSTs) on the outcome of acute lymphoblastic leukemia (ALL) treatment in Argentinean children. Two hundred and eighty-six patients with ALL treated with two Berlin-Frankfurt-Münster (BFM)-based protocols were analyzed. Ten genetic variants were studied. Toxicity was evaluated during the consolidation phase. Children who received 2 g/m(2)/day of methotrexate and carried at least one 677T allele in MTHFR showed an increased risk of developing severe leukopenia (p = 0.004) and neutropenia (p = 0.003). Intermediate-risk (IR) patients with a heterozygous TPMT genotype had a higher probability of event-free survival than those with a wild-type genotype. Genotyping of MTHFR polymorphisms might be useful to optimize consolidation therapy, reducing the associated severe hematologic toxicity. Further studies are necessary to establish the usefulness of MTHFR and TPMT variants as additional markers to predict outcome in the IR group.

Estudio comparativo del maíz morado (Zea mays L. ) y simvastatina en la reducción de lípidos séricos de pacientes diabéticos normotensos con dislipidemia / Comparative study of Peruvian purple corn (Zea mays L. ) and simvastatin in serum lipids reduction in normotense dyslipidemic diabetics

Objetivos: Determinar la eficacia de la administración del maíz morado (Zea mays) en la reducción de los niveles de lípidos séricos (efecto hipolipemiante) en pacientes diabéticos no hipertensos con dislipidemia. Comparar el efecto hipolipemiante del maíz morado con simvastatina. Diseño: Ensayo clínico. Institución: Instituto de Investigaciones Clínicas, Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú. Participantes: Pacientes diabéticos dislipidémicos no hipertensos. Intervenciones: Entre enero y octubre 2006, se formó aleatoriamente dos grupos de investigación de 15 pacientes diabéticos dislipidémicos no hipertensos, de diagnóstico reciente, sin tratamiento previo y sin complicaciones crónicas; un grupo recibió simvastatina 40 mg/día y el otro grupo maíz morado (comprimidos deshidratados y micropulverizados 1g/día), por un período de 30 días. Los pacientes paralelamente realizaron dieta hipograsa con evaluación nutricional semanal y recibieron el tratamiento hipoglicemiante convencional con glibenclamida. Se realizó dosaje basal y postratamiento de lípidos séricos, glucosa basal, hemoglobina glicosilada, pruebas de función hepática y renal. El análisis estadístico se efectuó con la prueba t de student, con un intervalo de confianza de 95 por ciento. Principales medidas de resultados: Modificación de los valores séricos de colesterol, triglicéridos y glucosa. Resultados: Se observó que en ambos grupos se produjo reducción en los valores séricos de colesterol total, colesterol LDL, triglicéridos y glucosa en ayunas; asimismo, aumento de los niveles séricos de colesterol HDL. Al compararse los resultados basales y postratamiento para maíz morado, se encontró reducción significativa de los valores de triglicéridos y aumento significativo del colesterol HDL. Para el grupo tratado con simvastatina, hubo reducción estadísticamente significativa del colesterol total, colesterol LDL, triglicéridos y aumento estadísticamente significativo del colesterol HDL, en comparación con los valores basales. El maíz morado mostró optimizar el control de la glucosa, efecto muy superior y estadísticamente significativo en comparación con la simvastatina. Se encontró diferencia estadísticamente significativa para los valores postratamiento de colesterol total, colesterol LDL, colesterol HDL y triglicéridos a favor del grupo que recibió simvastatina en comparación con el que recibió maíz morado. Conclusiones: A la dosis estudiada, el maíz morado mostró ser eficaz para reducir los niveles de triglicéridos, aumentar el colesterol HDL y optimizar el control de la glucosa en pacientes diabéticos no hipertensos. Simvastatina fue más eficaz que el maíz morado en el tratamiento de la dislipidemia, sin efectos importantes sobre la glicemia.

Objectives: To determine the effectiveness of Peruvian purple corn (Zea mays) administration in serum lipids levels reduction (hypolipidemic effect) in non hypertensive diabetic patients with dyslipidemia; to compare hypolipidemic effect of Peruvian purple corn and simvastatin. Design: Clinical essay. Setting: Instituto de Investigaciones Clinicas, Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Peru. Participants: Non hypertensive dyslipidemic diabetic patients. Interventions: Between January and October 2006 two groups of 15 non hypertensive dyslipidemic diabetic patients were randomly formed, patients with recent diagnosis, without previous treatment and without chronic complications; one group recieved simvastatin 40 mg/day and the other group Peruvian purple corn (dehydrated and micropulverized pills 1g/day) for 30 days. Patients had low fat diet with weekly nutritional evaluation and received conventional hypoglicemic treatment with glibenclamide. Serum lipids, glucose, glycosylated hemoglobin, hepatic and renal function tests were done before and after treatment. Statistical analysis used Student t test with 95 per cent confidence interval. Main outcome measures: Serum cholesterol, triglycerids and glucose levels variation. Results: There was reduction in both groups of total cholesterol, LDL cholesterol, triglycerides and fasting glucose serum levels; HDL cholesterol serum levels increased. Comparing basal and post treatment results for purple corn, there was significant reduction of triglycerides levels and significant increase of HDL cholesterol. In the simvastatin group there was significant statistical reduction of total cholesterol, LDL cholesterol, triglycerides and statistically significant increase in HDL cholesterol compared with basal levels. Compared with simvastatin purple corn optimized glucose control more significantly. There was significant statistical difference for post treatment values of total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides in favor of the group that received simvastatin compared with purple corn. Conclusions: At doses studied Peruvian purple corn was effective in reducing triglyceride levels, increasing HDL cholesterol and optimizing glucose control in non hypertensive diabetic patients. Simvastatin was more efficacious than Peruvian purple corn in treatment of dyslipidemia without important effects on glycemia.