Association of TP53 germline variant and choledochal cyst among clinically diagnosed Filipino pediatric patients

@#Background and Objective. Choledochal cysts (CC) are rare congenital, cystic dilations of the biliary tree occurring predominantly in Asian populations and in females. Patients are usually children presenting with any of the following: abdominal pain, palpable abdominal mass, and jaundice. Its congenital nature hints at a potential genetic cause. A possible causal gene is TP53, a tumor suppressor with a germline variant called rs201753350 (c.91G>A) that changed from a G allele to an A allele, decreasing the cell proliferation suppressing activity of its functional protein. Currently, there is no information on the TP53 rs201753350 germline variant available for the Filipino population. This study determined the prevalence of rs201753350 and the association between the functional G allele, the rs201753350 germline variant A allele, and the occurrence of CCs in Filipino pediatric patients in a tertiary government hospital. Methods. Genomic DNA was extracted from blood samples of pediatric patients clinically diagnosed with CC. Controls were DNA samples collected from a previous study. The samples underwent PCR, electrophoresis, and sequencing. Results. A total of 109 participants (22 cases and 87 controls) were included in the study. The A allele (22.94%) occurs at a lower frequency than the G allele (77.06%) among both cases and controls. More individuals have a homozygous G/G genotype (54.13%) than a heterozygous A/G genotype (45.87%) while the homozygous A/A genotype was not observed. The estimated risk of choledochal cyst occurrence is significantly lower in individuals with the A allele (PR: 0.08, 95% CI: 0.01 – 0.55) and the A/G genotype (PR: 0.06, 95% CI: 0.01 – 0.40). Conclusion. There is no significant evidence to suggest an association between the TP53 rs201753350 germline variant and the occurrence of choledochal cysts in Filipinos. It is recommended that other mutations within and beyond the TP53 gene be investigated for possible associations with choledochal cyst occurrence.

Conservation of Organs (Heart, Brain and Kidney) of Canine by Cold-Temperature Silicone Plastination in an Animal Anatomy Laboratory in Ecuador / Conservación de Órganos (Corazón, Encéfalo y Riñón) de Canino Mediante la Técnica de Plastinación en Silicona al Frío Realizada en Laboratorio de Anatomía Animal en Ecuador

SUMMARY: For the purposes of teaching anatomy, the use of cadaver preparations is considered the most efficient way of ensuring that students retain knowledge. Nevertheless, in Ecuador the use of animal specimens in universities must comply with the internationally accepted principles of replacement, reduction and refinement (3Rs). Plastination is an alternative technique which allows organs to be conserved in the long term and complies with the 3Rs. The object of the present work was to use cold-temperature silicone plastination with Biodur® products to obtain long-lasting, easy-to-handle canine organs for use as tools for the teaching of animal anatomy. Six canine cadavers were obtained from local animal protection charities. The hearts, brains and kidneys of the cadavers were dissected and fixed with formaldehyde 10 %. They were then dehydrated with acetone at -20 °C. The specimens were impregnated with Biodur® S10:S3 (-20 °C) and finally cured with Biodur® S6. We plastinated six hearts, twelve kidneys, four brains and one encephalic slice of canine. The application of cold-temperature plastination to canine organs followed the parameters established for the conventional protocol, enabling us to obtain organs of brilliant appearance, free of odours, in which the anatomical form was preserved. Thus the technique helped us to comply with the 3Rs, as we obtained easy-to-handle teaching models to replace fresh or formaldehyde-fixed samples for the teaching-learning of the canine anatomy.

En la enseñanza de la Anatomía, el uso de preparaciones cadavéricas se considera el método que permite a los estudiantes retener el conocimiento de una forma más eficiente. No obstante, en Ecuador, el uso de especímenes animales en las universidades se debe realizar bajo el principio internacional de reemplazo, reducción y refinamiento (3Rs). La técnica de plastinación es una técnica alternativa que permite preservar órganos a largo plazo y que se adapta al principio de las 3Rs. El objetivo del trabajo fue utilizar la técnica de plastinación en silicona al frío con productos Biodur® para obtener órganos caninos duraderos y manejables útiles como herramienta para la enseñanza de la anatomía animal. Se obtuvieron seis cadáveres de caninos de fundaciones locales para la protección animal. Se realizaron disecciones de corazones, cerebros y riñones de los cadáveres caninos. Los órganos se fijaron con formalina al 10 %. A continuación, se llevó a cabo la deshidratación con acetona a -20 °C. Los especímenes fueron impregnados con S10:S3 Biodur® (-20 °C) y al final fueron curados con Biodur® S6. Se lograron plastinar seis corazones, doce riñones, cinco encéfalos y un tallo encefálico de canino. La técnica de plastinación al frío utilizada para obtener órganos de canino conservó los parámetros empleados en el protocolo convencional y permitió obtener órganos que presentaron aspecto brillante, ausencia de olores y mantuvieron la forma anatómica. Por lo que, la técnica facilitó cumplir con el principio de las 3Rs al obtenerse modelos didácticos fáciles de manipular que pueden reemplazar muestras frescas o formolizadas en el proceso de enseñanza-aprendizaje de la anatomía del canino.

Reemplazar ideas, reducir equívocos y refinar argumentos: una reinterpretación de las 3R de la experimentación animal

Propósito/Contexto. En el presente trabajo se llevará a cabo una reinterpretación de las tres erres (3R) propuestas por William Russell y Rex Burch (reemplazo, reducción y refinamiento), con el objetivo de ampliar su alcance y mejorar las prácticas de experimentación con animales no humanos. Metodología/Enfoque. Se revisará el sentido que le dieron Russell y Burch a las 3R y se evaluará el modo en que cada una de ellas podría redefinirse o complementarse a la luz de las prácticas científicas, las posibilidades técnicas y los conocimientos bioéticos actuales vinculados al uso de animales en investigación. Resultados/Hallazgos. El artículo mostrará que 1) no solo habrían de reemplazarse animales, sino también las ideas equívocas que tenemos, tanto sobre ellos, como sobre la importancia de la educación bioética en la formación científica, 2) que la reducción, además de referirse al número de sujetos utilizados en cada experimento, debería servir para acabar con investigaciones innecesarias, repetitivas y superfluas, así como con algunos persistentes equívocos sobre el modo de operar de la ciencia y 3) que el refinamiento tendría que salir del espacio experimental para extenderse al modo en que pensamos sobre ética animal en el ámbito de la investigación. Discusión/Conclusiones/Contribuciones. El trabajo da cuenta de la importancia que tiene la incorporación del conocimiento bioético contemporáneo en las prácticas de experimentación con animales para mejorar el carácter reflexivo y ético de la ciencia.

Purpose/Background. In the present work, a reinterpretation of the 3Rs (3Rs) proposed by William Russell and Rex Burch (Replacement, Reduction and Refinement) will be carried out with the aim of broadening its scope and improving nonhuman animal experimentation practices. Methodology/Approach. The meaning given by Russell and Burch to the 3Rs will be reviewed and the way in which each of them could be redefined or complemented in the light of current scientific practices, technical possibilities and bioethical knowledge related to the use of animals in research will be evaluated. Results/Findings. The article will show that 1) not only animals should be replaced, but also the misconceptions we have, both about them and about the importance of bioethics education in scientific training, 2) that the reduction, in addition to the number of subjects used in each experiment, should serve to end unnecessary, repetitive and superfluous research, as well as some persistent misconceptions about the way science operates, and 3) that refinement should go beyond the experimental space to extend to the way we think about animal ethics in the research setting. Discussion/Conclusions/Contributions. The paper reports on the importance of incorporating contemporary bioethical knowledge into animal experimentation practices to enhance the reflexive and ethical character of science.

Objetivo/Contexto. Neste documento, uma reinterpretação dos 3Rs (3Rs) propostos por William Russell e Rex Burch (Substituição, Redução e Refinamento) será realizada com o objetivo de ampliar seu escopo e melhorar as práticas não-humanas de testes em animais. Metodologia/ Abordagem. Revisaremos o significado dado por Russell e Burch aos 3Rs e avaliaremos como cada um deles poderia ser redefinido ou complementado à luz das práticas científicas atuais, possibilidades técnicas e conhecimentos bioéticos relacionados ao uso de animais na pesquisa. Resultados/Descobertas. O artigo mostrará que 1) não somente os animais devem ser substituídos, mas também conceitos errôneos sobre eles e a importância da educação bioética no treinamento científico, 2) que a redução, além do número de sujeitos utilizados em cada experimento, deve servir para eliminar pesquisas desnecessárias, repetitivas e supérfluas, assim como alguns conceitos errôneos persistentes sobre a maneira como a ciência funciona, e 3) que o refinamento deve se estender além do espaço experimental para a maneira como pensamos sobre a ética animal na pesquisa. Discussão/Conclusões/Contribuições. O artigo explica a importância de incorporar o conhecimento bioético contemporâneo nas práticas de experimentação animal para realçar o caráter reflexivo e ético da ciência.

Reducción, reutilización y reciclaje: Una revisión crítica del conocimiento científico sobre las pérdidas y desperdicios de alimentos en Chile

Reducir, reutilizar y reciclar, "regla de las tres R", son estrategias que promueven una actitud responsable hacia el medioambiente y contribuyen al desarrollo sostenible. El objetivo de esta revisión fue analizar las publicaciones científicas generadas en Chile en el área de las pérdidas y desperdicios de alimentos (PDA), con enfoque en su cuantificación y basadas en "la regla de las tres R". Se realizó una búsqueda de literatura en tres bases de datos: Web of Science, Pubmed y Scopus. Los artículos originales seleccionados se clasificaron según tipo de acción, etapa de la cadena de suministro de alimentos, grupo de alimentos, cuantificación de PDA y tipo de estrategia (reducción, reutilización o reciclaje). Se encontraron 5 artículos de revisión y 31 artículos originales. La revalorización de subproductos agroindustriales fue la principal acción involucrada en los estudios de PDA (n= 22). El tipo de subproducto también fue analizado, y se encontró que los compuestos fenólicos provenientes de frutales son los más estudiados. Solo el 32% (12/31) de los artículos reportaron información sobre cuantificación de PDA. La revalorización de subproductos sumada a la recuperación de alimentos para producción de energía (n= 4) y de compostaje (n= 2) hacen que el reciclaje sea la estrategia más investigada. Estos antecedentes evidencian la necesidad de complementar la investigación nacional a nivel de acciones que apunten más hacia la reducción y reutilización de PDA y su cuantificación. Este conocimiento permitirá establecer líneas base y planes de monitoreo que contribuyan al cumplimiento de los Objetivos de Desarrollo Sostenible en Chile.

Reduce, reuse, and recycle "the 3Rs rule" are strategies that promote a responsible attitude towards the environment and contribute to sustainable development. The objective of this review was to analyze the scientific publications generated in Chile in the area of food loss and waste (FLW), with a focus on its quantification and based on "the 3Rs rule". A literature search was carried out in three databases: Web of Science, Pubmed, and Scopus. The selected original articles were classified according to the type of action, stage of the food supply chain, food group, FLW quantification, and type of strategy (reduction, reuse, or recycling). Five review articles and 31 original articles were found. The revalorization of agro-industrial by-products was the main initiative involved in the FLW studies (n= 22). The type of by-product was also analyzed, and it was found that the phenolic compounds from fruits are the most studied. Only 32% (12/31) of the articles reported information on FLW quantification. The revalorization of by-products added to food recovery for energy production (n= 4) and composting (n= 2) make recycling the most researched strategy. These antecedents show the need to complement the national research at the level of actions that point more towards reducing and reusing of FLW and its quantification. This knowledge will allow the establishment of baselines and monitoring plans that contribute to the fulfillment of the Sustainable Development Goals in Chile.

Educação e saúde nos territórios de Pontão-RS: resgatando memórias e compartilhando saberes / Education and health in the territories of Pontão-RS: rescuing memories and sharing knowledge

Esta obra trata da sistematização de algumas das experiências desenvolvidas no município de Pontão-RS através do Programa de Extensão "Círculos de cultura: diálogos em saúde na escola e na comunidade" da Universidade Federal da Fronteira Sul (UFFS) Campus Passo Fundo, em parceria com as Secretarias de Educação, Saúde e Assistência Social de Pontão-RS. Evidencia a sistematização de parte dos processos desenvolvidos através de ações intersetoriais de formação de professores (as), de apoio aos processos pedagógicos nas escolas e de experiências de interação entre estudantes e professoras do curso de graduação em Medicina da UFFS, com profissionais da Secretaria da Saúde e de Assistência Social junto às escolas, grupos e comunidades. Resultado também de um esforço coletivo de todas as escolas e professores (as) do município de Pontão sobre trajetórias e dinâmicas de cada território e comunidade onde as escolas estão inseridas, trazendo as principais marcas do processo pedagógico de cada escola. Uma obra construída por muitas mãos e que apresenta inovações produzidas como dispositivo de implementação de políticas públicas intersetoriais e de base territorial.

An Investigation of the Effects of B7-H4 Gene rs10754339 and miR-125a Gene rs12976445 on Cancer Susceptibility / 生物医学与环境科学（英文）

OBJECTIVE@#To investigate the effects of the B7-H4 gene rs10754339 and miR-125a gene rs12976445 on cancer susceptibility through a case-control study and meta-analysis.@*METHODS@#A total of 1,490 cancer patients (lung/gastric/liver/: 550/460/480) and 800 controls were recruited in this case-control study. The meta-analysis was performed by pooling the data from previous related studies and the present study.@*RESULTS@#The results of this study showed that in the Hubei Han Chinese population, the rs10754339 gene was significantly associated with the risk of lung and gastric cancer but not liver cancer, and the rs12976445 gene was significantly associated with the risk of lung cancer but not liver or gastric cancer. The meta-analysis results indicated that rs10754339 and rs12976445 contributed to cancer susceptibility in the Chinese population and also revealed a significant association between rs10754339 and breast cancer risk, as well as between rs12976445 and lung cancer risk.@*CONCLUSION@#The B7-H4 gene rs10754339 and miR-125a gene rs12976445 may be the potential genetic markers for cancer susceptibility in the Chinese population, which should be validated in future studies with larger sample sizes in other ethnic populations.

Association of the brain-derived neurotrophic factor gene polymorphisms and clinical symptoms in patients with schizophrenia / 四川精神卫生

BackgroundIn relation to neurodevelopmental hypothesis in the etiology of schizophrenia， brain-derived neurotrophic factor （BDNF） as a neurotrophin occupies a relatively dominant position in neuronal development and is a potential biomarker for schizophrenia， and previous studies have suggested that its serum concentration and genetic polymorphisms play a vital role in the pathogenesis of schizophrenia， but this remains controversial. ObjectiveTo analyze the difference in BDNF serum concentration between schizophrenic patients and healthy controls， and to explore the correlation of three BDNF single nucleotide polymorphism （SNPs） including rs11030101， rs2030324 and rs6265 with BDNF serum concentration and clinical symptoms in patients with schizophrenia， thus providing references for the clinical treatment of schizophrenia. MethodsA case-control study was conducted on 55 patients with schizophrenia who attended the Zhongshan Third People's Hospital from January 2019 to December 2020 and met the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5）， and 31 healthy controls concurrently recruited from the hospital or general population. Positive and Negative Symptom Scale （PANSS） was utilized to evaluate the psychiatric symptoms of patients with schizophrenia. BDNF serum concentration in all participants was measured using enzyme-linked immunosorbent assay （ELISA）， and the genotype distributions of three BDNF SNPs （rs11030101， rs2030324， rs6265） were investigated by polymerase chain reaction sequence-based typing method. ResultsBDNF serum concentration in patient group was lower than that in control group， with statistical difference （t=-3.804， P<0.01）. In terms of clinical symptoms， PANSS total score， excitement/hostility domain score， and depression/anxiety domain score demonstrated statistical difference among patients with different genotypes at SNP rs11030101 （t=2.022， Z=-2.696， -2.467， P<0.05 or 0.01）. No statistical difference was noted in BDNF serum concentration in patients with different genotypes at three BDNF SNPs （Z=1.483， F=2.584， 0.417， P>0.05）. ConclusionPatients with schizophrenia are found to have low BDNF serum concentration， and the three BDNF SNPs （rs11030101， rs2030324， rs6265） are not associated with BDNF serum concentration， whereas the BDNF rs11030101 polymorphism may contribute to the manifestation of clinical symptoms of excitement/hostility and depression/anxiety in patients with schizophrenia. Furthermore， BDNF serum concentration seems to be more dependent on clinical diagnosis effect rather than genetic polymorphism. ［Funded by Guangdong Province Medical Science and Technology Research Fund Project （number， A2021205）； Zhongshan Medical Research Program （number， 2022J221）］

Clinical and molecular genetic study of a Chinese Han family with X-linked retinoschisis / 中华实验眼科杂志

Objective:To study the clinical phenotype and molecular genetic characteristics of a Chinese Han family with X-linked retinoschisis (XLRS), and to determine the associated gene variations.Methods:A pedigree investigation was performed.The clinical characteristics and pedigree analysis of a Han Chinese family line with XLRS was conducted in August 2021 at the Xiamen Eye Center Affiliated to Xiamen University.All patients and the carriers underwent comprehensive medical history collection and routine ophthalmological examinations, including visual acuity, non-contact tonometer, slit lamp microscope, direct ophthalmoscope, and optical coherence tomography.The proband and some patients underwent medical optometry, fundus photography or wide-angle fundus photography, and electroretinogram examination.Peripheral venous blood samples were collected from the family members, and whole exome sequencing (WES) analysis was performed on the proband samples.For variants screened by WES, the expanded verification in other patients and normal persons in the family was carried out by Sanger sequencing.Multiple bioinformatic tools were used to analyze the pathogenicity of variants.This study protocol was approved by the Ethics Committee of Xiamen Eye Center of Xiamen University (No.XMYKZX-KY-2021-012). Written informed consent forms were obtained from each subject or guardian of minors.CADD, FATHMM and other bioinformatics tools were used to analyze the pathogenicity of the variation sites.Results:The Han XLRS pedigree consisted of 8 individuals in 3 generations.Out of the 3 cases diagnosed with XLRS based on clinical evaluation, all were male.The mother of the proband was a carrier of related genes.There were 5 persons with normal phenotypes.There was no history of consanguineous marriages within the family, and the disease was shown to be intergenerational, which is consistent with the recessive inheritance of the X chromosome.None of the patients had a history of systemic disease or any other abnormal manifestations.The prevailing feature of ophthalmopathy was poor binocular vision since childhood.The proband and his younger brother had spoke split in the macula, and their grandfather showed atrophy of retinal nerve fibers.Genetic analysis revealed a hemizygous variation c. 214G>C: p.Glu72Gln in the RS1 gene in all the patients in this family.The proband's mother was heterozygous at this site, and all other phenotypically normal family members exhibited wild type at this site.This variant was predicted to be a deleterious variation and likely to cause disease based on bioinformatics analysis. Conclusions:The proband and patients in this Han Chinese family have the known c. 214G>C: p.Glu72Gln hemizygous variation of the RS1 gene and exhibit mild XLRS, which was consistent with the recessive inheritance of X chromosome.

Impact of genetic ancestry on the distribution of interferon-λ4 rs12979860 polymorphism in a global population of Buenos Aires, Argentina / Impacto de la ancestría genética en la distribución del polimorfismo de interferón-λ4 rs12979860 en una población global de Buenos Aires, Argentina

ABSTRACT Human interferon-λ4 is a cytokine involved in early stages of antiviral responses. Strikingly, some allelic variants with diminished antiviral activity reduce the susceptibility to viral infections, thus they would have suffered a positive selection pressure throughout the evolutionary history of the genus Homo. An intronic variant within the IFNλ4 locus (rs12979860, T˃C) emerged as one of the main gene determinants of the response to HCV and other viruses. The rs12979860-C allele has a differential frequency in African, European and Native American populations, though South American data are scarce. Here we characterize for the first time the distribution of rs12979860 genotypes in a sample of the global population of Buenos Aires, Argentina, assessing its association with European, Native American and African parental components. The rs12979860 genotypes were determined by PCR-RFLP in DNA samples from donors of a blood banks of Buenos Aires (n=96), whose genetic individual ancestry (European, African or Native American) had been previously determined using molecular markers. The distribution of rs12979860-CC, CT and TT was 29.17%, 50.0% and 20.83%, respectively. A significant increase in the frequency of CC among donors with a strong European contribution and a greater impact of the Native American component among donors carrying the T allele were observed. Native American and European components were associated to the rs12979860 distribution in a sample of the global population of Buenos Aires, while no differences were directly attributable to the African ancestry. Considering interferon´s key role in antiviral responses, our results may contribute to both bioanthropological and immunogenetic studies associated with infectious diseases.

RESUMEN El interferón-λ4 humano es una citoquina involucrada en la respuesta antiviral. Algunas variantes alélicas con menor actividad antiviral, paradójicamente, reducen la susceptibilidad a infecciones virales, por lo que habrían sufrido una presión de selección positiva en la historia evolutiva del gיnero Homo. Una variante dentro del locus de IFNλ4 (rs12979860, T˃C), con distribución diferencial en poblaciones africanas, europeas y nativas americanas, surgió como uno de los principales determinantes genéticos de la respuesta al HCV y otros virus. Aquí caracterizamos por primera vez la distribución de los genotipos de rs12979860 en una muestra de la población cosmopolita de Buenos Aires, Argentina, evaluando el impacto de su ancesrtría. Se determinaron diferentes genotipos de rs12979860 por PCR-RFLP en muestras de ADN de donantes de bancos de sangre de Buenos Aires (n=96), cuya ancestría individual había sido previamente determinada mediante diferentes marcadores moleculares. La distribución global de rs12979860-CC, CT y TT fue 29,17%; 50,0% y 20,83%, respectivamente. Se observó un aumento significativo de la frecuencia del genotipo CC entre individuos con fuerte aporte europeo y un mayor impacto del componente nativo-americano entre portadores del alelo T. Los componentes nativo-americano y europeo se asociaron a la distribución rs12979860 en una muestra poblacional global de Buenos Aires, mientras que no se vieron diferencias directamente asociadas a la ancestría africana. Considerando el papel clave del interferón en la respuesta antiviral, nuestros resultados pueden contribuir a estudios con un enfoque bioantropológico así como a estudios inmunogenéticos asociados a enfermedades infecciosas.

Association between interleukin-17F rs763780 polymorphism and psoriasis risk: A meta-analysis

Background: The polymorphism of interleukin-17F rs763780 has been found to have a probable association with increased risk of developing psoriasis. Aims: This study aims to get a more convincing estimation of the association between the interleukin-17F rs763780 T/C polymorphism and psoriasis risk. Methods: Two authors independently searched the databases including PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, Wanfang and Chinese Biomedical Literature Databases for case–control studies which reported the odds ratios with 95% confidence intervals comparing genotype and allele frequencies of the interleukin-17F rs763780 polymorphism in patients with psoriasis versus participants without psoriasis. Results: A total of seven case–control studies incorporating 1824 cases and 1585 controls were identified. The pooled odds ratios indicated that interleukin-17F rs763780 C allele was a risk factor for psoriasis in allele frequency, recessive model and homozygote model (P < 0.05). Subgroup analysis by ethnicity further indicated that the C allele was closely related to increased risk of psoriasis in Asian populations (P < 0.05), but not in Caucasians. Limitations: Only a few studies on the interleukin-17F rs763780 polymorphism in psoriasis have been reported till date, thus the data is insufficient. Only one gene polymorphic site was selected for this study, and it is not clear whether other genetic mutation functional sites affect the gene. Further studies on confounding effects of other genetic polymorphisms are needed. Conclusion: The present meta-analysis results suggested that the interleukin-17F rs763780 T/C is significantly associated with psoriasis risk in Asians

Cuestionario Revisado de Personalidad de Eysenck (versión reducida): análisis con la teoría de respuesta al ítem / Revised Eysenck Personality Questionnaire (Brief Version): Analysis with Item Response Theory

Resumen El objetivo de este trabajo es aportar nuevas evidencias de calidad psicométrica para la adaptación argentina de la versión reducida del Cuestionario de Personalidad de Eysenck (EPQ-RS). Participaron 1136 personas de población general (52.5% femenino, edad media = 29.6 años, DE = 11.9) residentes en Buenos Aires, Argentina. La adaptación argentina se compone de 42 ítems con formato de respuesta dicotómica. Se realizó un análisis factorial confirmatorio a partir de la matriz de correlaciones tetracóricas. Esto permitió replicar la estructura propuesta por Eysenck para el modelo PEN (Psicoticismo-Extraversión-Neuroticismo) y la escala Sinceridad. Posteriormente, se ajustó el modelo logístico de dos parámetros por separado para los ítems de cada escala. Los ítems no mostraron funcionamiento diferencial según género. La discriminación de los ítems resultó moderada-alta. Los parámetros b se localizaron en rangos acotados de cada uno de los rasgos medidos, lo que originó que la precisión de las escalas varíe en el recorrido de los continuos. La escala Neuroticismo aporta más información en niveles medios del rasgo, Psicoticismo en los medio-bajos y Extraversión en los medio-altos. La escala Sinceridad mostró una función de información relativamente plana en todo el recorrido del rasgo. Se brindan evidencias de validez basadas en la relación con otras pruebas que miden facetas del neuroticismo y sintomatología. Las evidencias de validez y confiabilidad obtenidas ofrecen garantías de calidad suficientes para la aplicación de este instrumento en el contexto local y confirman la vigencia del modelo teórico que operacionaliza el EPQ-RS.

Abstract The aim of this work is to provide new evidence of psychometric quality for the Argentinean adaptation of the brief version of the Eysenck Personality Questionnaire (EPQ-RS). 1136 people from the general population (52.5% female, mean age = 29.6 years, SD = 11.9) residing in Buenos Aires, Argentina participated. The Argentinean adaptation consists of 42 items with dichotomous response format. A confirmatory factor analysis was performed from the tetrachoric correlation matrix. This allowed replicating the structure proposed by Eysenck for the PEN model (Psychoticism - Extroversion - Neuroticism) and the Lie scale. Subsequently, the two-parameter logistic model was adjusted separately for the items of each scale. The items did not show differential functioning by gender. Items discrimination was moderate-high. Parameters b were located in narrow ranges of each one of the measured traits, which caused the precision of the scales to vary along the trait continuums. The Neuroticism scale provides more information at medium levels of the trait, Psychoticism in the medium-low and Extraversion in the medium-high. The Lie scale showed a relatively flat information function throughout the trait. Evidence of validity based on the relationship with other tests that measure facets of neuroticism and symptomatology is provided. The evidence of validity and reliability obtained offers sufficient quality guarantees for the application of this instrument in the local context and confirms topicality of the theoretical model that operationalizes the EPQ-RS.

Investigating possible effects of aryl hydrocarbon receptor G1661A polymorphism on asthma severity in adults

Aryl hydrocarbon Receptor (AhR) is a ligand-activated transcription factor with an important role in lung health. The association of AhR polymorphisms with asthma severity has not been yet investigated. We analyzed the association of G1661A, the most prevalent polymorphism of AhR, with the asthma stages in a population-based study including 555 asthmatics (Intermittent: 93, Mild: 240, Moderate: 158, and Severe: 64). The SNP was genotyped using allele-specific PCR. Obtained data were analyzed using the Generalized-Ordered Logit Estimates. Genotypes GA (OR: 0.53, CI: 0.32-0.90, P=0.019) and AA (OR: 0.22, CI: 0.06-0.76, P=0.017) were associated with decreased risk of Severe, Moderate, Mild vs. Intermittent stage; and Severe, Moderate, vs. Mild, Intermittent stages respectively. However, Genotype GA (OR: 1.90, CI: 1.05-3.44, P=0.033), dominant model GA+AA (OR: 2.04, CI: 1.17-3.57, P=0.012), and allele A (OR: 1.68, CI: 1.06-2.66, P=0.027) were associated with increased risk of Severe stage vs. Moderate, Mild, Intermittent stages. Also, male sex and higher age were associated with an increased odds ratio for severe asthma. Furthermore, significant associations with asthma stages were found for the interactions of the SNP and sex, smoking, and alcohol consumption. In conclusion, we revealed that the mutant allele of AhR-G1661A may interact with independent variables and act as a protective factor against lower stages of asthma but it may increase the risk of severe asthma.

Association of single nucleotide polymorphisms in microRNAs with the risk of chronic spontaneous urticaria / 中华皮肤科杂志

Objective:To investigate the association between single nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) and the risk of chronic spontaneous urticaria (CSU) .Methods:A case-control study was conducted. A total of 98 patients with CSU (CSU group) were collected from Department of Dermatology, Affiliated Hospital of Jining Medical University from January to June in 2019, and 148 health checkup examinees (control group) were collected at the same time, all of whom were of Han nationality from Shandong province. Genomic DNA was extracted from venous blood samples, and polymorphic sites rs2431697 (miRNA-146a) , rs57095329 (miRNA-146a) , rs3746444 (miRNA-499) , rs11614913 (miRNA-196a2) and rs895819 (miRNA-27a) were analyzed for SNP genotyping by multiplex PCR amplification and single-base extension. Chi-square test was used to analyze differences in the distribution of alleles, genotypes and genetic models between the two groups, and unconditional logistic regression to analyze the relationship between gene SNPs and the risk of CSU.Results:All samples were successfully genotyped by analysis of the 5 polymorphic sites. The alleles of the miRNA-196a2 SNP rs11614913 were T/C, and the absolute frequency of T allele was 110 (56.1%) in the CSU group and 131 (44.3%) in the control group; there was a significant difference in the T/C allele frequency distribution between the two groups ( χ2 = 6.64, P = 0.010) , and the T allele might be a risk factor for CSU ( OR=1.61, 95% CI: 1.12-2.32) . In addition, the absolute frequencies of CC, CT and TT genotypes of rs11614913 were 16 (16.3%) , 54 (55.1%) , 28 (28.6%) in the CSU group, and 48 (32.4%) , 69 (46.6%) , 31 (20.9%) in the control group respectively, and there was a significant difference in the genotype distribution between the two groups ( χ2 = 8.16, P = 0.017) ; the distribution of the dominant genetic model (TT + CT vs. CC) also significantly differed between the two groups ( χ2 = 7.95, P = 0.005) , which might increase the risk of CSU ( OR=2.46, 95% CI: 1.30-4.65) . Conclusion:The miRNA-196a2 SNPs may be associated with the risk of CSU in the Han population in Shandong, China, and the rs11614913 polymorphism may increase the risk of CSU.

The interaction between 5-HTT gene rs6354 polymorphism and family factors on the adaptability of Mongolian school-age children / 中华行为医学与脑科学杂志

Objective:To explore the effects of rs6354 polymorphism of 5-HTT gene and family factors on the adaptability of Mongolian school-age children.Methods:The adaptability of 453 primary school students was assessed based on the middle childhood temperament questionnaire(MCTQ). The polymorphism of 5-HTT gene rs6354 was determined by improved multiple ligase detection reaction(iMLDR) technology. SPSS18.0 statistical software was used for data processing and analysis.Results:(1) The adaptability scores of children with GG/GT and TT genotype at rs6354 locus of 5-HTT gene were(2.88±0.73) and(3.03±0.76). (2) Univariate analysis showed that the adaptability scores of Mongolian school-age children were significantly different among different education levels of their parents (father F=2.580, P=0.037; mother F=3.245, P=0.012). (3) Multiple regression analysis showed that mother's educational level( B=-0.079, P=0.010) and rs6354 polymorphism( B=0.165, P=0.041) were inflencing factors of the adaptability score of Mongolian school-age children. (4) Logistic regression analysis showed that father's education level was a significant impact factor of the adaptive level of Mongolian school-age children( B=0.453, P<0.05, OR=1.573, 95% CI=1.023-2.417). Conclusion:rs6354 polymorphism is weakly correlated with children's adaptability, and the education level of parents, especially fathers, may be an important factor affecting the adaptability of Mongolian school-age children.

Regulation of calcium oscillations by IP3R and RyR in neonatal rat cardiomyocytes / 西安交通大学学报(医学版)

【Objective】 To explore the roles of 1,4,5-trisphosphate receptor (IP3Rs) and ryanodine receptors (RyRs), the two main Ca2+ release channels in sarcoplasmic reticulum (SR), in the regulation of intracellular Ca2+ oscillations in neonatal rat cardiomyocytes (NRCMs). 【Methods】 We isolated and cultured NRCMs for different days, then loaded them with Ca2+ indicator fura-2 and performed real-time fluorescent imaging. To distinguish the effects of IP3Rs and RyRs, NRCMs were pre-treated with phenylephrine (PE, IP3Rs agonist), caffeine (RyRs agonist), 2-APB (IP3Rs antagonist), and tetracaine (RyRs antagonists), respectively. 【Results】 The cultured monolayer NRCMs showed spontaneous synchronized Ca2+ oscillations. PE activation or 2-APB blockade of IP3Rs increased or reduced the frequency of Ca2+ oscillations in NRCMs, accordingly, with no significant effect on the amplitude of Ca2+ oscillations. Activation of RyRs with caffeine increased the frequency of Ca2+ oscillations, but unsynchronized the intercellular rhythm of calcium release and beating pace, while blocking RyRs with tetracaine completely abolished the Ca2+ oscillations and beats in NRCMs. In addition, the effect of PE stimulation on Ca2+ oscillation frequency gradually decreased along with cultured days. 【Conclusion】 IP3Rs regulate the rhythm of calcium oscillations, whereas RyRs are the main channel for bulky store Ca2+ release.

The single nucleotide polymorphism rs1814521 in long non-coding RNA ADGRG3 associates with the susceptibility to silicosis: a multi-stage study

BACKGROUND@#This study aimed to evaluate the correlation between long non-coding RNA (lncRNA)-related single nucleotide polymorphisms (SNPs) and susceptibility to silicosis.@*METHODS@#First, RNA-sequencing (RNA-seq) data were comprehensively analyzed in the peripheral blood lymphocytes of eight participants (four silicosis cases and four healthy controls) exposed to silica dust to identify differentially expressed lncRNAs (DE-lncRNAs). The functional SNPs in the identified DE-lncRNAs were then identified using several databases. Finally, the association between functional SNPs and susceptibility to silicosis was evaluated by a two-stage case-control study. The SNPs of 155 silicosis cases and 141 healthy silica-exposed controls were screened by genome-wide association study (GWAS), and the candidate SNPs of 194 silicosis cases and 235 healthy silica-exposed controls were validated by genotyping using the improved Mutiligase Detection Reaction (iMLDR) system.@*RESULTS@#A total of 76 DE-lncRNAs were identified by RNA-seq data analysis (cut-offs: fold change > 2 or fold change < 0.5, P < 0.05), while 127 functional SNPs among those 76 DE-lncRNAs were identified through multiple public databases. Furthermore, five SNPs were found to be significantly correlated with the risk of silicosis by GWAS screening (P < 0.05), while the results of GWAS and iMLDR validation indicated that the variant A allele of rs1814521 was associated with a reduced risk of silicosis (OR = 0.76, 95% CI = 0.62-0.94, P = 0.011).@*CONCLUSION@#The presence of the SNP rs1814521 in the lncRNA ADGRG3 is associated with susceptibility to silicosis. Moreover, ADGRG3 was found to be lowly expressed in silicosis cases. The underlying biological mechanisms by which lncRNA ADGRG3 and rs1814521 regulate the development of silicosis need further study.

Effects of inulin， resistant starch RS3 and their complexes on blood lipid levels and intestinal flora in mice / 上海预防医学

Objective To explore the effects of different dietary induction models of inulin， resistant starch RS3 and their complexes on the body weight and intestinal flora in mice. Methods A total of 64 C57BL/6 mice were randomly divided into low-fat control group， low-fat inulin group， low-fat resistant starch RS3 group， low-fat composite group and high-fat control group， high-fat inulin group， high-fat resistant starch RS3 group and high-fat composite group for dietary intervention. The mice were weighed and fresh feces were collected weekly. Diet intervention was continued until the weight of the high-fat control group was more than 14% higher than that of the low-fat control group. The mice were then sacrificed after overnight fasting. Liver and epididymal fat were weighed， and the colon contents were collected for 16S amplicon sequencing analysis. Results In low-fat diet fed mice， the combined induction of inulin and resistant starch RS3 caused a significant decrease in body weight gain. In high-fat diet fed mice， inulin alone and the combined induction both caused a significant reduction in weight gain， and there was no significant difference between the two methods. In the high-fat diet groups， inulin， resistant starch RS3， and the compound could be distinguished by Bacteroides， Bifidobacterium and Alloprevotella respectively. In the low-fat diet groups， inulin， resistant starch RS3， and the composite groups could be distinguished by Coriobacteriaceae_UCG_002， Bacteroides and Helicobacter， respectively. Conclusion Inulin and resistant starch RS3 diet induction can significantly reduce the weight gain of C57BL/6 mice， change the structure of intestinal flora， and show the difference between high-fat and low-fat diets. Inulin and resistant starch RS3 may reduce body weight and promote fat metabolism by changing the structure of intestinal flora.

Mechanism of Combination of Pungent Dispersing Bitter Evacuant in Treatment of Asthma Based on Theory of Five Flavor Compatibility / 中国实验方剂学杂志

Bronchial asthma， a chronic inflammatory airway disease， belongs to the category of wheezing disease in the system of traditional Chinese medicine （TCM）. The wheezing symptom of this disease is mainly caused by the imbalance of lung Qi. According to the theory of five flavor compatibility， the Chinese medicinal materials with five different flavors （pungent， bitter， sour， sweet， and salty） can be combined to produce new functions. The pungent medicinal materials have dispersing effect and the bitter medicinal materials have discharging effect， which are important components in the theory of five flavor compatibility. Pungent herbs and bitter herbs can relieve the adverse lung Qi， occupying an important position in the current medication for the treatment of asthma. However， there is still a lack of in-depth analysis of the TCM theory and mechanism of the compatibility of pungent herbs and bitter herbs in the treatment of asthma. The molecular mechanisms of action of pungent herbs and bitter herbs are closely related to transient receptor potential （TRP） channels and bitter taste receptors （TAS2Rs）， respectively. Ca2+ signaling has been recognized in the process of asthma and is involved in the development of multiple symptoms of asthma. The TRP channels and TAS2Rs located on the cell membrane have been proved to directly regulate the intracellular Ca2+ signal and play a role in the treatment of asthma. Therefore， the dispersing effect of pungent herbs and the discharging effect of bitter herbs may be realized through the Ca2+ signaling pathway mediated by TRPs/TAS2Rs. We summarized the theoretical understanding and modern studies of pungent herbs dispersing lung Qi and bitter herbs discharging lung Qi， aiming to explain the internal relationship and mechanism of the compatibility of pungent herbs and bitter herbs in the treatment of asthma from the perspective of TCM theory and modern medicine. The compatibility of pungent herbs and bitter herbs based on the theory of five flavor compatibility for the treatment of asthma has a solid theoretical basis of TCM， and its mechanism can be verified by modern research. Therefore， it may be a main research direction in the treatment of asthma by Chinese medicinal herbs in the future.

Smart Spectrophotometric Methods for Concurrent Determination of Furosemide and Spironolactone Mixture in Their Pharmaceutical Dosage Forms

Abstract Simple, precise, accurate and specific spectrophotometric methods are progressed and validated for concurrent analysis of Furosemide (FUR) and Spironolactone (SPR) in their combined dosage form depend on spectral analysis procedures. Furosemide (FUR) in the binary mixture could be analyzed at its λmax 274 nm using its recovered zero order absorption spectrum using constant multiplication method (CM). Spironolactone (SPR) in the mixture could be analyzed at its λmax 238 nm by ratio subtraction method (RS). Concurrent determination for FUR and SPR in their mixture could be applied by amplitude modulation method (AM), absorbance subtraction method (AS) and ratio difference (RD). Linearity ranges of FUR and SPR were (2.0µg/mL-22.0 µg/mL) and (3.0µg/mL-30.0 µg/mL), respectively. Specificity of the proposed spectrophotometric methods was examined by analyzing the prepared mixtures in laboratory and was applied successfully for pharmaceutical dosage form analysis which have the cited drugs without additives contribution. The proposed spectrophotometric methods were also validated as per as the guidelines of ICH. Statistical comparison was performed between the obtained results with those from the official methods of the cited drugs, using one-way ANOVA, F-test and student t-test. The results are exhibiting insignificant difference concerning precision and accuracy

Homozygotes NAT2*5B slow acetylators are highly associated with hepatotoxicity induced by anti-tuberculosis drugs

BACKGROUND Distinct N-acetyltransferase 2 (NAT2) slow acetylators genotypes have been associated with a higher risk to develop anti-tuberculosis drug-induced hepatotoxicity (DIH). However, studies have not pointed the relevance of different acetylation phenotypes presented by homozygotes and compound heterozygotes slow acetylators on a clinical basis. OBJECTIVES This study aimed to investigate the association between NAT2 genotypes and the risk of developing DIH in Brazilian patients undergoing tuberculosis treatment, focusing on the discrimination of homozygotes and compound heterozygotes slow acetylators. METHODS/FINDINGS The frequency of NAT2 genotypes was analysed by DNA sequencing in 162 patients undergoing tuberculosis therapy. The mutation analyses revealed 15 variants, plus two new NAT2 mutations, that computational simulations predicted to cause structural perturbations in the protein. The multivariate statistical analysis revealed that carriers of NAT2*5/*5 slow acetylator genotype presented a higher risk of developing anti-tuberculosis DIH, on a clinical basis, when compared to the compound heterozygotes presenting NAT2*5 and any other slow acetylator haplotype [aOR 4.97, 95% confidence interval (CI) 1.47-16.82, p = 0.01]. CONCLUSION These findings suggest that patients with TB diagnosis who present the NAT2*5B/*5B genotype should be properly identified and more carefully monitored until treatment outcome in order to prevent the occurrence of anti-tuberculosis DIH.