Phenocopy in a patient with triple negative breast cancer: a case report

ABSTRACT A total of 1.67 million breast cancer cases per year are reported worldwide. Of these, 5%-10% are caused by inherited mutations. Phenocopy is a rare phenomenon, with only a few cases reported in the literature. In phenocopies, phenotypes identical to those with genetic origin occur because of environmental factors rather than familial mutations. We describe a case of phenocopy in a 44-year-old female patient with triple-negative breast cancer. The mother and sister wee heterozygous for c.1813delA, p.Ile605TyrfsTer9 in BRCA2 . The patient underwent genetic testing for BRCA1 and BRCA2 and exome sequencing. Familial or other cancer variants were not detected. The most accepted phenocopy theory is that patients without genetic variants but who are carriers of these mutations undergo cellular changes due to environmental factors, increasing the risk of breast cancer. Therefore, the detection of phenocopy in patients with breast cancer is important in clinical practice.

Endoplasmic reticulum aminopeptidase 1 and genetic susceptibility to pre-eclampsia / 中华围产医学杂志

Objective:To investigate whether endoplasmic reticulum aminopeptidase 1 ( ERAP1) is a susceptible gene for pre-eclampsia (PE) and the possible mechanism in the pathogenesis. Methods:This retrospective study included 990 PE patients (case group) and 1 240 healthy pregnant women (control group) in six prefecture-level tertiary hospitals in Shandong Province, including the Affiliated Hospital of Qingdao University and Zaozhuang Maternal and Child Health Hospital, from September 2018 to April 2021. Peripheral blood were collected for DNA extraction. Single-nucleotide polymorphisms in the ERAP1 gene (rs30187, rs27044, and rs469783 loci) were analyzed by Taqman probe polymerase chain reaction (PCR). Two missense mutant plasmids, rs30187(c.1583A>G) and rs27044(c.2188C>G), were constructed by point mutation induction based on wild-type plasmids. Six groups (knock-down control, knock-down, over-expression control, over-expression, variant 1 and 2 groups) were set up in this study. After transfecting Htr8 cells with different transfection molecules, the expression of ERAP1 at mRNA and protein levels were detected. Besides, the effects of different transfections on cell function were detected using Transwell migration assay, Transwell invasion assay, cell scratch assay, and CCK-8 assay. Statistical analysis was performed using two independent samples t-test, rank sum test, and Chi-square test. Results:(1) There were significant differences in the genetic distribution of rs30187 (Genotype: χ2=29.25, Allele: χ2=4.68) and rs469783 (Genotype: χ2=7.01, Allele: χ2=6.45) as well as the genotype distribution of rs27044 ( χ2=28.95) between the case group and the control group (all P<0.05). Statistical analysis of the genetic model revealed that rs30187 and rs27044, both recessive models, were statistically different between the two groups with a higher frequency of CC genotypes in the case group ( χ2=20.82 and 19.97, both P<0.05), but a lower frequency in CC dominant gene pattern for rs469783 ( χ2=5.82, P=0.016). (2) Compared with the knock-down control group, the knock-down group showed significantly inhibited expression of ERAP1 (mRNA: 0.5±0.1 vs 1.0±0.0, t=7.49; protein: 0.4±0.1 vs 0.7±0.1, t=2.81; both P<0.05), reduced cell migration rate after 48 h of scratching [(16.5%±1.8%) vs (23.8%±2.4%), t=3.33, P=0.031] and decreased number of cells crossing Transwell chambers after 24 h of culture (423.7±21.3 vs 499.0±24.6, t=3.29, P=0.031). Compared with the over-expression group, variant 1 group and variant 2 group showed significantly inhibited expression of ERAP1 at mRNA (both P<0.001) and protein ( P=0.003 and 0.006) levels after transfection, decreased number of cells crossing Transwell chambers ( P=0.001 and 0.032) and down-regulated cell migration rate after 48 h of scratching [variant 1: P=0.004; variant 2: (21.1±4.6)% vs (28.3±1.1)%, t=2.10, P=0.099]. ERAP1 expression at both mRNA ( P<0.001) and protein ( P=0.008) levels, as well as cell proliferation ( P<0.001) and invasion ability ( P<0.001), were all enhanced in the over-expression group than those in the over-expression control group. Moreover, the migration rate of cells after 48 h of scratching ( P=0.002) and the number of cells crossing Transwell chambers after 24 h of culture ( P=0.001) were also increased. Conclusions:The rs30187, rs27044, and rs46978 on ERAP1 gene were all associated with PE susceptibility, with more carriers of the CC genotype in PE patients at rs30187 and rs27044 loci and more carriers of the CC genotype in healthy gravida at rs469783 locus. ERAP1 may be involved in the pathogenesis of PE by affecting the migratory and invasive ability of trophoblast cells.

Association of AluYb8 insertion in the MUTYH gene with the risk of decreased left ventricular diastolic function in elderly diabetic patients / 中华老年医学杂志

Objective:To explore the relationship between AluYb8 insertion in the MUTYH gene and the risk of decreased left ventricular diastolic function in the elderly.Methods:In the retrospective analysis, 498 elderly patients with decreased left ventricular diastolic function(the disease group)and 155 people without left ventricular diastolic function(the control group)were recruited.Polymerase chain reaction was employed to analyze the genotype distribution of AluYb8 insertion in MUTYH gene.Cardiac function was measured by high-resolution color Doppler ultrasound.Results:The frequencies of the A/A, A/P and P/P genotypes were 30.1%(150/498), 48.4%(241/498)and 21.5%(107/498)in patients with decreased left ventricular diastolic function, and 27.7%(43/155), 54.8%(85/155)and 17.5%(27/155)in the control group, respectively.There were no significant differences in genotype( χ2=2.162, P=0.339)and allele frequency( χ2=1.342, P=0.794)between the two groups.Further analysis after stratification revealed that there were statistically significant differences in genotype( χ2=7.173, P=0.028)and allele frequency( χ2=8.352, P=0.015). Multivariate Logistic regression analysis showed that, in elderly patients with diabetes, P-allele carriers had a higher risk of decreased left ventricular diastolic function than non-carriers( OR=3.450, 95% CI: 1.148-10.372, P=0.027). Conclusions:AluYb8 insertion in the MUTYH gene may be associated with the risk of decreased left ventricular diastolic function in the elderly with diabetes.

Surgical Correction of Ascending Aortic Aneurysm Without Coronary Dilatation After Kawasaki Disease in a 3-Year-Old Child

Abstract Kawasaki disease (KD) is an inflammatory condition that may affect genetically predisposed individuals in pediatric ages after infectious/environmental triggering. An infrequent finding associated with KD is ascending aortic aneurysm during or after the acute phase of the disease. In this Multimedia presentation, we describe a three-year-old girl submitted to surgical treatment.

Interaction analysis of FTO and IRX3 genes with obesity and related metabolic disorders in an admixed Latin American population: a possible risk increases of body weight excess / Análisis de la interacción entre los genes FTO e IRX3 con obesidad y desórdenes metabólicos relacionados en una población mixta de América Latina: un posible aumento del riesgo de exceso de peso

Abstract Background: Fat Mass and Obesity-related (FTO) has been one of the genes consistently related to common obesity. Single nucleotide polymorphisms (SNPs) in FTO have been linked with the IRX3 gene. Aim: This study was designed by testing the hypothesis that: i) common SNPs in FTO and IRX3 are associated with obesity and related disorders; ii) there is significant linkage disequilibrium between both genes. Methods: A cross-sectional study was carried out on the Colombian Caribbean Coast. Anthropometric and biochemical variables were measured, and obesity and metabolic disorders were diagnosed. Four SNPs were genotyped: 3 at FTO locus (rs17817449, rs8050136, rs9939609) and one at IRX3 locus (rs3751723). LD between these SNPs was estimated. A logistic regression model was applied to estimate associations. Results: A total of 792 subjects were included. FTO and IRX3 were not in LD (D'≤ 0.03; R2≤ 0.03). TT genotype (rs9939609) was found to be associated with waist circumference (p= 0.04; adj-p= 0.01), and IRX3 SNP with Body Weight Excess (BWE) (OR= 1.06, adj-p= 0.03). One FTO-IRX3 haplotype was associated with BWE (G-A-A-T, rs17817449-rs8050136-rs9939609-rs3751723; OR= 0.67, p= 0.04). The statistical significance of these relations continued after admixture adjustment for a three-hybrid population (p= 0.03). Conclusions: FTO was related to waist circumference, and IRX3 was associated with BWE in Latin American adults. This relation remained statistically significant after an adjustment for sex, age, and genetic ancestry was performed. Despite that these genes were not in LD, findings of a haplotype involving FTO-IRX3 suggest a gene-gene interaction associated with an increased risk of BWE.

Resumen Introducción: FTO (Fat Mass and Obesity-related) se ha relacionado de manera consistente con la obesidad. Recientemente, Polimorfismos de Nucleótido Único (SNP) en este gen se han relacionado con el gen IRX3. Objetivo: Probar la hipótesis de que: i) SNPs en FTO e IRX3 están asociados con la obesidad y trastornos relacionados; ii) existe desequilibrio de ligamiento (LD) significativo entre ambos genes. Métodos: se realizó un estudio transversal en la costa caribe colombiana. Se valoraron variables antropométricas y bioquímicas, la obesidad y trastornos metabólicos. Se genotipificaron 4 SNPs: 3 en FTO (rs17817449, rs8050136, rs9939609) y uno en IRX3 (rs3751723). Se estimó el LD entre estos SNPs. Se aplicó un modelo de regresión logística para estimar asociaciones. Resultados: Se incluyeron 792 sujetos. FTO e IRX3 no se encontraron en LD (D' ≤0.03; R2 ≤0.03). El genotipo TT (rs9939609) se encontró asociado con la circunferencia de la cintura (p= 0.04; adj-p= 0.01), y el SNP IRX3 con el Exceso de Peso (EP) (OR= 1.06, adj-p= 0.03). Se encontró un haplotipo FTO-IRX3 asociado con EP (G-A-A-T, rs17817449-rs8050136-rs9939609-rs3751723; OR= 0.67, p= 0.04). Esta asociación persistió después del ajuste para una población mixta (p= 0.03). Conclusiones: FTO se encontró asociado con la circunferencia de la cintura e IRX3 con EP en adultos latinoamericanos. Estas asociaciones persistieron tras el ajuste por sexo, edad y ascendencia genética. Aunque estos genes no estaban en LD, los hallazgos de un haplotipo entre FTO-IRX3 sugieren una interacción gen-gen asociada con un mayor riesgo de EP.

Genes humanos asociados a la infección por el SARS-CoV-2 / Human genes associated with SARS-CoV-2 infection

RESUMEN Fundamento: La variabilidad clínica de la infección por el SARS-CoV-2 se debe, en parte, a factores genéticos. Objetivo: Describir los principales genes de susceptibilidad a la Covid-19. Metodología: Se realizó una revisión bibliográfica en Google Académico, SciELO, Annual Reviews y PubMed Central. Los descriptores que se utilizaron para la búsqueda de los documentos fueron consultados en el DeCS, estos fueron: SARS-CoV-2, Covid-19, genética y predisposición genética a la enfermedad. Se seleccionaron artículos disponibles a texto completo en inglés y en español, preferentemente de revistas arbitradas por pares. Resultados: Entre los genes implicados en la infección por el SARS-CoV-2 se encuentran DDX1 que promueve la replicación viral, IFITM1, IFITM2, IFITM3, IFNAR2 que codifican proteínas inducidas por el interferón, los genes de receptores (ACE2, ANPEP, DPP4), los genes de proteasas (TMPRSS2, furin, TMPRSS11D, CTSL, CTSB) que contribuyen a la entrada viral, genes de la respuesta inmune como ABO y metalopeptidasas como la familia ADAM. Se han detectado polimorfismos genéticos de riesgo. Conclusiones: En la infección por el SARS-CoV-2 se produce una compleja interrelación entre factores ambientales y genéticos que determinan la susceptibilidad de las personas a la Covid y su gravedad. El papel de los genes en la susceptibilidad a la Covid-19 deberá continuar investigándose.

ABSTRACT Background: The clinical variability of SARS-CoV-2 infection is partially due to genetic factors. Objective: To describe the main Covid-19 susceptibility genes. Methodology: A literature review was performed in Google Scholar, SciELO, Annual Reviews and PubMed Central. The descriptors used to search the documents were consulted in DeCS: SARS-CoV-2, Covid-19, genetics and genetic predisposition to disease. Full text articles available in English and Spanish were selected, rather from peer-reviewed journals. Results: Genes involved in SARS-CoV-2 infection include DDX1 which promotes viral replication, IFITM1, IFITM2, IFITM3, IFNAR2 encoding interferon-induced proteins, receptor genes (ACE2, ANPEP, DPP4), protease genes (TMPRSS2, furin, TMPRSS11D, CTSL, CTSB) that contribute to viral entry, immune response genes such as ABO and metallopeptidases such as the ADAM family. Risk genetic polymorphisms have been detected. Conclusions: In SARS-CoV-2 infection, there is a complex interaction between environmental and genetic factors that determine the susceptibility of individuals to Covid and its severity. The role of genes in Covid-19 susceptibility should be further investigated.

Dermatoglifia como medio de hallazgo de diabetes mellitus: revisión sistemática / Dermatoglyphics as a means of finding diabetes mellitus: a systematic review

Introducción. La diabetes mellitus (DM) es una de las enfermedades crónicas más comunes, siendo una de las causas principales de mortalidad de la población mun-dial. La dermatoglifia es empleada como instrumento para el hallazgo de ciertos aspectos biológicos en diferentes poblaciones. Objetivo. Reconocer, a partir de una revisión sistemática, la relevancia que tiene la dermatoglifia como medio de hallazgo de diabetes mellitus. Metodología. Revisión de literatura científica en bases de datos como Sciencedi-rect, PubMed, Scopus y BVS, en las cuales se extrajo información después de co-rrer la ecuación de búsqueda con términos MESH. Posteriormente, fueron revisados para incluir aquellos artículos relacionados con DM y dermatoglifia. Para todo el proceso se siguió la metodología PRISMA, evaluando los artículos con la escala de sesgo de Cochrane y el nivel de evidencia y recomendación con escala SIGN. Resultados. Después de una revisión de 475 artículos, se incluyeron ocho artículos, y al ser evaluados fueron clasificados cinco artículos 2+ y tres 2-, con nivel de reco-mendación D. Conclusión. La dermatoglifía es una herramienta útil como medio de detección de la DM. Sin embargo, es necesario realizar estudios de cohortes para demostrarlo en di-ferentes poblaciones, como la colombiana. En ese sentido, se encuentra que el 70% de los artículos revisados demuestran que la predicción de hallazgo de DM es efectiva. Sin embargo, el 30% de las investigaciones dentro de esta revisión no consideran que sea una herramienta lo suficientemente óptima para descubrir la patología en la población.

Introduction. Diabetes mellitus (DM) is one of the most common chronic diseases, be-ing one of the main causes of mortality in the world population. Dermatoglyphics is used as an instrument for the discovery of certain biological aspects in different populations.Objective. To recognize, by doing a systematic review, the relevance of dermato-glyphics as a means of finding diabetes mellitus. Methodology. Review of scientific literature in databases such as Sciencedirect, PubMed, Scopus, and VHL, in which information was extracted after running the search equation with MESH terms. After that, they were revised to include those articles related to DM and dermatoglyphics. For the entire process, the PRISMA methodology was followed, evaluating the articles with the Cochrane bias scale and the level of evidence and recommendation with the SIGN scale. Results. After a review of 475 articles, eight articles were included, and when evalu-ated, five articles were classified as 2+ and three as 2-, with a level D recommendation. Conclusion. Dermatoglyphics is a useful tool as a means of detecting DM. However, it is necessary to carry out cohort studies to demonstrate this in different populations, such as the Colombian population. 70% of the reviewed articles show that the prediction of DM finding is effective. Nevertheless, 30% of the investigations within this review do not consider it to be a sufficiently optimal tool to discover the pathology in the population

Analysis of clinical characteristics and genetic susceptibility of steroid-induced ocular hypertension in patients with uveitis / 中华眼底病杂志

Objective:To observe the clinical characteristics of steroid-induced ocular hypertension (SIOH) in patients with uveitis, and explore the relationship between its clinical phenotype and gene polymorphism.Methods:A retrospective case-control study. From July 2019 to December 2020, 576 patients with uveitis who were treated with glucocorticoid eye drops in Tianjin Medical University Eye Hospital were included in the study. Among them, there were 175 confirmed glucocorticoid responders (SRs) and 401 glucocorticoid non-responders (NRs). Seventy cases of SRs (age ≥18 years) using 1 % prednisone acetate eye drops were selected as the experiment group and 64 cases of NRs were selected as the control group. The polymorphism of rs2523864 and rs3873352 of human leukocyte antigen complex group ( HCG) 22 gene were detected by Sanger sequencing. To observe the clinical characteristics of SIOH after the use of glucocorticoid eye drops, and the correlation between rs2523864 and rs3873352 and the occurrence of SIOH. Differences among groups were compared with the Chi-square test or Fisher's exact test. The correlation between the occurrence of SIOH and the range of intraocular pressure increases after glucocorticoid use and the rs2523864 and rs3873352 loci were compared using the odds ratio ( OR) and its 95% confidence interval ( CI). Results:SIOH occurred in 175 (30.4%, 175/576) of 576 patients. Among them, there were 96 males (54.9%, 96/175) and 79 females (45.1%, 79/175); the average age was 33.64±17.40 years. Steroid high responders (HRs) and steroid moderate responders (MRs) were 58 (33.1%, 58/175) and 117 (66.9%, 117/175) cases. The medication time for the increase in intraocular pressure in MRs that was 33 (19, 56) days, and in HRs that was 28 (14, 36) days, the difference of which was significant ( Z=-1.999, P=0.046). No differences were found in daily doses of ocular hypertension induced by 1% prednisone acetate eye drops between MRs which was 4.24 (3.46, 4.66) drops/day and HRs that was 4.32 (3.84, 5.36) drops/day ( Z=-1.676, P=0.094). The genotype and allele frequency distribution of the rs3873352 locus in the case group and HRs group were significantly different from those in the control group ( P<0.05). The intraocular pressure with rs3873352 GG genotype after the medication was higher than that with GC and CC genotype ( Z=2.855, 2.628; P=0.013, 0.026), whereas there was no significant difference between different genotypes of rs2523864 ( Z=3.580, P>0.05). Genetic model analysis revealed the risk of SIOH in rs3873352 G allele carriers (GG+GC) was 2.048 times that of non-G allele carriers ( OR=2.048, 95% CI: 1.027-4.081, P=0.041). The genotype and allele frequency of rs2523864 locus showed no significant difference between different group ( P>0.05). Conclusions:After the use of glucocorticoid eye drops, HRs have an earlier increase in intraocular pressure than MRs. HCG22-rs3873352 gene polymorphism is related to the occurrence of SIOH, GG genotype increases the risk of SIOH, and G allele is a risk gene for SIOH.

Progress in genetic epidemiology of gestational diabetes mellitus / 中华围产医学杂志

Gestational diabetes mellitus poses a substantial threat to the short- and long-term health of women and their offspring. Previous studies have identified a number of genetic risk factors for gestational diabetes through candidate gene strategy and whole genome studies. Many of these identified genetic variations have also been proved to be associated with type 2 diabetes, abnormal glycometabolism as well as insulin secretion and resistance. This article reviews the recent progress in the genetic epidemiology of gestational diabetes mellitus.

New clues to understand gastroschisis. Embryology, pathogenesis and epidemiology / Nuevas pistas para comprender la gastrosquisis. Embriología, patogénesis y epidemiología

Abstract gastroschisis is a congenital structural defect of the abdominal wall, most often to the right of the umbilicus, through which the abdominal viscera protrude. Its developmental, etiological and epidemiological aspects have been a hot topic of controversy for a long time. However, recent findings suggest the involving of genetic and chromosomal alterations and the existence of a stress-inducing pathogenetic pathway, in which risk factors such as demographic and environmental ones can converge. . We have conducted a review of the medical literature that gathers information on the embryonic development of the ventral body wall, the primitive intestine, and the ring-umbilical cord complex, as well as on the theories about its origin, pathogenesis and recent epidemiological evidence, for which we consulted bibliographic databases and standard search engines

Resumen La gastrosquisis es un defecto estructural congénito de la pared abdominal, localizado con mayor frecuencia a la derecha del ombligo, a través del cual sobresalen las vísceras abdominales. Durante mucho tiempo, sus aspectos evolutivos, etiológicos y epidemiológicos han sido un tema candente de controversia, aunque hallazgos recientes sugieren la participación de alteraciones genéticas, cromosómicas, y la existencia de una vía patogénica inductora de estrés, en la que factores de riesgo como los demográficos y ambientales pueden converger. Con el objetivo de ampliar la frontera del conocimiento sobre una malformación que ha mostrado una creciente prevalencia global, hemos efectuado una revisión que incluye información, del desarrollo embrionario de la pared corporal ventral, el intestino primitivo, el complejo anillo-cordón umbilical, y de las teorías acerca de su origen, patogénesis e información epidemiológica reciente.

Predição do risco de adoecimento por hanseníase em contatos de casos da doença de uma região endêmica brasileira / Risk prediction of illness due to leprosy in contacts of cases in an endemic Brazilian region

O objetivo deste estudo foi analisar os determinantes da infecção pelo Mycobacterium leprae e do adoecimento por hanseníase em contatos de casos da doença, residentes na Microrregião de Almenara, Minas Gerais, Brasil, a fim de compor um modelo de predição da hanseníase em contatos inseridos em regiões endêmicas. Trata-se de uma coorte retrospectiva de contatos domiciliares de casos de hanseníasecom período de acompanhamento de 1999 a 2018. Foi realizada coleta de dados com entrevista, aplicação de questionário semiestruturado, contendo informações sociodemográficas e de saúde, coleta de amostras biológicas e exame dermatoneurológico. As amostras biológicas subsidiaram a avaliação de polimorfismos genéticos e reatividade aos testes sorológicos. A escolha das variáveis explicativas incluídas nas análises se fundamentou no modelo teórico dos determinantes da hanseníase em contatos, elaborado a partir da realização de revisão sistemática. A análise de associação utilizou modelo de regressão logística por meio do método de estimação Generalized Estimating Equations. A construção do modelo de predição envolveu análise exploratória dos dados e aplicação de algoritmos de aprendizagem de máquina. Os determinantes da infecção pelo M. leprae foram: a cor de pele negra e parda, a presença de genótipos contendo o polimorfismo rs8057341 no gene NOD2 (Nucleotide-binding Oligomerization Domain Containing 2) e o convívio com caso apresentando incapacidades físicas no diagnóstico. Os determinantes do adoecimento por hanseníase foram: consanguinidade com o caso índice e a continuidade do convívio em intradomicílio ou peridomicílio após o diagnóstico do caso. A idade, o contato domiciliar e peridomiciliar, o convívio com mais de um caso e a presença de incapacidades físicas no diagnóstico foram determinantes para o risco à infecção e ao adoecimento em contatos. O genótipo heterozigoto contendo o polimorfismo rs2430561 no gene IFNG (Interferon-gama) foi fator protetor para a infecção e adoecimento em contatos. Os algoritmos de aprendizagem supervisionada Naive Bayes com discretização das variáveis numéricas, J48 e Random Forest tiveram os melhores desempenhos nos conjuntos de dados avaliados. Os determinantes do processo de infecção e adoecimento por hanseníase foram capazes de compor modelos de predição com a acurácia e sensibilidade superiores a 90% e indicam que a vigilância de contatos pode ser aprimorada pela utilização destas tecnologias nos serviços de Atenção Primária à Saúde, principalmente, em áreas de alta endemicidade.

This study aimed to investigate the determinants of Mycobacterium leprae infection and illness due to leprosy in contacts of cases of the disease in the Microregion of Almenara, Minas Gerais, Brazil, to support the construction of a leprosy prediction model in contacts of patients from endemic regions. We conducted a retrospective cohort of household contacts of leprosy patients with a follow-up period from 1999 to 2018. The researchers performed interviews using a semi-structured questionnaire containing sociodemographic and health questions, biological samples collection, and dermatological examination. Biological samples supported the evaluation of genetic polymorphisms and reactivity to serological tests. The choice of the explanatory variables included in the analysis was based on the theoretical model of the determinants of leprosy in contacts, developed from a systematic review. The association analysis used a logistic regression model using the Generalized Estimating Equations estimation method. The construction of the prediction model involved exploratory data analysis and applied machine learning algorithms. The determinants of M. leprae infection were: black and mixed skin color, homozygous and heterozygous genotypes containing the rs8057341 polymorphism in the NOD2 gene (Nucleotide-binding Oligomerization Domain Containing 2), and living with a leprosy patient with disabilities at diagnosis. The determinants of illness due to leprosy in contacts were: consanguinity with the index case and living in the same household or yard after the diagnosis of the leprosy patient. Age, living in the same household or lot, with more than one leprosy patient that presented disabilities at the diagnosis were determinants for the risk of infection and illness in contacts. The heterozygous genotype that carried the rs2430561 polymorphism in the IFNG gene (Interferon-gamma) was a protective factor for M. leprae infection and leprosy in contacts of patients. The supervised learning algorithms Naive Bayes with the discretization of numerical variables, J48 and Random Forest had the best performances in the evaluated datasets. The determinants of the process of infection and illness due to leprosy were able to compose prediction models with accuracy and sensitivity higher than 90%. These results indicate that using these technologies in Primary Health Care services can improve contact surveillance, especially in highly endemic areas.

Endothelin-1 gene Lys198Asn polymorphism and ischemic stroke / 国际脑血管病杂志

Endothelin (ET) is a potent vasoconstrictor peptide produced by endothelial cells, which is closely associated with vascular endothelial dysfunction and cardio-cerebrovascular diseases. Recent studies have shown that ET-1 gene Lys198Asn polymorphism can be used as a new biomarker of cerebrovascular diseases. This article reviews the research progress on the relationship between the gene polymorphism and susceptibility to ischemic stroke, and discusses its clinical significance.

Apolipoprotein E genotypes and vascular cognitive impairment / 国际脑血管病杂志

Vascular cognitive impairment is the only cognitive impairment disease that can be intervened at present. In recent years, the research on its genetic factors has attracted much attention. Among them, apolipoprotein E (ApoE) and its genotypes are closely associated with lipid metabolism, β-amyloid aggregation and deposition, the changes of brain structure and function, and are closely correlated with the pathogenesis of dementia. This article discusses some possible mechanisms of ApoE and its genotypes affecting cognitive function, in order to provide reference for the management of cognitive function in patients with vascular cognitive impairment.

Genetic and genomics in congenital heart disease: a clinical review / Genética e genômica na cardiopatia congênita: uma revisão clínica

Abstract Objective: Discuss evidence referring to the genetic role in congenital heart diseases, whether chromosomic alterations or monogenic diseases. Data source: LILACS, PubMed, MEDLINE, SciELO, Google Scholar, and references of the articles found. Review articles, case reports, book chapters, master's theses, and doctoral dissertations were included. Summary of findings: Congenital heart diseases are among the most common type of birth defects, afflicting up to 1% of the liveborn. Traditionally, the etiology was defined as a multifactorial model, with both genetic and external contribution, and the genetic role was less recognized. Recently, however, as the natural evolution and epidemiology of congenital heart diseases change, the identification of genetic factors has an expanding significance in the clinical and surgical management of syndromic or non-syndromic heart defects, providing tools for the understanding of heart development. Conclusions: Concrete knowledge of congenital heart disease etiology and recognition of the genetic alterations may be helpful in the bedside management, defining prognosis and anticipating complications.

Resumo Objetivo: Discutir as evidências referentes ao papel genético em cardiopatias congênitas, sejam alterações cromossômicas ou doenças monogênicas. Fonte de dados: Lilacs, PubMed, Medline, SciELO, Google Scholar e referências dos artigos encontrados. Artigos de revisão, relatos de casos, capítulos de livros, dissertações de mestrado e teses de doutorado foram incluídos. Síntese dos dados: As cardiopatias congênitas estão entre os tipos mais comuns de defeitos congênitos, afetando até 1% dos nascidos vivos. Tradicionalmente, a etiologia era definida como um modelo multifatorial, com contribuição tanto genética quanto externa, sendo o papel genético menos reconhecido. Recentemente, no entanto, à medida que a evolução natural e a epidemiologia das cardiopatias congênitas mudaram, a identificação de fatores genéticos tem adquirido importância crescente no tratamento clínico e cirúrgico de defeitos cardíacos sindrômicos e não-sindrômicos, fornecendo ferramentas para a compreensão do desenvolvimento do coração. Conclusões: O conhecimento concreto da etiologia das cardiopatias congênitas e o reconhecimento das alterações genéticas podem ser úteis no tratamento à beira do leito, definindo o prognóstico e antecipando as complicações.

Evaluación de riesgo de cáncer en personas expuestas ocupacionalmente a solventes orgánicos / Cancer risk evaluation in individuals occupationally exposed to organic solvents

RESUMEN Objetivo Evaluar la frecuencia de micronúcleos (MN) e influencia de los polimorfismos en los genes del metabolismo GSTM1 y GSTT1 como biomarcadores de riesgo de cáncer en pintores de carros (n=152) con respecto a individuos no expuestos (n=152). Métodos Estudio Epidemiológico Molecular, tipo Corte Transversal analítico, interacción gen-ambiente. La evaluación de MNs y polimorfismos genéticos se determinó con pruebas moleculares en linfocitos de los individuos objeto de estudio. Resultados Se determinó que la frecuencia de MNs es 1.6 más alta en el grupo expuesto con relación al grupo referente (1.39±0.92 versus 0,87±0.78, p<0,0001). No se determinó un incremento en la frecuencia de MNs asociado a los polimorfismos en GSTM1 y GSTT1. Conclusiones El incremento de MNs en pintores de carros sirve para alertar al incremento de riesgo de cáncer en esta población expuesta a solventes orgánicos. Estos resultados pueden servir en Programas de Vigilancia Epidemiológica Ocupacional, como estrategia de prevención y en otros países con un amplio sector informal de individuos expuestos a estos químicos para reducir el riesgo de cáncer.(AU)

ABSTRACT Objective To evaluate the frequency of micronuclei (MNs) and influence of GSTM1 and GSTT1 gene polymorphisms as biomarkers of cancer risk in car painters (n=152) compared to unexposed individuals (n=152). Methods Molecular epidemiology study, cross-sectional analysis of gen and environment interaction. The evaluation of MN and genetic polymorphisms was determined by molecular tests in lymphocytes from subjects involved in the study. Results It was determined that the frequency of MNs is 1.6 higher in the exposed group compared to the reference group (1.39 ± 0.92 versus 0.87 ± 0.78, p<0.0001). There was no increase in the frequency of MNs associated with the polymorphisms in GSTM1 and GSTT1. Conclusions The increase of MNs in car painters serves to alert the increased risk of cancer in this population exposed to organic solvents. These results can be used in Occupational Epidemiological Surveillance Programs, as a prevention strategy and policies to regulate and control the use of solvents at a national level and in other countries with a large informal sector of individuals exposed to these chemicals to reduce the risk of cancer.(AU)

Intervenção da fisioterapia na síndrome de Menkes: relato de caso / Intervention of physiotherapy in Menkes syndrome: case report

Objetivo: Descrever a intervenção da fisioterapia motora e respiratória no caso de uma criança com Síndrome de Menkes. Método: Relato de caso, com base em registros retrospectivos, no qual são apresentados dados referentes ao acompanhamento fisioterapêutico de uma criança com o diagnóstico de Síndrome de Menkes. Os dados foram obtidos por meio do prontuário, entrevista com familiares e informações dos profissionais envolvidos. O referido paciente foi encaminhado para assistência fisioterapêutica aos 5 meses de vida, devido ao quadro de pneumonia com presença de atelectasia, associado as manifestações típicas da Síndrome, sendo então acompanhado por um período de 04 meses. Foram realizados 76 atendimentos, de um total de 91 agendamentos, os quais incluíram fisioterapia motora e respiratória, sendo aplicados métodos, técnicas, manuseios e posturas, para estimulação do desenvolvimento neuropsicomotor, e realizadas técnicas e recursos fisioterapêuticos para desobstrução e reexpansão pulmonar. Resultados: A cada sessão, a criança apresentou evidente melhora imediata no padrão e tipo respiratório, na frequência respiratória, na ausculta pulmonar e nos sinais de desconforto respiratório. Além disso, a estimulação motora e manutenção do quadro músculo esquelético, impediram agravos e deformidades. Segundo relato da mãe, a criança mostrava-se menos agitada após as sessões, com melhora no padrão e conforto respiratório, o que impactou de forma positiva na sua qualidade de vida. Conclusão: A fisioterapia motora e respiratória se apresentam como terapêuticas favoráveis para condição de saúde geral de pacientes com Síndrome de Menkes e novos estudos devem ser conduzidos no sentido de elucidar essa intervenção, com amostras maiores.

Objective: To describe the intervention of motor and respiratory physiotherapy in the case of a child with Menkes Syndrome. Method: Case report based on retrospective registers in which data are presented regarding the physical therapy accompaniment of a child with the diagnosis of Menkes Syndrome. The data were obtained based on the records of the child's chart, interview with relatives and information of the professionals involved. The patient was referred for physiotherapeutic assistance at 5 months of age, due to the presence of atelectasis pneumonia associated with the typical manifestations of Menkes' Syndrome, followed by a period of 4 months. A total of 76 appointments were performed, including motor and respiratory physiotherapy, and methods, techniques and manipulations were used to stimulate neuropsychomotor development, as well as techniques and physiotherapeutic resources were used to clear and reexpans the lungs. Results: At each session, the child showed evident immediate improvement in respiratory pattern and type, respiratory rate, pulmonary auscultation, and signs of respiratory discomfort. In addition, the motor stimulation and maintenance of the skeletal muscle of the child, prevented injuries and deformities. According to the mother's report, the child was less agitated after the sessions, with improved breathing pattern and comfort, which positively impacted his quality of life. Conclusion: Motor and respiratory physiotherapy are presented as favorable therapies for the general health condition of patients with Menkes-Syndrome, and further studies should be conducted to elucidate this intervention in a bigger sample.

Enfermedad celíaca y desarrollo de patologías secundarias / Celiac disease and the development of secondary disorders

La enfermedad celíaca es una patología autoinmune sistémica caracterizada por un estado inflamatorio crónico de la mucosa y submucosa intestinal, de origen multifactorial y detonada por factores ambientales como la ingesta de gluten en individuos genéticamente predispuestos a sensibilizarse a dicha proteína. La prevalencia de la enfermedad a nivel mundial se estima entre 1,1% y 1,7%, según datos de seroprevalencia. Sin embargo, se considera que existe una importante cantidad de individuos no diagnosticados, quienes podrían llegar a desarrollar una serie de complicaciones debido a que no reciben el manejo adecuado. Por ello, el objetivo de esta revisión comprende valorar algunas de las patologías secundarias más frecuentes asociadas a la enfermedad celíaca, evidenciando la afectación sistémica que puede presentar un individuo con esta enfermedad.

Celiac disease is a systemic autoimmune pathology characterized by a chronic inflammatory state of the intestinal mucosa and submucosa, of multifactorial origin and triggered by environmental factors such as gluten intake in individuals genetically predisposed to become sensitized to such protein. The worldwide prevalence of the disease is estimated to be between 1.1% and 1.7%, based on seroprevalence data. However, it is considered that there are a significant number of undiagnosed individuals, who could develop a series of complications due to not receiving adequate management. For this reason, the objective of this review is to assess some of the most frequent secondary disorders associated with celiac disease, evidencing the systemic involvement that an individual with this disease can develop.

Rastreio de câncer na prática clínica: recomendações para a população de risco habitual / Cancer screening in clinical practice: recommendations for average risk population

Objetivo: Compilar as evidências da literatura e as recomendações das principais sociedades médicas mundiais para o rastreamento populacional de câncer, contextualizando com a relevância epidemiológica de cada subtipo da doença. Métodos: Trata-se de revisão narrativa da literatura, realizada por levantamento na base de dados PubMed® e consulta aos posicionamentos de instituições governamentais e sociedades médicas nas áreas específicas. Resultados: O rastreamento populacional sistemático foi recomendado apenas para as neoplasias de mama, colo do útero e colorretal, utilizando-se métodos, idade e periodicidade específicos. O rastreio do câncer de próstata mostrou-se controverso, e o pulmonar e o hepático recomendados apenas em tabagistas com alta carga tabágica e cirróticos, respectivamente. Não houve evidência para se recomendar atualmente o rastreamento sistemático da população geral para as neoplasias de pele, tireoide, esôfago, estômago, pâncreas, ovário, endométrio, bexiga, rins, dentre outras. Conclusão: O exame periódico de saúde do paciente saudável abrangeu a prevenção e o rastreamento do câncer para redução de morbidade e mortalidade pela doença, e a estratificação das evidências atuais teve o potencial de melhorar o direcionamento dos esforços, aumentando a cobertura, havendo maior benefício e reduzindo riscos e custos de exames desnecessários.

Objective: To gather evidence from the literature, and recommendations of the main medical societies worldwide for the population screening of cancer, contextualizing with the epidemiological relevance of each subtype of the disease. Methods: This is a narrative review of the literature, carried out through research on PubMed® database, and consultation to the governmental institutions and medical societies' opinions in specific areas. Results: Systematic population screening was recommended only for breast, cervix and colorectal cancers, using specific methods, age and periodicity. Prostate cancer screening showed to be controversial, and pulmonary and hepatic screening are recommended only in heavy smokers and cirrhotic patients, respectively. Currently, there is no evidence to recommend the screening of the general population for neoplasms of skin, thyroid, esophagus, stomach, pancreas, ovary, endometrium, bladder, and kidneys. Conclusion: The periodic health screening of the healthy patient covered the prevention and screening for cancer to reduce morbidity and mortality from the disease; the stratification of current evidence has the potential to improve the direction of efforts, broadening coverage, with more benefit, and reducing risks and costs of unnecessary tests.