Association of Germline Variation in Driver Genes with Breast Cancer Risk in Chilean Population.

Cancer is a genomic disease, with driver mutations contributing to tumorigenesis. These potentially heritable variants influence risk and underlie familial breast cancer (BC). This study evaluated associations between BC risk and 13 SNPs in driver genes MAP3K1, SF3B1, SMAD4, ARID2, ATR, KMT2C, MAP3K13, NCOR1, and TBX3, in BRCA1/2-negative Chilean families. SNPs were genotyped using TaqMan Assay in 492 cases and 1285 controls. There were no associations between rs75704921:C>T (ARID2); rs2229032:A>C (ATR); rs3735156:C>G (KMT2C); rs2276738:G>C, rs2293906:C>T, rs4075943T:>A, rs13091808:C>T (MAP3K13); rs178831:G>A (NCOR1); or rs3759173:C>A (TBX3) and risk. The MAP3K1 rs832583 A allele (C/A+A/A) showed a protective effect in families with moderate BC history (OR = 0.7 [95% CI 0.5-0.9] p = 0.01). SF3B1 rs16865677-T (G/T+T/T) increased risk in sporadic early-onset BC (OR = 1.4 [95% CI 1.0-2.0] p = 0.01). SMAD4 rs3819122-C (A/C+C/C) increased risk in cases with moderate family history (OR = 2.0 [95% CI 1.3-2.9] p ≤ 0.0001) and sporadic cases diagnosed ≤50 years (OR = 1.6 [95% CI 1.1-2.2] p = 0.006). SMAD4 rs12456284:A>G increased BC risk in G-allele carriers (A/G + G/G) in cases with ≥2 BC/OC cases and early-onset cases (OR = 1.2 [95% CI 1.0-1.6] p = 0.04 and OR = 1.4 [95% CI 1.0-1.9] p = 0.03, respectively). Our study suggests that specific germline variants in driver genes MAP3K1, SF3B1, and SMAD4 contribute to BC risk in Chilean population.

Polygenic prediction of bipolar disorder in a Latin American sample.

To date, bipolar disorder (BD) genetic studies and polygenic risk scores (PRSs) for BD are based primarily on populations of European descent (EUR) and lack representation from other ancestries including Latin American (LAT). Here, we describe a new LAT cohort from the Mayo Clinic Bipolar Biobank (MCBB), a multisite collaboration with recruitment sites in the United States (EUR; 1,443 cases and 777 controls) and Mexico and Chile (LAT; 211 cases and 161 controls) and use the sample to explore the performance of a BD-PRS in a LAT population. Using results from the largest genome-wide association study of BD in EUR individuals, PRSice2 and LDpred2 were used to compute BD-PRSs in the LAT and EUR samples from the MCBB. PRSs explained up to 1.4% (PRSice) and 4% (LDpred2) of the phenotypic variance on the liability scale in the LAT sample compared to 3.8% (PRSice2) and 3.4% (LDpred2) in the EUR samples. Future larger studies should further explore the differential performance of different PRS approaches across ancestries. International multisite studies, such as this one, have the potential to address diversity-related limitations of prior genomic studies and ultimately contribute to the reduction of health disparities.

Association of FANCM Mutations with Familial and Early-Onset Breast Cancer Risk in a South American Population.

Breast cancer (BC) is the most common cancer among women worldwide. BRCA1/2 are responsible for 16-20% of the risk for hereditary BC. Other susceptibility genes have been identified; Fanconi Anemia Complementation Group M (FANCM) being one of these. Two variants in FANCM, rs144567652 and rs147021911, are associated with BC risk. These variants have been described in Finland, Italy, France, Spain, Germany, Australia, the United States, Sweden, Finnish, and the Netherlands, but not in the South American populations. Our study evaluated the association of the SNPs rs144567652 and rs147021911 with BC risk in non-carriers of BRCA1/2 mutations from a South American population. The SNPs were genotyped in 492 BRCA1/2-negative BC cases and 673 controls. Our data do not support an association between FANCM rs147021911 and rs144567652 SNPs and BC risk. Nevertheless, two BC cases, one with a family history of BC and the other with sporadic early-onset BC, were C/T heterozygotes for rs144567652. In conclusion, this is the first study related contribution of FANCM mutations and BC risk in a South American population. Nevertheless, more studies are necessary to evaluate if rs144567652 could be responsible for familial BC in BRCA1/2-negatives and for early-onset non-familial BC in Chilean BC cases.

Pre-domestication bottlenecks of the cultivated seaweed Gracilaria chilensis.

Gracilaria chilensis is the main cultivated seaweed in Chile. The low genetic diversity observed in the Chilean populations has been associated with the over-exploitation of natural beds and/or the founder effect that occurred during post-glacial colonization from New Zealand. How these processes have affected its evolutionary trajectory before farming and incipient domestication is poorly understood. In this study, we used 2232 single nucleotide polymorphisms (SNPs) to assess how the species' evolutionary history in New Zealand (its region of origin), the founder effect linked to transoceanic dispersion and colonization of South America, and the recent over-exploitation of natural populations have influenced the genetic architecture of G. chilensis in Chile. The contrasting patterns of genetic diversity and structure observed between the two main islands in New Zealand attest to the important effects of Quaternary glacial cycles on G. chilensis. Approximate Bayesian Computation (ABC) analyses indicated that Chatham Island and South America were colonized independently near the end of the Last Glacial Maximum and emphasized the importance of coastal and oceanic currents during that period. Furthermore, ABC analyses inferred the existence of a recent and strong genetic bottleneck in Chile, matching the period of over-exploitation of the natural beds during the 1970s, followed by rapid demographic expansion linked to active clonal propagation used in farming. Recurrent genetic bottlenecks strongly eroded the genetic diversity of G. chilensis prior to its cultivation, raising important challenges for the management of genetic resources in this incipiently domesticated species.

Antimicrobial Activity of Biogenic Silver Nanoparticles from Syzygium aromaticum against the Five Most Common Microorganisms in the Oral Cavity.

Syzygium aromaticum (clove) has been used as a dental analgesic, an anesthetic, and a bioreducing and capping agent in the formation of metallic nanoparticles. The main objective of this study was to evaluate the antimicrobial effect in oral microorganisms of biogenic silver nanoparticles (AgNPs) formed with aqueous extract of clove through an ecofriendly method "green synthesis". The obtained AgNPs were characterized by UV-Vis (ultraviolet-visible spectroscopy), SEM-EDS (scanning electron microscopy-energy dispersive X-ray spectroscopy), TEM (transmission electron microscopy), and ζ potential, while its antimicrobial effect was corroborated against oral Gram-positive and Gram-negative microorganisms, as well as yeast that is commonly present in the oral cavity. The AgNPs showed absorption at 400-500 nm in the UV-Vis spectrum, had an average size of 4-16 nm as observed by the high-resolution transmission electron microscopy (HR-TEM), and were of a crystalline nature and quasi-spherical form. The antimicrobial susceptibility test showed inhibition zones of 2-4 mm in diameter. Our results suggest that AgNPs synthesized with clove can be used as effective growth inhibitors in several oral microorganisms.

Accumulation and fluxes of potentially toxic elements in a large coastal lagoon (southern Gulf of Mexico) from 210Pb sediment chronologies.

Three 210Pb-dated sediment cores were used to evaluate the contamination degree and flux ratios of potentially toxic elements (PTEs; As, Cd, Cr, Cu, Ni, Pb, V, and Zn) in seagrass meadows from the northern margin of Términos Lagoon (TL), southern Gulf of Mexico. The sediments displayed minor Cd, Ni, V, and Zn enrichments but moderate to strong enrichment by As. Results from a chemometric analysis revealed that: 1) salinization and grain size, along with 2) the terrigenous inputs are the major factors influencing the PTEs accumulation. The historical trends of PTEs flux ratios nearly follow the large-scale land-use changes around TL, linked to the growth of the Mexican oil industry in the area since the 1970s. Our findings showed the critical role of seagrass meadows as PTEs sinks. This information is useful for decision-makers to develop restoration projects for a vulnerable site within the largest coastal lagoon ecosystem in Mexico.

Valor del strain longitudinal global en la detección precoz de cardiotoxicidad inducida por quimioterapia / Global longitudinal strain value in the early detection of chemotherapy-induced cardiotoxicity

RESUMEN Introducción: Los avances en la detección precoz y el tratamiento del cáncer han reducido de manera significativa la mortalidad. El resultado neto es el surgimiento de una cohorte de pacientes cuya supervivencia es suficiente para evidenciar los efectos secundarios de las terapias utilizadas. La cardiotoxicidad es el conjunto de enfermedades cardiovasculares derivadas de los tratamientos onco-hematológicos. Objetivos: Evaluar el papel de la deformación miocárdica (strain) longitudinal global en la detección precoz de cardiotoxicidad en pacientes con tratamiento quimioterápico. Método: Se realizó un estudio cuantitativo, analítico, longitudinal, prospectivo en 44 pacientes con diagnóstico de cáncer de mama o linfoma, que iniciaron tratamiento con quimioterapia en el Instituto de Oncología y Radiobiología de Cuba, en el período comprendido entre febrero de 2017 y abril de 2018. Se utilizaron métodos primarios y secundarios para la recolección del dato primario y se emplearon varias pruebas estadísticas para su análisis. Resultados: Las medias de edad y tiempo de tratamiento fueron de 47,7 años y 5,05 meses, respectivamente. Predominó la hipertensión arterial (18,1%) como factor de riesgo y la mayor cardiotoxicidad (27,8%) en pacientes con disfunción diastólica previa. Entre los que desarrollaron cardiotoxicidad, la variable que demostró mayor afectación fue el strain longitudinal global (p<0,0001), con una reducción de 19,6% respecto al basal. Conclusiones: El strain longitudinal global es un índice ecocardiográfico de deformación miocárdica, que presentó un valor discriminante significativo con respecto a la cardiotoxicidad en pacientes que recibieron tratamiento quimioterápico.

ABSTRACT Introduction: Advances in early detection and treatment of cancer have significantly reduced mortality. The net result is the emergence of a cohort of patients whose survival is sufficient to evidence the side effects of the used therapies. Cardiotoxicity is the set of cardiovascular diseases resulting from onco-hematological treatments. Objectives: To evaluate the role of global longitudinal strain in the early detection of cardiotoxicity in patients undergoing chemotherapy. Method: A quantitative, analytical, prospective, longitudinal study was carried out in 44 patients diagnosed with breast cancer or lymphoma, who started chemotherapy treatment at the Instituto de Oncología y Radiobiología of Cuba, from February 2017 to April 2018. Primary and secondary methods were used for raw data collection and several statistical tests were used for its analysis. Results: The mean age and treatment period were 47.7 years old and 5.05 months, respectively. The most prevalent risk factor was high blood pressure and cardiotoxicity was higher (27.8%) in patients with previous diastolic dysfunction. Among those who developed cardiotoxicity, the variable that showed the greatest affectation was global longitudinal strain (p<0.0001), with a reduction of 19.6% with respect to the basal one. Conclusions: Global longitudinal strain is an echocardiographic index of myocardial performance, which presented a significant discriminating value with respect to cardiotoxicity in patients who received chemotherapeutic treatment.

Gene expression in peripheral blood in treatment-free major depression.

BACKGROUND: Peripheral gene expression of several molecular pathways has been studied in major depressive disorder (MDD) with promising results. We sought to investigate some of these genes in a treatment-free Latino sample of Mexican descent. MATERIAL AND METHODS: The sample consisted of 50 MDD treatment-free cases and 50 sex and age-matched controls. Gene expression of candidate genes of neuroplasticity (BDNF, p11, and VGF), inflammation (IL1A, IL1B, IL4, IL6, IL7, IL8, IL10, MIF, and TNFA), the canonical Wnt signaling pathway (TCF7L2, APC, and GSK3B), and mTOR, was compared in cases and controls. RNA was obtained from blood samples. We used bivariate analyses to compare subjects versus control mean mRNA quantification of target genes and lineal regression modelling to test for effects of age and body mass index on gene expression. RESULTS: Most subjects were female (66%) with a mean age of 26.7 (SD 7.9) years. Only GSK3B was differentially expressed between cases and controls at a statistically significant level (p = 0.048). TCF7L-2 showed the highest number of correlations with MDD-related traits, yet these were modest in size. DISCUSSION: GSK3B encodes a moderator of the canonical Wnt signaling pathway. It has a role in neuroplasticity, neuroprotection, depression, and other psychiatric phenotypes. We found that adding population diversity has the potential to elicit distinct peripheral gene expression markers in MDD and MDD-related traits. However, our results should only be considered as hypothesis-generating research that merits further replication in larger cohorts of similar ancestry.

Heterosexual Self-Presentation and Other Individual- and Community-Based Correlates of HIV testing among Latino Men Who Have Sex With Men.

From 2010 to 2014, HIV diagnoses among Latino men who have sex with other men (LMSM) have increased by 14%, while diagnoses declined by 11% among white, non-Latino MSM. This health disparity is in part due to exposure to other LMSM with undiagnosed HIV infections. To effectively engage LMSM who are unaware of their serostatus, profiles of men differing in theorized determinants of HIV testing must be considered. In this retrospective study, we examined data from 546 LMSM to investigate whether hypothesized individual- (traditional masculine gender role conformity; sexual identity development status; alcohol and illicit drug use; sexual risk behaviors; perceived HIV susceptibility; and HIV stigma) and community-based (HIV prevention programming, access to health care, social support, neighborhood collective efficacy) factors were associated with differences in HIV testing. Latent profile analysis was used to identify profiles of men, and subsequent analyses examined whether profiles exhibited differential proportions of HIV testing. Four latent profiles were observed. One profile (50.3% tested) differed markedly from all other profiles (5.1 to 11% tested) in HIV testing. Characteristics of participants in this unique profile included reporting lower levels of heterosexual self-presentation, sexual identity uncertainty (and high levels of sexual identity commitment), condom use, HIV stigma, education, and perceived HIV susceptibility than all other profiles. Findings could improve HIV testing rates among LMSM by specifying ways in which public health advertisements/campaigns and community-based testing outreach efforts could be tailored to men most at-risk for transmitting HIV due to unknown serostatus.

Fine-scale hierarchical genetic structure and kinship analysis of the ascidian Pyura chilensis in the southeastern Pacific.

Studying population structure and genetic diversity at fine spatial scales is key for a better understanding of demographic processes that influence population connectivity. This is particularly important in marine benthic organisms that rely on larval dispersal to maintain connectivity among populations. Here, we report the results of a genetic survey of the ascidian Pyura chilensis from three localities along the southeastern Pacific. This study follows up on a previous report that described a genetic break in this region among localities only 20 km apart. By implementing a hierarchical sampling design at four spatial levels and using ten polymorphic microsatellite markers, we test whether differences in fine-scale population structure explain the previously reported genetic break. We compared genetic spatial autocorrelations, as well as kinship and relatedness distributions within and among localities adjacent to the genetic break. We found no evidence of significant autocorrelation at the scale up to 50 m despite the low dispersal potential of P. chilensis that has been reported in the literature. We also found that the proportion of related individuals in close proximity (<1 km) was higher than the proportion of related individuals further apart. These results were consistent in the three localities. Our results suggest that the spatial distribution of related individuals can be nonrandom at small spatial scales and suggests that dispersal might be occasionally limited in this species or that larval cohorts can disperse in the plankton as clustered groups. Overall, this study sheds light on new aspects of the life of this ascidian as well as confirms the presence of a genetic break at 39°S latitude. Also, our data indicate there is not enough evidence to confirm that this genetic break can be explained by differences in fine-scale genetic patterns among localities.

Difference between manual and digital measurements of dental arches of orthodontic patients.

The objective of this study was to compare the differences between the measurements performed manually to those obtained using a digital model scanner of patients with orthodontic treatment.A cross-sectional study was performed in a sample of 30 study models from patients with permanent dentition who attended a university clinic between January 2010 and December 2015. For the digital measurement, a Maestro 3D Ortho Studio scanner (Italy) was used and Mitutoyo electronic Vernier calipers (Kawasaki, Japan) were used for manual measurement. The outcome variables were the measurements for maxillary intercanine width, mandibular intercanine width, maxillary intermolar width, mandibular intermolar width, overjet, overbite, maxillary arch perimeter, mandibular arch perimeter, and palate height. The independent variables, besides age and sex, were a series of arc characteristics. The Student t test, paired Student t test, and Pearson correlation in SPSS version 19 were used for the analysis.Of the models, 60% were from women. Two of nine measurements for pre-treatment and 6 of 9 measurements for post-treatment showed a difference. The variables that were different between the manual and digital measurements in the pre-treatment were maxillary intermolar width and palate height (P < .05). Post-treatment, differences were found in mandibular intercanine width, palate height, overjet, overbite, and maxillary and mandibular arch perimeter (P < .05).The models measured manually and digitally showed certain similarities for both vertical and transverse measurements. There are many advantages offered to the orthodontist, such as easy storage; savings in time and space; facilitating the reproducibility of information; and conferring the security of not deteriorating over time. Its main disadvantage is the cost.

Aspectos actuales de la economía de la salud, en la búsqueda de una mayor eficiencia / Current aspects of the Economy of Health in the search of a superior efficiency

Con el objetivo de exponer aspectos de la Economía de la Salud en el contexto actual de la Medicina cubana, se efectuó una revisión sobre los pilares de esta joven ciencia. Además se expuso la organización del presupuesto del Estado en cuanto a las actividades de la salud, la eficiencia económica a partir de costos y resultados y la definición y clasificación de los costos. Se realizó una reflexión sobre la relación costo-calidad, la ética médica y la evaluación económica. Se concluyó que los beneficios de una buena salud contribuyen a la promoción del crecimiento de la economía en muchos sentidos, pues se traducen en mayor desempeño educacional, aumento de la productividad laboral y mayor estabilidad social y económica(AU)

This paper is aimed at presenting the aspects of the Economy of Health in Cuban current context of medical services, a review about this young science and its mainstays was carried out. The organization of the State budget regarding health activities, the economic efficiency from the costs, results, definition and classifications of costs were analyzed; accomplishing a reflection on the relation cost-quality, medical ethics plus an economical assessment. Concluding that; the benefits of a good health contribute to the promotion and increase of the economy in all aspects, since these would be transformed into major educational performance, enhancement of working efficiency and a greater social-economical stability(AU)