Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations.

The prevalence and spectrum of germline mutations in BRCA1 and BRCA2 have been reported in single populations, with the majority of reports focused on White in Europe and North America. The Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) has assembled data on 18,435 families with BRCA1 mutations and 11,351 families with BRCA2 mutations ascertained from 69 centers in 49 countries on six continents. This study comprehensively describes the characteristics of the 1,650 unique BRCA1 and 1,731 unique BRCA2 deleterious (disease-associated) mutations identified in the CIMBA database. We observed substantial variation in mutation type and frequency by geographical region and race/ethnicity. In addition to known founder mutations, mutations of relatively high frequency were identified in specific racial/ethnic or geographic groups that may reflect founder mutations and which could be used in targeted (panel) first pass genotyping for specific populations. Knowledge of the population-specific mutational spectrum in BRCA1 and BRCA2 could inform efficient strategies for genetic testing and may justify a more broad-based oncogenetic testing in some populations

Sí, Yo Puedo Curricula: Latinas Examining Domestic Violence and Self

In 2013–2014, a mixed-method study was conducted examining the experiences of 14 immigrant Latina women using a culturally specific curriculum: Sí, Yo Puedo. The purpose of using the curriculum among participants was to assess self-esteem and knowledge of healthy relationships, dating, and domestic violence (DV). The curriculum is a 2-hr, topic-specific educational program, conducted in Spanish, offered over a period of 11 weeks in a group format. Participants reported an increase in self-esteem and knowledge of DV after completing the program. Implications include the promotion of a curriculum for mental health professionals who work with immigrant Latinas in community-based agencies

The causes, consequences, and treatment of left or right heart failure

Pablo Pazos-López, Jesús Peteiro-Vázquez, Ana Carcía-Campos, Lourdes García-Bueno, Juan Pablo Abugattas de Torres, Alfonso Castro-BeirasDepartment of Cardiology, Complejo hospitalario Universitario A Coruña, A Coruña, SpainAbstract: Chronic heart failure (HF) is a cardiovascular disease of cardinal importance because of several factors: a) an increasing occurrence due to the aging of the population, primary and secondary prevention of cardiovascular events, and modern advances in therapy, b) a bad prognosis: around 65% of patients are dead within 5 years of diagnosis, c) a high economic cost: HF accounts for 1% to 2% of total health care expenditure. This review focuses on the main causes, consequences in terms of morbidity, mortality and costs and treatment of HF.Keywords: heart failure, cause, consequence, treatmen

Community voices on factors influencing COVID-19 concerns and health decisions among racial and ethnic minorities in the school setting

Racial and ethnic minority communities have been disproportionately affected by COVID-19, but the uptake of COVID-19 mitigation strategies like vaccination and testing have been slower in these populations. With the continued spread of COVID-19 while in-person learning is a priority, school-aged youth and their caregivers must make health-related decisions daily to ensure health at school. It is critical to understand factors associated with COVID-related health decisions such as vaccination, testing, and other health behaviors (e.g., wearing masks, hand washing). Community-engaged campaigns are necessary to overcome barriers to these health behaviors and promote health equity. The aim of this study was to examine COVID-19-related concerns and influences on health decisions in middle and high schools serving primarily racial and ethnic minority, low-income families. Seven focus groups were conducted with school staff, parents, and students (aged 16 years and older). Qualitative data were analyzed using a general inductive approach. Factors related to COVID-19 concerns and health decisions centered on (1) vaccine hesitancy, (2) testing hesitancy, (3) developmental stage (i.e., ability to engage in health behaviors based on developmental factors like age), (4) cultural and family traditions and beliefs, (5) compatibility of policies and places with recommended health behaviors, (6) reliability of information, and (7) perceived risk. We explore sub-themes in further detail. It is important to understand the community's level of concern and identify factors that influence COVID-19 medical decision making to better address disparities in COVID-19 testing and vaccination uptake

CRISPR-Cas13d Induces Efficient mRNA Knockdown in Animal Embryos

Early embryonic development is driven exclusively by maternal gene products deposited into the oocyte. Although critical in establishing early developmental programs, maternal gene functions have remained elusive due to a paucity of techniques for their systematic disruption and assessment. CRISPR-Cas13 systems have recently been employed to degrade RNA in yeast, plants, and mammalian cell lines. However, no systematic study of the potential of Cas13 has been carried out in an animal system. Here, we show that CRISPR-RfxCas13d (CasRx) is an effective and precise system to deplete specific mRNA transcripts in zebrafish embryos. We demonstrate that zygotically expressed and maternally provided transcripts are efficiently targeted, resulting in a 76% average decrease in transcript levels and recapitulation of well-known embryonic phenotypes. Moreover, we show that this system can be used in medaka, killifish, and mouse embryos. Altogether, our results demonstrate that CRISPR-RfxCas13d is an efficient knockdown platform to interrogate gene function in animal embryos.This work was supported by Ramon y Cajal program (RyC-2017-23041) and grants PGC2018-097260-B-I00 and MDM-2016-0687 from Spanish Ministerio de Ciencia, Innovación y Universidades and the Springboard program from CABD (M.A.M.-M.) and the Stowers Institute for Medical Research (A.A.B.). M.A.M.-M. was the recipient of the Genome Engineer Innovation 2019 Grant from Synthego. A.A.B. was awarded with Pew Innovation Fund. J.R.M.-M. is supported by BFU2017-86339-P and MDM-2016-0687 grants (Spanish Ministerio de Ciencia, Innovación y Universidades). E.M.-T. and J.A.-N.d.P. are supported by INNOVATE PERÚ grant 168-PNICP-PIAP-2015 and FONDECYT travel grant 043-2019

Clinical validation of RCSMS: A rapid and sensitive CRISPR-Cas12a test for the molecular detection of SARS-CoV-2 from saliva.

Peru's holds the highest COVID death rate per capita worldwide. Key to this outcome is the lack of robust, rapid, and accurate molecular tests to circumvent the elevated costs and logistics of SARS-CoV-2 detection via RT-qPCR. To facilitate massive and timely COVID-19 testing in rural and socioeconomically deprived contexts, we implemented and validated RCSMS, a rapid and sensitive CRISPR-Cas12a test for the molecular detection of SARS-CoV-2 from saliva. RCSMS uses the power of CRISPR-Cas technology and lateral flow strips to easily visualize the presence of SARS-CoV-2 even in laboratories with limited equipment. We show that a low-cost thermochemical treatment with TCEP/EDTA is sufficient to inactivate viral particles and cellular nucleases in saliva, eliminating the need to extract viral RNA with commercial kits, as well as the cumbersome nasopharyngeal swab procedure and the requirement of biosafety level 2 laboratories for molecular analyses. Notably, RCSMS performed outstandingly in a clinical validation done with 352 patients from two hospitals in Lima, detecting as low as 50 viral copies per 10 μl reaction in 40 min, with sensitivity and specificity of 96.5% and 99.0%, respectively, relative to RT-qPCR. The negative and positive predicted values obtained from this field validation indicate that RCSMS can be confidently deployed in both high and low prevalence settings. Like other CRISPR-Cas-based biosensors, RCSMS can be easily reprogrammed for the detection of new SARS-CoV-2 variants. We conclude that RCSMS is a fast, efficient and inexpensive alternative to RT-qPCR for expanding COVID-19 testing capacity in Peru and other low- and middle-income countries with precarious healthcare systems

Breast cancer subtype and survival among Indigenous American women in Peru.

Latina women in the U.S. have relatively low breast cancer incidence compared to Non-Latina White (NLW) or African American women but are more likely to be diagnosed with the more aggressive "triple negative" breast cancer (TNBC). Latinos in the U.S. are a heterogeneous group originating from different countries with different cultural and ancestral backgrounds. Little is known about the distribution of tumor subtypes in Latin American regions. Clinical records of 303 female Peruvian patients, from the Peruvian National Cancer Institute, were analyzed. Participants were diagnosed with invasive breast cancer between 2010 and 2015 and were identified as residing in either the Selva or Sierra region. We used Fisher's exact test for proportions and multivariable Cox Proportional Hazards Models to compare overall survival between regions. Women from the Selva region were more likely to be diagnosed with TNBC than women from the Sierra region (31% vs. 14%, p = 0.01). In the unadjusted Cox model, the hazard of mortality was 1.7 times higher in women from the Selva than the Sierra (p = 0.025); this survival difference appeared to be largely explained by differences in the prevalence of TNBC. Our results suggest that the distribution of breast cancer subtypes differs between highly Indigenous American women from two regions of Peru. Disentangling the factors that contribute to this difference will add valuable information to better target prevention and treatment efforts in Peru and improve our understanding of TNBC among all women. This study demonstrates the need for larger datasets of Latin American patients to address differences between Latino subpopulations and optimize targeted prevention and treatment

Breast cancer subtype and survival among Indigenous American women in Peru

Latina women in the U.S. have relatively low breast cancer incidence compared to Non-Latina White (NLW) or African American women but are more likely to be diagnosed with the more aggressive "triple negative" breast cancer (TNBC). Latinos in the U.S. are a heterogeneous group originating from different countries with different cultural and ancestral backgrounds. Little is known about the distribution of tumor subtypes in Latin American regions. Clinical records of 303 female Peruvian patients, from the Peruvian National Cancer Institute, were analyzed. Participants were diagnosed with invasive breast cancer between 2010 and 2015 and were identified as residing in either the Selva or Sierra region. We used Fisher's exact test for proportions and multivariable Cox Proportional Hazards Models to compare overall survival between regions. Women from the Selva region were more likely to be diagnosed with TNBC than women from the Sierra region (31% vs. 14%, p = 0.01). In the unadjusted Cox model, the hazard of mortality was 1.7 times higher in women from the Selva than the Sierra (p = 0.025); this survival difference appeared to be largely explained by differences in the prevalence of TNBC. Our results suggest that the distribution of breast cancer subtypes differs between highly Indigenous American women from two regions of Peru. Disentangling the factors that contribute to this difference will add valuable information to better target prevention and treatment efforts in Peru and improve our understanding of TNBC among all women. This study demonstrates the need for larger datasets of Latin American patients to address differences between Latino subpopulations and optimize targeted prevention and treatment