Ovarian Cancer Genetics: Subtypes and Risk Factors

The genetics of ovarian cancer are a complex, ever evolving concept that presents hurdles in classification, diagnosis, and treatment in the clinic. Instead of common driver mutations, genomic instability is one of the hallmarks of ovarian cancer. While ovarian cancer is stratified into different clinical subtypes, there still exists extensive genetic and progressive diversity within each subtype. In high-grade serous ovarian cancer, the most common subtype, TP53 is mutated in over 90% of all patients while the next most common mutation is less than 20%. However, next-generation sequencing and biological statistics have shown that mutations within DNA repair pathways, including BRCA1 and BRCA2, are common in about 50% of all high-grade serous patients leading to the development of a breakthrough therapy of poly ADP ribose polymerase (PARP) inhibitors. This is just one example of how a better understanding of the complex genetic background of ovarian cancer can improve clinical treatment. A thorough review of ovarian cancer genetics and the effect it has on disease development, diagnosis, progression, and treatment will enhance the understanding of how to better research and treat ovarian cancer

Qualitative Study of First-Generation Latinas: Understanding Motivation for Choosing and Persisting in Engineering

Latina undergraduates pursuing an engineering degree continue to be an underrepresented group at four-year universities. Compared to their male counterparts, fewer women enter the field of engineering; however, of those Latino/as who do matriculate, they have the same likelihood of persisting as their White counterparts. Furthermore, a dearth of underrepresented students such as Latino/as and first-generation college students enter or remain in the field of engineering. The need for increased gender and racial/ethnic representation in engineering is a documented need allowing for the production of a wider range of innovative products that take into consideration different perspectives that represent the make-up of the nation as a whole. Recent studies demonstrate that Latinas who are enrolled in the field of engineering remain in engineering at higher rates than other ethnic minorities. In order to increase and retain greater ethnic and gender diversity in engineering, this research seeks to examine what motivates first-generation Latinas in engineering at an urban public university to pursue engineering and persist. Past research has investigated the experiences of first-generation students more generally, without distinguishing specific populations or their choice of study. In addition, several studies investigate why first-generation and underrepresented students drop out of college; some have found that it is due to an unclear purpose for college, adjustment issues to the college environment, and feelings of isolation. The perspectives of first-generation Latina engineering students are captured through conducting eight qualitative in-depth interviews and through analyzing their narratives. This research elucidates some of the reasons why Latinas choose engineering in college and why they continue in engineering using Achievement Goal Theory (AGT) as the theoretical framework. This theory posits that goals are cognitive accounts of what a person tries to accomplish and one’s purposes or reasons for doing the task. This research demonstrates that participants displayed a higher sense of purpose, not only in mastery and performance, but also in a sense of self-reliance and intellectual self. This research serves as a point of departure towards highlighting ways in which the field of engineering can become a more desirable major for first-generation Latina women. The results of this work point to specific methods for accomplishing this goal

Elderly Parents' Expectations and Realizations of Informal Care from Adult Children: An Economic Perspective

Over the next 50 years, the U.S. will see a tremendous growth in the elderly population due to the aging baby boomers and rising life expectancies. Currently, forty-five percent of seniors need assistance with activities of daily living. Medicare and Medicaid provide little coverage for these services, leaving the elderly to rely on informal care. While previous research has examined who provides care and the process by which children and parents arrange care, I use the Study of Assets and Health Dynamics among the Oldest Old (AHEAD) to examine parents' expectations about future care from children and the implications of those predictions after the onset of a disability. Using a probit framework, I examine who anticipates care from children among non-disabled households and who actually receives care among disabled households. The household characteristics correlated with anticipating future care differ from those correlated with the true probability of receiving care. For example, an additional daughter increases the probability that an elderly household expects future care, however an additional daughter is not statistically significantly related to the true probability of receiving care. Conversely, parents' socioeconomic status is not statistically significantly related to the probability of expecting future care, but lower socioeconomic households are more likely to receive care. I directly evaluate the accuracy of parents' predictions using the panel nature of the data. Among households that expect future care from children, over 60 percent do not receive care after the initial onset of a disability and nearly 50 percent still do not receive care after living with disabilities for five years. Among households that do not anticipate care from children, approximately 25 percent unexpectedly receive care after the initial onset of a disability, while slightly more than 50 percent receive care after needing help for five years. Further analysis reveals that inaccurately predicting care from children is associated with some economic and psychological costs, whereas unexpectedly receiving care is correlated with some economic and psychological benefits

Integrated immunoisolation and protein analysis of circulating exosomes using microfluidic technology

Developing blood-based tests is appealing for non-invasive disease diagnosis, especially when biopsy is difficult, costly, and sometimes not even an option. Tumor-derived exosomes have attracted increasing interest in non-invasive cancer diagnosis and monitoring of treatment response. However, the biology and clinical value of exosomes remains largely unknown due in part to current technical challenges in rapid isolation, molecular classification and comprehensive analysis of exosomes. Here we developed a new microfluidic approach to streamline and expedite the exosome analysis pipeline by integrating specific immunoisolation and targeted protein analysis of circulating exosomes. Compared to the conventional methods, our approach enables selective subpopulation isolation and quantitative detection of surface and intravesicular biomarkers directly from a minimally invasive amount of plasma samples (30 μL) within ~100 min with markedly improved detection sensitivity. Using this device, we demonstrated phenotyping of exosome subpopulations by targeting a panel of common exosomal and tumor-specific markers and multiparameter analyses of intravesicular biomarkers in the selected subpopulation. We were able to assess the total expression and phosphorylation levels of IGF-1R in non-small-cell lung cancer patients by probing plasma exosomes as a non-invasive alternative to conventional tissue biopsy. We foresee that the microfluidic exosome analysis platform will form the basis for critically needed infrastructures for advancing the biology and clinical utilization of exosomes

Long-term Outcomes of Childhood Family Income Supplements on Adult Functioning

ImportanceDuring an ongoing longitudinal cohort study, a casino opening created a natural cash transfer experiment. Some participating families received income supplements, and others did not. The children in this study are now adults.ObjectiveTo assess the long-term outcomes of family income supplements received in childhood.Design, Setting, and ParticipantsThis community-representative longitudinal cohort study set in western North Carolina assessed 1266 participants aged 9, 11, and 13 years at intake up to 11 times up to age 30 years from January 1993 to December 2015. Data were analyzed from January to December 2021.ExposuresIn 1996, a southeastern American Indian tribe implemented a cash transfer program of approximately $5000 annually per person for tribal members. Participants were compared on whether their family ever received the cash transfers (American Indian vs non–American Indian), the duration of the transfers, and annual amount based on the number of parents.Main Outcomes and MeasuresParticipants were followed up at ages 25 and 30 years to assess mental health symptoms, substance use symptoms, and functional outcomes (physical health, risky or illegal behaviors, and financial and social functioning).ResultsOf 1266 included participants, 320 (25.3%) were American Indian and 581 (49.7%) were female. Participants whose families received cash transfers during childhood reported fewer anxiety symptoms (relative risk [RR], 0.33; 95% CI, 0.25-0.44), depressive symptoms (RR, 0.51; 95% CI, 0.42-0.62), and cannabis symptoms (RR, 0.47; 95% CI, 0.27-0.82). They also reported improved physical health (RR, 0.66; 95% CI, 0.55-0.80) and financial functioning (RR, 0.78; 95% CI, 0.67-0.89) and fewer risky or illegal behaviors (RR, 0.57; 95% CI, 0.46-0.72) compared with those who did not receive the cash transfer. This pattern was supported by a series of heterogeneity analyses in which children whose families received the transfers for the longest duration and whose families received the largest transfer (due to having multiple American Indian parents) had the lowest levels of symptoms and the highest levels of functioning.Conclusions and RelevanceIn this natural experiment, a family cash transfer in childhood was associated with positive adult functioning 20 years later. The findings support programs like the child tax credit or universal basic income that provide cash directly to families with children

The childhood trauma questionaire: validity, reliability and factor structure among adolescents in Calabar, Nigeria

Introduction: Child abuse is a cause of increasing concern globally and is known to have significant negative effects on the physical and psychological well-being of children. Validated instruments for screening child abuse in Nigeria are scarce.Aim: This study aimed to determine the validity, reliability and factor structure of the 28 item version of the Childhood Trauma Questionnaire among Secondary School students in Calabar South, Cross River state, Nigeria.Methodology: In a cross-sectional study, a sample of 161 students was drawn from two secondary schools in Calabar South, Cross River State, using multi-stage technique. A socio-demographic questionnaire, the Childhood Trauma questionnaire (CTQ-28), the General Health Questionnaire (GHQ-12) and the Self-reporting Questionnaire (SRQ-20) were administered to the selected students. Convergent validity between CTQ and other scales, reliability using Cronbach alpha and the factor structure of CTQ using principal component analysis were assessed. The data was analyzed with the Statistical Package for Social Sciences, 21st edition (SPSS-21).Results: Cronbach alpha was 0.80. Internal consistency for the subscales were 0.69 for emotional abuse, 0.60 for physical abuse, 0.60 for sexual abuse, 0.79 for emotional neglect and 0.21 for physical neglect. For convergent validity, correlation coefficients with the GHQ-12 and the SRQ-20 were 0.39 and 0.45 respectively (p<0.05). Principal Components Analysis yielded a four factor solution.Conclusion: The 28 item version of the Childhood Trauma Questionnaire has acceptable reliability and validity and can be useful as a screen for child abuse among adolescents in Nigeria.Key words: CTQ, validity, reliability, factor structure, adolescent

Potent antitrypanosomal activities of 3-aminosteroids against African trypanosomes: investigation of cellular effects and of cross-resistance with existing drugs. Molecules

Treatment of animal African trypanosomiasis (AAT) requires urgent need for safe, potent and affordable drugs and this has necessitated this study. We investigated the trypanocidal activities and mode of action of selected 3-aminosteroids against Trypanosoma brucei brucei. The in vitro activity of selected compounds of this series against T. congolense (Savannah-type, IL3000), T. b. brucei (bloodstream trypomastigote, Lister strain 427 wild-type (427WT)) and various multi-drug resistant cell lines was assessed using a resazurin-based cell viability assay. Studies on mode of antitrypanosomal activity of some selected 3-aminosteroids against Tbb 427WT were also carried out. The tested compounds mostly showed moderate-to-low in vitro activities and low selectivity to mammalian cells. Interestingly, a certain aminosteroid, holarrhetine (10, IC50 = 0.045 ± 0.03 µM), was 2 times more potent against T. congolense than the standard veterinary drug, diminazene aceturate, and 10 times more potent than the control trypanocide, pentamidine, and displayed an excellent in vitro selectivity index of 2130 over L6 myoblasts. All multi-drug resistant strains of T. b. brucei tested were not significantly cross-resistant with the purified compounds. The growth pattern of Tbb 427WT on long and limited exposure time revealed gradual but irrecoverable growth arrest at ≥ IC50 concentrations of 3-aminosteroids. Trypanocidal action was not associated with membrane permeabilization of trypanosome cells but instead with mitochondrial membrane depolarization, reduced adenosine triphosphate (ATP) levels and G2/M cell cycle arrest which appear to be the result of mitochondrial accumulation of the aminosteroids. These findings provided insights for further development of this new and promising class of trypanocide against African trypanosomes

When it just won\u27t go away: oral artemisinin monotherapy in Nigeria, threatening lives, threatening progress.

BACKGROUND: Oral artemisinin monotherapy (AMT), an important contributor to multi-drug resistant malaria, has been banned in Nigeria. While oral AMT has scarcely been found for several years now in other malaria-endemic countries, availability has persisted in Nigeria\u27s private sector. In 2015, the ACTwatch project conducted a nationally representative outlet survey. Results from the outlet survey show the extent to which oral AMT prevails in Nigeria\u27s anti-malarial market, and provide key product information to guide strategies for removal. RESULTS: Between August 10th and October 3rd, 2015 a total of 13,480 outlets were screened for availability of anti-malarials and/or malaria blood testing services. Among the 3624 anti-malarial outlets, 33,539 anti-malarial products were audited, of which 1740 were oral AMT products, primarily artesunate (n = 1731). Oral AMT was imported from three different countries (Vietnam, China and India), representing six different manufacturers and 11 different brands. Availability of oral AMT was highest among pharmacies (84.0%) and Patent Propriety Medicine Vendors (drug stores, PPMVs) (38.7%), and rarely found in the public sector (2.0%). Oral AMT consisted of 2.5% of the national anti-malarial market share. Of all oral AMT sold or distributed, 52.3% of the market share comprised of a Vietnamese product, Artesunat CONCLUSION: Oral AMT is commonly available in Nigeria\u27s private sector. Cessation of oral AMT registration and enforcement of the oral AMT ban for removal from the private sector are needed in Nigeria. Strategies to effectively halt production and export are needed in Vietnam, China and India

Attending to what’s important: what heat maps may reveal about attention, inhibitory control, and fraction arithmetic performance

Math proficiency is an important predictor of educational attainment and life success. However, developing mathematical competency is challenging, and some content (e.g., fractions) can be enigmatic. Numerous factors are suspected to influence math performance, including strategy knowledge, attention, and executive functions. In two online studies, we investigated the relationship between adults’ fraction arithmetic performance, confidence judgments, inhibitory control (a component of executive functions), and attention to strategy-relevant fraction components. We explored the utility of heat maps (based on mouse clicks) to measure adults’ attention to strategy-relevant fraction arithmetic components (operationalized according to each mathematical operation). In Study 1, attending to strategy-relevant fraction components was correlated with inhibitory control, but this finding did not replicate in Study 2. Across both studies, inhibitory control and attention to strategy-relevant fraction components were correlated with arithmetic accuracy. Intraindividual variability in participants’ attention to strategy-relevant fraction components was also found. Our findings suggest that heat map questions may be a viable alternative to assess participants’ attention during fraction tasks and that attention to specific fraction-arithmetic problem features is related to problem-solving accuracy