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Coronavirus disease 2019 (COVID-19) has been the most talked-about disease of the past few years. Patients with significant comorbidities have been at particular risk of adverse outcomes. This study looked at the outcomes and risk factors for adverse outcomes among patients on chronic hemodialysis for end-stage renal disease, a group of patients known to be particularly susceptible to infectious complications.To assess outcomes and risk factors for adverse outcomes of COVID-19 infection among patients on chronic hemodialysis.We searched PubMed/MEDLINE, EMBASE,Of the 920 studies identified through the initial database search, only 17 were included in the final analysis. The studies included in the analysis were mostly carried out during the first wave. We found that COVID-19 incidence among patients on hemodialysis was significant, over 10% in some studies. Those who developed COVID-19 infection were most likely going to be hospitalized, and over 1 in 5 died from the infection. Intensive care unit admission rate was lower than the infection lethality rate. Biochemical abnormalities and dyspnea were generally reported to be associated with adverse outcomes.This systematic review confirms that patients on chronic hemodialysis are very high-risk individuals for COVID-19 infections, and a significant proportion was infected during the first wave. Their prognosis is overall much worse than in the general population, and every effort needs to be made to decrease their exposure.

The constructivist strategy is the teacher's conscious decision-making to develop the skills of their students; The objective of this research is to explain the constructivist strategies for learning physiotherapy. Based on a bibliographic review in the EBSCO, Google Scholar, Dialnet, SciELO, Redalyc, BMC Medicine databases, among others, published from 2009 to 2021, with open access, with a search strategy by keyword, theme, tricks of search and author bibliographic references, the 105 documents found were subjected to a process of validity, reliability and relevance, leaving 67 articles. Learning concepts were addressed as an active process of acquiring abilities, skills and knowledge through experience, observation or study. The active methodologies used in physiotherapy such as problem-based learning, team-based learning and simulation-based learning. The flipped classroom combines asynchronous and synchronous learning, respects learning styles. The use of constructivist strategies in physiotherapy is still insufficient, it is suggested for future studies to deepen and expand the application step by step by inserting methodologies, tools of concrete use in detail in the educational context in this field.

In germ cell transplantation experiments, the use of sterile recipients that do not produce their own gametes is an important prerequisite. Triploidization and dnd gene knockdown (KD) methods have been widely used to produce sterile fish. However, triploidization does not produce complete sterility in some fish species, and gene KD is labor and time intensive since it requires microinjection into individual fertilized eggs. To overcome these problems, in this study, we generated homozygous mutants of the dead end (dnd) gene in rainbow trout (Oncorhynchus mykiss) using the clustered regulatory interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) system, analyzed their reproductive capacity, and evaluated their suitability as recipients for germ cell transplantation. By crossing F1 heterozygous mutants produced from founders subjected to genome editing, an F2 generation consisting of approximately 1/4 homozygous knockout mutants (dnd KO) was obtained. The dnd KO hatchlings retained the same number of primordial germ cells (PGCs) as the wild-type (WT) individuals, after which the number gradually decreased. At 1 year of age, germ cells were completely absent in all analyzed individuals. To evaluate the dnd KO individuals as recipients for germ cell transplantation, germ cells prepared from donor individuals were transplanted into the abdominal cavity of dnd KO hatchlings. These cells migrated to the recipient gonads, where they initiated gametogenesis. The mature recipient individuals produced only donor-derived sperm and eggs in equivalent numbers to WT rainbow trout. These results indicate that dnd KO rainbow trout are suitable recipient candidates possessing a high capacity to nurse donor-derived germ cells.

Natural killer (NK) cells are an innate immune cell type that serves at the first level of defense against pathogens and cancer. NK cells have clinical potential, however, multiple current limitations exist that naturally hinder the successful implementation of NK cell therapy against cancer, including their effector function, persistence, and tumor infiltration. To unbiasedly reveal the functional genetic landscape underlying critical NK cell characteristics against cancer, we perform perturbomics mapping of tumor infiltrating NK cells by jointin vivoAAV-CRISPR screens and single cell sequencing. We establish a strategy with AAV-SleepingBeauty(SB)- CRISPR screening leveraging a custom high-density sgRNA library targeting cell surface genes, and perform four independentin vivotumor infiltration screens in mouse models of melanoma, breast cancer, pancreatic cancer, and glioblastoma. In parallel, we characterize single-cell transcriptomic landscapes of tumor-infiltrating NK cells, which identifies previously unexplored sub-populations of NK cells with distinct expression profiles, a shift from immature to mature NK (mNK) cells in the tumor microenvironment (TME), and decreased expression of mature marker genes in mNK cells.CALHM2,a calcium homeostasis modulator that emerges from both screen and single cell analyses, shows bothin vitroandin vivoefficacy enhancement when perturbed in chimeric antigen receptor (CAR)-NK cells. Differential gene expression analysis reveals thatCALHM2knockout reshapes cytokine production, cell adhesion, and signaling pathways in CAR- NKs. These data directly and systematically map out endogenous factors that naturally limit NK cell function in the TME to offer a broad range of cellular genetic checkpoints as candidates for future engineering to enhance NK cell-based immunotherapies.

Nephrotic syndrome is a condition characterized by damage to podocytes that results in significant proteinuria, edema, hyperlipidemia, and hypercoagulability. Infections and malignancies are frequently associated with nephrotic syndrome. The COVID-19 virus has been associated with several atypical presentations of upper respiratory infections and acute kidney injury. Considering that COVID-19 causes systemic inflammatory changes, it seems plausible that it may also lead to nephrotic syndrome. This study aimed to investigate if an association between COVID-19 and the different types of nephrotic syndromes exists. Data were extracted into a spreadsheet. Statistical analysis was performed using Statistical Package for Social Sciences (SPSS, IBM Corp., Armonk, NY, USA). We performed a systematic search of PubMed/Medline and Embase databases using both medical subject headings (MeSH) and regular keywords associated with COVID-19 and nephrotic syndrome, including different types of nephrotic syndromes. The search was performed on 17th December 2021. We included case reports and case series about adult patients who developed findings suggestive of nephrotic syndrome shortly after infection or vaccination. We excluded cases involving children, pregnant women, articles written in languages other than English, and those that were not retrievable. The relevance and quality of identified articles were assessed. We included 32 articles in the study, primarily case reports and case series. In our study, COVID-19 and the COVID-19 vaccine have been associated with the development of nephrotic syndrome, primarily a collapsing form of focal segmental glomerulosclerosis, although other forms have been observed as well. There was little consistency in patient histories, clinical presentations, clinical courses, or treatment regimens, although it appeared that most cases eventually resolved. More cases need to be reported and analyzed before more definitive conclusions can be reached. In conclusion, nephrotic syndrome is a possible complication of both COVID-19 infection and the COVD-19 vaccine and should be considered in patients exhibiting sudden onset edemas or deterioration in kidney function. While the majority of cases respond to standard treatment, clearer guidelines will need to be developed once more data is available.

Purpose: A strong interpersonal relationship after stroke is important for the prevention of depression in survivors and family caregivers. This study aimed to test the feasibility of quality of relationship intervention for stroke dyads called Hand in Hand (HiH). Methods: Sixteen dyads were randomized into either the HiH group ( n = 8) or information, support, and referral (ISR) control group ( n = 8). HiH dyads received up to eight sessions, with topics prioritized according to a 17-item screening tool. ISR dyads received up to eight sessions that included information, active listening, and referrals. Feasibility, acceptability, and outcomes data were collected for both groups. Results: The HiH and ISR groups were feasible and acceptable. Caregivers in both groups, as well as survivors in the ISR group, experienced improvements in depressive symptoms and other select outcomes. Conclusions: Findings suggest that HiH is feasible to implement with stroke dyads and that it merits further refinement and testing.

The COVID-19 pandemic represents an unprecedented situation, impacting all productive sectors. Human resources departments have been instrumental in migrating from a functional to a strategic perspective, contributing to the strengthening of organisations. This chapter aims to analyse workplace responses to the COVID-19 pandemic and the adoption of human resources practices through a systematic literature review. Findings indicate that the main responses to the pandemic were creating a work team to manage the crisis; virtual work at the individual and group levels; encouraging virtual leadership; psychological, financial, and health support; fostering a work environment favourable to empowerment, shared decision-making, and participation. Other frequently mentioned human resources practices were compensation, flexible working, work design, performance management, remote working, work-family balance, recognition programmes, and training and development practices.

BACKGROUND: Twenty-nine years since the National Institutes of Health (NIH) Revitalization Act was passed to encourage minority participation in clinical trials (CTs), and yet there remains a deficit of minorities recruited into CT. This induces the idea that Women-of-Color (WoC) (Blacks, Latinas, Native Americans, Asians) are less likely to participate than their Northern/European White (NE/W) counterparts. Using a mixed methods study that included quantitative surveys and qualitative interviews, we dive into understanding how a diverse group of women understand and perceive CT, along with concerns and attitudes towards clinical research. METHOD: The interview script was designed to capture patients’ understanding and concerns of clinical research, reasons for agreeing or declining participation, and facilitators or barriers to participation. The CRAs were trained in establishing rapport with the patient, clearly communicating the questions, and probing for more elaboration of responses. Interviewees and interviewers were matched based on gender and race. A total of four CRAs conducted the interviews – two Asian CRAs interviewed the Asian participants, one Latina CRA interviewed Latinas and White, non-Hispanics, and one African American CRA who interviewed the African American participants. Structured individual interviews were conducted by trained CRAs. The audio-recordings of all interviews were transcribed word for word and reviewed for accuracy. Two independent coders then read and coded each transcript and extracted a set of quotes (phrases or sentences) that reflected the themes. RESULTS: A total of 44 women were accrued between August 2019 and February 2020. The racial/ethnic makeup include the following: 20 Latinas ([White/Hispanic] - one Salvadorian, one half Mexican/half Armenian, and 18 Mexican), 8 Asian (one half Chinese/half Japanese, one Indian, three Chinese, two Vietnamese, one Thai), 8 African American/non-Hispanic, and 8 White/non-Hispanic (two Iranian and 6 European). Age range of women were 27 to 71 years of age. Seventeen women declined participation. CONCLUSION: The in-person interviews highlighted feelings of cultural mistrust among the WoC participants and not in the NE/W participating in the study. The results highlight the influence of cultural mistrust as a barrier and the importance of diversity of the clinical research team in overcoming this barrier, particularly among WoC clinical trial participants. Of course, there is undeniable heterogeneity within the WoC population; each community is influenced by its own historical and present contexts that influence its relationship with the medical system. Approaches to overcome this barrier must address the specific needs of each community. Diversity of the clinical research team and the ability of the team to address culturally relevant beliefs can increase trial diversity. The generalizability, quality, and effectiveness of healthcare treatment requires diverse representation in all clinical trials. Citation Format: Veronica Jones, Noe Chavez, Vanessa M. Robles, Laura Kruper, Lily Lai, Amy Polverini, Lusine Tumyan, Lesley Taylor, James Waisman, Angelica Sanchez, Christine Thai, Tanya Chavez, Nikita Wright. A qualitative exploration of women’s understanding of clinical research and decisions to participate: Improving diversity in clinical research [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B076.

Background Hyperinsulinemia, the presence of excess insulin relative to glucose in the blood, is considered to be a poor prognostic indicator for patients with triple-negative breast cancer (TNBC). mTOR, a downstream effector of insulin, enhances mitochondrial biogenesis and activity, thereby increasing acetyl-CoA precursors. Increased acetyl-CoA can, in turn, be utilized by nuclear acetyltransferases for histone acetylation, a critical feature of genome regulation. While signaling pathways downstream of insulin have been established for sometime, the effect of insulin on chromatin remains unclear. We hypothesized that hyperinsulinemia-induced metabolic changes lead to genome-wide changes in histone acetylation in TNBC. Results MDA-MB-231 cells were xenografted into hyperinsulinemic and wild-type mice. Tumors in the hyperinsulinemic mice displayed elevated levels of histone acetylation compared to tumors in normal insulin conditions. We show that insulin treatment in vitro leads to global increase in chromatin-associated histone acetylation, in particular at H3K9, through the PI3K/AKT/mTOR pathway. Genome-wide analyses revealed that most promoter regions have an increase in histone acetylation upon insulin treatment. In addition, insulin induces higher levels of reactive oxygen species and DNA damage foci in cells. Conclusions These results demonstrate the impact of hyperinsulinemia on altered gene regulation through chromatin and the importance of targeting hyperinsulinemia-induced processes that lead to chromatin dysfunction in TNBC. Electronic supplementary material The online version of this article (10.1186/s13072-019-0290-9) contains supplementary material, which is available to authorized users.

Given that the COVID-19 pandemic resulted in an unprecedented scenario, there were no previous lessons learned about the organizational responses to social problems. As a result of the above, this chapter describes the practices used by seven Colombian organizations to face the first months of the pandemic based on corporate social innovation framework. A qualitative approach was used to carry out the study and a qualitative content analysis as a research method. The results obtained indicate that the companies participating in the research developed actions in the four pillars, with actions associated with social issues being more prevalent, especially concerning workers and vulnerable populations.

During puberty, a woman’s breasts are vulnerable to environmental damage (“window of vulnerability”). Early exposure to environmental carcinogens, endocrine disruptors, and unhealthy foods (refined sugar, processed fats, food additives) are hypothesized to promote molecular damage that increases breast cancer risk. However, prospective human studies are difficult to perform and effective interventions to prevent these early exposures are lacking. It is difficult to prevent environmental exposures during puberty. Specifically, young women are repeatedly exposed to media messaging that promotes unhealthy foods. Young women living in disadvantaged neighborhoods experience additional challenges including a lack of access to healthy food and exposure to contaminated air, water, and soil. The purpose of this review is to gather information on potential exposures during puberty. In future directions, this information will be used to help elementary/middle-school girls to identify and quantitate environmental exposures and develop cost-effective strategies to reduce exposures.

The United States is experiencing growth in populations from culturally diverse backgrounds. Studies suggest that Latinx and American Indians experience chronic conditions such as cancer, heart disease, and diabetes in greater numbers than whites. Literature also suggests that Latinx and American Indian families play a significant role as informal caregivers for loved ones with chronic illness. However, little information is available about interventions to assist these patient-family caregiver dyads cope. The purpose of this systematic review is to synthesize published studies about psychosocial interventions developed or adapted for Latinx and American Indian care dyads in order to determine: (1) the benefits of these interventions; (2) their distinguishing features or adaptations, and; (3) recommendations for future intervention development. The protocol for this review was registered in advance with the International Prospective Register of Systematic Reviews (PROSPERO). We searched the databases CINAHL, PsycINFO, MEDLINE, and PubMeb using MeSH-derived keywords developed in consultation with a research librarian. Studies were included/excluded based upon pre-specified criteria. Three-hundred thirty-five records were identified, screened by the research team, and tracked according to PRISMA guidelines. After removing duplicates (n=9), studies that did not pertain to the conditions of interest (n=13), and studies that did not meet inclusion criteria (n=305), eight studies remained. Relevant information was abstracted from the final studies and synthesized by the research team. The majority of interventions for these populations are in cancer. Findings about benefits are largely inconclusive. Adaptations include a focus on cultural contexts, as well as culturally-based strengths, caregiving norms, and values.

Objective: Microscopic colitis (MC) is a chronic inflammatory disease of the colon that is characterized by chronic, watery, nonbloody diarrhea. Concern regarding a potential association between proton-pump inhibitors (PPIs) and MC has recently emerged. We sought to systematically review and summarize the evidence for the potential association between PPIs and MC. Data Sources: We systematically searched EMBASE, MEDLINE, Cochrane Database of Systematic Reviews, International Pharmaceutical Abstracts, and Google Scholar using the terms proton-pump inhibitors (omeprazole, lansoprazole, dexlansoprazole, rabeprazole, pantoprazole, or esomeprazole), microscopic colitis, collagenous colitis, and lymphocytic colitis. Study Selection: Full-text, English-language reports of case reports/series, observational studies, experimental studies, and systematic reviews/meta-analyses published between January 2000 to August 2016 were included. Bibliographies from pertinent publications were reviewed for additional references. Outcome was defined as the development of biopsy-confirmed MC. Data Extraction/Synthesis: A total of 19 publications were identified: 5 case control studies and 14 case reports/series (encompassing a total of 32 cases). All studies were limited by small sample sizes. Risk of MC by dose or specific PPI agent was not investigated in any of the studies. A review of the current body of evidence reveals a possible association between PPIs and MC. Conclusions: There is a need for large observational studies of high quality to examine the differential effect of specific PPIs and whether the magnitude of association is dose dependent. Given their widespread use, clinicians should routinely question whether patients are receiving unnecessary treatment with PPIs and discontinue therapy where appropriate.

A strong interpersonal relationship after stroke is important for the well-being of survivors and family caregivers. However, few interventions are designed to strengthen the relationship between members of the care dyad in order to prevent depression and other poor outcomes. The aim of this study was to feasibility test a quality of relationship intervention for stroke dyads called Hand in Hand (HiH). Sixteen survivor-caregiver dyads were recruited and randomized into either the HiH intervention group (n=8) or the Information, Support, and Referral (ISR) control group (n=8). HiH dyads received up to 8 sessions with a social worker in-person, by telephone, or by Zoom web conference, prioritized according to a 17-item screening tool with 17 corresponding HiH content areas. ISR dyads received up to 8 sessions that included information, active listening, and referrals as needed. Process, satisfaction, and pre/post outcomes data were collected for both groups. Seventy-five percent of HiH dyads completed over half the sessions which lasted, on average, 55 minutes (range 26-76). Sixty-two percent of ISR dyads completed over half the sessions which lasted, on average, 21 minutes (range 15-33). Dyads in both groups reported being satisfied with the program materials and processes. Survivors and caregivers in both groups experienced improvements in outcomes, particularly caregivers in the HiH group who showed improvements in communication, coping, subjective relationship quality, and depressive symptoms. Findings suggest that HiH is feasible to implement with stroke dyads and has promise for improving outcomes for participants. Additional research is needed to determine program efficacy.

Despite cancer being the leading cause of death across most racial/ethnic groups, Hispanic women have the second highest mortality rate attributed to diabetes (4.7%) according to the Centers for Disease Control and Prevention (CDC). While cancer and diabetes are two distinct diseases, previous studies have demonstrated that diabetic women have a poor chance of breast cancer survival when compared to nondiabetic women. Well-known key drivers of hyperinsulinemia and insulin resistance, such as insulin and AMPK, are also those involved in breast cancer. This link could possibly contribute to the increased mitogenic effects and risk for aggressive breast cancers in Hispanic women. Based on these findings, metformin, a drug standardly used to treat and prevent hyperglycemia, may be a possible alternative (other than tamoxifen) for breast cancer prevention. Eat, Move, Live (EML), a 5-week community-based program, focuses on targeting possible treatments of chronic diseases and risk reduction through attitude and lifestyle modifications. Exercise, nutritional and health awareness classes were implemented to change participants' perspectives regarding chronic diseases and their susceptibility to other morbidities. Questionnaires were given to the participants at baseline and at two follow-ups (5 weeks and 12 weeks) to assess any changes in their attitudes, behaviors, nutrition, lifestyle and beliefs around taking medication for preventative treatments. A total of 56 participants' pretreatment responses were collected via a five-point Likert scale (1-strongly disagree, 5-strongly agree). Demographic data showed that 69% of the respondents were Hispanic women, of whom 46% completed an education level of high school or less. A majority of the responses averaged a “neutral” response to taking medication for management and prevention of diabetes. We infer that their inability to select a stance in their responses may be associated with the lack of knowledge that the community has regarding chronic diseases and risk-prevention methods. Therefore, we anticipate that availability of proper education tools and resources is essential to potentially prevent future morbidities and mortalities. Ultimately, we aim to establish a pilot study that emphasizes the necessity and importance of interventional programs, like EML, to enhance chemoprevention using metformin and improve health outcomes in high-risk breast cancer populations. Citation Format: Mayra Serrano, Angelica Sanchez, Christine Thai, Katty Nerio, Cristal Resto, Marisela Garcia, Tanya A. Chavez, Laura L. Kruper, Veronica C. Jones, Lisa D. Yee, Alan Nuñez, Ellen J. Rippberger, Angela K. Wong, Noé R. Chávez, Karen Herold, Chidimma M.K. Kalu, Jackelyn A. Alva-Ornelas, Jerneja Tomsic, Krista M. Round, Regina Agulto, Margarita Robles, Ombeni M. Idassi, Kendall J. Kennedy, Christopher Sistrunk, Victoria L. Seewaldt. Receptiveness of metformin as a breast cancer prevention drug within the Hispanic community [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr B119.

The United States is increasingly racially and ethnically diverse. In fact, California is now a majority-minority region, with a greater percentage of its population comprised of racial minorities than whites. Yet, minorities are continually under-represented in clinical research trials, which provide crucial information on which the future of cancer treatments is built. Without representative inclusion of participants of color in clinical research, we cannot develop effective preventative and treatment approaches for everyone. This current study investigates the factors, including characteristics of study consenters, that may influence women—particularly women of color (WOC)—to accept or decline participation in breast cancer-related trials. We assess these factors through a brief survey, administered to patients immediately after they were invited to participate in a breast cancer-related clinical study. From the beginning of study accrual to the present, twenty-three patients have taken the survey. We anticipate accruing 200 participants at a rate of 25 per month. For the preliminary analyses, we split participants in two groups: white women (WW) (n = 14) and women of color (WOC) (n = 9). We conducted independent sample t-tests to compare the responses of WW and WOC. More WOC (M = 1.44, SD = 0.73) reported that it is important that their consenter is of the same ethnicity or race than WW (M = 1.00, SD = .00), t (21) = -2.32, p < .05. Similarly, WOC (M = 1.44, SD = .73) also reported that it is important that the person inviting them to participate in research look like people in their community, compared to the importance placed on this factor by WW (M = 1.00, SD = .00), t (21) = -2.32, p < .05). More WOC (M = 2.33, SD = 1.23) also cited “feeling overwhelmed” with their medical condition as influential in their decision to participate in clinical research than WW (M = 1.31, SD = .48), t (20) = -2.75, p < .05. Although both groups positively rated their interaction with the consenter, we observed marginal differences between WOC and WW. WOC (M = 7.00, SD = .00) gave higher ratings to the variable of “consenter created an atmosphere of trust and support” compared to ratings given by WW (M = 6.29, SD = 1.07), t (21) = -1.99, p = .06. Though participants are generally satisfied with their consenter interaction, different factors influence WW and WOC as they decide whether to participate in clinical research. When identified, these factors can be used to inform more inclusive consenting processes. Citation Format: Noe R. Chavez, Alan Nunez, Angela K. Wong, Tanya A. Chavez, Ellen Rippberger, Christine Thai, Angelica Sanchez, Ombeni M. Idassi, Krista M. Round, Kendall Kennedy, Margarita Robles, Jackelyn A. Alva-Ornelas, Jerneja Tomsic, Chidimma M.K. Kalu, Laura L. Kruper, Veronica C. Jones, Sharon Clancy, Amy C. Polverini, Courtney Vito, Karen Harold, Terry Hyslop, Carola M. Zalles, Daniel B. Schmolze, Christopher Sistrunk, Victoria L. Seewaldt. Influencing women's attitudes toward participation in breast cancer clinical research: Improving inclusion of women of color [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr A082.

The United States (US) is racially and culturally diverse. Still, white women disproportionately comprise clinical trial participants, stemming largely from the fact that minorities often decline participation. Clinical trial findings, therefore, have not been representative of the diverse patient population, and have stymied progress in precision medicine and cancer prevention. According to the CDC, among Asian/Pacific Islander females, the leading cause of death is cancer. Moreover, they have more total cancer-related deaths than any other racial group. Per the 2017 US Census, Asians are the third largest minority group of the population (6.6%). Despite the grave health disparities faced by a sizable proportion of the population, the literature is sparse with regards to their research engagement. For example, several studies have focused on Black and Hispanic consenting rates, including one study that demonstrated no significant differences between the two groups (Wendler, Kington, Madans, Wye, Christ-Schmidt, Pratt et al., 2005) and another that indicated relatively lower enrollment rates among Hispanics and Blacks (Murthy, Krumholz, Gross, 2004). This gap in research is largely due to the marked heterogeneity with respect to language, nationality, and acculturation status. We examined Asian participation in three therapeutic, noninterventional trials that aim to develop early detection methods and accurate prognosis in women at high risk for breast cancer. Primarily, we collect leftover tissue and/or cells from fine needle aspirations (FNA) to better understand the cellular microenvironment that correlates with breast cancer development. We analyzed demographic data across these studies to investigate refusal rates among Asian women. Across the three trials, 3,119 participants were screened. Of the total number screened, 426 participants were eligible, 368 consented, and 58 declined. Of those who declined, 23.5% were Asians, 13.9% Hispanic, 8.3% Blacks, 5.6% Native Americans, and 11.4% White/non-Hispanic. Notably, Asians had the highest refusal rate. Fisher's exact test (two-tailed) was conducted to examine refusal rates for Asians compared to Whites, Blacks, and Hispanics. Results suggest that Asians had significantly higher rates of compared to Whites (p = .02, observed odds ratio = .42, 95% CI [.20, .86]), but were not significantly different than Blacks or Hispanics. The under-representation of Asians in research may exacerbate health disparities. Thus, further studies should examine ways, such as increasing racial and cultural competency, for increasing Asian representation in clinical research studies. Ultimately, we believe that illuminating under-representation of the “forgotten” Asian population in clinical research can inform future interventions that promote chemoprevention and treatment of this high-risk population. Citation Format: Stacey N. Doan, Christine Thai, Angela K. Wong, Tanya A. Chavez, Angelica Sanchez, Laura L. Kruper, Veronica C. Jones, Sharon Clancy, Amy C. Polverini, Lisa D. Yee, Courtney Vito, Alan Nunez, Ellen J. Rippberger, Noe R. Chavez, Karen Herold, Chidimma M.K. Kalu, Jackelyn A. Alva-Ornelas, Jerneja Tomsic, Krista M. Round, Margarita Robles, Ombeni M. Idassi, Kendall J. Kennedy, Christopher Sistrunk, Victoria L. Seewaldt. The forgotten race: Under-representation of Asians in clinical research [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr A084.

Purpose: To highlight the importance of building a high-risk breast cancer clinic for women who do not have a BRCA 1, BRCA 2 or other highly penetrant cancer susceptibility mutation. Background: Breast cancer is the most common cancer in women and the second most prevalent cause of cancer death of women in the United States; the lifetime risk for breast cancer in women is approximately 12%. Women may be at increased risk for breast cancer for many reasons including family history, genetic alterations, age, reproductive status and menstrual history. Most women who are at increased risk of developing breast cancer do not have a BRCA 1, BRCA 2 or other mutation. The majority of breast cancer diagnoses are due to acquired somatic mutations; only 5 to 10% of breast cancer diagnoses are attributable to highly penetrant Mendelian cancer susceptibility genes. White women with Ashkenazi Jewish ancestry tend to have a higher incidence of BRCA 1 and 2 mutations; traditionally, most research efforts about highly penetrant genes have been focused on this group rather than other racial and ethnic groups. However, there is a great need to study breast cancer risk-reduction strategies in racial and ethnic minorities in the United States, particularly because most breast cancers are not caused by BRCA 1 and 2 mutations. City of Hope is located approximately 21 miles northeast of Los Angeles and operates 13 clinical practice locations including Los Angeles, Orange, Riverside, San Bernardino and Ventura counties. These five counties are home to the majority of California's multicultural and ethnic residents where San Bernardino County has the highest percentage of Hispanics (49.9%) and blacks (8.3%), Ventura County has the highest percentage of whites (48.1%), and Orange County has the highest concentration of Asians (18.2%). It has been established in the literature that the greatest benefit from breast cancer prevention strategies comes from treating women who are at high risk of the disease. While it is important to build a high-risk breast cancer clinic for women with genetic mutations, it is equally important to build a high-risk breast clinic for women who are at increased risk of breast cancer but do not have a mutation, particularly because most breast cancer is diagnosed in this population. In addition, it is crucial to educate high-risk patients that although they may have tested negative for a genetic mutation if they have a family history of breast cancer, they warrant close clinical surveillance. Methods: We are proposing a retrospective, descriptive study of data that will be collected as part of a high-risk breast cancer program implemented by City of Hope. Results/Conclusions: We expect to discuss the findings related to serving women of all races and ethnicities who do not have a mutation in a highly penetrant gene mutation. Citation Format: Karen Herold, Lisa D. Yee, Chidimma M. Kalu, Laura L. Kruper, Veronica C. Jones, Amy C. Polverini, Sharon Clancy, Tanya A. Chavez, Jackelyn A. Alva-Ornelas, Noe R Chavez, Ellen J. Rippberger, Jerneja Tomsic, Christopher Sistrunk, Ombeni Idassi, Daniel B. Schmolze, Courtney Vito, Alan Nunez, Angela K. Wong, Krista M. Round, Christine Thai, Angelica Sanchez, Margarita Robles, Kendall Kennedy, Terry Hyslop, Victoria L. Seewaldt. Architecture of increased breast cancer risk [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr B109.

Background: Recruiting participants who are representative of the population as a whole is essential to ensure the development of treatments that benefit all rather than a select few. Understanding the reasons patients accept or decline participation, and then making adjustments to the recruiting process based on these findings, is one way to encourage study participation. Aim: To better understand what factors influence a potential participant's decision to either accept or decline participation in breast cancer trials. Methods: These are preliminary data from a pilot study that uses a short questionnaire to investigate which factors influence a woman's consent or decline to study participation. Women are approached for this study after being asked to participate in one of three other breast cancer trials targeting women who either have breast cancer or are at high risk for breast cancer. Women are approached for this study regardless of their decision to participate in the previous study. Participants are asked a set of questions about 1. the specific interaction they had with the consenter from the previous study, 2. general characteristics of a consenter, and 3. research in general. Demographic information is also collected for future analysis of responses based on race/ethnicity, income, education level, and primary language. Results: A total of 24 participants have completed the questionnaire so far, with an accrual rate of approximately 25 patients per month. Participants ranked the importance of the various factors on a 4-point scale with 1 being “not important at all” and 4 being “very important.” Factors that participants indicated were the least important to their decision to participate were: financial compensation (xÌ… 1.07), racial/ethnic parity between consenter and consentee (\bar x $ 1.19), consenter looking like someone from their community (\bar x $ 1.19), gender parity (\bar x $ 1.19), religious beliefs (\bar x $ 1.38), pleasing their doctor (\bar x $ 1.56), and feeling overwhelmed (\bar x $ 1.85). Factors participants indicated were the most important to them were: the desire to benefit others in the future (\bar x $ 3.63), to benefit their family (\bar x $ 3.56), to acknowledge the contributions of past generations (\bar x $ 3.20), the feeling participation was “the right thing to do” (\bar x $ 3.15), presence or lack of potential side effects associated with participation ((\bar x $ 3.15), feeling empowered by the consenter (\bar x $ 3.15), feeling the consenter was listening (\bar x $ 3.11), and trust in research (\bar x $ 3.07). Conclusions: Concerning the consenter, physical characteristics such as race/ethnicity and gender parity were less important than the actual interaction with the consenter, including their flexibility, listening skills, and ability to make the patient feel empowered. For research in general, the idea of contributing to the “greater good” emerged as a powerful motivation to participate. An emphasis on this, as well as well-trained consenters, may help studies attract more participants. Note: This abstract was not presented at the conference. Citation Format: Ellen Rippberger, Noe Chavez, Tanya Chavez, Christine Thai, Angelica Sanchez, Angela Wong, Karen Herold, Alan Nenez, Krista Rounds, Victoria Seewaldt. Factors influencing women's attitudes toward participation in breast cancer clinical research [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr A086.

Background: Breast cancer (BC) prevention clinical trials (CTs) play a vital role in the progress of preventative measures and treatments for all races and ethnicities. However, Northern European whites (NE/W) continue to be disproportionally enrolled (e.g., 93.5% were non-Hispanic white in the STAR trial), while minorities such as Asians, blacks, Latinas, and Native Americans (NA) lag in participation. Current studies suggest that minorities are not approached as frequently as NE/W; however, they are just as willing to participate. Here we present a successful recruitment strategy to improving minority accrual in CTs at a Comprehensive Cancer Center located in Duarte, CA. Method: Results from community focus groups suggested the need to mentor local youth who strive to pursue a career in the medical field. Consequently, from February 2016 to July 2018, four bilingual, bicultural clinical research assistants (CRAs) were recruited from the catchment area of City of Hope (CoH). The CRAs, in collaboration with seven surgeons, two radiologists, and one medical oncologist, led the recruitment for three nontherapeutic BC prevention CTs at CoH. Results: All four CRAs were 1) first-generation American, 2) fluent in Spanish or Vietnamese, 3) born and raised in Southern California, and 4) pre-health. Of the 3,148 patients who were screened, 398 were eligible for enrollment, 369 consented, and 58 declined. Primary languages and races/ethnicities of those who declined include the following: 7% Armenian, 9% Chinese, 78% English, 2% Thai, and 5% Spanish; 28% Asian, 3% black, 28% Latina, 2% NA, and 67% white (22% NE, 17% Middle Eastern/North African). Demographics of the consenting population include the following: primary language - >1% Armenian, 4% Chinese, 89% English, >1% Korean, and 7% Spanish; race/ethnicity - 14% Asian, 6% black, 30% Latina, 5% NA, and 75% white (40% NE). Of the white population (n = 277), 11% were Middle Eastern/North African, 53% NE, and 36% Latina. Accrual surpassed both the CoH catchment area (11.3% Asian, 8% black, 24% Hispanic, 1% NA, and 32% NE/W) and the CoH interventional/nontherapeutic CT population (10% Asian/Pacific Islander, 4% black, 21% Hispanic, >1% NA, and 55% NE/W). Conclusion: Contrary to current accrual of CTs, here we show that minorities can have a large representation in CT accrual, as long as they are provided the opportunity. Accrual of Asians, Latinas, and NAs exceeded the catchment area and accrual of other CoH CTs. Interestingly, Chinese-speaking women comprised the highest declination group of the non-English speakers, and Asians and Latinas declined the most outside of non-whites. Cultural competency and bilingualism appear to be characteristics of a CRA that may help in accruing minority women into CTs. Our findings suggest that they are just as willing to participate, and the first step is to simply ask. Citation Format: Tanya A. Chavez, Christine Thai, Angelica Sanchez, Laura L. Kruper, Veronica C. Jones, Sharon Clancy, Amy C. Polverini, Lisa D. Yee, Courtney A. Vito, Noé R. Chávez, Alan Nuñez, Ellen J. Rippberger, Angela K. Wong, Karen Herold, Chidimma M.K. Kalu, Jackelyn A. Alva-Ornelas, Jerneja Tomsic, Krista M. Round, Margarita Robles, Ombeni Idassi, Kendall J. Kennedy, Terry Hyslop, Carola M. Zalles, Christopher Sistrunk, Victoria L. Seewaldt. Diversifying breast cancer clinical trial accrual: An approach to recruitment at a Comprehensive Cancer Center [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr A083.

Excess levels of insulin relative to glucose in the blood, or hyperinsulinemia, is considered to be a poor prognostic indicator for patients with triple negative breast cancer (TNBC). While this association has been recognized for some time, the mechanistic role of hyperinsulinemia in promoting TNBC remains unclear. We show that insulin treatment leads to genome-wide increase in histone acetylation, in particular at H3K9, through the PI3K/AKT/mTOR pathway in MDA-MB-231 cells. Genome-wide analysis showed that the increase in histone acetylation occurs primarily at gene promoters. In addition, insulin induces higher levels of reactive oxygen species and DNA damage foci in cells. In vivo, hyperinsulinemia also enhances growth of MDA-MB-231 derived tumors through increased histone acetylation. These results demonstrate the impact of hyperinsulinemia on altered gene regulation through chromatin and the importance of targeting hyperinsulinemia-induced processes that lead to chromatin dysfunction in TNBC.

The present study was aimed to investigate the relationship between normal serum concentrations of thyrotropin (TSH) and urinary incontinence (IU), urinary infections, and quality of life in old women. Euthyroid post-menopausal women without sarcopenia, estrogen replacement, emotional illness, and-or cancer were enrolled as participants. Anthropometric indicators, serum glucose and estradiol, and thyroid profile were measured. Sociodemographic, clinical, physical activity, and quality of life (SF-36) surveys were applied. One-hour pad test and International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) were used to determine UI. Urinalysis was also done. In agreement with results from the pad test (cut-off point ≥ 1.4 g), the ICIQ-SF reveled ~50% of incontinent women. A high percentage of women had moderate-high bacteriuria and urinary infections. Logistic regression analysis showed that age is a risk factor for both UI and urinary infection. Nor diabetes, number of pregnancies or childbirths, urinary infections, and bacteriuria influenced in the presence of UI. To allocate women into four groups according to their age (

Microscopic colitis (MC) is a chronic inflammatory disease of the colon that is characterized by chronic, watery, nonbloody diarrhea. Concern regarding a potential association between proton-pump inhibitors (PPIs) and MC has recently emerged. We sought to systematically review and summarize the evidence for the potential association between PPIs and MC.We systematically searched EMBASE, MEDLINE, Cochrane Database of Systematic Reviews, International Pharmaceutical Abstracts, and Google Scholar using the terms proton-pump inhibitors (omeprazole, lansoprazole, dexlansoprazole, rabeprazole, pantoprazole, or esomeprazole), microscopic colitis, collagenous colitis, and lymphocytic colitis.Full-text, English-language reports of case reports/series, observational studies, experimental studies, and systematic reviews/meta-analyses published between January 2000 to August 2016 were included. Bibliographies from pertinent publications were reviewed for additional references. Outcome was defined as the development of biopsy-confirmed MC.A total of 19 publications were identified: 5 case control studies and 14 case reports/series (encompassing a total of 32 cases). All studies were limited by small sample sizes. Risk of MC by dose or specific PPI agent was not investigated in any of the studies. A review of the current body of evidence reveals a possible association between PPIs and MC.There is a need for large observational studies of high quality to examine the differential effect of specific PPIs and whether the magnitude of association is dose dependent. Given their widespread use, clinicians should routinely question whether patients are receiving unnecessary treatment with PPIs and discontinue therapy where appropriate.

Although the zebrafish is a major model organism, how they determine sex is not well understood. In domesticated zebrafish, sex determination appears to be polygenic, being influenced by multiple genetic factors that may vary from strain to strain, and additionally can be influenced by environmental factors. However, the requirement of germ cells for female sex determination is well documented: animals that lack germ cells, or oocytes in particular, develop exclusively as males. Recently, it has been determined that oocytes are also required throughout the adult life of the animal to maintain the differentiated female state. How oocytes control sex differentiation and maintenance of the sexual phenotype is unknown. We therefore generated targeted mutations in genes for two oocyte produced signaling molecules, Bmp15 and Gdf9 and here report a novel role for Bmp15 in maintaining adult female sex differentiation in zebrafish. Females deficient in Bmp15 begin development normally but switch sex during the mid- to late- juvenile stage, and become fertile males. Additionally, by generating mutations in the aromatase cyp19a1a, we show that estrogen production is necessary for female development and that the function of Bmp15 in female sex maintenance is likely linked to the regulation of estrogen biosynthesis via promoting the development of estrogen-producing granulosa cells in the oocyte follicle., Author Summary Domesticated zebrafish use a polygenic mechanism for sex determination, where oocytes play a key role in both promoting primary female sex determination and maintenance of female sex in adults. All animals that cannot produce oocytes during the larval stage develop as males and adult females that cease oocyte production readily sex revert to a male phenotype. These results have led to the hypothesis that oocytes produce a signal that instructs the somatic gonad to develop as an ovary and to suppress testis development. In this report we present evidence that the oocyte-produced signaling protein Bmp15 is required for females to maintain their sexual phenotype, but plays no role in primary female sex determination. Specifically, zebrafish bmp15 mutants can initially develop as females, but during the juvenile stage they sex revert to fertile males. In addition, we show that the ovary-expressed estrogen- producing enzyme, Cyp19a1a aromatase, is a key somatic gonad-produced protein that promotes female development. Our results define for the first time, specific genetic components of the mechanism by which zebrafish promote and maintain their sex, and may also provide insight into the mechanism(s) that allows 2% of all teleost species to reverse their sex as adults.

INTRODUCTION Fish is a good source of nutrients, including protein and omega-3 fatty acids. However, there is growing concern over the potentially harmful effects of persistent organic pollutants (...

Germ cell tumors (GCTs) are malignant cancers that arise from embryonic precursors known as Primordial Germ Cells. GCTs occur in neonates, children, adolescents and young adults and can occur in the testis, the ovary or extragonadal sites. Because GCTs arise from pluripotent cells, the tumors can exhibit a wide range of different histologies. Current cisplatin-based combination therapies cures most patients, however at the cost of significant toxicity to normal tissues. While GWAS studies and genomic analysis of human GCTs have uncovered somatic mutations and loci that might confer tumor susceptibility, little is still known about the exact mechanisms that drive tumor development, and animal models that faithfully recapitulate all the different GCT subtypes are lacking. Here, we summarize current understanding of germline development in humans and zebrafish, describe the biology of human germ cell tumors, and discuss progress and prospects for zebrafish GCT models that may contribute to better understanding of human GCTs.

293 Pags.- 36 Figs.- 28 Tabls., La embriogénesis de la microspora, mediante el cultivo de anteras o microsporas aisladas, es el método de producción de DH5 en cereales con mayor potencialidad. Aunque los protocolos de producción de DH5 mediante la embriogénesis de la microspora se han mejorado durante los últimos años, sigue existiendo un gran desconocimiento de los mecanismos moleculares que controlan este proceso. Esta tesis doctoral tiene como objetivo principal el estudio de los mecanismos moleculares implicados en el inicio del patrón de desarrollo embriogénico de la microspora en cereales. Para abordar este objetivo se ha tomado la cebada como especie modelo, y el trigo como especie que presenta una mayor dificultad en la producción de DH5. Para cumplir este objetivo se ha planteado los siguientes subobjetivos: 1- Identificación y caracterización de genes que se expresan al inicio del patrón de desarrollo embriogénico de la microspora en cebada y trigo panadero. 2- Comparación de la expresión génica entre embriogénesis de la microspora y embriogénesis zigótica en cebada y trigo panadero. 3- Comparación de la expresión génica entre genotipos de distinta respuesta a la embriogénesis de la microspora en cebada y trigo panadero. 4- Estudio de la expresión de genes implicados en síntesis, degradación y regulación de Acido Abscísico (ABA) durante la embriogénesis de la microspora en cebada. 5- Identificación de genes asociados al efecto inductor de los ovarios en cultivo de anteras de trigo panadero., Este trabajo ha sido realizado con cargo a los Proyectos del Plan Nacional de Recursos y Tecnologías Agroalimentarias AGL2007- 62930/AGR y AGL2O1O-17509, y con la ayuda de una beca Predoctoral de la Junta de Ampliación de Estudios del Consejo Superior de Investigaciones Científicas.

Background Neural tube defects (NTDs) are common birth defects (~1 in 1000 pregnancies in the US and Europe) that have complex origins, including environmental and genetic factors. A low level of maternal folate is one well-established risk factor, with maternal periconceptional folic acid supplementation reducing the occurrence of NTD pregnancies by 50-70%. Gene variants in the folate metabolic pathway (e.g., MTHFR rs1801133 (677 C > T) and MTHFD1 rs2236225 (R653Q)) have been found to increase NTD risk. We hypothesized that variants in additional folate/B12 pathway genes contribute to NTD risk. Methods A tagSNP approach was used to screen common variation in 82 candidate genes selected from the folate/B12 pathway and NTD mouse models. We initially genotyped polymorphisms in 320 Irish triads (NTD cases and their parents), including 301 cases and 341 Irish controls to perform case–control and family based association tests. Significantly associated polymorphisms were genotyped in a secondary set of 250 families that included 229 cases and 658 controls. The combined results for 1441 SNPs were used in a joint analysis to test for case and maternal effects. Results Nearly 70 SNPs in 30 genes were found to be associated with NTDs at the p MFTC, CDKN2A, ADA, PEMT, CUBN, GART, DNMT3A, MTHFD1 and T (Brachyury)) and included the known NTD risk factor MTHFD1 R653Q (rs2236225). The single strongest signal was observed in a new candidate, MFTC rs17803441 (OR = 1.61 [1.23-2.08], p = 0.0003 for the minor allele). Though nominally significant, these associations did not remain significant after correction for multiple hypothesis testing. Conclusions To our knowledge, with respect to sample size and scope of evaluation of candidate polymorphisms, this is the largest NTD genetic association study reported to date. The scale of the study and the stringency of correction are likely to have contributed to real associations failing to survive correction. We have produced a ranked list of variants with the strongest association signals. Variants in the highest rank of associations are likely to include true associations and should be high priority candidates for further study of NTD risk.