Differential Distribution of the DNA-PKcs Inhibitor Peposertib Selectively Radiosensitizes Patient-derived Melanoma Brain Metastasis Xenografts.

Radioresistance of melanoma brain metastases limits the clinical utility of conventionally fractionated brain radiation in this disease, and strategies to improve radiation response could have significant clinical impact. The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) is critical for repair of radiation-induced DNA damage, and inhibitors of this kinase can have potent effects on radiation sensitivity. In this study, the radiosensitizing effects of the DNA-PKcs inhibitor peposertib were evaluated in patient-derived xenografts of melanoma brain metastases (M12, M15, M27). In clonogenic survival assays, peposertib augmented radiation-induced killing of M12 cells at concentrations ≥100 nmol/L, and a minimum of 16 hours exposure allowed maximal sensitization. This information was integrated with pharmacokinetic modeling to define an optimal dosing regimen for peposertib of 125 mpk dosed just prior to and 7 hours after irradiation. Using this drug dosing regimen in combination with 2.5 Gy × 5 fractions of radiation, significant prolongation in median survival was observed in M12-eGFP (104%; P = 0.0015) and M15 (50%; P = 0.03), while more limited effects were seen in M27 (16%, P = 0.04). These data support the concept of developing peposertib as a radiosensitizer for brain metastases and provide a paradigm for integrating in vitro and pharmacokinetic data to define an optimal radiosensitizing regimen for potent DNA repair inhibitors.

Understanding the Experiences of Latinx LGBTQ Texans at the Beginning of the COVID-19 Pandemic.

Marginalized communities have been disproportionately affected by COVID-19, including both racial/ethnic minority and sexual minority populations. To date, there has been little research examining the impact of the COVID-19 pandemic at the intersections of marginalized identities. Furthermore, available national data on COVID-19 outcomes may obscure our understanding of region-specific outcomes, particularly in the U.S. South. Using an intersectional approach, we explore differences in worries over COVID-19, preventative behaviors, and COVID-19 outcomes in the early months of the pandemic in a diverse sample of LGBTQ people (N = 1076) living in Texas. Our findings indicated that LGBTQ Latinx people in Texas reported more COVID-19 related worries and adverse outcomes than non-Latinx LGBTQ people. These findings are in line with previous research that found that the increased risk to Latinx and LGBTQ populations in public health crises is often overlooked and can be attributed to many factors such as socioeconomic status, occupational propensity, disparities in physical health, and barriers to healthcare access. Furthermore, our findings suggest the necessity of utilizing an intersectional approach when examining the disproportionate burden marginalized communities face in public health crises.

What is the "modified" CTAB protocol? Characterizing modifications to the CTAB DNA extraction protocol.

Cetyltrimethylammonium bromide (CTAB)-based methods are widely used to isolate DNA from plant tissues, but the unique chemical composition of secondary metabolites among plant species has necessitated optimization. Research articles often cite a "modified" CTAB protocol without explicitly stating how the protocol had been altered, creating non-reproducible studies. Furthermore, the various modifications that have been applied to the CTAB protocol have not been rigorously reviewed and doing so could reveal optimization strategies across study systems. We surveyed the literature for modified CTAB protocols used for the isolation of plant DNA. We found that every stage of the CTAB protocol has been modified, and we summarized those modifications to provide recommendations for extraction optimization. Future genomic studies will rely on optimized CTAB protocols. Our review of the modifications that have been used, as well as the protocols we provide here, could better standardize DNA extractions, allowing for repeatable and transparent studies.

Optimizing the lysis step in CTAB DNA extractions of silica-dried and herbarium leaf tissues.

Premise: The use of cetyltrimethylammonium bromide (CTAB) is an effective and inexpensive method of extracting DNA from plants. The CTAB protocol is frequently modified to optimize DNA extractions, but experimental approaches rarely perturb a single variable at a time to systematically infer their effect on DNA quantity and quality. Methods and Results: We investigated how chemical additives, incubation temperature, and lysis duration affected DNA quantity and quality. Altering those parameters influenced DNA concentrations and fragment lengths, but only extractant purity was significantly affected. CTAB and CTAB plus polyvinylpyrrolidone buffers produced the highest DNA quality and quantity. Extractions from silica gel-preserved tissues had significantly higher DNA yield, longer DNA fragments, and purer extractants compared to herbarium-preserved tissues. Conclusions: We recommend DNA extractions of silica gel-preserved tissues that include a shorter and cooler lysis step, which results in purer extractions compared to a longer and hotter lysis step, while preventing fragmentation and reducing time.

Sexual Behaviors and Human Papillomavirus Vaccination in a Heterosexually Active Adult Population at Increased Risk for HIV Infection.

Human papillomavirus (HPV) is the most common sexually acquired infection in the US. Vaccination is effective against infection with high-risk HPV strains, yet HPV vaccine coverage is lower in the US than the national target. This study aimed to determine the relationship between sexual behaviors and HPV vaccination in a heterosexually active population at increased risk for HIV infection. Data from 380 participants aged 18-45 years obtained from the National HIV Behavioral Surveillance system increased risk heterosexuals cycle 5 (2019) in Houston, Texas, was analyzed. RDS-Analyst was used to generate population-based descriptive statistics. Modified Poisson regression models clustered on recruitment chain were conducted in SAS 9.4 to assess the relationship between sexual behaviors and HPV vaccination. Only 11.5% of participants had received at least one dose of the HPV vaccine. Regarding behaviors within the past 12 months, 44.8% reported having condomless casual sex, 51.3% reported having concurrent sexual partnerships while in their most recent relationship, 14.5% reported exchanging sex, and participants had an average of 4-5 sex partners. Further, those who exchanged sex had a significantly lower prevalence of HPV vaccine uptake when compared to those who did not exchange sex (adjusted prevalence ratio 0.23; confidence interval 0.10-0.52), while all other measures of sexual behavior were not significantly associated with HPV vaccination. More research is needed to understand the relationship between exchange sex and low prevalence of vaccination, specifically in women who bear the highest burden of poor HPV-related morbidity and mortality.

Timing of Introduction of Complementary Foods and Beverages to Infants of Low-Income Women.

Background: Although rates of complementary food and beverage (CFB) consumption among infants under 4 to 6 months of age have been declining, they remain well above the American Academy of Pediatrics (AAPs) recommendations. It is unclear if women with low income in the United States are more likely than other women to introduce CFBs early. We examined timing of introduction of CFBs to infants of mothers with low income to further illuminate infant feeding practices in this potentially vulnerable population. Materials and Methods: We analyzed infant feeding data collected prospectively from 443 mother-infant dyads. Data were obtained by interview at 1, 3, and 6 months postpartum. We used Kaplan-Meier curves to show time to introduction of CFBs overall and by type of CFB, and log-rank tests to compare timing by demographic and clinical characteristics. Results: Participants were mostly non-Hispanic black or white, with a high school education or less. By month 3, 48% of infants were fed at least one CFB, increasing to over 83% by month 5. Women who did not work outside the home introduced CFBs significantly earlier than those who worked, as did women who smoked compared with those who did not. Timing did not differ by other participant characteristics. Conclusions: Introduction of CFBs before 4-6 months was common. Clinical guidance and intervention programs should support mothers toward the goal of improving infant diets in this at-risk population.

Association between Clostridioides difficile infection and multidrug-resistant organism colonization or infection among hospitalized adults: A case-control study.

Using an ambidirectional case-control study, we found that the odds of Clostridioides difficile infection (CDI) were 3.38 (P = .01) times higher for patients with multidrug-resistant organism (MDRO) colonization compared to those without. MDRO colonization or infection 1-12 months before CDI testing significantly increased risk of positive CDI diagnosis (odds ratio 4.71, P = .02 and odds ratio = 5.03, P = .05, respectively) independent of antibiotic use, age, and comorbidity status. MDRO colonization and infection are associated with CDI, most significantly if they precede CDI.

Demographic and clinical characteristics of dominican adults admitted to a diabetic foot clinic in the Dominican Republic, 2015.

AIM: To identify the demographic and clinical characteristics of Dominican adults admitted to a diabetic foot clinic and compare these characteristics by sex to better characterize and understand the severity of diabetes in the Dominican Republic. METHODS: We conducted a retrospective medical chart review of Dominican adults admitted to the National Institute of Diabetes, Endocrinology, and Nutrition's (INDEN) diabetic foot clinic between January 1st, 2015 and December 31st, 2015. We generated descriptive statistics and compared results by sex. RESULTS: We assessed 447 medical charts of patients admitted in 2015. More men visited the clinic than women (65% vs. 35%). The average duration of diabetes was 14.4 ±â€¯8.9 years. Abscess was the most common foot problem (74% in men, 68% in women, p = 0.164). A slightly smaller proportion of men received amputations than women (46% vs. 51%, p = 0.390). Women were older (p < 0.001), less educated (p = 0.004), and less likely to be married (p < 0.001). Women also exhibited higher rates of obesity (p = 0.003), hypertension (p = 0.005), cardiovascular disease (p = 0.011), ischemic foot (p = 0.008), and above the knee amputations (p = 0.002). CONCLUSION: Implementation of diabetes education programs, introduction of proper foot care, and improved resources for lifestyle management are needed to increase awareness and subsequently decrease diabetes and its negative impact on the health and economy of the Dominican Republic. Our findings suggest that various risk factors and comorbidities important to the development of diabetes may be disproportionately affecting women. Interventions should focus on women and their behaviors that increase risk for diabetes.

Reasons for Early Cessation of Breastfeeding Among Women with Low Income.

Background: Most women in the United States do not meet their breastfeeding goals, and low-income women breastfeed at lower rates than the general population. While risk factors for early cessation have been documented, specific reasons for discontinuing among this population are less understood. We examined reasons for cessation among low-income mothers to inform the development of targeted strategies to address breastfeeding disparities. Materials and Methods: We performed a secondary data analysis using prospective data collected during a randomized intervention trial of Special Supplemental Nutrition Program for Women, Infants, and Children (WIC)-eligible women interviewed in the third trimester and at 1, 3, and 6 months postpartum. We included the 221 women who initiated breastfeeding and stopped by 6 months. Women's reasons for discontinuing breastfeeding were grouped by thematic category and compared by time of breastfeeding cessation. Results: The most common reasons reported overall for breastfeeding cessation were concerns about breast milk supply and latch difficulty. Some reasons differed significantly by time of cessation. Latch difficulty was reported most often by women who breastfed for 1 month or less; supply concerns increased with increasing breastfeeding duration. Returning to work/school was uncommonly reported for those who stopped by 1 month, but more frequently reported in those with later cessation. Conclusions: We found that low-income women reported similar reasons for early breastfeeding cessation as have been reported for other populations of women. These results underscore the need for appropriately timed, culturally sensitive interventions to reduce disparities in duration of breastfeeding, specifically to address latch difficulty in the first few weeks and supply concerns as infants grow.

A Randomized Trial of Prenatal Video Education to Improve Breastfeeding Among Low-Income Women.

Background: Many women initiate breastfeeding but do not meet their duration goals, and low-income women initiate and continue breastfeeding at lower rates than their counterparts. One-on-one counseling is associated with increased breastfeeding but requires significant resources. In contrast, video education, which requires fewer resources and is effective in other health care settings, such as vaccine uptake, has gone untested for prolonging breastfeeding duration among low-income women. Objective: To determine whether use of an educational breastfeeding video shown individually to low-income pregnant women in the prenatal clinic would prolong duration of any and exclusive breastfeeding. Methods: A multicenter, randomized, controlled trial was conducted in four prenatal clinics. Low-income pregnant women were randomized to view the intervention (breastfeeding education) or control (prenatal nutrition) video in the third trimester and interviewed by telephone at 1, 3, and 6 months postpartum about infant feeding practices. Kaplan-Meier survival curves with log-rank tests and Cox proportional hazards regression were utilized to compare groups. Results: Of the 816 eligible women approached, 64% participated: 263 assigned to the intervention, and 259 assigned to the control. Six-month data were obtained for 211 (80%) and 220 (85%) women, respectively. Rate of breastfeeding cessation did not differ by group (hazard ratios; HR = 1.00, 95% confidence interval [CI]: 0.81-1.24 and HR = 0.93, 95% CI: 0.76-1.14, for any and exclusive breastfeeding, respectively). Conclusion: A single viewing of a breastfeeding education video shown in the prenatal clinic did not impact breastfeeding duration or exclusivity among low-income women in this study. Although not sufficient alone, educational videos may be useful as one component of a comprehensive program to promote breastfeeding.

The Impact of a Prenatal Education Video on Rates of Breastfeeding Initiation and Exclusivity during the Newborn Hospital Stay in a Low-income Population.

BACKGROUND: Guidelines recommend prenatal education to improve breastfeeding rates; however, effective educational interventions targeted at low-income, minority populations are needed as they remain less likely to breastfeed. OBJECTIVE: To determine whether a low-cost prenatal education video improves hospital rates of breastfeeding initiation and exclusivity in a low-income population. METHODS: A total of 522 low-income women were randomized during a prenatal care visit occurring in the third trimester to view an educational video on either breastfeeding or prenatal nutrition and exercise. Using multivariable analyses, breastfeeding initiation rates and exclusivity during the hospital stay were compared. RESULTS: Exposure to the intervention did not affect breastfeeding initiation rates or duration during the hospital stay. The lack of an effect on breastfeeding initiation persisted even after controlling for partner, parent, or other living at home and infant complications (adjusted odds ratio [OR] = 1.05, 95% CI, 0.70-1.56). In addition, breastfeeding exclusivity rates during the hospital stay did not differ between the groups (P = .87). CONCLUSION: This study suggests that an educational breastfeeding video alone is ineffective in improving the hospital breastfeeding practices of low-income women. Increasing breastfeeding rates in this at-risk population likely requires a multipronged effort begun early in pregnancy or preconception.

Exploring intended infant feeding decisions among low-income women.

BACKGROUND: Low-income women have the lowest rates of breastfeeding in the United States. Greater understanding of factors that predict intention to feed artificial breastmilk substitute is needed to inform the design and timing of interventions to promote breastfeeding among vulnerable women. This study aimed to identify demographic and reproductive characteristics and other factors associated with intent to feed artificial breastmilk substitute among low-income women. MATERIALS AND METHODS: Data from 520 low-income women interviewed at 24-41 weeks of gestation during enrollment in a prenatal breastfeeding education intervention study were analyzed. Participant characteristics, reasons for feeding decision, and sources and types of information received were compared among women intending to feed only artificial breastmilk substitute and other women. RESULTS: Most participants (95%) had already chosen an infant feeding method at the time of interview. There were no differences in plans to return to work by feeding plan. Women reporting intention to feed only artificial breastmilk substitute were less likely to report receiving information about the benefits of breastfeeding, how to breastfeed, and pumps and were more likely to cite personal preference and convenience as reasons for their decision. Women were more likely to intend to feed artificial breastmilk substitute if they had a previous live birth or had not breastfed a child, including the most recent. CONCLUSIONS: These findings suggest breastfeeding promotion should target women early and include sensitive, effective ways to promote breastfeeding among women who have not previously successfully breastfed. Breastfeeding history should be elicited, and plans to pump should be supported prenatally.

Prevalence of baby bottle versus breastfeeding graphics on products in national chain stores.

OBJECTIVE: This study surveyed the prevalence of bottle versus breastfeeding graphic images on products marketed for pregnant mothers and young children available for purchase in national chain stores. STUDY DESIGN AND METHODS: This was a product survey/content analysis. Eighteen national chain stores located in a 10-mile radius of Charlottesville, VA were visited. In total, 2,670 individual items in 11 categories of baby shower and baby gift merchandise (shower invitations, greeting cards, gift wrap, shower decorations, baby dolls, baby books, infant clothing, bibs, nursery decorations, baby blankets, and disposable diapers) were assessed. The main outcome measures were prevalences of baby bottle and breastfeeding graphic images. RESULTS: Baby bottle images were found on products in eight of the 11 categories of items surveyed. Thirty-five percent of baby dolls were marketed with a baby bottle. The prevalence of bottle images on items in all other categories, however, was low. Of the 2,670 items surveyed, none contained a breastfeeding image. CONCLUSIONS: The low prevalence of baby bottle images on commonly purchased baby gift and baby shower items is encouraging. However, the absence of breastfeeding images and the relatively high prevalence of baby dolls marketed with a baby bottle demonstrate that breastfeeding is not portrayed as the physiologic norm on these products. Product designers should explore ways to promote breastfeeding, consumers should make informed choices in product selection, and advocacy groups should promote guidelines for these products.

Measuring menstrual discomfort: a comparison of interview and diary data.

BACKGROUND: Menstrual discomfort is common among women of reproductive age and can be debilitating. The accuracy of self-report of menstrual discomfort is unknown. METHODS: At enrollment into the DES Reproductive Health Study in 1990, premenopausal women classified their frequency of any menstrual discomfort as "always," "often," "sometimes," and "never." Subsequently, women provided daily diary information for up to 6 months regarding any menstrual discomfort and medication used for menstrual pain. RESULTS: A total of 324 women contributed data on 4 or more menstrual cycles in the prospective study. At enrollment, 10% had reported never having menstrual discomfort. Of these, 65% recorded at least 1 day of menstrual discomfort during follow-up. For the 27% who had reported always having discomfort, 88% recorded discomfort in all cycles. The enrollment statement of discomfort was more strongly correlated with the percentage of cycles in which women took medication for menstrual pain; respondents who said they never had menstrual discomfort reported use of pain medication in 3% of cycles; sometimes, 36%; often, 67%; and always, 92%. The average number of days per cycle with prospectively recorded menstrual discomfort was also correlated with the enrollment response. CONCLUSIONS: A single question regarding frequency of menstrual discomfort was positively correlated with prospectively recorded menstrual discomfort and especially with pain requiring medication.

Phenomenological study of nurses caring for dying patients.

Little is known about how nurses experience caring for dying patients. Yet, entering the patient's world often involves dealing with death and dying and is a major challenge to oncology nurses. The purpose of this article is to describe the shared practices of oncology nurses caring for dying patients. Stories from staff nurses on an oncology unit were analyzed using a hermeneutic method to identify and describe four themes: knowing the patient, preserving hope, easing the struggle, and providing for privacy. The four themes contribute to knowledge development about how nurses enter into and experience caring for dying patients. The growing body of knowledge previously reported has included descriptions of critical behaviors in caring for dying patients, coping strategies nurses used when caring for dying patients and their families, and the meaning of oncology nursing practice. The four themes described in this article expand our understanding of the nurses' experience in caring for dying patients.

Noninvasive monitoring of the neonatal respiratory system.

The development and use of a large variety of nonivasive respiratory monitors have provided the neonatal intensive care unit clinician with invaluable tools for continuous monitoring. Thorough understanding of how each monitor functions, what it measures, and factors that contribute to monitor errors and injuries is vital for appropriate use of this technology and for proper interpretation of monitor values. On-going patient assessment and a good understanding of physiologic principles affecting respiratory status and monitoring also are imperative to interpreting monitor values. Noninvasive monitors have raised a controversy about home use of monitors to prevent sudden infant death syndrome--a review of National Institute of Health recommendations is helpful when cardiorespiratory monitoring is an issue. Family teaching and support are beneficial for discharge planning.