Lactational transfer of sulforaphane-N-acetylcysteine in vivo and in human breast milk.

Sulforaphane (SFN) is a bioactive phytonutrient found in cruciferous vegetables. There is a lack of detailed information on the lactational transfer of SFN and SFN metabolites, and potential pharmacological effects on breastfeeding infants. We carried out two maternal supplementation studies in a mouse model, wherein lactating dams received either vehicle, 300 or 600 ppm SFN from postnatal day (PND) 1 to 5, or in a second experiment, vehicle or 600 ppm SFN from PND 1 to 14. The parent compound was only detectable in milk and plasma from dams receiving 600 ppm SFN for five days. The predominant metabolite SFN-N-acetylcysteine (SFN-NAC) was readily detected in milk from dams receiving 300 and 600 ppm SFN for five days or 600 ppm for 14 days. Maternal SFN-NAC plasma levels were elevated in both 600 ppm groups. Maternal hepatic and pulmonary expression of NRF2-related genes, Nqo1, Gsta2, Gstm1, and Gstp1, were significantly increased, generally following a dose-response; however, offspring induction varied. PND5 neonates in the 600-ppm group exhibited significantly elevated expression of Nqo1, Gsta2, and Gstp1 in liver, and Gstm1 and Gstp1 in lung. Findings support maternal dietary supplementation with SFN induces NRF2-related gene expression in neonates via lactational transfer of SFN-NAC. However, NQO1 enzyme activity was not significantly elevated, highlighting the need to optimize dosing strategy. Additionally, in a pilot investigation of lactating women consuming a typical diet, without any purified SFN supplementation, 7 out of 8 breast milk samples showed SFN-NAC above the limit of quantification (LOQ). Notably, the one sample below the LOQ was collected from the only participant who reported no consumption of cruciferous vegetables in the past 24 h. The parent compound was not detected in any of the human breast milk samples. Overall, these data indicate lactational transfer of SFN-NAC at dietary relevant levels. Future studies are needed to evaluate pharmacokinetics and pharmacodynamics of lactational transfer for potential preventive or therapeutic effects in breastfeeding children.

Exploring Challenges Related to Breast Cancer to Identify Opportunities for Advocacy in Hawassa City, Southern Ethiopia: A Community-Based, Qualitative Study.

PURPOSE: The aim of this study was to explore breast cancer (BC) challenges to identify opportunities for advocacy in southern Ethiopia in 2022. METHODS: Twenty-five participants from four local districts (kebeles) in Hawassa City were selected as key contributors to future work. Semistructured in-depth interviews were held for two clinicians, two local health bureau managers, two media managers, and three religious leaders. Two focus group discussions were conducted: one included six BC survivors and a caregiver; the other included two health extension workers, three members of the Women's Development Group, two community volunteers, one kebele leader, and one traditional healer. RESULTS: To our knowledge, our study was the first time that most participants had assembled. Many referred to patients as victims and BC as a killer disease or curse. Community and religious leaders were concerned about challenges and willing to collaborate. Survivors, providers, and religious leaders were identified as key sources of information, positive messages, and leadership. CONCLUSION: Recommendations for advocacy work in Hawassa include lobbying for BC as a health priority; including BC within the health extension package; initiating programs for earlier detection; educating the community to remove stigmas of the disease and treatments; working with media to disseminate messages that are inclusive of people in remote areas and speaking different languages; improving availability, affordability, and access to care; and assisting patients with psychosocial support. A strategic collaboration between religious leaders and health care providers was identified to increase community awareness and support advocacy for patients.

In Utero Ultrafine Particulate Exposure Yields Sex- and Dose-Specific Responses to Neonatal Respiratory Syncytial Virus Infection.

Exposure to particulate matter (PM) is associated with lower respiratory tract infections. The role of ultrafine particles (UFPs, ≤0.1 µm) in respiratory disease is not fully elucidated, especially in models of immunologically immature populations. To characterize the effects of maternal UFP exposure on neonatal infection, we exposed time-mated C57Bl/6n mice to filtered air or UFPs at a low dose (LD, ∼55 µg/m3) and high dose (HD, ∼275 µg/m3) throughout gestation. At 5 days of age, offspring were infected with a respiratory syncytial virus (RSV) strain known to mimic infant infection or sham control. Offspring body weights were significantly reduced in response to infection in the LD RSV group, particularly females. Pulmonary gene expression analysis demonstrated significantly increased levels of oxidative stress- and inflammation-related genes in HD-exposed male offspring in sham and RSV-infected groups. In males, the highest grade of inflammation was observed in the HD RSV group, whereas in females, the LD RSV group showed the most marked inflammation. Overall, findings highlight neonatal responses are dependent on offspring sex and maternal UFP dose. Importantly, infant RSV pathology may be enhanced following even low dose UFP exposure signifying the importance of preventing maternal exposure.

Association of an Acute Myocardial Infarction Readmission-Reduction Program With Mortality and Readmission.

BACKGROUND: Reducing hospital readmission after acute myocardial infarction (AMI) has the potential to both improve quality and reduce costs. As such, readmission after AMI has been a target of financial penalties through Medicare. However, substantial concern exists about potential adverse effects and efficacious readmission-reduction strategies are not well validated. METHODS AND RESULTS: We started an AMI readmissions reduction program in November 2017. Between July 2016 and February 2019, hospital billing data were queried to detect all inpatient hospitalizations at the Massachusetts General Hospital for AMI. Thirty-day readmission was identified through hospital billing data, and mortality was extracted from our electronic health record. The data set was merged with claims data for patients in accountable care organizations to detect readmission at other hospitals. We performed segmented linear regression, adjusting for secular trend and case mix, to assess the independent association of our program on both outcome variables. After inclusion and exclusion criteria were applied, the study population included 2020 patients. The overall 30-day readmission rate was higher before the intervention than after the intervention (15.5% versus 10.7%, P=0.002). The overall 30-day mortality rate was similar in both time periods (1.8% versus 1.4%, P=0.457). The program was associated with initial reduction in 30-day readmission (-9.8%, P=0.0002) and 30-day mortality (-2.6%, P=0.041). The program did not change trend in 30-day readmission (+0.19% readmissions/mo, P=0.554) and trend in 30-day mortality (-0.21% deaths/mo, P=0.119). CONCLUSIONS: An AMI readmissions reduction program that increases outpatient and emergency department (ED) access to cardiology care is associated with reduced 30-day readmission and 30-day mortality. Similar statistical techniques can be used to conduct a rigorous, mechanistic program evaluation of other quality improvement initiatives.

Referral for Expert Physical Activity Counseling: A Pragmatic RCT.

INTRODUCTION: Primary care physicians are well placed to offer physical activity counseling, but insufficient time is a barrier. Referral to an exercise specialist is an alternative. In Australia, exercise specialists are publicly funded to provide face-to-face counseling to patients who have an existing chronic illness. This trial aimed to (1) determine the efficacy of primary care physicians' referral of insufficiently active patients for counseling to increase physical activity, compared with usual care, and (2) compare the efficacy of face-to-face counseling with counseling predominantly via telephone. STUDY DESIGN: Three-arm pragmatic RCT. SETTING/PARTICIPANTS: Two hundred three insufficiently active (<7,000 steps/day) primary care practice patients (mean age 57 years; 70% female) recruited in New South Wales, Australia, in 2011-2014. INTERVENTION: (1) Five face-to-face counseling sessions by an exercise specialist, (2) one face-to-face counseling session followed by four telephone calls by an exercise specialist, or (3) a generic mailed physical activity brochure (usual care). The counseling sessions operationalized social cognitive theory via a behavior change counseling framework. MAIN OUTCOME MEASURES: Change in average daily step counts between baseline and 12 months. Data were analyzed in 2016. RESULTS: Forty (20%) participants formally withdrew; completion rates at 3 and 6 months were 64% and 58%, respectively. Intervention attendance was high (75% received five sessions). The estimated mean difference between usual care and the combined intervention groups at 12 months was 1,002 steps/day (95% CI=244, 1,759, p=0.01). When comparing face-to-face with predominantly telephone counseling, the telephone group had a non-significant higher mean daily step count (by 619 steps) at 12 months. CONCLUSIONS: Provision of expert physical activity counseling to insufficiently active primary care patients resulted in a significant increase in physical activity (approximately 70 minutes of walking per week) at 12 months. Face-to-face only and counseling conducted predominantly via telephone were both effective. This trial provides evidence to expand public funding for expert physical activity counseling and for delivery via telephone in addition to face-to-face consultations. TRIAL REGISTRATION: This trial is registered at www.anzctr.org.au/ ACTRN12611000884909.

Discrepancies between NCCN and ESMO guidelines in the management of anal cancer: a qualitative review.

There is an ever-growing need, with the ongoing developments in research and the progress towards patient centered care, to delineate standardized protocols of management of anal cancer. However, guidelines from different societies show some degree of disagreement. This is a systematic review of the literature to identify similarities and discrepancies between the guidelines for the management of anal cancer drafted by the European Society for Medical Oncology (ESMO) and by the National Comprehensive Cancer Network (NCCN). We found essentially similar management for investigation, diagnosis, chemotherapy regimens, and radiotherapy doses in both ESMO and NCCN recommendations in the management of anal cancer. There were few differences, which included the levels of evidence and grades of recommendations, the delineation of radiotherapy fields, and the treatment of the elderly and personalized medicine based on genetics. The follow-up regime is also marginally different in the first 2 years. Even if the observed differences may be justified by a different implementation of evidence-based medicine among different countries for particular management modalities of anal cancer, we identified the grey areas which need further study. In addition, these facets should be assessed more carefully when planning future guidelines.

A nano-selenium reactive barrier approach for managing mercury over the life-cycle of compact fluorescent lamps.

Compact fluorescent lamps contain small quantities of mercury, release of which can lead to human exposures of potential concern in special cases involving multiple lamps, confined spaces, or young children. The exposure scenarios typically involve solid lamp debris that slowly releases elemental mercury vapor to indoor spaces. Here we propose and demonstrate a reactive barrier approach for the suppression of that mercury release, and demonstrate the concept using uncoated amorphous nanoselenium as the reactive component. Multilayer structures containing an impregnated reactive layer and a mercury vapor barrier are fabricated, characterized, and evaluated in three exposure prevention scenarios: carpeted break sites, disposal/recycling bags, and boxes as used for retail sales, shipping, and collection. The reactive barriers achieve significant suppression of mercury release to indoor spaces in each of thethree scenarios. The nanoselenium barriers also exhibit a unique indicator function that can reveal the location of Hg contamination by local reaction-induced change in optical properties. The article also presents results on equilibrium Hg vapor pressure above lamp debris, mathematical modeling of reaction and transport processes within reactive barriers, and landfill stability of nanoselenium and its reaction products.