Experiences of hereditary cancer care among transgender and gender diverse people: "It's gender. It's cancer risk it's everything".

Transgender and gender diverse (TGD) individuals are a significant yet underrepresented population within genetic counseling research and broader LGBTQI+ health studies. This underrepresentation perpetuates a cycle of exclusion from the production of medical knowledge, impacting the quality and equity of care received by TGD individuals. This issue is particularly poignant in cancer genetic counseling, where TGD individuals with elevated cancer risk receive risk assessment, counseling, and referral to support based on risk figures and standards of care developed for cisgender individuals. The experiences of TGD individuals navigating inherited cancer syndromes remain largely undocumented in medical literature, posing challenges to the provision of inclusive care by genetics providers. To bridge this knowledge gap, we conducted a cross-sectional qualitative study. Nineteen semi-structured interviews were held with gender diverse adults having hereditary cancer syndromes, family histories of such syndromes, or personal histories of chest cancer. Our study employed thematic analysis using combined inductive and deductive methods to illuminate how hereditary cancer care intersects with participants' gender identities, gender expression, and gender-affirming care experiences. Participants reflected on care experiences that felt affirming or triggered gender dysphoria. Participants also discussed the interplay between risk-reducing mastectomy and top surgery, exploring co-emergent dynamics between cancer risk management and gender expression. Significantly, participants identified actionable strategies for healthcare providers to enhance support for gender diverse patients, including the mindful use of gendered language, collaborative decision-making, and conveying allyship. These findings offer valuable insights into tailoring genetic counseling to meet the unique needs of TGD individuals, advancing the path toward inclusive and appropriate care for LGBTQI+ individuals with hereditary cancer syndromes.

Evaluation of an Integrated Intervention to Address Clinical Care and Social Needs Among Patients with Type 2 Diabetes.

BACKGROUND: The Providence Diabetes Collective Impact Initiative (DCII) was designed to address the clinical challenges of type 2 diabetes and the social determinants of health (SDoH) challenges that exacerbate disease impact. OBJECTIVE: We assessed the impact of the DCII, a multifaceted intervention approach to diabetes treatment that employed both clinical and SDoH strategies, on access to medical and social services. DESIGN: The evaluation employed a cohort design and used an adjusted difference-in-difference model to compare treatment and control groups. PARTICIPANTS: Our study population consisted of 1220 people (740 treatment, 480 control), aged 18-65 years old with a pre-existing type 2 diabetes diagnosis who visited one of the seven Providence clinics (three treatment and four control) in the tri-county area of Portland, Oregon, between August 2019 and November 2020. INTERVENTIONS: The DCII threaded together clinical approaches such as outreach, standardized protocols, and diabetes self-management education and SDoH strategies including social needs screening, referral to a community resource desk, and social needs support (e.g., transportation) to create a comprehensive, multi-sector intervention. MAIN MEASURES: Outcome measures included SDoH screens, diabetes education participation, HbA1c, blood pressure, and virtual and in-person primary care utilization, as well as inpatient and emergency department hospitalization. KEY RESULTS: Compared to patients at the control clinics, patients at DCII clinics saw an increase in diabetes education (15.5%, p<0.001), were modestly more likely to receive SDoH screening (4.4%, p<0.087), and had an increase in the average number of virtual primary care visits of 0.35 per member, per year (p<0.001). No differences in HbA1c, blood pressure, or hospitalization were observed. CONCLUSIONS: DCII participation was associated with improvements in diabetes education use, SDoH screening, and some measures of care utilization.

[Assessment of available and currently applied typing methods of zoonotic pathogens using the example of Shiga toxin-producing and enterohemorrhagic Escherichia coli (STEC/EHEC)]. / Bestandsaufnahme der verfügbaren und aktuell eingesetzten Typisierungsmethoden von zoonotischen Erregern am Beispiel von Shiga Toxin-bildenden bzw. enterohämorrhagischen Escherichia coli (STEC/EHEC).

INTRODUCTION: In order to improve patient care and to increase food safety within the framework of One Health, the project "Integrated Genomic Surveillance of Zoonotic Agents (IGS-Zoo)" aims to develop concepts for a genomic surveillance of Shiga toxin(Stx)-producing and enterohemorrhagic Escherichia coli (STEC/EHEC) in Germany. METHODS: An online survey was conducted to assess the currently available and applied STEC/EHEC typing methods in the federal laboratories of veterinary regulation, food control, and public health service. RESULTS: Twenty-six questionnaires from 33 participants were evaluated with regard to STEC/EHEC. The number of STEC/EHEC-suspected samples that the laboratories process per year ranges between 10 and 3500, and out of these they obtain between 3 and 1000 pathogenic isolates. Currently the most frequently used typing method is the determination of Stx- and intimin-coding genes using polymerase chain reaction (PCR). Whole genome sequencing (WGS) is currently used by eight federal state laboratories, and nine are planning to implement it in the future. The most common obstacle for further typing of STEC/EHEC is that isolation from sample material is often unsuccessful despite apparent PCR detection of the stx genes. DISCUSSION: The results of the survey should facilitate the integration of the analysis methods developed in the project and emphasize the target groups' individual needs for corresponding training concepts.

Combined interprofessional education and system intervention to improve screening older adults for dementia and falls.

The objective of this study was to increase screening for falls and dementia by improving interprofessional (IP) providers' and staffs' knowledge and attitudes toward the care of older patients and team-based care. An intervention, including education about screening and an electronic health record (EHR) flowsheet, was rolled-out across eight Federally Qualified Health Centers (FQHC). Participants were 262 IP health providers who served 6670 patients ≥ age 65 > age 65 . An EHR flowsheet with two-item screeners for falls and dementia triggered automatically for patients ≥ age 65. Documentation of screening for falls and dementia was abstracted from the EHR for the year prior to and the year after the interventions began. Baseline screening rates for falls and dementia were flat; from the start of education intervention until EHR live date, screening rates increased significantly; after EHR live date, the screening rates continued increasing significantly. A combined education-system intervention can improve screening for falls and dementia in FQHC.

Health care workers' perspectives on care for patients with injection drug use associated infective endocarditis (IDU-IE).

BACKGROUND: Despite high morbidity and mortality, patients with injection drug use associated infective endocarditis (IDU-IE) lack standardized care, and experience prolonged hospitalization and variable substance use disorder (SUD) management. Our study's objective was to elicit perspectives of health care workers (HCWs) who deliver care to this population by understanding their perceived patient, provider, and system-level resources and barriers. METHODS: This qualitative study included interviews of HCWs providing care to patients with IDU-IE from January 2017 to December 2019 at a single Midwest academic center. Based on electronic medical record queries to determine high and low rates of referral to SUD treatment, HCWs were selected using stratified random sampling followed by convenience sampling of non-physician HCWs and a patient. Study participants were recruited via email and verbal consent was obtained. The final sample included 11 hospitalists, 3 specialists (including 2 cardiovascular surgery providers), 3 case managers, 2 social workers, 1 nurse, and 1 patient. Qualitative semi-structured interviews explored challenges and resources related to caring for this population. Qualitative Data Analysis (QDA) Minor Lite was used for thematic data using an inductive approach. RESULTS: Three major thematic categories emerged relative to patient-level barriers (e.g., pain control, difficult patient interactions, social determinants of health), provider-level barriers (e.g., inequity, expectations for recovery, varying levels of hope, communication style, prescribing medication for SUD), and system-level barriers (e.g., repeat surgery, placement, resources for SUD and mental health). The need to address underlying SUD was a prominent theme. CONCLUSION: Practical steps we can take to improve treatment for this population include training and coaching HCWs on a more person-centered approach to communication and transparent decision-making around pain management, surgery decisions, and expectations for SUD treatment.

Differences in access to virtual and in-person primary care by race/ethnicity and community social vulnerability among adults diagnosed with COVID-19 in a large, multi-state health system.

BACKGROUND: Research exploring telehealth expansion during the COVID-19 pandemic has demonstrated that groups disproportionately impacted by COVID-19 also experience worse access to telehealth. However, this research has been cross-sectional or short in duration; geographically limited; has not accounted for pre-existing access disparities; and has not examined COVID-19 patients. We examined virtual primary care use by race/ethnicity and community social vulnerability among adults diagnosed with COVID-19 in a large, multi-state health system. We also assessed use of in-person primary care to understand whether disparities in virtual access may have been offset by improved in-person access. METHODS: Using a cohort design, electronic health records, and Centers for Disease Control and Prevention Social Vulnerability Index, we compared changes in virtual and in-person primary care use by race/ethnicity and community social vulnerability in the year before and after COVID-19 diagnosis. Our study population included 11,326 adult patients diagnosed with COVID-19 between March and July 2020. We estimated logistic regression models to examine likelihood of primary care use. In all regression models we computed robust standard errors; in adjusted models we controlled for demographic and health characteristics of patients. RESULTS: In a patient population of primarily Hispanic/Latino and non-Hispanic White individuals, and in which over half lived in socially vulnerable areas, likelihood of virtual primary care use increased from the year before to the year after COVID-19 diagnosis (3.6 to 10.3%); while in-person use remained stable (21.0 to 20.7%). In unadjusted and adjusted regression models, compared with White patients, Hispanic/Latino and other race/ethnicity patients were significantly less likely to use virtual care before and after COVID-19 diagnosis; Hispanic/Latino, Native Hawaiian/Pacific Islander, and other race/ethnicity patients, and patients living in socially vulnerable areas were also significantly less likely to use in-person care during these time periods. CONCLUSIONS: Newly expanded virtual primary care has not equitably benefited individuals from racialized groups diagnosed with COVID-19, and virtual access disparities have not been offset by improved in-person access. Health systems should employ evidence-based strategies to equitably provide care, including representative provider networks; targeted, empowering outreach; co-developed culturally and linguistically appropriate tools and technologies; and provision of enabling resources and services.

Gaining Insights about Forest Health Prescriptions from Loggers and Foresters: Understudied Voices in the Human Dimensions of Forest Health.

Maintaining healthy forests requires multiple individuals, including foresters who develop timber sale silvicultural prescriptions and loggers who implement those prescriptions, resulting in the transplantation of forest health science into workable management plans. However, data on the experiences, attitudes, and opinions of these two groups are often missing when developing or refining forest health treatment strategies. To explore the role that these groups play in sustaining forest health, we examined timber sale administrators' and loggers' perspectives on treatment approaches for eastern spruce dwarf mistletoe (Arceuthobium pusillum) (ESDM), a parasitic plant native to Minnesota that increases mortality and reduces growth rate and regeneration success of black spruce (Picea mariana). While ESDM has been managed for decades in black spruce stands in Minnesota, little is known about the effectiveness of the management approaches. Data were gathered through interviews and focus groups with loggers, as well as an online survey and focus groups with foresters who administer timber sales. Study participants identified a range of field-based barriers, knowledge gaps, and uncertainties that hamper the ability to effectively implement ESDM treatment strategies as designed, including financial, administrative, informational, policy-related, and environmental factors. These factors have a significant bearing on the ability to effectively implement ESDM treatment approaches; yet may be factors that were not known or considered when developing treatment strategies. This case study underscores the value of nurturing a science-management partnership to ensure that a broad set of voices are considered when developing or revising forest health treatment strategies.

Preparing advanced learners for geriatric team care: A short-term curricular model that works.

Health outcomes for complex older adults are enhanced by interprofessional collaboration. Funded by a Geriatrics Workforce Enhancement Program (GWEP), an interprofessional team of educators developed a short-term geriatrics experience, including four hours of pre-clinical education and 12-20 hours of immersion in team-based care for advanced learners in nursing (n = 70 APN), social work (n = 48 MSW), and medicine (n = 122 medical students). Content focused on five areas: medication management, dementia, depression, falls, and myths about aging. Learners completed pre/post surveys measuring knowledge of geriatrics, attitudes toward geriatric patients and team care, and post-surveys regarding perceptions of the overall clinical experience. Results showed significant improvement in knowledge and attitudes toward older adults and interprofessional (IP) team practice. Qualitative comments reflected increased empathy toward and enthusiasm for working with older adults, valuing IP teams, and a desire for geriatrics content earlier in their respective curricula.

Perioperative Continuation of Buprenorphine at Low-Moderate Doses Was Associated with Lower Postoperative Pain Scores and Decreased Outpatient Opioid Dispensing Compared with Buprenorphine Discontinuation.

OBJECTIVE: An increasing number of individuals are prescribed buprenorphine as medication-assisted treatment for opioid use disorder. Our institution developed guidelines for perioperative buprenorphine continuation with an algorithm for dose reduction based upon the surgical procedure and patient's maintenance dose. The objective of this study was to compare the effects of buprenorphine continuation with those of discontinuation on postoperative pain scores and outpatient opioid dispensing. DESIGN: Retrospective observational study. SUBJECTS: Surgical patients on buprenorphine from March 2018 to October 2018. Patients on buprenorphine for chronic pain and those with minor procedures were excluded from analysis. METHODS: We compared postoperative outpatient opioid dispensing and postanesthesia care unit (PACU) pain scores in patients where buprenorphine was continued compared with held perioperatively, collecting single surgical subspecialty prescriber data on outpatient full mu-opioid agonist prescriptions dispensed, converted into mean morphine equivalents. Buprenorphine formulations were not included in our morphine milligram equivalents (MME) total. RESULTS: There were 55 patients total (38 cont. vs 17 held). There was no difference in postoperative buprenorphine treatment adherence (91% cont. vs 88% held, P = 0.324). The number of opioid prescriptions dispensed was significantly higher with buprenorphine discontinuation (53% cont. vs 82% held, P = 0.011), as was MME dispensed (mean of 229 cont. vs mean of 521 held, P = 0.033). PACU pain scores were higher with buprenorphine discontinuation (mean 2.9 cont. vs mean 7.6 held, P < 0.001). CONCLUSIONS: There was a significant reduction in opioid prescriptions filled, MME dispensed, and PACU pain scores in patients where buprenorphine was continued vs held perioperatively. We provide evidence to support that buprenorphine can be continued perioperatively and that continuation is associated with decreased postoperative pain and decreased outpatient opioid dispensing. These results contribute to the existing literature supporting the perioperative continuation of buprenorphine.

"You Only Teach PE and It Doesn't Really Matter": Middle School PE Teachers' Perspectives on Intervention Efforts to Increase Physical Activity.

Physical education (PE) is a frequent site of public health intervention to promote physical activity (PA); however, intervention research frequently overlooks the perspective of PE teachers. The purpose of this qualitative study was to explore teachers' experiences with and perceptions of a PA curriculum intervention. Six findings within three categories were identified and described in detail. In-depth one-on-one semistructured interviews were conducted with nine PE teachers from eight middle schools in Los Angeles. Feeling underappreciated and having a "muddled mission" within PE were driving factors in teacher morale and practice. Teachers had positive experiences with the curriculum, but significant barriers remained and limited the potential for PA during PE classes. PE teachers are pulled in multiple directions and perceive a lack of necessary support systems to achieve student health goals. Interventions aimed at leveraging PE as a site of PA promotion must incorporate the perspectives of PE teachers.

Weight perception and perceived attractiveness associated with self-rated health in young adults.

Self-rated health (SRH) is a widely used and valid marker of overall health and wellbeing and demographic differences in SRH are well-established. To date, few studies have examined how multiple components of body image shape young adults' SRH. The purpose of this study was to investigate the contributions of weight perception and perceived attractiveness on SRH among young adults. Data were from Wave IV (2007-2008) of the National Longitudinal Study of Adolescent to Adult Health (Add Health) and young women and men ages 24-34 were analyzed (n = 7044 women, n = 6594 men) in April 2018. All analyses were weighted and stratified by gender. Design-based F test and ordinal multinomial logistic regression were used. For both genders, relative to Whites, Hispanic, Black, and Asian young adults reported poorer health; women and men with higher education and income reported better health. Independent of measured body mass index (BMI), young adults who thought they were underweight or overweight reported poorer health relative to those who thought their weight was normal. Both young women and young men who thought they were more attractive also reported better health. This study demonstrates that weight status, perceived weight status, and perceived attractiveness independently impact SRH for both young men and women controlling for race/ethnicity, nativity status, marital status, education, income, and number of health conditions.

Physical Activity Correlates in Middle School Adolescents: Perceived Benefits and Barriers and Their Determinants.

The purpose of this study was to examine the determinants of benefits and barriers and their relationship with physical activity (PA) among predominantly Latino middle school students. Data were collected in a cross-sectional survey of 4,773 seventh-grade students recruited from a large, urban school district in Los Angeles. Hierarchical logistic regression models were used to assess determinants of benefits and barriers as well as their association with self-reported PA. Differences in benefits and barriers were observed by gender, ethnicity, and body size. Barriers were negatively correlated with all three PA outcomes while benefits were positively associated with exercising at least 60 min daily. A deeper understanding of benefits and barriers can facilitate the development of interventions and collaborative efforts among physical education teachers, school nurses, and administrators to implement comprehensive approaches that encourage students' participation in PA inside and outside of the classroom.

Ultrasmall Superparamagnetic Iron Oxide Imaging Identifies Tissue and Nerve Inflammation in Pain Conditions.

Objective: Correlation between radiologic structural abnormalities and clinical symptoms in low back pain patients is poor. There is an unmet clinical need to image inflammation in pain conditions to aid diagnosis and guide treatment. Ferumoxytol, an ultrasmall superparamagnetic iron oxide (USPIO) nanoparticle, is clinically used to treat iron deficiency anemia and showed promise in imaging tissue inflammation in human. We explored whether ferumoxytol can be used to identify tissue and nerve inflammation in pain conditions in animals and humans. Methods: Complete Freud's adjuvant (CFA) or saline was injected into mice hind paws to establish an inflammatory pain model. Ferumoxytol (20 mg/kg) was injected intravenously. Magnetic resonance imaging (MRI) was performed prior to injection and 72 hours postinjection. The changes in the transverse relaxation time (T2) before and after ferumoxytol injection were compared between mice that received CFA vs saline injection. In the human study, we administered ferumoxytol (4 mg/kg) to a human subject with clinical symptoms of lumbar radiculopathy and compared the patient with a healthy subject. Results: Mice that received CFA exhibited tissue inflammation and pain behaviors. The changes in T2 before and after ferumoxytol injection were significantly higher in mice that received CFA vs saline (20.8 ± 3.6 vs 2.2 ± 2.5, P = 0.005). In the human study, ferumoxytol-enhanced MRI identified the nerve root corresponding to the patient's symptoms, but the nerve root was not impinged by structural abnormalities, suggesting the potential superiority of this approach over conventional structural imaging techniques. Conclusions: Ferumoxytol-enhanced MRI can identify tissue and nerve inflammation and may provide a promising diagnostic tool in assessing pain conditions in humans.

Supporting Stabilization: A Qualitative Evaluation of a Pilot Program to Integrate Personal Caregiving Services Into Housing Settings.

Three organizations in Clark County, WA, partnered together to implement a pilot program to expand access to personal caregiving services in the homeless crisis response system. The aim of this study is to describe staff and clients' experiences of the program and its impact on clients' daily living activities, health and wellbeing, and housing stability. Using a qualitative descriptive design, semi-structured, in-depth interviews were conducted with 12 clients and 5 pilot staff, representing 4 housing service providers. Interviews were analyzed descriptively to examine staff and clients' perspectives and experiences with the personal care services pilot program. Caregivers helped clients establish routines, find companionship, and connect to health and social services both logistically and socioemotionally, supporting clients' stabilization and reducing barriers to healthcare. Hiring and retaining caregivers remained difficult due to the challenging nature of the work. Staff interviews highlight the need for additional supports to better retain caregivers. Findings from the evaluation have important implications for addressing the needs of individuals exiting homelessness and suggest that personal caregivers can play an important role in supporting the stabilization process. However, employing strategies such as training and increasing wages and benefits that support the needs of the caregiving workforce is essential to sustain this type of service delivery model.

Assessing the impact of recovery housing on healthcare utilization in Portland, Oregon.

Introduction: Central City Concern (CCC) operates several recovery housing sites in the Portland, Oregon metropolitan region, including the Blackburn Center (Blackburn) and the Richard L. Harris Building (Harris). This retrospective, observational study was designed to assess recovery housing's impact on inpatient detoxification readmission rates and healthcare utilization patterns. Methods: Our study population consisted of individuals discharged from CCC's Hooper Detox Stabilization Center from June 2019 to September 2020. A total of 75 clients housed at Blackburn, 63 clients housed at Harris, and 57 clients discharged as unhoused were included in the study sample. Using logistic regression for each of the two recovery housing groups relative to the unhoused group, we examined differences in readmissions to inpatient detoxification after their qualifying discharge. We then used Difference-In-Difference model to compare the per member per year (PMPY) use of different domains of health care before and after their qualifying discharge. Results: Compared to clients discharged as unhoused, Blackburn and Harris residents had lower risk of readmissions to inpatient detoxification treatment at 90- and 180-days post-discharge. Additionally, while the mean number of PMPY emergency department visits increased for clients discharged as unhoused in the post period, the average number of emergency department visits decreased for clients who obtained recovery housing at Blackburn (DiD=-3.65 PMPY, p-value=0.02) and at Harris (DiD=-3.87 PMPY, p-value=0.01). Conclusion: Findings highlight the impact and importance of recovery housing for individuals managing a substance use disorder and the value of healthcare system and public sector investment housing like Blackburn and Harris.

Participant Perspectives on Community Health Workers' Critical Role in Their Experience of the Pathways Program to Address Complex Needs.

This study aimed to describe participants' experiences of Pathways, a community hub care coordination model, including its impact on their lives and their relationship with the Pathways community health worker (CHW). The research team conducted semistructured, in-depth interviews with Pathways participants (n = 13) and analyzed interviews using thematic analysis. Interviews reveal how Pathways helps individuals navigate systems more confidently, increases access to needed resources, and improves well-being. CHWs defined participants' experience, providing a safe, reliable setting to make progress toward goals. Our findings support the evidence base for Pathways as an effective model of care coordination for people with complex needs.

Racial Differences in Retention in a Community-based Addiction Reduction Program Implemented by Peer Recovery Coaches for Women of Reproductive Age.

To identify program characteristics that influence the retention of women of reproductive age in the Community-based Addiction Reduction program (CARE), mixed-method analyses of CARE survey data and CARE Peer Recovery Coach (PRC) narrative entries of participant encounters were performed. About 251 women were enrolled in this prospective community-based implementation science intervention. We compared survey responses by race for treatment status, treatment motivation scales, and retention in the program at intake, 2-, 6-, 9-, and 12-month follow ups using Chi-square/T-tests. Qualitative analysis of PRC narrative entries was conducted following thematic analysis and crystallization immersion analytic methods. White compared with Black women in CARE were significantly more likely to be in treatment at intake (P < .001) and more motivated to engage in recovery treatment (P < .001). However, Black women were retained longer in CARE at 2- (P < .006), 6- (P < .011), and 9- (P < .004) months. PRC narrative entries were coded, and emergent themes mapped well to the 4 types of supports provided by PRC as outlined by the Substance Abuse and Mental Health Services Administration: emotional, instrumental, informational, and affiliational. Analysis of narrative entries by race revealed that Black women were given more detailed information, communications with PRC were more encouraging and proactive in identifying and meeting needs, and PRC took a more hands-on approach when assisting and linking to resources. The inclusion of PRC as integral members of SUD recovery programs may preferentially provide Black women with SUD the opportunity to build more trusting relationships with these peer coaches, thereby increasing their participation and retention.

The epigenetic hallmark of early-life α-hexabromocyclododecane exposure: From cerebellar 6-mA levels to locomotor performance in adulthood.

There is a growing evidence that methylation at the N6 position of adenine (6-mA), whose modulation occurs primarily during development, would be a reliable epigenetic marker in eukaryotic organisms. The present study raises the question as to whether early-life exposure to α-hexabromocyclododecane (α-HBCDD), a brominated flame retardant, may trigger modifications in 6-mA epigenetic hallmarks in the brain during the development which, in turn could affect the offspring behaviour in adulthood. Pregnant Wistar rats were split into two groups: control and α-HBCDD (66 ng/kg/per os, G0-PND14). At PND1, α-HBCDD levels were assessed in brain and liver by LC-MS/MS. At PND14, DNA was isolated from the offspring's cerebellum. DNA methylation was measured by 6-mA-specific immunoprecipitation and Illumina® sequencing (MEDIP-Seq). Locomotor activity was finally evaluated at PND120. In our early-life exposure model, we confirmed that α-HBCDD can cross the placental barrier and be detected in pups at birth. An obvious post-exposure phenotype with locomotor deficits was observed when the rats reached adulthood. This was accompanied by sex-specific over-methylation of genes involved in the insulin signaling pathway, MAPK signaling pathway as well as serotonergic and GABAergic synapses, potentially altering the normal process of neurodevelopment with consequent motor impairments crystalized at adulthood.

Epidemiology and zoonotic transmission of mcr-positive and carbapenemase-producing Enterobacterales on German turkey farms.

Introduction: The emergence of carbapenem-resistant bacteria causing serious infections may lead to more frequent use of previously abandoned antibiotics like colistin. However, mobile colistin resistance genes (mcr) can jeopardise its effectiveness in both human and veterinary medicine. In Germany, turkeys have been identified as the food-producing animal most likely to harbour mcr-positive colistin-resistant Enterobacterales (mcr-Col-E). Therefore, the aim of the present study was to assess the prevalence of both mcr-Col-E and carbapenemase-producing Enterobacterales (CPE) in German turkey herds and humans in contact with these herds. Methods: In 2018 and 2019, 175 environmental (boot swabs of turkey faeces) and 46 human stool samples were analysed using a combination of enrichment-based culture, PCR, core genome multilocus sequence typing (cgMLST) and plasmid typing. Results: mcr-Col-E were detected in 123 of the 175 turkey farms in this study (70.3%). mcr-Col-E isolates were Escherichia coli (98.4%) and Klebsiella spp. (1.6%). Herds that had been treated with colistin were more likely to harbour mcr-Col-E, with 82.2% compared to 66.2% in untreated herds (p = 0.0298). Prevalence also depended on husbandry, with 7.1% mcr-Col-E in organic farms compared to 74.5% in conventional ones (p < 0.001). In addition, four of the 46 (8.7%) human participants were colonised with mcr-Col-E. mcr-Col-E isolates from stables had minimum inhibitory concentrations (MICs) from 4 to ≥ 32 mg/l, human isolates ranged from 4 to 8 mg/l. cgMLST showed no clonal transmission of isolates. For one farm, plasmid typing revealed great similarities between plasmids from an environmental and a human sample. No CPE were found in turkey herds or humans. Discussion: These findings confirm that mcr-Col-E-prevalence is high in turkey farms, but no evidence of direct zoonotic transmission of clonal mcr-Col-E strains was found. However, the results indicate that plasmids may be transmitted between E. coli isolates from animals and humans.

Circulating cell-free methylated DNA reveals tissue-specific, cellular damage from radiation treatment.

Radiation therapy is an effective cancer treatment, although damage to healthy tissues is common. Here we analyzed cell-free, methylated DNA released from dying cells into the circulation to evaluate radiation-induced cellular damage in different tissues. To map the circulating DNA fragments to human and mouse tissues, we established sequencing-based, cell-type-specific reference DNA methylation atlases. We found that cell-type-specific DNA blocks were mostly hypomethylated and located within signature genes of cellular identity. Cell-free DNA fragments were captured from serum samples by hybridization to CpG-rich DNA panels and mapped to the DNA methylation atlases. In a mouse model, thoracic radiation-induced tissue damage was reflected by dose-dependent increases in lung endothelial and cardiomyocyte methylated DNA in serum. The analysis of serum samples from patients with breast cancer undergoing radiation treatment revealed distinct dose-dependent and tissue-specific epithelial and endothelial responses to radiation across multiple organs. Strikingly, patients treated for right-sided breast cancers also showed increased hepatocyte and liver endothelial DNA in the circulation, indicating the impact on liver tissues. Thus, changes in cell-free methylated DNA can uncover cell-type-specific effects of radiation and provide a readout of the biologically effective radiation dose received by healthy tissues.