piRNA expression patterns in high vs. low fertility bovine sperm.

PIWI-interacting RNAs (piRNAs) are 24-32 nucleotide RNA sequences primarily expressed in germ cells and developing embryos that suppress transposable element expression to protect genomic integrity during epigenetic reprogramming events. We characterized the expression of piRNA sequences and their encoding clusters in sperm samples from an idiopathic fertility model of Holstein bulls with high and low Sire Conception Rates. The piRNA populations were determined to be mostly similar between fertility conditions when investigated by principal component and differential expression analysis, suggesting that a high degree of conservation in the piRNA system is likely necessary for the production of viable sperm. Both fertility conditions demonstrated evidence of 'ping-pong' activity - a secondary biogenesis pathway associated with active transposable element targeting and suppression. Most sperm-borne piRNAs were between 29-30 nucleotides in length and originated from 226 clusters across the genome, with the exception of chromosome 20. Mapping analysis revealed abundant targeting of several transposable element families, suggesting a suppressive function of sperm piRNAs consistent with their established roles. Expression of genes targeted by sperm-borne piRNAs is significantly reduced throughout early embryogenesis compared to the mRNA population. Limited transposable element expression is known to be essential for spermatogenesis, thus epigenetic regulation of this pathway is likely to influence sperm quality and fertilizing capacity.

Antibody-mediated immunological memory correlates with long-term Lyme veterinary vaccine protection in mice.

Lyme disease, caused by the bacterium Borrelia burgdorferi, is the most common tick-borne illness in the United States. Despite the rise in Lyme disease incidence, there is no vaccine against B. burgdorferi approved for human use. Little is known about the immune correlates of protection needed to prevent Lyme disease. In this work, a mouse model was used to characterize the immune response and compare the protection provided by two USDA-approved vaccines for use in canines: Duramune (bacterin vaccine) and Vanguard crLyme (subunit vaccine composed of two outer surface proteins, OspA and OspC). C3H/HeNCrl mice were immunized with two doses of either Duramune or Vanguard, and immune responses and protection against B. burgdorferi were assessed in short (35 days) and long-term (120 days) studies. Flow cytometry, ELISPOT detection of antibody-producing cells, and antibody affinity studies were performed to identify correlates of vaccine-mediated protection. Both vaccines induced humoral responses, with high IgG titers against B. burgdorferi. However, the levels of anti-B. burgdorferi antibodies decayed over time in Vanguard-vaccinated mice. While both vaccines triggered the production of antibodies against both OspA and OspC, antibody levels against these proteins were also lower in Vanguard-vaccinated mice 120 days post-vaccination. Both vaccines only provided partial protection against B. burgdorferi at the dose used in this model. The protection provided by Duramune was superior to Vanguard 120 days post-vaccination, and was characterized by higher antibody titers, higher abundance of long-lived plasma cells, and higher avidity antibodies than Vanguard. Overall, these studies provide insights into the importance of the humoral memory response to veterinary vaccines against Lyme disease and will help inform the development of future human vaccines.

One-Stop-Shop Cancer Screening Clinic: Acceptability Testing.

Cancer screenings aid in the early detection of cancer and can help reduce cancer-related mortality. The current model of care for cancer screening is often siloed, based on the targeted cancer site. We tested the acceptability of a new model of care, called the One-Stop-Shop Cancer Screening Clinic, that centralizes cancer screenings and offers patients the option to complete all their recommended cancer screenings within one to two visits. We administered surveys to 59 community members and 26 healthcare providers to gather feedback about the One-Stop-Shop model of care. Both community members and providers identified potential benefits (e.g., decreased patient burden, increased completion of cancer screenings) and also potential challenges (e.g., challenges with workflow and timing of care) of the model of care. The results of the study support the acceptability of the model of care. Of the community members surveyed, 89.5% said, if offered, they would be interested in participating in the One-Stop-Shop Cancer Screening Clinic. Future studies are needed to formally evaluate the impact and cost effectiveness of the One-Stop-Shop Cancer Screening Clinic.

An Online Mindfulness-Based Group Intervention for Tics: A Pilot Randomized Controlled Trial.

BACKGROUND: Current treatments for Tourette syndrome (TS) and persistent tic disorder (PTD) are often insufficiently effective, inaccessible, and frequently associated with adverse events. Thus, we must continue to develop and test effective, accessible, and safe treatment options. OBJECTIVE: We aimed to conduct a pilot randomized controlled trial (RCT) comparing a novel, videoconference-delivered group mindfulness-based intervention for tics (MBIT) to videoconference-delivered group psychoeducation, relaxation, and supportive therapy (PRST) for adults with TS or PTD. METHODS: Thirty-two adults with TS or PTD were randomly assigned to receive 8 weeks of either MBIT or PRST. Tic severity, tic-related impairment, and global improvement were assessed by a trained, independent evaluator who was masked to treatment condition at baseline (week 0), posttreatment (week 9), 1-month follow-up, and 6-month follow-up. All study procedures were conducted online via secure videoconferencing. RESULTS: Twenty-eight participants began treatment and were included in analyses. MBIT, relative to PRST, was associated with a significantly greater decline in tic severity (d = 0.85) and tic-related impairment (d = 0.99) from baseline to posttreatment. Treatment response was significantly higher in MBIT (69%) than in PRST (13%). Neither treatment resulted in serious adverse effects. The durability of treatment outcomes is also reported and discussed. CONCLUSIONS: The results from this pilot RCT suggest that videoconference-delivered group MBIT may be an efficacious, accessible, and safe intervention for adults with tics. Future research is necessary to confirm these preliminary findings. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Sensitivity of Magnetic Resonance Imaging in Detection of Choroidal Metastases.

Introduction: The objective of this study was to determine the sensitivity of brain magnetic resonance imaging (MRI) in the detection of choroidal metastasis (CM) from systemic primary cancers. Methods: A retrospective chart review identified patients with clinically confirmed CM seen on the Oncology Service (Byers Eye Institute) between January 2018 and March 2022. Patients had an MRI brain and/or orbits performed within 3 months of CM diagnosis. Evaluation of CM detection by MRI was then divided into two parts: an initial "standard read," where determination of CM detection was based solely on the original radiology report, to reflect real-world performance, and a subsequent "dedicated read," for which a board-certified neuroradiologist, blinded to the laterality and location of the CM, reevaluated the studies to provide an objective "gold standard" interpretation regarding the radiographic detection of CM. Results: The study included 42 eyes of 40 patients with confirmed CM. On standard read, MRI detection of CM occurred in 21 of 42 eyes (50%), with no significant difference between MRI brain and orbit protocols (p = 0.249). Features associated with improved detection were increased tumor basal diameter (p < 0.001) and ultrasonographic tumor thickness (p = 0.003). On dedicated read, MRI detection of CM improved to 26 of 33 eyes (76%; limited to eyes with full complement of pre- and post-gadolinium sequences). Post-gadolinium 3D fluid-attenuated inversion recovery (FLAIR) sequence with fat suppression was the most sensitive (88%) for CM detection. 42% and 58% of lesions were visualized using conventional pre-gadolinium T1- and T2-weighted imaging, respectively. Conclusions: MRI sensitivity to detect CM improved from 50% to 76% with focused reinterpretation. Increased utilization of the post-gadolinium 3D FLAIR sequence and increased ocular scrutiny in cancer patients undergoing brain imaging may facilitate earlier diagnosis of CM.

Dyspnea and Palliative Care in Advanced Chronic Obstructive Pulmonary Disease: A Rapid Review.

Dyspnea is the most common and activity-limiting symptom for those with chronic obstructive pulmonary disease (COPD). Treatment is complex, palliative care (PC) dyspnea relief interventions are poorly understood, and PC remains underutilized in COPD despite national guidelines and recommendations. The purpose of this rapid review was to explore the concept of dyspnea and role of PC through the lens of providers, caregivers, and patients with COPD. A systematic approach for synthesis was used to identify 13 articles published between January 2018 and October 2023. Team members compared data via visualization and theme clustering to identify key conclusions describing operationalization of dyspnea, management, and PC implications. Dyspnea operationalization was challenging, with inconsistent measurement and terminology. Dyspnea was a significant burden in COPD and contributed to complexity of treatment. Opioids were used most often to treat dyspnea, but provider perspectives and biases can influence treatment decisions and perceptions of opioid therapy by the patient and caregiver. Evidence-based clinical practice guidelines and policies are needed to clarify the use of opioid therapy for dyspnea management to reduce stigmatization and barriers to treatment. Provider education should emphasize a multipronged approach to treatment of dyspnea in COPD with integration of PC early in the care continuum.

Association of Burnout and Other Factors Within Physicians and Advanced Practice Providers in an Academic Surgery Department.

BACKGROUND: Provider burnout is a work-related syndrome that is under-recognized, under-reported, and has negative repercussions on the individual, system, and patients. This study investigated burnout incidence and its association with wellness characteristics such as resilience, psychological safety, and perceptions of the workplace to inform future work in improving well-being. METHODS: Electronic surveys were sent to 153 physicians and advanced practice providers (APPs) in the department of surgery at a single institution. Survey topics included demographics, intention to stay, engagement, and items from validated measures for workplace perceptions including work pace/stress (Mini Z), burnout, psychological safety, and resilience. Descriptive statistics, bivariate associations, and logistic regression were used to evaluate responses. RESULTS: Overall response rate was 47%. The majority of providers reported feeling burned out (56%), and 48% indicated they would probably leave the organization within three years. Additionally, 61% reported being satisfied with their job and 55% felt that they contributed professionally in the ways they value most (meaningful work/engagement). Significant predictors for burnout included negative work environment perceptions (work pace/stress), low resilience, low meaningful work, and professional role (physician vs APP). DISCUSSION: Maintaining a healthy workforce requires investigation into the factors that support workplace well-being. The strongest predictors of burnout were work pace/stress. Protective factors against burnout were psychological safety and resilience. An organizational culture that promotes psychological safety, as well as workplace improvements to enhance providers' sense of meaning in work, and decreasing work pace and stress may contribute to the prevention of burnout and the retention.

Protective role for kidney TREM2high macrophages in obesity- and diabetes-induced kidney injury.

Diabetic kidney disease (DKD), the most common cause of kidney failure, is a frequent complication of diabetes and obesity, and yet to date, treatments to halt its progression are lacking. We analyze kidney single-cell transcriptomic profiles from DKD patients and two DKD mouse models at multiple time points along disease progression-high-fat diet (HFD)-fed mice aged to 90-100 weeks and BTBR ob/ob mice (a genetic model)-and report an expanding population of macrophages with high expression of triggering receptor expressed on myeloid cells 2 (TREM2) in HFD-fed mice. TREM2high macrophages are enriched in obese and diabetic patients, in contrast to hypertensive patients or healthy controls in an independent validation cohort. Trem2 knockout mice on an HFD have worsening kidney filter damage and increased tubular epithelial cell injury, all signs of worsening DKD. Together, our studies suggest that strategies to enhance kidney TREM2high macrophages may provide therapeutic benefits for DKD.

Multi-cancer early detection (MCED) tests: prioritizing equity from bench to bedside.

Multi-cancer early detection (MCED) tests are blood-based tests designed to screen for signals of multiple cancers. There is growing interest and investment in examining the potential benefits and applications of MCED tests. If MCED tests are shown to have clinical utility, it is important to ensure that all people-regardless of their demographic or socioeconomic background-equitably benefit from these tests. Unfortunately, with health care innovation, such considerations are often ignored until after inequities emerge. We urge for-profit companies, scientists, clinicians, payers, and government agencies to prioritize equity now-when MCEDs are still being developed and researched. In an effort to avoid creating and exacerbating cancer inequities, we propose 9 equity considerations for MCEDs.

Examining workplace behaviors in adult women with urinary incontinence: A pilot study.

BACKGROUND: Urinary incontinence is a growing issue among adult women globally. Limited data exist examining the impact of occupational, environmental, and behavioral factors on urinary incontinence. OBJECTIVE: This quantitative, cross-sectional pilot study examined the workplace behaviors of adult women experiencing urinary incontinence. It was hypothesized that specific jobs and work environments would be associated with increased urinary incontinence and urgency based on identified behaviors and work-related conditions. DESIGN: This study is a quantitative, cross-sectional survey. METHODS: Adult women (18 years and older) with a history of urinary incontinence were recruited from August 2022 to February 2023 to complete a one-time survey consisting of multiple-choice and short answer questions identifying specific workplace behaviors and symptoms of urinary incontinence. Descriptive statistics and data categorization were used to observe outcomes and examine relationships between urinary incontinence and particular professions. RESULTS: Urinary incontinence and urgency-related symptoms affected healthcare and business professionals at a higher prevalence. The most commonly reported behaviors across all professions consisted of withholding urine and utilizing absorbance products. CONCLUSION: The results of this study will help guide women's health practitioners in exploring current workplace behaviors that may contribute to urinary incontinence in adult women. With this knowledge, practitioners can provide meaningful education to employers and employees to prioritize toileting behaviors in the workplace.

Use of Ecological Momentary Assessment to Measure Dyspnea in COPD.

Dyspnea is an unpredictable and distressing symptom of chronic obstructive pulmonary disease (COPD). Dyspnea is challenging to measure due to the heterogeneity of COPD and recall bias associated with retrospective reports. Ecological Momentary Assessment (EMA) is a technique used to collect symptoms in real-time within a natural environment, useful for monitoring symptom trends and risks of exacerbation in COPD. EMA can be integrated into mobile health (mHealth) platforms for repeated data collection and used alongside physiological measures and behavioral activity monitors. The purpose of this paper is to discuss the use of mHealth and EMA for dyspnea measurement, consider clinical implications of EMA in COPD management, and identify needs for future research in this area.

Defining Types of Leadership Within an Academic Surgery Department to Promote Change for Decreasing Rates of Burnout.

OBJECTIVES: Successful leaders influence the group they represent. Effective surgical care is tied to its leadership climate. However, most surgical providers are not attuned to their individual strengths which if known they could leverage them within their teams. This study identifies leadership types within a department of surgery which may be used to better understand and cultivate their strengths. METHODS: In 2022, 172 providers in an academic surgery department were offered the GallupTM CliftonStrengths assessment, a proprietary instrument that maps 34 strengths across 4 domains of leadership. The assessment provides a respondent with their top 5 strengths and the domain in which they naturally "lead". RESULTS: Of 172 providers, 127 (74%) completed the assessment. While providers have strengths in multiple domains, they "lead with" a specific domain. Mapped from the providers' top 10 strengths, the most common "lead with" domain for surgical providers was Executing: the ability to implement ideas and produce results. Strategic Thinking: those who are analytical and push teams forward and Relationship Building: the ability to create strong and effective teams were followed by the least common domain. Influencing: the ability to communicate ideas and lead others. Formal leaders were significantly more likely to lead with Strategic Thinking. There were no significant differences between APPs and physicians. CONCLUSION: A majority of surgical providers "lead with" the GallupTM Executing domain. Those who lead with executing skills work tirelessly to produce outcomes. Learning to leverage the strengths of our teams to create cohesion and efficiency may improve engagement and retention.

Hospital Facility Prices Declined As A Result Of Oregon's Hospital Payment Cap.

Hospital prices for commercially insured people are high and vary widely, prompting states to seek ways to control hospital price growth. In October 2019, the Oregon state employee health insurance plan instituted a cap on hospital payments. Using 2014-21 data from the Oregon All Payer All Claims Reporting Program database, we performed a difference-in-differences analysis to test the impact of the cap on hospital facility prices for Oregon's state employee plan enrollees. We found that the cap was not associated with a significant reduction in inpatient facility prices across the post period (-$901.9 per admission) but was associated with a significant reduction in the second year after implementation (-$2,774.20). The cap was associated with a significant reduction in outpatient facility prices over the course of the first twenty-seven months of the policy (-$130.50 per procedure). We estimated $107.5 million (or 4 percent of total plan spending) in savings to the state employee plan during the first two years. The hospital payment cap successfully reduced hospital prices for enrollees in that plan.

Academic performance in moderately and late preterm children in the United States: are they catching up?

OBJECTIVE: To determine whether preterm birth of 32-36 6/7 weeks gestation affected school performance from kindergarten through fifth grade. STUDY DESIGN: We assessed 14350 term infants and 1195 32-36 6/7 weeks gestation infants followed in the Early Childhood Longitudinal Study Kindergarten 2011 cohort for classroom performance in kindergarten-fifth grade. Multivariable regression was performed for comparisons, and data were weighted to be representative of the US population. RESULTS: Children born 35-36 6/7 weeks gestation had no significant difference in their academic scores or performance, while 32-34 6/7 weeks' children had lower academic scores and teacher performance scores when compared to term children. Children born between 32 and 36 6/7 weeks gestation had higher odds of individualized education plan needs and had learning disability diagnoses compared to term children. CONCLUSIONS: Children born between 32 and 34 6/7 weeks gestation have poor school performance compared to term children. Children born between 32 and 36 6/7 weeks gestation are at risk for learning disabilities and likely benefit from continued support and services to improve achievement throughout school.

A Case of an Obstructed Delivery by a Large, Lower Uterine Segment Fibroid Interlocked with a Fetal Mentum.

Uterine leiomyomata are associated with many pregnancy complications and will likely become increasingly common as the average age of childbearing increases. We describe a case of an obstructed delivery by a large fibroid. A 37-year-old G2P1001 with a 10-cm anterior, lower uterine segment fibroid presented for labor induction. Labor was complicated by arrest of descent due to suspected obstruction of the fetal body by the fibroid after descent of the fetal head, and delivery during cesarean section was complicated by apparent interlocking of the fetal mentum with the fibroid. Large, anterior lower uterine segment fibroids have the potential to obstruct delivery of the fetal head or of the fetal body, and these patients should be counseled regarding the potential for complications via both vaginal and cesarean deliveries.

Macrophage Ontogeny, Phenotype, and Function in Ischemia Reperfusion-Induced Injury and Repair.

AKI is characterized by a sudden, and usually reversible, decline in kidney function. In mice, ischemia-reperfusion injury (IRI) is commonly used to model the pathophysiologic features of clinical AKI. Macrophages are a unifying feature of IRI as they regulate both the initial injury response as well as the long-term outcome following resolution of injury. Initially, macrophages in the kidney take on a proinflammatory phenotype characterized by the production of inflammatory cytokines, such as CCL2 (monocyte chemoattractant protein 1), IL-6, IL-1 ß , and TNF- α . Release of these proinflammatory cytokines leads to tissue damage. After resolution of the initial injury, macrophages take on a reparative role, aiding in tissue repair and restoration of kidney function. By contrast, failure to resolve the initial injury results in prolonged inflammatory macrophage accumulation and increased kidney damage, fibrosis, and the eventual development of CKD. Despite the extensive amount of literature that has ascribed these functions to M1/M2 macrophages, a recent paradigm shift in the macrophage field now defines macrophages on the basis of their ontological origin, namely monocyte-derived and tissue-resident macrophages. In this review, we focus on macrophage phenotype and function during IRI-induced injury, repair, and transition to CKD using both the classic (M1/M2) and novel (ontological origin) definition of kidney macrophages.

Emotional and Financial Stressors in New York City During the COVID-19 Pandemic: A Consecutive Cross-Sectional Analysis.

Mental and financial hardship during the COVID-19 pandemic in New York City was severe, but how vulnerable groups have been disproportionately impacted is incompletely understood. In partnership with community stakeholders, we administered a web-based survey to a convenience sample of New York City residents (18 + years) from May 2020 to April 2021 to evaluate their financial and emotional stressors. We analyzed outcomes by race, ethnicity, and education level. A total of 1854 adults completed the survey across three consecutive non-overlapping samples. Fifty-five percent identified other than non-Latinx White. Sixty-four percent reported emotional stress; 38%, 32%, and 32% reported symptoms of anxiety, depression, and post-traumatic stress disorder respectively; and 21% reported a large adverse financial impact. The leading unmet needs were mental health and food services (both 19%), and health services (18%). Need for both resources grew over time. Adverse financial impact directly correlated with presence of all four adverse mental health outcomes above. In multivariate analysis, non-White race and lack of college degree were associated with adverse financial impact, whereas LGBT identity and lack of college degree were associated with mental health impact. Throughout the COVID-19 pandemic, participants in this research demonstrated a large and growing mental and financial strain, disproportionately associated with lower education level, non-White race, and LGBT status. Our findings suggest an urgent need to differentially target COVID-19 mental health and resource support in New York City to persons in these vulnerable communities.

Loss of Preproinsulin Interaction with Signal Recognition Particle Activates Protein Quality Control, Decreasing mRNA Stability.

Many insulin gene variants alter the protein sequence and result in monogenic diabetes due to insulin insufficiency. However, the molecular mechanisms of various disease-causing mutations are unknown. Insulin is synthesized as preproinsulin containing a signal peptide (SP). SPs of secreted proteins are recognized by the signal recognition particle (SRP) or by another factor in a SRP-independent pathway. If preproinsulin uses SRP-dependent or independent pathways is still debatable. We demonstrate by the use of site-specific photocrosslinking that the SRP subunit, SRP54, interacts with the preproinsulin SP. Moreover, SRP54 depletion leads to the decrease of insulin mRNA and protein expression, supporting the involvement of the RAPP protein quality control in insulin biogenesis. RAPP regulates the quality of secretory proteins through degradation of their mRNA. We tested five disease-causing mutations in the preproinsulin SP on recognition by SRP and on their effects on mRNA and protein levels. We demonstrate that the effects of mutations are associated with their position in the SP and their severity. The data support diverse molecular mechanisms involved in the pathogenesis of these mutations. We show for the first time the involvement of the RAPP protein quality control pathway in insulin biogenesis that is implicated in the development of neonatal diabetes caused by the Leu13Arg mutation.

Financial conflicts of interest among presenters, panellists and moderators at haematology and oncology FDA workshops.

OBJECTIVE: To assess the characteristics and financial conflicts of interest of presenters, panellists and moderators at haematology and oncology workshops held jointly with or hosted by the US FDA. SETTING: We included information on all publicly available haematology or oncology FDA workshop agendas held between 1 January 2018 and 31 December 2022. EXPOSURE: General and research payments reported on Open Payments, industry funding to patient advocacy organizations reported on their webpages or 990 tax forms and employment in both pharmaceutical and regulatory settings. RESULTS: Among physicians eligible for payments, 78% received at least one payment from the industry between 2017 and 2021. The mean general payment amount was $82,170 for all years ($16,434 per year) and the median was $14,906 for all years ($2981 per year). Sixty-nine per cent of patient advocacy speakers were representing organizations that received financial support from the pharmaceutical industry. Among those representing regulatory agencies or pharmaceutical companies, 16% had worked in both settings during their careers. CONCLUSIONS AND RELEVANCE: Our findings in this cross-sectional study show a majority of US-based physician presenters at haematology and oncology workshops held jointly with members of the US FDA have some financial conflict of interest with the pharmaceutical industry. These findings support the need for clear disclosures and suggest that a more balanced selection of presenters with fewer conflicts may help to limit bias in discussions between multiple stakeholders.