Expanding Access to Contraceptive Services in a Family Medicine Residency Clinic: The Rapid Access to Contraception Clinic Model.

BACKGROUND AND OBJECTIVES: Learning to provide long-acting reversible contraception (LARC) during family medicine residency is an important step in building capacity for the primary care workforce to meet the reproductive health care needs of communities. We aimed to measure the impact of adding a contraceptive visit type (CVT) allowing for rapid access to contraception (RAC) on family medicine resident LARC procedure numbers. METHODS: Our program created a CVT in which patients were seen only for contraceptive services. We added the CVT to third-year family medicine resident continuity clinic schedules and a block of CVTs (the RAC clinic) to the third-year gynecology rotation. Residents self-reported LARC procedure numbers performed throughout residency, and the totals were compared for graduating residents from 2023 (post-RAC cohort) to 2022 graduates and 2018-2022 graduates (pre-RAC cohort). RESULTS: Post-RAC cohort residents reported a statistically significant increase in intrauterine device (IUD; P=.015) and contraceptive implant (P=.010) removals compared to the 2022 pre-RAC cohort. Insertions of IUDs and contraceptive implants were unchanged when compared to the pre-RAC cohort. IUD removals (P=.004) and insertions (P=.034), and contraceptive implant removals (P=.028) were significantly increased for post-RAC compared to 2022 graduates, with no difference in contraceptive implant insertions (P=.211). CONCLUSIONS: The addition of the CVT and RAC clinic contributed to an increase in LARC removals in both comparisons, and IUD insertions between 2022 and 2023. This clinic model offers an opportunity for other family medicine residency programs to improve access to contraceptive services and increase resident training in LARC management.

Elevated Mood Induced by Subthalamic Nucleus Deep Brain Stimulation: A Video-Recorded Case Report.

Background: Deep brain stimulation (DBS) can be an effective therapy to control motor signs in patients with Parkinson's disease (PD). However, subthalamic nucleus (STN) DBS can induce undesirable psychiatric adverse effects, including elevated mood. Case report: We reported a video case of a 73-year-old male implanted with bilateral STN DBS who experienced stimulation-induced elevated mood. A correlation between mood changes and enhanced activation of the ventromedial region in the left STN was observed. Discussion: This video case report illustrates STN DBS-induced elevated mood and enhances early symptom recognition for patients and diagnostic awareness for professionals.

The Drosophila hematopoietic niche assembles through collective cell migration controlled by neighbor tissues and Slit-Robo signaling.

Niches are often found in specific positions in tissues relative to the stem cells they support. Consistency of niche position suggests that placement is important for niche function. However, the complexity of most niches has precluded a thorough understanding of how their proper placement is established. To address this, we investigated the formation of a genetically tractable niche, the Drosophila Posterior Signaling Center (PSC), the assembly of which had not been previously explored. This niche controls hematopoietic progenitors of the lymph gland (LG). PSC cells were previously shown to be specified laterally in the embryo, but ultimately reside dorsally, at the LG posterior. Here, using live-imaging, we show that PSC cells migrate as a tight collective and associate with multiple tissues during their trajectory to the LG posterior. We find that Slit emanating from two extrinsic sources, visceral mesoderm and cardioblasts, is required for the PSC to remain a collective, and for its attachment to cardioblasts during migration. Without proper Slit-Robo signaling, PSC cells disperse, form aberrant contacts, and ultimately fail to reach their stereotypical position near progenitors. Our work characterizes a novel example of niche formation and identifies an extrinsic signaling relay that controls precise niche positioning.

The Integration of Sleep Research Into Eating Disorders Research: Recommendations and Best Practices.

OBJECTIVE: Sleep disturbance is common among individuals with eating disorders (EDs), with approximately 50% of patients with EDs reporting sleep disturbance. Sleep problems may promote, exacerbate, or maintain ED symptoms through a variety of hypothesized mechanisms, such as impaired executive function, increased negative affect, and disruptions to appetitive rhythms. Although research investigating the role of sleep in EDs is growing, the current literature suffers from methodological limitations and inconsistencies, which reduce our ability to translate findings to improve clinical practice. The purpose of this forum is to propose a coordinated approach to more seamlessly integrate sleep research into ED research with particular emphasis on best practices in the definition and assessment of sleep characteristics. METHODS: In this article, we will describe the current status of sleep-related research and relevant gaps within ED research practices, define key sleep characteristics, and review common assessment strategies for these sleep characteristics. Throughout the forum, we also discuss study design considerations and recommendations for future research aiming to integrate sleep research into ED research. RESULTS/DISCUSSION: Given the potential role of sleep in ED maintenance and treatment, it is important to build upon preliminary findings using a rigorous and systematic approach. Moving forward as a field necessitates a common lens through which future research on sleep and EDs may be conducted, communicated, and evaluated.

Responsive Versus Continuous Deep Brain Stimulation for Speech in Essential Tremor: A Pilot Study.

BACKGROUND: Responsive deep brain stimulation (rDBS) uses physiological signals to deliver stimulation when needed. rDBS is hypothesized to reduce stimulation-induced speech effects associated with continuous DBS (cDBS) in patients with essential tremor (ET). OBJECTIVE: To determine if rDBS reduces cDBS speech-related side effects while maintaining tremor suppression. METHODS: Eight ET participants with thalamic DBS underwent unilateral rDBS. Both speech evaluations and tremor severity were assessed across three conditions (DBS OFF, cDBS ON, and rDBS ON). Speech was analyzed using intelligibility ratings. Tremor severity was scored using the Fahn-Tolosa-Marin Tremor Rating Scale (TRS). RESULTS: During unilateral cDBS, participants experienced reduced speech intelligibility (P = 0.025) compared to DBS OFF. rDBS was not associated with a deterioration of intelligibility. Both rDBS (P = 0.026) and cDBS (P = 0.038) improved the contralateral TRS score compared to DBS OFF. CONCLUSIONS: rDBS maintained speech intelligibility without loss of tremor suppression. A larger prospective chronic study of rDBS in ET is justified. © 2024 International Parkinson and Movement Disorder Society.

Lower achievement of guideline recommended care in Canadian adults with early-onset diabetes: A population-based cohort study.

AIMS: Adults with early-onset diabetes (age < 40 years) have an increased risk of complications, and it is unclear whether they are receiving guideline recommended care. We compared the frequency and results of haemoglobin A1c (HbA1c) testing in adults with early-onset and usual-onset diabetes and assessed factors related to guideline concordance. METHODS: Population-level databases from Alberta, Canada (∼4.5 million) were used to identify adults with incident diabetes. The cohort was stratified by age at diagnosis (< 40 vs. ≥ 40 years) and then followed for 365 days for HbA1c testing. Adjusted multivariable analyses were used to identify clinical and sociodemographic factors associated with guideline concordance. RESULTS: Among 23,643 adults with incident diabetes (mean age 54.1 ± 15.4 years; 42.1 % female), 18.9 % had early-onset diabetes. Early-onset diabetes was associated with lower frequency of testing (adjusted odds ratio (aOR), 0.80; 95 % CI 0.70-0.90) and above target glycaemic levels compared to usual-onset diabetes (aOR, 1.45; 95 % CI 1.29-1.64). Factors associated with guideline concordant frequency of HbA1c testing were rural residence and insulin use. CONCLUSIONS: In our universal care setting with premium-free health care, early-onset diabetes was associated with lower rates of HbA1c testing and sub-optimal glycaemic control compared to those with usual-onset diabetes.

Frontline immune checkpoint inhibitors in patients ≥ 90 years with advanced urothelial cancer: a single center experience.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) are approved for advanced urothelial cancer alone and as first-line in combination with enfortumab vedotin. Platinum based chemotherapy which is another frontline choice is often not a treatment option for older patients due to comorbidities that increase with age. Despite ICIs being better tolerated compared to traditional chemotherapy little is known about their efficacy and toxicity in patients ≥ 90 years due to the rarity of this population in clinical trials. Our objective was to analyze the efficacy and toxicity of immune checkpoint inhibitors in patients ≥ 90 years. MATERIALS AND METHODS: We conducted a single center retrospective review of patients ≥ 90 years treated between July 2019 and September 2023 with standard of care ICIs for advanced urothelial cancer. RESULTS: Six patients treated with pembrolizumab were identified. Four (66.7%) were male and mean age was 93.5 years at the time of treatment initiation. Response rate was 66.7% (4 patients) with 3 complete responses, which were durable off therapy. Median follow up was 18.2 months. Median progression free survival (PFS) was 10.2 months [95%confidence interval (95%CI): 1.77, not reached (NR)] and median overall survival (OS) was 18.2 months (95%CI: 12.1, NR). Side effects presented in 4 (66.7%) patients and included hypothyroidism, diarrhea, anemia, thrombocytopenia, rash, and bullous dermatitis. One patient developed grade 3 anemia and no patients experienced grade 4 events or required hospitalization due to treatment side effects. CONCLUSIONS: Our experience in a small cohort of patients ≥ 90 years indicate that ICIs are well tolerated and effective for the treatment of advanced urothelial carcinoma in this patient population.

Prolonged administration of oral phenylbutazone and firocoxib in horses has no impact on selected cytokine and growth factor concentrations in platelet-rich plasma and autologous protein solution.

OBJECTIVE: To determine the effects of prolonged administration of the oral NSAIDs phenylbutazone and firocoxib on concentrations of cytokines and growth factors in platelet-rich plasma (PRP) and autologous protein solution (APS). ANIMALS: 6 adult University owned horses. METHODS: Horses were randomized to receive phenylbutazone (1 g, orally, q 12 h) or firocoxib (57 mg, orally, q 24 h) for 6 days. Blood was obtained and processed for APS (Pro-Stride) and PRP (Restigen) before the administration of NSAIDs and at 7 days (1 day following cessation of NSAIDs). Horses underwent a two-week washout period, during which blood was obtained at 14 days and 21 days. The protocol was repeated with a crossover design. PRP and APS were analyzed for concentrations of platelets, leukocytes, and several cytokines (IL-1ß, IL-10, IL-6, IL-8, and tumor necrosis factor-α) and growth factors (PDGF, FGF-2, and TGF-ß1) using immunoassays. Plasma was evaluated for drug concentrations. RESULTS: No significant differences existed in concentrations of growth factors and cytokines before or after prolonged administration of NSAIDs. There were significant differences in concentrations of leukocytes and platelets in PRP compared to APS, with higher concentrations of leukocytes at the day 7 time point (T) in APS (phenylbutazone) and in concentrations of platelets in APS at T0 (firocoxib) and in APS at T7 (phenylbutazone). CLINICAL RELEVANCE: Veterinarians can recommend the administration of these oral NSAIDs prior to obtaining blood for PRP and APS provided a single-day washout period is instituted.

Engagement in binge eating and fasting associated with poorer sleep quality in an online sample of adults.

OBJECTIVES: Both disordered eating and disturbed sleep represent significant threats to mental health. Accumulating evidence suggests that disordered eating behaviors and sleep problems co-occur. A majority of current research, however, has focused on these behaviors as components of eating disorder diagnoses, rather than investigating the independent associations of transdiagnostic disordered eating behaviors and sleep. The present study sought to examine fasting, binge eating, self-induced vomiting, laxative or diuretic misuse, and driven exercise as predictors of sleep quality complaints. METHOD: An online sample of 648 U.S. adults completed the Eating Disorder Examination - Questionnaire, the Pittsburgh Sleep Quality Index, and the Patient Health Care Questionnaire-2 as part of a larger parent study. RESULTS: Results of a hierarchical linear regression revealed that, collectively, disordered eating behaviors predicted worse sleep quality [R2 = 0.30, F(7, 640) = 31.21, p < .001], and that both binge eating and fasting, but not other compensatory behaviors, accounted for unique variance in sleep quality after controlling for BMI and depression. CONCLUSIONS: Overall, findings suggest that transdiagnostic disordered eating behaviors are associated with sleep quality complaints. Improved understanding of the specific relationships between individual eating behaviors and sleep characteristics can help refine the identification of individuals at high risk for sleep disturbance and address the potential reciprocal influence of sleep quality on disordered eating behaviors.

Metabolic Reprogramming of Tumor-Associated Macrophages Using Glutamine Antagonist JHU083 Drives Tumor Immunity in Myeloid-Rich Prostate and Bladder Cancers.

Glutamine metabolism in tumor microenvironments critically regulates antitumor immunity. Using the glutamine-antagonist prodrug JHU083, we report potent tumor growth inhibition in urologic tumors by JHU083-reprogrammed tumor-associated macrophages (TAMs) and tumor-infiltrating monocytes. We show JHU083-mediated glutamine antagonism in tumor microenvironments induced by TNF, proinflammatory, and mTORC1 signaling in intratumoral TAM clusters. JHU083-reprogrammed TAMs also exhibited increased tumor cell phagocytosis and diminished proangiogenic capacities. In vivo inhibition of TAM glutamine consumption resulted in increased glycolysis, a broken tricarboxylic acid (TCA) cycle, and purine metabolism disruption. Although the antitumor effect of glutamine antagonism on tumor-infiltrating T cells was moderate, JHU083 promoted a stem cell-like phenotype in CD8+ T cells and decreased the abundance of regulatory T cells. Finally, JHU083 caused a global shutdown in glutamine-utilizing metabolic pathways in tumor cells, leading to reduced HIF-1α, c-MYC phosphorylation, and induction of tumor cell apoptosis, all key antitumor features. Altogether, our findings demonstrate that targeting glutamine with JHU083 led to suppressed tumor growth as well as reprogramming of immunosuppressive TAMs within prostate and bladder tumors that promoted antitumor immune responses. JHU083 can offer an effective therapeutic benefit for tumor types that are enriched in immunosuppressive TAMs.

Time-resolved cryogenic electron tomography for the study of transient cellular processes.

Cryogenic electron tomography (cryo-ET) is the highest resolution imaging technique applicable to the life sciences, enabling subnanometer visualization of specimens preserved in their near native states. The rapid plunge freezing process used to prepare samples lends itself to time-resolved studies, which researchers have pursued for in vitro samples for decades. Here, we focus on developing a freezing apparatus for time-resolved studies in situ. The device mixes cellular samples with solution-phase stimulants before spraying them directly onto an electron microscopy grid that is transiting into cryogenic liquid ethane. By varying the flow rates of cell and stimulant solutions within the device, we can control the reaction time from tens of milliseconds to over a second before freezing. In a proof-of-principle demonstration, the freezing method is applied to a model bacterium, Caulobacter crescentus, mixed with an acidic buffer. Through cryo-ET we resolved structural changes throughout the cell, including surface-layer protein dissolution, outer membrane deformation, and cytosolic rearrangement, all within 1.5 s of reaction time. This new approach, Time-Resolved cryo-ET (TR-cryo-ET), enhances the capabilities of cryo-ET by incorporating a subsecond temporal axis and enables the visualization of induced structural changes at the molecular, organelle, or cellular level.

Common principles for odour coding across vertebrates and invertebrates.

The olfactory system is an ideal and tractable system for exploring how the brain transforms sensory inputs into behaviour. The basic tasks of any olfactory system include odour detection, discrimination and categorization. The challenge for the olfactory system is to transform the high-dimensional space of olfactory stimuli into the much smaller space of perceived objects and valence that endows odours with meaning. Our current understanding of how neural circuits address this challenge has come primarily from observations of the mechanisms of the brain for processing other sensory modalities, such as vision and hearing, in which optimized deep hierarchical circuits are used to extract sensory features that vary along continuous physical dimensions. The olfactory system, by contrast, contends with an ill-defined, high-dimensional stimulus space and discrete stimuli using a circuit architecture that is shallow and parallelized. Here, we present recent observations in vertebrate and invertebrate systems that relate the statistical structure and state-dependent modulation of olfactory codes to mechanisms of perception and odour-guided behaviour.

Acute and Long-Term Management of Blunt Cerebrovascular Injury at a Quaternary Referral Level 1 Trauma Center: The Memphis Experience and Comparison of a New Scoring System.

BACKGROUND AND OBJECTIVES: The management of blunt cerebrovascular injuries (BCVIs) remains an important topic within trauma and neurosurgery today. There remains a lack of consensus within the literature and significant variation across institutions. The purpose of this study was to evaluate management of BCVI at a large, tertiary referral trauma center. METHODS: Institutional Review Board approval was obtained to conduct a retrospective review of patients with BCVI at our Level 1 Trauma Center. Computed tomography angiography was used to identify BCVI for each patient. Patient information was collected, and statistical analysis was performed. With the included risk factors for ischemic complications, a novel scoring system based on ischemic risk, the "Memphis Score," was developed and evaluated to grade BCVI. RESULTS: Two hundred seventeen patients with BCVI from July 2020 to August 2022 were identified. The most common mechanism of injury was motor vehicle collision (141, 65.0%). Vertebral arteries were the most common vessel injured (136, 51.1%) with most injuries occurring at a high cervical location (101, 38.0%). Denver Grade 1 injuries (89, 33.5%) and a Memphis Score of 1 were most frequent (172, 64.6%), and initial anticoagulation with heparin drip was initiated 56.7% of the time (123). Endovascular treatment was required in 24 patients (11.1%) and was usually performed in the first 48 hours (15, 62.5%). While Denver Grade (P = .019) and Memphis Score (P < .00001) were significantly higher in those patients undergoing endovascular treatment, only the Memphis Score demonstrated a significant difference between those patients who had stroke or worsening on follow-up imaging and those who did not (P = .0009). CONCLUSION: Although BCVI management has improved since early investigative efforts, institutions must evaluate and share their data to help clarify outcomes. The novel "Memphis Score" presents a standardized framework to communicate ischemic risk and guide management of BCVI.

An actomyosin network organizes niche morphology and responds to feedback from recruited stem cells.

Stem cells often rely on signals from a niche, which in many tissues adopts a precise morphology. What remains elusive is how niches are formed, and how morphology impacts function. To address this, we leverage the Drosophila gonadal niche, which affords genetic tractability and live-imaging. We have previously shown mechanisms dictating niche cell migration to their appropriate position within the gonad, and the resultant consequences on niche function. Here, we show that once positioned, niche cells robustly polarize filamentous actin (F-actin) and Non-muscle Myosin II (MyoII) towards neighboring germ cells. Actomyosin tension along the niche periphery generates a highly reproducible smoothened contour. Without contractility, niches are misshapen and exhibit defects in their ability to regulate germline stem cell behavior. We additionally show that germ cells aid in polarizing MyoII within niche cells, and that extrinsic input is required for niche morphogenesis and function. Our work reveals a feedback mechanism where stem cells shape the niche that guides their behavior.

Associations of tubal ligation and hysterectomy with serum androgen and estrogen metabolites among postmenopausal women in the Women's Health Initiative Observational Study.

PURPOSE: Hysterectomy is associated with subsequent changes in circulating hormone levels, but the evidence of an association for tubal ligation is unclear. We evaluated whether circulating concentrations of androgens and estrogens differ by tubal ligation or hysterectomy status in postmenopausal women from the Women's Health Initiative (WHI)-Observational Study (OS). METHODS: Serum androgens and estrogens were measured in 920 postmenopausal women who did not use menopausal hormone therapy at the time of blood draw, of whom 139 self-reported a history of tubal ligation and 102 reported hysterectomy (with intact ovaries). Geometric mean hormone concentrations (GMs) and 95% confidence intervals (CIs) associated with a history of tubal ligation or hysterectomy (ever/never), as well as time since procedures, were estimated using adjusted linear regression with inverse probability of sampling weights to account for selection. RESULTS: Circulating levels of 12 androgen/androgen metabolites and 20 estrogen/estrogen metabolites did not differ by tubal ligation status. Among women reporting prior hysterectomy compared to women without hysterectomy, we observed lower levels of several androgens (e.g., testosterone (nmol/L): GMyes 0.46 [95% CI:0.37-0.57] vs. GMno 0.62 [95% CI:0.53-0.72]) and higher levels of estrogen metabolites, for example, 2-hydroxyestrone-3-methyl ether (GMyes 11.1 [95% CI:8.95-13.9] pmol/L vs. GMno 8.70 [95% CI:7.38-10.3]) and 4-methoxyestrone (GMyes 6.50 [95% CI:5.05-8.37] vs. GMno 4.92 [95% CI:4.00-6.05]). CONCLUSION: While we did not observe associations between prior tubal ligation and postmenopausal circulating hormone levels, our findings support that prior hysterectomy was associated with lower circulating testosterone levels and higher levels of some estrogen metabolites, which may have implications for future hormone-related disease risks.

Effect of video angle on detection of induced front limb lameness in horses.

BACKGROUND: Lameness examinations are commonly performed in equine medicine. Advancements in digital technology have increased the use of video recordings for lameness assessment, however, standardization of ideal video angle is not available yielding videos of poor diagnostic quality. The objective of this study was to evaluate the effect of video angle on the subjective assessment of front limb lameness. A randomized, blinded, crossover study was performed. Six horses with and without mechanically induced forelimb solar pain were recorded using 9 video angles including horses trotting directly away and towards the video camera, horses trotting away and towards a video camera placed to the left and right side of midline, and horses trotting in a circle with the video camera placed on the inside and outside of the circle. Videos were randomized and assessed by three expert equine veterinarians using a 0-5 point scoring system. Objective lameness parameters were collected using a body-mounted inertial sensor system (Lameness Locator®, Equinosis LLC). Interobserver agreement for subjective lameness scores and ease of grading scores were determined. RESULTS: Induction of lameness was successful in all horses. There was excellent agreement between objective lameness parameters and subjective lameness scores (AUC of the ROC = 0.87). For horses in the "lame" trials, interobserver agreement was moderate for video angle 2 when degree of lameness was considered and perfect for video angle 2 and 9 when lameness was considered as a binary outcome. All other angles had no to fair agreement. For horses in the "sound" trials, interobserver agreement was perfect for video angle 5. All other video angles had slight to moderate agreement. CONCLUSIONS: When video assessment of forelimb lameness is required, a video of the horse trotting directly towards the video camera at a minimum is recommended. Other video angles may provide supportive information regarding lameness characteristics.

Exploring the impact of coping self-efficacy on psychological distress among violence-affected people living with HIV.

ABSTRACTThis study examines the relationship between coping self-efficacy, concurrent stress, and psychological distress (borderline/clinical anxiety, depression, and PTSD symptoms) among people living with HIV (PLWH). Using data from a cohort of PLWH living in a southern peri-urban area, logistic regression analyses were conducted to determine the effects of self-reported coping self-efficacy on psychological distress in a sample of 85 violence-affected PLWH. We also tested the moderating effect of coping self-efficacy on the concurrent stress-psychological distress relationships. In adjusted models, coping self-efficacy was significantly associated with symptoms of anxiety and PTSD, but not depressive symptoms. Findings indicate that high coping self-efficacy may reduce one's likelihood of anxiety and PTSD symptoms among PLWH.

Chronic intracranial recordings in the globus pallidus reveal circadian rhythms in Parkinson's disease.

Circadian rhythms have been shown in the subthalamic nucleus (STN) in Parkinson's disease (PD), but only a few studies have focused on the globus pallidus internus (GPi). This retrospective study investigates GPi circadian rhythms in a large cohort of subjects with PD (130 recordings from 93 subjects) with GPi activity chronically recorded in their home environment. We found a significant change in GPi activity between daytime and nighttime in most subjects (82.4%), with a reduction in GPi activity at nighttime in 56.2% of recordings and an increase in activity in 26.2%. GPi activity in higher frequency bands ( > 20 Hz) was more likely to decrease at night and in patients taking extended-release levodopa medication. Our results suggest that circadian fluctuations in the GPi vary across individuals and that increased power at night might be due to the reemergence of pathological neural activity. These findings should be considered to ensure successful implementation of adaptive neurostimulation paradigms in the real-world.