Targeted single cell expression profiling identifies integrators of sleep and metabolic state.

Animals modulate sleep in accordance with their internal and external environments. Metabolic cues are particularly potent regulators of sleep, allowing animals to alter their sleep timing and amount depending on food availability and foraging duration. The fruit fly, Drosophila melanogaster, suppresses sleep in response to acute food deprivation, presumably to forage for food. This process is dependent on a single pair of Lateral Horn Leucokinin (LHLK) neurons, that secrete the neuropeptide Leucokinin. These neurons signal to insulin producing cells and suppress sleep under periods of starvation. The identification of individual neurons that modulate sleep-metabolism interactions provides the opportunity to examine the cellular changes associated with sleep modulation. Here, we use single-cell sequencing of LHLK neurons to examine the transcriptional responses to starvation. We validate that a Patch-seq approach selectively isolates RNA from individual LHLK neurons. Single-cell CEL-Seq comparisons of LHLK neurons between fed and 24-hr starved flies identified 24 genes that are differentially expressed in accordance with starvation state. In total, 12 upregulated genes and 12 downregulated genes were identified. Gene-ontology analysis showed an enrichment for Attacins, a family of anti-microbial peptides, along with several transcripts with diverse roles in regulating cellular function. Targeted knockdown of differentially expressed genes identified multiple genes that function within LHLK neurons to regulate sleep-metabolism interactions. Functionally validated genes include an essential role for the E3 ubiquitin Ligase insomniac, the sorbitol dehydrogenase Sodh1, as well as AttacinC and AttacinB in starvation-induced sleep suppression. Taken together, these findings provide a pipeline for identifying novel regulators of sleep-metabolism interactions within individual neurons.

Aging is associated with a modality-specific decline in taste.

Deficits in chemosensory processing are associated with healthy aging, as well as numerous neurodegenerative disorders, including Alzheimer's disease (AD). The fruit fly, Drosophila melanogaster, is a powerful model for studying chemosensation, aging, and aging-related pathologies, yet the effects of aging and neurodegeneration on taste function remain largely unexplored. Aging impaired response to sugars, but not medium-chain fatty acids that are sensed by a shared population of neurons. Selective expression of the human amyloid beta (Aß) peptide phenocopied the effects of aging. Functional imaging of gustatory axon terminals revealed reduced response to sugar, but not fatty acids. Axonal innervation of the fly taste center was largely intact in aged flies; however, axonal innervation was reduced upon expression of Aß. A comparison of transcript expression within the sugar-sensing taste neurons revealed age-related changes in 66 genes. Together, these findings suggest that different mechanisms underly taste deficits in aged and AD model flies.

Efforts to Reduce Bias in Clerkship Evaluations: A CERA Study.

Introduction: As the number of medical students who identify as underrepresented in medicine (URiM) increases, the disparities related to gender and URiM status persist. This study examines the current initiatives within family medicine clerkships to reduce bias in evaluations. Methods: Our 10-item survey was included as a module in the 2022 Council of Academic Family Medicine Educational Research Alliance national survey of family medicine clerkship directors. Our survey questions asked about whether programs had strategies to reduce bias in student evaluations, antiracism initiatives, perceptions on effectiveness of the initiatives, and type and cadence of faculty development on evaluations for preceptors. Results: The overall response rate for the survey was 59.12% (94/159); all respondents completed our module. Seventy percent said they had implemented strategies to reduce bias in evaluations, 60% felt these were effective, and 80% felt that reducing bias in evaluations was a priority. The majority, 89/91(95%), indicated that their medical schools had a current social justice, diversity, or antiracism initiative. We identified a positive association between specific antibias medical school initiatives and clerkship directors undertaking practices to reduce bias in evaluations (P=.005). Conclusions: Most programs had implemented strategies to reduce bias and felt that doing so was a priority. Community-based preceptors were less likely to have faculty development around reducing bias compared to those in academics. Further improvements may need to prioritize including community preceptors in educational efforts to reduce bias.

Urinary Metal Levels and Coronary Artery Calcification: Longitudinal Evidence in the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Exposure to metals, a newly recognized risk factor for cardiovascular disease (CVD), could be related to atherosclerosis progression. OBJECTIVES: The authors hypothesized that higher urinary levels of nonessential (cadmium, tungsten, uranium) and essential (cobalt, copper, zinc) metals previously associated with CVD would be associated with baseline and rate of change of coronary artery calcium (CAC) progression, a subclinical marker of CVD in MESA (Multi-Ethnic Study of Atherosclerosis). METHODS: We analyzed data from 6,418 MESA participants with spot urinary metal levels at baseline (2000-2002) and 1 to 4 repeated, continuous measures of CAC over a 10-year period. We used linear mixed-effect models to assess the association of baseline urinary metal levels with baseline CAC and cumulative change in CAC over a 10-year period. Urinary metals (µg/g creatinine) and CAC were log transformed. Models were adjusted for baseline sociodemographic factors, estimated glomerular filtration rate, lifestyle factors, and clinical factors. RESULTS: At baseline, the median CAC was 6.3 (Q1-Q3: 0.7-58.2). Comparing the highest to lowest quartile of urinary cadmium, CAC levels were 51% (95% CI: 32%, 74%) higher at baseline and 75% (95% CI: 47%, 107%) higher over the 10-year period. For urinary tungsten, uranium, and cobalt, the corresponding CAC levels over the 10-year period were 45% (95% CI: 23%, 71%), 39% (95% CI: 17%, 64%), and 47% (95% CI: 25%, 74%) higher, respectively, with no difference for models with and without adjustment for clinical factors. For copper and zinc, the corresponding estimates dropped from 55% to 33% and from 85% to 57%, respectively, after adjustment for clinical factors. The associations of metals with CAC were comparable in magnitude to those for classical CVD risk factors. CONCLUSIONS: Exposure to metals was generally associated with extent of coronary calcification at baseline and follow-up. These findings support that metals are associated with the progression of atherosclerosis, potentially providing a novel strategy for the prevention and treatment of atherosclerosis progression.

Physical medicine and rehabilitation clinical experiences: A narrative review of curricula and educational interventions.

Physical medicine and rehabilitation (PM&R) is a specialty of medicine that focuses on function and the care of people with disabilities. Many medical schools offer PM&R content by means of PM&R clerkships for career development purposes with varying curricula and assessments; however, there is limited information regarding the optimal way to teach clinical skills relating to the field of PM&R. This narrative review study was performed to evaluate PM&R specific clinical curricular interventions. The review included a PubMed search that yielded 63 articles and a Cumulated Index to Nursing and Allied Health Literature (CINAHL) search of 175 articles. A total of 14 articles were selected for review. PM&R clerkships were found to have a variety of educational interventions, including inpatient and outpatient clinical experiences, lectures, Objective Structured Clinical Examinations (OSCEs), case discussions, written examinations, physical examination sessions, cadaver sessions, small group discussions, and virtual education. PM&R rotations can improve neurologic and musculoskeletal physical examination skills, PM&R specific knowledge, and confidence in PM&R skills. More research is needed to determine the optimal methods to teach and assess PM&R knowledge and skills in the clinical setting to drive future PM&R curriculum development and educational innovations.

Patterns and predictors of COVID-19 vaccination among young adults at 44 US sites: Secondary analysis of a randomized, controlled, open-label trial, March - December 2021.

BACKGROUND: The introduction of vaccines during the COVID-19 pandemic provided an opportunity to slow transmission of SARS-CoV-2, but initial uptake of COVID-19 vaccination was slow. We analyzed data from a randomized clinical trial of the mRNA-1273 vaccine (NCT04811664) to describe the patterns of uptake of COVID-19 vaccines among young adults. METHODS: The CoVPN 3006 trial randomized adults ages 18-29 from 44 sites in the United States to receive 1) immediate mRNA-1273 vaccination from the study site, or 2) standard of care, including the option to seek vaccination at any time in the future. Randomization occurred between March and November 2021, and an observational arm of adults who declined vaccination was enrolled beginning June 2021. Among participants in the standard of care (SoC) or Vaccine Declined arms, we estimated demographic, behavioral, and health history correlates of vaccination, and the four-month cumulative incidence of COVID-19 vaccination using inverse probability weighted Kaplan-Meier estimators. RESULTS: Among 728 SoC and 470 Vaccine Declined participants, 79% and 16% received COVID-19 vaccination, respectively. SoC and Vaccine Declined participants were more likely to seek and receive vaccination if they reported COVID-19 preventive behaviors, including wearing masks, physically distancing, and avoiding large gatherings. We identified strong predictors of vaccination in the Vaccine Declined arm, including attending class in person (adjusted risk ratio [aRR]: 0.47, 95% confidence interval [CI] 0.21, 1.03), having a COVID-19 relevant medical condition (aRR: 1.95, 95% CI: 0.89, 4.26), and avoiding large gatherings (aRR: 2.24, 95% CI: 1.18, 4.25), though low vaccination rates in this arm led to imprecise estimates. CONCLUSIONS: Individuals who initially decline vaccination can be convinced to vaccinate, particularly if they are already practicing other forms of COVID-19 prevention. Continued outreach and education from the scientific community can combat low vaccine confidence.

Influence of structural racism on cancer health disparities: Tailoring measures relevant to multiple myeloma.

This commentary highlights a need for comprehensive measures of structural racism tailored to cancer health disparities, in particular Black-White disparities in multiple myeloma (MM). Recent political and social calls and advances in the ability to quantitate structural racism have led to rapidly growing research on the health consequences of structural racism. However, to date, most studies have used unidimensional measures of structural racism that do not capture cumulative influences or enable the identification of factors most responsible for driving disparities. Furthermore, measures may not reflect aspects of structural racism most relevant to underlying disease processes and risks. This study proposes a multifaceted approach to measuring structural racism relevant to MM that includes comprehensive, disease- and at-risk population-tailored social and environmental data and biomarkers of susceptibility and progression related to underlying biological changes associated with structural racism. Such novel measures of structural racism may improve the ability to assess the influence of structural racism on cancer health disparities, which may advance understanding of disease etiology and differences observed by racialized groups.

Academy of Breastfeeding Medicine Clinical Protocol #19: Breastfeeding Promotion in the Prenatal Period (Revised 2024).

Background: The Academy of Breastfeeding Medicine revised the 2015 version of this clinical protocol to review the evidence and provide recommendations related to breastfeeding promotion in the prenatal period. Key Information: Promoting and normalizing breastfeeding in the prenatal period can improve breastfeeding outcomes including initiation and duration of breastfeeding. Ideally, prenatal interventions should be a part of a comprehensive longitudinal breastfeeding support program. Recommendations: Clinicians or other health workers should discuss breastfeeding at each prenatal visit. Counseling topics should include the health benefits of breastfeeding versus not breastfeeding, the basics of breastfeeding (e.g., physiology, positioning), what to expect of hospital-based and immediate postpartum breastfeeding support (i.e., Baby-Friendly Ten Steps), and the risks of unnecessary supplementation. Medical, anatomical, and other risk factors for breastfeeding challenges should be identified, and targeted anticipatory guidance should be given. Prenatal counseling should include distribution of structured breastfeeding education at low literacy levels and in the parent's preferred language. Counseling should be culturally sensitive and patient-centered, including family members when appropriate. Prenatal support may integrate various health workers (e.g., medical doctors, midwives, community health workers, lactation consultants, among others) and include various modalities including telecommunication. Enhancing breastfeeding education for prenatal care providers is also imperative. Additional themes related to implementation of recommendations for specific populations are also reviewed.

The empathy project: Staff confidence and training needs in psychosocial patient care.

INTRODUCTION: Radiation Therapists (RT) must balance highly technical procedures and psychosocial patient care during their daily work practices. While RTs are in a unique position to form rapport with patients and provide support and information, many RTs lack confidence in the psychosocial care of patients, and struggle to identify and address emotional cues. This study aimed to assess the confidence, competence, and training needs of RTs regarding psychosocial patient care. METHODS: All RTs at the Radiation Oncology Princess Alexandra Hospital Deparmtents were invited to participate in an electronic survey in May 2021, and May 2023 via email. The survey was distributed using SurveyMonkey and utilised a series of Likert-scale and open-ended questions. RESULTS: Staff reported high confidence in addressing technical treatment issues (98 % of respondents) and communicating with anxious (78 %) and distressed (78 %) patients. However, lower confidence was indicated with managing patient conflict (58 %) and communicating with patients who were depressed (53 %) or suffering mental health conditions (74 %). Staff were concerned about saying the wrong thing and experienced stress when they couldn't adequately communicate with patients requiring psychosocial support. The most significant barriers to providing adequate psychosocial care included time, staff numbers, and workload. Staff requested training in emotional cues, communication, anxiety and depression, and understanding psychosocial and mental health conditions. CONCLUSION: While staff perceptions and motivations of psychosocial care were overwhelmingly positive, further training is required to improve patient psychosocial care. Future steps include implementing psychosocial training resources in the departments, and reassessing staff confidence post training.

Anthropometric traits and risk of multiple myeloma: differences by race, sex and diagnostic clinical features.

BACKGROUND: Obesity is an established modifiable risk factor for multiple myeloma (MM). However, associations of obesity and MM risk in Black populations, for whom obesity and MM are more common, is less clear. METHODS: Using participants enrolled in the Integrative Molecular And Genetic Epidemiology study, we evaluated the association of anthropometric traits with MM risk overall, stratified by race and sex. Among cases, we assessed the association of BMI with the presence of myeloma-defining events. RESULTS: We observed an 18% increase in MM risk for every 5 kg/m2 increase in usual adult BMI. Participants with severe obesity (BMI ≥ 40 kg/m2) had the highest risk compared to those with a normal usual adult BMI (18.5-24.9 kg/m2; OR = 1.87, 95% CI 1.25-2.80), particularly among Black men (OR = 3.94, 95% CI 0.90-17.36). Furthermore, MM cases with overweight/obesity (BMI ≥ 25 kg/m2) were more likely to present at diagnosis with low renal function (OR = 1.62, 95% CI 1.09-2.40), deletion 13q (OR = 1.73, 95% CI 1.08-2.76) and lytic lesions or compression fractures (OR = 2.39, 95% CI 0.82-7.01) and less likely to present with severe diffuse osteopenia (OR = 0.51, 95% CI 0.31-0.81). CONCLUSIONS: Findings underscore the importance of obesity as a modifiable risk factor for MM, particularly in high-risk populations, and for the clinical presentation of disease.

History of Rectal Product Use and Country of Residence Influence Preference for Rectal Microbicide Dosage Forms Among Young Sexual and Gender Minorities: A Multi-country Trial Comparing Placebo Douche, Suppository, and Insert Products.

The DESIRE Study (MTN-035) explored product preference among three placebo rectal microbicide (RM) formulations, a rectal douche (RD), a suppository, and an insert, among 210 sexually active transgender people and men who have sex with men in five counties: the United States, Peru, Thailand, South Africa, and Malawi. Participants used each product prior to receptive anal sex (RAS) for 1 month, following a randomly assigned sequence, then selected their preferred product via computer assisted self-interview. In-depth interviews examined reasons for preference. We compared product preference and prior product use by country to explore whether geographic location and experience with the similar products impacted preference. A majority in the United States (56%) and Peru (58%) and nearly half in South Africa (48%) preferred the douche. Most in Malawi (59%) preferred the suppository, while half in Thailand (50%) and nearly half in South Africa (47%) preferred the insert. Participants who preferred the douche described it as quick and easy, already routinized, and serving a dual purpose of cleansing and protecting. Those who preferred the insert found it small, portable, discreet, with quick dissolution. Those who preferred the suppository found the size and shape acceptable and liked the added lubrication it provided. Experience with product use varied by country. Participants with RD experience were significantly more likely to prefer the douche (p = 0.03). Diversifying availability of multiple RM dosage forms can increase uptake and improve HIV prevention efforts globally.

RESUMEN: El estudio DESIRE (MTN-035) exploró la preferencia de producto entre tres formulaciones de microbicida rectal (MR) de placebo, una ducha rectal, un supositorio y un inserto, entre 210 personas transgénero y hombres que tienen sexo con hombres en cinco países: los Estados Unidos, Perú., Tailandia, Sudáfrica y Malawi. Los participantes utilizaron cada producto antes del sexo anal receptive (SAR) durante un mes, siguiendo una secuencia asignada al azar, luego seleccionaron su producto preferido mediante una autoentrevista asistida por computadora. Las entrevistas en profundidad examinaron los motivos de preferencia. Comparamos la preferencia de producto y el uso previo del producto por país para explorar si la ubicación geográfica y la experiencia con la forma farmacéutica impactaron la preferencia. Una mayoría en los Estados Unidos (56%) y Perú (58%) y casi la mitad en Sudáfrica (48%) prefirieron la ducha rectal. La mayoría en Malawi (59%) prefirió el supositorio, mientras que la mitad en Tailandia (50%) y casi la mitad en Sudáfrica (47%) prefirió el inserto. Los participantes que prefirieron la ducha rectal la describieron como rápida y fácil, ya parte de su rutina y que tenía el doble propósito de limpiar y proteger. Los que prefirieron el inserto lo consideraron pequeño, portátil, discreto y de rápida disolución. Los que prefirieron el supositorio encontraron que tenía un tamaño y forma aceptables y proveía lubricación adicional. La experiencia con el uso del producto varió según el país. Los participantes con experiencia con duchas rectales tenían significativamente más probabilidades de preferir la ducha rectal (p = 0,03). Diversificar la disponibilidad de múltiples formas farmacéuticas de MR puede aumentar la aceptación y mejorar los esfuerzos de prevención del VIH a nivel mundial.

Correction to "Solvent-Free Nonthermal Destruction of PFAS Chemicals and PFAS in Sediment by Piezoelectric Ball Milling".

[This corrects the article DOI: 10.1021/acs.estlett.2c00902.].

Clinical experience of a tattoo application device.

Introduction: The use of tattoos for radiation therapy (RT) treatment is common practice. The Comfort Marker 2.0 (CQ Medical, Iowa, USA) has been designed to apply tattoos with a controlled depth injection, potentially resulting in tattoos that fade over time. The aim of this study was to investigate the clinical implementation of the Comfort Marker 2.0 tattoo device including the patient experience and clinical workflow. Methods: Patients undergoing RT treatment for breast cancer were invited to participate in this prospective pilot study. Patients completed a questionnaire after the planning session rating the level of pain experienced during tattoo application. Staff rated ease of use after each patient recording any feedback regarding the device. To evaluate tattoo fading, patients were followed up at 6 and 12 months after treatment to assess if tattoos could be visualised. Results: Between August and December 2021, 50 breast cancer patients were recruited to the study. All patients received at least 3 tattoos. The majority of patients (80%) rated their pain between not hurting or hurting a little. More than 85% of staff indicated the device was easy or very easy to use. The three most common areas staff identified for improvement were: cordless device (39.1%), pen size (20.3%) and consumable rubbish (13.0%). All tattoos remained visible at the final follow up appointment. Conclusion: Clinical implementation of the Comfort Marker tattoo device has been successful. Overall, patients found the process reasonably painless and staff found the device easy to use, providing a consistent result.

Concordance between SARS-CoV-2 index individuals and their household contacts on index individual COVID-19 transmission cofactors: a comparison of self-reported and contact-reported information.

BACKGROUND: Following the outbreak of the COVID-19 pandemic, several clinical trials have evaluated postexposure prophylaxis (PEP) among close contacts of an index individual with a confirmed SARS-CoV-2 infection. Because index individuals do not directly inform the efficacy of prevention interventions, they are seldom enrolled in COVID-19 PEP studies. However, adjusting for prognostic covariates such as an index individual's COVID-19 illness and risk behaviors can increase precision in PEP efficacy estimates, so approaches to accurately collecting this information about the index individual are needed. This analysis aimed to assess whether surveying household contacts captures the same information as surveying the index individual directly. METHODS: REGN 2069/CoVPN 3502, a randomized controlled trial of COVID-19 PEP, enrolled household contacts of SARS-CoV-2 index individuals. CoVPN 3502-01 retrospectively enrolled and surveyed the index individuals. We compared responses to seven similar questions about the index individuals' transmission cofactors that were asked in both studies. We estimated the percent concordance between index individuals and their household contacts on each question, with 50% concordance considered equivalent to random chance. RESULTS: Concordance between index individuals and contacts was high on the most objective questions, approximately 97% (95% CI: 90-99%) for index individual age group and 96% (88-98%) for hospitalization. Concordance was moderate for symptoms, approximately 85% (75-91%). Concordance on questions related to the index individual's behavior was only slightly better or no better than random: approximately 62% (51-72%) for whether they received COVID-19 treatment, 68% (57-77%) for sharing a bedroom, 70% (59-79%) for sharing a common room, and 49% (39-60%) for mask wearing at home. However, while contacts were surveyed within 96 h of the index individual testing positive for SARS-CoV-2, the median time to enrollment in CoVPN 3502-01 was 240 days, which may have caused recall bias in our results. CONCLUSIONS: Our results suggest a need to survey index individuals directly in order to accurately capture their transmission cofactors, rather than relying on their household contacts to report on their behavior. The lag in enrolling participants into CoVPN 3502-01 also highlights the importance of timely enrollment to minimize recall bias.

Patient Perceptions of Audio-Only Versus Video Telehealth Visits: A Qualitative Study Among Patients in an Academic Medical Center Setting.

Introduction: Telehealth utilization surged during the COVID-19 pandemic, offering expanded health care access. Audio-only visits emerged as a crucial tool for patients facing technology or connectivity barriers to still use telehealth. This qualitative study aims to better understand patient perceptions of audio-only versus video telehealth visits during the COVID-19 pandemic, and how patients perceive the role of each in their overall health care. Methods: Semi-structured interviews were conducted with 14 adult patients seeking care at an academic medical center located in the Southeast region of the United States. Patients had experienced both an audio-only and video telehealth visit within the past 6 months. Topics covered in the interview included comfort, preference, quality, and communication during each type of visit. Interviews were transcribed verbatim, coded, and analyzed using a general inductive approach. Results: Participants valued having both modalities available largely due to convenience and saw these visits as supplemental or supporting their in-person care. Preferences for visit types were varied among participants and were context-specific, influenced by visit purpose and provider rapport. Patients viewed audio-only visits favorably for informational follow-ups and highlighted their convenience, particularly for multitasking and caregiving duties. In contrast, video visits were seen as more effective for communication due to visual cues and better suited for demonstrating health conditions. Audio-only visits were also seen as less technology-dependent and served as a vital back-up to failed video encounters. Discussion: Despite varied preferences, patients perceived both modalities as complementary to in-person care. Concerns around the quality of care were mitigated by patients' and providers' judicious use of visit types based on clinical appropriateness and existing rapport. The results emphasize the necessity and flexibility of audio-only visits in ensuring equitable access to telehealth, especially for those with technology limitations or demanding responsibilities. To maintain the access and convenience afforded by telehealth and ensure these benefits are offered equitably, policy makers and health care organizations must continue to provide flexible telehealth options, including audio-only visits.