filoVision - using deep learning and tip markers to automate filopodia analysis.

Filopodia are slender, actin-filled membrane projections used by various cell types for environment exploration. Analyzing filopodia often involves visualizing them using actin, filopodia tip or membrane markers. Due to the diversity of cell types that extend filopodia, from amoeboid to mammalian, it can be challenging for some to find a reliable filopodia analysis workflow suited for their cell type and preferred visualization method. The lack of an automated workflow capable of analyzing amoeboid filopodia with only a filopodia tip label prompted the development of filoVision. filoVision is an adaptable deep learning platform featuring the tools filoTips and filoSkeleton. filoTips labels filopodia tips and the cytosol using a single tip marker, allowing information extraction without actin or membrane markers. In contrast, filoSkeleton combines tip marker signals with actin labeling for a more comprehensive analysis of filopodia shafts in addition to tip protein analysis. The ZeroCostDL4Mic deep learning framework facilitates accessibility and customization for different datasets and cell types, making filoVision a flexible tool for automated analysis of tip-marked filopodia across various cell types and user data.

Prevalence of lifestyle-related behavioral information in claims data in the U.S.

OBJECTIVE: Given their association with varying health risks, lifestyle-related behaviors are essential to consider in population-level disease prevention. Health insurance claims are a key source of information for population health analytics, but the availability of lifestyle information within claims data is unknown. Our goal was to assess the availability and prevalence of data items that describe lifestyle behaviors across several domains within a large U.S. claims database. METHODS: We conducted a retrospective, descriptive analysis to determine the availability of the following claims-derived lifestyle domains: nutrition, eating habits, physical activity, weight status, emotional wellness, sleep, tobacco use, and substance use. To define these domains, we applied a serial review process with three physicians to identify relevant diagnosis and procedure codes within claims for each domain. We used enrollment files and medical claims from a large national U.S. health plan to identify lifestyle relevant codes filed between 2016 and 2020. We calculated the annual prevalence of each claims-derived lifestyle domain and the proportion of patients by count within each domain. RESULTS: Approximately half of all members within the sample had claims information that identified at least one lifestyle domain (2016 = 41.9%; 2017 = 46.1%; 2018 = 49.6%; 2019 = 52.5%; 2020 = 50.6% of patients). Most commonly identified domains were weight status (19.9-30.7% across years), nutrition (13.3-17.8%), and tobacco use (7.9-9.8%). CONCLUSION: Our study demonstrates the feasibility of using claims data to identify key lifestyle behaviors. Additional research is needed to confirm the accuracy and validity of our approach and determine its use in population-level disease prevention.

Creating community: Expanding access to psychosocial programs for Latina breast cancer survivors.

OBJECTIVE: Breast cancer survivors often derive benefits from psychosocial interventions, but less is known about Latina women's experiences. Given the disproportionately high disease burden faced by Latina survivors, it is critical to examine ways to enhance access for this population. Thus, the present study aimed to (a) examine women's perceptions of factors associated with effective delivery of a psychosocial program designed for Spanish speaking women with limited access to care, and (b) identify the mechanisms by which the program enhanced women's psychological well-being. METHODS: In a qualitative study, in-depth interviews were conducted with 15 immigrant Latina breast cancer survivors who previously received psychosocial services at a community-based organization. Grounded theory was used to analyze the data. RESULTS: Through open, axial, and selective coding, we arrived at the core category achieving a sense of community. The psychosocial program promoted access and enhanced women's psychological well-being by creating a sense of community among participants. This was facilitated by three primary aspects of service provision: access factors, a holistic approach to health, and therapeutic factors imparted through a biweekly support group. CONCLUSIONS: Psychosocial services promoted a sense of community among Latina breast cancer survivors while reflecting their cultural values and unique psychosocial needs. Findings may guide the development of interventions to increase access to care, enhance health outcomes, and create and maintain a sense of community among medically underserved populations.

Obesity Management in Adults: A Review.

Importance: Obesity affects approximately 42% of US adults and is associated with increased rates of type 2 diabetes, hypertension, cardiovascular disease, sleep disorders, osteoarthritis, and premature death. Observations: A body mass index (BMI) of 25 or greater is commonly used to define overweight, and a BMI of 30 or greater to define obesity, with lower thresholds for Asian populations (BMI ≥25-27.5), although use of BMI alone is not recommended to determine individual risk. Individuals with obesity have higher rates of incident cardiovascular disease. In men with a BMI of 30 to 39, cardiovascular event rates are 20.21 per 1000 person-years compared with 13.72 per 1000 person-years in men with a normal BMI. In women with a BMI of 30 to 39.9, cardiovascular event rates are 9.97 per 1000 person-years compared with 6.37 per 1000 person-years in women with a normal BMI. Among people with obesity, 5% to 10% weight loss improves systolic blood pressure by about 3 mm Hg for those with hypertension, and may decrease hemoglobin A1c by 0.6% to 1% for those with type 2 diabetes. Evidence-based obesity treatment includes interventions addressing 5 major categories: behavioral interventions, nutrition, physical activity, pharmacotherapy, and metabolic/bariatric procedures. Comprehensive obesity care plans combine appropriate interventions for individual patients. Multicomponent behavioral interventions, ideally consisting of at least 14 sessions in 6 months to promote lifestyle changes, including components such as weight self-monitoring, dietary and physical activity counseling, and problem solving, often produce 5% to 10% weight loss, although weight regain occurs in 25% or more of participants at 2-year follow-up. Effective nutritional approaches focus on reducing total caloric intake and dietary strategies based on patient preferences. Physical activity without calorie reduction typically causes less weight loss (2-3 kg) but is important for weight-loss maintenance. Commonly prescribed medications such as antidepressants (eg, mirtazapine, amitriptyline) and antihyperglycemics such as glyburide or insulin cause weight gain, and clinicians should review and consider alternatives. Antiobesity medications are recommended for nonpregnant patients with obesity or overweight and weight-related comorbidities in conjunction with lifestyle modifications. Six medications are currently approved by the US Food and Drug Administration for long-term use: glucagon-like peptide receptor 1 (GLP-1) agonists (semaglutide and liraglutide only), tirzepatide (a glucose-dependent insulinotropic polypeptide/GLP-1 agonist), phentermine-topiramate, naltrexone-bupropion, and orlistat. Of these, tirzepatide has the greatest effect, with mean weight loss of 21% at 72 weeks. Endoscopic procedures (ie, intragastric balloon and endoscopic sleeve gastroplasty) can attain 10% to 13% weight loss at 6 months. Weight loss from metabolic and bariatric surgeries (ie, laparoscopic sleeve gastrectomy and Roux-en-Y gastric bypass) ranges from 25% to 30% at 12 months. Maintaining long-term weight loss is difficult, and clinical guidelines support the use of long-term antiobesity medications when weight maintenance is inadequate with lifestyle interventions alone. Conclusion and Relevance: Obesity affects approximately 42% of adults in the US. Behavioral interventions can attain approximately 5% to 10% weight loss, GLP-1 agonists and glucose-dependent insulinotropic polypeptide/GLP-1 receptor agonists can attain approximately 8% to 21% weight loss, and bariatric surgery can attain approximately 25% to 30% weight loss. Comprehensive, evidence-based obesity treatment combines behavioral interventions, nutrition, physical activity, pharmacotherapy, and metabolic/bariatric procedures as appropriate for individual patients.

Natural Language Processing of Nursing Notes: An Integrative Review.

Natural language processing includes a variety of techniques that help to extract meaning from narrative data. In healthcare, medical natural language processing has been a growing field of study; however, little is known about its use in nursing. We searched PubMed, EMBASE, and CINAHL and found 689 studies, narrowed to 43 eligible studies using natural language processing in nursing notes. Data related to the study purpose, patient population, methodology, performance evaluation metrics, and quality indicators were extracted for each study. The majority (86%) of the studies were conducted from 2015 to 2021. Most of the studies (58%) used inpatient data. One of four studies used data from open-source databases. The most common standard terminologies used were the Unified Medical Language System and Systematized Nomenclature of Medicine, whereas nursing-specific standard terminologies were used only in eight studies. Full system performance metrics (eg, F score) were reported for 61% of applicable studies. The overall number of nursing natural language processing publications remains relatively small compared with the other medical literature. Future studies should evaluate and report appropriate performance metrics and use existing standard nursing terminologies to enable future scalability of the methods and findings.

Predictors of posttraumatic growth among hematopoietic cell transplant recipients.

OBJECTIVE: Prior research has shown that cancer survivors often report positive psychological changes from the experience of cancer, or posttraumatic growth (PTG). However, few studies have focused on PTG in cancer patients recovering from hematopoietic cell transplantation (HCT). The present study measured PTG at specific milestones during the year following HCT and investigated psychosocial and treatment-related factors that may hinder or facilitate PTG. METHODS: Participants (N = 430) completed assessments of PTG, social support, and coping pre-transplant. Posttraumatic growth was also assessed at 1, 3, 6, and 12 months post-transplant. Information about treatment regimen and post-transplant complications was abstracted from medical records. Mixed-effects linear regression models were used to evaluate the extent to which pre-transplant social support, coping approaches, treatment intensity, and post-transplant complications predicted PTG. RESULTS: Compared to pre-transplant, PTG scores were significantly higher at 6- and 12-month post-transplant. Greater pre-transplant social support significantly predicted greater PTG across the assessment points. Use of emotional engagement coping strategies also strongly predicted post-transplant PTG. Conversely, coping styles characterized by emotional avoidance generally were not predictive of PTG. No treatment-related factors or post-transplant complications were predictive of PTG. CONCLUSIONS: Findings indicate that supportive social relationships and coping by engaging with difficult emotions may facilitate PTG following HCT. Moreover, these factors were more important than medical characteristics in explaining PTG. Findings may guide the development of interventions to enhance positive psychological outcomes after HCT.

Hypoglycemia Communication in Primary Care Visits for Patients with Diabetes.

BACKGROUND: Hypoglycemia is a common and serious adverse effect of diabetes treatment, especially for patients using insulin or insulin secretagogues. Guidelines recommend that these patients be assessed for interval hypoglycemic events at each clinical encounter and be provided anticipatory guidance for hypoglycemia prevention. OBJECTIVE: To determine the frequency and content of hypoglycemia communication in primary care visits. DESIGN: Qualitative study PARTICIPANTS: We examined 83 primary care visits from one urban health practice representing 8 clinicians and 33 patients using insulin or insulin secretagogues. APPROACH: Using a directed content analysis approach, we analyzed audio-recorded primary care visits collected as part of the Achieving Blood Pressure Control Together study, a randomized trial of behavioral interventions for hypertension. The coding framework included communication about interval hypoglycemia, defined as discussion of hypoglycemic events or symptoms; the components of hypoglycemia anticipatory guidance in diabetes guidelines; and hypoglycemia unawareness. Hypoglycemia documentation in visit notes was compared to visit transcripts. KEY RESULTS: Communication about interval hypoglycemia occurred in 24% of visits, and hypoglycemic events were reported in 16%. Despite patients voicing fear of hypoglycemia, clinicians rarely assessed hypoglycemia frequency, severity, or its impact on quality of life. Hypoglycemia anticipatory guidance was provided in 21% of visits which focused on diet and behavior change; clinicians rarely counseled on hypoglycemia treatment or avoidance of driving. Limited discussions of hypoglycemia unawareness occurred in 8% of visits. Documentation in visit notes had low sensitivity but high specificity for ascertaining interval hypoglycemia communication or hypoglycemic events, compared to visit transcripts. CONCLUSIONS: In this high hypoglycemia risk population, communication about interval hypoglycemia and counseling for hypoglycemia prevention occurred in a minority of visits. There is a need to support clinicians to more regularly assess their patients' hypoglycemia burden and enhance counseling practices in order to optimize hypoglycemia prevention in primary care.

Development and validation of early warning score system: A systematic literature review.

OBJECTIVES: This review aims to: 1) evaluate the quality of model reporting, 2) provide an overview of methodology for developing and validating Early Warning Score Systems (EWSs) for adult patients in acute care settings, and 3) highlight the strengths and limitations of the methodologies, as well as identify future directions for EWS derivation and validation studies. METHODOLOGY: A systematic search was conducted in PubMed, Cochrane Library, and CINAHL. Only peer reviewed articles and clinical guidelines regarding developing and validating EWSs for adult patients in acute care settings were included. 615 articles were extracted and reviewed by five of the authors. Selected studies were evaluated based on the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) checklist. The studies were analyzed according to their study design, predictor selection, outcome measurement, methodology of modeling, and validation strategy. RESULTS: A total of 29 articles were included in the final analysis. Twenty-six articles reported on the development and validation of a new EWS, while three reported on validation and model modification. Only eight studies met more than 75% of the items in the TRIPOD checklist. Three major techniques were utilized among the studies to inform their predictive algorithms: 1) clinical-consensus models (n = 6), 2) regression models (n = 15), and 3) tree models (n = 5). The number of predictors included in the EWSs varied from 3 to 72 with a median of seven. Twenty-eight models included vital signs, while 11 included lab data. Pulse oximetry, mental status, and other variables extracted from electronic health records (EHRs) were among other frequently used predictors. In-hospital mortality, unplanned transfer to the intensive care unit (ICU), and cardiac arrest were commonly used clinical outcomes. Twenty-eight studies conducted a form of model validation either within the study or against other widely-used EWSs. Only three studies validated their model using an external database separate from the derived database. CONCLUSION: This literature review demonstrates that the characteristics of the cohort, predictors, and outcome selection, as well as the metrics for model validation, vary greatly across EWS studies. There is no consensus on the optimal strategy for developing such algorithms since data-driven models with acceptable predictive accuracy are often site-specific. A standardized checklist for clinical prediction model reporting exists, but few studies have included reporting aligned with it in their publications. Data-driven models are subjected to biases in the use of EHR data, thus it is particularly important to provide detailed study protocols and acknowledge, leverage, or reduce potential biases of the data used for EWS development to improve transparency and generalizability.

Overcoming the Challenges of Direct Observation and Feedback Programs: A Qualitative Exploration of Resident and Faculty Experiences.

Problem: Prior studies have reported significant negative attitudes amongst both faculty and residents toward direct observation and feedback. Numerous contributing factors have been identified, including insufficient time for direct observation and feedback, poorly understood purpose, inadequate training, disbelief in the formative intent, inauthentic resident-patient clinical interactions, undermining of resident autonomy, lack of trust between the faculty-resident dyad, and low-quality feedback information that lacks credibility. Strategies are urgently needed to overcome these challenges and more effectively engage faculty and residents in direct observation and feedback. Otherwise, the primary goals of supporting both formative and summative assessment will not be realized and the viability of competency-based medical education will be threatened. Intervention: Toward this end, recent studies have recommended numerous strategies to overcome these barriers: protected time for direct observation and feedback; ongoing faculty and resident training on goals and bidirectional, co-constructed feedback; repeated direct observations and feedback within a longitudinal resident-supervisor relationship; utilization of assessment tools with evidence for validity; and monitoring for engagement. Given the complexity of the problem, it is likely that bundling multiple strategies together will be necessary to overcome the challenges. The Direct Observation Structured Feedback Program (DOSFP) incorporated many of the recommended features, including protected time for direct observation and feedback within longitudinal faculty-resident relationships. Using a qualitative thematic approach the authors conducted semi-structured interviews, during February and March, 2019, with 10 supervisors and ten residents. Participants were asked to reflect on their experiences. Interview guide questions explored key themes from the literature on direct observation and feedback. Transcripts were anonymized. Two authors independently and iteratively coded the transcripts. Coding was theory-driven and differences were discussed until consensus was reached. The authors then explored the relationships between the codes and used a semantic approach to construct themes. Context: The DOSFP was implemented in a psychiatry continuity clinic for second and third year residents. Impact: Faculty and residents were aligned around the goals. They both perceived the DOSFP as focused on growth rather than judgment even though residents understood that the feedback had both formative and summative purposes. The DOSFP facilitated educational alliances characterized by trust and respect. With repeated practice within a longitudinal relationship, trainees dropped the performance orientation and described their interactions with patients as authentic. Residents generally perceived the feedback as credible, described feedback quality as high, and valued the two-way conversation. However, when receiving feedback with which they did not agree, residents demurred or, at most, would ask a clarifying question, but then internally discounted the feedback. Lessons Learned: Direct observation and structured feedback programs that bundle recent recommendations may overcome many of the challenges identified by previous research. Yet, residents discounted disagreeable feedback, illustrating a significant limitation and the need for other strategies that help residents reconcile conflict between external data and one's self-appraisal.

Exploring Residents' Experience of Career Development Scholarship Tracks: A Qualitative Case Study Using Social Cognitive Career Theory.

Problem: Trainees enter graduate medical education with professional aspirations that often extend beyond the role of clinician to roles such as educator, innovator, leader, advocate, or researcher. Many residency programs have implemented academic tracks to support career development in these areas. With the exception of research tracks, these tracks generally do not include significant longitudinal protected time and often rely upon 'extra-curricular' effort and possess insufficient structure, mentorship, and accountability. Most prior studies of non-research scholarship tracks have not been theory driven and do not explore in depth the experience of residents who participate. Approach: To address this gap in the literature, we conducted a qualitative case study informed by Social Cognitive Career Theory to explore the professional identity development of residents who participated in a non-research scholarship track that incorporates recommended best practices. The track, Pathways to Expertise Program, incorporates features of successful research tracks: protected time, longitudinal experience, mentorship, platforms for recognition, and accountability. Participants from the first three cohorts were interviewed at the time of their graduation (2017-2019). Semi-structured interviews were conducted, transcribed, and independently coded. Social Cognitive Career Theory informed the organization of codes into themes. Context: The Pathways to Expertise Program was implemented in a psychiatry residency training program in a large urban academic teaching hospital. Impact: Fifteen residents entered Pathways to Expertise Program during the study period and all 15 participated in the study. Fourteen completed the program and presented their projects at the department grand rounds. For dissemination, 12 presented their project findings at one or more national meetings in the form of a poster (20 distributed across 11 residents), workshop (six distributed across four residents), or presentation (two across two residents). Six residents accounted for a total of seven first author publications in peer reviewed journals. All participants described how their self-efficacy increased as a result of new skills (e.g., content, methodology, and scientific communication), mentorship (e.g., content and process guidance), peer and broader support (e.g., small group supervision), persuasive communications (e.g., recognition both locally and nationally), and positive emotional reactions (e.g., triumph). The residents also described expecting compelling benefits (e.g., stronger application for fellowship and expanded career opportunities). Participants indicated that the experience influenced their career goals and how they perceived their professional identities. Lessons Learned: These findings suggest that a longitudinal academic track that incorporates features of successful research tracks (protected time, mentorship, peer support, and accountability for deliverables) can be instrumental in forming and maturing professional identities for non-clinical roles. These tracks can accomplish several important goals, including enhancing resilience via identity formation around passion and purpose and meeting society's need for physicians who are engaged in inquiry and innovation. Implications for the design of academic tracks in general are explored.

Use of Varenicline in Smokeless Tobacco Cessation: A Systematic Review and Meta-Analysis.

OBJECTIVE: Conduct a systematic review and meta-analysis on the effectiveness and safety of varenicline in smokeless tobacco (SLT) cessation. METHODS: PubMed, EMBASE, clinicaltrials.gov, and the Cochrane Registry were searched up to February 1, 2014, for randomized clinical trials (RCTs) comparing varenicline to placebo. Random effects Mantel-Haenszel summary relative risks (RRs), risk difference (RD), and 95% CIs were used for analysis and reporting of outcomes. Primary and secondary outcomes were the 7-day point prevalence of SLT abstinence at the end of 12 and 26 weeks, respectively. Adverse events reported include nausea, sleep disturbance, and mood disorders. RESULTS: Three published RCTs involving 744 SLT users with a mean age of 39.7 years, of which greater than 88% were males, were randomized to varenicline (n = 370) and placebo (n = 374). Subjects in the varenicline arm had a significantly higher 7-day point prevalence of SLT abstinence at 12 weeks (48% vs. 33%; RR = 1.45, 95% CI = 1.22-1.72, p < .0001, I2 = 0%; RD = 13%, 95% CI = 4%-23%, p = .008) but not at 26 weeks (49% vs. 39%; RR = 1.38, 95% CI = 0.93-2.03, p = .11, I2 = 51%). There were no statistically significant differences in the incidences of adverse events between the 2 arms but interpretation is limited by high heterogeneity. CONCLUSION: This pooled analysis suggests that varenicline is effective in achieving a 7-day point prevalence of SLT abstinence at 12 weeks but showed that this effect was not sustained at 26 weeks.

Dynamic mitochondrial-nuclear redistribution of the immunophilin FKBP51 is regulated by the PKA signaling pathway to control gene expression during adipocyte differentiation.

Glucocorticoids play an important role in adipogenesis through the glucocorticoid receptor (GR) that forms a heterocomplex with Hsp90•Hsp70 and one high molecular weight immunophilin, either FKBP51 or FKBP52. When 3T3-L1 preadipocytes are induced to differentiate, FKBP51 expression progressively increases, whereas FKBP52 decreases, and Hsp90, Hsp70, p23 and Cyp40 remain unchanged. Interestingly, FKBP51 rapidly translocates from mitochondria to the nucleus where it is retained upon its interaction with chromatin and the nuclear matrix. FKBP51 nuclear localization is transient, and after 48 hours it cycles back to mitochondria. Importantly, this dynamic FKBP51 mitochondrial-nuclear shuttling depends on PKA signaling, because its inhibition by PKI or knockdown of PKA-cα by siRNA, prevented FKBP51 nuclear translocation induced by IBMX. In addition, the electrophoretic pattern of migration of FKBP51 is altered by treatment of cells with PKI or knockdown of PKA-cα, suggesting that FKBP51 is a PKA substrate. In preadipocytes, FKBP51 colocalizes with PKA-cα in mitochondria. When adipogenesis is triggered, PKA-cα also moves to the nucleus colocalizing with FKBP51 mainly in the nuclear lamina. Moreover, FKBP51 and GR interaction increases when preadipocytes are induced to differentiate. GR transcriptional capacity is reduced when cells are incubated in the presence of IBMX, forskolin or dibutyryl-cAMP, compounds that induced FKBP51 nuclear translocation, but not by a specific activator of EPAC. FKBP51 knockdown facilitates adipogenesis, whereas ectopic expression of FKBP51 blocks adipogenesis. These findings indicate that the dynamic mitochondrial-nuclear shuttling of FKBP51 regulated by PKA may be key in fine-tuning the transcriptional control of GR target genes required for the acquisition of adipocyte phenotype.

The role of egg-nest contrast in the rejection of brood parasitic eggs.

Hosts of avian brood parasites can avoid the reproductive costs of raising genetically unrelated offspring by rejecting parasitic eggs. The perceptual cues and controls mediating parasitic egg discrimination and ejection are well studied: hosts are thought to use differences in egg color, brightness, maculation, size and shape to discriminate between their own and foreign eggs. Most theories of brood parasitism implicitly assume that the primary criteria to which hosts attend when discriminating eggs are differences between the eggs themselves. However, this assumption is confounded by the degree to which chromatic and achromatic characteristics of the nest lining co-vary with egg coloration, so that egg-nest contrast per se might be the recognition cue driving parasitic egg detection. Here, we systematically tested whether and how egg-nest contrast itself contributes to foreign egg discrimination. In an artificial parasitism experiment, we independently manipulated egg color and nest lining color of the egg-ejector American robin (Turdus migratorius), a host of the obligate brood parasitic brown-headed cowbird (Molothrus ater). We hypothesized that the degree of contrast between foreign eggs and the nest background would affect host egg rejection behavior. We predicted that experimentally decreasing egg-nest chromatic and achromatic contrast (i.e. rendering parasitic eggs more cryptic against the nest lining) would decrease rejection rates, while increasing egg-nest contrast would increase rejection rates. In contrast to our predictions, egg-nest contrast was not a significant predictor of egg ejection patterns. Instead, egg color significantly predicted responses to parasitism. We conclude that egg-egg differences are the primary drivers of egg rejection in this system. Future studies should test for the effects of egg-nest contrast per se in predicting parasitic egg recognition in other host-parasite systems, including those hosts building enclosed nests and those parasites laying cryptic eggs, as an alternative to hypothesized effects of egg-egg contrast.

Understanding the Information Needs of Pharmacy Staff Using CancelRx: A Qualitative Study of the Use of Prescription E-cancellation.

Background: Although electronic prescription cancellation such as via CancelRx can facilitate critical communication between prescribers and pharmacy staff about discontinued medications, there is little work that explores whether CancelRx meets the needs of pharmacy staff users. Objective: This study leverages qualitative interviews with pharmacy staff to address the following question: When medication changes are made by a prescriber using CancelRx, what information is needed by pharmacy staff to make correct and effective decisions in their roles in medication management? Methods: We conducted an inductive thematic analysis of interviews with 11 pharmacy staff members (pharmacists and pharmacy technicians) across three outpatient community pharmacy sites within an academic health care system. Results: Three information needs themes were consistently identified by both pharmacists and pharmacy technicians: prescriber intent when initiating the CancelRx, clinical rationale for the medication change, and intended medication regimen. Notably, both pharmacists and pharmacy technicians often reported seeking multiple information needs not fully addressed by CancelRx in the electronic health record (EHR) to achieve the shared goals of correct dispensing of medications and supporting patient self-management. Conclusions: Our qualitative analysis reveals that outpatient community pharmacy staff in an academic health care system often seek additional information from the (EHR) following medication changes communicated by CancelRx to meet their information needs. Ideally, the prescriber would provide sufficient information through CancelRx to automatically identify all discontinued prescriptions. These limitations highlight the need for design features that support routine communication of needed information at the time of a medication change, such as structured data elements.

Use of medications associated with weight change among participants in the All of Us research programme.

Our objective was to describe the use of medications associated with weight change among US adults with overweight/obesity, including anti-obesity medications (AOMs), weight-loss-promoting and weight-gain-promoting medications. We performed a cross-sectional analysis of data from the nationwide All of Us Research Programme. We included adults with measured body mass index (BMI) ≥ 27 kg/m2 enrolled between 2018 and 2022 across the United States. We used linked electronic health record data to determine medication use ±12 months of BMI measure. Our 132 057 participants had mean age 54 years and mean BMI 34 kg/m2 ; 60% of participants were women, 62% White, and 32% Black. Only 1% used any AOM, and 14% used at least one weight-loss-promoting medication. We found that 36% used at least one weight-gain-promoting medication, and approximately 20% used multiple weight-gain-promoting medications. While AOMs are underutilized by participants with overweight/obesity, weight-gain-promoting medication use is common. Our results raise concern about potential iatrogenic weight gain from medications. Future research is needed to estimate the long-term effect of weight-gain-promoting medications on weight status and determine whether weight-loss benefits occur with their discontinuation. Clinician education on AOMs and weight-loss-promoting medications may be needed to increase their use.

Fumarase Deficiency and Its Effect on Infertility: A Case Series.

Background: Fumarase deficiency is an autosomal recessive condition characterized by severe neurologic abnormalities due to homozygous mutations in the fumarate hydratase (FH) gene. Heterozygous carriers of FH mutations have increased risk of developing uterine fibroids that can be associated with hereditary leiomyomatosis and renal cell cancer (HLRCC). The association between FH mutations and infertility remains uncertain. The objective of our study was to characterize the infertility diagnoses, treatments, and outcomes in women presenting to a fertility center who were found to be carriers of fumarase deficiency based on the presence of heterozygous FH mutations. Case Presentation: A retrospective case series was conducted including 10 women presenting to an academic fertility center who were found to be FH carriers based on genetic carrier screening. Of the 9 women who were engaged in further workup, 2 had imaging results consistent with uterine fibroids. One woman underwent hysteroscopic myomectomy prior to two courses of ovulation induction with timed intercourse (OI/TIC) followed by one successful cycle of IVF. Of the remaining patients, only 1 woman successfully delivered after a cycle of ovulation induction with intrauterine insemination (OI/IUI). Other patients pursuing OI/IUI, OI/TIC, or monitored natural cycles had unsuccessful experiences. Conclusion: Patients with infertility who are offered genetic testing should be screened for FH mutations, as the carriers are at risk of developing HLRCC-associated uterine fibroids, which can influence fertility and pregnancy. Additional research is needed to investigate the impacts of FH mutations on infertility.

Visualization by BiFC of different C/EBPß dimers and their interaction with HP1α reveals a differential subnuclear distribution of complexes in living cells.

How the co-ordinated events of gene activation and silencing during cellular differentiation are influenced by spatial organization of the cell nucleus is still poorly understood. Little is known about the molecular mechanisms controlling subnuclear distribution of transcription factors, and their interplay with nuclear proteins that shape chromatin structure. Here we show that C/EBPß not only associates with pericentromeric heterochromatin but also interacts with the nucleoskeleton upon induction of adipocyte differentiation of 3T3-L1 cells. Different C/EBPß dimers localize in different nuclear domains. Using BiFC in living cells, we show that LAP (Liver Activating Protein) homodimers localize in euchromatin and heterochromatin. In contrast, LIP (Liver Inhibitory Protein) homodimers localize exclusively in heterochromatin. Importantly, their differential subnuclear distribution mirrors the site for interaction with HP1α. HP1α inhibits LAP transcriptional capacity and occupies the promoter of the C/EBPß-dependent gene c/ebpα in 3T3-L1 preadipocytes. When adipogenesis is induced, HP1α binding decreases from c/ebpα promoter, allowing transcription. Thus, the equilibrium among different pools of C/EBPß associated with chromatin or nucleoskeleton, and dynamic changes in their interaction with HP1α, play key roles in the regulation of C/EBP target genes during adipogenesis.