Fellowship for Academic Generalists in Obstetrics and Gynecology: Is It Overdue?

Academic specialists in general obstetrics and gynecology are clinicians practicing the full breadth of the specialty while also contributing to medical education and scientific discovery. Residency programs in obstetrics and gynecology provide exposure to research training that is variable but frequently limited. This creates challenges for junior faculty and in many cases limits their research productivity, typically measured by published original research articles and grant funding. This frequently disadvantages academic specialists in promotion compared with their subspecialty fellowship-trained colleagues. A few research fellowship programs were recently launched to address this issue. However, these programs are not uniform and encounter challenges such as sustainable funding. In this article, building on knowledge from current academic specialist fellowship programs, we discuss the needs, challenges, and proposed solutions. We also propose some details needing further discussion among the academic obstetrics and gynecology community. We discuss how such fellowships can integrate with current development and training opportunities such as the Women's Reproductive Health Research award, Building Interdisciplinary Research Careers in Women's Health award, other K and K-type career development programs, NIH T32 grants, and clinical research courses for obstetricians and gynecologists. Academic specialist fellowship programs can have synergy with other women's health fellowship programs offered by other specialties. They can additionally leverage institutional resources. We conclude by summarizing a proposed model for academic specialist research fellowship programs.

Crohn's patients and healthy infants share immunodominant B cell response to commensal flagellin peptide epitopes.

BACKGROUND AND AIMS: Inflammatory bowel disease is a chronic manifestation of dysregulated immune response to the gut microbiota in genetically pre-disposed hosts. Nearly half of patients with Crohn's disease (CD) develop selective serum IgG response to flagellin proteins expressed by bacteria in the Lachnospiraceae family. This study aimed to identify the binding epitopes of these IgG antibodies and assess their relevance in CD and in homeostasis. METHODS: Sera from an adult CD cohort, a treatment-naïve pediatric CD cohort, and three independent non-IBD infant cohorts were analyzed using novel techniques including a flagellin peptide microarray and a flagellin peptide cytometric bead array. RESULTS: A dominant B cell peptide epitope in CD patients was identified, locating in the highly conserved "hinge region" between the D0 and D1 domains at the amino-terminus of Lachnospiraceae flagellins. Elevated serum IgG reactivity to the hinge peptide was strongly associated with incidence of CD and the development of disease complications in children with CD up to five years in advance. Notably, high levels of serum IgG to the hinge epitope were also found in most infants from 3 different geographic regions (Uganda, Sweden, and the USA) at one year of age, which decrements rapidly afterwards. CONCLUSIONS: These findings identified a distinct subset of CD patients, united by a shared reactivity to a dominant commensal bacterial flagellin epitope that may represent failure of a homeostatic response to the gut microbiota beginning in infancy.

Thermophysical properties of tetrabutylammonium chloride, paraffin and fatty acids for thermal energy applications.

Investigating the thermophysical properties of substances is crucial for using them as phase change materials (PCMs) and heat transfer fluids (HTFs) in thermal energy applications. In this study, the thermophysical properties of three medium-temperature PCMs (around 338 K) and one ionic liquid, tetrabutylammonium chloride ([N4444 +][Cl-]), were evaluated and compared. The commercial PCMs were two fatty acids (OM65 and stearic acid) and one paraffin (RT64HC). The characterised thermophysical properties were the viscosity, density, phase change temperatures, melting and solidification enthalpies, and thermal conductivity for the solid and liquid phases. The uncertainties for each property were calculated, and two empirical equations were obtained from the correlation of viscosity and thermal conductivity data along isotherms. This paper also compared the thermophysical properties of commercial PCMs and HTFs against the ionic liquid, discussing the potential use of the ionic liquid as a thermal energy storage material and HTFs.

Taphonomic signatures of early scavenging by black and turkey vultures.

Scavenging is critical for nutrient cycling and maintenance of healthy ecosystems. While there is substantial research into the identification of taphonomic signatures from facultative mammalian scavengers, early stage scavenging signatures by vultures remain unknown. Further, some vulture species are opportunistic predators, highlighting the need to define signatures observed in the course of normal scavenging behavior. We placed stillborn neonatal calves in an unoccupied pasture and used motion-trigger camera traps to quantify scavenging effort, then conducted necropsies to evaluate the effect of black vulture (Coragyps atratus) and turkey vulture (Cathartes aura) scavenging effort on carcass consumption. We measured the order of consumption of different tissue types to delineate which anatomic structures vultures consume first. Scavenging trials with higher numbers of vultures feeding on the carcass for longer were associated with decreased remaining tongue and abdominal viscera, and a larger umbilical wound. Greater maximum flock sizes were associated with decreased remaining tongue and abdominal viscera, a larger umbilical wound, and greater biomass consumption. Black vultures targeted the perineum and tongue earlier, while turkey vultures targeted the eyes, perineum, and tongue. These results are consistent with the idea that vultures prefer tissues that are easy to access and contain high nutrient content. These patterns form a distinctive taphonomic signature that can be used to identify early scavenging by black and turkey vultures. Our results demonstrate that criteria commonly used to identify livestock depredation by black vultures only document vulture presence and not predation. This distinction implies that new and more definitive criteria need to be developed and put into practice for more accurate decision criteria in livestock depredation compensation programs.

Cardiovascular Risks in People With Narcolepsy: Expert Panel Consensus Recommendations.

BACKGROUND: Observational and retrospective studies suggest that people with narcolepsy may have an increased prevalence of cardiovascular and cardiometabolic comorbidities and may be at greater risk for future cardiovascular events. An expert consensus panel was formed to establish agreement on the risk of hypertension and cardiovascular/cardiometabolic disease in people with narcolepsy and to develop strategies to mitigate these risks. METHODS AND RESULTS: Experts in sleep medicine and cardiology were selected to participate in the panel. After reviewing the relevant literature, the experts identified key elements, drafted recommendation statements, and developed discussion points to provide supporting evidence for the recommendations. The draft and final recommendations were rated on a scale from 0 (not at all agree) to 4 (very much agree). All experts had an agreement rating of 4.0 for all 14 revised recommendation statements for patients with narcolepsy. These statements comprised 3 themes: (1) recognize the risk of hypertension and cardiovascular/cardiometabolic disease, (2) reduce the risk of hypertension and cardiovascular/cardiometabolic disease, and (3) reduce sodium intake to lower the risk of hypertension and cardiovascular disease. CONCLUSIONS: These consensus recommendations are intended to increase awareness of potential cardiovascular/cardiometabolic risks in patients with narcolepsy for all clinicians. Early monitoring for, and prevention of, cardiovascular risks in this population are of great importance, especially as narcolepsy usually develops in adolescents and young adults, who will be exposed to adverse effects of the disease for decades. Prospective systematic studies are needed to determine association and causation of narcolepsy with cardiovascular/cardiometabolic disorders.

Therapeutic DBS for OCD Suppresses the Default Mode Network.

Background: Deep brain stimulation (DBS) of the anterior limb of the internal capsule (ALIC) is an emerging treatment for severe, refractory obsessive-compulsive disorder (OCD). The therapeutic effects of DBS are hypothesized to be mediated by direct modulation of a distributed cortico-striato-thalmo-cortical network underlying OCD symptoms. However, the exact underlying mechanism by which DBS exerts its therapeutic effects still remains unclear. Method: In five participants receiving DBS for severe, refractory OCD (3 responders, 2 non-responders), we conducted a DBS On/Off cycling paradigm during the acquisition of functional MRI to determine the network effects of stimulation across a variety of bipolar configurations. We also performed tractography using diffusion-weighted imaging (DWI) to relate the functional impact of DBS to the underlying structural connectivity between active stimulation contacts and functional brain networks. Results: We found that therapeutic DBS had a distributed effect, suppressing BOLD activity within regions such as the orbitofrontal cortex, dorsomedial prefrontal cortex, and subthalamic nuclei compared to non-therapeutic configurations. Many of the regions suppressed by therapeutic DBS were components of the default mode network (DMN). Moreover, the estimated stimulation field from the therapeutic configurations exhibited significant structural connectivity to core nodes of the DMN. Conclusions: Therapeutic DBS for OCD suppresses BOLD activity within a distributed set of regions within the DMN relative to non-therapeutic configurations. We propose that these effects may be mediated by interruption of communication through structural white matter connections surrounding the DBS active contacts.

Medicaid long-term services and supports and caregiving needs of caregivers of individuals with intellectual and developmental disabilities.

BACKGROUND: Long-term care services are funded primarily by Medicaid long-term services and support in the United States, where eligibility is based on care needs of the individual with intellectual and developmental disability alone. Impact of Medicaid waiver services on self-reported caregiver needs is not well understood. METHOD: Caregivers (n = 405) of individuals with intellectual and developmental disabilities across four states (NY, OH, TX, and PA) completed an online survey. RESULTS: Caregivers reported a moderate degree of burden and susceptibility of stress-induced health breakdown. Despite controlling for the activities of daily living of the care recipient, caregivers of individuals with Medicaid Waiver services reported greater difficulty managing medications (p = .013) and finding paid help (p < .001) than caregivers of individuals without services.

Modernizing the Data Infrastructure for Clinical Research to Meet Evolving Demands for Evidence.

Importance: The ways in which we access, acquire, and use data in clinical trials have evolved very little over time, resulting in a fragmented and inefficient system that limits the amount and quality of evidence that can be generated. Observations: Clinical trial design has advanced steadily over several decades. Yet the infrastructure for clinical trial data collection remains expensive and labor intensive and limits the amount of evidence that can be collected to inform whether and how interventions work for different patient populations. Meanwhile, there is increasing demand for evidence from randomized clinical trials to inform regulatory decisions, payment decisions, and clinical care. Although substantial public and industry investment in advancing electronic health record interoperability, data standardization, and the technology systems used for data capture have resulted in significant progress on various aspects of data generation, there is now a need to combine the results of these efforts and apply them more directly to the clinical trial data infrastructure. Conclusions and Relevance: We describe a vision for a modernized infrastructure that is centered around 2 related concepts. First, allowing the collection and rigorous evaluation of multiple data sources and types and, second, enabling the possibility to reuse health data for multiple purposes. We address the need for multidisciplinary collaboration and suggest ways to measure progress toward this goal.

Person-Centered, Goal-Oriented Care Helped My Patients Improve Their Quality of Life.

When the goal is to help patients improve their quality of life, it makes sense to focus directly on the activities and relationships that are most important to each patient. This can be accomplished most effectively by following a three-step process that includes 1) connecting with the patient around what matters to them, 2) co-creating a goal-oriented plan, and 3) collaborating with patient, family, team members, and consultants to increase the probability of success. Once this approach has been mastered and the necessary systems, processes, and relationships are in place, this should not take more time than a problem-oriented approach, and it will almost certainly be more satisfying for both physician and patient. The impact on population-based quality metrics is uncertain. Though fewer patients may choose to follow standard recommendations, those who do may be more likely to adhere to them.

End-of-life practices in Hong Kong intensive care units: results from the Ethicus-2 study.

INTRODUCTION: The need for end-of-life care is common in intensive care units (ICUs). Although guidelines exist, little is known about actual end-of-life care practices in Hong Kong ICUs. The study aim was to provide a detailed description of these practices. METHODS: This prospective, multicentre observational sub-analysis of the Ethicus-2 study explored end-of-life practices in eight participating Hong Kong ICUs. Consecutive adult ICU patients admitted during a 6-month period with life-sustaining treatment (LST) limitation or death were included. Follow-up continued until death or 2 months from the initial decision to limit LST. RESULTS: Of 4922 screened patients, 548 (11.1%) had LST limitation (withholding or withdrawal) or died (failed cardiopulmonary resuscitation/brain death). Life-sustaining treatment limitation occurred in 455 (83.0%) patients: 353 (77.6%) had decisions to withhold LST and 102 (22.4%) had decisions to withdraw LST. Of those who died without LST limitation, 80 (86.0%) had failed cardiopulmonary resuscitation and 13 (14.0%) were declared brain dead. Discussions of LST limitation were initiated by ICU physicians in most (86.2%) cases. Shared decision-making between ICU physicians and families was the predominant model; only 6.0% of patients retained decision-making capacity. Primary medical reasons for LST limitation were unresponsiveness to maximal therapy (49.2%) and multiorgan failure (17.1%). The most important consideration for decision-making was the patient's best interest (81.5%). CONCLUSION: Life-sustaining treatment limitations are common in Hong Kong ICUs; shared decision-making between physicians and families in the patient's best interest is the predominant model. Loss of decision-making capacity is common at the end of life. Patients should be encouraged to communicate end-of-life treatment preferences to family members/surrogates, or through advance directives.

Biochemical features of the Cry4B toxin of Bacillus thuringiensis subsp. israelensis and its interaction with BT-R3, a bitopic cadherin G-protein coupled receptor in Anopheles gambiae.

Introduction: The cadherin G-protein coupled receptor BT-R3 in the mosquito Anopheles gambiae is a single membrane-spanning α-helical (bitopic) protein that represents the most abundant and functionally diverse group of membrane proteins. Binding of the Cry4B toxin of Bacillus thuringiensis subsp. israelensis (Bti) to BT-R3 triggers a Mg2+-dependent signalling pathway in the mosquito that involves stimulation of G protein α-subunit, which subsequently launches a coordinated signalling cascade involving Na+/K+-ATPase. Described in this study is the behaviour of the Cry4B purified active protein toxin in solution relative to its protoxin predecessor produced by Bti as well as identification of the region within BT-R3 of An. gambiae to which the toxin binds. Materials and Methods: The relationship and behaviour of protoxin and toxin were ascertained in vitro by solubility studies in an alkaline environment like that of the mosquito larval midgut. To identify the specific toxin-binding site within BT-R3, the full-length coding sequence of the bt-r3 gene was amplified and cloned in pENTR/D-TOTO and subcloned in pXINSECT-DEST38 resulting in recombinant pXINSECT-DEST38-bt-r3. Cytotoxicity was analysed using Trichoplusia ni High Five™ insect cells transfected with the pXINSECT-DEST38-bt-r3 plasmid rendering them susceptible to the Cry4B toxin. Truncation mutational analyses, receptor-toxin binding studies and live cell experiments were used to elucidate the toxin-binding site in BT-R3. Results: The N-terminal half of the Cry4B protoxin was cleaved releasing active Cry4B toxin. The nontoxic C-terminal portion was degraded into small peptide fragments. The receptor BT-R3 contained a single toxin-binding site--a 106-amino acid polypeptide bounded by Ile1359 and Ser1464 (1359IS1464) localized in the 11th cadherin repeat of the receptor. Conclusions: The structural features of the toxin-binding site are critical to the specificity, selectivity and affinity of the active toxin and for the design and development of novel Bti-based biopesticides.

VCP/p97-associated proteins are binders and debranching enzymes of K48-K63-branched ubiquitin chains.

Branched ubiquitin (Ub) chains constitute a sizable fraction of Ub polymers in human cells. Despite their abundance, our understanding of branched Ub function in cell signaling has been stunted by the absence of accessible methods and tools. Here we identify cellular branched-chain-specific binding proteins and devise approaches to probe K48-K63-branched Ub function. We establish a method to monitor cleavage of linkages within complex Ub chains and unveil ATXN3 and MINDY as debranching enzymes. We engineer a K48-K63 branch-specific nanobody and reveal the molecular basis of its specificity in crystal structures of nanobody-branched Ub chain complexes. Using this nanobody, we detect increased K48-K63-Ub branching following valosin-containing protein (VCP)/p97 inhibition and after DNA damage. Together with our discovery that multiple VCP/p97-associated proteins bind to or debranch K48-K63-linked Ub, these results suggest a function for K48-K63-branched chains in VCP/p97-related processes.

Managing medications among individuals with mild cognitive impairment and dementia: Patient-caregiver perspectives.

BACKGROUND: With changing cognitive abilities, individuals with mild cognitive impairment (MCI) and dementia face challenges in successfully managing multidrug regimens. We sought to understand how individuals with MCI or dementia and their family caregivers manage multidrug regimens and better understand patient-to-caregiver transitions in medication management responsibilities. METHODS: We conducted qualitative interviews among patient-caregiver dyads. Eligibility included: patients with a diagnosis of MCI, mild or moderate dementia, managing ≥3 chronic conditions, ≥5 prescription medications, who also had a family caregiver ≥18 years old. Semi-structured interview guides, informed by the Medication Self-Management model, ascertained roles and responsibilities for medication management and patient-to-caregiver transitions in medication responsibilities. RESULTS: We interviewed 32 patient-caregiver dyads. Older adults and caregivers favored older adult autonomy in medication management, and individuals with MCI and mild dementia largely managed their medications independently using multiple strategies (e.g., establishing daily routines, using pillboxes). Among individuals with moderate dementia, caregivers assumed all medication-related responsibilities except when living separately. In those scenarios, caregivers set up organizers and made reminder calls, but did not observe family members taking medications. Patient-to-caregiver transitions in medication responsibilities frequently occurred after caregivers observed older adults making errors with medications. As caregivers sought to assume greater responsibilities with family members' medicines, they faced multiple barriers. Most barriers were dyadic; they affected both the older adult and the caregiver and/or the relationship. Some barriers were specific to caregivers; these included caregivers' competing responsibilities or inaccurate perceptions of dementia, while other barriers were related to the healthcare system. CONCLUSIONS: To ease medication management transitions, balance must be sought between preservation of older adult autonomy and early family caregiver involvement. Clinicians should work to initiate conversations with family caregivers and individuals living with MCI or dementia about transitioning medication responsibilities as memory loss progresses, simplify regimens, and deprescribe, as appropriate.

Why Evidence Generation Should Matter to Payers and How They Can Help.

Importance: The US leads the world in bringing new medical products to market, but the ability to generate evidence to inform clinical practice in postmarket settings needs improvement. Although a diverse group of stakeholders is working to improve postmarket evidence generation, the role of private payers has been underappreciated. Observations: Payers are crucial allies in improving evidence generation because better data would better inform coverage decisions, their policies and practices influence the conduct of care and research, and their claims data are a source of real-world evidence used in medical product evaluation. In addition, payers have a stake in improving evidence generation because the kinds of evidence needed to inform health care and coverage decisions are often not available when a product enters the market and may not be generated without their involvement. Here, we describe several key steps payers could take to improve evidence generation, including participating in efforts to reduce administrative and financial barriers to the conduct of clinical trials, directly incentivizing evidence generation on high-priority questions by funding potential cost-saving trials, increasing engagement with the medical products industry on evidentiary needs for coverage decisions, and improving usability of claims data by reducing data lags and routinely recording unique device identifiers. Broad payer engagement with US Food and Drug Administration recommendations regarding evidence generation will ensure that the opportunities to participate in clinical research are extended to all communities and that evidence needed to inform care is generated in trials and surveillance systems that reflect the clinical reality across the US. Conclusions and Relevance: Increasing payer involvement in evidence generation can benefit all participants in the medical innovation ecosystem. The importance of payers in these efforts will continue to grow in response to imperatives to increase integration of care and research, engage a diverse set of communities in clinical research, and move toward alternative payment models.

Pyrene-functionalized poly(methacrylic acid) acts as an efficient stabilizer for graphene nanoplatelets and facilitates their use in waterborne latex formulations.

HYPOTHESIS: Pyrene derivatives are effective motifs when designing graphene-philic surfactants, enabling the use of hydrophobic graphene-based nanomaterials in waterborne formulations. Hence, novel pyrene end-functionalized polymeric stabilizers show promise for stabilizing aqueous graphene nanomaterial dispersions, and offer benefits over traditional small molecule surfactants. EXPERIMENTS: Pyrene end-functionalized poly(methacrylic acid) (Py-PMAAn, where n = 68 to 128) was synthesized by reversible addition-fragmentation chain-transfer (RAFT) polymerization of MAA using a pyrene-containing RAFT chain-transfer agent. These polymers were evaluated as aqueous graphene nanoplatelet (GNP) stabilizers. Subsequently, polymer-stabilized GNPs were formulated into film-forming polymer latex dispersions and the properties of the resulting GNP-containing films measured. FINDINGS: Py-PMAAn homopolymers with well-defined molecular weights were prepared via RAFT solution polymerization. They served as efficient stabilizers for aqueous GNP dispersions and performed better than a traditional small molecule surfactant and non-functionalized PMAA, especially at higher pH and with higher molecular weight polymers. The use of Py-PMAAn allowed GNPs to be readily formulated into waterborne latex coatings. When compared to controls, the resulting films were significantly reinforced due to the improved homogeneity of dried nanocomposite films and chain entanglement between the polymer matrix and stabilizers. Thus, the ability to readily incorporate GNPs into aqueous formulations and enhance GNP/polymer matrix interfaces was demonstrated for these novel amphiphilic stabilizers.

Psychometric Testing of the Korean version of the Self-Care of Coronary Heart Disease Inventory Version 3.

PURPOSE: This methodological study evaluated the psychometric properties of the Self-Care of Coronary Heart Disease Inventory version 3 (SC-CHDI v3) in a Korean context. METHODS: The SC-CHDI v3 was translated into Korean following a rigorous translation process. Participants were 452 patients who had experienced coronary heart disease (CHD), all recruited from a tertiary hospital in Korea. Exploratory and confirmatory factor analyses were performed to test construct validity. Concurrent validity was examined by correlating scores from the Korean version of the SC-CHDI v3 with those from the Cardiac Self-Efficacy Scale. Internal consistency was analyzed using Cronbach's alpha and McDonald's omega. RESULTS: The Korean version of the SC-CHDI v3 consists of 21 items, excluding two from the original instrument. The self-care maintenance subscale identified a two-factor structure: "treatment adherence" and "health-promoting behaviors." The goodness-of-fit indices were satisfied: χ2 = 18.19, p = .110, comparative fit index (CFI) = .97, Tucker-Lewis Index (TLI) = .95, and standardized root mean square residual (SRMR) = .04. The self-care monitoring subscale consisted of a one-dimensional structure ("monitoring behaviors") and the goodness-of-fit indices were satisfied: χ2 = 19.19, p = .059, CFI = .99, TLI = .99, and SRMR = .04. The self-care management subscales had a two-factor structure of "consulting behaviors" and "problem-solving behaviors." The goodness-of-fit indices were satisfied: χ2 = 16.44, p = .037, CFI = .99, TLI = .98, and SRMR = .03. Scores from the Cardiac Self-Efficacy Scale showed a positive correlation with the Korean version of SC-CHDI v3 subscales. Reliability estimates were ≥ .80 for all subscales except for the self-care maintenance subscale. CONCLUSIONS: The Korean version of the SC-CHDI v3 consists of 21 items in 3 subscales and is a valid and reliable instrument. Therefore, healthcare providers can effectively utilize it to assess the self-care levels of patients with CHD.