Functional architecture of pancreatic islets identifies a population of first responder cells that drive the first-phase calcium response.

Insulin-secreting ß-cells are functionally heterogeneous. Whether there exist cells driving the first-phase calcium response in individual islets, has not been examined. We examine "first responder" cells, defined by the earliest [Ca2+] response during first-phase [Ca2+] elevation, distinct from previously identified "hub" and "leader" cells. We used islets isolated from Mip-CreER; Rosa-Stop-Lox-Stop-GCamP6s mice (ß-GCamP6s) that show ß-cell-specific GCamP6s expression following tamoxifen-induced CreER-mediated recombination. First responder cells showed characteristics of high membrane excitability and lower electrical coupling to their neighbors. The first-phase response time of ß-cells in the islet was spatially organized, dependent on the cell's distance to the first responder cell, and consistent over time up to approximately 24 h. When first responder cells were laser ablated, the first-phase [Ca2+] was slowed down, diminished, and discoordinated compared to random cell ablation. Cells that were next earliest to respond often took over the role of the first responder upon ablation. In summary, we discover and characterize a distinct first responder ß-cell state, critical for the islet first-phase response to glucose.

Metal-Free Homogeneous O2 Reduction by an Iminium-Based Electrocatalyst.

The oxygen reduction reaction (ORR) is important for alternative energy and industrial oxidation processes. Herein, an iminium-based organoelectrocatalyst (im+) for the ORR with trifluoroacetic acid as a proton source in acetonitrile solution under both electrochemical and spectrochemical conditions using decamethylferrocene as a chemical reductant is reported. Under spectrochemical conditions, H2O2 is the primary reaction product, while under electrochemical conditions H2O is produced. This difference in selectivity is attributed to the interception of the free superoxide intermediate under electrochemical conditions by the reduced catalyst, accessing an alternate inner-sphere pathway.

Defining Complex Patient Populations: Implications for Population Size, Composition, Utilization, and Costs.

BACKGROUND: Interventions to support patients with complex needs have proliferated in recent years, but the question of how to identify patients with complex needs has received relatively little attention. There are innumerable ways to structure inclusion and exclusion criteria for complex care interventions, and little is known about the implications of choices made in designing patient selection criteria. OBJECTIVE: To provide insights into the design of patient selection criteria for interventions, by implementing criteria sets within a large health plan member population and comparing the characteristics of the resulting complex patient cohorts. DESIGN: Retrospective observational descriptive study. SUBJECTS: Patients identified as having complex needs, within the membership population of Kaiser Permanente Southern California, a large, population-based health plan with more than 4 million members. We characterize five commonly used archetypes of complex needs: high-cost patients, patients with multiple chronic conditions, frail elders, emergency department high-utilizers, and inpatient high-utilizers. MEASURES: We selected an initial set of criteria for identifying patients in each of the archetypical complex populations, based on available administrative data. We then tested multiple variants of each definition. We compared the resulting patient cohorts using univariate and bivariate descriptive statistics. KEY RESULTS: Overall, 32.7% of the 3,112,797 adults in our population-based sample were selected by at least one of the 25 definitions of complexity we tested. Across definitions the total number of patients identified as complex ranged from 622,560 to 1583 and complex patient cohorts varied widely in demographic characteristics, chronic conditions, healthcare utilization, spending, and survival. CONCLUSIONS: Choice of patient population is critical to the design of complex care programs. Exploratory analyses of population criteria can provide useful information for program planning in the setting of limited resources for interventions. Data such as these should be generated as a key step in program design.

Gram Scalable Method to Synthesize Biscarbodiimides and Asymmetric Monocarbodiimides: A Platform to Access an Array of Phosphaguanidines, Amidines, and Guanidines.

A mild, broadly functional group tolerant methodology has been developed to access a variety of mono- and bis-carbodiimides in good yield and high purity on multigram scale. Direct addition into these versatile motifs facilitated the rapid synthesis of a library of novel amidinines, guanidines, and phosphaguandines.

Factors associated with smokefree rules in the homes of Black/African American women smokers residing in low-resource rural communities.

Little is known about the implementation of voluntary policies in the homes of Black/African American women smokers who live in rural areas where health care access is limited. This paper examines 1) the sample's prevalence of comprehensive smoke-free rules; 2) sociodemographic, social, and smoking characteristics of women by home rule type; and 3) the association of social indicators with the outcome complete ban on smoked tobacco use in the home (n = 191). Families Rising to Enforce Smokefree Homes collected baseline data from 2019 to 2021 prior to randomization to an intervention that aimed to increase comprehensive smokefree policies in the homes African American women living in the rural Delta region of Arkansas. The primary outcome was implementation of a complete ban on all smoked tobacco products anywhere inside the home. Results showed that 26% of women had a rule that completely banned all smoked tobacco products in the home. Women who reported having no ban were more likely to be employed part-time (50.0%), while women with a partial (66.9%) or complete ban (60.0%) were more likely to not currently work for pay. Women who indicated that they just meet basic expenses and meet needs with little left had significantly lower odds of having a complete ban on smoked tobacco in the home than women who indicated that they live comfortably. Perceived financial security may be a motivating factor that helps women keep their homes free from all smoked tobacco products (# NCT03476837).

Knowledge and Attitudes of Potential Community Health Worker Employers: Findings from the State of Arkansas, USA.

Community health workers (CHWs) are critical to health equity efforts, but sustaining CHW programs is challenging. Understanding stakeholders' knowledge and attitudes about CHWs can inform strategies to advance this important workforce. The authors implemented an online survey of potential CHW employers to learn their perceptions of CHWs' roles, outcomes, and abilities to affect important health outcomes, and of key issues that affect CHW employment. The survey was disseminated statewide to a diverse group of stakeholders working in healthcare in Arkansas. A total of 151 surveys were collected and included in the analysis. The organizations represented by respondents primarily included state and local agencies and clinics, followed by healthcare systems. The main professional roles of survey respondents were administrators and clinicians, followed by healthcare staff. Over 90% of respondents agreed that CHWs have the ability to conduct community outreach, serve as a liaison, navigate health systems, provide coaching support, and participate in care coordination. Over 90% of healthcare administrators, clinicians, and policymakers agreed that standardized training and a clear definition of role and scope of practice are important to CHW employment. However, almost two-thirds of respondents' organizations were not employing CHWs, adding to previous research which has primarily focused on CHW employers' attitudes. Understanding and addressing attitudes of those who lack experience with CHWs can help to identify actions needed to promote and increase adoption of CHWs. The authors share how they are using these data to engage stakeholders in decision-making and adoption of CHWs in their state.

Assessing the Feasibility of an Online Training Designed to Enable Community Health Workers to Deliver a Comprehensive, Evidence-Based Weight Loss Intervention for Rural African Americans of Faith.

Obesity is a critical modifiable risk factor in cancer prevention, control, and survivorship. Comprehensive weight loss interventions (e.g., Diabetes Prevention Program (DPP)) have been recommended by governmental agencies to treat obesity. However, their high implementation costs limit their reach, especially in underserved African American (AA) communities. Community health workers (CHWs) or trusted community members can help increase access to obesity interventions in underserved regions facing provider shortages. CHW-led interventions have increased weight loss. However, in-person CHW training can be costly to deliver and often requires extensive travel to implement. Web-based trainings have become common to increase reach at reduced cost. However, the feasibility of an online CHW training to deliver the DPP in AAs is unknown. The feasibility of an online CHW training to deliver the DPP adapted for AAs was assessed. The online training was compared to an in-person DPP training with established effectiveness. CHW effectiveness and satisfaction were assessed at baseline and 6 weeks. Nineteen participants (in-person n = 10; online n = 9) were recruited. At post-training, all scored higher than the 80% on a knowledge test required to deliver the intervention. All participants reported high levels of training satisfaction (88.9% of online participants and 90% of in-person participants rated the training as at least 6 on a 1-7 scale) and comfort to complete intervention tasks (78% of online participants and 60% of in-person participants scored at least 6 on a 1-7 scale). There were no significant differences in outcomes by arm. An online CHW training to deliver the DPP adapted for AAs faith communities produced comparable effectiveness and satisfaction to an evidence-based in-person CHW training. Further research is needed to assess the cost-effectiveness of different CHW training modalities to reduce obesity.

Increasing Reach of the Diabetes Prevention Program in African American Churches: Project FIT Lessons Learned in Using an Interprofessional Student Service-Learning Approach.

The Diabetes Prevention Program (DPP) is an evidence-based lifestyle intervention proven to reduce/delay diabetes onset with diet change, physical activity, and modest weight loss. However, access to the program is limited in low-resource communities. Having health profession students facilitate DPP groups as a service learning course-credit opportunity may benefit their interprofessional training while also expanding DPP access in underserved communities. We sought to use student reflections to identify themes to assist with program evaluation and to inform program refinements. Students (N=95) from the University of Missouri-Kansas City (UMKC) medical, physician assistant, and pharmacy programs led DPP groups in urban Kansas City African American churches alongside church health liaisons as part of an interprofessional service-learning course. Students reported creating satisfying, ongoing relationships with participants; developing a deeper understanding of obstacles to weight loss; and learning the role of other health professionals in the care of patients. They also identified obstacles to successful program implementation, such as needing less time in training and having equal participation from students across their interprofessional teams. Students learned important lessons by leading the DPP, but interprofessional service-learning courses have multiple obstacles to successful delivery. Still, this approach has great potential to increase access to the DPP in African American communities and promote skill development in health profession students.

Outcomes of infants and children undergoing surgical repair of ventricular septal defect: a review of the literature and implications for research with an emphasis on pulmonary artery hypertension.

BACKGROUND: Pulmonary vascular disease resulting from CHDs may be the most preventable cause of pulmonary artery hypertension worldwide. Many children in developing countries still do not have access to early closure of clinically significant defects, and the long-term outcomes after corrective surgery remain unclear. Focused on long-term results after isolated ventricular septal defect repair, our review sought to determine the most effective medical therapy for the pre-operative management of elevated left-to-right shunts in patients with an isolated ventricular septal defect. METHODS: We identified articles specific to the surgical repair of isolated ventricular septal defects. Specific parameters included the pathophysiology and pre-operative medical management of pulmonary over-circulation and outcomes. RESULTS: Studies most commonly focused on histologic changes to the pulmonary vasculature and levels of thromboxanes, prostaglandins, nitric oxide, endothelin, and matrix metalloproteinases. Only 2/44 studies mentioned targeted pharmacologic management to any of these systems related to ventricular septal defect repair; no study offered evidence-based guidelines to manage pulmonary over-circulation with ventricular septal defects. Most studies with long-term data indicated a measurable frequency of pulmonary artery hypertension or diminished exercise capacity late after ventricular septal defect repair. CONCLUSION: Long-term pulmonary vascular and respiratory changes can occur in children after ventricular septal defect repair. Research should be directed at providing an evidenced-based approach to the medical management of infants and children with ventricular septal defects (and naturally all CHDs) to minimise consequences of pulmonary artery hypertension, particularly as defect repair may occur late in underprivileged societies.

Segmentation of High-Cost Adults in an Integrated Healthcare System Based on Empirical Clustering of Acute and Chronic Conditions.

BACKGROUND: High-cost patients are a frequent focus of improvement projects based on primary care and other settings. Efforts to characterize high-cost, high-need patients are needed to inform care planning, but such efforts often rely on a priori assumptions, masking underlying complexities of a heterogenous population. OBJECTIVE: To define recognizable subgroups of patients among high-cost adults based on clinical conditions, and describe their survival and future spending. DESIGN: Retrospective observational cohort study. PARTICIPANTS: Within a large integrated delivery system with 2.7 million adult members, we selected the top 1% of continuously enrolled adults with respect to total healthcare expenditures during 2010. MAIN MEASURES: We used latent class analysis to identify clusters of alike patients based on 53 hierarchical condition categories. Prognosis as measured by healthcare spending and survival was assessed through 2014 for the resulting classes of patients. RESULTS: Among 21,183 high-cost adults, seven clinically distinctive subgroups of patients emerged. Classes included end-stage renal disease (12% of high-cost population), cardiopulmonary conditions (17%), diabetes with multiple comorbidities (8%), acute illness superimposed on chronic conditions (11%), conditions requiring highly specialized care (14%), neurologic and catastrophic conditions (5%), and patients with few comorbidities (the largest class, 33%). Over 4 years of follow-up, 6566 (31%) patients died, and survival in the classes ranged from 43 to 88%. Spending regressed to the mean in all classes except the ESRD and diabetes with multiple comorbidities groups. CONCLUSIONS: Data-driven characterization of high-cost adults yielded clinically intuitive classes that were associated with survival and reflected markedly different healthcare needs. Relatively few high-cost patients remain persistently high cost over 4 years. Our results suggest that high-cost patients, while not a monolithic group, can be segmented into few subgroups. These subgroups may be the focus of future work to understand appropriateness of care and design interventions accordingly.

Development of an e-learning package for sepsis care.

Severe sepsis is a major cause of morbidity and mortality in the UK. This article describes the collaborative development and implementation of an interactive online learning package to understand the key role nurses have in recognising and then starting to apply the Sepsis Six care bundle in clinical practice. The e-learning package, developed in a UK teaching hospital, uses a case study approach to address the knowledge that is required to be able to recognise sepsis, to understand the processes that occur and the ongoing care and treatment required. The package is relevant to final-year student nurses, newly registered nurses in preceptorship and other health professionals involved in assessing and treating patients who may be developing sepsis.

Real-Time Monitoring of Cellular Bioenergetics with a Multianalyte Screen-Printed Electrode.

Real-time monitoring of changes to cellular bioenergetics can provide new insights into mechanisms of action for disease and toxicity. This work describes the development of a multianalyte screen-printed electrode for the detection of analytes central to cellular bioenergetics: glucose, lactate, oxygen, and pH. Platinum screen-printed electrodes were designed in-house and printed by Pine Research Instrumentation. Electrochemical plating techniques were used to form quasi-reference and pH electrodes. A Dimatix materials inkjet printer was used to deposit enzyme and polymer films to form sensors for glucose, lactate, and oxygen. These sensors were evaluated in bulk solution and microfluidic environments, and they were found to behave reproducibly and possess a lifetime of up to 6 weeks. Linear ranges and limits of detection for enzyme-based sensors were found to have an inverse relationship with enzyme loading, and iridium oxide pH sensors were found to have super-Nernstian responses. Preliminary measurements where the sensor was enclosed within a microfluidic channel with RAW 264.7 macrophages were performed to demonstrate the sensors' capabilities for performing real-time microphysiometry measurements.

The phenomenon of phototoxicity and long-term risks of commonly prescribed and structurally diverse drugs.

Photosensitivity to structurally diverse drugs is a common but under-reported adverse cutaneous reaction and can be classified as phototoxic or photoallergic. Phototoxic reactions occur when the skin is exposed to sunlight after administering topical or systemic medications that exhibit photosensitizing activity. These reactions depend on the dose of medication, degree of exposure to ultraviolet light, type of ultraviolet light, and sufficient skin distribution volume. Accurate prediction of the incidence and phototoxic response severity is challenging due to a paucity of literature, suggesting that phototoxicity may be more frequent than reported. This paper reports an extensive literature review on phototoxic drugs; the review employed pre-determined search criteria that included meta-analyses, systematic reviews, literature reviews, and case reports freely available in full text. Additional reports were identified from reference sections that contributed to the understanding of phototoxicity. The following drugs and/or drug classes are discussed: amiodarone, voriconazole, chlorpromazine, doxycycline, fluoroquinolones, hydrochlorothiazide, nonsteroidal anti-inflammatory drugs, and vemurafenib. In reviewing phototoxic skin reactions, this review highlights drug molecular structures, their reactive pathways, and, as there is a growing association between photosensitizing drugs and the increasing incidence of skin cancer, the consequential long-term implications of photocarcinogenesis.

The relative importance of predation risk and water temperature in maintaining Bergmann's rule in a marine ectotherm.

Bergmann's rule-an increase in body size with latitude-correlates with latitudinal declines in ambient temperature and predation risk, but relatively few studies simultaneously explore the relative importance of these factors. Along temperate Atlantic shorelines, the isopod Idotea balthica from high latitudes are 53% longer on average than isopods from low latitudes. When reared at 6°-24°C, juveniles increased growth and development rates with temperature. Because the increase in growth rate with temperature outstripped increases in development rate, female size at maturity increased with temperature. This thermal sensitivity of growth cannot account for the latitudinal pattern in body size. Within temperature treatments, females from low latitudes reached sexual maturity at younger ages and at a smaller size than did females from higher latitudes. This shift in life-history strategy is predicted by latitudinal declines in predation pressure, which we tested using field-tethering experiments. Overall, isopods at low latitudes had a 44% greater mortality risk from daytime predators relative to isopods at higher latitudes. We conclude that a latitudinal gradient in predation risk, not temperature, is principally responsible for Bergmann's rule in I. balthica. Increases in body size during future warming of oceans may be constrained by local patterns of predation risk.

Reappraisal and literature review of primary cutaneous cribriform apocrine carcinoma.

Primary cutaneous cribriform apocrine carcinoma (PCCAC) is an exceedingly rare sweat gland carcinoma. Clinically, it most often presents as a singular, asymptomatic nodule or cyst on the extremities of middle-aged patients and follows an indolent course. Both visceral and cutaneous cribriform tumors exist in nature. While a cribriform pattern is well recognized in tumors of visceral organs, there is a paucity in the literature on the defining characteristics for primary cutaneous tumors. Consensus regarding diagnostic criteria, etiology, and management protocols has yet to be achieved. We conducted an extensive literature review using pre-determined search criteria, resulting in 12 identified case reports and series on PCCAC that were subsequently analyzed. All data were compiled to provide a comprehensive update on the existing information regarding clinical presentation, histopathology, and management of reported PCCACs, as well as differential diagnosis, controversial issues, and recommendations for future considerations.

How to do an ultrasound or computed tomography guided hook-wire localization excisional biopsy of non-palpable lymph nodes.

This article describes the use of USS or CT guided hook-wire localization to aid the excisional biopsy of non-palpable lymph nodes in the cervical, axillary and inguinal regions. This technique allows a more focussed surgical approach intra-operatively to reduce surgical time and morbidity for the patients.

Social influence and the likelihood of using cannabis: Role of source physical attractiveness.

The presence of another individual may increase or decrease the likelihood a person will use drugs, depending on factors such as whether the source (i.e., the other individual) is also using drugs. The purpose of this study was to determine whether the physical attractiveness of the source influences the likelihood a person will use cannabis. Heterosexual men and women were recruited via a crowdsourcing platform and asked to rank order the physical attractiveness of 13 opposite-gender people. Participants were then presented with hypothetical scenarios in which they reported the likelihood of engaging in drug use (i.e., "use marijuana") and a nondrug control activity ("enjoy the view" from a private balcony) when they were alone versus in the presence of an opposite-gender person they rated low, moderate, or high in relative physical attractiveness. The likelihood of participating in both drug and nondrug activities increased as a function of the relative physical attractiveness of the other individual (i.e., the source); however, notable gender differences were observed in the likelihood of using cannabis. Women were less likely to use cannabis in the presence of less attractive men relative to using cannabis alone, whereas men were more likely to use cannabis in the presence of more attractive women than using cannabis alone. These data suggest the presence of an opposite-gender person can either inhibit or facilitate drug use depending on the physical attractiveness of the source and gender of the subject. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Hospital Readmissions by Variation in Engagement in the Health Care Hotspotting Trial: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Variability in intervention participation within care management programs can complicate standard analysis strategies. Objective: To evaluate whether care management was associated with reduced hospital readmissions among individuals with higher participation probabilities. Design, Setting, and Participants: A total of 800 hospitalized patients aged 18 years and older were randomized as part of the Health Care Hotspotting randomized clinical trial, which was conducted in Camden, New Jersey, from June 2014 to September 2017. Data were collected through October 2018. In this new analysis performed between April 6, 2022, and April 23, 2023, the distillation method was applied to account for variable intervention participation. A gradient-boosting machine learning model produced predicted probabilities of engaged participation using baseline covariates only. Predicted probabilities were used to trim both intervention and control populations in an equivalent manner, and intervention effects were reevaluated within study population subsets that were increasingly concentrated with patients having higher participation probabilities. Patients had 2 or more hospitalizations in the 6-month preenrollment period and documented evidence of chronic illness and social complexity. Intervention: Multidisciplinary teams provided services to patients in the intervention arm for a mean 120 days after hospital discharge. Patients in the control group received usual postdischarge care. Main Outcomes and Measures: Hospital readmission rates and counts 30, 90, and 180 days postdischarge. Results: Of 800 eligible patients, 782 had complete discharge information and were included in this analysis (mean [SD] age, 56.6 [12.7] years; 395 [50.5%] female). In the intent-to-treat analysis, the unadjusted 180-day readmission rate for treatment and control groups was 60.1% vs 61.7% (adjusted odds ratio, 0.95; 95% CI, 0.71-1.28; P = .73) and the mean (SD) number of 180-day readmissions was 1.45 (1.89) vs 1.48 (1.94) (adjusted incidence rate ratio, 0.99, 95% CI, 0.88-1.12; P = .86). Among the population with the highest participation probabilities, the mean (SD) 180-day readmission count was 1.22 (1.74) vs 1.57 (1.74) and the incidence rate ratio attained statistical significance (adjusted incidence rate ratio, 0.74; 95% CI, 0.56-0.99; P = .045). Adjusted odds ratios and adjusted incidence rate ratios for 30- and 90-day outcomes reached statistical significance after population distillation. Conclusions and Relevance: This secondary analysis of a randomized clinical trial found that care management was associated with reduced readmissions among patients with higher participation probabilities, suggesting that program operation could be improved by addressing barriers to participation and refining inclusion criteria to identify patients most likely to benefit. Trial Registration: ClinicalTrials.gov Identifier: NCT02090426.