Assessing the quality of antimicrobial prescribing in solid organ transplant recipients: a new frontier in antimicrobial stewardship.

Background: Post-transplant infections remain a leading cause of morbidity and mortality in solid organ transplant recipients (SOTRs) and local standardized antimicrobial treatment guidelines may contribute to improved clinical outcomes. Our study assessed the rate of therapeutic compliance with local standard guidelines in the treatment of common infections in SOTR, and their associated outcomes. Methods: Consecutive adult SOTRs admitted to the transplant floor from January-September 2020 and were treated for an infectious syndrome were followed until discharge or for 30 days following the date of diagnosis, whichever was shorter. Data was extracted from electronic medical records. Guideline compliance was characterized as either appropriate, effective but unnecessary, undertreatment, or inappropriate. Results: Nine hundred and thirty-six SOTR were admitted to the transplant ward, of which 328 patients (35%) received treatment for infectious syndromes. Guidelines were applicable to 252 patients, constituting 275 syndromes: 86 pneumonias; 82 urinary tract infections; 40 intra-abdominal infections; 38 bloodstream infections; and 29 C. difficile infections. 200/246 (81%) of infectious syndromes received appropriate or effective but unnecessary empiric treatment. In addition, appropriate tailoring of antimicrobials resulted in a significant difference in 30-day all-cause mortality (adjusted OR of 0.07, 95% CI 0.01-0.38; P = .002). Lastly, we found that guideline-compliant empiric therapy was found to prevent the development of multi-drug resistance in a time-dependent analysis (adjusted HR of 0.21, 95% CI 0.08-0.52; P = .001). Conclusion: Our data show that adherence to locally developed guidelines was associated with reduced mortality and resistant-organism development in our cohort of SOTR.

Sexual and reproductive health among forcibly displaced persons in urban environments in low and middle-income countries: scoping review findings.

BACKGROUND: Most forcibly displaced persons are hosted in low- and middle-income countries (LMIC). There is a growing urbanization of forcibly displaced persons, whereby most refugees and nearly half of internally displaced persons live in urban areas. This scoping review assesses the sexual and reproductive health (SRH) needs, outcomes, and priorities among forcibly displaced persons living in urban LMIC. METHODS: Following The Joanna Briggs Institute scoping review methodology we searched eight databases for literature published between 1998 and 2023 on SRH needs among urban refugees in LMIC. SHR was operationalized as any dimension of sexual health (comprehensive sexuality education [CSE]; sexual and gender based violence [GBV]; HIV and STI prevention and control; sexual function and psychosexual counseling) and/or reproductive health (antental, intrapartum, and postnatal care; contraception; fertility care; safe abortion care). Searches included peer-reviewed and grey literature studies across quantitative, qualitative, or mixed-methods designs. FINDINGS: The review included 92 studies spanning 100 countries: 55 peer-reviewed publications and 37 grey literature reports. Most peer-reviewed articles (n = 38) discussed sexual health domains including: GBV (n = 23); HIV/STI (n = 19); and CSE (n = 12). Over one-third (n = 20) discussed reproductive health, including: antenatal, intrapartum and postnatal care (n = 13); contraception (n = 13); fertility (n = 1); and safe abortion (n = 1). Eight included both reproductive and sexual health. Most grey literature (n = 29) examined GBV vulnerabilities. Themes across studies revealed social-ecological barriers to realizing optimal SRH and accessing SRH services, including factors spanning structural (e.g., livelihood loss), health institution (e.g., lack of health insurance), community (e.g., reduced social support), interpersonal (e.g., gender inequitable relationships), and intrapersonal (e.g., low literacy) levels. CONCLUSIONS: This review identified displacement processes, resource insecurities, and multiple forms of stigma as factors contributing to poor SRH outcomes, as well as producing SRH access barriers for forcibly displaced individuals in urban LMIC. Findings have implications for mobilizing innovative approaches such as self-care strategies for SRH (e.g., HIV self-testing) to address these gaps. Regions such as Africa, Latin America, and the Caribbean are underrepresented in research in this review. Our findings can guide SRH providers, policymakers, and researchers to develop programming to address the diverse SRH needs of urban forcibly displaced persons in LMIC. Most forcibly displaced individuals live in low- and middle-income countries (LMICs), with a significant number residing in urban areas. This scoping review examines the sexual and reproductive health (SRH) outcomes of forcibly displaced individuals in urban LMICs. We searched eight databases for relevant literature published between 1998 and 2023. Inclusion criteria encompassed peer-reviewed articles and grey literature. SRH was defined to include various dimensions of sexual health (comprehensive sexuality education; sexual and gender-based violence; HIV/ STI prevention; sexual function, and psychosexual counseling) and reproductive health (antenatal, intrapartum, and postnatal care; contraception; fertility care; and safe abortion care). We included 90 documents (53 peer-reviewed articles, 37 grey literature reports) spanning 100 countries. Most peer-reviewed articles addressed sexual health and approximately one-third centered reproductive health. The grey literature primarily explored sexual and gender-based violence vulnerabilities. Identified SRH barriers encompassed challenges across structural (livelihood loss), health institution (lack of insurance), community (reduced social support), interpersonal (gender inequities), and individual (low literacy) levels. Findings underscore gaps in addressing SRH needs among urban refugees in LMICs specifically regarding sexual function, fertility care, and safe abortion, as well as regional knowledge gaps regarding urban refugees in Africa, Latin America, and the Caribbean. Self-care strategies for SRH (e.g., HIV self-testing, long-acting self-injectable contraception, abortion self-management) hold significant promise to address SRH barriers experienced by urban refugees and warrant further exploration with this population. Urgent research efforts are necessary to bridge these knowledge gaps and develop tailored interventions aimed at supporting urban refugees in LMICs.

A Transfer Hydrogenation Approach to Activity-Based Sensing of Formate in Living Cells.

Formate is a major reactive carbon species in one-carbon metabolism, where it serves as an endogenous precursor for amino acid and nucleic acid biosynthesis and a cellular source of NAD(P)H. On the other hand, aberrant elevations in cellular formate are connected to progression of serious diseases, including cancer and Alzheimer's disease. Traditional methods for formate detection in biological environments often rely on sample destruction or extensive processing, resulting in a loss of spatiotemporal information. To help address these limitations, here we present the design, synthesis, and biological evaluation of a first-generation activity-based sensing system for live-cell formate imaging that relies on iridium-mediated transfer hydrogenation chemistry. Formate facilitates an aldehyde-to-alcohol conversion on various fluorophore scaffolds to enable fluorescence detection of this one-carbon unit, including through a two-color ratiometric response with internal calibration. The resulting two-component probe system can detect changes in formate levels in living cells with a high selectivity over potentially competing biological analytes. Moreover, this activity-based sensing system can visualize changes in endogenous formate fluxes through alterations of one-carbon pathways in cell-based models of human colon cancer, presaging the potential utility of this chemical approach to probe the continuum between one-carbon metabolism and signaling in cancer and other diseases.

Chronic Glucocorticoid Exposure Induced an S1PR2-RORγ Axis to Enhance Hepatic Gluconeogenesis in Male Mice.

It is well established that chronic glucocorticoid exposure causes hyperglycemia. While glucocorticoid receptor (GR) stimulates hepatic gluconeogenic gene transcription, additional mechanisms are activated by chronic glucocorticoid exposure to enhance gluconeogenesis. We found that chronic glucocorticoid treatment activated sphingosine-1-phosphate (S1P)-mediated signaling. Hepatic knockdown of hepatic S1P receptor 1 (S1PR1) had no effect on chronic glucocorticoid-induced glucose intolerance but elevated fasting plasma insulin levels. In contrast, hepatic S1PR3 knockdown exacerbated chronic glucocorticoid-induced glucose intolerance without affecting fasting plasma insulin levels. Finally, hepatic S1PR2 knockdown attenuated chronic glucocorticoid-induced glucose intolerance and reduced fasting plasma insulin levels. Here, we focused on dissecting the role of S1PR2 signaling in chronic glucocorticoid response on glucose homeostasis. We found that chronic glucocorticoid-induced hepatic gluconeogenesis, gluconeogenic gene expression, and GR recruitment to the glucocorticoid response elements (GREs) of gluconeogenic genes were all reduced in hepatic S1PR2 knockdown male mice. Hepatic S1PR2 knockdown also enhanced glucocorticoid suppression of RAR-related orphan receptor γ (RORγ) expression. Hepatic RORγ overexpression in hepatic S1PR2 knockdown mice restored glucocorticoid-induced glucose intolerance, gluconeogenic gene expression, and GR recruitment to their GREs. Conversely, RORγ antagonist and the reduction of hepatic RORγ expression attenuated such glucocorticoid effects. Thus, chronic glucocorticoid exposure induces an S1PR2-RORγ axis to cooperate with GR to enhance hepatic gluconeogenesis. Overall, this work provides novel mechanisms of and pharmaceutical targets against steroid-induced hyperglycemia.

The Role of Adaptation in Collective Human-AI Teaming.

This paper explores a framework for defining artificial intelligence (AI) that adapts to individuals within a group, and discusses the technical challenges for collaborative AI systems that must work with different human partners. Collaborative AI is not one-size-fits-all, and thus AI systems must tune their output based on each human partner's needs and abilities. For example, when communicating with a partner, an AI should consider how prepared their partner is to receive and correctly interpret the information they are receiving. Forgoing such individual considerations may adversely impact the partner's mental state and proficiency. On the other hand, successfully adapting to each person's (or team member's) behavior and abilities can yield performance benefits for the human-AI team. Under this framework, an AI teammate adapts to human partners by first learning components of the human's decision-making process and then updating its own behaviors to positively influence the ongoing collaboration. This paper explains the role of this AI adaptation formalism in dyadic human-AI interactions and examines its application through a case study in a simulated navigation domain.

Sexual and reproductive health outcomes for forcibly displaced persons living in urban environments in low- and middle-income countries: a scoping review protocol.

OBJECTIVE: The objective of this review is to characterize the state of literature regarding forcibly displaced persons' sexual and reproductive health in urban areas in low- and middle-income countries. Specific objectives include describing the sexual and reproductive health outcomes among forcibly displaced persons relocating in urban environments. INTRODUCTION: As a result of persecution, conflict, violence, human rights violations, and disruptive events, 89.3 million people worldwide were forcibly displaced as of the end of 2021. Forcibly displaced people face a wide range of sexual and reproductive health challenges in their countries of origin, en route to final destinations, and on arrival in host communities. There is a growing urbanization of forcibly displaced persons, yet there is limited attention on sexual and reproductive health outcomes of this population. INCLUSION CRITERIA: This review will consider studies that include sexual and/or reproductive health outcomes and needs of forcibly displaced persons within urban environments in low- and middle-income countries. Published and unpublished evidence, including quantitative, qualitative, mixed methods research, and gray literature, will be eligible for inclusion. METHODS: MEDLINE, Embase, PsycINFO, CINAHL, IBSS, ASSIA, SSCI, and Global Medicus Index will be searched for English-language articles. Titles and abstracts will be screened against the inclusion criteria, followed by full-text review of potentially eligible studies, which will be independently assessed by 2 reviewers. Eligible articles will be extracted and charted. Results from extracted data will be tabulated and accompanied by a narrative summary to summarize and contextualize the extracted data to describe how the results relate to the review's objectives and question.

Smoking, life expectancy, and chronic disease in South Korea, Singapore, and the United States: A microsimulation model.

The substantial social and economic burden attributable to smoking is well-known, with heavy smokers at higher risk of chronic disease and premature mortality than light smokers and nonsmokers. In aging societies with high rates of male smoking such as in East Asia, smoking is a leading preventable risk factor for extending lives (including work-lives) and healthy aging. However, little is known about whether smoking interventions targeted at heavy smokers relative to light smokers lead to disproportionately larger improvements in life expectancy and prevalence of chronic diseases and how the effects vary across populations. Using a microsimulation model, we examined the health effects of smoking reduction by simulating an elimination of smoking among subgroups of smokers in South Korea, Singapore, and the United States. We found that life expectancy would increase by 0.2 to 1.5 years among light smokers and 2.5 to 3.7 years among heavy smokers. Whereas both interventions led to an increased life expectancy and decreased the prevalence of chronic diseases in all three countries, the life-extension benefits were greatest for those who would otherwise have been heavy smokers. Our findings illustrate how smoking interventions may have significant economic and social benefits, especially for life extension, that vary across countries.

Completing the ß,γ-CXY-dNTP Stereochemical Probe Toolkit: Synthetic Access to the dCTP Diastereomers and 31P and 19F NMR Correlations with Absolute Configurations.

Nucleoside 5'-triphosphate (dNTP) analogues in which the ß,γ-oxygen is mimicked by a CXY group (ß,γ-CXY-dNTPs) have provided information about DNA polymerase catalysis and fidelity. Definition of CXY stereochemistry is important to elucidate precise binding modes. We previously reported the (R)- and (S)-ß,γ-CHX-dGTP diastereomers (X = F, Cl), prepared via P,C-dimorpholinamide CHCl (6a, 6b) and CHF (7a, 7b) bisphosphonates (BPs) equipped with an (R)-mandelic acid as a chiral auxiliary, with final deprotection using H2/Pd. This method also affords the ß,γ-CHCl-dTTP (11a, 11b), ß,γ-CHF (12a, 12b), and ß,γ-CHCl (13a, 13b) dATP diastereomers as documented here, but the reductive deprotection step is not compatible with dCTP or the bromo substituent in ß,γ-CHBr-dNTP analogues. To complete assembly of the toolkit, we describe an alternative synthetic strategy featuring ethylbenzylamine or phenylglycine-derived chiral BP synthons incorporating a photolabile protecting group. After acid-catalyzed removal of the (R)-(+)-α-ethylbenzylamine auxiliary, coupling with activated dCMP and photochemical deprotection, the individual diastereomers of ß,γ-CHBr- (33a, 33b), ß,γ-CHCl- (34a, 34b), ß,γ-CHF-dCTP (35a, 35b) were obtained. The ß,γ-CH(CH3)-dATPs (44a, 44b) were obtained using a methyl (R)-(-)-phenylglycinate auxiliary. 31P and 19F NMR Δδ values are correlated with CXY stereochemistry and pKa2-4 values for 13 CXY-bisphosphonic acids and imidodiphosphonic acid are tabulated.

Quality of Life in Pediatric Neurosurgery: Comparing Parent and Patient Perceptions.

BACKGROUND: In the pediatric neurosurgical population, understanding how to mitigate the effects of disease on children's physical ability, social and psychological well-being, and education can have lasting effects on their development and family. Understanding parents' perceptions of their children's health-related quality of life (HRQoL) is crucial in proper counseling, management of expectations, establishment of a healthy patient/parent-physician relationship, and understanding the role and impact of health care. In this study we sought to examine the differences between patient and parent perceptions of HRQoL and the factors that influence these differences. METHODS: A standardized survey (PedsQL Inventory) to assess physical, psychological, and social function and school performance was administered to both parents and patients in a general pediatric neurosurgery outpatient clinic from 2015-2018. RESULTS: 197 encounters with 179 patients occurred in the study period. There were 105 male and 92 female patients across various ethnic backgrounds. The most common diagnoses were tumor (23.4%) and vascular malformation (16.2%). Parent overall scores were lower than their children's (72.5 vs. 76.4, P < 0.01). Parent scores of physical function (74.3 vs. 78.7, P < 0.01) and overall psychosocial function (71.5 vs. 75.3, P < 0.01) were also lower. Parent scores in all domains of the PedsQL were correlated with overall score difference (P < 0.01), but only child scores of overall psychosocial (P < 0.03) and school function (P < 0.04) were correlated with overall score difference. CONCLUSIONS: Parents have more negative assessments of their children's HRQoL compared with their children in all domains assessed by the PedsQL. Further research is needed to identify factors that contribute to these discrepancies.

Hepatitis C Virus Infection in the Dallas County Jail: Implications for Screening, Prevention, and Linkage to Care.

OBJECTIVES: Screening for hepatitis C virus (HCV) infection in jail provides an opportunity to educate and offer care to a high-risk population. We aimed to (1) estimate the prevalence of HCV infection in jail; (2) describe the demographic characteristics, risk factors, and pre-incarceration health insurance status associated with HCV infection; and (3) examine the implementation of HCV screening in jail. METHODS: We conducted a retrospective analysis of an opt-out HCV screening program with HCV RNA confirmation and patient education at the Dallas County Jail from April 1 through November 2, 2017. We extracted data on test results, demographic characteristics, and release destination from electronic medical records. A nurse navigator recorded data on patient self-reported risk factors and pre-incarceration health insurance status. RESULTS: Of 4089 incarcerated persons screened, 708 (17.3%) had a positive HCV antibody result. Of these, 641 (90.5%) had an HCV RNA test ordered; 576 (89.9%) had RNA tests completed, of whom 413 (71.7%) had a positive HCV RNA result. Of these 413, 352 (85.2%) received patient education. Half of HCV RNA-positive incarcerated persons (n = 207, 50.1%) were born outside the birth cohort (1945-1965). Among those with HCV infection, commonly reported risk factors were injection drug use (168 of 352; 47.8%) and tattoos (82 of 352; 23.4%). Most incarcerated persons with HCV infection (284 of 350; 81.1%) did not have health insurance. HCV antibody prevalence was higher among incarcerated persons released to prison (232 of 961; 24.1%) than to outside agencies (38 of 403; 9.4%) or the community (178 of 1026; 17.4%). CONCLUSIONS: Screening for HCV with RNA confirmation in jail provides an opportunity for disease education, transmission prevention, and navigation to HCV treatment. Future efforts should examine post-incarceration linkage to care.

Comparing demographic and health characteristics of new and existing SNAP recipients: application of a machine learning algorithm.

BACKGROUND: The Supplemental Nutrition Assistance Program (SNAP) expanded significantly after the Great Recession of 2008-2009, but no studies have characterized this new group of recipients. Few data sets provide details on whether an individual is a new or established recipient of SNAP. OBJECTIVE: We sought to identify new and existing SNAP recipients, and to examine differences in sociodemographic characteristics, health, nutritional status, and food purchasing behavior between new and existing recipients of SNAP after the recession. METHODS: We created a probabilistic algorithm to identify new and existing SNAP recipients using the 1999-2013 waves of the Panel Study of Income Dynamics. We applied this algorithm to the National Household Food Acquisition and Purchase Survey (FoodAPS), fielded during 2012-2013, to predict which individuals were likely to be new SNAP recipients. We then compared health and nutrition characteristics between new, existing, and never recipients of SNAP in FoodAPS. RESULTS: New adult SNAP recipients had higher socioeconomic status, better self-reported health, and greater food security relative to existing recipients, and were more likely to smoke relative to never recipients. New child SNAP recipients were less likely to eat all meals and had lower BMI relative to existing recipients. New SNAP households exhibited differences in food access and expenditures, although dietary quality was similar to that of existing SNAP households. CONCLUSION: We developed a novel algorithm for predicting new and existing SNAP recipiency that can be applied to other data sets, and subsequently demonstrated differences in health characteristics between new and existing recipients. The expansion of SNAP since the Great Recession enrolled a population that differed from the existing SNAP population and that may benefit from different types of nutritional and health services than those traditionally offered.

Direct regulation of blood pressure by smooth muscle cell mineralocorticoid receptors.

Hypertension is a cardiovascular risk factor present in over two-thirds of people over age 60 in North America; elevated blood pressure correlates with increased risk of heart attack, stroke and progression to heart and kidney failure. Current therapies are insufficient to control blood pressure in almost half of these patients. The mineralocorticoid receptor (MR), acting in the kidney, is known to regulate blood pressure through aldosterone binding and stimulation of sodium retention. However, recent studies support the concept that the MR also has extrarenal actions and that defects in sodium handling alone do not fully explain the development of hypertension and associated cardiovascular mortality. We and others have identified functional MR in human vascular smooth muscle cells (SMCs), suggesting that vascular MR might directly regulate blood pressure. Here we show that mice with SMC-specific deficiency of the MR have decreased blood pressure as they age without defects in renal sodium handling or vascular structure. Aged mice lacking MR in SMCs (SMC-MR) have reduced vascular myogenic tone, agonist-dependent contraction and expression and activity of L-type calcium channels. Moreover, SMC-MR contributes to angiotensin II­induced vascular oxidative stress, vascular contraction and hypertension. This study identifies a new role for vascular MR in blood pressure control and in vascular aging and supports the emerging hypothesis that vascular tone contributes directly to systemic blood pressure.