Health risk and germ cell toxicity of five commercially available sachet waters in Nigeria: a public health concern.

Background: Sachet water is the most common form of portable water commercially available in Nigeria. Methodology: Using the murine sperm count and sperm abnormality assay, the germ cell toxicity of five common commercially available sachet waters in Nigeria was assessed in this study. The levels of hormones such as Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH) and Total Testosterone (TT); and activities of catalase (CAT), alanine aminotransferase (ALT), superoxide dismutase (SOD), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were evaluated. The heavy metal and physicochemical parameters of the sachet waters were also analyzed. Healthy male mice were allowed to freely drink the sachet waters for 35 days after which they were sacrificed. Results: The findings indicated that the concentrations of some heavy metals (As, Cr, and Cd) in the sachet waters exceeded the limit by regulatory organizations. The data of the total carcinogenic risk (TCR) and total non-carcinogenic risk (THQ) of some heavy metals associated with the ingestion of sachet water for adults and children showed that the values exceeded the acceptable threshold, and thus, is indicative of a high non-carcinogenic and carcinogenic risks. The data of the sperm abnormality assay showed that in the exposed mice, the five sachet waters induced a statistically significant (P < 0.05) increase in abnormal sperm cells and a significantly lower mean sperm count. Additionally noted were changes in the serum activities of TT, FSH, ALP, AST, ALT, and LH. Conclusion: Thus, the sachet waters studied contained agents that can induce reproductive toxicity in exposed humans. This is of public health importance and calls for immediate action by regulatory bodies.

Beyond Mastectomy: The Incidence of Subsequent Aesthetic Procedures after Mastectomy with and without Breast Reconstruction.

Background: Mastectomy poses significant challenges to a woman's body image and psychological well-being, and breast reconstruction plays a pivotal role in postoperative quality of life. Following breast reconstruction, many patients choose to have subsequent aesthetic procedures. Data on the prevalence of such subsequent aesthetic interventions are lacking in the literature. The aim of this study was to analyze trends in aesthetic procedures in patients following mastectomy with and without breast reconstruction. Methods: The PearlDiver database was queried within its capabilities for patients who underwent mastectomy with and without breast reconstruction, and a variety of aesthetic procedures after mastectomy. Aesthetic procedure rates were compared between cohorts. Results: We identified 365,525 mastectomy patients: 282,815 without reconstruction and 82,710 with reconstruction. In total, 609 patients with reconstruction and 329 without underwent subsequent aesthetic procedures. The rate of aesthetic procedures was higher in the reconstruction group (0.7%) compared with the nonreconstruction group (0.1%; P < 0.001). Conclusions: Patients who chose to have breast reconstruction after mastectomy underwent significantly more subsequent aesthetic procedures compared with those who chose mastectomy alone. Our findings provide insights on the prevalence of aesthetic procedures in postmastectomy patients, highlighting the potentially longitudinal nature of the reconstructive and aesthetic journey beyond the index oncologic procedure. Further research is needed to address motivations for such procedures as well as patient-reported outcomes and satisfaction.

Outcomes of Biodegradable Temporizing Matrix for Soft Tissue Reconstruction of the Hand and Extremities.

Background: NovoSorb biodegradable temporizing matrix (BTM) is a novel, bilayer, synthetic skin substitute made of biodegradable polyurethane foam covered with a sealing membrane. BTM has demonstrated excellent outcomes in burn literature; however, few studies have been published for hand and extremity soft tissue reconstruction. Methods: All patients who underwent extremity reconstruction with BTM from 2018 to 2023 were reviewed. Demographics, presentations, and clinical outcomes were recorded. Results: A total of 86 cases from 54 patients (53.7% pediatric; age range: 0-81 years) were included. Common indications included trauma (36%), infection (18.6%), and malignancy (11.6%). BTM was placed over exposed tendon (38.4%), bone (19%), joints (12.8%), nerves (8.1%), and/or blood vessels (7%). BTM served as temporary wound coverage in 26 cases. Complications included hematoma (8.1%), infection (4.7%), and spontaneous delamination (4.7%). Wound closure was successfully obtained without flap use in 93.3%. Poor BTM take was associated with peripheral vascular disease, hypertension, immunosuppression, and BTM hematoma and infection (<0.05). Conclusion: This study contributes to the growing body of evidence favoring BTM use in challenging reconstructive cases. Although prospective comparative studies are forthcoming, BTM likely has broad applications in reconstructive surgery.

The Impact of Medicaid Institutions for Mental Disease Exclusion Waivers on the Availability of Substance Abuse Treatment Services and the Varying Effect by Ownership Type.

Policy Points The adoption of Medicaid institutions for mental disease (IMD) exclusion waivers increases the likelihood of substance abuse treatment facilities offering mental health and substance abuse treatment for co-occurring disorders, especially in residential facilities. There are differential responses to IMD waivers based on facility ownership. For-profit substance abuse treatment facilities are responsive to the adoption of IMD substance use disorder waivers, whereas private not-for-profit and public entities are not. The response of for-profit facilities suggests that integration of substance abuse and mental health treatment for individuals in residential facilities may be cost-effective. CONTEXT: Access to integrated care for those with co-occurring mental health (MH) and substance use disorders (SUDs) has been limited because of an exclusion in Medicaid on paying for SUD care for those in institutions for mental disease (IMDs). Starting in 2015, the federal government encouraged states to pursue waivers of this exclusion, and by the end of 2020, 28 states had done so. It is unclear what impact these waivers have had on the availability of care for co-occurring disorders and the characteristics of any facilities that expanded care because of them. METHODS: Using data from the National Survey of Substance Abuse Treatment Services, we estimate a two-stage residual inclusion model including time- and state-fixed effects to examine the effect of state IMD SUD waivers on the percentage of facilities offering co-occurring MH and SUD treatment, overall and for residential facilities specifically. Separate analyses are conducted by facility ownership type. FINDINGS: Results show that the adoption of an IMD SUD waiver is associated with 1.068 greater odds of that state having facilities offering co-occurring MH and substance abuse (SA) treatment a year or more later. The adoption of a waiver increases the odds of a state's residential treatment facility offering co-occurring MH and SA treatment by 1.129 a year or more later. Additionally, the results suggest 1.163 higher odds of offering co-occurring MH/SA treatment in private for-profit SA facilities in states that adopt an IMD SUD waiver while suggesting no significant impact on offered services by private not-for-profit or public facilities. CONCLUSIONS: Our study findings suggest that Medicaid IMD waivers are at least somewhat effective at impacting the population targeted by the policy. Importantly, we find that there are differential responses to these IMD waivers based on facility ownership, providing new evidence for the literature on the role of ownership in the provision of health care.

Measuring the Direct Medical Costs of Hospital-Onset Infections Using an Analogy Costing Framework.

BACKGROUND: The majority of recent estimates on the direct medical cost attributable to hospital-onset infections (HOIs) has focused on device- or procedure-associated HOIs. The attributable costs of HOIs that are not associated with device use or procedures have not been extensively studied. OBJECTIVE: We developed simulation models of attributable cost for 16 HOIs and estimated the total direct medical cost, including nondevice-related HOIs in the USA for 2011 and 2015. DATA AND METHODS: We used total discharge costs associated with HOI-related hospitalization from the National Inpatient Sample and applied an analogy costing methodology to develop simulation models of the costs attributable to HOIs. The mean attributable cost estimate from the simulation analysis was then multiplied by previously published estimates of the number of HOIs for 2011 and 2015 to generate national estimates of direct medical costs. RESULTS: After adjusting all estimates to 2017 US dollars, attributable cost estimates for select nondevice-related infections attributable cost estimates ranged from $7661 for ear, eye, nose, throat, and mouth (EENTM) infections to $27,709 for cardiovascular system infections in 2011; and from $8394 for EENTM to $26,445 for central nervous system infections in 2016 (based on 2015 incidence data). The national direct medical costs for all HOIs were $14.6 billion in 2011 and $12.1 billion in 2016. Nondevice- and nonprocedure-associated HOIs comprise approximately 26-28% of total HOI costs. CONCLUSION: Results suggest that nondevice- and nonprocedure-related HOIs result in considerable costs to the healthcare system.

Prostate-Specific Membrane Antigen Use in Glioma Management: Past, Present, and Future.

BACKGROUND: Prostate-specific membrane antigen (PSMA) is a membrane-bound metallopeptidase highly expressed in the neovasculature of many solid tumors including gliomas. It is a particularly enticing therapeutic target due to its ability to internalize, thereby delivering radioligands or pharmaceuticals to the intracellular compartment. Targeting the neovasculature of gliomas using PSMA for diagnosis and management has been a recent area of increased study and promise. The purpose of this review is to synthesize the current state and future directions of PSMA use in the histopathologic study, imaging, and treatment of gliomas. METHODS: PubMed and Scopus databases were used to conduct a literature review on PSMA use in gliomas in June 2023. Terms searched included "PSMA," "Prostate-Specific Membrane Antigen" OR "PSMA" OR "PSMA PET" AND "glioma" OR "high grade glioma" OR "glioblastoma" OR "GBM." RESULTS: Ninety-four publications were screened for relevance with 61 studies, case reports, and reviews being read to provide comprehensive context for the historical, contemporary, and prospective use of PSMA in glioma management. CONCLUSIONS: PSMA PET imaging is currently a promising and accurate radiographic tool for the diagnosis and management of gliomas. PSMA histopathology likely represents a viable tool for helping predict glioma behavior. More studies are needed to investigate the role of PSMA-targeted therapeutics in glioma management, but preliminary reports have indicated its potential usefulness in treatment.

CT in musculoskeletal imaging: still helpful and for what?

Computed tomography (CT) is a common modality employed for musculoskeletal imaging. Conventional CT techniques are useful for the assessment of trauma in detection, characterization and surgical planning of complex fractures. CT arthrography can depict internal derangement lesions and impact medical decision making of orthopedic providers. In oncology, CT can have a role in the characterization of bone tumors and may elucidate soft tissue mineralization patterns. Several advances in CT technology have led to a variety of acquisition techniques with distinct clinical applications. These include four-dimensional CT, which allows examination of joints during motion; cone-beam CT, which allows examination during physiological weight-bearing conditions; dual-energy CT, which allows material decomposition useful in musculoskeletal deposition disorders (e.g., gout) and bone marrow edema detection; and photon-counting CT, which provides increased spatial resolution, decreased radiation, and material decomposition compared to standard multi-detector CT systems due to its ability to directly translate X-ray photon energies into electrical signals. Advanced acquisition techniques provide higher spatial resolution scans capable of enhanced bony microarchitecture and bone mineral density assessment. Together, these CT acquisition techniques will continue to play a substantial role in the practices of orthopedics, rheumatology, metabolic bone, oncology, and interventional radiology.

Patient-reported outcomes in HSCT for autoimmune diseases: Considerations on behalf of the EBMT ADWP, PAC, and Nurses Group.

Background: Over the last 3 decades, hematopoietic stem cell transplantation (HSCT) has been successfully used to treat severe and refractory autoimmune diseases (AIDs). A multidisciplinary appraisal of potential benefits and risks by disease and transplant specialists is essential to determine individual suitability for HSCT. Objective: Our aim was to observe that patient-reported outcomes (PROs) and health-related quality of life instruments can capture the unique patient perspective on disease burden and impact of treatment. Methods: Herein, we describe the basis and complexity of end points measuring patient-reported perceptions of efficacy and tolerability used in clinical practice and trials for patients with AIDs undergoing autologous HSCT. Results: PRO measures and patient-reported experience measures are key tools to evaluate the impact and extent of disease burden for patients affected by AIDs. For formal scientific assessment, it is essential that validated general instruments are used, whereas adaptations have resulted in disease-specific instruments that may help guide tailored interventions. An additional approach relates to qualitative evaluations, from carefully structured qualitative research to informal narratives, as patient stories. The patients' subjectively reported responses to HSCT may be influenced by their preprocedure expectations and investment in the HSCT journey. Conclusions: The complexity of AIDs advocates for individualized and multidisciplinary approach to positively affect the patient journey. PROs and health-related quality of life need to be collected using validated instruments in clinical practice and trials to enable robustness of data and to ensure the impact of the intervention is comprehensively assessed, addressing the main questions and needs of the involved stakeholders.

Benefits for children with suspected cancer from routine whole-genome sequencing.

Clinical whole-genome sequencing (WGS) has been shown to deliver potential benefits to children with cancer and to alter treatment in high-risk patient groups. It remains unknown whether offering WGS to every child with suspected cancer can change patient management. We collected WGS variant calls and clinical and diagnostic information from 281 children (282 tumors) across two English units (n = 152 from a hematology center, n = 130 from a solid tumor center) where WGS had become a routine test. Our key finding was that variants uniquely attributable to WGS changed the management in ~7% (20 out of 282) of cases while providing additional disease-relevant findings, beyond standard-of-care molecular tests, in 108 instances for 83 (29%) cases. Furthermore, WGS faithfully reproduced every standard-of-care molecular test (n = 738) and revealed several previously unknown genomic features of childhood tumors. We show that WGS can be delivered as part of routine clinical care to children with suspected cancer and can change clinical management by delivering unexpected genomic insights. Our experience portrays WGS as a clinically impactful assay for routine practice, providing opportunities for assay consolidation and for delivery of molecularly informed patient care.

An electrophysiological correlate of sleep in a shark.

Sleep is a prominent physiological state observed across the animal kingdom. Yet, for some animals, our ability to identify sleep can be masked by behaviors otherwise associated with being awake, such as for some sharks that must swim continuously to push oxygenated seawater over their gills to breathe. We know that sleep in buccal pumping sharks with clear rest/activity cycles, such as draughtsboard sharks (Cephaloscyllium isabellum, Bonnaterre, 1788), manifests as a behavioral shutdown, postural relaxation, reduced responsiveness, and a lowered metabolic rate. However, these features of sleep do not lend themselves well to animals that swim nonstop. In addition to video and accelerometry recordings, we tried to explore the electrophysiological correlates of sleep in draughtsboard sharks using electroencephalography (EEG), electromyography, and electrooculography, while monitoring brain temperature. The seven channels of EEG activity had a surprising level of (apparent) instability when animals were swimming, but also when sleeping. The amount of stable EEG signals was too low for replication within- and across individuals. Eye movements were not measurable, owing to instability of the reference electrode. Based on an established behavioral characterization of sleep in draughtsboard sharks, we offer the original finding that muscle tone was strongest during active wakefulness, lower in quietly awake sharks, and lowest in sleeping sharks. We also offer several critical suggestions on how to improve techniques for characterizing sleep electrophysiology in future studies on elasmobranchs, particularly for those that swim continuously. Ultimately, these approaches will provide important insights into the evolutionary confluence of behaviors typically associated with wakefulness and sleep.

Lipid Trolling to Optimize A3 Adenosine Receptor-Positive Allosteric Modulators (PAMs).

A3 adenosine receptor (A3AR) positive allosteric modulators (PAMs) (2,4-disubstituted-1H-imidazo[4,5-c]quinolin-4-amines) allosterically increase the Emax of A3AR agonists, but not potency, due to concurrent orthosteric antagonism. Following mutagenesis/homology modeling of the proposed lipid-exposed allosteric binding site on the cytosolic side, we functionalized the scaffold, including heteroatom substitutions and exocyclic phenylamine extensions, to increase allosteric binding. Strategically appended linear alkyl-alkynyl chains with terminal amino/guanidino groups improved allosteric effects at both human and mouse A3ARs. The chain length, functionality, and attachment position were varied to modulate A3AR PAM activity. For example, 26 (MRS8247, p-alkyne-linked 8 methylenes) and homologues increased agonist Cl-IB-MECA's Emax and potency ([35S]GTPγS binding). The putative mechanism involves a flexible, terminally cationic chain penetrating the lipid environment for stable electrostatic anchoring to cytosolic phospholipid head groups, suggesting "lipid trolling", supported by molecular dynamic simulation of the active-state model. Thus, we have improved A3AR PAM activity through rational design based on an extrahelical, lipidic binding site.

Controlled Study of Metabolic Syndrome Among Offspring of Parents With Bipolar Disorder.

Objectives: Bipolar disorder (BD) is highly heritable and associated with increased rates of metabolic syndrome (MetS). However, little is known about MetS in offspring of parents with BD. We therefore examined this topic in the Pittsburgh Bipolar Offspring Study cohort.Methods: Participants included 199 parents (n = 116 BD, diagnosed using DSM-IV; n = 83 non-BD) and 330 offspring (mean age 19.9 ± 5.3 years), including 198 high-risk offspring of parents with BD (n = 80 affected with a mood disorder) and 132 control offspring. We defined MetS and its components using International Diabetes Federation (IDF) guidelines (primary) and National Cholesterol Education Program (NCEP) guidelines (secondary). Multivariable analyses controlled for age and socioeconomic status in offspring. Sensitivity analyses controlled for psychotropic medications.Results: There was higher prevalence of MetS in parents with BD as compared to controls. NCEP-defined MetS was significantly more prevalent among affected high-risk offspring (16.3%) and controls (15.2%) vs unaffected high-risk offspring (6.0%; χ2 = 6.54, P = .04). There was greater mean number of MetS components (IDF: 1.7 ± 1.1; NCEP: 1.4 ± 1.0) among affected high-risk offspring vs unaffected high-risk offspring (IDF: 1.2 ± 1.0; NCEP: 1.0 ± 1.0) and controls (IDF: 1.3 ± 1.2; NCEP: 1.1 ± 1.1; IDF: H[2] = 10.26, P = .006; NCEP: H[2] = 9.18, P = .01). Most findings became nonsignificant in multivariable analyses. Some between-group results became nonsignificant after controlling for second-generation antipsychotics.Conclusions: This preliminary study found increased risk of MetS among affected high-risk offspring, which may be attributable to socioeconomic status. Prospective studies may determine timing of MetS onset in relation to mood disorder onset, and the role of socioeconomic status in moderating this association.

Race-specific FRAX models are evidence-based and support equitable care: a response to the ASBMR Task Force report on Clinical Algorithms for Fracture Risk.

Task Force on 'Clinical Algorithms for Fracture Risk' commissioned by the American Society for Bone and Mineral Research (ASBMR) Professional Practice Committee has recommended that FRAX® models in the US do not include adjustment for race and ethnicity. This position paper finds that an agnostic model would unfairly discriminate against the Black, Asian and Hispanic communities and recommends the retention of ethnic and race-specific FRAX models for the US, preferably with updated data on fracture and death hazards. In contrast, the use of intervention thresholds based on a fixed bone mineral density unfairly discriminates against the Black, Asian and Hispanic communities in the US. This position of the Working Group on Epidemiology and Quality of Life of the International Osteoporosis Foundation (IOF) is endorsed both by the IOF and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).

A cluster-randomized trial of client and provider directed financial interventions to align incentives with appropriate case management in private medicine retailers: Results of the TESTsmART trial in Lagos, Nigeria.

Malaria remains a major health priority in Nigeria. Among children with fever who seek care, less than a quarter gets tested for malaria, leading to inappropriate use of the recommended treatment for malaria; Artemisinin-based Combination Therapy (ACT). Here we test an innovative strategy to target ACT subsidies to clients seeking care in Nigeria's private retail health sector who have a confirmed malaria diagnosis. We supported point-of-care malaria testing (mRDTs) in 48 Private Medicine Retailers (PMRs) in the city of Lagos, Nigeria and randomized them to two study arms; a control arm offering subsidized mRDT testing for USD $0.66, and an intervention arm where, in addition to access to subsidized testing as in the control arm, clients who received a positive mRDT at the PMR were eligible for a free (fully subsidized) first-line ACT and PMRs received USD $0.2 for every mRDT performed. Our primary outcome was the proportion of ACTs dispensed to individuals with a positive diagnostic test. Secondary outcomes included proportion of clients who were tested at the PMR and adherence to diagnostic test results. Overall, 23% of clients chose to test at the PMR. Test results seemed to inform treatment decisions and resulted in enhanced targeting of ACTs to confirmed malaria cases with only 26% of test-negative clients purchasing an ACT compared to 58% of untested clients. However, the intervention did not offer further improvements, compared to the control arm, in testing rates or dispensing of ACTs to test-positive clients. We found that ACT subsidies were not passed on to clients testing positive in the intervention arm. We conclude that mRDTs could reduce ACT overconsumption in Nigeria's private retail health sector, but PMR-oriented incentive structures are difficult to implement and may need to be complemented with interventions targeting clients of PMRs to increase test uptake and adherence. Trials registration: Clinical Trials Registration Number: NCT04428307. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816435/ Correction: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9476591/.

Mobile App-Based Mindfulness Intervention for Addressing Psychological Distress Among Survivors of Hospitalization for COVID-19 Infection.

BACKGROUND: Psychological distress symptoms are present and persistent among many patients who survive a critical illness like COVID-19. RESEARCH QUESTION: Could a self-directed mobile app-delivered mindfulness intervention be feasibly and rapidly implemented within a clinical trials network to reduce distress symptoms? STUDY DESIGN AND METHODS: A randomized clinical trial was conducted between January 2021 and May 2022 at 29 US sites and included survivors of hospitalization due to COVID-19-related illness with elevated symptoms of depression at discharge. Participants were randomized to intervention or usual care control. The intervention consisted of four themed weeks of daily audio, video, and text content. All study procedures were virtual. The primary outcome was depression symptoms assessed with the Patient Health Questionnaire 9 at 3 months. Secondary outcomes included anxiety (Generalized Anxiety Disorder 7-item scale), quality of life (EQ-5D), and adherence. We used general linear models to estimate treatment arm differences in outcomes over time. RESULTS: Among 56 randomized participants (mean age ± SD, 51.0 ± 13.2 years; 38 female [67.9%]; 14 Black participants [25%]), 45 (intervention: n = 23 [79%]; control: n = 22 [81%]) were retained at 6 months. There was no difference in mean improvement between intervention and control participants at 3 months in Patient Health Questionnaire 9 (-0.5 vs 0.1), Generalized Anxiety Disorder 7-item scale (-0.3 vs 0.1), or EQ-5D (-0.03 vs 0.02) scores, respectively; 6-month results were similar. Only 15 participants (51.7%) initiated the intervention, whereas the mean number ± SD of the 56 prescribed intervention activities completed was 12.0 ± 15.2. Regulatory approvals delayed trial initiation by nearly a year. INTERPRETATION: Among survivors of COVID-19 hospitalization with elevated psychological distress symptoms, a self-directed mobile app-based mindfulness intervention had poor adherence. Future psychological distress interventions mobilized at broad scale should focus efforts on patient engagement and regulatory simplification to enhance success. TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT04581200; URL: www.clinicaltrials.gov.

The impact of exchanging the light and heavy chains on the structures of bovine ultralong antibodies.

The third complementary-determining regions of the heavy-chain (CDR3H) variable regions (VH) of some cattle antibodies are highly extended, consisting of 48 or more residues. These `ultralong' CDR3Hs form ß-ribbon stalks that protrude from the surface of the antibody with a disulfide cross-linked knob region at their apex that dominates antigen interactions over the other CDR loops. The structure of the Fab fragment of a naturally paired bovine ultralong antibody (D08), identified by single B-cell sequencing, has been determined to 1.6 Šresolution. By swapping the D08 native light chain with that of an unrelated antigen-unknown ultralong antibody, it is shown that interactions between the CDR3s of the variable domains potentially affect the fine positioning of the ultralong CDR3H; however, comparison with other crystallographic structures shows that crystalline packing is also a major contributor. It is concluded that, on balance, the exact positioning of ultralong CDR3H loops is most likely to be due to the constraints of crystal packing.

Using GPS-defined venue-based affiliation networks among Black sexually minoritized men and transgender women to identify locations for HIV prevention interventions.

PURPOSE: HIV biomedical intervention uptake is suboptimal among Black sexually minoritized men (SMM) and transgender women (TW). Venues where people meet and interact shape HIV-related risk and prevention behaviors. We aimed to construct GPS-defined venue-based affiliation networks and identify the unique set of venues that could maximize reach of HIV biomedical interventions among Black SMM and TW. METHODS: We used baseline survey and GPS data from 272 Black SMM and TW in the Neighborhoods and Networks (N2) Cohort Study in Chicago, Illinois (2018-2019). We mapped participants' GPS data to the nearest pre-identified SMM- and TW-friendly venue (n = 222) to construct affiliation networks. Network analyses were performed to identify influential venues that can yield high reach to intervention candidates. RESULTS: Participants were affiliated with 75.5 % of all pre-identified venues based on GPS data. Two influential venues were identified in the non-PrEP use network, which when combined, could reach 52.5 % of participants not taking PrEP. Participants that could be reached through these two influential venues reported more non-main sex partners than participants not affiliated with either venue (p = 0.049). CONCLUSION: We demonstrate a potential for GPS-defined venue-based affiliation networks to identify unique combinations of venues that could maximize the impact of HIV prevention interventions.

Glutamine metabolism improves left ventricular function but not macrophage-mediated inflammation following myocardial infarction.

Glutamine is a critical amino acid that serves as an energy source, building block, and signaling molecule for the heart tissue and the immune system. However, the role of glutamine metabolism in regulating cardiac remodeling following myocardial infarction (MI) is unknown. In this study, we show in adult male mice that glutamine metabolism is altered both in the remote (contractile) area and in infiltrating macrophages in the infarct area after permanent left anterior descending artery occlusion. We found that metabolites related to glutamine metabolism were differentially altered in macrophages at days 1, 3, and 7 after MI using untargeted metabolomics. Glutamine metabolism in live cells was increased after MI relative to no MI controls. Gene expression in the remote area of the heart indicated a loss of glutamine metabolism. Glutamine administration improved LV function at days 1, 3, and 7 after MI, which was associated with improved contractile and metabolic gene expression. Conversely, administration of BPTES, a pharmacological inhibitor of glutaminase-1, worsened LV function after MI. Neither glutamine nor BPTES administration impacted gene expression or bioenergetics of macrophages isolated from the infarct area. Our results indicate that glutamine metabolism plays a critical role in maintaining LV contractile function following MI, and that glutamine administration improves LV function. Glutamine metabolism may also play a role in regulating macrophage function, but macrophages are not responsive to exogenous pharmacological manipulation of glutamine metabolism.