Translational genetics identifies a phosphorylation switch in CARD9 required for innate inflammatory responses.

Population genetics continues to identify genetic variants associated with diseases of the immune system and offers a unique opportunity to discover mechanisms of immune regulation. Multiple genetic variants linked to severe fungal infections and autoimmunity are associated with caspase recruitment domain-containing protein 9 (CARD9). We leverage the CARD9 R101C missense variant to uncover a biochemical mechanism of CARD9 activation essential for antifungal responses. We demonstrate that R101C disrupts a critical signaling switch whereby phosphorylation of S104 releases CARD9 from an autoinhibited state to promote inflammatory responses in myeloid cells. Furthermore, we show that CARD9 R101C exerts dynamic effects on the skin cellular contexture during fungal infection, corrupting inflammatory signaling and cell-cell communication circuits. Card9 R101C mice fail to control dermatophyte infection in the skin, resulting in high fungal burden, yet show minimal signs of inflammation. Together, we demonstrate how translational genetics reveals molecular and cellular mechanisms of innate immune regulation.

Candida albicans extracellular vesicles trigger type I IFN signalling via cGAS and STING.

The host type I interferon (IFN) pathway is a major signature of inflammation induced by the human fungal pathogen, Candida albicans. However, the molecular mechanism for activating this pathway in the host defence against C. albicans remains unknown. Here we reveal that mice lacking cyclic GMP-AMP synthase (cGAS)-stimulator of IFN genes (STING) pathway components had improved survival following an intravenous challenge by C. albicans. Biofilm-associated C. albicans DNA packaged in extracellular vesicles triggers the cGAS-STING pathway as determined by induction of interferon-stimulated genes, IFNß production, and phosphorylation of IFN regulatory factor 3 and TANK-binding kinase 1. Extracellular vesicle-induced activation of type I IFNs was independent of the Dectin-1/Card9 pathway and did not require toll-like receptor 9. Single nucleotide polymorphisms in cGAS and STING potently altered inflammatory cytokine production in human monocytes challenged by C. albicans. These studies provide insights into the early innate immune response induced by a clinically significant fungal pathogen.

Corneal Changes and Strategies to Improve Survival of Hypomorphic Collagen VII-Deficient Mice for the Study of Ocular Dystrophic Epidermolysis Bullosa.

Ophthalmic study of collagen CVII hypomorphic mice is uniquely challenging due to the strain's published survival rate to weaning of 24%. Because chronic ocular fibrosis requires time to develop, optimizing the survival rate is of critical importance. In this study, standard husbandry practices were enhanced by the addition of sterilized diet and drug delivery gels, acidified water, irradiated food pellets, cellulose fiber bedding, minimal handling, removal of siblings within 2-3 wk from birth, and a preferred housing location. Survival rates per breeding cycle, sex, weight, and cause of early euthanasia were recorded and analyzed over 43 mo. Overall, 49% of mice survived to weaning and 76% of weaned mice survived to 20 wk of age. Corneal opacities were seen in 65% of mice by 20 wk, but only 10% of eyes showed the sustained opacification that was indicative of fibrosis. Corneal opacities occurred at the same rate as in humans with epidermolysis bullosa. 66% of the mice showed weight loss at 11 wk. Males required early euthanasia 4 times more often than did females. Euthanasia was required for urinary obstruction due to penile prolapse in 88% of males. With our enhanced care protocol, hypomorphic mice in our colony survived at twice the published rate. With this revised husbandry standard, experiments planned with termination endpoints of 14 wk for males and 17 wk for females are more likely to reach completion.

Low acceptance of intimate partner violence by pregnant women in Uganda predicts higher uptake of HIV self-testing among their male partners.

Introduction: Heterosexual couples are at high risk for HIV acquisition in sub-Saharan Africa, and HIV self-testing (HST) is an additional approach to expand access to HIV testing services. However, it is not well known how gender equality is associated with HST.Methods: We used intervention-arm data from a cluster-randomised controlled HST intervention trial (N = 1 618) conducted in Uganda to determine the association between attitudes towards intimate partner violence (IPV), decision-making power and male partner's uptake of HST among heterosexual couples expecting a child in south-central Uganda. The original study question was to assess the impact of providing pregnant women with HST kits to improve male partner's HIV testing rates. For this analysis, the primary exposures were gender equality (measured by male partner's and female partner's attitudes towards IPV and the female partner's household decision-making power), and the primary outcome was the male partner's uptake of HST. Multivariate logistic regression was used for analysis.Results: We found that male partner HST uptake did not vary depending on male partner's attitudes towards IPV or decision-making power; however, male partner HST uptake did depend on the female partner's attitude towards IPV, with 1.76 times more testing (95% CI 1.06-2.92) in couples where the woman had "medium" versus "high" acceptance of IPV, and 1.82 times more testing (95% CI 1.08-3.08) in couples where the woman had "low" versus "high" acceptance of IPV.Conclusions: This study shows the importance of appropriate negative attitudes by women to IPV in increasing male partner's HST uptake to integrate HST into national health care policies.

Cutaneous leiomyosarcoma with visceral metastases in a White Carneau pigeon and literature review.

Cutaneous leiomyosarcomas are malignant mesenchymal tumors of smooth muscle origin and are reported occasionally in avian species. A 14-y-old male laboratory White Carneau pigeon (Columba livia) was presented for surgical excision of a cervical soft tissue mass. Ultrasonography with color flow Doppler imaging revealed multiple cavitations of mixed echogenicity within the mass and vascularization. Histologically, the dermis and subcutis were expanded by a densely cellular multinodular mass comprised of fusiform cells forming haphazardly arranged broad streams and short interwoven bundles, often surrounding blood vessels and variably sized cavitations. Neoplastic cells were strongly immunopositive for desmin and α-smooth muscle actin, and negative for pancytokeratin, S100, and von Willebrand factor. Based on histopathology and IHC findings, the cutaneous mass was diagnosed as leiomyosarcoma (LMS). The pigeon died 312 d post-operatively. Postmortem examination revealed masses infiltrating the left and right pulmonary airways and one hepatic nodule, but no regrowth at the surgical site. Histologic and IHC evaluation of the pulmonary and hepatic masses were consistent with LMS, representing metastatic foci from the primary cutaneous LMS. Our case highlights the malignant behavior and histomorphologic features of cutaneous LMS in an avian species.

Socio-demographic predictors of gender inequality among heterosexual couples expecting a child in south-central Uganda.

BACKGROUND: Gender inequality is a pervasive problem in sub-Saharan Africa, and has negative effects on health and development. OBJECTIVE: Here, we sought to identify socioeconomic predictors of gender inequality (measured by low decision-making power and high acceptance of intimate partner violence) within heterosexual couples expecting a child in south-central Uganda. METHOD: We used data from a two-arm cluster randomized controlled HIV self-testing intervention trial conducted in three antenatal clinics in south-central Uganda among 1,618 enrolled women and 1,198 male partners. Analysis included Cochran Mantel-Haenzel, proportional odds models, logistic regression, and generalized linear mixed model framework to account for site-level clustering. RESULTS: Overall, we found that 31.1% of men had high acceptance of IPV, and 15.9% of women had low decision-making power. We found religion, education, HIV status, age, and marital status to significantly predict gender equality. Specifically, we observed lower gender equality among Catholics, those with lower education, those who were married, HIV positive women, and older women. CONCLUSION: By better understanding the prevalence and predictors of gender inequality, this knowledge will allow us to better target interventions (increasing education, reducing HIV prevalence in women, targeting interventions different religions and married couples) to decrease inequalities and improve health care delivery to underserved populations in Uganda.

Delivery and implementation of an algorithm for smoking cessation treatment for people living with HIV and AIDS.

Compared to the general population, persons living with HIV (PLWH) have higher rates of tobacco use and an increased risk of morbidity from tobacco-related diseases. We conducted a single-arm pilot study of the real-world feasibility of integrating a smoking cessation decisional algorithm within routine clinic visits to engage non-treatment-seeking smokers in smoking cessation therapies. Smokers had an initial study visit during routine care followed by phone contacts at one and three months. Participants completed a baseline survey, followed by the algorithm which resulted in a recommendation for a smoking cessation medication, which was prescribed during the visit. Follow-up phone surveys assessed changes in smoking behavior and use of cessation medications at 1 and 3 months. Participants' (N = 60) self-reported smoking decreased from a baseline average of 14.4 cigarettes/day to 7.1 cigarettes/day at 3 months (p = .001). Nicotine dependence (FTND) decreased from 5.6 at baseline to 3.6 at 3 months (p < .001). Twenty-seven (45%) made a 24-h quit attempt and 39 (65%) used cessation medication. Insurance prior-authorization delayed medication receipt for seven participants and insurance denial occurred for one. Motivational status did not significantly influence outcomes. The algorithm was successful in engaging participants to use cessation medications and change smoking behaviors.

Intermittent Occlusion of the Superior Vena Cava Reduces Cardiac Filling Pressures in Preclinical Models of Heart Failure.

Congestion is a major determinant of clinical outcomes in heart failure (HF). We compared the acute hemodynamic effects of occlusion of the superior (SVC) versus the inferior vena cava (IVC) and tested a novel SVC occlusion system in swine models of HF. IVC occlusion acutely reduced left ventricular (LV) systolic and diastolic pressures, LV volumes, cardiac output (CO), and mean arterial pressure (MAP). SVC occlusion reduced LV diastolic pressure and volumes without affecting CO or MAP. The preCARDIA system is a balloon occlusion catheter and pump console which enables controlled delivery and removal of fluid into the occlusion balloon. At 6, 12, and 18 h, SVC therapy with the system provided a sustained reduction in cardiac filling pressures with stable CO and MAP. Intermittent SVC occlusion is a novel approach to reduce biventricular filling pressures in HF. The VENUS-HF trial will test the safety and feasibility of SVC therapy in HF.

"That Can't Be!": Perceptions of HIV and Hepatitis C Screening during Admission to an Acute Care Surgery Service.

BACKGROUND: A large number of patients live with undiagnosed HIV and/or hepatitis C despite broadened national screening guidelines. European studies, however, suggest many patients falsely believe they have been screened during a prior hospitalization. This study aims to define current perceptions among trauma and emergency general surgery (EGS) patients regarding HIV and hepatitis C screening practices. METHODS: Prospective survey administered to adult (>18 years old) acute care surgery service (trauma and EGS) patients at a Level 1 academic trauma center. The survey consisted of 13 multiple choice questions: demographics, whether admission tests included HIV and hepatitis C at index and prior hospital visits and whether receiving no result indicated a negative result, prior primary care screening. Response percentages calculated in standard fashion. RESULTS: One hundred and twenty-five patients were surveyed: 80 trauma and 45 EGS patients. Overall, 32% and 29.6% of patients believed they were screened for HIV and hepatitis C at admission. There was no significant difference in beliefs between trauma and EGS. Sixty-eight percent of patients had a hospital visit within 10 years of these, 49.3% and 44.1% believe they had been screened for HIV and hepatitis C. More EGS patients believed they had a prior screen for both conditions. Among patients who believed they had a prior screen and did not receive any results, 75.9% (HIV) and 80.8% (hepatitis C) believed a lack of results meant they were negative. Only 28.9% and 23.6% of patients had ever been offered outpatient HIV and hepatitis C screening. CONCLUSIONS: A large portion of patients believe they received admission or prior hospitalization HIV and/or hepatitis C screening and the majority interpreted a lack of results as a negative diagnosis. Due to these factors, routine screening of trauma/EGS patients should be considered to conform to patient expectations and national guidelines, increase diagnosis and referral for medical management, and decrease disease transmission.

Relationship Gender Equality and Couples' Uptake of Oral Human Immunodeficiency Virus Self-Testing Kits Delivered by Pregnant Women in Kenya.

BACKGROUND: Higher gender equality is associated with many human immunodeficiency virus (HIV) preventive behaviors, including HIV testing. HIV self-testing is a relatively new testing technology that could assist with HIV prevention. However, there are no studies examining gender equality and HIV self-testing. We examined the associations between gender equality and couples' uptake of HIV self-testing among heterosexual couples expecting a child in central Kenya. METHODS: This analysis used data from a HIV self-testing randomized intervention trial among pregnant women attending antenatal care and their male partners. The primary exposures were gender equality (measured by the male partner's attitudes toward intimate partner violence, and the woman's report on her household decision making power), and the primary outcome was couples' uptake of HIV self-testing. Generalized linear mixed models framework was used to account for site-level clustering. RESULTS: In comparison to male partners reporting high acceptance of intimate partner violence, couples with male partners reporting medium acceptance (odds ratio, 2.36; 95% confidence interval, 0.99-5.63) or low acceptance (odds ratio, 2.50; 95% confidence interval, 1.20-5.21) were significantly more likely to use HIV self-testing. Gender equality measured by decision making power was not associated with couples' uptake of HIV self-testing. CONCLUSIONS: This study is the first of its kind to examine the association between gender equality and couples' HIV self-testing. This holds important implications for HIV self-testing as we strive to achieve the United Nations Programme on HIV/acquired immune deficiency syndrome goal that 90% of individuals living with HIV should know their status.

Social and Demographic Predictors of Gender Inequality Among Heterosexual Couples Expecting a Child in Central Kenya.

Imbalance of power and equality in sexual relationships is linked to health in various ways, including (1) reduced ability to get information or take action, (2) increased violence between partners, and (3) influence on the reduced use of health services. While there has been research assessing multiple social and economic variables related to gender inequality, studies have used many different definitions of gender inequality, and there is a lack of this research within a pregnancy context. Here, we attempt to identify social and economic predictors of gender inequality (measured by decision-making power and acceptance of intimate partner violence) within heterosexual couples expecting a child in central Kenya. We ran a secondary data analysis using data from a three-arm individually randomized controlled HIV self-testing intervention trial conducted in 14 antenatal clinics in central and eastern Kenya among 1410 women and their male partners. The analysis included Cochran Mantel-Haenszel, logistic regression, proportional odds models, and generalized linear mixed model (GLMM) framework to account for site-level clustering. Overall, we show that there are significant social and economic variables associated with acceptance of intimate partner violence including higher age, being married, "other" religion, lower partner education, higher wealth status, and variables associated with decision-making power including lower partner education and lack of equality in earnings. This study contributes to the literature on the influence of social and economic factors on gender inequality, especially in Kenya which has a high burden of HIV/AIDS. Our results show some areas to improve these specific factors (including education and employment opportunities) or create interventions for targeted populations to potentially improve gender equality in heterosexual pregnant couples in Kenya.

A different form of injury prevention: Successful screening and referral for human immunodeficiency virus and hepatitis C virus in a trauma population.

BACKGROUND: In the United States, millions of patients are living with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) (0.44% and 1.5%) and many are currently undiagnosed. Because highly effective treatments are now available, early identification of these patients is extremely important to achieve improved clinical outcomes. Prior data and trauma-associated risk factors suggest a higher prevalence of both diseases in the trauma population. We hypothesized that a screening program could be successfully initiated among trauma activation patients and that a referral and linkage-to-care program could be developed. METHODS: Hepatitis C virus and HIV screening tests were added to standard trauma activation laboratory orders at an academic Level I Trauma Center. Confirmatory viral load was sent when indicated. Patients with positive results were educated about their disease and referred to disease-specific follow-up. Data were collected prospectively from January 1, 2016, until June 30, 2017. Total and new diagnosis, referral rates, and linkage-to-care rates were analyzed. RESULTS: One thousand eight hundred ninety-eight patients arrived as trauma activations. One thousand two hundred seventeen (64.1%) patients were screened (Level A, 75.6%; Level B, 60.2%). Seven percent of the screened patients were initially positive, and 5.5% were confirmed positive. Rates of both HIV (1.1%) and HCV (4.4%) were almost triple the national average. Overall, 3.3% screened positive for a new diagnosis. For HCV, the rate of new diagnosis was twice the national average (3%). Over 85% of all cases were referred for follow-up, and the combined linkage-to-care rate was 43.3%. CONCLUSION: The majority of patients were screened and referred for follow-up, indicating successful implementation of our trauma screening program. Routine screening of trauma patients should be considered to increase diagnosis rate, increase linkage-to-care rates, and decrease disease transmission. These screening efforts would help bridge the health care gap that exists in the trauma population due to lower insurance rates and limited access to primary care. LEVEL OF EVIDENCE: Therapeutic/Care management, level III.

A multidisciplinary international collaborative implementing low cost, high fidelity 3D printed airway models to enhance Ethiopian anesthesia resident emergency cricothyroidotomy skills.

BACKGROUND: Similar to other sub-Saharan countries, Ethiopia suffers from a severe shortage of adequately trained health professionals. Academic partnerships can support sustainable training programs and build capacity for low-resource settings. 3D modeling and simulation-based training provide necessary tools, especially for rarely-encountered clinical situations, such as needle cricothyroidotomy. METHODS: Departments of Anesthesiology, Otolaryngology, and Learning Health Sciences collaborated to develop a low-cost, high-fidelity simulator and Cricothryoidotomy Skills Maintenance Program (CSMP). Twelve anesthesia residents at St. Paul's Hospital Medical Millennium College in Addis Ababa, Ethiopia participated in CSMP. The program consisted of a didactic session with presentation and demonstration and an immersive CICO scenario. Program evaluation was performed using pre/post-training knowledge and 2 procedural performance assessments-the CSMP Global Rating Scale and the Checklist. With consent, performances were videotaped and rated independently by 3 University of Michigan faculty. RESULTS: Improvements were identified in all areas, including residents' knowledge, measured by mean summed test scores (Mpre = 3.31,Mpost = 4.46,p = 0.003), time to perform cricothyroidotomy (Mpre = 96.64,Mpost = 72.82,p = 0.12), residents' performance quality, measured by overall mean Global ratings, (Mpre = 0.20; Mpost = 0.70) with improvements identified at the item-level, p = 0.001 with moderate-large effect sizes, and residents' ability to complete tasks, measured by mean Checklist ratings (Mpre = 0.51,Mpost = 0.90, with item-level improvements observed, p ≤ 0.01, with small-large effect sizes. Residents' self-reported confidence also improved (Mpre = 1.69, Mpost = 3.08,p = 0.001). CONCLUSION: Our work shows that cricothyroidotomy skills taught to anesthesia residents at SPHMMC with a 3D printed laryngotracheal model improves knowledge, skills, and confidence. The creation of a low-cost, high-fidelity simulator and a CSMP has the potential to impact patient care and safety world-wide.

Association of Substance Use With Hospitalization and Virologic Suppression in a Southern Academic HIV Clinic.

BACKGROUND: Persons with HIV infection who do not achieve virologic suppression contribute significantly to the ongoing HIV epidemic and have an increased risk of clinical sequelae related to immunosuppression. The extent to which substance use and mental health diagnoses affect HIV outcomes and the care continuum has not been previously assessed at the Medical University of South Carolina (MUSC), a large academic HIV clinic. METHODS: To address this knowledge gap and identify targets for intervention, we performed a retrospective chart review to examine associations of substance use and mental health diagnoses with hospitalization and virologic suppression. RESULTS: Patients with substance use or mental health diagnoses had increased rates of hospitalization and lower rates of sustained longitudinal HIV suppression. Prevalence of distinct substance-related disorders differed by race and sex. Although cocaine, alcohol and cannabis use were common, documented opiate use disorder was surprisingly infrequent given the ongoing opioid epidemic in South Carolina. CONCLUSIONS: These data suggest effective assessment and treatment of substance use disorders will help improve the HIV care continuum in South Carolina.

Use of an Outreach Coordinator to Reengage and Retain Patients at Risk of Falling Out of HIV Care, Does the Amount of Time Matter?

Retention in care remains a major problem for people living with HIV and it is well known that retention in high quality HIV care improves clinical outcomes. This project used an outreach coordinator to perform phone and letter interventions to improve retention in patients at risk of falling out of care. Sixty-one (5%) patients were at risk in 2015 and received an intervention by the outreach coordinator. Fifty (82%) had a visit and 22 (36%) met the HRSA definition of retention. The mean time per patient was 59 min; therefore, it took 2.7 h to achieve each retained patient or 1.2 h for each patient with a visit. By calculation, minutes over 75 appeared to be the point of diminishing returns. Cost analysis resulted in a cost of less than $100 per patient.

Isolation and molecular characterization of group B Streptococcus from laboratory Long-Evans rats (Rattus norvegicus) with and without invasive group B streptococcal disease.

Purpose. Group B Streptococcus (S. agalactiae, GBS) is a Gram-positive opportunistic pathogen that inhabits the respiratory, urogenital and gastrointestinal tracts of humans and animals. Maternal colonization of GBS is a risk factor for a spectrum of clinical diseases in humans and a principle cause of neonatal meningitis and septicaemia.Methodology. We describe polymicrobial sepsis including GBS in two gravid adult female Long-Evans rats experiencing acute mortality from a colony of long-term breeding pairs. Fluorescent in situ hybridization confirmed GBS association with pathological changes in affected tissues, including the heart and uterus.Results. Characterization of seven GBS strains obtained from clinically affected and non-affected animals indicated similar antibiotic resistance and susceptibility patterns to that of human strains of GBS. The rat strains have virulence factors known to contribute to pathogenicity, and shared serotypes with human invasive isolates. Phylogenetic analyses revealed that one rat-derived GBS strain was more closely related to human-derived strains than other rat-derived strains, strengthening the notion that interspecies transmission is possible.Conclusions. To our knowledge, this is the first investigation of genotypic and phenotypic features of rat-derived GBS strains and their comparison to human- and other animal-derived GBS strains. Since GBS commonly colonizes commercially available rats, its exclusion as a potential pathogen for immunocompromised or stressed animals is recommended.

Calpain-1 regulates platelet function in a humanized mouse model of sickle cell disease.

One of the major contributors to sickle cell disease (SCD) pathobiology is the hemolysis of sickle red blood cells (RBCs), which release free hemoglobin and platelet agonists including adenosine 5'-diphosphate (ADP) into the plasma. While platelet activation/aggregation may promote tissue ischemia and pulmonary hypertension in SCD, modulation of sickle platelet dysfunction remains poorly understood. Calpain-1, a ubiquitous calcium-activated cysteine protease expressed in hematopoietic cells, mediates aggregation of platelets in healthy mice. We generated calpain-1 knockout Townes sickle (SSCKO) mice to investigate the role of calpain-1 in steady state and hypoxia/reoxygenation (H/R)-induced sickle platelet activation and aggregation, clot retraction, and pulmonary arterial hypertension. Using multi-electrode aggregometry, which measures platelet adhesion and aggregation in whole blood, we determined that steady state SSCKO mice exhibit significantly impaired PAR4-TRAP-stimulated platelet aggregation as compared to Townes sickle (SS) and humanized control (AA) mice. Interestingly, the H/R injury induced platelet hyperactivity in SS and SSCKO, but not AA mice, and partially rescued the aggregation defect in SSCKO mice. The PAR4-TRAP-stimulated GPIIb-IIIa (αIIbß3) integrin activation was normal in SSCKO platelets suggesting that an alternate mechanism mediates the impaired platelet aggregation in steady state SSCKO mice. Taken together, we provide the first evidence that calpain-1 regulates platelet hyperactivity in sickle mice, and may offer a viable pharmacological target to reduce platelet hyperactivity in SCD.

Early HIV Diagnosis Leads to Significantly Decreased Costs in the First 2 Years of HIV Care in an Urban Charity Hospital in New Orleans.

We undertook a retrospective cohort study of patients with a positive HIV test in the emergency department who were then linked to care. Inpatient, outpatient, and emergency costs were collected for the first 2 years after HIV diagnosis. Fifty-six patients met the inclusion criteria; they were predominantly uninsured (73%) and African American (89%). The median total cost for a newly diagnosed patient over the first 2 years was US$36 808, driven predominantly by outpatient costs of US$17 512. Median inpatient and total costs were significantly different between the lowest (<200 cells/mm3) and highest (>499 cells/mm3) CD4 count categories (US$21 878 vs US$6607, P <.05; US$61 378 vs US$18 837, P <.05, respectively). Total costs were significantly different between viral load categories <100 000 HIV-RNA copies/mL and ≥100 000 HIV-RNA copies/mL (US$28 219 vs US$49 482, P <.05). Costs were significantly lower among patients diagnosed earlier in their disease. Decreased cost is another factor supporting early diagnosis and linkage to care for patients with HIV.

Use of an Outreach Coordinator to Reengage and Retain Patients with HIV in Care.

It is well established that retention in high-quality care and regular visits with an HIV/AIDS provider improve outcomes for people living with HIV/AIDS (PLWHA). However, nationally and regionally in South Carolina, retention rates remain low. We piloted an outreach program focused on characterizing out of care (OOC) patients to identify PLWHA who were lost to care and attempt reengagement through phone call, letter, and home visit interventions. Primary outcomes were reengagement, defined as attendance to a clinic appointment, and retention in care, defined by the Health Resources and Services Administration (HRSA) definition (two visits at least 90 days apart in 2015). There were 1242 adult clinic patients in 2014. A total of 233 patients were included in the OOC cohort, according to the inclusion criteria. Of these 233, the outreach coordinator found that a majority of patients, 119 (51%), were lost to care. Reengagement was seen in 52 (44%) patients lost to care, and among those who reengaged, 26 (50%) were retained in care in 2015. This report represents one of few interventions that target reengagement for patients who are lost to care. The use of an outreach coordinator was successful in reengaging and retaining patients in care. It represents an uncomplicated intervention, functional within the current clinic design and available funding structure of the Ryan White grant. Poor engagement and retention in care continue to be significant problems among PLWHA with resultant poor clinical outcomes. Continued focus on new interventions to improve retention in care is necessary to improve clinical outcomes.

Autophagy in Dendritic Cells and B Cells Is Critical for the Inflammatory State of TLR7-Mediated Autoimmunity.

Individuals suffering from autoimmune disorders possess a hyperactive cellular phenotype where tolerance to self-antigens is lost. Autophagy has been implicated in both the induction and prevention of autoimmunity, and modulators of this cellular recycling process hold high potential for the treatment of autoimmune diseases. In this study, we determine the effects of a loss of autophagy in dendritic cells (DCs), as well as both B cells and DCs, in a TLR7-mediated model of autoimmunity, similar to systemic lupus erythematosus, where both cell types are critical for disease. Although a loss of DC autophagy slowed disease, the combined loss of autophagy in both cell types resulted in a lethal sepsis-like environment, which included tissue inflammation and hyperproduction of inflammasome-associated cytokines. Ablation of B cell signaling reversed this phenotype, indicating that activation of these cells is an essential step in disease induction. Thus, autophagy plays a dichotomous role in this model of disease.