Tetracistronic minigenomes elucidate a functional promoter for Ghana virus and unveils Cedar virus replicase promiscuity for all henipaviruses.

Batborne henipaviruses, such as Nipah and Hendra viruses, represent a major threat to global health due to their propensity for spillover, severe pathogenicity, and high mortality rate in human hosts. Coupled with the absence of approved vaccines or therapeutics, work with the prototypical species and uncharacterized, emergent species is restricted to high biocontainment facilities. There is a scarcity of such specialized spaces for research, and often, the scope and capacity of research, which can be conducted at BSL-4, is limited. Therefore, there is a pressing need for innovative life-cycle modeling systems to enable comprehensive research within lower biocontainment settings. This work showcases tetracistronic, transcription, and replication-competent minigenomes for the Nipah, Hendra, and Cedar viruses, which encode viral proteins facilitating budding, fusion, and receptor binding. We validate the functionality of all encoded viral proteins and demonstrate a variety of applications to interrogate the viral life cycle. Notably, we found that the Cedar virus replicase exhibits remarkable promiscuity, efficiently driving replication and transcription of minigenomes from all tested henipaviruses. We also apply this technology to Ghana virus (GhV), an emergent species that has so far not been isolated in culture. We demonstrate that the reported sequence of GhV is incomplete, but that this missing sequence can be substituted with analogous sequences from other henipaviruses. The use of our GhV system establishes the functionality of the GhV replicase and identifies two antivirals that are highly efficacious against the GhV polymerase. IMPORTANCE: Henipaviruses are recognized as significant global health threats due to their high mortality rates and lack of effective vaccines or therapeutics. Due to the requirement for high biocontainment facilities, the scope of research which may be conducted on henipaviruses is limited. To address this challenge, we developed innovative tetracistronic, transcription, and replication-competent minigenomes. We demonstrate that these systems replicate key aspects of the viral life cycle, such as budding, fusion, and receptor binding, and are safe for use in lower biocontainment settings. Importantly, the application of this system to the Ghana virus revealed that its known sequence is incomplete; however, substituting the missing sequences with those from other henipaviruses allowed us to overcome this challenge. We demonstrate that the Ghana virus replicative machinery is functional and can identify two orally efficacious antivirals effective against it. Our research offers a versatile system for life-cycle modeling of highly pathogenic henipaviruses at low biocontainment.

Weighing the Options: Which PrEP (Pre-exposure Prophylaxis) Modality Attributes Influence Choice for Young Gay and Bisexual Men in the United States?

Pre-exposure prophylaxis (PrEP) is effective in preventing HIV transmission, but uptake and adherence among young men who have sex with men (YMSM) remains suboptimal. New PrEP formulations may enhance PrEP use, but little is known about their acceptability. We enrolled 39 cis- and transgender YMSM (age 18-34) from Boston, MA; Jackson, MS; Birmingham, AL; and New Orleans, LA, who participated in video-based focus groups (n = 30) or in-depth interviews (n = 9) to examine how new PrEP products (e.g., injections, monthly pills, implants) are perceived and might be improved for YMSM. Focus groups were transcribed, coded, and analyzed using grounded theory and content analysis. Nearly half (46%) of participants were Black; 11% identified as Hispanic. Seventy-nine percent were PrEP experienced. Product preference was driven by the desire for flexible, safe, effective, and affordable PrEP options. A majority of participants preferred subcutaneous injections every 6 months or monthly pills dispersed in 3 or 4 doses. Subcutaneous injections and batched monthly pills were favored by those with demanding schedules and those who desired fewer provider visits; monthly pills were more appealing for those who feared needles. Despite broad preferences for longer-acting products for convenience, participants raised concerns regarding side effects and waning protection after missed doses. Participants felt that more education about safety and efficacy profiles of new products could influence their attitudes. These findings suggest that it is important to prioritize YMSM's dynamic lifestyles during product development, and that product safety and efficacy information should be accessible in youth-friendly language.

Nipah Virus Bangladesh Infection Elicits Organ-Specific Innate and Inflammatory Responses in the Marmoset Model.

The common marmoset (Callithrix jacchus) is increasingly recognized as an ideal nonhuman primate (NHP) at high biocontainment due to its smaller size and relative ease of handling. Here, we evaluated the susceptibility and pathogenesis of Nipah virus Bangladesh strain (NiVB) infection in marmosets at biosafety level 4. Infection via the intranasal and intratracheal route resulted in fatal disease in all 4 infected marmosets. Three developed pulmonary edema and hemorrhage as well as multifocal hemorrhagic lymphadenopathy, while 1 recapitulated neurologic clinical manifestations and cardiomyopathy on gross pathology. Organ-specific innate and inflammatory responses were characterized by RNA sequencing in 6 different tissues from infected and control marmosets. Notably, a unique transcriptome was revealed in the brainstem of the marmoset exhibiting neurological signs. Our results provide a more comprehensive understanding of NiV pathogenesis in an accessible and novel NHP model, closely reflecting clinical disease as observed in NiV patients.

Patterns of Pre-exposure Prophylaxis (PrEP) Use in a Population Accessing PrEP in Jackson, Mississippi.

Pre-exposure prophylaxis (PrEP) persistence is suboptimal in the United States. In the Deep South, a region with high rates of new HIV diagnosis, patterns of PrEP discontinuation remain unexplored. We evaluated data from a clinic-based PrEP program in Jackson, Mississippi and included patients initiating PrEP between August 2018 and April 2021. We considered patients to have a gap in PrEP coverage if they had at least 30 days without an active PrEP prescription; those who restarted PrEP after 30 days were classified as 'stopped and restarted' and those who never obtained a new PrEP prescription were classified as 'stopped and did not restart'. Patients without a gap in coverage were considered 'continuously on PrEP'. We estimated median time to first PrEP discontinuation and examined factors associated with time to first PrEP discontinuation. Of 171 patients who received an initial 90-day PrEP prescription; 75% were assigned male at birth and 74% identified as Black. The median time to first discontinuation was 90 days (95% CI 90-114). Twenty-two percent were continuously on PrEP, 28% stopped and restarted (median time off PrEP = 102 days), and 50% stopped and did not restart. Associations with early PrEP stoppage were notable for patients assigned sex female vs male (adjusted hazard ratio [aHR] = 1.6, 95% CI 1.0-2.5) and those living over 25 miles from clinic vs. 0-10 miles (aHR 1.89, 95% CI 1.2-3.0). Most patients never refilled an initial PrEP prescription though many patients re-started PrEP. Interventions to improve persistence and facilitate re-starts are needed.

VAMP8 Contributes to the TRIM6-Mediated Type I Interferon Antiviral Response during West Nile Virus Infection.

Several members of the tripartite motif (TRIM) family of E3 ubiquitin ligases regulate immune pathways, including the antiviral type I interferon (IFN-I) system. Previously, we demonstrated that TRIM6 is involved in IFN-I induction and signaling. In the absence of TRIM6, optimal IFN-I signaling is reduced, allowing increased replication of interferon-sensitive viruses. Despite having evolved numerous mechanisms to restrict the vertebrate host's IFN-I response, West Nile virus (WNV) replication is sensitive to pretreatment with IFN-I. However, the regulators and products of the IFN-I pathway that are important in regulating WNV replication are incompletely defined. Consistent with WNV's sensitivity to IFN-I, we found that in TRIM6 knockout (TRIM6-KO) A549 cells, WNV replication is significantly increased and IFN-I induction and signaling are impaired compared to wild-type (wt) cells. IFN-ß pretreatment was more effective in protecting against subsequent WNV infection in wt cells than TRIM6-KO, indicating that TRIM6 contributes to the establishment of an IFN-induced antiviral response against WNV. Using next-generation sequencing, we identified VAMP8 as a potential factor involved in this TRIM6-mediated antiviral response. VAMP8 knockdown resulted in reduced JAK1 and STAT1 phosphorylation and impaired induction of several interferon-stimulated genes (ISGs) following WNV infection or IFN-ß treatment. Furthermore, VAMP8-mediated STAT1 phosphorylation required the presence of TRIM6. Therefore, the VAMP8 protein is a novel regulator of IFN-I signaling, and its expression and function are dependent on TRIM6 activity. Overall, these results provide evidence that TRIM6 contributes to the antiviral response against WNV and identify VAMP8 as a novel regulator of the IFN-I system.IMPORTANCE WNV is a mosquito-borne flavivirus that poses a threat to human health across large discontinuous areas throughout the world. Infection with WNV results in febrile illness, which can progress to severe neurological disease. Currently, there are no approved treatment options to control WNV infection. Understanding the cellular immune responses that regulate viral replication is important in diversifying the resources available to control WNV. Here, we show that the elimination of TRIM6 in human cells results in an increase in WNV replication and alters the expression and function of other components of the IFN-I pathway through VAMP8. Dissecting the interactions between WNV and host defenses both informs basic molecular virology and promotes the development of host- and virus-targeted antiviral strategies.

Barriers, Facilitators, and Cost of Integrating HIV-Related Activities Into Sexually Transmitted Disease Partner Services in Jackson, Mississippi.

BACKGROUND: Many US health departments now integrate HIV-related outcomes (e.g., relinkage to HIV care and preexposure prophylaxis [PrEP]) into sexually transmitted disease (STD) partner services (PS) programs. We sought to determine the barriers, facilitators, and cost of integrating these activities into PS. METHODS: From 2016 to 2018, the Mississippi State Department of Health integrated 3 new activities into STD PS: HIV testing for partners of HIV-negative men who have sex with men with gonorrhea/chlamydia, relinkage to HIV care for STD PS recipients previously diagnosed with HIV, and PrEP referrals. We conducted direct observations and interviews with disease intervention specialists (DIS) in Jackson to assess barriers and facilitators to implementing these activities. We completed time and motion studies with 8 DIS and case tracking forms for 90 unique cases to estimate the incremental staff time and associated personnel cost of added services compared with a standard PS case. RESULTS: Disease intervention specialists were optimistic about integrating HIV-related activities but noted disparate data systems, nonsystematic documentation, and lack of training as barriers. The mean time for a standard STD PS case without HIV-related activities was 195 minutes (cost, $77.69/case). The cost to conduct PS for HIV-negative men who have sex with men with gonorrhea/chlamydia was 36% higher than a standard case. Integrating relinkage to care and PrEP referrals resulted in a 44% and 20% increase in cost, respectively. CONCLUSIONS: Integrating HIV care relinkage and PrEP referrals into STD partner services was generally acceptable by DIS and added marginal cost per case. Coupling these cost metrics with an assessment of the effectiveness of these activities can inform prioritization of partner services activities.

Syphilis and HIV Co-infection in Mississippi: Implications for Control and Prevention.

Syphilis and HIV are important public health issues in the United States, especially in the southeastern region. This study aimed to determine and describe the co-infection pattern in Mississippi by using a case-controlled design to analyze cases diagnosed with syphilis or HIV from 2007 to 2016. Direct matching was employed to identify cases that were co-infected during the same calendar year, and binary logistic regression analysis was used to determine predictors of co-infection. Results showed that 1736 (34.0%) of syphilis and HIV cases were co-infected during the same calendar year. Binary logistic regression results demonstrated that race, gender, age group, and exposure category were independently associated with co-infection status. These analyses highlighted the progressive increase of co-infection rates in Mississippi. Collaboration between STI/HIV surveillance teams may identify high-risk individuals and reduce transmission of both diseases.

Integrating Human Immunodeficiency Virus Testing Into Syphilis Partner Services in Mississippi to Improve Human Immunodeficiency Virus Case Finding.

BACKGROUND: Mississippi has the 10th highest rate of new human immunodeficiency virus (HIV) infections in the United States. The Mississippi State Department of Health (MSDH) integrated partner HIV testing into syphilis partner services (PS) in 2014, but the effectiveness of this as an HIV case finding strategy has not been evaluated. METHODS: We identified all early syphilis (primary, secondary, and early latent) case records reported from July 1, 2014, to December 31, 2016, excluding case records for people concurrently newly diagnosed with HIV. Among sex partners of these people, we identified new diagnoses of early syphilis and HIV. We calculated the number needed to interview as the number of syphilis index case patients interviewed divided by the number of partners newly diagnosed with early syphilis or HIV. RESULTS: A total of 1535 (95%) of the 1619 early syphilis index case patients were interviewed for PS. These case patients named 2267 partners, of whom 1868 (82%) were contacted by MSDH. Among partners, 1508 (81%) tested for syphilis and 745 (56%) of 1321 partners not previously diagnosed with HIV were tested for HIV. Partner services identified 696 new early syphilis case patients (46%) and 24 (3.2%) new HIV case patients among partners. Sixty-four index case patient interviews were needed to identify 1 new case of HIV, and 2 interviews were needed to identify 1 new case of syphilis among partners. CONCLUSIONS: Syphilis PS allowed MSDH to interact with 1592 men who have sex with men over a 30-month period and was effective for identifying people newly infected with early syphilis and HIV. Increasing HIV testing among partners of syphilis case patients could increase HIV case finding in Mississippi.

Human neural stem cell-derived neuron/astrocyte co-cultures respond to La Crosse virus infection with proinflammatory cytokines and chemokines.

BACKGROUND: La Crosse virus (LACV) causes pediatric encephalitis in the USA. LACV induces severe inflammation in the central nervous system, but the recruitment of inflammatory cells is poorly understood. A deeper understanding of LACV-induced neural pathology is needed in order to develop treatment options. However, there is a severe limitation of relevant human neuronal cell models of LACV infection. METHODS: We utilized human neural stem cell (hNSC)-derived neuron/astrocyte co-cultures to study LACV infection in disease-relevant primary cells. hNSCs were differentiated into neurons and astrocytes and infected with LACV. To characterize susceptibility and responses to infection, we measured viral titers and levels of viral RNA, performed immunofluorescence analysis to determine the cell types infected, performed apoptosis and cytotoxicity assays, and evaluated cellular responses to infection using qRT-PCR and Bioplex assays. RESULTS: hNSC-derived neuron/astrocyte co-cultures were susceptible to LACV infection and displayed apoptotic responses as reported in previous in vitro and in vivo studies. Neurons and astrocytes are both targets of LACV infection, with neurons becoming the predominant target later in infection possibly due to astrocytic responses to IFN. Additionally, neuron/astrocyte co-cultures responded to LACV infection with strong proinflammatory cytokine, chemokine, as well as MMP-2, MMP-7, and TIMP-1 responses. CONCLUSIONS: hNSC-derived neuron/astrocyte co-cultures reproduce key aspects of LACV infection in humans and mice and are useful models to study encephalitic viruses. Specifically, we show astrocytes to be susceptible to LACV infection and that neurons and astrocytes are important drivers of the inflammatory responses seen in LACV infection through the production of proinflammatory cytokines and chemokines.

African American Clergy Perspectives About the HIV Care Continuum: Results From a Qualitative Study in Jackson, Mississippi.

Mississippi has some of the most pronounced racial disparities in HIV infection in the country; African Americans comprised 37% of the Mississippi population but represented 80% of new HIV cases in 2015. Improving outcomes along the HIV care continuum, including linking and retaining more individuals and enhancing adherence to medication, may reduce the disparities faced by African Americans in Mississippi. Little is understood about clergy's views about the HIV care continuum. We assessed knowledge of African American pastors and ministers in Jackson, Mississippi about HIV and the HIV care continuum. We also assessed their willingness to promote HIV screening and biomedical prevention technologies as well as efforts to enhance linkage and retention in care with their congregations. Four focus groups were conducted with 19 African American clergy. Clergy noted pervasive stigma associated with HIV and believed they had a moral imperative to promote HIV awareness and testing; they provided recommendations on how to normalize conversations related to HIV testing and treatment. Overall, clergy were willing to promote and help assist with linking and retaining HIV positive individuals in care but knew little about how HIV treatment can enhance prevention or new biomedical technologies such as pre-exposure prophylaxis (PrEP). Clergy underscored the importance of building coalitions to promote a collective local response to the epidemic. The results of this study highlight important public health opportunities to engage African American clergy in the HIV care continuum in order to reduce racial disparities in HIV infection.

Emerging Regional and Racial Disparities in the Lifetime Risk of Human Immunodeficiency Virus Infection Among Men who Have Sex With Men: A Comparative Life Table Analysis in King County, WA and Mississippi.

BACKGROUND: Little is known about the lifetime risk of human immunodeficiency virus (HIV) diagnosis among US men who have sex with men (MSM), trends in risk and how risk varies between populations. METHODS: We used census and HIV surveillance data to construct life tables to estimate the cumulative risk of HIV diagnosis among cohorts of MSM born 1940 to 1994 in King County, Washington (KC) and Mississippi (MS). RESULTS: The cumulative risk of HIV diagnosis progressed in 3 phases. In phase 1, risk increased among MSM in successive cohorts born 1940 to 1964. Among men born 1955 to 1965 (the peak risk cohort), by age 55 years, 45% of white KC MSM, 65% of black KC MSM, 22% of white MS MSM, and 51% of black MS MSM had been diagnosed with HIV. In phase 2, men born 1965 to 1984, risk of diagnosis among KC MSM declined almost 60% relative to the peak risk cohort. A similar pattern of decline occurred in white MS MSM, with a somewhat smaller decline observed in black MS MSM. In phase 3, men born 1985 to 1994, the pattern of risk diverged. Among white KC MSM, black KC MSM, and white MS MSM, HIV risk increased slightly compared with men born 1975 to 1984, with 6%, 14%, and 2% diagnosed by age 27 years, respectively. Among black MS MSM born 1985 to 1994, HIV risk rose dramatically, with 35% HIV diagnosed by age 27 years. CONCLUSIONS: The lifetime risk of HIV diagnosis has substantially declined among MSM in KC and among white MSM in MS, but is rising dramatically among black MSM in MS.

Late Diagnoses of HIV Infection in Mississippi: Implications for Improved Testing Strategies and Treatment.

INTRODUCTION: According to the Centers for Disease Control and Prevention, more than 1.1 million people in the United States are living, with HIV infection, and approximately 1 in 6 (18%) are unaware of their infection. People living with undiagnosed HIV are more likely to progress to AIDS, transmit the virus to others, and have poorer overall health outcomes. In 2013, Mississippi had the 6th highest estimated AIDS diagnoses rate among adults and adolescents in the United States and when comparing persons living with AIDS, the Jackson, MS metropolitan area had the tenth highest rate among all MSAs. OBJECTIVE: The objective of this study is to describe people who are diagnosed with HIV late in their course of illness and to identify characteristics associated with late diagnoses. METHODS: Demographic data was obtained for all Mississippi residents who were diagnosed with HIV infection between Janary 1, 2004 and December 31,2014. Late diagnoses of HIV infection is defined as an AIDS diagnosis made within 12 months from an initial HIV diagnosis. Prevalence trends, demographics, and predictors of late diagnoses were measured. Results: Among 4,864 cases of -IV disease, 35% (1,682) were late diagnoses. Late diagnoses were more likely to occur among males, individuals over the age of 34, and individuals who were diagnosed outside of Mississippi State Department of Health clinics. CONCLUSION: A large proportion of individuals had late diagnoses of HIV infection and this proportion has slightly declined in recent years. Routine testing in medical settings and in areas with high morbidity may increase early HIV diagnosis.

State of the ART: Characteristics of HIV infected patients receiving care in Mississippi (MS), USA from the Medical Monitoring Project, 2009-2010.

BACKGROUND: Mississippi, the poorest state in the US, has a very high prevalence of HIV and among the highest HIV infection rates and AIDS-adjusted mortality rates in the country. African Americans, who suffer the worst health care disparities in the US, account for 76% of people with HIV in MS. The purpose of this study is to describe those in care for HIV and determine the factors associated with anti-retroviral treatment (ART) and viral suppression. METHODS: The CDC's Medical Monitoring Project collects surveillance data from 23 project areas in the US, including Mississippi, using annual probability sampling of persons in care for HIV. Data were collected from in-person interviews and medical record abstraction in 2009. The surveillance period was the 12 months prior to the interview date. RESULTS: 212 randomly selected participants represented a nationally representative weighted sample of 3190.4. Participants had a mean of 3.71 provider visits during the surveillance period. Geometric mean for CD4 count = 438.91 (95% CI 402.25-475.56). Overall 80.80% (95% CI 75.30%- 86.29%) were on ART, and 68.12% (95% CI 62.69%-73-56%) had undetectable viral load. Males (65.15%) were less likely to achieve undetectable viral load compared to females (78.30%) after controlling for individuals who were on ART (p = 0.01). Viral suppression was not associated with age, race or sexual risk factors. CONCLUSIONS: Although Mississippi has a high proportion of individuals out of HIV care, the majority in care is on ART and has suppressed viral loads. However, men are less likely to achieve virological suppression than females.

Assessing the Impact of Social Determinants of Health on HIV Care Engagement in the Southern United States: A Cross-Sectional Study.

Recent studies have shown social determinants of health (SDOH) to impact HIV care engagement. This cross-sectional study (Oct 20-Apr 21) assessed the impact of a range of SDOH on HIV care engagement using data from HIV Care Connect, a consortium of three HIV care facility-led programs (Alabama, Florida, Mississippi). The exposures were captured using the PRAPARE (Protocol for Responding to and Assessing Patient Assets, Risks, and Experiences) scale. The outcome was captured using the Index of Engagement in HIV Care scale. Participants (n = 132) were predominantly non-White (87%) and male (52%) with a median age of 41 years. Multivariable logistic regression adjusted for various sociodemographics showed lower HIV care engagement to be associated with being uninsured/publicly insured, having 1-3 unmet needs, socially integrating ≤five times/week, and having stable housing. Factors such as unmet needs, un-/underinsurance, and social integration may be addressed by healthcare and community organizations.

Assessing How Social Drivers of Health Affect Engagement in HIV Care in the Southern United StatesIt has been found that social factors that have a direct impact on health affect engagement in HIV Care among people living with HIV. We included various social drivers of health to see how they affect engagement in HIV Care. We used data between October 2020 and April 2021 from a project titled HIV Care Connect, which is a group of three facilities providing HIV care in Alabama, Florida, and Mississippi. We used social drivers of health as risk factors from a scale called PRAPARE (Protocol for Responding to and Assessing Patient Assets, Risks, and Experiences). Engagement in HIV care was measured by using a scale called Index of Engagement in HIV Care. A total of 132 participants were included. Majority of the participants were of races other than white (87%), male (52%) and were aged 41 years on average. Statistical analysis showed that participants without insurance or with public insurance, participants with 1-3 unsatisfied needs, participants that met with other people less than or equal to five times a week, and participants that had reliable housing had lower engagement in HIV care. These factors have a potential to be addressed by healthcare and community organizations.

Tetracistronic Minigenomes Elucidate a Functional Promoter for Ghana Virus and Unveils Cedar Virus Replicase Promiscuity for all Henipaviruses.

Batborne henipaviruses, such as Nipah virus and Hendra virus, represent a major threat to global health due to their propensity for spillover, severe pathogenicity, and high mortality rate in human hosts. Coupled with the absence of approved vaccines or therapeutics, work with the prototypical species and uncharacterized, emergent species is restricted to high biocontainment facilities. There is a scarcity of such specialized spaces for research, and often the scope and capacity of research which can be conducted at BSL-4 is limited. Therefore, there is a pressing need for innovative life-cycle modeling systems to enable comprehensive research within lower biocontainment settings. This work showcases tetracistronic, transcription and replication competent minigenomes for Nipah virus, Hendra virus, Cedar virus, and Ghana virus, which encode viral proteins facilitating budding, fusion, and receptor binding. We validate the functionality of all encoded viral proteins and demonstrate a variety of applications to interrogate the viral life cycle. Notably, we found that the Cedar virus replicase exhibits remarkable promiscuity, efficiently rescuing minigenomes from all tested henipaviruses. We also apply this technology to GhV, an emergent species which has so far not been isolated in culture. We demonstrate that the reported sequence of GhV is incomplete, but that this missing sequence can be substituted with analogous sequences from other henipaviruses. Use of our GhV system establishes the functionality of the GhV replicase and identifies two antivirals which are highly efficacious against the GhV polymerase.

In Vivo Imaging of Nipah Virus Infection in Small Animal Rodent Models.

In vivo imaging system (IVIS) is a powerful tool for the study of infectious diseases, providing the ability to non-invasively follow viral infection in an individual animal over time. Recombinant henipaviruses expressing bioluminescent or fluorescent reporter proteins can be used both to monitor the spatial and temporal progression of Nipah virus (NiV) infection in vivo as well as in ex vivo tissues. Virally produced luciferases react with systemically administered substrate to produce bioluminescence that can then be detected via IVIS imaging, while fluorescent reporters inherently generate detectable fluorescence without a substrate. Here we describe protocols applying bioluminescent or fluorescent reporter expressing recombinant viruses to in vivo or ex vivo imaging of NiV infection.

HIV Incidence Among Individuals Accessing Pre-Exposure Prophylaxis in Jackson, Mississippi.

Although pre-exposure prophylaxis (PrEP) is an efficacious biomedical intervention, the effectiveness of same-day PrEP programs has not been widely studied. We utilized data from three of the four largest PrEP providers in Mississippi from September 2018 to September 2021 linked to the Mississippi State Department of Health's Enhanced HIV/AIDS reporting system. HIV diagnosis was defined as testing newly positive for HIV at least 2 weeks after the initial PrEP visit. We calculated the cumulative incidence and incidence rate of HIV per 100 person-years (PY). Person-time was calculated as time from the initial PrEP visit to (1) HIV diagnosis or (2) December 31, 2021 (HIV surveillance data end date). We did not censor individuals if they discontinued PrEP to obtain an estimate of PrEP effectiveness rather than efficacy. Among the 427 clients initiating PrEP during the study period, 2.3% [95% confidence interval (CI): 0.9-3.8] subsequently tested positive for HIV. The HIV incidence rate was 1.18 per 100 PY (95% CI: 0.64-2.19) and median time to HIV diagnosis after the initial PrEP visit was 321 days (95% CI: 62-686). HIV incidence rates were highest among transgender and nonbinary individuals [10.35 per 100 PY (95% CI: 2.59-41.40)] compared with cisgender men and women, and among people racialized as Black [1.45 per 100 PY (95% CI: 0.76-2.80)] compared with White and other racialized groups. These findings indicate a need for more clinical and community interventions that support PrEP persistence and restarts among those at high risk of HIV acquisition.

The tainted altruism effect: a successful pre-registered replication.

Newman and Cain (Newman, Cain 2014 Psychol. Sci. 25, 648-655 (doi:10.1177/0956797613504785)) reported that observers view a person's choices as less ethical when that person has acted in response to both altruistic and selfish (commercial) motivations, as compared with purely selfish interests. The altruistic component reduces the observers' approval rather than raising it. This puzzling phenomenon termed the 'tainted altruism' effect, has attracted considerable interest but no direct replications in prior research. We report direct replications of Newman and Cain's Experiments 2 and 3, using a larger sample (n = 501) intended to be fairly representative of the US population. The results confirm the original findings in considerable detail.

Quantification of Immunostained Caspase-9 in Retinal Tissue.

The family of caspases is known to mediate many cellular pathways beyond cell death, including cell differentiation, axonal pathfinding, and proliferation. Since the identification of the family of cell death proteases, there has been a search for tools to identify and expand the function of specific family members in development, health, and disease states. However, many of the currently commercially available caspase tools that are widely used are not specific for the targeted caspase. In this report, we delineate the approach we have used to identify, validate, and target caspase-9 in the nervous system using a novel inhibitor and genetic approaches with immunohistochemical read-outs. Specifically, we used the retinal neuronal tissue as a model to identify and validate the presence and function of caspases. This approach enables the interrogation of cell-type specific apoptotic and non-apoptotic caspase-9 functions and can be applied to other complex tissues and caspases of interest. Understanding the functions of caspases can help to expand current knowledge in cell biology, and can also be advantageous to identify potential therapeutic targets due to their involvement in disease.

Locating the Risk: Using Participatory Mapping to Contextualize Perceived HIV Risk across Geography and Social Networks among Men Who Have Sex with Men in the Deep South.

HIV incidence among African American (AA) young men who have sex with men (YMSM) has remained stable even though they made up the largest number of new HIV diagnoses among men who have sex with men (MSM) in 2017. HIV spreads at increased rates in dense sexual networks. Identifying the location of risk behaviors "activity spaces" could inform geographically circumscribed HIV prevention interventions. Utilizing the modified social ecological model we completed five semi-structured focus groups incorporating a modified social mapping technique, based on Singer et al.'s approach. Participants included 27 AA YMSM. Focus groups explored how and where HIV transmission happens in Jackson, Mississippi. Result themes included: 1) location of sexual behaviors, 2) knowledge of geographic hotspots of HIV infection in Jackson, and 3) traveling to meet partners: at home and away. HIV transmission or "activity spaces" may be occurring outside identified HIV hot spots. Mixed geospatial and qualitative methods offered a comprehensive assessment of where HIV transmission occurs, and suggests that geographically circumscribed interventions may need to focus on where individuals living with HIV reside and in specific geographic locations where they engage in behaviors that raise their HIV acquisition risks.