Combination Immune Checkpoint Blockade Enhances IL-2 and CD107a Production from HIV-Specific T Cells Ex Vivo in People Living with HIV on Antiretroviral Therapy.

In people with HIV (PWH) on antiretroviral therapy (ART), immune dysfunction persists, including elevated expression of immune checkpoint (IC) proteins on total and HIV-specific T cells. Reversing immune exhaustion is one strategy to enhance the elimination of HIV-infected cells that persist in PWH on ART. We aimed to evaluate whether blocking CTL-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), T cell Ig domain and mucin domain 3 (TIM-3), T cell Ig and ITIM domain (TIGIT) and lymphocyte activation gene-3 (LAG-3) alone or in combination would enhance HIV-specific CD4+ and CD8+ T cell function ex vivo. Intracellular cytokine staining was performed using human PBMCs from PWH on ART (n = 11) and expression of CD107a, IFN-γ, TNF-α, and IL-2 was quantified with HIV peptides and Abs to IC. We found the following: 1) IC blockade enhanced the induction of CD107a and IL-2 but not IFN-γ and TNF-α in response to Gag and Nef peptides; 2) the induction of CD107a and IL-2 was greatest with multiple combinations of two Abs; and 3) Abs to LAG-3, CTLA-4, and TIGIT in combinations showed synergistic induction of IL-2 in HIV-specific CD8+ and CD107a and IL-2 production in HIV-specific CD4+ and CD8+ T cells. These results demonstrate that the combination of Abs to LAG-3, CTLA-4, or TIGIT can increase the frequency of cells expressing CD107a and IL-2 that associated with cytotoxicity and survival of HIV-specific CD4+ and CD8+ T cells in PWH on ART. These combinations should be further explored for an HIV cure.

Overlap between birth trauma and mistreatment: a qualitative analysis exploring American clinician perspectives on patient birth experiences.

INTRODUCTION: Research exploring the mistreatment of birthing people in the United States is emerging rapidly within the context of increasingly poor maternal health outcomes that include unacceptable racial disparities. Previous research has explored overlap between psychological birth trauma and mistreatment using patient descriptions of birth experiences, but no previous studies have explored these issues from the perspectives of clinicians. The aim of this study was to explore whether maternity care providers' descriptions of patient birth trauma overlap with categories of mistreatment from a globally accepted typology. METHODS: Content analysis was performed on a qualitative data set of 28 semi-structured interviews about patient birth trauma, completed in 2018-2019 with U.S. maternity care clinicians, including obstetricians, family physicians, midwives and labor/delivery nurses. The interviews were part of a larger study exploring maternity clinician perspectives and experiences of patient birth trauma. For this analysis Krippendorff's method of categoric distinction was used, with categories from a globally recognized typology of maternity patient mistreatment. RESULTS: Clinicians' descriptions of their experiences with patient birth trauma mapped onto all seven mistreatment categories, although no interview questions specifically asked about mistreatment. In more than 30 hours of interviews, transcribed to more than 800 pages, the word mistreatment appears only once, suggesting that some healthcare providers may use the phrase "birth trauma" as a euphemism to describe mistreatment. Eighteen of 28 interviews included at least one description that fit into a mistreatment category. "Failure to meet professional standards of care" was the category with the most mapped clinician statements, followed by "Stigma and discrimination" and "Poor rapport between women and providers." CONCLUSIONS: This study contributes new insight into maternity clinicians' conceptualization of patient trauma and how their descriptions of birth trauma overlap with mistreatment. Clinicians implicitly connected mistreatment with some patient experiences of birth trauma, even when they were not specifically asked about mistreatment. Findings point to a need for further research into mistreatment, including routinized "everyday care" that may include mistreatment, particularly for marginalized and historically excluded birthing people. Future research also must explore the potential role of mistreatment in poor and inequitable U.S. birth outcomes.

Many people giving birth in the United States experience poor health outcomes, and there is a wide racial disparity, with people of color more likely to experience poor outcomes. In recent research, birthing people reported that they were mistreated during their labor and delivery, including being shouted at, scolded, or threatened. Mistreatment accounts were more frequent among women of color. Previous research has looked at patient reports about their birth experiences to explore whether their descriptions of psychological trauma include overlap with mistreatment, but no other studies have looked at descriptions of birth trauma from the perspectives of medical clinicians. The objective of this study was to explore whether maternity care providers' descriptions of patient birth trauma overlap with categories of mistreatment from a globally accepted list. This study analyzed the content of 28 semi-structured interviews about patient birth trauma, completed in 2018­2019 with obstetricians, family physicians, midwives and labor/delivery nurses. In the interviews, participant descriptions of patient birth trauma fit into all seven mistreatment categories. Participant descriptions included examples of patients receiving medical procedures or treatments without first giving consent, nurses avoiding the rooms of patients who do not speak English, and other forms of mistreatment. Participants were not asked specifically about mistreatment, but they described birth trauma by giving examples of mistreatment, which suggests that some healthcare providers may use the phrase "birth trauma" when talking about "mistreatment." This study shows a need for further research into mistreatment, including routine "everyday care" that may include mistreatment.

Examining the Supports and Advice That Women With Intimate Partner Violence Experience Received in Online Health Communities: Text Mining Approach.

BACKGROUND: Intimate partner violence (IPV) is an underreported public health crisis primarily affecting women associated with severe health conditions and can lead to a high rate of homicide. Owing to the COVID-19 pandemic, more women with IPV experiences visited online health communities (OHCs) to seek help because of anonymity. However, little is known regarding whether their help requests were answered and whether the information provided was delivered in an appropriate manner. To understand the help-seeking information sought and given in OHCs, extraction of postings and linguistic features could be helpful to develop automated models to improve future help-seeking experiences. OBJECTIVE: The objective of this study was to examine the types and patterns (ie, communication styles) of the advice offered by OHC members and whether the information received from women matched their expressed needs in their initial postings. METHODS: We examined data from Reddit using data from subreddit community r/domesticviolence posts from November 14, 2020, through November 14, 2021, during the COVID-19 pandemic. We included posts from women aged ≥18 years who self-identified or described experiencing IPV and requested advice or help in this subreddit community. Posts from nonabused women and women aged <18 years, non-English posts, good news announcements, gratitude posts without any advice seeking, and posts related to advertisements were excluded. We developed a codebook and annotated the postings in an iterative manner. Initial posts were also quantified using Linguistic Inquiry and Word Count to categorize linguistic and posting features. Postings were then classified into 2 categories (ie, matched needs and unmatched needs) according to the types of help sought and received in OHCs to capture the help-seeking result. Nonparametric statistical analysis (ie, 2-tailed t test or Mann-Whitney U test) was used to compare the linguistic and posting features between matched and unmatched needs. RESULTS: Overall, 250 postings were included, and 200 (80%) posting response comments matched with the type of help requested in initial postings, with legal advice and IPV knowledge achieving the highest matching rate. Overall, 17 linguistic or posting features were found to be significantly different between the 2 groups (ie, matched help and unmatched help). Positive title sentiment and linguistic features in postings containing health and wellness wordings were associated with unmatched needs postings, whereas the other 14 features were associated with postings with matched needs. CONCLUSIONS: OHCs can extract the linguistic and posting features to understand the help-seeking result among women with IPV experiences. Features identified in this corpus reflected the differences found between the 2 groups. This is the first study that leveraged Linguistic Inquiry and Word Count to shed light on generating predictive features from unstructured text in OHCs, which could guide future algorithm development to detect help-seeking results within OHCs effectively.

Pre-exposure prophylaxis (PrEP) for HIV prevention among people who inject drugs: a global mapping of service delivery.

BACKGROUND: The World Health Organization (WHO) recommends oral pre-exposure prophylaxis (PrEP) for all people at substantial risk of HIV as part of combination prevention. The extent to which this recommendation has been implemented globally for people who inject drugs is unclear. This study mapped global service delivery of PrEP for people who inject drugs. METHODS: Between October and December 2021, a desk review was conducted to obtain information on PrEP services for people who inject drugs from drug user-led networks and HIV, harm reduction, and human rights stakeholders. Websites of organizations involved in HIV prevention or services for people who inject drugs were searched. Models of service delivery were described in terms of service location, provider, and package. RESULTS: PrEP services were identified in 27 countries (15 high-income). PrEP delivery models varied within and across countries. In most services, PrEP services were implemented in healthcare clinics without direct links to other harm reduction services. In three countries, PrEP services were also provided at methadone clinics. In 14 countries, PrEP services were provided through community-based models (outside of clinic settings) that commonly involved peer-led outreach activities and integration with harm reduction services. CONCLUSIONS: This study indicates limited PrEP availability for people who inject drugs. There is potential to expand PrEP services for people who inject drugs within harm reduction programs, notably through community-based and peer-led services. PrEP should never be offered instead of evidence-based harm reduction programs for people who inject drugs; however, it could be offered as an additional HIV prevention choice as part of a comprehensive harm reduction program.

Antiretroviral Initiation at ≥800 CD4+ Cells/mm3 Associated With Lower Human Immunodeficiency Virus Reservoir Size.

BACKGROUND: Identifying factors that determine the frequency of latently infected CD4+ T cells on antiretroviral therapy (ART) may inform strategies for human immunodeficiency virus (HIV) cure. We investigated the role of CD4+ count at ART initiation for HIV persistence on ART. METHODS: Among participants of the Strategic Timing of Antiretroviral Treatment Study, we enrolled people with HIV (PWH) who initiated ART with CD4+ T-cell counts of 500-599, 600-799, or ≥ 800 cells/mm3. After 36-44 months on ART, the levels of total HIV-DNA, cell-associated unspliced HIV-RNA (CA-US HIV-RNA), and two-long terminal repeat HIV-DNA in CD4+ T cells were quantified and plasma HIV-RNA was measured by single-copy assay. We measured T-cell expression of Human Leucocyte Antigen-DR Isotype (HLA-DR), programmed death-1, and phosphorylated signal transducer and activator of transcription-5 (pSTAT5). Virological and immunological measures were compared across CD4+ strata. RESULTS: We enrolled 146 PWH, 36 in the 500-599, 60 in the 600-799, and 50 in the ≥ 800 CD4 strata. After 36-44 months of ART, total HIV-DNA, plasma HIV-RNA, and HLA-DR expression were significantly lower in PWH with CD4+ T-cell count ≥ 800 cells/mm3 at ART initiation compared with 600-799 or 500-599 cells/mm3. The median level of HIV-DNA after 36-44 months of ART was lower by 75% in participants initiating ART with ≥ 800 vs 500-599 cells/mm3 (median [interquartile range]: 16.3 [7.0-117.6] vs 68.4 [13.7-213.1] copies/million cells, respectively). Higher pSTAT5 expression significantly correlated with lower levels of HIV-DNA and CA-US HIV-RNA. Virological measures were significantly lower in females. CONCLUSIONS: Initiating ART with a CD4+ count ≥ 800 cells/mm3 compared with 600-799 or 500-599 cells/mm3 was associated with achieving a substantially smaller HIV reservoir on ART.

Global assessment of existing HIV and key population stigma indicators: A data mapping exercise to inform country-level stigma measurement.

BACKGROUND: Stigma is an established barrier to the provision and uptake of HIV prevention, diagnostic, and treatment services. Despite consensus on the importance of addressing stigma, there are currently no country-level summary measures to characterize stigma and track progress in reducing stigma around the globe. This data mapping exercise aimed to assess the potential for existing data to be used to summarize and track stigma, including discrimination, related to HIV status, or key population membership at the country level. METHODS AND FINDINGS: This study assessed existing indicators of stigma related to living with HIV or belonging to 1 of 4 key populations including gay men and other men who have sex with men, sex workers, people who use drugs, and transgender persons. UNAIDS Strategic Information Department led an initial drafting of possible domains, subdomains, and indicators, and a 3-week e-consultation was held to provide feedback. From the e-consultation, 44 indicators were proposed for HIV stigma; 14 for sexual minority stigma (including sexual behavior or orientation) related to men who have sex with men; 12 for sex work stigma; 10 for drug use stigma; and 17 for gender identity stigma related to transgender persons. We conducted a global data mapping exercise to identify and describe the availability and quality of stigma data across countries with the following sources: UNAIDS National Commitments and Policies Instrument (NCPI) database; Multiple Indicator Cluster Surveys (MICS); Demographic and Health Surveys (DHS); People Living with HIV Stigma Index surveys; HIV Key Populations Data Repository; Integrated Biological and Behavioral Surveys (IBBS); and network databases. Data extraction was conducted between August and November 2020. Indicators were evaluated based on the following: if an existing data source could be identified; the number of countries for which data were available for the indicator at present and in the future; variation in the indicator across countries; and considerations of data quality or accuracy. This mapping exercise resulted in the identification of 24 HIV stigma indicators and 10 key population indicators as having potential to be used at present in the creation of valid summary measures of stigma at the country level. These indicators may allow assessment of legal, societal, and behavioral manifestations of stigma across population groups and settings. Study limitations include potential selection bias due to available data sources to the research team and other biases due to the exploratory nature of this data mapping process. CONCLUSIONS: Based on the current state of data available, several indicators have the potential to characterize the level and nature of stigma affecting people living with HIV and key populations across countries and across time. This exercise revealed challenges for an empirical process reliant on existing data to determine how to weight and best combine indicators into indices. However, results for this study can be combined with participatory processes to inform summary measure development and set data collection priorities going forward.

Diverse effects of interferon alpha on the establishment and reversal of HIV latency.

HIV latency is the major barrier to a cure for people living with HIV (PLWH) on antiretroviral therapy (ART) because the virus persists in long-lived non-proliferating and proliferating latently infected CD4+ T cells. Latently infected CD4+ T cells do not express viral proteins and are therefore not visible to immune mediated clearance. Therefore, identifying interventions that can reverse latency and also enhance immune mediated clearance is of high interest. Interferons (IFNs) have multiple immune enhancing effects and can inhibit HIV replication in activated CD4+ T cells. However, the effects of IFNs on the establishment and reversal of HIV latency is not understood. Using an in vitro model of latency, we demonstrated that plasmacytoid dendritic cells (pDC) inhibit the establishment of HIV latency through secretion of type I IFNα, IFNß and IFNω but not IFNε or type III IFNλ1 and IFNλ3. However, once latency was established, IFNα but no other IFNs were able to efficiently reverse latency in both an in vitro model of latency and CD4+ T cells collected from PLWH on suppressive ART. Binding of IFNα to its receptor expressed on primary CD4+ T cells did not induce activation of the canonical or non-canonical NFκB pathway but did induce phosphorylation of STAT1, 3 and 5 proteins. STAT5 has been previously demonstrated to bind to the HIV long terminal repeat and activate HIV transcription. We demonstrate diverse effects of interferons on HIV latency with type I IFNα; inhibiting the establishment of latency but also reversing HIV latency once latency is established.

HIV awareness, pre-exposure prophylaxis perceptions and experiences among people who exchange sex: qualitative and community based participatory study.

BACKGROUND: People who exchange sex for money, favors, goods or services, combat higher risk of acquiring sexually transmitted diseases (STDs) and human immunodeficiency virus (HIV). Understanding barriers to STD and HIV related healthcare from the perspective of this stigmatized and marginalized community may improve access to sexual health services including pre-exposure prophylaxis (PrEP).  METHODS: We used community-partnered participatory and qualitative methods to conduct anonymous one-on-one interviews with people who exchange sex to understand their perspectives and experiences related to pre-exposure prophylaxis (PrEP) to prevent HIV acquisition. We conducted twenty-two interviews and coded them to perform thematic analysis.  RESULTS: We identified five themes: (1) Appreciation of HIV risk and prevention strategies grew from information accumulated over time. (2) PrEP information came from a variety of sources with mixed messages and uncertain credibility. (3) Decision-making about use of PrEP was relative to other behavioral decisions regarding exchange sex. (4) The multi-step process of obtaining PrEP presented multiple potential barriers. (5) Healthcare providers were seen as powerful facilitators to PrEP utilization. CONCLUSIONS: Our findings suggest that PrEP education and care needs to be made more relevant and accessible to individuals who exchange sex.

Provider perceptions of medication for opioid used disorder (MOUD): A qualitative study in communities with high opioid overdose death rates.

BACKGROUND: Medication for Opioid Use Disorder (MOUD) has been shown to be a safe, cost-effective intervention that successfully lowers risk of opioid overdose. However, access to and use of MOUD has been limited. Our objective was to explore attitudes, opinions, and beliefs regarding MOUD among healthcare and social service providers in a community highly impacted by the opioid overdose epidemic. METHODS: As part of a larger ethnographic study examining neighborhoods in Allegheny County, PA, with the highest opioid overdose death rates, semi-structured qualitative in-person and telephone interviews were conducted with forty-five providers treating persons with opioid use disorders in these communities. An open coding approach was used to code interview transcripts followed by thematic analysis. RESULTS: Three major themes were identified related to MOUD from the perspectives of our provider participants. Within a variety of health and substance use service roles and settings, provider reflections revealed: (1) different opinions about MOUD as a transition to abstinence or as a long-term treatment; (2) perceived lack of uniformity and dissemination of accurate information of MOUD care, permitting differences in care, and (3) observed barriers to entry and navigation of MOUD, including referrals as a "word-of-mouth insider system" and challenges of getting patients MOUD services when they need it. CONCLUSIONS: Even in communities hard hit by the opioid overdose epidemic, healthcare providers' disagreement about the standard of care for MOUD can be a relevant obstacle. These insights can inform efforts to improve MOUD treatment and access for people with opioid use disorders.

Ending AIDS as a public health threat by 2030: Time to reset targets for 2025.

Paul De Lay and co-authors introduce a Collection on the design of targets for ending the AIDS epidemic.

Barriers to help-seeking among intimate partner violence survivors with opioid use disorder.

Intimate partner violence is common among people with opioid use disorder (OUD), but little research has focussed on identifying barriers survivors with OUD face when trying to leave an abusive relationship. Semi-structured interviews were conducted with 40 postpartum women with OUD. Interview questions were designed to identify barriers to help-seeking and facilitators and supports that have helped survivors make positive changes. Qualitative data were coded and analyzed, using a phenomenological approach to develop emerging themes. Most participants were white, 24-29 years old, single, unemployed, Medicaid insured, and used medications for OUD. All participants (n = 40, 100%) shared that a current or past partner physically, sexually, emotionally, or verbally abused them. Participants identified multiple barriers to help-seeking including abusive partner control of money and resources, fear of retaliatory violence, and concerns related to police and child welfare. Participants also described supports that helped them make positive changes, including being treated with care and support from domestic violence shelters and treatment programs. Finally, survivors offered suggestions for ways providers can better meet survivors' needs. Clinicians and policymakers should prioritize overcoming multiple barriers to service access and engagement faced by survivors and their children.

Peer driven or driven peers? A rapid review of peer involvement of people who use drugs in HIV and harm reduction services in low- and middle-income countries.

INTRODUCTION: Peer involvement of people who use drugs within HIV and harm reduction services is widely promoted yet under-utilised. Alongside political and financial barriers is a limited understanding of the roles, impacts, contexts and mechanisms for peer involvement, particularly in low- and middle-income settings. We conducted a rapid review of available literature on this topic. METHODS: Within a community-academic partnership, we used a rapid review approach, framed by realist theory. We used a network search strategy, focused on core journals and reference lists of related reviews. Twenty-nine studies were included. We developed thematic summaries framed by a realist approach of exploring interventions, their mechanisms, outcomes and how they are shaped by contexts. RESULTS: Reported outcomes of peer involvement included reduced HIV incidence and prevalence; increased service access, acceptability and quality; changed risk behaviours; and reduced stigma and discrimination. Mechanisms via which these roles work were trust, personal commitment and empathy, using community knowledge and experience, as well as 'bridge' and 'role model' processes. Contexts of criminalisation, under-resourced health systems, and stigma and discrimination were found to shape these roles, their mechanisms and outcomes. Though contexts and mechanisms are little explored within the literature, we identified a common theme across contexts, mechanisms and outcomes. Peer outreach interventions work through trust, community knowledge and expertise, and 'bridge' mechanisms (M) to counter criminalisation and constraining clinic and service delivery environments (C), contributing towards changed drug-using behaviours, increased access, acceptability and quality of harm reduction services and decreased stigma and discrimination (O). CONCLUSION: Peer involvement in HIV and harm reduction services in low- and middle-income settings is linked to positive health outcomes, shaped by contexts of criminalisation, stigma, and resource scarcity. However, peer involvement is under-theorised, particularly on how contexts shape mechanisms and ultimately outcomes. Efforts to study peer involvement need to develop theory and methods to evaluate the complex mechanisms and contexts that have influence. Finally, there is a need to expand the range of peer roles, to embrace the capacities and expertise of people who use drugs.

The intersection of intimate partner violence and substance use among women with opioid use disorder.

BACKGROUND: Women with opioid use disorder (OUD) report high rates of intimate partner violence (IPV) and there is limited understanding of how IPV influences substance use behaviors among women with OUD. Methods: Semi-structured qualitative interviews were conducted with a sample of 40 women with OUD participating in an ongoing clinical trial evaluating postpartum contraceptive utilization patterns for this population. Interviews were audio-recorded, transcribed verbatim and lasted approximately 45 min. Interview questions focused on women's perceptions and experiences with IPV and how these experiences impacted their substance use behaviors. Transcripts were coded independently in Atlas.ti and qualitatively analyzed using a general qualitative inquiry approach for emerging themes. Results: Participants were aged 24-29, and the majority were white, single, unemployed, had Medicaid insurance and a high school degree. Although personal IPV experiences were not necessary to be selected for this qualitative sub-study, all participants reported some lifetime experience with IPV. Four overarching themes emerged: (1) women attributed physical IPV to their partner's substance use; (2) emotional abuse prevented women from fully engaging in their recovery; (3) financial abuse prevented women from gaining independence from abusive partners; and (4) women coped with IPV experiences through substance use. Conclusions: IPV had a significant influence on women's substance use behaviors including their perceived risk of relapse and treatment discontinuation. These findings demonstrate the need to integrate assessment, evaluation and management of IPV into substance use treatment settings.

"Stories of starting": Understanding the complex contexts of opioid misuse initiation.

Background: The impacts of opioid use disorder and opioid-involved overdose are known, but less is known about the contexts in which people first misuse opioids, and the motivations for continued misuse. Methods: In-depth interviews with 26 individuals in Allegheny County, Pennsylvania with current or past histories of opioid misuse were conducted. Narratives were analyzed to understand the circumstances and influences contributing to initial and continued misuse of opioids. Results: Participants described social and familial contexts that normalized or accepted opioid misuse-this often included their own use of other illicit substances prior to initiating opioids. Participants also described initial use of opioids as related to efforts to cope with physical pain. They also described recognizing and then seeking psychological/emotional benefits from opioids. All three of these themes often overlapped and intersected in these stories of starting opioid misuse. Conclusions: Opioid misuse stemmed from complex interacting influences involving coping with physical and psychological pain, perception that opioids are needed to feel "normal", and acceptance or normalization of opioid use. This suggests a multi-pronged approach to both prevention and treatment are needed.

A rapid-cycle assessment strategy for understanding the opioid overdose epidemic in local communities.

Background: Certain communities in the United States experience greater opioid-involved overdose mortality than others. Interventions to stem overdose benefit from contextual understandings of communities' needs and strengths in addressing the opioid crisis. This project aims to understand multiple stakeholder perspectives on the opioid epidemic in communities disproportionately affected by opioid-involved overdose mortality. Methods: We performed a rapid-cycle qualitative assessment study utilizing in-depth interviews with community stakeholders and observations of community meetings in eight communities in Allegheny County, Pennsylvania, USA, disproportionately impacted by opioid-involved overdose mortality. Stakeholder categories included: current and past illicit users of opioids; medical and social service providers; emergency medical services; law enforcement; spouse or other family members of illicit users/former users of opioids; government officials; school officials; community members. Content analysis was utilized to identify themes and answer study questions. Regular feedback to stakeholders was provided to support targeted interventions. Results: We performed semi-structured, in-depth interviews with 130 community stakeholders and 29 community meeting observations in 2018-2019. Participants perceived similar economic and social determinants as origins of the opioid overdose epidemic including lack of economic resources, loss of jobs, transient populations and dilapidated housing. However, they differed in their awareness of and attention to the epidemic. Awareness was dependent on the visibility of opioid use (presence of paraphernalia litter, location of drug users, media coverage, and relationship to users). Overall, there was good knowledge of naloxone for opioid overdose reversal but less knowledge about local syringe services programs. Perceptions of harm reduction efforts were ambivalent. Conclusions: Members of communities impacted by the opioid epidemic perceived that economic downturn was a major factor in the opioid overdose epidemic. However, the varied beliefs within and between communities suggest that interventions need to be tailored according to the cultural norms of place.

Navigating the university transition among women who self-report an eating disorder: A qualitative study.

OBJECTIVE: Although developmental milestones have been observed to alter eating disorder (ED) symptom burden, it remains unknown how the transition to university affects symptomatology. To address this gap, we designed a qualitative study to elucidate how students with an ED perceive their general university experience and to describe how the university environment shapes their ED. METHOD: Undergraduate students who self-reported an ED were recruited through fliers, an undergraduate advocacy organization, and local treatment centers. We conducted audio-recorded semi-structured individual interviews. Two investigators separately coded verbatim transcripts using an editing approach, and final themes emerged from the pattern of descriptors. RESULTS: Fifteen undergraduate students participated. Participants endorsed a variety of ED symptoms and sought various levels of treatment. Most participants transitioned to university with an already-established diagnosis. Participants described that ED symptoms tended to worsen in university for a variety of reasons including (a) minimization of ED severity, (b) loss of external accountability, (c) use of ED symptoms as a coping mechanism, and (d) glorification of ED behaviors in campus diet culture. Subsequently, the ED disrupted the university experience by (e) hindering participants' ability to focus on academic responsibilities and (f) leading to social isolation on campus. DISCUSSION: We identified challenges unique to the university experience that can be addressed by ED treatment teams in order to provide anticipatory guidance and patient-centered care. Study limitations include lack of formal diagnostic ED assessment by research team and sampling of students from one university.

Human Services Utilization Among Male IPV Perpetrators: Relationship to Timing and Completion of Batterer Intervention Programs.

Limited information exists on the extent to which male perpetrators of Intimate Partner Violence (IPV) are engaged in the use of human services for co-occuringpsychosocial and health issues. The current analysis uses administrative data from one batterer intervention program (BIP) and data from the local Department of Human Services to explore perpetrators' engagement with human services, and the relationship of that use to timing and completion of the BIP. Data for 330 adult male clients referred to the participating BIP from 2010 to 2015 were collected. A majority (63%) had engaged in at least one human service program. The most common kind of service was mental health (46%). The most specific service engagement was child welfare as a parent (41%). Engagement largely concluded prior to beginning the BIP. BIP completers had less service use overall. Future work should explore how these services could be utilized to improve the success of BIPs and reduce perpetration.

Seamless gene correction of ß-thalassemia mutations in patient-specific iPSCs using CRISPR/Cas9 and piggyBac.

ß-thalassemia, one of the most common genetic diseases worldwide, is caused by mutations in the human hemoglobin beta (HBB) gene. Creation of human induced pluripotent stem cells (iPSCs) from ß-thalassemia patients could offer an approach to cure this disease. Correction of the disease-causing mutations in iPSCs could restore normal function and provide a rich source of cells for transplantation. In this study, we used the latest gene-editing tool, CRISPR/Cas9 technology, combined with the piggyBac transposon to efficiently correct the HBB mutations in patient-derived iPSCs without leaving any residual footprint. No off-target effects were detected in the corrected iPSCs, and the cells retain full pluripotency and exhibit normal karyotypes. When differentiated into erythroblasts using a monolayer culture, gene-corrected iPSCs restored expression of HBB compared to the parental iPSCs line. Our study provides an effective approach to correct HBB mutations without leaving any genetic footprint in patient-derived iPSCs, thereby demonstrating a critical step toward the future application of stem cell-based gene therapy to monogenic diseases.

Preferred Physical Characteristics of Vaginal Film Microbicides for HIV Prevention in Pittsburgh Women.

Unprotected heterosexual intercourse is the leading cause of HIV acquisition in women. Due to the complex nature of correct and consistent condom use by both men and women, developing alternative female-controlled HIV prevention options is a global health priority. Vaginal films containing antiretroviral drugs are a potential delivery system for the prevention of HIV acquisition through sexual contact. In this study, we explored women's preferences regarding physical characteristics of microbicide vaginal films through questionnaires and focus groups. Eighty-four sexually active, ethnically diverse women 18-30 years of age from Pittsburgh, Pennsylvania, participated in the study. Women visually and manually examined a variety of vaginal films, as well as three other vaginal products undergoing evaluation for HIV prevention: tablet, ring, and gel. Means and standard deviations or frequencies and 95 % confidence intervals were calculated for questionnaire data. Focus groups were audio-recorded, transcribed verbatim, and coded for content analysis. Women most frequently preferred vaginal films to be smooth and thin (63 %), translucent (48 %), and 2″ × 2″ square size (36 %). Driving these preferences were five major themes: ease and accuracy of use, desire for efficacy, discretion, intravaginal comfort and minimal impact, and minimizing disruption of sexual mood/activities. Women's preferences for various microbicide vaginal film physical attributes represented a balance of multiple values. In general, women desired a comfortable, efficacious, easy to use, and minimally intrusive product.