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Although the introduction of antiretroviral therapy has rendered HIV a chronic illness, inconsistent engagement in HIV care by key populations limits its public health impact. Poor engagement in care is especially prevalent among vulnerable populations with mental health and substance use disorders. Beyond structural and health system considerations, psychosocial factors may present challenges to sustained engagement. We conducted a qualitative study using in-depth interviews with 31 primarily African American, urban-based individuals, many with past or current drug use and mental disorders, living with HIV. Participants identified several psychosocial barriers that detract from their motivation to attend appointments and take medication. These included mental distress or detachment over a lack of purpose in life; denial about the need to be engaged in care; insufficient trust in the efficacy of care or the health system; deaths of loved ones leading to bereavement or loss of social support; and engagement in specific avoidance behaviors like drugs and alcohol. The study findings suggest that more comprehensive HIV care, which integrates mental health and substance abuse services in order to enhance meaning and address coping and grief, may be important. Considering these services in addition to improving the logistical components of care such as cues/reminders, accessibility, and patient-provider communication may improve intervention packages.

Background: Global health education is in high demand in the United States, across the continuum of learning, and field experiences are an essential part of this education. However, evaluations of these programs are limited. Objectives: The aim of this study was to evaluate a field placement program at Johns Hopkins University, in Baltimore, Maryland, to understand how to better support student training overseas and faculty mentorship. Methods: We used qualitative and quantitative methods to gather data from program reporting requirements (152 student surveys and 46 experiential narrative essays), followed by 17 semistructured interviews, and 2 focus groups. Data were analyzed through manual coding and a socioecological model served as an analytical and a synthesizing framework. Findings: A series of factors influence the participants' experience in overseas placements spanning across 4 aggregate levels, from individual to societal, including opportunity for professional advancement, independence, loneliness and illness, mentorship quality, funding, institutional partnership building, opportunity for public health contribution, and for development of cultural competency. Faculty and students thought that the program was beneficial to the learning experience, particularly for its contribution to experiential knowledge of a low- and middle-income country setting and for developing cross-cultural relationships. Communication and scope of work were 2 areas in which students and faculty members often had different expectations and many students emerged having cultivated different skills than they or their mentor initially expected. Students found the experience useful for both their academic and professional careers and faculty members saw mentorship, one of their professional responsibilities, emerge. Conclusions: Many socioecological factors influence an overseas field experience, which in turn produces important effects on students' career choices, and faculty members appreciate the opportunity to serve as mentors. The most vital support mechanisms suggested for faculty and students included available funding, clear preparation, and communication facilitation across the experiential continuum.

Insulin-like growth factor binding protein (IGFBP)-3 regulates cell proliferation and apoptosis in esophageal squamous cell carcinoma (ESCC) cells. We have investigated how the hypoxic tumor microenvironment in ESCC fosters the induction of IGFBP3. RNA interference experiments revealed that hypoxia-inducible factor (HIF)-1α, but not HIF-2α, regulates IGFBP3 mRNA induction. By chromatin immunoprecipitation and transfection assays, HIF-1α was found to transactivate IGFBP3 through a novel hypoxia responsive element (HRE) located at 57 kb upstream from the transcription start site. Metabolic labeling experiments demonstrated hypoxia-mediated inhibition of global protein synthesis. 7-Methyl GTP-cap binding assays suggested that hypoxia suppresses cap-dependent translation. Experiments using pharmacological inhibitors for mammalian target of rapamycin (mTOR) suggested that a relatively weak mTOR activity may be sufficient for cap-dependent translation of IGFBP3 under hypoxic conditions. Bicistronic RNA reporter transfection assays did not validate the possibility of an internal ribosome entry site as a potential mechanism for cap-independent translation for IGFBP3 mRNA. Finally, IGFBP3 mRNA was found enriched to the polysomes. In aggregate, our study establishes IGFBP3 as a direct HIF-1α target gene and that polysome enrichment of IGFBP3 mRNA may permit continuous translation under hypoxic conditions.—Natsuizaka, M., Naganuma, S., Kagawa, S., Ohashi, S., Ahmadi, A., Subramanian, H., Chang, S., Nakagawa, K. J., Ji, X., Liebhaber, S. A., Klein-Szanto, A. J., Nakagawa, H. Hypoxia induces IGFBP3 in esophageal squamous cancer cells through HIF-1α-mediated mRNA transcription and continuous protein synthesis.

Despite the existence of highly active antiretroviral therapy, HIV/AIDS morbidity and mortality continue to be public health burdens in the United States due to difficulties in engaging people living with HIV/AIDS (PLWHA) in continuous, effective care. In comparison to studies investigating patient-level characteristics associated with starting and remaining in care, there is relatively little research on how structural factors, such as those pertaining to healthcare providers and the infrastructure for delivery of health services, influence patients’ engagement in HIV care. Our study, based in the city of Baltimore, Maryland, uses qualitative research methods with a population of predominantly African American PLWHA who have a history of drug abuse, to examine facilitators and barriers regarding adherence to antiretroviral therapy (ART) and HIV care appointment attendance. Data collection involved conducting one-on-one, in-depth interviews with 31 study participants, and data analysis entailed thematic coding of interview transcripts and writing analytic memos to develop ideas and concepts. Among other findings, factors described as influential by our study participants related to appointment reminders and scheduling, the attitudes and communication styles of HIV clinicians, and the disposition and availability of other healthcare workers on the care “team.” Thus, improving quality of HIV care and means of delivering it may help mitigate the numerous points in the continuum of HIV care when a patient may disengage.

Sex work is rarely an occupation of choice for Iranian women and is often described as a last resort. While several factors play a role in creating an environment where individuals become involved in sex work, female sex workers' experiences regarding entry into sex work in Iran are poorly understood. In this qualitative study, a convenience sample of 24 participants was recruited from a drop-in centre for vulnerable women in Kerman, Iran. Through in-depth interviews, participants were asked about their personal lived experiences of initiating sex work. Grounded theory was used to analyse findings from this research. We learned that major factors impacting on women's initiation into sex work circulated around their vulnerability and chronic poverty. Participants continued to sell sex due to their limited opportunities, drug dependence and financial needs. Improving sex workers' economic status could be a vital intervention in providing vulnerable women with options other than sex work. Female sex workers should be provided with government support and educational programmes delivered through special centres. Despite the illegal status of their work, sex workers' needs should be recognised across all aspects of policy and legislation.

Hymenoplasty is a controversial surgery in Iran, where a woman's failure to present herself as virginal for marriage may result in severe social repercussions. Critical literature surrounding this clandestine surgery is sparse. During ethnographic fieldwork in Tehran, I interviewed women who have and have not undergone hymenoplasty and physicians who perform it. Using a Foucauldian framework, I argue that the medicalization of virginity is a form of female social control in Iran. The resulting narratives and discourses suggest that hymenoplasty is a covert form of resistance against socioculturally prescribed sexual inegalitarianism that restricts women to the social sphere of premarital chastity. By manipulating the medicalization of virginity, women inadvertently resist dichotomous gendered classifications that constrain them as either the deviant woman who has premarital sex or the normal woman who remains virginal until marriage. These women deviate from a fixed notion of gender embodiment, eroding socioculturally constituted categorical boundary markers regarding femininity.

Insulin-like growth factor-binding protein (IGFBP)-3 is overexpressed frequently in esophageal squamous cell carcinoma. Yet, the role of IGFBP3 in esophageal tumor biology remains to be elucidated. We find that IGFBP3 facilitates transforming growth factor (TGF)-beta1-mediated epithelial-to-mesenchymal transition (EMT) in transformed human esophageal epithelial cells, EPC2-hTERT-EGFR-p53(R175H). In organotypic 3D culture, a form of human tissue engineering, laser-capture microdissection revealed concurrent upregulation of TGF-beta target genes, IGFBP3 and EMT-related genes in the cells invading into the stromal compartment. IGFBP3 enhanced TGF-beta1-mediated EMT as well as transcription factors essential in EMT by allowing persistent SMAD2 and SMAD3 phosphorylation. TGF-beta1-mediated EMT and cell invasion were enhanced by ectopically expressed IGFBP3 and suppressed by RNA interference directed against IGFBP3. The IGFBP3 knockdown effect was rescued by IGFBP3(I56G/L80G/L81G), a mutant IGFBP3 lacking an insulin-like growth factor (IGF)-binding capacity. Thus, IGFBP3 can regulate TGF-beta1-mediated EMT and cell invasion in an IGF or insulin-like growth factor 1 receptor-independent manner. IGFBP3(I56G/L80G/L81G) also promoted EMT in vivo in a Ras-transformed human esophageal cell line T-TeRas upon xenograft transplantation in nude mice. In aggregate, IGFBP3 may have a novel IGF-binding independent biological function in regulation of TGF-beta1-mediated EMT and cell invasion.

Hymenoplasty, practiced in societies wherein a woman's virginity signifies honour, is a controversial surgery raising a multitude of ethical issues. There is a dearth of research uncovering the views of physicians who perform hymenoplasty, especially in sexually conservative cultures, such as Iran. Interviews were conducted with five Iranian physicians who perform hymenoplasty to determine their ethical views on the surgery. The interview findings suggest that Iranian physicians risk punitive consequences if they are discovered to be offering hymenoplasty. However, some continue to cautiously perform the procedure out of a moral obligation to protect the welfare of women seeking it, even if they are personally conflicted about the surgery.