The Family and Pregnancy Pop-Up Village: Developing a one-stop shop of services to reduce pregnancy care-related inequities in San Francisco.

INTRODUCTION: Centering affected individuals and forming equitable institutional-community partnerships are necessary to meaningfully transform care delivery systems. We describe our use of the PRECEDE-PROCEED framework to design, plan, and implement a novel care delivery system to address perinatal inequities in San Francisco. METHODS: Community engagement (PRECEDE phases 1-2) informed the "Pregnancy Village" prototype, which would unite key organizations to deliver valuable services alongside one another, as a recurring "one-stop-shop" community-based event, delivered in an uplifting, celebratory, and healing environment. Semi-structured interviews with key partners identified participation facilitators and barriers (PRECEDE phases 3-4) and findings informed our implementation roadmap. We measured feasibility through the number of events successfully produced and attended, and organizational engagement through meeting attendance and surveys. RESULTS: The goals of Pregnancy Village resonated with key partners. Most organizations identified resource constraints and other participation barriers; all committed to the requested 12-month pilot. During its first year, 10 pilot events were held with consistent organizational participation and high provider engagement. CONCLUSION: Through deep engagement and equitable partnerships between community and institutional stakeholders, novel systems of care delivery can be implemented to better meet comprehensive community needs.

Elevating Women's Voices: The Illinois Maternal Health Digital Storytelling Project.

Numerous initiatives at the national, state, and local levels are focused on addressing the U.S. maternal health crisis. However, most efforts fail to center women's voices and personal perspectives about pregnancy experiences and complications. This article describes the Illinois Maternal Health Digital Storytelling Project conducted by the University of Illinois at Chicago, in partnership with StoryCenter, a storytelling nonprofit organization based in Berkeley, California. The project aimed to elevate voices (stories) to complement other sources of data on maternal outcomes. We relied on partners to help recruit storytellers with a self-identified perinatal-related challenge. We screened interested individuals using a trauma-informed approach and a social worker provided storytellers with support during the project. Two groups participated in this project, one in 2021 and another in 2022, culminating with 10 digital stories. Both instances were conducted virtually and included group and individual skills-based sessions where storytellers learned to create and edit their digital stories. The storytellers own their digital stories and provided consent to include them in ongoing dissemination efforts. In September 2021, a webpage was launched to house the stories, and this resource is being shared widely. Evaluation efforts of the webpage are ongoing to understand how these digital stories are being used to inform maternal health efforts. Digital stories add richness to ongoing maternal health prevention work and may serve as a powerful tool to elicit understanding among providers, practitioners, and constituents.

'Asram is really killing us here': attribution for pregnancy losses and newborn mortality in the Ashanti Region of Ghana.

While overall neonatal mortality rates are improving in Ghana, the Ashanti Region has the highest mortality rate in the country. The clinical causes of newborn deaths are well known, yet local beliefs about illness aetiology, cause of death and care-seeking are less well understood. This exploratory qualitative study sought to understand how community members perceive and respond to neonatal illness. Researchers worked with public health nurses, community health nurses and opinion leaders in the Ashanti Region of Ghana to identify women who had lost a baby, either during pregnancy or after delivery. In-depth interviews and focus group discussions were conducted about knowledge, attitudes and beliefs regarding neonatal mortality. The transcripts were coded and analysed using NVivo 10.0. A total of 100 participants were interviewed: 24% reported a previous stillbirth; 37% reported a previous miscarriage; and 45% reported losing a baby who was born alive. Nine per cent experienced more than one type of loss. The local illness of asram - an illness with supernatural causes - was cited as a leading cause of death of newborns. Every participant reported hearing of, knowing someone, or having a child who had become ill with asram. While women gave varying information on symptoms, method of contraction and treatment, all participants agreed that asram was common and often fatal. Four overarching themes emerged: 1) asram is not a hospital sickness; 2) there is both a fear of traditional healers as a source of asram, as well as a reliance upon them to cure asram; 3) there are rural/urban differences in perceptions of asram; and 4) asram may serve as a mechanism of social control for pregnant women and new mothers. Local beliefs and practices must be better understood and incorporated into health education campaigns if neonatal mortality is to be reduced in Ghana.

'This sickness is not hospital sickness': a qualitative study of the evil eye as a source of neonatal illness in Ghana.

Previous research has described the evil eye as a source of illness for pregnant women and their newborns. This study sought to explore the perceptions of the evil eye among mothers whose newborns had experienced a life-threatening complication across three regions of Ghana. As part of a larger, quantitative study, trained research assistants identified pregnant and newly delivered women (and their newborns) who had survived a life-threatening complication at three tertiary care hospitals in southern Ghana to participate in open-ended, qualitative interviews about their experiences in March-August 2015. All interviews were audio-recorded and transcribed verbatim into English and analysis using the constant comparative method of theme generation. A total of 37 mothers were interviewed, 20 about neonatal illnesses and 17 about maternal illnesses. Six of the 20 mothers interviewed about their newborn's illnesses spoke at length about the evil eye being a potential cause of newborn illness. The evil eye was described in a variety of terms, but commonalities included a person looking at a pregnant woman, her newborn baby, the baby's clothes and even the mother's food, causing harm, even unintentionally. Prevention required mothers covering themselves while pregnant and keeping the baby away from others until it was old enough to ward off the evil eye. Treatment required traditional medicine, yet some indicated that allopathic medicine could help. The evil eye appears to serve a social control mechanism, encouraging pregnant women to dress modestly, stay indoors as much as possible and behave appropriately. The evil eye is a pervasive, universally understood phenomenon across three regions of Ghana, even amongst a hospitalized population receiving allopathic health care for life-threatening complications of childbirth. Understanding the role of the evil eye in newborn illness attribution is important for clinicians, researchers and programmatic staff to effectively address barriers to care seeking.

Neonatal near-misses in Ghana: a prospective, observational, multi-center study.

BACKGROUND: For every newborn who dies within the first month, as many as eight more suffer life-threatening complications but survive (termed 'neonatal near-misses' (NNM)). However, there is no universally agreed-upon definition or assessment tool for NNM. This study sought to describe the development of the Neonatal Near-Miss Assessment Tool (NNMAT) for low-resource settings, as well as findings when implemented in Ghana. METHODS: This prospective, observational study was conducted at two tertiary care hospitals in southern Ghana from April - July 2015. Newborns with evidence of complications and those admitted to the NICUs were screened for inclusion using the NNMAT. Incidence of suspected NNM at enrollment and confirmed near-miss (surviving to 28 days) was determined and compared against institutional neonatal mortality rates. Suspected NNM cases were compared with newborns not classified as a suspected near-miss, and all were followed to 28 days to determine odds of survival. Confirmed near-misses were those identified as suspected near-misses at enrollment who survived to 28 days. The main outcome measures were incidence of NNM, NNM:mortality ratio, and factors associated with NNM classification. RESULTS: Out of 394 newborns with complications, 341 (86.5%) were initially classified as suspected near-misses at enrollment using the NNMAT, with 53 (13.4%) being classified as a non-near-miss. At 28-day follow-up, 68 (17%) had died, 52 (13%) were classified as a non-near-miss, and 274 were considered confirmed near-misses. Those newborns with complications who were classified as suspected near-misses using the NNMAT at enrollment had 12 times the odds of dying before 28 days than those classified as non-near-misses. While most confirmed near-misses qualified as NNM via intervention-based criteria, nearly two-thirds qualified based on two or more of the four NNMAT categories. When disaggregated, the most predictive elements of the NNMAT were gestational age < 33 weeks, neurologic dysfunction, respiratory dysfunction, and hemoglobin < 10 gd/dl. The ratio of near-misses to deaths was 0.55: 1, yet this varied across the study sites. CONCLUSIONS: This research suggests that the NNMAT is an effective tool for assessing neonatal near-misses in low-resource settings. We believe this approach has significant systems-level, continuous quality improvement, clinical and policy-level implications.

Murine thymic NK cells are distinct from ILC1s and have unique transcription factor requirements.

Group 1 innate lymphoid cells include natural killer (NK) cells and ILC1s, which mediate the response to intracellular pathogens. Thymic NK (tNK) cells were described with hybrid features of immature NK cells and ILC1 but whether these cells are related to NK cells or ILC1 has not been fully investigated. We report that murine tNK cells expressed the NK-cell associated transcription factor EOMES and developed independent of the essential ILC1 factor TBET, confirming their placement within the NK lineage. Moreover, tNK cells resemble NK cells rather than ILC1 in their requirements for the E protein transcription factor inhibitor ID2. We provide further insight into the mechanisms governing tNK-cell development by showing that the transcription factor ETS1 prevented tNK cell acquisition of the conventional NK-cell maturation markers CD11b and KLRG1. Our data reveal few ILC1 in the thymus and clarify the identity and developmental requirements of tNK cells.

Understanding how COVID-19 affected black pregnant women early in the pandemic: A cross-sectional survey.

OBJECTIVE: Previous research has shown that the COVID-19 pandemic significantly increased anxiety among pregnant women, and at the same time, COVID-19 has disproportionately affected communities of color in the United States. We sought to understand how self-identied Black pregnant women in the United States were affected in the early days of the COVID-19 pandemic. DESIGN: Cross-sectional, online survey distributed via social media SETTING: Online PARTICIPANTS: Non-probability, convenience sample of self-identified Black pregnant women in the United States between April 3 and 24, 2020 who responded to an online inquiry seeking women who were pregnant at the outset of the COVID-19 pandemic. MEASUREMENTS AND FINDINGS: An anonymous, self-administered, online survey of pregnant women was conducted, including both quantitative assessment of demographics, COVID-related anxiety, and pregnancy-related anxiety as well as open-ended prompts for qualitative assessment of the impact of COVID on prenatal care, birth plans, anxiety and overall experience of pregnancy. Quantitative data were analyzed using Stata 15.0, qualitative data were thematically analyzed using NVivo12.1. Results were compared using joint display methodology. Of 87 self-identified Black or African-American women who responded, the most common concerns related to fear of getting infected with COVID (89.7 %, N = 78) and concerns related to loss of job/income (67.8 %, N = 59). More than half (55.2 %, N = 48) reported either themselves or their family members working in essential services. Findings indicate that uncertainty, lack of support, perceived quality of care, and heightened anxiety worked together to define Black women's experiences of pregnancy in the early days of the COVID-19 pandemic in the U.S. While quantitative data did not explicitly capture reports of discrimination as impacting perceived quality of care, the qualitative data suggest a link between fears of discrimination, the need for self-advocacy, and heightened anxiety. KEY CONCLUSIONS: Despite being a relatively well-educated sample of Black women from around the United States, many respondents spoke of the fears of discrimination, the need for self-advocacy, and heightened anxiety, reinforcing that discrimination and fear of discrimation for Black women in healthcare settings are pervasive, regardless of a woman's level of education or other socioeconomic status indicators. IMPLICATIONS FOR PRACTICE: These findings suggest that in times of uncertainty, such as the early days of the COVID-19 pandemic, it is more important than ever to provide thoughtful, supportive care to pregnant women of color who are primed for negative experiences in the healthcare settting.

"These are good problems to have ": establishing a collaborative research partnership in East Africa.

In the context of a long-term institutional 'twinning' partnership initiated by Indiana and Moi Universities more than 22 years ago, a vibrant program of research has arisen and grown in size and stature. The history of the AMPATH (Academic Model Providing Access to Healthcare) Research Program is described, with its distinctive attention to Kenyan-North American equity, mutual benefit, policies that support research best practices, peer review within research working groups/cores, contributions to clinical care, use of healthcare informatics, development of research infrastructure and commitment to research workforce capacity. In the development and management of research within our partnership, we describe a number of significant challenges we have encountered that require ongoing attention, many of which are "good problems" occasioned by the program's success and growth. Finally, we assess the special value a partnership program like ours has created and end by affirming the importance of organizational diversity, solidarity of purpose, and resilience in the 'research enterprise.'

Advanced Age in Humans and Mouse Models of Glioblastoma Show Decreased Survival from Extratumoral Influence.

PURPOSE: Glioblastoma (GBM) is the most common aggressive primary malignant brain tumor in adults with a median age of onset of 68 to 70 years old. Although advanced age is often associated with poorer GBM patient survival, the predominant source(s) of maladaptive aging effects remains to be established. Here, we studied intratumoral and extratumoral relationships between adult patients with GBM and mice with brain tumors across the lifespan. EXPERIMENTAL DESIGN: Electronic health records at Northwestern Medicine and the NCI SEER databases were evaluated for GBM patient age and overall survival. The commercial Tempus and Caris databases, as well as The Cancer Genome Atlas were profiled for gene expression, DNA methylation, and mutational changes with varying GBM patient age. In addition, gene expression analysis was performed on the extratumoral brain of younger and older adult mice with or without a brain tumor. The survival of young and old wild-type or transgenic (INK-ATTAC) mice with a brain tumor was evaluated after treatment with or without senolytics and/or immunotherapy. RESULTS: Human patients with GBM ≥65 years of age had a significantly decreased survival compared with their younger counterparts. While the intra-GBM molecular profiles were similar between younger and older patients with GBM, non-tumor brain tissue had a significantly different gene expression profile between young and old mice with a brain tumor and the eradication of senescent cells improved immunotherapy-dependent survival of old but not young mice. CONCLUSIONS: This work suggests a potential benefit for combining senolytics with immunotherapy in older patients with GBM.

A systematic review of pharmacologic treatment efficacy for depression in older patients with cancer.

Background: Older adults ≥65 years of age represent the majority of new cancer diagnoses and are vulnerable to developing depression-like symptoms. Evaluation and management of depression in older cancer patients is underappreciated despite its high prevalence and impact on health-related quality of life. Although antidepressants are the primary pharmacologics used to treat depressive-like symptoms, the efficacy and overall benefit(s) are not well-characterized in older adult patients with cancer. The objective of this investigation was to review what is known about the efficacy of pharmacologic treatment for older adults with depression and cancer. Methods: PubMed (Medline) and EMBASE (Elsevier) databases were analyzed for relevant literature in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: 1,919 unique studies were identified for title and abstract screening. Forty-eight publications were retrieved for full review. None of the identified studies evaluated the potential for benefit after pharmacological treatment among older adults with cancer and depression. Twenty-seven publications met all study criteria except for an analysis focused on older patients. Conclusion: We discovered a universal absence of literature with a relevance to pharmacologic antidepressant treatment effects in older adult patients with cancer. This included a lack of evaluation in patients with brain tumors who have an unusually high predilection for developing depression. Our findings suggest that new research is critically needed for understanding optimal clinical management strategies in older adults with cancer and depression who are treated with antidepressants.

Identification and Characterization of a Novel Indoleamine 2,3-Dioxygenase 1 Protein Degrader for Glioblastoma.

Indoleamine 2,3-dioxygenase 1 (IDO1) is a potent immunosuppressive enzyme that inhibits the antitumor immune response through both tryptophan metabolism and non-enzymatic functions. To date, most IDO1-targeted approaches have focused on inhibiting tryptophan metabolism. However, this class of drugs has failed to improve the overall survival of patients with cancer. Here, we developed and characterized proteolysis targeting chimeras (PROTACs) that degrade the IDO1 protein. IDO1-PROTACs were tested for their effects on IDO1 enzyme and non-enzyme activities. After screening a library of IDO1-PROTAC derivatives, a compound was identified that potently degraded the IDO1 protein through cereblon-mediated proteasomal degradation. The IDO1-PROTAC: (i) inhibited IDO1 enzyme activity and IDO1-mediated NF-κB phosphorylation in cultured human glioblastoma (GBM) cells, (ii) degraded the IDO1 protein within intracranial brain tumors in vivo, and (iii) mediated a survival benefit in mice with well-established brain tumors. This study identified and characterized a new IDO1 protein degrader with therapeutic potential for patients with glioblastoma.

Police brutality and unmet need for mental health care.

OBJECTIVE: National movements have raised awareness of the adverse mental health effects of police brutality. This study examines the relationship between perceived police brutality and unmet need for mental health care. DATA SOURCES: We used the 2018 Survey of the Health of Urban Residents (N = 4338), a quota sample survey of adults in urban areas in the contiguous United States. STUDY DESIGN: Multivariate regressions were used to understand the association between police brutality and unmet need for mental health care. Unmet need was regressed on police brutality (the independent variable), controlling for sociodemographic and health status characteristics of respondents and access to care. We then stratified the sample by experiences of police brutality (no negative encounters with the police, encounters that were perceived as necessary, and encounters that were considered unnecessary) and described how medical mistrust and perceived respect within health care settings were associated with odds of unmet need for each subsample. DATA COLLECTION: Data were collected online. PRINCIPAL FINDINGS: Negative police encounters perceived as necessary were associated with greater odds of unmet need compared to no negative police encounters (odds ratio [OR] = 1.98, confidence interval [CI] = 1.30-2.65). Odds of unmet need were also higher among persons with negative and unnecessary police encounters (OR = 1.28, CI = 1.05-1.56). Greater respect was associated with lower odds of unmet need among persons who reported negative unnecessary encounters with the police (OR = 0.88, CI = 0.72-0.97). Medical mistrust was associated with greater odds of unmet need among those with negative unnecessary police encounters (OR = 1.52, CI = 1.12-1.93). CONCLUSIONS: Persons who are exposed to police brutality are also likely to be those who experience unmet need for mental health care. Ensuring that they feel respected within medical settings and establishing conditions that build trust in medical institutions are important for eliminating unmet need for mental health care.

Tumor Cell IDO Enhances Immune Suppression and Decreases Survival Independent of Tryptophan Metabolism in Glioblastoma.

PURPOSE: Glioblastoma (GBM) is an incurable primary brain tumor that has not benefited from immunotherapy to date. More than 90% of GBM expresses the tryptophan (Trp) metabolic enzyme, indoleamine 2,3-dioxygenase 1 (IDO). This observation supported the historical hypothesis that IDO suppresses the antitumor immune response solely through a mechanism that requires intratumoral Trp depletion. However, recent findings led us to investigate the alternative hypothesis that IDO suppresses the anti-GBM immune response independent of its association with Trp metabolism. EXPERIMENTAL DESIGN: IDO-deficient GBM cell lines reconstituted with IDO wild-type or IDO enzyme-null cDNA were created and validated in vitro and in vivo. Microarray analysis was conducted to search for genes that IDO regulates, followed by the analysis of human GBM cell lines, patient GBM and plasma, and The Cancer Genome Atlas (TCGA) database. Ex vivo cell coculture assays, syngeneic and humanized mouse GBM models, were used to test the alternative hypothesis. RESULTS: Nonenzymic tumor cell IDO activity decreased the survival of experimental animals and increased the expression of complement factor H (CFH) and its isoform, factor H like protein 1 (FHL-1) in human GBM. Tumor cell IDO increased CFH and FHL-1 expression independent of Trp metabolism. Increased intratumoral CFH and FHL-1 levels were associated with poorer survival among patients with glioma. Similar to IDO effects, GBM cell FHL-1 expression increased intratumoral regulatory T cells (Treg) and myeloid-derived suppressor cells while it decreased overall survival in mice with GBM. CONCLUSIONS: Our study reveals a nonmetabolic IDO-mediated enhancement of CFH expression and provides a new therapeutic target for patients with GBM.

Glioblastoma as an age-related neurological disorder in adults.

BACKGROUND: Advanced age is a major risk factor for the development of many diseases including those affecting the central nervous system. Wild-type isocitrate dehydrogenase glioblastoma (IDHwt GBM) is the most common primary malignant brain cancer and accounts for ≥90% of all adult GBM diagnoses. Patients with IDHwt GBM have a median age of diagnosis at 68-70 years of age, and increasing age is associated with an increasingly worse prognosis for patients with this type of GBM. METHODS: The Surveillance, Epidemiology, and End Results, The Cancer Genome Atlas, and the Chinese Glioma Genome Atlas databases were analyzed for mortality indices. Meta-analysis of 80 clinical trials was evaluated for log hazard ratio for aging to tumor survivorship. RESULTS: Despite significant advances in the understanding of intratumoral genetic alterations, molecular characteristics of tumor microenvironments, and relationships between tumor molecular characteristics and the use of targeted therapeutics, life expectancy for older adults with GBM has yet to improve. CONCLUSIONS: Based upon the results of our analysis, we propose that age-dependent factors that are yet to be fully elucidated, contribute to IDHwt GBM patient outcomes.

The association of COVID-19 infection in pregnancy with preterm birth: A retrospective cohort study in California.

INTRODUCTION: Our understanding of the association between coronavirus disease 19 (COVID-19) and preterm or early term birth among racially and ethnically diverse populations and people with chronic medical conditions is limited. METHODS: We determined the association between COVID-19 and preterm (PTB) birth among live births documented by California Vital Statistics birth certificates between July 2020 and January 2021 (n=240,147). We used best obstetric estimate of gestational age to classify births as very preterm (VPTB, <32 weeks), PTB (< 37 weeks), early term (37 and 38 weeks), and term (39-44 weeks), as each confer independent risks to infant health and development. Separately, we calculated the joint effects of COVID-19 diagnosis, hypertension, diabetes, and obesity on PTB and VPTB. FINDINGS: COVID-19 diagnoses on birth certificates increased for all racial/ethnic groups between July 2020 and January 2021 and were highest for American Indian/Alaska Native (12.9%), Native Hawaiian/Pacific Islander (11.4%), and Latinx (10.3%) birthing people. COVID-19 diagnosis was associated with an increased risk of VPTB (aRR 1.6, 95% CI [1.4, 1.9]), PTB (aRR 1.4, 95% CI [1.3, 1.4]), and early term birth (aRR 1.1, 95% CI [1.1, 1.2]). There was no effect modification of the overall association by race/ethnicity or insurance status. COVID-19 diagnosis was associated with elevated risk of PTB in people with hypertension, diabetes, and/or obesity. INTERPRETATION: In a large population-based study, COVID-19 diagnosis increased the risk of VPTB, PTB, and early term birth, particularly among people with medical comorbidities. Considering increased circulation of COVID-19 variants, preventative measures, including vaccination, should be prioritized for birthing persons. FUNDING: UCSF-Kaiser Department of Research Building Interdisciplinary Research Careers in Women's Health Program (BIRCWH) National Institute of Child Health and Human Development (NICHD) and the Office of Research on Women's Health (ORWH) [K12 HD052163] and the California Preterm Birth Initiative, funded by Marc and Lynn Benioff.

Assessment of changes in condom use among female sex workers in a prospective cohort study introducing diaphragm use for disease prevention.

Changes in the rates of condom use and number of sexual partners were evaluated among 140 female sex workers in Kibera, Kenya, participating in a 6-month study of diaphragm safety and acceptability for prevention of sexually transmitted infections conducted in 2004-2005. Analyses were stratified by partner type. Multivariable Tobit regression modeling was used to assess the association between study visit and proportion of acts protected. Participants completed 140 baseline visits and 390 bimonthly follow-up visits. The mean percentage of coital acts reported as protected by a condom increased from 56% at baseline to 68% at the 6-month visit (P < 0.01). Similar increases were observed for condom use by all partner types. Additionally, the mean number of sexual partners decreased over the study. Furthermore, consistent (i.e., 100%) diaphragm use during follow-up was associated with a higher proportion of coital acts protected by a condom in analyses adjusted for study visit and coital frequency. These findings suggest that, despite concerns that introduction of the diaphragm would result in more risky sexual behaviors, reported condom use increased and number of partners decreased.

Intravaginal practices among female sex workers in Kibera, Kenya.

OBJECTIVES: To assess vaginal cleansing and lubricant use among female sex workers (FSW) in Kenya participating in a 6-month, prospective study of the acceptability of the use of the diaphragm. METHODS: The study is based on 140 FSW in Nairobi, who completed 140 baseline visits and 390 bi-monthly follow-up visits. Participants were instructed to wear the diaphragm for all coital acts during follow-up and to refrain from vaginal cleansing while wearing the diaphragm. Logistic regression was used to identify predictors of recent vaginal cleansing to 'tighten' the vagina reported at baseline; recent vaginal cleansing to prevent infection reported at baseline; recent vaginal cleansing with the diaphragm in place reported during follow-up; and recent use of oil-based lubricant during coitus reported at baseline. RESULTS: At baseline, 99% of women reported vaginal cleansing in the previous 2 weeks for purposes of hygiene or to remove evidence of past coitus. Approximately 41% of women also reported cleansing in the past 2 weeks to 'tighten' the vagina. Women reported vaginal cleansing with the diaphragm in place in the past 2 weeks at 14% of follow-up visits in which the diaphragm was used. Predictors of such cleansing included young age, 6-month study visit, being divorced or widowed and higher educational level. CONCLUSIONS: While vaginal cleansing is a modifiable behaviour, given that cleansing for hygiene was almost universal among this study population at baseline and that more women reported cleansing while wearing the diaphragm as the study progressed, the complete eradication of the practice would probably be difficult.

Diaphragm for STI and HIV prevention: is it a safe method for women at high risk?

Female sex workers (n = 140) were enrolled in a 6-month acceptability trial of the diaphragm. We randomized a subset (n = 40) to receive colposcopies after 1 month of diaphragm use or after 1 month of observation before commencing diaphragm use. Adverse events were mild in nature. Frequency of colposcopic findings did not differ between women randomized to immediate versus delayed diaphragm use (P = 0.25).

Experience implementing electronic health records in three East African countries.

INTRODUCTION: Efficient use of health care resources in low-income countries by providers and local and national managers requires timely access to patient data. OBJECTIVE: To implement electronic health records (EHRs) in HIV clinics in Kenya, Tanzania, and Uganda. RESULTS: We initially developed and implemented an EHR in Kenya through a mature academic partnership. The EHR was then implemented in six HIV clinics in Tanzania and Uganda in collaboration with their National AIDS Control Programmes. All implementations were successful, but the system's use and sustainability varied depending on who controlled clinic funding. CONCLUSIONS: Successful EHR use and sustainability were enhanced by local control of funds, academic partnerships (mainly by leveraging research funds), and in-country technology support.

Immunosuppressive IDO in Cancer: Mechanisms of Action, Animal Models, and Targeting Strategies.

Indoleamine 2, 3-dioxygenase 1 (IDO; IDO1; INDO) is a rate-limiting enzyme that metabolizes the essential amino acid, tryptophan, into downstream kynurenines. Canonically, the metabolic depletion of tryptophan and/or the accumulation of kynurenine is the mechanism that defines how immunosuppressive IDO inhibits immune cell effector functions and/or facilitates T cell death. Non-canonically, IDO also suppresses immunity through non-enzymic effects. Since IDO targeting compounds predominantly aim to inhibit metabolic activity as evidenced across the numerous clinical trials currently evaluating safety/efficacy in patients with cancer, in addition to the recent disappointment of IDO enzyme inhibitor therapy during the phase III ECHO-301 trial, the issue of IDO non-enzyme effects have come to the forefront of mechanistic and therapeutic consideration(s). Here, we review enzyme-dependent and -independent IDO-mediated immunosuppression as it primarily relates to glioblastoma (GBM); the most common and aggressive primary brain tumor in adults. Our group's recent discovery that IDO levels increase in the brain parenchyma during advanced age and regardless of whether GBM is present, highlights an immunosuppressive synergy between aging-increased IDO activity in cells of the central nervous system that reside outside of the brain tumor but collaborate with GBM cell IDO activity inside of the tumor. Because of their potential value for the in vivo study of IDO, we also review current transgenic animal modeling systems while highlighting three new constructs recently created by our group. This work converges on the central premise that maximal immunotherapeutic efficacy in subjects with advanced cancer requires both IDO enzyme- and non-enzyme-neutralization, which is not adequately addressed by available IDO-targeting pharmacologic approaches at this time.