Biophysical characterization of chloride intracellular channel 6 (CLIC6).

Chloride intracellular channels (CLICs) are a family of proteins that exist in soluble and transmembrane forms. The newest discovered member of the family CLIC6 is implicated in breast, ovarian, lung gastric, and pancreatic cancers and is also known to interact with dopamine-(D(2)-like) receptors. The soluble structure of the channel has been resolved, but the exact physiological role of CLIC6, biophysical characterization, and the membrane structure remain unknown. Here, we aimed to characterize the biophysical properties of this channel using a patch-clamp approach. To determine the biophysical properties of CLIC6, we expressed CLIC6 in HEK-293 cells. On ectopic expression, CLIC6 localizes to the plasma membrane of HEK-293 cells. We established the biophysical properties of CLIC6 by using electrophysiological approaches. Using various anions and potassium (K+) solutions, we determined that CLIC6 is more permeable to chloride-(Cl-) as compared to bromide-(Br-), fluoride-(F-), and K+ ions. In the whole-cell configuration, the CLIC6 currents were inhibited after the addition of 10 µM of IAA-94 (CLIC-specific blocker). CLIC6 was also found to be regulated by pH and redox potential. We demonstrate that the histidine residue at 648 (H648) in the C terminus and cysteine residue in the N terminus (C487) are directly involved in the pH-induced conformational change and redox regulation of CLIC6, respectively. Using qRT-PCR, we identified that CLIC6 is most abundant in the lung and brain, and we recorded the CLIC6 current in mouse lung epithelial cells. Overall, we have determined the biophysical properties of CLIC6 and established it as a Cl- channel.

HIV Linkage to Care and Pre-Exposure Prophylaxis Among Persons in Non-Health Care Sites Who Are Tested for HIV for the First Time, United States, 2019.

CONTEXT: The Centers for Disease Control and Prevention recommends that all persons aged 13 to 64 years are tested for human immunodeficiency virus (HIV). However, results from US surveys show that 50% of persons and less had ever tested for HIV. PROGRAM: The Centers for Disease Control and Prevention annually funds 60 health departments to conduct comprehensive HIV prevention and surveillance activities that include HIV testing. IMPLEMENTATION: We selected the 31 health departments with quality data (ie, ≤20% missing or invalid values for variables to verify linkage to HIV medical care and new HIV diagnoses) in 2019. Main outcomes were new HIV diagnoses, linkage, and pre-exposure prophylaxis (PrEP) awareness and referrals. We used SAS 9.4 to conduct descriptive, chi-square, and multivariate regression analyses. Our objectives were to determine outcomes and characteristics of persons in non-health care settings who tested for HIV for the first time. EVALUATION: Compared with persons who previously tested for HIV, persons who tested for the first time were more likely to be aged 13 to 29 years than aged 30 years and older (62.0% [24 295/39 192] vs 42.1% [61 911/147 087], P < .001) and have a higher percentage of new HIV diagnoses (0.6% [242/39 320] vs 0.5% [667/147 475], P < .001). Among persons who tested for the first time, overall percentages of linkage, PrEP awareness, and PrEP referral were 73.4%, 33.3%, and 30.8%, respectively. Compared with referent groups, persons who tested for the first time in the South and had a new HIV diagnosis were less likely to be linked (adjusted prevalence ratio [aPR] = 0.72, 95% confidence interval [CI]: 0.59-0.89); persons who inject drugs were less likely to be aware of PrEP (aPR = 0.84, 95% CI: 0.77-0.91); and persons in the Northeast were less likely to receive PrEP referrals (aPR = 0.28, 95% CI: 0.26-0.31). DISCUSSION: Non-health care sites should consider increasing HIV testing, PrEP awareness, and prompt referrals to PrEP and HIV treatment services for persons who have never previously tested.

Factors Associated With Partner Notification, Testing, and Positivity in HIV Partner Services Programs in the United States, 2013 to 2017.

BACKGROUND: Human immunodeficiency virus (HIV) partner services are an essential component of comprehensive HIV prevention and care. We examined factors associated with partner notification, HIV testing, and HIV positivity among partners of HIV-diagnosed persons (index persons) contacted by Centers for Disease Control and Prevention (CDC)-funded state and local health departments. METHODS: We analyzed partner service data submitted to the CDC by 61 state and local health departments from 2013 to 2017. Using multivariate Poisson regression-adjusted for clustering effects among partners reported by a common index person-we assessed associations between 3 outcomes of interest (partner notification, HIV testing, and HIV positivity) and the demographic characteristics, risk behaviors, geographic region, and service year of index persons and their partners. RESULTS: A total of 51,368 sexual and/or needle-sharing partners were matched with 33,524 index persons. Of notifiable partners, 97.2% were notified of their potential HIV exposure, and 52.3% were tested for HIV. Among 21,842 notified and tested partners, 23.8% were newly diagnosed with an HIV infection. Partner notification, HIV testing, and HIV positivity were associated with both partner and index person characteristics (individually and interactively), geographic region, and year of service. CONCLUSIONS: Partner service programs provided through CDC-funded health departments were effective in both partner notification and identification of undiagnosed HIV infection among partners. However, HIV testing rate among notified partners remained low. Implementing strategies to address gaps in HIV testing can contribute toward ending the HIV epidemic in the United States.

Trends in Condomless Sex Among MSM Who Participated in CDC-Funded HIV Risk-Reduction Interventions in the United States, 2012-2017.

Consistent and correct use of condoms can reduce the risk for sexually transmitted diseases, including HIV/AIDS. Studies have reported that condomless sex among men who have sex with men (MSM) has steadily increased in recent years. We analyzed data reported by 51 health departments regarding 82 556 HIV-positive and HIV-negative MSM 13 years or older and participated in Centers for Disease Control and Prevention-funded behavioral risk-reduction intervention programs during 2012-2017. The percentages of condomless sex increased from 56.3% to 72.0% (estimated annual percent change [EAPC] = 7.1%) among HIV-positive MSM and from 46.0% to 70.5% (EAPC = 4.1%) among HIV-negative MSM. Continued increases in condomless sex might disrupt progress in ending the HIV/AIDS epidemic. Transmission risk associated with condomless sex can be reduced by ensuring that HIV-positive persons know their status early and are linked to care to achieve viral suppression and those at risk for acquiring HIV/AIDS can readily access preexposure prophylaxis.

HIV Preexposure Prophylaxis Awareness and Referral to Providers Among Hispanic/Latino Persons - United States, 2019.

Hispanic or Latino* (Hispanic) persons are disproportionately affected by HIV in the United States. In 2019, Hispanic persons accounted for 18% of the U.S. population, but for 29% of new diagnoses of HIV infection (1). The Ending the HIV Epidemic in the U.S. (EHE) initiative aims to reduce new HIV infections by 90% by 2030 (2). Preexposure prophylaxis (PrEP), medication taken to prevent acquisition of HIV, is an effective strategy for preventing HIV infection.† To examine PrEP awareness and referral to providers among Hispanic persons, CDC analyzed 2019 National HIV Prevention Program Monitoring and Evaluation HIV testing data. Approximately one quarter (27%) of Hispanic persons tested for HIV at CDC-funded sites (n = 310,954) were aware of PrEP, and 22% of those who received a negative HIV test result and were eligible for referral (111,644) were referred to PrEP providers. PrEP awareness and referrals among Hispanic persons were lower compared with those among non-Hispanic White persons. Among Hispanic persons, significant differences were found in PrEP awareness and referrals by age, gender, race, population group, geographic region, and test setting. HIV testing programs can expand PrEP services for Hispanic persons by implementing culturally and linguistically appropriate strategies that routinize PrEP education and referral, collaborating with health care and other providers, and addressing social and structural barriers.

Human Immunodeficiency Virus Testing, Diagnosis, Linkage to Care, and Prevention Services Among Persons Who Inject Drugs, United States, 2012-2017.

BACKGROUND: Human immunodeficiency virus (HIV) testing and early diagnosis is associated with effective disease management and reduction in HIV transmission among persons who inject drugs (PWID). We examined trends in HIV testing outcomes among PWID during 2012-2017. METHODS: Centers for Disease Control and Prevention (CDC)-funded HIV testing data submitted by 61 health departments and 150 directly-funded community-based organizations during 2012-2017 were analyzed. We calculated estimated annual percentage changes (EAPC) to assess trends for HIV testing and testing outcomes. RESULTS: A total of 19 739 857 CDC-funded HIV tests were conducted during 2012-2017. Of these, 529 349 (2.7%) were among PWID. The percentage of newly diagnosed HIV increased from .7% in 2012 to .8% in 2017 (EAPC, 4.15%). The percentage interviewed for partner services increased from 46.7% in 2012 to 66.3% in 2017 (EAPC, 1.81%). No significant change was identified in trends for linkage to HIV medical care ≤90 days after diagnosis (EAPC, 0.52%) or referral to HIV prevention services (EAPC, 0.98%). CONCLUSIONS: Human immunodeficiency virus testing data revealed an increasing trend in newly diagnosed HIV among PWID but not linkage to HIV medical care or referral to prevention services. Expanding efforts to increase HIV testing and enhance linkage to services can lead to reductions in HIV transmission and improved health outcomes.

HIV Partner Service Delivery Among Transgender Women - United States, 2013-2017.

Transgender women* in the United States are disproportionately affected by human immunodeficiency virus (HIV) infection because of multiple factors, including stigma related to gender identity, unstable housing, limited employment options, and high-risk behaviors, such as sex work, unprotected receptive anal intercourse, and injection drug use, that tend to increase their vulnerability to becoming infected with HIV (1,2). In a recent meta-analysis of 88 U.S. studies conducted during 2006-2017, the mean estimated laboratory-confirmed prevalence of HIV infection among transgender women was 14.2%, and the mean self-reported prevalence estimate was 21.0% (3). The Ending the HIV Epidemic initiative calls for accelerating the implementation of evidence-based strategies in the right geographic areas targeted to the right persons to end the HIV epidemic in the United States (4). HIV partner services are effective strategies offered by public health workers to persons with a diagnosis of HIV infection (index persons) and their sex or needle-sharing partners (partners), who are notified of potential HIV exposure and offered HIV testing and related services. CDC analyzed HIV partner services data submitted by 61 health departments† during 2013-2017. Among 208,304 index persons, 1,727 (0.8%) were transgender women. Overall, 71.5% of index transgender women were interviewed for partner services, which was lower than that for all index persons combined (81.1%). Among 1,089 transgender women named as partners by index persons, 71.2% were notified of potential HIV exposure, which was lower than that for all partners combined (77.1%). Fewer than half (46.5%) of notified transgender women partners were tested for HIV, and approximately one in five (18.6%) of those who were tested received a new diagnosis of HIV infection, slightly higher than for all partners combined (17.6%). Additional efforts are needed to effectively implement partner services among transgender women and identify those whose infection with HIV is undiagnosed, provide timely prevention and care services, reduce HIV transmission, and contribute to ending the HIV epidemic.

HIV Testing Outcomes Among Blacks or African Americans - 50 Local U.S. Jurisdictions Accounting for the Majority of New HIV Diagnoses and Seven States with Disproportionate Occurrences of HIV in Rural Areas, 2017.

Identifying persons with human immunodeficiency virus (HIV) infection who are unaware of their status and linking them to care are critical steps in achieving viral suppression and reducing the risk for transmitting HIV (1). In 2017, 43% of new diagnoses of HIV infection were among persons who self-identify as blacks or African Americans (blacks) (2), who represent 13% of the U.S. population (3). Fewer blacks, compared with whites, were linked to HIV medical care within 90 days of diagnosis, retained in care, or virally suppressed (4). Ending the HIV Epidemic (EHE) is an initiative intended to reduce new HIV infections by 90% from 2020 to 2030 (5). EHE's Phase 1 is focused on 50 jurisdictions* that accounted for >50% of new diagnoses during 2016-2017 and seven states† with disproportionate HIV prevalence in rural areas (5). The purpose of this analysis was to examine HIV testing outcomes among blacks in high prevalence EHE jurisdictions, using CDC's 2017 National HIV Prevention Program Monitoring and Evaluation data. Blacks accounted for 43.2% of CDC-funded tests and 49.1% of new diagnoses of HIV infection. Seventy-nine percent of blacks with newly diagnosed HIV infection were linked to HIV medical care within 90 days (below the 2010 National HIV/AIDS Strategy goal of 85%), 71.4% interviewed for partner services, and 81.8% referred to prevention services. To achieve the goals of EHE, HIV prevention programs should focus on locally tailored evidence-based§ testing strategies to enhance and overcome barriers for linkage to and retention in care and reduce onward HIV transmission and HIV-related disparities.

Control of mitochondrial structure and function by the Yorkie/YAP oncogenic pathway.

Mitochondrial structure and function are highly dynamic, but the potential roles for cell signaling pathways in influencing these properties are not fully understood. Reduced mitochondrial function has been shown to cause cell cycle arrest, and a direct role of signaling pathways in controlling mitochondrial function during development and disease is an active area of investigation. Here, we show that the conserved Yorkie/YAP signaling pathway implicated in the control of organ size also functions in the regulation of mitochondria in Drosophila as well as human cells. In Drosophila, activation of Yorkie causes direct transcriptional up-regulation of genes that regulate mitochondrial fusion, such as opa1-like (opa1) and mitochondria assembly regulatory factor (Marf), and results in fused mitochondria with dramatic reduction in reactive oxygen species (ROS) levels. When mitochondrial fusion is genetically attenuated, the Yorkie-induced cell proliferation and tissue overgrowth are significantly suppressed. The function of Yorkie is conserved across evolution, as activation of YAP2 in human cell lines causes increased mitochondrial fusion. Thus, mitochondrial fusion is an essential and direct target of the Yorkie/YAP pathway in the regulation of organ size control during development and could play a similar role in the genesis of cancer.

HIV Partner Service Delivery Among Blacks or African Americans - United States, 2016.

Identifying persons with human immunodeficiency virus (HIV) infection who are unaware of their infection status, linking them to HIV care, and reducing racial/ethnic disparities are important national HIV prevention goals (1). Blacks/African Americans (blacks)* are disproportionately affected by HIV infection in the United States. Although blacks represent 13% of the U.S. population (2), in 2017, 44% of diagnoses of HIV infection were in blacks, and the rate of new diagnoses in blacks (41.1 per 100,000 persons) was approximately eight times that of non-Hispanic whites (5.1) (3). HIV partner services are offered by health officials to persons with diagnosed HIV infection (index patients) and their sex- or needle-sharing partners, who are notified of their potential HIV exposure and offered HIV testing and related services (4). CDC analyzed 2016 data from the National HIV Prevention Program Monitoring and Evaluation system submitted by 59 health departments.† Among 49,266 index patients identified as potential candidates for partner services, 21,191 (43%) were black. The percentage of black index patients interviewed for partner services (76%) was higher than that for all index patients combined (73%). Among the 11,088 black partners named by index patients, 78% were notified of their potential HIV exposure. Fewer than half (47%) of those notified were tested for HIV infection. Among those tested, one in six (17%) received a new HIV diagnosis. The prevalence of newly diagnosed HIV infection was particularly high among black partners who were gay, bisexual, and other men who have sex with men (MSM) (37%) and transgender persons (38%). Effective implementation of partner services is important to identify HIV infection, link patients to care or reengage them in care, and provide prevention services to reduce HIV transmission.

HIV Testing, Linkage to HIV Medical Care, and Interviews for Partner Services Among Youths - 61 Health Department Jurisdictions, United States, Puerto Rico, and the U.S. Virgin Islands, 2015.

Identifying persons living with human immunodeficiency virus (HIV) who are unaware of their infection, linking them to HIV medical care, and reducing health disparities are important national goals (1). Of the 8,841 teens and young adults aged 13-24 years (collectively referred to as youths in this report) who received a diagnosis of HIV in 2014, 70% were young men who have sex with men (MSM) (2). In the same year, an estimated 52% of young MSM living with HIV were unaware of their infection compared with 15% among all persons living with HIV (3). An average of 22% of high school students who have had sexual intercourse and 33% of young adults (persons aged 18-24 years) reported ever receiving an HIV test (4). CDC recommends screening all persons aged 13-64 years, with annual rescreening for persons at high risk for HIV infection (5). Analysis of CDC-funded program data for youths submitted by 61 health departments in 2015 revealed that young MSM, who accounted for 83% of new diagnoses among all youths in non-health care facilities, received 28% of HIV tests.* The 2020 national goal is to link at least 85% of HIV-positive persons to HIV medical care within 30 days of diagnosis. In this analysis, 66% of youths who received positive test results for HIV infection were linked to care within 90 days of diagnosis. Increasing the number of youths at risk for HIV infection who are tested for HIV on a regular basis and ensuring that youths who receive positive test results for HIV are rapidly linked to and retained in appropriate medical care, including early initiation of antiretroviral therapy, are essential steps for reducing HIV infection in this vulnerable population.

Mitochondrial Changes in Cancer.

Mitochondrial structural and functional integrity defines the health of a cell by regulating cellular metabolism. Thus, mitochondria play an important role in both cell proliferation and cell death. Cancer cells are metabolically altered compared to normal cells for their ability to survive better and proliferate faster. Resistance to apoptosis is an important characteristic of cancer cells and given the contribution of mitochondria to apoptosis, it is imperative that mitochondria could behave differently in a tumor situation. The other feature associated with cancer cells is the Warburg effect, which engages a shift in metabolism. Although the Warburg effect often occurs in conjunction with dysfunctional mitochondria, the relationship between mitochondria, the Warburg effect, and cancer cell metabolism is not clearly decoded. Other than these changes, several mitochondrial gene mutations occur in cancer cells, mitochondrial biogenesis is affected and mitochondria see structural and functional variations. In cancer pharmacology, targeting mitochondria and mitochondria associated signaling pathways to reduce tumor proliferation is a growing field of interest. This chapter summarizes various changes in mitochondria in relevance to cancer, behavior of mitochondria during tumorigenesis, and the progress on using mitochondria as a therapeutic target for cancer.

Invadolysin acts genetically via the SAGA complex to modulate chromosome structure.

Identification of components essential to chromosome structure and behaviour remains a vibrant area of study. We have previously shown that invadolysin is essential in Drosophila, with roles in cell division and cell migration. Mitotic chromosomes are hypercondensed in length, but display an aberrant fuzzy appearance. We additionally demonstrated that in human cells, invadolysin is localized on the surface of lipid droplets, organelles that store not only triglycerides and sterols but also free histones H2A, H2Av and H2B. Is there a link between the storage of histones in lipid droplets and the aberrantly structured chromosomes of invadolysin mutants? We have identified a genetic interaction between invadolysin and nonstop, the de-ubiquitinating protease component of the SAGA (Spt-Ada-Gcn5-acetyltransferase) chromatin-remodelling complex. invadolysin and nonstop mutants exhibit phenotypic similarities in terms of chromosome structure in both diploid and polyploid cells. Furthermore, IX-14(1)/not(1) transheterozygous animals accumulate mono-ubiquitinated histone H2B (ubH2B) and histone H3 tri-methylated at lysine 4 (H3K4me3). Whole mount immunostaining of IX-14(1)/not(1) transheterozygous salivary glands revealed that ubH2B accumulates surprisingly in the cytoplasm, rather than the nucleus. Over-expression of the Bre1 ubiquitin ligase phenocopies the effects of mutating either the invadolysin or nonstop genes. Intriguingly, nonstop and mutants of other SAGA subunits (gcn5, ada2b and sgf11) all suppress an invadolysin-induced rough eye phenotype. We conclude that the abnormal chromosome phenotype of invadolysin mutants is likely the result of disrupting the histone modification cycle, as accumulation of ubH2B and H3K4me3 is observed. We further suggest that the mislocalization of ubH2B to the cytoplasm has additional consequences on downstream components essential for chromosome behaviour. We therefore propose that invadolysin plays a crucial role in chromosome organization via its interaction with the SAGA complex.

Nutritional regulation of stem and progenitor cells in Drosophila.

Stem cells and their progenitors are maintained within a microenvironment, termed the niche, through local cell-cell communication. Systemic signals originating outside the niche also affect stem cell and progenitor behavior. This review summarizes studies that pertain to nutritional effects on stem and progenitor cell maintenance and proliferation in Drosophila. Multiple tissue types are discussed that utilize the insulin-related signaling pathway to convey nutritional information either directly to these progenitors or via other cell types within the niche. The concept of systemic control of these cell types is not limited to Drosophila and may be functional in vertebrate systems, including mammals.

HIV Testing and Outcomes Among Hispanics/Latinos - United States, Puerto Rico, and U.S. Virgin Islands, 2014.

The 2015 National HIV/AIDS Strategy provides an updated plan to address health disparities in communities at high risk for human immunodeficiency virus (HIV) infection (1,2). Hispanics/Latinos* are disproportionately affected by HIV in the United States. In 2014, 23% of HIV diagnoses were among Hispanics/Latinos, who represented 16% of the U.S. population (3). To examine HIV testing services, CDC analyzed 2014 data from the National HIV Prevention Program Monitoring and Evaluation (NHM&E) system submitted by 60 CDC-funded health departments† and 151 community-based organizations. Among Hispanics/Latinos tested, gay, bisexual, and other men who have sex with men (MSM) had the highest percentage of HIV diagnoses (2%). MSM accounted for 19.8% of HIV test events conducted among Hispanics/Latinos and 63.8% of Hispanics/Latinos who received an HIV diagnosis in non-health care settings.§ Approximately 60% of Hispanics/Latinos who received an HIV diagnosis were linked to HIV medical care within 90 days; this percentage was lower in the South than in other U.S. Census regions. HIV prevention programs that are focused on expanding routine HIV screening and targeting and improving linkage to medical care and other services (e.g., partner services) for Hispanics/Latinos can help identify undiagnosed HIV cases and reduce HIV transmission.

The BKCa (slo) channel regulates the cardiac function of Drosophila.

The large conductance, calcium, and voltage-active potassium channels (BKCa) were originally discovered in Drosophila melanogaster as slowpoke (slo). They are extensively characterized in fly models as ion channels for their roles in neurological and muscular function, as well as aging. BKCa is known to modulate cardiac rhythm and is localized to the mitochondria. Activation of mitochondrial BKCa causes cardioprotection from ischemia-reperfusion injury, possibly via modulating mitochondrial function in adult animal models. However, the role of BKCa in cardiac function is not well-characterized, partially due to its localization to the plasma membrane as well as intracellular membranes and the wide array of cells present in mammalian hearts. Here we demonstrate for the first time a direct role for BKCa in cardiac function and cardioprotection from IR injury using the Drosophila model system. We have also discovered that the BKCa channel plays a role in the functioning of aging hearts. Our study establishes the presence of BKCa in the fly heart and ascertains its role in aging heart function.

Chloride ions in health and disease.

Chloride is a key anion involved in cellular physiology by regulating its homeostasis and rheostatic processes. Changes in cellular Cl- concentration result in differential regulation of cellular functions such as transcription and translation, post-translation modifications, cell cycle and proliferation, cell volume, and pH levels. In intracellular compartments, Cl- modulates the function of lysosomes, mitochondria, endosomes, phagosomes, the nucleus, and the endoplasmic reticulum. In extracellular fluid (ECF), Cl- is present in blood/plasma and interstitial fluid compartments. A reduction in Cl- levels in ECF can result in cell volume contraction. Cl- is the key physiological anion and is a principal compensatory ion for the movement of the major cations such as Na+, K+, and Ca2+. Over the past 25 years, we have increased our understanding of cellular signaling mediated by Cl-, which has helped in understanding the molecular and metabolic changes observed in pathologies with altered Cl- levels. Here, we review the concentration of Cl- in various organs and cellular compartments, ion channels responsible for its transportation, and recent information on its physiological roles.

HIV Positivity, Linkage to Medical Care, Interview for Partner Services, and Pre-Exposure Prophylaxis Awareness and Referral Among Men Who Have Sex With Men Tested in Non-healthcare Settings in the United States, 2019.

OBJECTIVES: Gay, bisexual, and other men who have sex with men (MSM) are disproportionately affected by HIV. This study reports data on HIV testing program outcomes among MSM tested for HIV in non-healthcare settings in the United States. METHODS: We analyzed Centers for Disease Control and Prevention's National HIV Prevention Program Monitoring and Evaluation data collected in 2019. Descriptive and multivariate robust Poisson regression analyses were conducted to summarize the patterns of HIV testing program outcomes [ie, positivity, linkage to HIV medical care within 30 days of diagnosis, interview for partner services (PS), and pre-exposure prophylaxis (PrEP) awareness and referral] by demographic characteristics, HIV prevalence, and testing site type. RESULTS: A total of 123,251 HIV tests were conducted among MSM; of these, 1773 (1.4%) were newly diagnosed with HIV. Among MSM newly diagnosed with HIV, 75% were linked to HIV medical care and 80% were interviewed for PS. Among MSM who tested HIV-negative, 63% were aware of PrEP and 47% of those who were eligible for PrEP were referred to PrEP providers. Referral or linkage to services varied by demographic characteristics or other factors. CONCLUSIONS: Linkage to HIV medical care and interview for PS among MSM newly diagnosed with HIV in non-healthcare settings were below national or funding program targets. Most MSM with risk factors for HIV infection were not referred to PrEP providers. Expanded efforts to address barriers to equitable access to services may help improve HIV-related outcomes among MSM and contribute to ending the HIV epidemic in the United States.

Intrauterine Administration of Autologous Platelet-Derived Growth Factor Concentrate (aka Autologous Blood Cell Derivative) Improves the Endometrial Thickness in 'Thin' Endometrium in the Frozen Embryo Transfer Cycle.

Context: Thin endometrium during the frozen embryo transfer cycles leads to cycle cancellation. The embryo transfer cycle getting deferred is an unpleasant experience for the patients and the fertility specialist. Aims: The purpose of this study is to evaluate the effectiveness of Autologous Blood Cell Derivative (ABCD) growth factor concentrate to obtain an optimal thickness of endometrium for embryo transfer during IVF treatments, where rapid regeneration is crucial for the expected therapeutic outcome. Settings and Design: A retrospective cohort study was conducted in Manipal Assisted Reproduction Center, a referral center in Southern India. Methods and Material: Fifty-six patients with thin endometrium were administered three doses of ABCD growth factor concentrate as per the protocol after informed consent. All of them had a history of embryo transfer (ET) cancellation in frozen-thawed embryo cycles due to inadequate growth of the endometrium despite therapy with estrogens and drugs for improving uterine blood circulation. Results: The endometrium thickness during the implantation window in the patients included in the study averaged 6.48 ± 1.19 mm. After the intervention, 55 out of 56 patients (98.2%) showed a considerable change in the thickness of the endometrium layer with an average thickness of 8.48 ± 1.32 mm (< 0.0001, SE 0.233, 95% CI 1.58-2.5). Out of the 55 patients, 20 got pregnant, i.e., 36.4% pregnancy rate. Till date, thirteen pregnancies had live births (65%), three pregnancies (15%) were biochemical pregnancies, 1 (5%) was ectopic, and three pregnancies (15%) had spontaneous miscarriage before eight weeks. When we compared the endometrial thickness (EMT) in the pregnant and non-pregnant groups pre- and post-ABCD instillation, (6.47 ± 1.31 mm vs 6.48 ± 1.4 mm, p = 0.98 and 8.68 ± 1.32 mm vs 8.48 ± 1.32 mm, p value 0.59) the p value was not statistically significant. Conclusions: The implantation, clinical pregnancy and live birth rates were 36.4, 30 and 65%, respectively. This result is a significant improvement for patients with thin endometrium for whom we would otherwise cancel the frozen transfer. An autologous resource is a safe, readily available and inexpensive treatment modality.