CDC-Funded HIV Testing Services Outcomes in Ending the HIV Epidemic in the U.S. (EHE) and Non-EHE Jurisdictions, 2021.

BACKGROUND: Ending the HIV Epidemic in the U.S. (EHE) aims to end the HIV epidemic by focusing on 57 jurisdictions most impacted by HIV. METHODS: Using 2021 data from the National HIV Prevention Program Monitoring and Evaluation system, we calculated distributions of CDC-funded HIV tests and HIV testing services outcomes in EHE and non-EHE jurisdictions. We conducted chi-square tests and robust Poisson regression to compare differences in outcomes. RESULTS: Of the 1,753,873 tests conducted, a greater proportion were conducted in EHE (65.7%) versus non-EHE (34.3%) jurisdictions (p<0.001). Greater number of persons newly diagnosed were identified in EHE (n=5,861) versus non-EHE (n=2,329) jurisdictions; newly diagnosed positivity was higher in EHE (0.5%) versus non-EHE (0.4%; PR=1.31, 95% CI: 1.25-1.38) jurisdictions. Among persons newly diagnosed, there were no differences in proportion of linkage to care within 30 days in EHE jurisdictions (77.9%) versus non-EHE jurisdictions (77.1%; PR=1.01, 95% CI: 0.95-1.07). Proportion of persons newly diagnosed interviewed for partner services was lower in EHE (69.0%) versus non-EHE (84.8%; PR=0.81, 95% CI: 0.76-0.87) jurisdictions. CONCLUSION: CDC-funded HIV testing services in EHE jurisdictions conducted more HIV testing and diagnosed more persons. Jurisdictions can further expand HIV testing and related services to continue striving toward EHE goals.

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.

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.

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.

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 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.

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.

Crossing the Hurdle of a Low Oocyte Yield in an in vitro Fertilization Cycle to Obtain Mature Oocytes.

The complex process of oocyte maturation involves a coordinated set of events to take place so that an adequate number of oocytes can be obtained during an oocyte pickup procedure following controlled ovarian stimulation. A weak link in any of the steps can yield a sparse number of oocytes which can be a setback in the process.

Random Start Ovarian Stimulation.

Fertility preservation is emerging in recent years as an important option for various indications many of which being for cancer patients and for certain benign conditions as well. In the present case report, we set out to utilise the same protocol, however, for different indications.

Inhibition of BKCa channels protects neonatal hearts against myocardial ischemia and reperfusion injury.

BKCa channels are large-conductance calcium and voltage-activated potassium channels that are heterogeneously expressed in a wide array of cells. Activation of BKCa channels present in mitochondria of adult ventricular cardiomyocytes is implicated in cardioprotection against ischemia-reperfusion (IR) injury. However, the BKCa channel's activity has never been detected in the plasma membrane of adult ventricular cardiomyocytes. In this study, we report the presence of the BKCa channel in the plasma membrane and mitochondria of neonatal murine and rodent cardiomyocytes, which protects the heart on inhibition but not activation. Furthermore, K+ currents measured in neonatal cardiomyocyte (NCM) was sensitive to iberiotoxin (IbTx), suggesting the presence of BKCa channels in the plasma membrane. Neonatal hearts subjected to IR when post-conditioned with NS1619 during reoxygenation increased the myocardial infarction whereas IbTx reduced the infarct size. In agreement, isolated NCM also presented increased apoptosis on treatment with NS1619 during hypoxia and reoxygenation, whereas IbTx reduced TUNEL-positive cells. In NCMs, activation of BKCa channels increased the intracellular reactive oxygen species post HR injury. Electrophysiological characterization of NCMs indicated that NS1619 increased the beat period, field, and action potential duration, and decreased the conduction velocity and spike amplitude. In contrast, IbTx had no impact on the electrophysiological properties of NCMs. Taken together, our data established that inhibition of plasma membrane BKCa channels in the NCM protects neonatal heart/cardiomyocytes from IR injury. Furthermore, the functional disparity observed towards the cardioprotective activity of BKCa channels in adults compared to neonatal heart could be attributed to their differential localization.