Delays in sexual health care among patients attending New York City Sexual Health Clinics during the COVID-19 pandemic, March 2020 to February 2021.

BACKGROUND: Public health emergencies can lead to reduced or suspended services in sexual health clinics (SHCs), raising questions about optimal ways to maintain access to care. We examined changes in sexual behaviors, HIV pre-exposure prophylaxis (PrEP) use, telehealth preference, and correlates of delayed sexual health care among patients attending New York City (NYC) publicly funded SHCs during the COVID-19 pandemic. METHODS: 470 patients from four SHCs (July-September 2021) completed a self-administered survey that collected data on access to sexual health care, overall and over three distinct time periods [Spring 2020 (COVID-19 wave 1), Summer 2020, Fall 2020/Winter 2021 (COVID-19 wave 2)]. We used log-binomial models to examine factors associated with delayed sexual health care. RESULTS: Participants reporting multiple in-person sexual contacts increased from 28% to 57% (P < 0.0001) between the first and second wave. Almost half of participants (35/72) taking HIV PrEP cited decreased use. Over 90% (423/460) of participants preferred in-person clinic visits over telehealth. Overall, delays in routine and urgent sexual health care were reported by 34% (129/375) and 12% (46/373) of participants, respectively. More men who have sex with men (MSM) and transgender/gender non-conforming/nonbinary (TGNCNB) individuals experienced delayed care compared with women [MSM: aPR 1.43 (95% CI, 1.00-2.03); TGNCNB: 1.67 (1.04-2.69)]. Compared with participants who primarily sought sexual health care from private providers, those who primarily used SHCs experienced significantly more delayed care [1.72 (1.14-2.59)]. CONCLUSIONS: Delays in sexual health care access can have serious implications for certain patient populations. Additional resources are needed to maintain access to sexual health clinic services.

SARS-CoV-2 bivalent mRNA vaccine with broad protection against variants of concern.

Introduction: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has rapidly spread around the globe. With a substantial number of mutations in its Spike protein, the SARS-CoV-2 Omicron variant is prone to immune evasion and led to the reduced efficacy of approved vaccines. Thus, emerging variants have brought new challenges to the prevention of COVID-19 and updated vaccines are urgently needed to provide better protection against the Omicron variant or other highly mutated variants. Materials and methods: Here, we developed a novel bivalent mRNA vaccine, RBMRNA-405, comprising a 1:1 mix of mRNAs encoding both Delta-derived and Omicron-derived Spike proteins. We evaluated the immunogenicity of RBMRNA-405 in BALB/c mice and compared the antibody response and prophylactic efficacy induced by monovalent Delta or Omicron-specific vaccine with the bivalent RBMRNA-405 vaccine in the SARSCoV-2 variant challenge. Results: Results showed that the RBMRNA-405 vaccine could generate broader neutralizing antibody responses against both Wuhan-Hu-1 and other SARS-CoV-2 variants, including Delta, Omicron, Alpha, Beta, and Gamma. RBMRNA-405 efficiently blocked infectious viral replication and lung injury in both Omicron- and Delta-challenged K18-ACE2 mice. Conclusion: Our data suggest that RBMRNA-405 is a promising bivalent SARS-CoV-2 vaccine with broad-spectrum efficacy for further clinical development.

RNA therapeutics: updates and future potential.

Recent advancements in the production, modification, and cellular delivery of RNA molecules facilitated the expansion of RNA-based therapeutics. The increasing understanding of RNA biology initiated a corresponding growth in RNA therapeutics. In this review, the general concepts of five classes of RNA-based therapeutics, including RNA interference-based therapies, antisense oligonucleotides, small activating RNA therapies, circular RNA therapies, and messenger RNA-based therapeutics, will be discussed. Moreover, we also provide an overview of RNA-based therapeutics that have already received regulatory approval or are currently being evaluated in clinical trials, along with challenges faced by these technologies. RNA-based drugs demonstrated positive clinical trial results and have the ability to address previously "undruggable" targets, which delivers great promise as a disruptive therapeutic technology to fulfill its full clinical potentiality.

Detemir vs neutral protamine Hagedorn insulin for diabetes mellitus in pregnancy: a comparative effectiveness, randomized controlled trial.

BACKGROUND: Insulin detemir, being used increasingly during pregnancy, may have pharmacologic benefits compared with neutral protamine Hagedorn. OBJECTIVE: We evaluated the probability that compared with treatment with neutral protamine Hagedorn, treatment with insulin detemir reduces the risk for adverse neonatal outcome among individuals with type 2 or overt type 2 diabetes mellitus (gestational diabetes mellitus diagnosed at <20 weeks' gestation). STUDY DESIGN: We performed a multiclinic randomized controlled trial (September 2018 to January 2020), which included women with singleton gestation with type 2 or overt type 2 diabetes mellitus who sought obstetrical care at ≤21 weeks' gestation. Participants were randomized to receive either insulin detemir or neutral protamine Hagedorn by a clinic-stratified scheme. The primary outcome was a composite of adverse neonatal outcomes, including shoulder dystocia, large for gestational age, neonatal intensive care unit admission, respiratory distress (defined as the need of at least 4 hours of respiratory support with supplemental oxygen, continuous positive airway pressure or ventilation at the first 24 hours of life), or hypoglycemia. The secondary neonatal outcomes included gestational age at delivery, small for gestational age, 5-minute Apgar score of <7, lowest glucose level, need for intravenous glucose, respiratory distress syndrome, need for mechanical ventilation or continuous positive airway pressure, neonatal jaundice requiring therapy, brachial plexus injury, and hospital length of stay. The secondary maternal outcomes included hypoglycemic events, hospital admission for glucose control, hypertensive disorder of pregnancy, maternal weight gain, cesarean delivery, and postpartum complications. We used the Bayesian statistics to estimate a sample size of 108 to have >75% probability of any reduction in the primary outcome, assuming 80% power and a hypothesized effect of 33% reduction with insulin detemir. All analyses were intent to treat under a Bayesian framework with neutral priors (a priori assumed a 50:50 likelihood of either intervention being better; National Clinical Trial identifier 03620890). RESULTS: There were 108 women randomized in this trial (57 in insulin detemir and 51 in neutral protamine Hagedorn), and 103 women were available for analysis of the primary outcome (n=5 for pregnancy loss before 24 weeks' gestation). Bayesian analysis indicated an 87% posterior probability of reduced primary outcome with insulin detemir compared with neutral protamine Hagedorn (posterior adjusted relative risk, 0.88; 95% credible interval, 0.61-1.12). Bayesian analyses for secondary outcomes showed consistent findings of lower adverse maternal outcomes with the use of insulin detemir vs neutral protamine Hagedorn: for example, maternal hypoglycemic events (97% probability of benefit; posterior adjusted relative risk, 0.59; 95% credible interval, 0.29-1.08) and hypertensive disorders (88% probability of benefit; posterior adjusted relative risk, 0.81; 95% credible interval, 0.54-1.16). CONCLUSION: In our comparative effectiveness trial involving individuals with type 2 or overt type 2 diabetes mellitus, use of insulin detemir resulted in lower rates of adverse neonatal and maternal outcomes compared with neutral protamine Hagedorn.

Identification of newborns with birthweight ≥ 4,500g: Ultrasound within one- vs. two weeks of delivery.

OBJECTIVE: Our objective was to compare the diagnostic characteristics of sonographic estimated fetal weight (SEFW) done within 7 versus 8-14 days before delivery for detection of fetal macrosomia (birthweight ≥ 4500 g). STUDY DESIGN: We performed a multicenter, retrospective cohort study of all non-anomalous singletons with SEFW ≥ 4000 g by Registered Diagnostic Medical Sonographers conducted within 14 days of delivery. Cohorts were grouped by time interval between ultrasound and delivery: 0-7 days versus 8-14 days. The detection rate (DR) and false positive rate (FPR) for detection of birthweight (BW) ≥ 4500 g were compared between groups with subgroup analysis for diabetic women. Area under the receiver operator curve (AUC) was calculated to analyze all possible SEFW cutoffs within our cohort. RESULTS: A total of 330 patients met inclusion criteria with 250 (75.8 %) having SEFW within 7 days and 80 (24.2 %) with SEFW 8-14 days prior to delivery. The rate of macrosomia was 15.1 % (N = 51). The DR for macrosomia was significantly higher when SEFW was performed within 7 days of delivery compared to 8-14 days among non-diabetic (73.0 % vs 7.1 %; p < 0.001) and diabetic women (76.5 % vs 16.7 %; p = 0.02). There was no significant change in FPR in either group. The AUC for detection of macrosomia was significantly higher when SEFW was performed within 7 days versus 8-14 days (0.89 vs 0.63; p < 0.01). CONCLUSION: With SEFW ≥ 4000 g, the detection of BW ≥ 4500 g is significantly higher when the sonographic examination is within 7 days of birth irrespective of maternal diabetes.

Cutting-edge endonasal surgical approaches to thyroid ophthalmopathy.

OBJECTIVE: Thyroid orbitopathy is a poorly understood extrathyroidal manifestation of Graves' disease that can cause disfiguring proptosis and vision loss. Orbital decompression surgery for Graves' orbitopathy (GO) can address both cosmetic and visual sequelae of this autoimmune condition. Endonasal endoscopic orbital decompression provides unmatched visualization and access to inferomedial orbital wall and orbital apex. This review examines the state of the art approaches employed in endonasal endoscopic orbital decompression for GO. METHODS: Review of literature evaluating novel surgical maneuvers for GO. RESULTS: Studies examining the efficacy of endonasal endoscopic orbital decompression are heterogenous and retrospective in design; however, they reveal this approach to be a safe and effective technique in the management of GO. CONCLUSION: Subtle variations in endoscopic techniques significantly affect postsurgical outcomes and can be tailored to the specific clinical indication in GO making endonasal endoscopic decompression the most versatile approach available. LEVEL OF EVIDENCE: NA.

Diffusion tensor tractography of the mammillothalamic tract in the human brain using a high spatial resolution DTI technique.

The mammillary bodies as part of the hypothalamic nuclei are in the central limbic circuitry of the human brain. The mammillary bodies are shown to be directly or indirectly connected to the amygdala, hippocampus, and thalami as the major gray matter structures of the human limbic system. Although it is not primarily considered as part of the human limbic system, the thalamus is shown to be involved in many limbic functions of the human brain. The major direct connection of the thalami with the hypothalamic nuclei is known to be through the mammillothalamic tract. Given the crucial role of the mammillothalamic tracts in memory functions, diffusion tensor imaging may be helpful in better visualizing the surgical anatomy of this pathway noninvasively. This study aimed to investigate the utility of high spatial resolution diffusion tensor tractography for mapping the trajectory of the mammillothalamic tract in the human brain. Fifteen healthy adults were studied after obtaining written informed consent. We used high spatial resolution diffusion tensor imaging data at 3.0 T. We delineated, for the first time, the detailed trajectory of the mammillothalamic tract of the human brain using deterministic diffusion tensor tractography.

NCoR1 restrains thymic negative selection by repressing Bim expression to spare thymocytes undergoing positive selection.

Thymocytes must pass both positive and negative selections to become mature T cells. Negative selection purges thymocytes whose T-cell receptors (TCR) exhibit high affinity to self-peptide MHC complexes (self pMHC) to avoid autoimmune diseases, while positive selection ensures the survival and maturation of thymocytes whose TCRs display intermediate affinity to self pMHCs for effective immunity, but whether transcriptional regulation helps conserve positively selected thymocytes from being purged by negative selection remains unclear. Here we show that the specific deletion of nuclear receptor co-repressor 1 (NCoR1) in T cells causes excessive negative selection to reduce mature thymocyte numbers. Mechanistically, NCoR1 protects positively selected thymocytes from negative selection by suppressing Bim expression. Our study demonstrates a critical function of NCoR1 in coordinated positive and negative selections in the thymus.Thymocytes are screened by two processes, termed positive and negative selections, which are permissive only for immature thymocytes with intermediate avidity to the selecting ligands. Here the authors show that the nuclear receptor NCoR1 suppresses Bim1 to inhibit negative selection and promote thymocyte survival.

Multimodal Detection of a Small Molecule Target Using Stimuli-Responsive Liposome Triggered by Aptamer-Enzyme Conjugate.

Nanomaterials which can respond to external stimuli have attracted considerable attention due to their potential applications in sensing and biomedicine. One of the most promising classes of such materials is the stimuli-responsive liposome that can release its contents in response to a specific target. Despite recent progress, development of liposomes responsive to small molecular targets remains a challenge, due to the difficulty in designing the transduction process to link between target binding and triggered release, even though small molecular metabolites play important roles in many biological processes. Herein, we demonstrate a combination of an aptamer (apt) for target recognition and enzyme phosphatidylcholine 2-acetylhydrolase (PLA2) for rupture of liposome. As a proof-of-concept, cocaine molecules were used to trigger the release of the enzyme. The exposure to DNA-PLA2 conjugates induced the rupture of liposome containing uranin and gadopentetic acid (Gd-DTPA), allowing multimodal fluorescent and MRI detection of cocaine. The strategy demonstrated in this work can be generally applied to other imaging modalities by loading different imaging agents, as well as other targets by using different functional DNAs.

State substance abuse treatment gaps.

This study estimated the adequacy of state substance abuse treatment rates relative to treatment needs. The investigators created composite drug and alcohol treatment need indexes from explicit-mention mortality and substance-defined arrest rates. The indexes were reliable and had evidence of construct validity, but alternative population-at-risk and survey-based need measures did not fair as well. States varied substantially in per capita alcohol and drug treatment needs, although the two did not correlate with each other. While the need indexes correlated significantly with state treatment rates, the adequacy of state treatment rates varied greatly. States with the largest treatment gaps were in the South, Southwest, and northern plains and mountain regions. The failure of the Block Grant formula to reflect the needs of rural states with high-risk minority populations may contribute to disparities in access to services.

Identifying substance abuse treatment gaps in substate areas.

Investigating concerns about uneven utilization of health services, especially affecting disadvantaged high-risk populations, the authors constructed composite indexes for identifying substance abuse treatment gaps in Rhode Island towns and multi-town planning areas. The Drug, Alcohol, and Substance Abuse Need Indexes combined multiple-year rates of substance-related deaths, hospital discharges, and arrests. These indicators were reliable and possessed convergent validity; the composite indexes were also reliable and had construct validity. Regression of treatment admissions rates on town Substance Abuse Need Index scores revealed that some areas had relative gaps in treatment services. Having an objective and validated method for identifying treatment gaps could help treatment planners ensure equal access to services throughout the state. Reducing travel to treatment facilities can increase treatment utilization and treatment retention.