Efficient remediation of different concentrations of Cr-contaminated soils by nano zero-valent iron modified with carboxymethyl cellulose and biochar.

Nano zero-valent iron (nZVI) is widely used in soil remediation due to its high reactivity. However, the easy agglomeration, poor antioxidant ability and passivation layer of Fe-Cr coprecipitates of nZVI have limited its application scale in Cr-contaminated soil remediation, especially in high concentration of Cr-contaminated soil. Herein, we found that the carboxymethyl cellulose on nZVI particles could increase the zeta potential value of soil and change the phase of nZVI. Along with the presence of biochar, 97.0% and 96.6% Cr immobilization efficiency through CMC-nZVI/BC were respectively achieved in high and low concentrations of Cr-contaminated soils after 90-days remediation. In addition, the immobilization efficiency of Cr(VI) only decreased by 5.1% through CMC-nZVI/BC treatment after 10 weeks aging in air, attributing to the strong antioxidation ability. As for the surrounding Cr-contaminated groundwater, the Cr(VI) removal capacity of CMC-nZVI/BC was evaluated under different reaction conditions through column experiments and COMSOL Multiphysics. CMC-nZVI/BC could efficiently remove 85% of Cr(VI) in about 400 hr when the initial Cr(VI) concentration was 40 mg/L and the flow rate was 0.5 mL/min. This study demonstrates that uniformly dispersed CMC-nZVI/BC has an excellent remediation effect on different concentrations of Cr-contaminated soils.

Who wants long-Acting injectable antiretroviral therapy? Treatment preferences among adults with HIV in Florida.

Long-acting injectable (LAI) antiretroviral therapy (ART) is available to people with HIV (PWH), but it is unknown which PWH prefer this option. Using the Andersen Behavioral Model this study identifies characteristics of PWH with greater preference for LAI ART. Cross-sectional data from the Florida Cohort, which enrolled adult PWH from community-based clinics included information on predisposing (demographics), enabling (transportation, income), and need (ART adherence <90%) factors. ART preference was assessed via a single question (prefer pills, quarterly LAI, or no preference). Confounder-adjusted multinomial logistic regressions compared those who preferred pills to the other preference options, with covariates identified using directed acyclic graphs. Overall, 314 participants responded (40% non-Hispanic Black, 62% assigned male, 63% aged 50+). Most (63%) preferred the hypothetical LAI, 23% preferred pills, and 14% had no preference. PWH with access to a car (aRRR 1.97 95%CI 1.05-3.71), higher income (aRRR 2.55 95%CI 1.04-6.25), and suboptimal ART adherence (aRRR 7.41 95% CI 1.52-36.23) were more likely to prefer the LAI, while those who reported having no social network were less likely to prefer the LAI (aRRR 0.32 95% CI 0.11-0.88). Overall LAI interest was high, with greater preference associated with enabling and need factors.

Bidirectional Copy-Paste Mamba for Enhanced Semi-Supervised Segmentation of Transvaginal Uterine Ultrasound Images.

Automated perimetrium segmentation of transvaginal ultrasound images is an important process for computer-aided diagnosis of uterine diseases. However, ultrasound images often contain various structures and textures, and these structures have different shapes, sizes, and contrasts; therefore, accurately segmenting the parametrium region of the uterus in transvaginal uterine ultrasound images is a challenge. Recently, many fully supervised deep learning-based methods have been proposed for the segmentation of transvaginal ultrasound images. Nevertheless, these methods require extensive pixel-level annotation by experienced sonographers. This procedure is expensive and time-consuming. In this paper, we present a bidirectional copy-paste Mamba (BCP-Mamba) semi-supervised model for segmenting the parametrium. The proposed model is based on a bidirectional copy-paste method and incorporates a U-shaped structure model with a visual state space (VSS) module instead of the traditional sampling method. A dataset comprising 1940 transvaginal ultrasound images from Tongji Hospital, Huazhong University of Science and Technology is utilized for training and evaluation. The proposed BCP-Mamba model undergoes comparative analysis with two widely recognized semi-supervised models, BCP-Net and U-Net, across various evaluation metrics including Dice, Jaccard, average surface distance (ASD), and Hausdorff_95. The results indicate the superior performance of the BCP-Mamba semi-supervised model, achieving a Dice coefficient of 86.55%, surpassing both U-Net (80.72%) and BCP-Net (84.63%) models. The Hausdorff_95 of the proposed method is 14.56. In comparison, the counterparts of U-Net and BCP-Net are 23.10 and 21.34, respectively. The experimental findings affirm the efficacy of the proposed semi-supervised learning approach in segmenting transvaginal uterine ultrasound images. The implementation of this model may alleviate the expert workload and facilitate more precise prediction and diagnosis of uterine-related conditions.

Perception and Acceptance of Telemedicine Use in Health Care Among the General Public in China: Web-Based Cross-Sectional Survey.

BACKGROUND: The COVID-19 pandemic is bringing about substantial changes in health care systems, leading to a significant shift toward telemedicine for the delivery of health care services. OBJECTIVE: This study aims to examine the relationship between perceived usefulness and ease of use of telemedicine services and their association with the behavioral intention to use telemedicine. METHODS: An anonymous cross-sectional survey was conducted in China. Partial least squares structural equation modeling was used to determine significant predictors of intention to use telemedicine consultation. Types of illnesses that favored seeking telemedicine consultation, as well as the most preferred platform for conducting telemedicine consultations, were also investigated. RESULTS: In total, 1006 participants completed the survey. A total of 44.3% (n=446) reported being very likely and 49.3% (n=496) reported being likely to seek telemedicine consultation. Overall, the majority of participants expressed strong agreement or agreement regarding the perceived usefulness of telemedicine. Likewise, the majority indicated strong agreement or agreement when it came to their perception of the ease of using telemedicine. In the partial least squares structural equation modeling, perceived usefulness (ß=0.322; P<.001) and perceived ease of use (ß=0.118; P=.01) were significantly associated with a higher likelihood of seeking telemedicine consultation. A considerable number of participants expressed willingness to use telemedicine services for various medical conditions, particularly respiratory (n=340, 33.8%), skin (n=316, 31.4%), and musculoskeletal issues (n=316, 31.4%) while showing less interest in seeking telemedicine consultations for reproductive health (n=44, 4.4%) and cancer (n=64, 6.4%). The majority preferred video chat (n=443, 44%) and text chat (n=317, 31.5%) as their most preferred platforms for telemedicine consultation, while a smaller proportion preferred telephone (n=193, 19.2%) and email (n=53, 5.3%). CONCLUSIONS: Telemedicine has the potential to play a larger role in China's health care system. The preferences for certain platforms over others may influence service design and implementation.

PCSK9 Inhibitor with Statin Therapy for Intracranial Artery Stenosis （PISTIAS): Rationale and design of a multicenter randomized controlled trial.

RATIONALE: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors enable an additional 54% to 75% reduction in low-density lipoprotein cholesterol (LDL-C) in statin-treated patients, demonstrating plaque regression in coronary artery disease. However, the impact of achieving an extremely low level of LDL-C with PCSK9 inhibitors (e.g., evolocumabEvolocumab) on symptomatic intracranial atherosclerosis remains unexplored. AIM AND HYPOTHESIS: To determine if combining evolocumabEvolocumab and statins achieves a more significant symptomatic intracranial plaque reduction than statin therapy solely. SAMPLE SIZE ESTIMATES: With a sample size of 1000 subjects, a two-sided of 0.05, and 20% lost to follow-up, the study will have 83.3% power to detect the difference in intracranial plaque burden. METHODS AND DESIGN: This is an investigator-initiated multicenter, randomized, open-label, outcome assessor-blinded trial, evaluating the impact of evolocumabEvolocumab on intracranial plaque burden assessed by high-resolution magnetic resonance imaging at baseline in patients undergoing a clinically indicated acute stroke or transient ischemic attack due to intracranial artery stenosis, and after 24 weeks of treatment. Subjects (n = 1000) will be randomized 1:1 into two groups to receive either evolocumabEvolocumab 140 mg every two weeks with statin therapy or solely statin therapy. STUDY OUTCOMES: The primary endpoint is the change in plaque burden assessed by high-resolution magnetic resonance imaging, performed at baseline and the end of the 24-week treatment period. DISCUSSION: This trial will explore whether more significant plaque regression is achievable with treatment after combining statins and PCSK9 inhibitors, providing information about important efficacy, mechanism, and safety data.Trial registration number: ChiCTR2300068868; https://www.chictr.org.cn/.

Advancing the Frontiers of Neuroelectrodes: A Paradigm Shift towards Enhanced Biocompatibility and Electrochemical Performance.

The aim of this study is the fabrication of unprecedented neuroelectrodes, replete with exceptional biological and electrical attributes. Commencing with the synthesis of polyethylene glycol and polyethyleneimine-modified iron oxide nanoparticles, the grafting of Dimyristoyl phosphatidylcholine was embarked upon to generate DMPC-SPION nanoparticles. Subsequently, the deposition of DMPC-SPIONs onto a nickel-chromium alloy electrode facilitated the inception of an innovative neuroelectrode-DMPC-SPION. A meticulous characterization of DMPC-SPIONs ensued, encompassing zeta potential, infrared spectroscopy, X-ray photoelectron spectroscopy, and X-ray diffraction analyses. Evaluations pertaining to hemolysis and cytotoxicity were conducted to ascertain the biocompatibility and biosafety of DMPC-SPIONs. Ultimately, a comprehensive assessment of the biocompatibility, electrochemical properties, and electrophysiological signal acquisition capabilities of DMPC-SPION neuroelectrodes was undertaken. These findings conclusively affirm the exemplary biocompatibility, electrochemical capabilities, and outstanding capability in recording electrical signals of DMPC-SPION neuroelectrodes, with an astounding 91.4% augmentation in electrode charge and a noteworthy 13% decline in impedance, with peak potentials reaching as high as 171 µV and an impressive signal-to-noise ratio of 15.92. Intriguingly, the novel DMPC-SPION neuroelectrodes herald an innovative pathway towards injury repair as well as the diagnosis and treatment of neurological disorders.

P4HA2 hydroxylates SUFU to regulate the paracrine Hedgehog signaling and promote B-cell lymphoma progression.

Aberrations in the Hedgehog (Hh) signaling pathway are significantly prevailed in various cancers, including B-cell lymphoma. A critical facet of Hh signal transduction involves the dynamic regulation of the suppressor of fused homolog (SUFU)-glioma-associated oncogene homolog (GLI) complex within the kinesin family member 7 (KIF7)-supported ciliary tip compartment. However, the specific post-translational modifications of SUFU-GLI complex within this context have remained largely unexplored. Our study reveals a novel regulatory mechanism involving prolyl 4-hydroxylase 2 (P4HA2), which forms a complex with KIF7 and is essential for signal transduction of Hh pathway. We demonstrate that, upon Hh pathway activation, P4HA2 relocates alongside KIF7 to the ciliary tip. Here, it hydroxylates SUFU to inhibit its function, thus amplifying the Hh signaling. Moreover, the absence of P4HA2 significantly impedes B lymphoma progression. This effect can be attributed to the suppression of Hh signaling in stromal fibroblasts, resulting in decreased growth factors essential for malignant proliferation of B lymphoma cells. Our findings highlight the role of P4HA2-mediated hydroxylation in modulating Hh signaling and propose a novel stromal-targeted therapeutic strategy for B-cell lymphoma.

Colorimetric aptasensor based on temporally controllable light-stimulated oxidase-mimicking fluorescein for the sensitive detection of exosomes in mild conditions.

Analysis of exosomes provides important information for rapid and non-invasive screening of tumors. However, sensitive and convenient detection of exosomes remains technically challenging to date. Herein, a colorimetric aptasensor based on the light-stimulated oxidase-mimicking activity of FITC was constructed for detecting ovarian cancer (OC) exosomes. The aptasensor contained an EpCAM aptamer to capture OC exosomes. Cholesterol and fluorescein (FITC) were used to modify either end of the DNA (DNA anchor). The DNA anchor could combine with exosomes through a hydrophobic reaction between cholesterol and the lipid membrane. FITC oxidized 3,3',5,5'-tetramethylbenzidine (TMB) under a 365 nm LED light source in a temporally controllable manner under mild conditions, causing the solution to change from colorless to blue, and the corresponding UV-vis absorbance increased. Based on this principle, the exosomes were qualitatively analyzed by observing the color change with the naked eye. In parallel, the exosome concentration was also detected using UV-vis spectrophotometry. The linear range was from 2 × 105 to 100 × 105 particles per mL with a limit of detection of 1.77 × 105 particles per mL. The developed aptasensor also exhibited favorable selectivity and could discriminate the exosomes from OC cells and normal cells. Besides, the receiver operating characteristic (ROC) curve demonstrates that it is possible to distinguish between patients with OC and healthy donors (HDs) using exosomes as the biomarker. Our technology may expand the applications of DNA-based detection method-enabled OC diagnostic tools.

Microglial gp91phox-mediated neuroinflammation and ferroptosis contributes to learning and memory deficits in rotenone-treated mice.

Apart from dopaminergic neurotoxicity, exposure to rotenone, a commonly used insecticide in agriculture, also adversely affects hippocampal and cortical neurons, resulting in cognitive impairments in mice. We recently established a role of microglia-mediated neuroinflammation in rotenone-elicited deficits of cognition, yet the mechanisms remain elusive. Here, we investigated the involvement of NADPH oxidase 2 (NOX2) catalytic subunit gp91phox in rotenone-induced cognitive deficits and the associated mechanisms. Our study demonstrated that rotenone exposure elevated expression of gp91phox and phosphorylation of the NOX2 cytosolic subunit p47phox, along with NADPH depletion in the hippocampus and cortex of mice, indicating NOX2 activation. Specific knockdown of gp91phox in microglia via adeno-associated virus delivery resulted in reduced microglial activation, proinflammatory gene expression and improved learning and memory capacity in rotenone-intoxicated mice. Genetic deletion of gp91phox also reversed rotenone-elicited cognitive dysfunction in mice. Furthermore, microglial gp91phox knockdown attenuated neuronal damage and synaptic loss in mice. This intervention also suppressed iron accumulation, disruption of iron-metabolism proteins and iron-dependent lipid peroxidation and restored the balance of ferroptosis-related parameters, including GPX4, SLC711, PTGS2, and ACSL4 in rotenone-lesioned mice. Intriguingly, pharmacological inhibition of ferroptosis with liproxstatin-1 conferred protection against rotenone-induced neurodegeneration and cognitive dysfunction in mice. In summary, our findings underscored the contribution of microglial gp91phox-dependent neuroinflammation and ferroptosis to learning and memory dysfunction in rotenone-lesioned mice. These results provided valuable insights into the pathogenesis of cognitive deficits associated with pesticide-induced Parkinsonism, suggesting potential therapeutic avenues for intervention.

Advances in the study of gastric organoids as disease models.

Gastric organoids are models created in the laboratory using stem cells and sophisticated three-dimensional cell culture techniques. These models have shown great promise in providing valuable insights into gastric physiology and advanced disease research. This review comprehensively summarizes and analyzes the research advances in culture methods and techniques for adult stem cells and induced pluripotent stem cell-derived organoids, and patient-derived organoids. The potential value of gastric organoids in studying the pathogenesis of stomach-related diseases and facilitating drug screening is initially discussed. The construction of gastric organoids involves several key steps, including cell extraction and culture, three-dimensional structure formation, and functional expression. Simulating the structure and function of the human stomach by disease modeling with gastric organoids provides a platform to study the mechanism of gastric cancer induction by Helicobacter pylori. In addition, in drug screening and development, gastric organoids can be used as a key tool to evaluate drug efficacy and toxicity in preclinical trials. They can also be used for precision medicine according to the specific conditions of patients with gastric cancer, to assess drug resistance, and to predict the possibility of adverse reactions. However, despite the impressive progress in the field of gastric organoids, there are still many unknowns that need to be addressed, especially in the field of regenerative medicine. Meanwhile, the reproducibility and consistency of organoid cultures are major challenges that must be overcome. These challenges have had a significant impact on the development of gastric organoids. Nonetheless, as technology continues to advance, we can foresee more comprehensive research in the construction of gastric organoids. Such research will provide better solutions for the treatment of stomach-related diseases and personalized medicine.

Increasing the Particle Size and Magnetic Property of Iron Oxide Nanoparticles through a Segregated Nucleation and Growth Process.

Iron oxide nanoparticles (IONs) with good water dispersibility were prepared by the thermal decomposition of iron acetylacetonate (Fe(acac)3) in the high-boiling organic solvent polyethylene glycol (PEG) using polyethyleneimine (PEI) as a modifier. The nucleation and growth processes of the crystals were separated during the reaction process by batch additions of the reaction material, which could inhibit the nucleation but maintain the crystal growth, and products with larger particle sizes and high saturation magnetization were obtained. The method of batch addition of the reactant prepared IONs with the largest particle size and the highest saturation magnetization compared with IONs reported using PEG as the reaction solvent. The IONs prepared by this method also retained good water dispersibility. Therefore, these IONs are potentially suitable for the magnetic separation of cells, proteins, or nucleic acids when large magnetic responses are needed.

[Transcriptomic characteristics analysis of bone from chronic osteomyelitis].

OBJECTIVE: To explore the molecular mechanism of chronic osteomyelitis and to clarify the role of MAPK signal pathway in the pathogenesis of chronic osteomyelitis, by collecting and analyzing the transcriptional information of bone tissue in patients with chronic osteomyelitis. METHODS: Four cases of traumatic osteomyelitis in limbs from June 2019 to June 2020 were selected, and the samples of necrotic osteonecrosis from chronic osteomyelitis (necrotic group), and normal bone tissue (control group) were collected. Transcriptome information was collected by Illumina Hiseq Xten high throughput sequencing platform, and the gene expression in bone tissue was calculated by FPKM. The differentially expressed genes were screened by comparing the transcripts of the Necrotic group and control group. Genes were enriched by GO and KEGG. MAP3K7 and NFATC1 were selected as differential targets in the verification experiments, by using rat osteomyelitis animal model and immunohistochemical analysis. RESULTS: A total of 5548 differentially expressed genes were obtained by high throughput sequencing by comparing the necrotic group and control group, including 2701 up-regulated and 2847 down-regulated genes. The genes enriched in MAPK pathway and osteoclast differentiation pathway were screened, the common genes expressed in both MAPK and osteoclast differentiation pathway were (inhibitor of nuclear factor κ subunit Beta, IκBKß), (mitogen-activated protein kinase 7, MAP3K7), (nuclear factor of activated t cells 1, NFATC1) and (nuclear factor Kappa B subunit 2, NFκB2). In rat osteomyelitis model, MAP3K7 and NFATC1 were highly expressed in bone marrow and injured bone tissue. CONCLUSION: Based on the transcriptome analysis, the MAPK signaling and osteoclast differentiation pathways were closely related to chronic osteomyelitis, and the key genes IκBKß, MAP3K7, NFATC1, NFκB2 might be new targets for clinical diagnosis and therapy of chronic osteomyelitis.

Association between sugar-sweetened beverages and pure fruit juice with risk of six cardiovascular diseases: a Mendelian randomization study.

BACKGROUND: In observational and prospective cohort studies, intake of sugar-sweetened beverages (SSBs) and pure fruit juice (PFJ) has been associated with cardiovascular disease (CVD). Still, the causality of the connection has not yet been determined. Our objective was to uncover the relationship between SSBs/PFJ and CVD. METHODS: Genetically predicted causal associations between SSBs/PFJ (obtained in a published genome-wide association study) and six common CVDs (atrial fibrillation (AF), angina, heart failure (HF), acute myocardial infarction, hypertension, and coronary atherosclerosis) were assessed using MR analytic modeling. The primary analysis method utilized was the inverse variance weighted (IVW) method, complemented by additional methods such as the weighted median method, MR Egger regression, Cochran's Q test, MR pleiotropy residual, funnel plot, Bonferroni correction, and others for MR analysis. To ensure the robustness of the findings, F-values were calculated as a complementary test to set looser thresholds for exposing genetic instrumental variables (P < 1e-5). RESULTS: The results of MR analysis suggested genetically causal associations between SSBs and AF (odds ratio (OR): 1.023; 95% confidence interval (CI) 1.007-1.038; P = 0.0039) as well as between PFJ and angina (OR: 0.968; 95% CI, 0.943-0.993; P = 0.0138) there was genetic causality. However, MR analysis showed no causal association between SSBs/PFJ and other CVD risks. CONCLUSION: This study suggests that there may be a potential causal relationship between SSBs intake and AF and a causal negative association between PFJ intake and angina.

Comorbidity Burden and Health Care Utilization by Substance use Disorder Patterns among People with HIV in Florida.

Substance use disorder (SUD), a common comorbidity among people with HIV (PWH), adversely affects HIV clinical outcomes and HIV-related comorbidities. However, less is known about the incidence of different chronic conditions, changes in overall comorbidity burden, and health care utilization by SUD status and patterns among PWH in Florida, an area disproportionately affected by the HIV epidemic. We used electronic health records (EHR) from a large southeastern US consortium, the OneFlorida + clinical research data network. We identified a cohort of PWH with 3 + years of EHRs after the first visit with HIV diagnosis. International Classification of Diseases (ICD) codes were used to identify SUD and comorbidity conditions listed in the Charlson comorbidity index (CCI). A total of 42,271 PWH were included (mean age 44.5, 52% Black, 45% female). The prevalence SUD among PWH was 45.1%. Having a SUD diagnosis among PWH was associated with a higher incidence for most of the conditions listed on the CCI and faster increase in CCI score overtime (rate ratio = 1.45, 95%CI 1.42, 1.49). SUD in PWH was associated with a higher mean number of any care visits (21.7 vs. 14.8) and more frequent emergency department (ED, 3.5 vs. 2.0) and inpatient (8.5 vs. 24.5) visits compared to those without SUD. SUD among PWH was associated with a higher comorbidity burden and more frequent ED and inpatient visits than PWH without a diagnosis of SUD. The high SUD prevalence and comorbidity burden call for improved SUD screening, treatment, and integrated care among PWH.

Sequencing hour-level temporal patterns of polysubstance use among persons who use cocaine, alcohol, and cannabis: A back-translational approach.

BACKGROUND: Polysubstance use is highly prevalent among persons who use cocaine; however, little is known about how alcohol and cannabis are used with cocaine. We identified temporal patterns of cocaine+alcohol and cocaine+cannabis polysubstance use to inform more translationally relevant preclinical models. METHODS: Participants who used cocaine plus alcohol and/or cannabis at least once in the past 30 days (n=148) were interviewed using the computerized Substance Abuse Module and the newer Polysubstance Use-Temporal Patterns Section. For each day in the past 30 days, participants reported whether they had used cocaine, alcohol, and cannabis; if any combinations of use were endorsed, participants described detailed hourly use of each substance on the most "typical day" for the combination. Sequence analysis and hierarchical clustering were applied to identify patterns of timing of drug intake on typical days of cocaine polysubstance use. RESULTS: We identified five temporal patterns among the 180 sequences of reported cocaine polysubstance use: 1) limited cocaine/cocaine+alcohol use (53%); 2) extensive cannabis then cocaine+alcohol+cannabis use (22%); 3) limited alcohol/cannabis then cocaine+alcohol use (13%); 4) extensive cocaine+cannabis then cocaine+alcohol+cannabis use (4%); and 5) extensive cocaine then cocaine+alcohol use (8%). While drug intake patterns differed, prevalence of use disorders did not. CONCLUSIONS: Patterns were characterized by cocaine, alcohol, and cannabis polysubstance use and by the timing, order, duration, and quantity of episode-level substance use. The identification of real-world patterns of cocaine polysubstance use represents an important step toward developing laboratory models that accurately reflect human behavior.

Spatial and temporal analysis of HIV clinical outcomes in Florida reveals counties with persistent racial and ethnic disparities during 2012-2019.

BACKGROUND: Racial/ethnic disparities in the HIV care continuum have been well documented in the US, with especially striking inequalities in viral suppression rates between White and Black persons with HIV (PWH). The South is considered an epicenter of the HIV epidemic in the US, with the largest population of PWH living in Florida. It is unclear whether any disparities in viral suppression or immune reconstitution-a clinical outcome highly correlated with overall prognosis-have changed over time or are homogenous geographically. In this analysis, we 1) investigate longitudinal trends in viral suppression and immune reconstitution among PWH in Florida, 2) examine the impact of socio-ecological factors on the association between race/ethnicity and clinical outcomes, 3) explore spatial and temporal variations in disparities in clinical outcomes. METHODS: Data were obtained from the Florida Department of Health for 42,369 PWH enrolled in the Ryan White program during 2008-2020. We linked the data to county-level socio-ecological variables available from County Health Rankings. GEE models were fit to assess the effect of race/ethnicity on immune reconstitution and viral suppression longitudinally. Poisson Bayesian hierarchical models were fit to analyze geographic variations in racial/ethnic disparities while adjusting for socio-ecological factors. RESULTS: Proportions of PWH who experienced viral suppression and immune reconstitution rose by 60% and 45%, respectively, from 2008-2020. Odds of immune reconstitution and viral suppression were significantly higher among White [odds ratio =2.34, 95% credible interval=2.14-2.56; 1.95 (1.85-2.05)], and Hispanic [1.70 (1.54-1.87); 2.18(2.07-2.31)] PWH, compared with Black PWH. These findings remained unchanged after accounting for socio-ecological factors. Rural and urban counties in north-central Florida saw the largest racial/ethnic disparities. CONCLUSIONS: There is persistent, spatially heterogeneous, racial/ethnic disparity in HIV clinical outcomes in Florida. This disparity could not be explained by socio-ecological factors, suggesting that further research on modifiable factors that can improve HIV outcomes among Black and Hispanic PWH in Florida is needed.

Synthetic Approaches to the New Drugs Approved During 2022.

In 2022, 23 new small molecule chemical entities were approved as drugs by the United States FDA, European Union EMA, Japan PMDA, and China NMPA. This review describes the synthetic approach demonstrated on largest scale for each new drug based on patent or primary literature. The synthetic routes highlight practical methods to construct molecules, sometimes on the manufacturing scale, to access the new drugs. Ten additional drugs approved in 2021 and one approved in 2020 are included that were not covered in the previous year's review.

The Effect of Veteran Status and Chronic Pain on Past 30-Day Sedative Use Among Community-Dwelling Adult Males.

INTRODUCTION: Given the high sedative prescription rate, the sedative-associated morbidity, and mortality nationally (especially among veterans), we aimed to test the hypothesis that veteran status in the presence of chronic pain would be associated with greater sedative use when compared with nonveteran status. METHODS: The study participants were recruited by Community Health Workers (CHWs) through the ongoing community engagement program (HealthStreet) at the University of Florida. CHWs collected information on sociodemographic factors, health status, and past 30-day drug use patterns. RESULTS: The study sample comprised 4,732 male participants, of which 21% were veterans, 58% were Blacks and 8.4% had used prescription sedatives in the past 30 days. Veterans (vs nonveterans) were twice as likely to have used prescription sedatives in the past 30 days in the presence of chronic pain. CONCLUSIONS: Veterans with chronic pain are a high-risk population for current prescription sedative use.

Demographics, Trends, and Clinical Characteristics of HIV Pre-Exposure Prophylaxis Recipients and People Newly Diagnosed with HIV from Large Electronic Health Records in Florida.

Florida is one of the HIV epicenters with high incidence and marked sociodemographic disparities. We analyzed a decade of statewide electronic health record/claims data-OneFlorida+-to identify and characterize pre-exposure prophylaxis (PrEP) recipients and newly diagnosed HIV cases in Florida. Refined computable phenotype algorithms were applied and a total of 2186 PrEP recipients and 7305 new HIV diagnoses were identified between January 2013 and April 2021. We examined patients' sociodemographic characteristics, stratified by self-reported sex, along with both frequency-driven and expert-selected descriptions of clinical conditions documented within 12 months before the first PrEP use or HIV diagnosis. PrEP utilization rate increased in both sexes; higher rates were observed among males with sex differences widening in recent years. HIV incidence peaked in 2016 and then decreased with minimal sex differences observed. Clinical characteristics were similar between the PrEP and new HIV diagnosis cohorts, characterized by a low prevalence of sexually transmitted infections (STIs) and a high prevalence of mental health and substance use conditions. Study limitations include the overrepresentation of Medicaid recipients, with over 96% of female PrEP users on Medicaid, and the inclusion of those engaged in regular health care. Although PrEP uptake increased in Florida, and HIV incidence decreased, sex disparity among PrEP recipients remained. Screening efforts beyond individuals with documented prior STI and high-risk behavior, especially for females, including integration of mental health care with HIV counseling and testing, are crucial to further equalize PrEP access and improve HIV prevention programs.