ETS2 promotes cardiomyocyte apoptosis and autophagy in heart failure by regulating lncRNA TUG1/miR-129-5p/ATG7 axis.

Heart failure (HF) is a chronic disease in which the heart is unable to provide enough blood and oxygen to the peripheral tissues. Cardiomyocyte apoptosis and autophagy have been linked to HF progression. However, the underlying mechanism of HF is unknown. In this study, H2 O2 -treated AC16 cells were used as a cell model of HF. The mRNA and protein levels of related genes were examined using RT-qPCR and western blot. Cell viability and apoptosis were assessed using CCK-8 and flow cytometry, respectively. The interactions between ETS2, TUG1, miR-129-5p, and ATG7 were validated by luciferase activity, ChIP, and RNA-Binding protein Immunoprecipitation assays. According to our findings, H2 O2 stimulation increased the expression of ETS2, TUG1, and ATG7 while decreasing the expression of miR-129-5p in AC16 cells. Furthermore, H2 O2 stimulation induced cardiomyocyte apoptosis and autophagy, which were reversed by ETS2 depletion, TUG1 silencing, or miR-129-5p upregulation. Mechanistically, ETS2 promoted TUG1 expression by binding to the TUG1 promoter, and TUG1 sponged miR-129-5p to increase ATG7 expression. Furthermore, TUG1 overexpression reversed ETS2 knockdown-mediated inhibition of cardiomyocyte apoptosis and autophagy and miR-129-5p inhibition abolished TUG1 depletion-mediated suppression of cardiomyocyte apoptosis and autophagy in H2 O2 -induced AC16 cells. As presumed, ATG7 overexpression reversed miR-129-5p mimics-mediated repression of cardiomyocyte apoptosis and autophagy in H2 O2 -induced AC16 cells. Finally, ETS2 silencing reduced cardiomyocyte apoptosis and autophagy to slow HF progression by targeting the ETS2/TUG1/miR-129-5p/ATG7 axis, which may provide new therapeutic targets for HF treatment.

Adherence to Antiretrovirals and HIV Viral Suppression Under COVID-19 Pandemic Interruption - Findings from a Randomized Clinical Trial Using Ingestible Sensors to Monitor Adherence.

The COVID-19 pandemic had a significant impact on vulnerable populations, including people living with HIV. California implemented a coronavirus lockdown (stay-at-home order) in March 2020, which ended in January 2021. We evaluated the pandemic's impact on both clinical outcomes of HIV RNA viral load (VL) and retention rate in a randomized clinical trial conducted from May 2018 to October 2020. The intervention group took co-encapsulated antiretrovirals (ARVs) with ingestible sensor (IS) pills from baseline through week 16. The IS system has the capacity to monitor adherence in real-time using a sensor patch, a mobile device, and supporting software. Both the IS and usual care (UC) groups were followed monthly for 28 weeks. Longitudinal mixed-effects models with random intercept and slope (RIAS) were used to fit log VL and self-reported adherence. The sample size of the study was 112 (54 in IS). Overall, the retention rate at week 28 was 86%, with 90% before the lockdown and 83% after the lockdown. The lockdown strengthened the associations between adherence and VL. Before the lockdown, a 10% increase in adherence was associated with a 0.2 unit decrease in log VL (ß = -1.88, p = 0.004), while during the lockdown, the association was a 0.41-unit decrease (ß = -2.27, p = 0.03). The pandemic did not have a significant impact on our adherence-focused intervention. Our findings regarding the intervention effect remain valid. TRIAL REGISTRATION NUMBER: NCT02797262. Date registration: September 2015.

Pandemic velocity: Forecasting COVID-19 in the US with a machine learning & Bayesian time series compartmental model.

Predictions of COVID-19 case growth and mortality are critical to the decisions of political leaders, businesses, and individuals grappling with the pandemic. This predictive task is challenging due to the novelty of the virus, limited data, and dynamic political and societal responses. We embed a Bayesian time series model and a random forest algorithm within an epidemiological compartmental model for empirically grounded COVID-19 predictions. The Bayesian case model fits a location-specific curve to the velocity (first derivative) of the log transformed cumulative case count, borrowing strength across geographic locations and incorporating prior information to obtain a posterior distribution for case trajectories. The compartmental model uses this distribution and predicts deaths using a random forest algorithm trained on COVID-19 data and population-level characteristics, yielding daily projections and interval estimates for cases and deaths in U.S. states. We evaluated the model by training it on progressively longer periods of the pandemic and computing its predictive accuracy over 21-day forecasts. The substantial variation in predicted trajectories and associated uncertainty between states is illustrated by comparing three unique locations: New York, Colorado, and West Virginia. The sophistication and accuracy of this COVID-19 model offer reliable predictions and uncertainty estimates for the current trajectory of the pandemic in the U.S. and provide a platform for future predictions as shifting political and societal responses alter its course.

Quantitative data collection approaches in subject-reported oral health research: a scoping review.

BACKGROUND: This scoping review reports on studies that collect survey data using quantitative research to measure self-reported oral health status outcome measures. The objective of this review is to categorize measures used to evaluate self-reported oral health status and oral health quality of life used in surveys of general populations. METHODS: The review is guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) with the search on four online bibliographic databases. The criteria include (1) peer-reviewed articles, (2) papers published between 2011 and 2021, (3) only studies using quantitative methods, and (4) containing outcome measures of self-assessed oral health status, and/or oral health-related quality of life. All survey data collection methods are assessed and papers whose methods employ newer technological approaches are also identified. RESULTS: Of the 2981 unduplicated papers, 239 meet the eligibility criteria. Half of the papers use impact scores such as the OHIP-14; 10% use functional measures, such as the GOHAI, and 26% use two or more measures while 8% use rating scales of oral health status. The review identifies four data collection methods: in-person, mail-in, Internet-based, and telephone surveys. Most (86%) employ in-person surveys, and 39% are conducted in Asia-Pacific and Middle East countries with 8% in North America. Sixty-six percent of the studies recruit participants directly from clinics and schools, where the surveys were carried out. The top three sampling methods are convenience sampling (52%), simple random sampling (12%), and stratified sampling (12%). Among the four data collection methods, in-person surveys have the highest response rate (91%), while the lowest response rate occurs in Internet-based surveys (37%). Telephone surveys are used to cover a wider population compared to other data collection methods. There are two noteworthy approaches: 1) sample selection where researchers employ different platforms to access subjects, and 2) mode of interaction with subjects, with the use of computers to collect self-reported data. CONCLUSION: The study provides an assessment of oral health outcome measures, including subject-reported oral health status and notes newly emerging computer technological approaches recently used in surveys conducted on general populations. These newer applications, though rarely used, hold promise for both researchers and the various populations that use or need oral health care.

Toxicity evaluation of mesoporous silica particles Santa Barbara No. 15 amorphous in human umbilical vein endothelial cells: influence of particle morphology.

Morphology plays a vital role in determining the biological effects of silica nanoparticles (NPs), but its influence on the toxicity of silica NPs in endothelial cells (ECs) is still inconclusive. We synthesized five kinds of Santa Barbara 15 amorphous (SBA-15) particles with different shapes and added them to human umbilical vein endothelial cells (HUVEC). After 24 After incubation and treatment with 100 ml, more than 80% of the cells are still alive. The microgram/ml of SBA-15 indicates that SBA-15 has high biocompatibility. Fibrous SBA-15 (5) leads to the highest Si element concentration in HUVEC. No NP reduces the release of NO, and NO is an important signaling molecule in the vascular system. Only the aggregated spherical SBA-15 (3) will moderately reduce the endothelial nitric oxide synthase (eNOS) protein. Regarding transcription factors regulating eNOS, we found that all SBA-15 types significantly increased Kruppel-like factor 2 (KLF2) protein, irregular SBA-15 (1), non-aggregated spherical SBA-15 (2) and aggregation The spherical SBA-15 (3) greatly reduces KLF4 by more than 50%. Overall, our results indicate that SBA-15 with different morphologies can be internalized into HUVEC and only cause moderate cytotoxicity. All silica NPs have the smallest effect on the NO-eNOS pathway, but the irregular spherical SBA-15 reduces the eNOS modifier KLF4. The rod-shaped SBA-15 (4) seems to have higher biocompatibility because they are internalized and have negligible adverse effects on HUVEC. These results provide new evidence for the toxic effects of different forms of silica nanoparticles on HUVEC.

Hybrid slot-waveguide fed antenna using hexagonal boron nitride D'yakonov polaritons.

Polaritonic slot waveguides have been explored as a means of manipulating nanoscale fields to compete in the race for the sub-diffractional confinement of light. Hexagonal boron nitride (h-BN), when incorporated into hyperbolic-insulator-hyperbolic (HIH) configurations, is a strong contender, with its naturally occurring anisotropy allowing it to strongly confine and enhance local fields. However, while the volumetric phonon polaritons of h-BN have been widely used for these means, its hyperbolic surface phonon polaritons (HSPhPs) or D'yakonov polaritons contain untapped potential and are widely unused. In this paper, we qualitatively discuss the hybridization of fundamental hyperbolic surface phonon polariton modes in an HIH slot waveguide. The resulting symmetric dark, or lower mode, is then used to design a patch antenn, which shows possibilities for applying the familiar microstrip transmission-line approach of antenna design to this HSPhP antenna.

Enhanced stability of crosslinked and charged unimolecular micelles from multigeometry triblock copolymers with short hydrophilic segments: dissipative particle dynamics simulation.

High micellar stability and well-performed drug loading and release are two conflicting factors for unimolecular micelles as an ideal drug delivery system. Achieving the formation of unimolecular micelles with short hydrophilic blocks is a challenging and promising approach to solve this bottleneck and limitation of current unimolecular micelle systems. In this work, dissipative particle dynamics (DPD) simulation is used to study the synergetic effect of crosslinking and electrostatic repulsion on stability of unimolecular micelles and to analyze the micro-mechanism and factors influencing this synergetic stabilization strategy. The strategy can generate unimolecular micelles with extremely high stability for various supramolecular polymers with short hydrophilic chains. Protonation of DEAEMA blocks leads to a large improvement in micellar hydrophilicity. The protonated middle layer further shrinks through crosslinking to produce the largest charge density, enlarging the electrostatic repulsion between colloidal particles. Additionally, the crosslinking and protonation treatment maximizes the extension degree of hydrophilic EO segments due to the increasing steric hindrance and poor compatibility between DEAHEMA and EO blocks. In this study, the relation between shrinkage degree of hydrophobic cores and stability of unimolecular micelles is first reported. The above-mentioned transition of micellar structures and properties results in the maximum degree of core shrinkage (Rg of MMA blocks) corresponding to the high stability of unimolecular micelles. Further study shows that the increasing cyclization degree, the mode of end cyclization, and the crosslinking and electrostatic repulsion of the middle layer all exert favorable effects on the stability of unimolecular micelles due to controlled shrinkage of hydrophobic cores.

Development of a parents' short form survey of their children's oral health.

BACKGROUND: Parents play an important role in their children's oral health behaviors, provide oral health access, initiate prevention, and coping strategies for health care. AIM: This paper develops a short form (SF) to assist parents to evaluate their children's oral health status using Patient-Reported Outcome Measurement Information System (PROMIS) framework that conceptualized health as physical, mental, and social components. DESIGN: Surveys of parents were conducted at dental clinics in Los Angeles County, together with an on-site clinical examination by dentists to determine clinical outcomes, Children's Oral Health Status Index (COHSI), and referral recommendations (RRs). Graded response models in item response theory were used to create the SF. A toolkit including SF, demographic information, and algorithms was developed to predict the COHSI and RRs. RESULTS: The final SF questionnaire consists of eight items. The square root mean squared error for the prediction of COHSI is 7.6. The sensitivity and specificity of using SF to predict immediate treatment needs (binary RRs) are 85% and 31%. CONCLUSIONS: The parent SF is an additional component of the oral health evaluation toolkit that can be used for oral health screening, surveillance program, policy planning, and research of school-aged children and adolescents from guardian perspectives.

Hybrid long-range hyperbolic phonon polariton waveguide using hexagonal boron nitride for mid-infrared subwavelength confinement.

Long propagation waveguides are critical for any photonic-on-chip applications. There has been an extensive investigation in using plasmon polaritons for near-infrared and optical networks, however, for mid- to long-wave IR applications phonon polaritons are required given that plasmonic polaritonic effects are negligible. In recent years, extensive research has been conducted on hexagonal boron nitride (h-BN), which has shown h-BN to have naturally occurring subwavelength, volumetrically confined hyperbolic phonon polaritons (HPhPs). This work presents numerical results for both long- and short-range phononic volumetric polariton modes in a slab of h-BN. A hybrid long-range phononic waveguide consisting of two identical dielectric cylinder wires symmetrically placed on each side of the h-BN slab is coupled to the long-range HPhP mode. Based on analytical coupled-mode theory and computational finite element analysis, we have investigated the modal characteristics of the hybrid long-range phonon polaritonic waveguide. Due to the strong coupling between the high index cylindrical-waveguide mode and the HPhPs in the h-BN thin film, subwavelength confinement can be achieved (modal area ranging from  10-2λo2 to  10-1λo2) while enabling long propagation distances (7λ0-370λ0).

Short form development for oral health patient-reported outcome evaluation in children and adolescents.

PURPOSE: Children and adolescents are vulnerable to dental problems and oral diseases. This paper presents the development of two multi-item self-report scales for use in assessing oral health status of children and adolescents. METHODS: Following the Patient-Reported Outcome Measurement Information System framework, survey questions were designed using a newly developed conceptual model. These items were administered to 334 children and adolescents (8-17 years) along with concurrent dental exams. Exploratory and confirmatory factor analyses were conducted and the item response theory graded response model was used to estimate item parameters and oral health status scores and to identify short-form items. The items were selected by high level of information and wide coverage of different domains to assess Child Oral Health Status Index (COHSI) and treatment referral recommendations (RR). RESULTS: The long form consists of 28 items. The short-form includes 12 items (8 for COHSI and 7 for RR with 3 common items).The intra-class correlations between long form and short-form were 0.90 for COHSI and 0.87 for RR. CONCLUSION: The short-forms provide a possible solution for the longstanding challenge of oral health evaluation for large populations of children and adolescents. The calibrated long form provides the foundation for computer adaptive test administration. These oral health assessment toolkits can be used for oral health screening, surveillance program, policy planning, and research.

[Researching on fingerprint of Inulacappa by HPLC].

OBJECTIVE: This study is to establish the fingerprint and find out the common chromatographic peaks of Inula cappa by HPLC. METHOD: The HPLC analysis was performed on an Agilent Eclipse Plus C18 column (2.1 mm x 150 mm, 1.8 µm) with 0.1% fomic acid aqueous solution-0.1% fomic acid acetonitrile solution as mobile phase at a flow rate of 0.3 · mL(-1) · min(-1); The detective wavelength is 325 nm; The column temperature is 45 °C. RESULT: The results indicated that 5 of 17 common peaks were identified . The similarity about 10 groups of Inulacappais is over 0.95. CONCLUSION: This method is able to be a scientific basis of quality assessment according to its convenient and reliable.

Alzheimer's Disease Knowledge Graph Enhances Knowledge Discovery and Disease Prediction.

Background: Alzheimer's disease (AD), a progressive neurodegenerative disorder, continues to increase in prevalence without any effective treatments to date. In this context, knowledge graphs (KGs) have emerged as a pivotal tool in biomedical research, offering new perspectives on drug repurposing and biomarker discovery by analyzing intricate network structures. Our study seeks to build an AD-specific knowledge graph, highlighting interactions among AD, genes, variants, chemicals, drugs, and other diseases. The goal is to shed light on existing treatments, potential targets, and diagnostic methods for AD, thereby aiding in drug repurposing and the identification of biomarkers. Results: We annotated 800 PubMed abstracts and leveraged GPT-4 for text augmentation to enrich our training data for named entity recognition (NER) and relation classification. A comprehensive data mining model, integrating NER and relationship classification, was trained on the annotated corpus. This model was subsequently applied to extract relation triplets from unannotated abstracts. To enhance entity linking, we utilized a suite of reference biomedical databases and refine the linking accuracy through abbreviation resolution. As a result, we successfully identified 3,199,276 entity mentions and 633,733 triplets, elucidating connections between 5,000 unique entities. These connections were pivotal in constructing a comprehensive Alzheimer's Disease Knowledge Graph (ADKG). We also integrated the ADKG constructed after entity linking with other biomedical databases. The ADKG served as a training ground for Knowledge Graph Embedding models with the high-ranking predicted triplets supported by evidence, underscoring the utility of ADKG in generating testable scientific hypotheses. Further application of ADKG in predictive modeling using the UK Biobank data revealed models based on ADKG outperforming others, as evidenced by higher values in the areas under the receiver operating characteristic (ROC) curves. Conclusion: The ADKG is a valuable resource for generating hypotheses and enhancing predictive models, highlighting its potential to advance AD's disease research and treatment strategies.

Development of short forms for screening children's dental caries and urgent treatment needs using item response theory and machine learning methods.

OBJECTIVES: Surveys can assist in screening oral diseases in populations to enhance the early detection of disease and intervention strategies for children in need. This paper aims to develop short forms of child-report and proxy-report survey screening instruments for active dental caries and urgent treatment needs in school-age children. METHODS: This cross-sectional study recruited 497 distinct dyads of children aged 8-17 and their parents between 2015 to 2019 from 14 dental clinics and private practices in Los Angeles County. We evaluated responses to 88 child-reported and 64 proxy-reported oral health questions to select and calibrate short forms using Item Response Theory. Seven classical Machine Learning algorithms were employed to predict children's active caries and urgent treatment needs using the short forms together with family demographic variables. The candidate algorithms include CatBoost, Logistic Regression, K-Nearest Neighbors (KNN), Naïve Bayes, Neural Network, Random Forest, and Support Vector Machine. Predictive performance was assessed using repeated 5-fold nested cross-validations. RESULTS: We developed and calibrated four ten-item short forms. Naïve Bayes outperformed other algorithms with the highest median of cross-validated area under the ROC curve. The means of best testing sensitivities and specificities using both child-reported and proxy-reported responses were 0.84 and 0.30 for active caries, and 0.81 and 0.31 for urgent treatment needs respectively. Models incorporating both response types showed a slightly higher predictive accuracy than those relying on either child-reported or proxy-reported responses. CONCLUSIONS: The combination of Item Response Theory and Machine Learning algorithms yielded potentially useful screening instruments for both active caries and urgent treatment needs of children. The survey screening approach is relatively cost-effective and convenient when dealing with oral health assessment in large populations. Future studies are needed to further leverage the customize and refine the instruments based on the estimated item characteristics for specific subgroups of the populations to enhance predictive accuracy.

LESA: Longitudinal Elastic Shape Analysis of Brain Subcortical Structures.

Over the past 30 years, magnetic resonance imaging has become a ubiquitous tool for accurately visualizing the change and development of the brain's subcortical structures (e.g., hippocampus). Although subcortical structures act as information hubs of the nervous system, their quantification is still in its infancy due to many challenges in shape extraction, representation, and modeling. Here, we develop a simple and efficient framework of longitudinal elastic shape analysis (LESA) for subcortical structures. Integrating ideas from elastic shape analysis of static surfaces and statistical modeling of sparse longitudinal data, LESA provides a set of tools for systematically quantifying changes of longitudinal subcortical surface shapes from raw structure MRI data. The key novelties of LESA include: (i) it can efficiently represent complex subcortical structures using a small number of basis functions and (ii) it can accurately delineate the spatiotemporal shape changes of the human subcortical structures. We applied LESA to analyze three longitudinal neuroimaging data sets and showcase its wide applications in estimating continuous shape trajectories, building life-span growth patterns, and comparing shape differences among different groups. In particular, with the Alzheimer's Disease Neuroimaging Initiative (ADNI) data, we found that the Alzheimer's Disease (AD) can significantly speed the shape change of ventricle and hippocampus from 60 to 75 years old compared with normal aging.

Preparation of reversible cross-linked amphiphilic polymeric micelles with pH-responsive behavior for smart drug delivery.

A new type of reversible cross-linked and pH-responsive polymeric micelle (PM), poly[polyethylene glycol methacrylate-co-2-(acetoacetoxy)ethyl methacrylate]-b-poly [2-(dimethylamino)ethyl methacrylate] [P(PEGMA-co-AEMA)-b-PDMAEMA], was synthesized for targeted delivery of curcumin. After reversible cross-linking of the micellar shell, the PMs with a typical core-shell structure exhibited excellent stability against extensive dilution and good reversibility of pH-responsiveness in solutions with different pH values. P(PEGMA9-co-AEMA6)-b-PDMAEMA10 has the lowest critical micelle concentration (CMC) value (0.0041 mg mL-1), the highest loading capacity (13.86%) and entrapment efficiency (97.03%). A slow sustained drug release at pH 7.4 with 12.36% in 108 h, while a fast release (42.36%) was observed at pH 5.0. Furthermore, a dissipative particle dynamics (DPD) simulation method was employed to investigate the self-assembly process and pH-responsive behavior of PMs. The optimal drug-carrier ratio (2%) and fraction of water (92%) were confirmed by analyzing the drug distribution and morphology of micelles during the self-assembly process of the block copolymer. The simulation results were consistent with experimental results, indicating DPD simulation shows potential to study the structure properties of reversible cross-linked micelles. The present findings provide a new method for the development of SDDS with good structural stability and controlled drug release properties.

An atlas of trait associations with resting-state and task-evoked human brain functional organizations in the UK Biobank.

Functional magnetic resonance imaging (fMRI) has been widely used to identify brain regions linked to critical functions, such as language and vision, and to detect tumors, strokes, brain injuries, and diseases. It is now known that large sample sizes are necessary for fMRI studies to detect small effect sizes and produce reproducible results. Here we report a systematic association analysis of 647 traits with imaging features extracted from resting-state and task-evoked fMRI data of more than 40,000 UK Biobank participants. We used a parcellation-based approach to generate 64,620 functional connectivity measures to reveal fine-grained details about cerebral cortex functional organizations. The difference between functional organizations at rest and during task was examined, and we have prioritized important brain regions and networks associated with a variety of human traits and clinical outcomes. For example, depression was most strongly associated with decreased connectivity in the somatomotor network. We have made our results publicly available and developed a browser framework to facilitate the exploration of brain function-trait association results (http://fmriatlas.org/).

Heart-brain connections: Phenotypic and genetic insights from magnetic resonance images.

Cardiovascular health interacts with cognitive and mental health in complex ways, yet little is known about the phenotypic and genetic links of heart-brain systems. We quantified heart-brain connections using multiorgan magnetic resonance imaging (MRI) data from more than 40,000 subjects. Heart MRI traits displayed numerous association patterns with brain gray matter morphometry, white matter microstructure, and functional networks. We identified 80 associated genomic loci (P < 6.09 × 10-10) for heart MRI traits, which shared genetic influences with cardiovascular and brain diseases. Genetic correlations were observed between heart MRI traits and brain-related traits and disorders. Mendelian randomization suggests that heart conditions may causally contribute to brain disorders. Our results advance a multiorgan perspective on human health by revealing heart-brain connections and shared genetic influences.

Pediatric patients with familially inherited sitosterolemia: Two case reports.

Background: Sitosterolemia is a rare recessive genetic abnormality of hyperlipidemia; it is characterized by increased levels and accumulation of sitosterol in the plasma and local tissues. Case descriptions: The study subjects were two siblings (brother and sister) who had sitosterolemia with systemic multiple xanthomas as the main manifestation. The main clinical manifestations were hypercholesterolemia, premature atherosclerosis, arrhythmia, systemic multiple xanthomas, etc. After genetic testing, it was found that the patients had a compound heterozygous mutation of c.1324+1de1G in exon 7 and exon 9 of chromosome 2p21 of the adenosine triphosphate binding cassette transporter G family member 5(ABCG5) gene; the mutation at c.904+1G>A was of maternal origin, and the mutation at c. 1324+1de1G was of paternal origin. The compound heterozygous mutation of these two genes led to a metabolic disorder of plant sterols in vivo. Conclusion: Sitosterolemia is an autosomal recessive disease that could be effectively controlled after dietary control and oral lipid-lowering therapy with Ezetimibe. Xanthomas, which affects function and appearance, could be surgically removed, and primary wound healing could be achieved.

The ATEAM study: Advances in technology to enhance PrEP adherence monitoring (ATEAM) among young men who have sex with men.

Young age has consistently correlated with lower adherence to pre-exposure prophylaxis (PrEP) in young men who have sex with men (YMSM). Digital medicine, a dynamic healthcare platform of wearable physiological sensors and mobile communication technology that can respond to medication nonadherence rapidly, has the potential in promoting PrEP adherence. We evaluated the feasibility and acceptability of Proteus Discover, a digital monitoring adherence system, to measure PrEP adherence and provide real-time feedback among cisgender YMSM and transgender women. One hundred HIV-negative young men and transgender women ages 16-24 years were enrolled in a 24-week randomized controlled crossover study to tenofovir disoproxil fumarate with emtricitabine (TDF/FTC) coencapsulated with Proteus Discover versus TDF/FTC standard-of-care. Participants in the 12-week Proteus Discover arm received weekly SMS text messages to promote pill taking based on Proteus Discover adherence data. Dried blood spots (DBS) were collected at 4-week intervals for tenofovir diphosphate (TFV-DP) in red blood cells as the referent and questionnaires were completed to assess acceptability, usability, and patterns of use. Linear mixed models analyzed the relationship between 30-day adherence measured by DBS and Proteus Discover. PrEP adherence was high overall. Adherence, as measured by DBS, was correlated with adherence as measured by Proteus Discover (p value = 0.03). Most participants reported that Proteus Discover helped them take their PrEP daily and that the system was easy to use. However, a majority (53.5%-60.5%) disagreed with the statement that wearing the patch was not an issue. There was an incremental increase in TFV-DP in DBS with adherence by Proteus Discover. More research is warranted to explore optimizing PrEP adherence for youth through real-time monitoring.

Therapeutic effect of sodium­glucose cotransporter 2 inhibitor and benazepril on diabetic nephropathic rats.

The present study aimed to compare the therapeutic effect of sodium/glucose cotransporter 2 (SGLT2) inhibitor and benazepril on diabetic nephropathy (DN) rats and provide a potential novel agent for the clinical treatment of DN. The DN model was established on rats. Animals were dosed orally with SGLT2 and benazepril daily for 4 weeks. The pathological state of renal tissues were evaluated using hematoxylin and eosin, Masson and periodic acid-Schiff staining. The change in the morphology of renal tissues was observed through transmission electron microscopy. Western blotting was utilized to determine the expression level of TGF-ß, N-terminal fragment of the B-type natriuretic peptide precursor (NT-proBNP) and matrix metalloproteinase-9 (MMP-9). The expression level of endothelin 1 (ET-1), von Willebrand factor (vWF), collagen (col)-I and α smooth muscle actin (α-SMA) in renal tissues was visualized using immunohistochemical assay. Significant pathological changes in the glomerular basement membrane, mesangial membrane, renal tubules, lumen, renal interstitial region and renal tubular epithelial cells were observed in DN rats, accompanied by increased collagen fibers. SGLT2 inhibitor treatment demonstrated more alleviatory effects on the pathological changes of renal tissues compared with benazepril. Compared with control, TGF-ß and NT-proBNP were upregulated in DN rats, accompanied by the downregulation of MMP-9, ET-1, vWF, col-I and α-SMA, which were markedly reversed by treatment with SGLT2 inhibitor and benazepril. Compared with benazepril, the effects of SGLT2 inhibitor on the expression level of TGF-ß, NT-proBNP, MMP-9, ET-1, vWF, col-I and α-SMA were more significant. Overall, SGLT2 inhibitor demonstrated an increased therapeutic effect against DN rats compared with benazepril by regulating cytokines, renal fibrosis and extracellular matrix degradation.