Relevance of Emotion of Anxiety and Fear of Dentistry as Motivational Conflict in Oral Health Behaviors.

AIM: This study was undertaken with an aim to explore the influence of factors associated with anxiety and fear of dentistry on oral health behavior. MATERIALS AND METHODS: A total of 84 patients aged 20-40 years visiting the dental institute for the management of gum diseases (gingivitis and periodontitis) and tooth decay (dental caries) were enrolled. Fear of dentistry and oral health behaviors were recorded employing a dental fear survey (DFS) and oral health behaviors checklist. Each of the 20-item scale of DFS was rated on a 5-point Likert scale. The oral health behavior checklist was based on oral hygiene habits, patterns of utilization of dental services, food habits, and use of tobacco products. Each of the 13-item checklist comprised a closed-ended statement with a high score corresponding to more positive oral health behavior. RESULTS: Domains of dental fear (avoidance of dentistry, physiological arousal, and fear of specific stimuli) and total dental fear did not predict oral hygiene habits and nutritional preferences (p > 0.05). Physiological arousal was a positive predictor of utilization of dental services (p = 0.009) and oral health behavior (p = 0.042). Oral health behaviors were found to be positively correlated with three factors of DFS. CONCLUSION: Anxiety and fear of dentistry are not found to influence personal preventive oral care with reference to oral hygiene habits. Avoidance of dentistry factor of DFS is positively correlated with oral health behavior. Dental fear and anxiety do not impact oral health behaviors adversely. CLINICAL SIGNIFICANCE: In this era of youth and beauty, the utilization of professional dental care services is not affected by fear of invasive nature of dental procedures. Establishing the groundwork for knowledge regarding the scope of fear appeals in anxiety for dentistry may help to augment positive oral health behaviors for effective primary prevention of oral diseases. Interactions among personality characteristics, attitudes, emotions, and health behavior need further exploration. How to cite this article: Supriya, Singh R, Ahsan A. Relevance of Emotion of Anxiety and Fear of Dentistry as Motivational Conflict in Oral Health Behaviors. J Contemp Dent Pract 2024;25(3):280-288.

Longitudinal Lower Airway Microbial Signatures of Acute Cellular Rejection in Lung Transplantation.

Rationale: Acute cellular rejection (ACR) after lung transplantation is a leading risk factor for chronic lung allograft dysfunction. Prior studies have demonstrated dynamic microbial changes occurring within the allograft and gut that influence local adaptive and innate immune responses. However, the lung microbiome's overall impact on ACR risk remains poorly understood. Objective: To evaluate whether temporal changes in microbial signatures were associated with the development of ACR. Methods: We performed cross-sectional and longitudinal analyses (joint modeling of longitudinal and time-to-event data and trajectory comparisons) of 16S rRNA gene sequencing results derived from lung transplant recipient lower airway samples collected at multiple timepoints. Measurements and Main Results: Among 103 lung transplant recipients, 25 (24.3%) developed ACR. In comparing samples acquired one month after transplant, subjects who never developed ACR demonstrated lower airway enrichment with several oral commensals (e.g., Prevotella and Veillonella spp.) compared to those with current or future (beyond one month) ACR. However, a subgroup analysis of those who developed ACR beyond one month revealed delayed enrichment with oral commensals occurring at the time of ACR diagnosis compared to baseline, when enrichment with more traditionally pathogenic taxa was present. In longitudinal models, dynamic changes in alpha diversity (characterized by an initial decrease and a subsequent increase) and in the taxonomic trajectories of numerous oral commensals were more commonly observed in subjects with ACR. Conclusion: Dynamic changes in the lower airway microbiota are associated with the development of ACR, supporting its potential role as a useful biomarker or in ACR pathogenesis.

Synbiotics as potent functional food: recent updates on therapeutic potential and mechanistic insight.

Synbiotics are the specific mixtures of prebiotics with probiotics intended to give health benefits to the host by stabilizing and supporting the gut microbiota.The prebiotic substance used in the synbiotics selectively favors the growth and metabolite production of probiotics. Gut microbiome dysbiosis may lead to generation and progression of various chronic diseases. Synbiotics act synergistically to modulate the gut ecosystem for improvement of metabolic health of the host. Probiotics have been found promising against various diseases being safer, effective, as an alternative or combinatorial therapy. Specific combinations of probiotics with suitable prebiotic substrate as synbiotics, may be the more effective therapeutic agents that can provide all benefits of probiotics as well as prebiotics. Though, effective combinations, dosage, mechanism of action, safety, cost effectiveness and other clinical investigations are required to be established along with other relevant aspects. Synbiotics have the potential to be functional food of importance in future. Present review summarizes the mechanistic overview of synbiotics related to gut microbiota, therapeutic potential and promising health benefits for human illnesses according to the available literature. In present scenario, synbiotics are more promising future alternatives as therapeutics to maintain healthy microbiota inside the host gut which directly affects the onset or development ofrelated disorders or diseases.

miRNA-194-3p represses NF-κB in gliomas to attenuate iPSC genes and proneural to mesenchymal transition.

Severe tumor heterogeneity drives the aggressive and treatment refractory nature of glioblastomas (GBMs). While limiting GBM heterogeneity offers promising therapeutic potential, the underlying mechanisms that regulate GBM plasticity remain poorly understood. We utilized 14 patient-derived and four commercially available cell lines to uncover miR-194-3p as a key epigenetic determinant of stemness and transcriptional subtype in GBM. We demonstrate that miR-194-3p degrades TAB2, an important mediator of NF-κB activity, decreasing NF-κB transcriptional activity. The loss in NF-κB activity following miR-194-3p overexpression or TAB2 silencing decreased expression of induced pluripotent stem cell (iPSC) genes, inhibited the oncogenic IL-6/STAT3 signaling axis, suppressed the mesenchymal transcriptional subtype in relation to the proneural subtype, and induced differentiation from the glioma stem cell (GSC) to monolayer (ML) phenotype. miR-194-3p/TAB2/NF-κB signaling axis acts as an epigenetic switch that regulates GBM plasticity and targeting this signaling axis represents a potential strategy to limit transcriptional heterogeneity in GBMs.

Do rainfed production systems have lower environmental impact over irrigated production systems?: On -farm mitigation strategies.

The intensive agriculture practices improved the crop productivity but escalated energy inputs (EI) and carbon foot print (CF) which contributes to global warming. Hence designing productive, profitable crop management practices under different production systems with low environmental impact (EI and CF) is the need of the hour. To identify the practices, quantification of baseline emissions and the major sources of emissions are required. Indian agriculture has diversified crops and production systems but there is dearth of information on both EI and CF of these production systems and crops. Hence the present study was an attempt to find hot spots and identify suitable strategies with high productivity, energy use efficiency (EUE) and carbon use efficiency (CUE). Energy and carbon balance of castor, cotton, chickpea, groundnut, maize, rice (both rainfed and irrigated), wheat, sugarcane (only irrigated), pigeon pea, soybean, sorghum, pearl millet (only rainfed) in different production systems was assessed. Field specific data on different crop management practices as well as grain and biomass yields were considered. Rainfed production systems had lower EI and CF than irrigated system. The nonrenewable sources of energy like fertilizer (64 %), irrigation (78 %), diesel fuel (75 %) and electricity (67 %) are the major source of energy input. Rainfed crops recorded higher CUE over irrigated condition. Adoption of technologies like efficient irrigation strategies (micro irrigation), enhancing fertilizer use efficiency (site specific nutrient management or slow release fertilizer), conservation agriculture (conservation or reduced tillage) rice cultivation methods (SRI or Direct seeded rice) were the mitigation strategies. These results will help policy makers and stake holders in adoption of suitable strategies for sustainable intensification.

Development of a decentralized cohort for studying post-acute sequelae of COVID-19 in India in the Data4life Study.

BACKGROUND: Decentralized, digital health studies can provide real-world evidence of the lasting effects of COVID-19 on physical, socioeconomic, psychological, and social determinant factors of health in India. Existing research cohorts, however, are small and were not designed for longitudinal collection of comprehensive data from India's diverse population. Data4Life is a nationwide, digitally enabled, health research initiative to examine the post-acute sequelae of COVID-19 across individuals, communities, and regions. Data4Life seeks to build an ethnically and geographically diverse population of at least 100,000 participants in India. METHODS: Here we discuss the feasibility of developing a completely decentralized COVID-19 cohort in India through qualitative analysis of data collection procedures, participant characteristics, participant perspectives on recruitment and reported study motivation. RESULTS: As of June 13th, 2022, more than 6,000 participants from 17 Indian states completed baseline surveys. Friend and family referral were identified as the most common recruitment method (64.8%) across all demographic groups. Helping family and friends was the primary reason reported for joining the study (61.5%). CONCLUSIONS: Preliminary findings support the use of digital technology for rapid enrollment and data collection to develop large health research cohorts in India. This demonstrates the potential for expansion of digitally enabled health research in India. These findings also outline the value of person-to-person recruitment strategies when conducting digital health research in modern-day India. Qualitative analysis reveals opportunities to increase diversity and retention in real time. It also informs strategies for improving participant experiences in the current Data4Life initiative and future studies.

Due to the vast geographical size and ethnic diversity of the population, India represents a huge challenge for conducting research studies. The Data4Life study was set up to understand if digital tools can be an effective way to study long-term effects of COVID-19 across India. We studied different ways of collecting the relevant information from participants, the background of each participant, reasons, and motivation of each participant for joining the study. The results showed that friend and family referrals were the most common recruitment reason. Helping family and friends was reported as the main motivation for joining the study. Overall, the findings support the use of digital tools as an effective recruitment method for research studies in India.

Mung bean as a potent emerging functional food having anticancer therapeutic potential: Mechanistic insight and recent updates.

Cancer is still a major challenge for humans. In recent years, researchers have focused on plant-based metabolites as a safe, efficient, alternative or combinatorial, as well as cost-effective preventive strategy against carcinogenesis. Mung bean is an important nutritious legume, and known for providing various health benefits due to various bioactive phytochemicals and easily digestible proteins. Regular intake of mung bean helps to regulate metabolism by affecting the growth and survival of good microbes in the host gut. Mung bean has also been reported to have anti-inflammatory, antioxidant, antiproliferative, and immunomodulatory properties. These properties may possess the preventive potential of mung bean against carcinogenesis. Bibliographic databases for peer-reviewed research literature were searched through a structured conceptual approach using focused review questions on mung beans, anticancer, therapeutics, and functional foods along with inclusion/exclusion criteria. For the appraisal of the quality of retrieved articles, standard tools were employed. A deductive qualitative content analysis methodology further led us to analyze outcomes of the research and review articles. The present review provides recent updates on the anticancer potential of mung bean and the possible mechanism of action thereof to prevent carcinogenesis and metastasis. Extensive research on the active metabolites and mechanisms of action is required to establish the anticancer potential of mung bean. Keeping the above facts in view, mung bean should be investigated for its bioactive compounds, to be considered as functional food of the future.

Can adoption of climate resilient management practices achieve carbon neutrality in traditional green revolution states of Punjab and Haryana?

Decreasing greenhouse gas (GHG) emissions and enhancing soil carbon (C) sequestration in cropland are necessary to achieve carbon neutrality at national scale. The major objective of this study is to quantify the GHG mitigation potential of adopted climate resilient (CR) practices in CR villages using Ex-ACT tool developed by Food and Agriculture Organization (FAO). Intensively cultivated area of Punjab and Haryana was selected for carrying out this study. In both the states, villages were selected by considering the climate for past 30 years. In the selected villages, a set of CR practices were implemented in annuals, perennials, irrigated rice, fertilizer use, land use change and livestock and quantified the GHG mitigation potential in these villages for next twenty years. The tool predicted that the CR practices adopted were successful in enhancing the overall sink (carbon balance) in all the study villages. The villages of Punjab had recorded higher mitigation potential as compared to the villages of Haryana. The overall sink potential in these villages ranged from -354 to -38309 Mg CO2-eq. The change in sink potential varied from 3.16 to 112% with lowest in Radauri and highest in Badhauchhi kalan village. The sink potential got doubled in Badhauchhi kalan village due to stopping rice straw burning and increase in area under perennials by 25%. The source potential varied from 6.33 to -7.44% across the study villages. Even with the implementation of NICRA, there was increase in source by 5.58 and 6.33% in Killi Nihal Singh Wala and Radauri due to irrigated rice, land use change and livestock. Majorly, rice straw burning was seen in most of the study villages, yet, with proper residue management and adoption of CR practices (mainly intermittent flooding) in rice cultivation resulted in emissions reduction up to 5-26% with enhanced productivity up to 15-18%, which can be considered for scaling up. Fertilizer management reduced the emissions by average of 13% across the study villages. Farm gate emission intensity per ton of milk and rice recorded highest emission intensity compared to annuals and perennials suggesting strict implementation of CR practices in rice cultivation and livestock sector. Implementation and scaling up of CR practices could potentially reduce the emissions and make the village C negative in intensive rice-wheat production system.

Seasonal variation in blood pressure control across US health systems.

OBJECTIVE: We aimed to characterize seasonal variation in US population-based blood pressure (BP) control and BP-related metrics and evaluate the association between outdoor temperature and BP control variation. METHODS: We queried electronic health records (EHRs) from 26 health systems, representing 21 states, to summarize BP metrics by quarters of 12-month periods from January 2017 to March 2020. Patients with at least one ambulatory visit during the measurement period and a hypertension diagnosis during the first 6 months or prior to the measurement period were included. Changes in BP control, BP improvement, medication intensification, average SBP reduction after medication intensification across quarters and association with outdoor temperature were analyzed using weighted generalized linear models with repeated measures. RESULTS: Among 1 818 041 people with hypertension, the majority were more than 65 years of age (52.2%), female (52.1%), white non-Hispanic (69.8%) and had stage 1/2 hypertension (64.8%). Overall, BP control and process metrics were highest in quarters 2 and 3, and lowest in quarters 1 and 4. Quarter 2 had the highest percentage of improved BP (31.95 ±â€Š0.90%) and average SBP reduction after medication intensification (16 ±â€Š0.23 mmHg). Quarter 3 had the highest percentage of BP controlled (62.25 ±â€Š2.55%) and lowest with medication intensification (9.73 ±â€Š0.60%). Results were largely consistent in adjusted models. Average temperature was associated with BP control metrics in unadjusted models, but associations were attenuated following adjustment. CONCLUSION: In this large, national, EHR-based study, BP control and BP-related process metrics improved during spring/summer months, but outdoor temperature was not associated with performance following adjustment for potential confounders.

E-sports: What mental health professionals from low & middle-income countries must know.

'E-sports' refers to organized videogames. As the number of online gamers and interest in esports continue to rise in low and middle-income countries, mental health professionals need to be aware of their possible psychological and clinical implications. Only a small fraction of esports players present with gaming addiction, but a relatively larger proportion with subtle impairment impacting domains such as self-esteem, performance-related issues, family conflict, sleep-related issues or physical health. An adequate knowledge of esports, its concept, origins, genre and current status should equip mental health professionals in developing a good rapport with these young clients and correctly evaluate them. This review provides an overview of esports and how it pertains to mental health professionals.

Microbial metabolite restricts 5-fluorouracil-resistant colonic tumor progression by sensitizing drug transporters via regulation of FOXO3-FOXM1 axis.

The survival rate of colorectal cancer patients is adversely affected by the selection of tumors resistant to conventional anti-cancer drugs such as 5-fluorouracil (5FU). Although there is mounting evidence that commensal gut microbiota is essential for effective colon cancer treatment, the detailed molecular mechanisms and the role of gut microbial metabolites remain elusive. The goal of this study is to decipher the impact and mechanisms of gut microbial metabolite, urolithin A (UroA) and its structural analogue, UAS03 on reversal of 5FU-resistant (5FUR) colon cancers. Methods: We have utilized the SW480 and HCT-116 parental (5FU-sensitive) and 5FUR colon cancer cells to examine the chemosensitization effects of UroA or UAS03 by using both in vitro and in vivo models. The effects of mono (UroA/UAS03/5FU) and combinatorial therapy (UroA/UAS03 + 5FU) on cell proliferation, apoptosis, cell migration and invasion, regulation of epithelial mesenchymal transition (EMT) mediators, expression and activities of drug transporters, and their regulatory transcription factors were examined using molecular, cellular, immunological and flowcytometric methods. Further, the anti-tumor effects of mono/combination therapy (UroA or UAS03 or 5FU or UroA/UAS03 + 5FU) were examined using pre-clinical models of 5FUR-tumor xenografts in NRGS mice and azoxymethane (AOM)-dextran sodium sulfate (DSS)-induced colon tumors. Results: Our data showed that UroA or UAS03 in combination with 5FU significantly inhibited cell viability, proliferation, invasiveness as well as induced apoptosis of the 5FUR colon cancer cells compared to mono treatments. Mechanistically, UroA or UAS03 chemosensitized the 5FUR cancer cells by downregulating the expression and activities of drug transporters (MDR1, BCRP, MRP2 and MRP7) leading to a decrease in the efflux of 5FU. Further, our data suggested the UroA or UAS03 chemosensitized 5FUR cancer cells to 5FU treatment through regulating FOXO3-FOXM1 axis. Oral treatment with UroA or UAS03 in combination with low dose i.p. 5FU significantly reduced the growth of 5FUR-tumor xenografts in NRGS mice. Further, combination therapy significantly abrogated colonic tumors in AOM-DSS-induced colon tumors in mice. Conclusions: In summary, gut microbial metabolite UroA and its structural analogue UAS03 chemosensitized the 5FUR colon cancers for effective 5FU chemotherapy. This study provided the novel characteristics of gut microbial metabolites to have significant translational implications in drug-resistant cancer therapeutics.

Implementing a pragmatic clinical trial to tailor opioids for acute pain on behalf of the IGNITE ADOPT PGx investigators.

Opioid prescribing for postoperative pain management is challenging because of inter-patient variability in opioid response and concern about opioid addiction. Tramadol, hydrocodone, and codeine depend on the cytochrome P450 2D6 (CYP2D6) enzyme for formation of highly potent metabolites. Individuals with reduced or absent CYP2D6 activity (i.e., intermediate metabolizers [IMs] or poor metabolizers [PMs], respectively) have lower concentrations of potent opioid metabolites and potentially inadequate pain control. The primary objective of this prospective, multicenter, randomized pragmatic trial is to determine the effect of postoperative CYP2D6-guided opioid prescribing on pain control and opioid usage. Up to 2020 participants, age ≥8 years, scheduled to undergo a surgical procedure will be enrolled and randomized to immediate pharmacogenetic testing with clinical decision support (CDS) for CYP2D6 phenotype-guided postoperative pain management (intervention arm) or delayed testing without CDS (control arm). CDS is provided through medical record alerts and/or a pharmacist consult note. For IMs and PM in the intervention arm, CDS includes recommendations to avoid hydrocodone, tramadol, and codeine. Patient-reported pain-related outcomes are collected 10 days and 1, 3, and 6 months after surgery. The primary outcome, a composite of pain intensity and opioid usage at 10 days postsurgery, will be compared in the subgroup of IMs and PMs in the intervention (n = 152) versus the control (n = 152) arm. Secondary end points include prescription pain medication misuse scores and opioid persistence at 6 months. This trial will provide data on the clinical utility of CYP2D6 phenotype-guided opioid selection for improving postoperative pain control and reducing opioid-related risks.

Design and rationale of GUARDD-US: A pragmatic, randomized trial of genetic testing for APOL1 and pharmacogenomic predictors of antihypertensive efficacy in patients with hypertension.

RATIONALE AND OBJECTIVE: APOL1 risk alleles are associated with increased cardiovascular and chronic kidney disease (CKD) risk. It is unknown whether knowledge of APOL1 risk status motivates patients and providers to attain recommended blood pressure (BP) targets to reduce cardiovascular disease. STUDY DESIGN: Multicenter, pragmatic, randomized controlled clinical trial. SETTING AND PARTICIPANTS: 6650 individuals with African ancestry and hypertension from 13 health systems. INTERVENTION: APOL1 genotyping with clinical decision support (CDS) results are returned to participants and providers immediately (intervention) or at 6 months (control). A subset of participants are re-randomized to pharmacogenomic testing for relevant antihypertensive medications (pharmacogenomic sub-study). CDS alerts encourage appropriate CKD screening and antihypertensive agent use. OUTCOMES: Blood pressure and surveys are assessed at baseline, 3 and 6 months. The primary outcome is change in systolic BP from enrollment to 3 months in individuals with two APOL1 risk alleles. Secondary outcomes include new diagnoses of CKD, systolic blood pressure at 6 months, diastolic BP, and survey results. The pharmacogenomic sub-study will evaluate the relationship of pharmacogenomic genotype and change in systolic BP between baseline and 3 months. RESULTS: To date, the trial has enrolled 3423 participants. CONCLUSIONS: The effect of patient and provider knowledge of APOL1 genotype on systolic blood pressure has not been well-studied. GUARDD-US addresses whether blood pressure improves when patients and providers have this information. GUARDD-US provides a CDS framework for primary care and specialty clinics to incorporate APOL1 genetic risk and pharmacogenomic prescribing in the electronic health record. TRIAL REGISTRATION: ClinicalTrials.govNCT04191824.

Isolation, characterization and biological activities of betulin from Acacia nilotica bark.

Medicinal plants are in use of humankind since ancient and still they are playing an important role in effective and safer natural drug delivery systems. Acacia nilotica (native of Egypt) commonly known as babul belongs to family Fabaceae, widely spread in India, Sri Lanka and Sudan. Being a common and important plant, using in many ways from fodder (shoots and leaves to animals) to dyeing (leather coloration) to medicine (root, bark, leaves, flower, gum, pods). The present study is focused on investigating the natural chemistry and important biological activities of the plant. Employing bioassay guided fractionation coupled with TLC and column chromatography, a pure fraction named AN-10 was isolated from ethyl acetate fraction of crude methanol extract which identified as "Betulin (Lupan-3ß,28-diol)" by Liebermann-Burchard test and structure elucidation by UV-Vis, NMR and MS techniques. A battery of in vitro biological assays for antioxidant, anti-inflammatory and anticancer were performed and betulin showed excellent potential in all assays. It was found that the inhibitory potential in all assays were dose dependent manner and after a range of concentration, the activities get leveled off with no further increase in activity.

The reckoning: The return of genomic results to 1444 participants across the eMERGE3 Network.

PURPOSE: The goal of Electronic Medical Records and Genomics (eMERGE) Phase III Network was to return actionable sequence variants to 25,084 consenting participants from 10 different health care institutions across the United States. The purpose of this study was to evaluate system-based issues relating to the return of results (RoR) disclosure process for clinical grade research genomic tests to eMERGE3 participants. METHODS: RoR processes were developed and approved by each eMERGE institution's internal review board. Investigators at each eMERGE3 site were surveyed for RoR processes related to the participant's disclosure of pathogenic or likely pathogenic variants and engagement with genetic counseling. Standard statistical analysis was performed. RESULTS: Of the 25,084 eMERGE participants, 1444 had a pathogenic or likely pathogenic variant identified on the eMERGEseq panel of 67 genes and 14 single nucleotide variants. Of these, 1077 (74.6%) participants had results disclosed, with 562 (38.9%) participants provided with variant-specific genetic counseling. Site-specific processes that either offered or required genetic counseling in their RoR process had an effect on whether a participant ultimately engaged with genetic counseling (P = .0052). CONCLUSION: The real-life experience of the multiarm eMERGE3 RoR study for returning actionable genomic results to consented research participants showed the impact of consent, method of disclosure, and genetic counseling on RoR.

Inflammation-specific targeted carriers for local drug delivery to inflammatory bowel disease.

Delivering drugs directly to the inflamed intestinal sites to treat inflammatory bowel disease (IBD), particularly Crohn's and ulcerative colitis, is highly challenging. Recent advances in colitis therapy medications are expanding opportunities for improving local on-site drug availability by minimising the associated systemic side-effects. Drug delivery with targeted carrier systems has shown the potential to increase site-specificity, stability, and therapeutic efficacy. Herein, we report the development of a strong anionic charged inflammation targeted nanocarriers (IT-NCs) loaded with an immunosuppressant model drug. This system showed preferential adhesion on a charge-modified surface in vitro, and in both dextran sulfate sodium (DSS) and TNBS colitis mice in vivo models. IT-NCs showed improved colitis phenotype therapeutic efficacy in both animal models compared to free drug. Furthermore, ex vivo study of colon tissue biopsies from patients with colitis revealed that IT-NCs adhered preferentially to inflamed biopsies compared to normal. Together, our results suggest that IT-NCs have promising therapeutic potential as delivery carriers' in colitis management.

Modulation of Gut Barrier Functions in Ulcerative Colitis by Hyaluronic Acid System.

The active stages of intestinal inflammation and the pathogenesis of ulcerative colitis are associated with superficial mucosal damage and intermittent wounding that leads to epithelial barrier defects and increased permeability. The standard therapeutic interventions for colitis have focused mainly on maintaining the remission levels of the disease. Nonetheless, such treatment strategies (using anti-inflammatory, immunomodulatory agents) do not address colitis' root cause, especially the mucosal damage and dysregulated intestinal barrier functions. Restoration of barrier functionality by mucosal healing or physical barrier protecting strategies shall be considered as an initial event in the disease suppression and progression. Herein, a biphasic hyaluronan (HA) enema suspension, naïve-HA systems that protect the dysregulated gut epithelium by decreasing the inflammation, permeability, and helping in maintaining the epithelial barrier integrity in the dextran sodium sulfate-induced colitis mice model is reported. Furthermore, HA-based system modulates intestinal epithelial junctional proteins and regulatory signaling pathways, resulting in attenuation of inflammation and mucosal protection. The results suggest that HA-based system can be delivered as an enema to act as a barrier protecting system for managing distal colonic inflammatory diseases, including colitis.

Arrhythmia Variant Associations and Reclassifications in the eMERGE-III Sequencing Study.

BACKGROUND: Sequencing Mendelian arrhythmia genes in individuals without an indication for arrhythmia genetic testing can identify carriers of pathogenic or likely pathogenic (P/LP) variants. However, the extent to which these variants are associated with clinically meaningful phenotypes before or after return of variant results is unclear. In addition, the majority of discovered variants are currently classified as variants of uncertain significance, limiting clinical actionability. METHODS: The eMERGE-III study (Electronic Medical Records and Genomics Phase III) is a multicenter prospective cohort that included 21 846 participants without previous indication for cardiac genetic testing. Participants were sequenced for 109 Mendelian disease genes, including 10 linked to arrhythmia syndromes. Variant carriers were assessed with electronic health record-derived phenotypes and follow-up clinical examination. Selected variants of uncertain significance (n=50) were characterized in vitro with automated electrophysiology experiments in HEK293 cells. RESULTS: As previously reported, 3.0% of participants had P/LP variants in the 109 genes. Herein, we report 120 participants (0.6%) with P/LP arrhythmia variants. Compared with noncarriers, arrhythmia P/LP carriers had a significantly higher burden of arrhythmia phenotypes in their electronic health records. Fifty-four participants had variant results returned. Nineteen of these 54 participants had inherited arrhythmia syndrome diagnoses (primarily long-QT syndrome), and 12 of these 19 diagnoses were made only after variant results were returned (0.05%). After in vitro functional evaluation of 50 variants of uncertain significance, we reclassified 11 variants: 3 to likely benign and 8 to P/LP. CONCLUSIONS: Genome sequencing in a large population without indication for arrhythmia genetic testing identified phenotype-positive carriers of variants in congenital arrhythmia syndrome disease genes. As the genomes of large numbers of people are sequenced, the disease risk from rare variants in arrhythmia genes can be assessed by integrating genomic screening, electronic health record phenotypes, and in vitro functional studies. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier; NCT03394859.

TGFß Drives Metabolic Perturbations during Epithelial Mesenchymal Transition in Pancreatic Cancer: TGFß Induced EMT in PDAC.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy wherein a majority of patients present metastatic disease at diagnosis. Although the role of epithelial to mesenchymal transition (EMT), mediated by transforming growth factor beta (TGFß), in imparting an aggressive phenotype to PDAC is well documented, the underlying biochemical pathway perturbations driving this behaviour have not been elucidated. We used high-resolution mass spectrometry (HRMS) based molecular phenotyping approach in order to delineate metabolic changes concomitant to TGFß-induced EMT in pancreatic cancer cells. Strikingly, we observed robust changes in amino acid and energy metabolism that may contribute to tumor invasion and metastasis. Somewhat unexpectedly, TGFß treatment resulted in an increase in intracellular levels of retinoic acid (RA) that in turn resulted in increased levels of extracellular matrix (ECM) proteins including fibronectin (FN) and collagen (COL1). These findings were further validated in plasma samples obtained from patients with resectable pancreatic cancer. Taken together, these observations provide novel insights into small molecule dysregulation that triggers a molecular cascade resulting in increased EMT-like changes in pancreatic cancer cells, a paradigm that can be potentially targeted for better clinical outcomes.

Tracking Blood Pressure Control Performance and Process Metrics in 25 US Health Systems: The PCORnet Blood Pressure Control Laboratory.

Background The National Patient-Centered Clinical Research Network Blood Pressure Control Laboratory Surveillance System was established to identify opportunities for blood pressure (BP) control improvement and to provide a mechanism for tracking improvement longitudinally. Methods and Results We conducted a serial cross-sectional study with queries against standardized electronic health record data in the National Patient-Centered Clinical Research Network (PCORnet) common data model returned by 25 participating US health systems. Queries produced BP control metrics for adults with well-documented hypertension and a recent encounter at the health system for a series of 1-year measurement periods for each quarter of available data from January 2017 to March 2020. Aggregate weighted results are presented overall and by race and ethnicity. The most recent measurement period includes data from 1 737 995 patients, and 11 956 509 patient-years were included in the trend analysis. Overall, 15% were Black, 52% women, and 28% had diabetes. BP control (<140/90 mm Hg) was observed in 62% (range, 44%-74%) but varied by race and ethnicity, with the lowest BP control among Black patients at 57% (odds ratio, 0.79; 95% CI, 0.66-0.94). A new class of antihypertensive medication (medication intensification) was prescribed in just 12% (range, 0.6%-25%) of patient visits where BP was uncontrolled. However, when medication intensification occurred, there was a large decrease in systolic BP (≈15 mm Hg; range, 5-18 mm Hg). Conclusions Major opportunities exist for improving BP control and reducing disparities, especially through consistent medication intensification when BP is uncontrolled. These data demonstrate substantial room for improvement and opportunities to close health equity gaps.