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Supplemental Digital Content is available in the text., Background: Thirty-day readmissions among patients with acute myocardial infarction (AMI) contribute to the US health care burden of preventable complications and costs. Digital health interventions (DHIs) may improve patient health care self-management and outcomes. We aimed to determine if patients with AMI using a DHI have lower 30-day unplanned all-cause readmissions than a historical control. Methods: This nonrandomized controlled trial with a historical control, conducted at 4 US hospitals from 2015 to 2019, included 1064 patients with AMI (DHI n=200, control n=864). The DHI integrated a smartphone application, smartwatch, and blood pressure monitor to support guideline-directed care during hospitalization and through 30-days post-discharge via (1) medication reminders, (2) vital sign and activity tracking, (3) education, and (4) outpatient care coordination. The Patient Activation Measure assessed patient knowledge, skills, and confidence for health care self-management. All-cause 30-day readmissions were measured through administrative databases. Propensity score–adjusted Cox proportional hazard models estimated hazard ratios of readmission for the DHI group relative to the control group. Results: Following propensity score adjustment, baseline characteristics were well-balanced between the DHI versus control patients (standardized differences

Patients infected with SARS-CoV-2 may deteriorate rapidly and therefore continuous monitoring is necessary. We conducted an observational study involving patients with mild COVID-19 to explore the potentials of wearable biosensors and machine learning-based analysis of physiology parameters to detect clinical deterioration. Thirty-four patients (median age: 32 years; male: 52.9%) with mild COVID-19 from Queen Mary Hospital were recruited. The mean National Early Warning Score 2 (NEWS2) were 0.59 ± 0.7. 1231 manual measurement of physiology parameters were performed during hospital stay (median 15 days). Physiology parameters obtained from wearable biosensors correlated well with manual measurement including pulse rate (r = 0.96, p r = 0.87, p p r = 0.75, p

Worldwide, ∼250 million people are chronically infected with the hepatitis B virus (HBV) and are at increased risk of cirrhosis and hepatocellular carcinoma. The HBV persists as covalently closed circular DNA (cccDNA), which acts as the template for all HBV mRNA transcripts. Nucleos(t)ide analogs do not directly target the HBV cccDNA and cannot eradicate the HBV. We have discovered a unique structural motif, a G-quadruplex in HBV’s pre-core promoter region that is conserved amongst nearly all genotypes, and is central to critical steps in the viral life-cycle including the production of pre-genomic RNA, core and polymerase proteins, and encapsidation. Thus, an increased understanding of the HBV pre-core may lead to the development of novel anti-HBV cccDNA targets. We utilized biophysical methods to characterize the presence of the G-quadruplex, employed assays using a known quadruplex- binding protein (DHX36) to pull-down HBV cccDNA, and compared HBV infection in HepG2 cells transfected with wild-type and mutant HBV plasmids. This study provides insights into the presence of a G-quadruplex in the HBV pre-core promoter region essential for HBV replication. The evaluation of this critical host-protein interaction site in the HBV cccDNA may ultimately facilitate the development of novel anti-HBV therapeutics against the resilient cccDNA template.

O-GlcNAcylation is an important post-translational modification of proteins. O-GlcNAcylated proteins have crucial roles in several cellular contexts both in eukaryotes and bacteria. O-GlcNActransferase (OGT) is the enzyme instrumental in O-GlcNAcylation of proteins. OGT is conserved across eukaryotes. The first bacterial OGT discovered is GmaR in Listeria monocytogenes. GmaR is a GT-2 family bifunctional protein that catalyzes glycosylation of the flagellin protein FlaA and controls transcription of flagellar motility genes in a temperature-dependent manner. Here, we provide methods for heterologous expression and purification of recombinant GmaR and FlaA, in vivo/in vitro glycosylation assays, analysis of the molecular form of recombinant GmaR and detailed enzyme kinetics. We study the structure and functional dynamics of GmaR. Using solution small-angle X-ray scattering and molecular modeling, we show that GmaR adopts an extended shape with two distinctly spaced structural units in the presence of cofactor Mg2+ and with donor UDP-GlcNAc and cofactor combined. Comparisons of restored structures revealed that in-solution binding of Mg2+ ions brings about shape rearrangements and induces structural-rigidity in hyper-variable regions at the N-terminus of GmaR protein. Taking function and shape data together, we describe that Mg2+ binding enables GmaR to adopt a shape that can bind the substrate. The manuscript provides the first 3D solution structure of a bacterial OGT of GT-2 family and detailed biochemical characterization of GmaR to facilitate its future applications.

Delineation of factors which affect wound healing would be of immense value to enable on-time or early healing and reduce comorbidities associated with infections or biochemical stress like diabetes. Plasma gelsolin has been identified earlier to significantly enable injury recovery compared to placebo. This study evaluates the role of rhuGSN for its antioxidant and wound healing properties in murine fibroblasts (3T3-L1 cell line). Total antioxidant capacity of rhuGSN increased in a concentration-dependent manner (0.75-200 μg/mL). Cells pretreated with 0.375 and 0.75 μg/mL rhuGSN for 24 h exhibited a significant increase in viability in a MTT assay. Preincubation of cells with rhuGSN for 24 h followed by oxidative stress induced by exposure to H2O2for 3 h showed cytoprotective effect. rhuGSN at 12.5 and 25 μg/mL concentration showed an enhanced cell migration after 20 h of injury in a scratch wound healing assay. The proinflammatory cytokine IL-6 levels were elevated in the culture supernatant. These results establish an effective role of rhuGSN against oxidative stress induced by H2O2and in wound healing of 3T3-L1 fibroblast cells.

Background: Immunization plays a crucial role in reducing childhood morbidity and mortality, and higher coverage rates are needed to maintain the expected benefits. Objective was to assess immunization coverage in children of 12-23 months of age group in rural field practice areas of Medical College, Visnagar, Gujarat, India.Methods: Using the purposive sampling method, a cross sectional community based study was conducted in rural field practice areas of Nootan Medical College and Research Center, Visnagar during June 2021 to December 2021. All 214 children of 24-35 months age group of the areas were included after taking verbal informed consent of their parents or guardians. Vaccination status of the children was verified using the immunization card. Analysis of study was done by using appropriate statistical software.Results: Total 1934 households were surveyed. There were 214 children in the 24-35 months age group. Mamta card or immunization record was available with 145 (67.8%) mothers of 24-35 months age group of children. Maximum coverage was seen for bacille Calmette-Guerin (BCG) (96.7%) followed by pentavalent/RVV/OPV first dose (95.8%). Measles-Rubella (MR) 2nd dose coverage was 84.6%. Overall, 75.7% of the children in the 24-35 months age group were completely immunized while only 6 children were unimmunized. Dropout rate proportion for pentavalent 1st dose to pentavalent 3rd dose was 3.44% while for BCG first dose to MR second dose was 12.51%.Conclusions: Complete immunization coverage in children of 24-35 months of age group in rural field practice areas of Medical College, Visnagar was 75.7%.

Background: Immunization plays a vital role in reducing childhood morbidity and mortality and higher coverage rates are needed to maintain the expected benefits. The objective was to assess immunization coverage in children of 12-23 months of age group in rural field practice areas of medical college, Visnagar, Gujarat, India.Methods: Using the purposive sampling method, a cross-sectional community-based study was conducted in rural field practice areas of Nootan medical college and research center, Visnagar during June-December 2021. All 212 children of 12-23 months age group of the areas were included after taking verbal informed consent of their parents or guardians. Vaccination status of the children was verified using the Mamta card (immunization card). In conditions where the Mamta card was not available, the mother/parents were asked about the site of vaccinations to confirm the vaccines being given. Analysis of study was done by using appropriate statistical software.Results: Total 1934 households were surveyed. There were 223 children in the 12-23 months age group. Mamta card or immunization record was available with 175 (78.5%) mothers of 12-23 months age group of children. Maximum coverage was seen for BCG (95.5%) followed by pentavalent/RVV/OPV first dose (93.3%). Measles-rubella (MR) 1st dose coverage was 89.2%. Overall, 86.5% of the children in the 12-23 months age group were fully immunized while only 5 children were unimmunized. Dropout rate proportion for pentavalent 1st dose to pentavalent 3rd dose was 2.46% while for pentavalent first dose to MR was 4.39%.Conclusions: Full immunization coverage in children of 12-23 months of age group in rural field practice areas of medical college, Visnagar was 86.8%.

As we enter the information age of health care, digital health technologies offer significant opportunities to optimize both clinical care delivery and clinical research. Despite their potential, the use of such information technologies in clinical care and research faces major data quality, privacy, and regulatory concerns. In hopes of addressing both the promise and challenges facing digital health technologies in the transformation of health care, we convened a think tank meeting with academic, industry, and regulatory representatives in December 2016 in Washington, DC. In this paper, we summarize the proceedings of the think tank meeting and aim to delineate a framework for appropriately using digital health technologies in healthcare delivery and research.

Background: The changing lifestyle factors in rural population are associated with increase in hypertension. Objective was to find out the epidemiological correlates of hypertension among the rural population.Methods: This was cross sectional study and conducted in rural areas of Mehsana district of Gujarat during January 2019 to June 2019. People living rural areas were selected by stratified random sampling. They were screened for hypertension by JNC VII criteria using sphygmomanometer and detailed personal, past and family history was taken after written and informed consent. Data was entered in Microsoft excel and analysis was done using SPSS statistical package.Results: Out of total 602 subjects, 93 (15.4%) were hypertensive. Out of total 93 hypertensive subjects, 50 (53.8%) were females. A blood pressure category and gender difference were not statically significant (p=0.89). Out of 93 hypertensive subjects, 42 (45.2%) subjects were in the age group of ≥60 years. The difference between age groups and blood pressure category was significant (p

Background:High blood pressure is considered both a disease and a risk factor, especially for cardiovascular diseases, and is one of the most serious public health problems. To find out the prevalence of hypertension among the rural population of Mehsana district of North Gujarat region, India.Methods:This was cross sectional study and conducted in rural areas of Mehsana district of Gujarat during January 2019 to June 2019. People living rural areas were selected by stratified random sampling. They were screened for hypertension by JNC VII criteria using sphygmomanometer after written and informed consent. Data was entered in Microsoft excel and analysis was done using statistical package for the social sciences (SPSS) statistical package.Results: Out of total 602, majority 293 (48.7%) subjects had normal blood pressure with mean age of 25.28±16.62 years, 271 subjects (45.0%) had pre hypertension with mean age of 40.30±14.32 years. Out of total, 25 (4.2%) subjects had hypertension stage 1 with mean age of 45.82±11.48 years and 13 (2.2%) subjects had hypertension stage 2 with mean age of 53.77±16.02 years. Out of total 271 subjects who had pre hypertension, 150 (55.3%) were males. Hypertension stage 1 and 2 were almost equally distributed among both gender. A blood pressure category and gender difference was statically significant. Out of total 38 hypertensive subjects, 19 (50%) subjects were in the age group of 40-59 years.Conclusions: Prevalence of hypertension among rural population was 6.4%.

Dharam J. Kumbhani, MD, SM, FACC, Chair Cathleen Biga, MSN, RN, FACC Thomas J. Lewandowski, MD, FACC Thomas M. Maddox, MD, MSc, FACC James K. Min, MD, FACC Michael J. Wolk, MD, MACC Healthcare transformation is the product of a shared vision between a broad range of stakeholders to

This is the first report describing temperature based initiation of gelsolin’s F-actin depolymerization activity, even in absence of free Ca2+ or low pH. Small angle X-ray scattering (SAXS) and circular dichroism (CD) studies revealed that temperature in the range of 30–40 °C is capable of opening the G1 domain alone, as remaining domains are held together by the Ca2+-sensitive C-tail latch without any loss in the secondary structural content. Full opening of all domains of tail-less gelsolin, and retention of closed shape for G2–G6 gelsolin merely by heating, further substantiated our findings. The Ca2+/pH independent activity of gelsolin near physiological temperature brought out a query: whether gelsolin is always active, and if not, what might deactivate it? Earlier, PIP2 has been reported to render gelsolin inactive with no structural insight. Reduction in shape parameters and modeling revealed that PIP2 reverses the temperature induced extension of g1-g2 linker leading to a compact shape seen for Ca2+-free gelsolin. Similar results for partially activated gelsolin (by low pH or Ca2+ ions below 0.1 μM) imply that inside cells, depolymerization, capping, and nucleation of F-actin by gelsolin is regulated by the culmination of local Ca2+ ion concentration, pH, temperature and PIP2 levels.

Although more than 98% of the human genome is non-coding

Supplemental Digital Content is available in the text., Objectives: Determining whether a patient has taken a direct oral anticoagulant (DOAC) is critical during the periprocedural and preoperative period in the emergency department. However, the inaccessibility of complete medical records, along with the generally inconsistent sensitivity of conventional coagulation tests to these drugs, complicates clinical decision making and puts patients at risk of uncontrollable bleeding. In this study, we evaluate the utility of inhibitor-II-X (i-II-X), a novel, microfluidics-based diagnostic assay for the detection and identification of Factor Xa inhibitors (FXa-Is) in an acute care setting. Design: First-in-human, 91-patient, single-center retrospective pilot study. Setting: Emergency room. Patients: Adult patients admitted into the emergency department, which received any clinician-ordered coagulation test requiring a 3.2% buffered sodium citrate blood collection tube. Interventions: None. Measurements and Main Results: Plasma samples from patients admitted to the emergency department were screened for the use of FXa-Is, including apixaban and rivaroxaban, within the past 24 hours using our new i-II-X microfluidic test. i-II-X results were then compared with results from conventional coagulation tests, including prothrombin time (PT) and international normalized ratio (INR), which were ordered by treating clinicians, and an anti-Xa assay for rivaroxaban. The i-II-X test detected DOACs in samples collected from the emergency department with 95.20% sensitivity and 100.00% specificity. Unlike PT and INR, i-II-X reliably identified patients who had prolonged clotting times secondary to the presence of a FXa-I. Conclusions: The i-II-X test overcomes the limitations of currently available coagulation tests and could be a useful tool by which to routinely screen patients for DOACs in emergency and critical care settings. Our new diagnostic approach is particularly relevant in clinical situations where medical records may be unavailable, or where precautions need to be taken prior to invasive interventions, such as specific reversal agent administration.

Automatic classification of abnormal beats in ECG signals is crucial for monitoring cardiac conditions and the performance of the classification will improve the success rate of the treatment. However, under certain circumstances, traditional classifiers cannot be adapted well to the variation of ECG morphologies or variation of different patients due to fixed hand-crafted features selection. Additionally, existing deep learning related solutions reach their limitation because they fail to use the beat-to-beat information together with single-beat morphologies. This paper applies a novel solution which converts one-dimensional ECG signal into spectro-temporal images and use multiple dense convolutional neural network to capture both beat-to-beat and single-beat information for analysis. The results of simulation on the MIT-BIH arrhythmias database demonstrate the effectiveness of the proposed methodology by showing an outstanding detection performance compared to other existing methods.

More than 50% of the whole world lives with chronic diseases leading to a global economic burden of 47 trillion dollars. Healthcare organizations are moving towards managing patients outside hospital, thereby improving patient safety and quality of life. Current at-home ambulatory remote monitoring analytics based on population level thresholds of individuals physiology have shown poor outcomes and high degree of false alarm burden. The personalized multivariate physiology analytics leverages readily-available low-cost wearable biosensors to detect subtle physiology changes precursor of patient's health deterioration. In this paper we present a novel personalized multivariate physiology analytics for remote patient monitoring in an ambulatory setting. We also present our verification and validation results using perturbation testing along with clinical trial results.

Background: Unplanned readmissions after hospitalization for acute myocardial infarction are among the leading causes of preventable morbidity, mortality, and healthcare costs. Digital health interventions could be an effective tool in promoting self-management, adherence to guideline-directed therapy, and cardiovascular risk reduction. A digital health intervention developed at Johns Hopkins—the Corrie Health Digital Platform (Corrie)—includes the first cardiology Apple CareKit smartphone application, which is paired with an Apple Watch and iHealth Bluetooth-enabled blood pressure cuff. Corrie targets: (1) self-management of cardiac medications, (2) self-tracking of vital signs, (3) education about cardiovascular disease through articles and animated videos, and (4) care coordination that includes outpatient follow-up appointments. Methods and Results: The 3 phases of the MiCORE study (Myocardial infarction, Combined-device, Recovery Enhancement) include (1) the development of Corrie, (2) a pilot study to assess the usability and feasibility of Corrie, and (3) a prospective research study to primarily compare time to first readmission within 30 days postdischarge among patients with Corrie to patients in the historical standard of care comparison group. In Phase 2, the feasibility of deploying Corrie in an acute care setting was established among a sample of 60 patients with acute myocardial infarction. Phase 3 is ongoing and patients from 4 hospitals are being enrolled as early as possible during their hospital stay if they are 18 years or older, admitted with acute myocardial infarction (ST-segment–elevation myocardial infarction or type I non–ST-segment–elevation myocardial infarction), and own a smartphone. Patients are either being enrolled with their own personal devices or they are provided an iPhone and/or Apple Watch for the duration of the study. Phase 3 started in October 2017 and we aim to recruit 140 participants. Conclusions: This article will provide an in-depth understanding of the feasibility associated with implementing a digital health intervention in an acute care setting and the potential of Corrie as a self-management tool for acute myocardial infarction recovery.

Members of the human Zyxin family are LIM domain-containing proteins that perform critical cellular functions and are indispensable for cellular integrity. Despite their importance, not much is known about their structure, functions, interactions and dynamics. To provide insights into these, we used a set of in-silico tools and databases and analyzed their amino acid sequence, phylogeny, post-translational modifications, structure-dynamics, molecular interactions, and functions. Our analysis revealed that zyxin members are ohnologs. Presence of a conserved nuclear export signal composed of LxxLxL/LxxxLxL consensus sequence, as well as a possible nuclear localization signal, suggesting that Zyxin family members may have nuclear and cytoplasmic roles. The molecular modeling and structural analysis indicated that Zyxin family LIM domains share similarities with transcriptional regulators and have positively charged electrostatic patches, which may indicate that they have previously unanticipated nucleic acid binding properties. Intrinsic dynamics analysis of Lim domains suggest that only Lim1 has similar internal dynamics properties, unlike Lim2/3. Furthermore, we analyzed protein expression and mutational frequency in various malignancies, as well as mapped protein-protein interaction networks they are involved in. Overall, our comprehensive bioinformatic analysis suggests that these proteins may play important roles in mediating protein-protein and protein-nucleic acid interactions.