Protocol for project IMPACT (improving millions hearts for provider and community transformation): a quasi-experimental evaluation of an integrated electronic health record and community health worker intervention study to improve hypertension management among South Asian patients.

BACKGROUND: The Million Hearts® initiative aims to prevent heart disease and stroke in the United States by mobilizing public and private sectors around a core set of objectives, with particular attention on improving blood pressure control. South Asians in particular have disproportionately high rates of hypertension and face numerous cultural, linguistic, and social barriers to accessing healthcare. Interventions utilizing Health information technology (HIT) and community health worker (CHW)-led patient coaching have each been demonstrated to be effective at advancing Million Hearts® goals, yet few studies have investigated the potential impact of integrating these strategies into a clinical-community linkage initiative. Building upon this initiative, we present the protocol and preliminary results of a research study, Project IMPACT, designed to fill this gap in knowledge. METHODS: Project IMPACT is a stepped wedge quasi-experimental study designed to test the feasibility, adoption, and impact of integrating CHW-led health coaching with electronic health record (EHR)-based interventions to improve hypertension control among South Asian patients in New York City primary care practices. EHR intervention components include the training and implementation of hypertension-specific registry reports, alerts, and order sets. Fidelity to the EHR intervention is assessed by collecting the type, frequency, and utilization of intervention components for each practice. CHW intervention components consist of health coaching sessions on hypertension and related risk factors for uncontrolled hypertensive patients. The outcome, hypertension control (<140 mmHg systolic blood pressure (BP) and <90 mmHg diastolic BP), is collected at the aggregate- and individual-level for all 16 clinical practices enrolled. DISCUSSION: Project IMPACT builds upon the evidence base of the effectiveness of CHW and Million Hearts® initiatives and proposes a unique integration of provider-based EHR and community-based CHW interventions. The project informs the effectiveness of these interventions in team-based care approaches, thereby, helping to develop relevant sustainability strategies for improving hypertension control among targeted racial/ethnic minority populations at small primary care practices. TRIAL REGISTRATION: This study protocol has been approved and is made available on Clinicaltrials.gov by NCT03159533 as of May 17, 2017.

Design, Synthesis, and Biological Evaluation of Novel Spiro Imidazobenzodiazepines to Identify Improved Inhaled Bronchodilators.

Novel gamma-aminobutyric acid receptor (GABAAR) ligands structurally related to imidazobenzodiazepine MIDD0301 were synthesized using spiro-amino acid N-carboxyanhydrides (NCAs). These compounds demonstrated increased resistance to phase 2 metabolism and avoided the formation of a 6H isomer. Compound design was guided by molecular docking using the available crystal structure of the α1ß3γ2 GABAAR and correlated with in vitro binding data. The carboxylic acid containing GABAAR ligands have high aqueous solubility, low permeability, and low cell toxicity. The inability of GABAAR ligands to cross the blood-brain barrier was confirmed in vivo by the absence of sensorimotor inhibition. Pharmacological activities at lung GABAARs were demonstrated by ex vivo relaxation of guinea pig airway smooth muscle and reduction of methacholine-induced airway hyperresponsiveness (AHR) in conscious mice. We identified bronchodilator 5c with an affinity of 9 nM for GABAARs that was metabolically stable in the presence of human and mouse microsomes.

Bonding of Clear Aligner Composite Attachments to Ceramic Materials: An In Vitro Study.

Background: We aim to evaluate the effect of surface conditioning, bonding agents and composite types on surface roughness (SR) and shear bond strength (SBS) of clear aligner composite attachments bonded to ceramics. Methods: One hundred and eighty IPS e.max CAD specimens were prepared. For SR, 60 specimens were divided according to surface conditioning (n = 15) into four groups: control, 9.6% hydrofluoric acid (HFA), 37% phosphoric acid (PhA), air abrasion (AA). SR was measured using a Profilometer and Atomic Force Microscopy. For SBS, 120 specimens were divided according to conditioning methods (n = 40) (9.6% HFA and 37% PhA or AA), then according to bonding agents (n = 20) (Assure universal bond (AUB) or Single bond universal (SBU)) and then according to composite type (n = 10): Filtek™ Z350 and Filtek™ Z350 XT flowable composite. SBS was measured using Instron testing machine. Descriptive and group comparison were calculated (p < 0.05). Results: AA had the highest SR, while the control had the lowest SR (p < 0.05). HFA had the highest, but insignificant SBS, followed by AA (p > 0.05). AUB had higher SBS than SBU (p < 0.001). Filtek™ Z350 produced higher SBS than Filtek™ Z350 XT flowable composite (p < 0.01). Conclusion: The combination of AA, AUB, and Filtek Z350 produced the highest SBS, followed by HFA, AUB, and Filtek Z350.

STAT4 single nucleotide gene polymorphisms and susceptibility to endometriosis-related infertility.

INTRODUCTION: Endometriosis is a multifactorial benign gynecologic disorder, characterized by the ectopic growth of misplaced endometrial cells with complex genetic inheritance and changing of some immune based factors and also shares some autoimmune characteristics. However, it is not clear yet that how and when these immunological factors affect the initiation or progression of the disease. It has been shown that STAT4 is a predisposing gene in the development of some autoimmune diseases. METHOD: The study group comprised 114 patients with endometriosis and 92 sex-, age-, and ethnicity-matched healthy controls of Iranian ancestry. Four SNPs (rs7574865, rs7601754, rs7582694 and rs11889341) were genotyped using the MGB TaqMan. RESULTS: A significant association in rs7582694 between C allele (P=0.002, OR=1.986, 95% CI: 1.262-3.126) and endometriosis was found in our study, while the G allele (P=0.002, OR=0.0503, 95% CI: 0.319-0.792) was significantly decreased in the patients population. The GC genotype (P=0.004, OR=2.234, 95% CI: 1.301-4.150) was also significantly overrepresented in the patients with endometriosis, while the frequency of GG genotype was significantly lower in the patient group, compared to the controls (P=0.007, OR=0.457, 95% CI: 0.256-0.813). CONCLUSIONS: Our results for the first time showed a significant association between rs7582694 alleles and genotypes and susceptibility to endometriosis in a population.

Immunomodulatory effects of human umbilical cord Wharton's jelly-derived mesenchymal stem cells on differentiation, maturation and endocytosis of monocyte-derived dendritic cells.

The Wharton's jelly of the umbilical cord is believed to be a source of mesenchymal stem cells (MSCs) which can be therapeutically applied in degenerative diseases.In this study, we investigated the immunomodulatory effect of umbilical cord derived-mesenchymal stem cells (UC-MSCs) and bone marrow-derived-mesenchymal stem cells (BM-MSCs) on differentiation, maturation, and endocytosis of monocyte-derived dendritic cells in a transwell culture system under laboratory conditions. Monocytes were differentiated into immature dendritic cells (iDCs) in the presence of GM-CSF and IL-4 for 6 days and then differentiated into mature dendritic cells (mDCs) in the presence of TNF-α for 2 days. In every stage of differentiation, immature and mature dendritic cells were separately co-cultured with UC-MSCs and BM-MSCs. The findings showed that UC-MSCs and BM-MSCs inhibited strongly differentiation and maturation of dendritic cells at higher dilution ratios (1:1). The BM-MSCs and UC-MSCs showed more inhibitory effect on CD1a, CD83, CD86 expression, and dendritic cell endocytic activity, respectively. On the other hand, these cells severely up-regulated CD14 marker expression. We concluded that UC-MSCs and BM-MSCs could inhibit differentiation, maturation and endocytosis in monocyte-derived DCs through the secreted factors and free of any cell-cell contacts under laboratory conditions. As DCs are believed to be the main antigen presenting cells for naïve T cells in triggering immune responses, it would be logical that their inhibitory effect on differentiation, maturation and function can decrease or modulate immune and inflammatory responses.