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Background: Cardiomyocytes proliferate rapidly during fetal life but lose their ability of proliferation soon after birth. However, before terminal withdrawal from the cell cycle, cardiomyocytes undergo another round of cell cycle during early postnatal life in mice. While a transient wave of increased DNA synthesis in cardiomyocyte has been observed in postnatal mouse hearts, the molecular mechanisms describing cardiomyocyte cell cycle re-entry remain poorly understood. Atrial and B-type natriuretic peptides (ANP and BNP) are abundantly expressed in embryonic heart ventricles. After birth, the expression of both genes is strongly reduced in the ventricular myocardium. Forkhead O (FOXO) transcription factors are expressed in both embryonic and postnatal heart ventricles. Their transcriptional activity negatively affects cardiomyocyte proliferation. Upon phosphorylation, FOXO is translocated to the cytoplasm and is transcriptionally inactive. Despite these important findings, it remains largely unknown whether natriuretic peptides and FOXO cooperatively play a role in regulating cardiomyocyte cell cycle activity during early postnatal life., Results: We observed that the expression of ANP and BNP and the level of phosphorylated FOXO were transiently increased in the postnatal mouse heart ventricles, which coincided with the burst of cardiomyocyte cell cycle re-entry during early postnatal life in mice. Cell culture studies showed that ANP/BNP signaling and FOXO cooperatively promoted cell cycle activity in neonatal mouse cardiomyocytes. The enhanced cell cycle activity observed in combined treatment of ANP/BNP and dominant-negative FOXO (DN-FOXO), which can bind FOXO recognition sites on DNA but cannot activate transcription, was primarily mediated through natriuretic peptide receptor 3 (Npr3). In mice, simultaneous application of ANP and DN-FOXO in postnatal hearts reactivated cell cycle in cardiomyocytes, resulting in reduced scar formation after experimental myocardial infarction., Conclusions: Our data demonstrate the cooperative effects of natriuretic peptide and DN-FOXO on promoting cardiomyocyte cell cycle activity and mouse cardiac repair and regeneration after injury.

Idiopathic pulmonary fibrosis (IPF) affects 200 000 patients in the United States of America. IPF is responsible for changes in the micro-architecture of the lung parenchyma, such as thickening of the alveolar walls, which reduces compliance and elasticity. In this study, we verify the hypothesis that changes in the microarchitecture of the lung parenchyma can be characterized by exploiting multiple scattering of ultrasound waves by the alveolar structure. Ultrasound propagation in a highly scattering regime follows a diffusion process, which can be characterized using the diffusion constant. We hypothesize that in a fibrotic lung, the thickening of the alveolar wall reduces the amount of air (compared with a healthy lung), thereby minimizing the scattering events. Pulmonary fibrosis is created in Sprague-Dawley rats by instilling bleomycin into the airway. The rats are studied within 3 weeks after bleomycin administration. Using a 128-element linear array transducer operating at 7.8 MHz, in vivo experimental data are obtained from Sprague-Dawley rats and the transport mean free path (L*) and backscatter frequency shift (BFS) are evaluated. Significant differences ( ) in the L* values between control and fibrotic rats and in the BFS values between fibrotic and edematous rats showcase the potential of these parameters for diagnosis and monitoring of IPF.

Myocarditis is an inflammatory disease of the myocardium with numerous different etiologies, the vast majority of which are infectious in origin. Patients afflicted with myocarditis can have variable presentations from flu-like symptoms to cardiogenic shock and sudden death, thus making the diagnosis difficult. The purpose of this study is the development of an algorithm for early identification and management of myocarditis based on a review of the published data and available literature. To validate the efficacy of this algorithm, a retrospective chart review of all the patient's presenting symptoms and diagnostic workup, treatment, and clinical progression was performed and applied to the algorithm to investigate whether they could be diagnosed at the time of presentation. Retrospective chart review was performed and all the patient's diagnosed with myocarditis between the years 2009 and 2017 were included in the study. 12 patients were identified on chart review and the algorithm was found to be 100% accurate at identifying all myocarditis patients at presentation by using the symptom identification.

Background: Use of procedural sedation to promote anxiolysis, analgesia, and amnesia enhances both pediatric patient experience and procedural outcomes. Sanford Children's outpatient sedation clinic currently uses oral midazolam for minimal sedation., Methods: A research survey was designed to evaluate parent/guardian satisfaction with midazolam for pediatric sedation in simple outpatient procedures including, bot linum toxin injections, voiding cystourethrogram (VCUG), and intravenous line placement. Parents'/ guardians' understanding of the sedation and procedural logistics were surveyed and their satisfaction with the child's comfort, recovery time, and overall satisfaction were assessed. Each component was rated on a scale of 1-10, 1 being not satisfied and 10 as extremely satisfied., Results: The study was conducted at a single pediatric outpatient center. Forty-one parents/guardians of patients aged 22 months-17 years were recruited; of these, 41 consented and enrolled in the study. Average age was 6.1 years with 22 females and 19 males. Of the surveys collected, 30 were botulinum toxin injections, eight VCUG, one contrast enema, and two were not recorded. Mean survey results were 8.7 (95 percent CI, 8.2-9.2) for satisfaction of recovery time, 8.0 (95 percent CI, 7.4-8.6) for control of discomfort and 8.4 (95 percent CI, 7.9-8.9) for overall satisfaction., Conclusion: When evaluating midazolam as a sedation agent in pediatric procedures, parents/guardians were most satisfied with the duration of recovery and had the lowest satisfaction on control of the patient's discomfort. Overall, it can be concluded that midazolam is a moderately good agent for pediatric patients receiving minimal sedation, with the greatest satisfaction in the duration of recovery., (Copyright© South Dakota State Medical Association.)

Consumers prefer home and community-based long-term care (LTC) services (HCBS) but lack information on those services. We examined the use of community health workers (CHWs) to find and help Medicaid beneficiaries with unmet LTC needs access HCBS compared to standard HCBS outreach approaches. We found that CHWs were very effective at finding persons with greater needs and were better able to help them access a greater range of HCBS services. We also found that five times fewer HCBS beneficiaries helped by CHWs had to use nursing home care services than those not helped by the CHWs despite the fact that their health status was poorer than those not helped by the CHWs. Our study provides evidence of the effectiveness of CHWs for HCBS service awareness and navigation.

Background: Hereditary colon cancer is characterized by the inheritance of an abnormal gene mutation which predisposes to malignancy. Recent advances in genomic medicine have identified mutations in "novel" genes as conferring an increased risk of colorectal cancer. Mutations in the BRIP1 gene (BRCA1 Interacting Protein C- terminal helicase 1) are known to increase the risk of ovarian and breast cancers, but this genes association with colon cancer has not been previously reported., Case Presentation: We describe two patients with colon cancer whose tumor tissue were found to harbor BRIP1 mutations on analysis by next-generation sequencing. These patients were confirmed by analysis of lymphocytes to carry the mutation in the germline as well., Conclusions: These case reports highlight a previously unreported association of BRIP1 germline mutations with colon cancer predisposition.

Limited provider participation within Medicaid and narrow provider networks on health insurance Marketplaces pose potential barriers to accessing and using the health care system for people with behavioral health needs. We compared employer-sponsored insurance, Medicaid, and Marketplace coverage for people with psychological distress across three domains of health care: access, utilization, and financial strain. We found evidence that adults with psychological distress reported greater difficulty accessing health care relative to those without such distress, regardless of insurance source. Among adults with psychological distress, Medicaid enrollees were more likely to use care and less likely to experience health-related financial strain than those enrolled in employer-sponsored insurance were. However, people with Marketplace coverage were more likely to experience barriers across all domains, relative to people with the other two coverage sources. Policy makers should be cognizant of the participation of providers within Medicaid and the Marketplaces and work to make network breadth more transparent.

Background: We developed and validated NLP-PAC, a natural language processing (NLP) algorithm based on predetermined asthma criteria (PAC) for asthma ascertainment using electronic health records at Mayo Clinic., Objective: To adapt NLP-PAC in a different health care setting, Sanford Children Hospital, by assessing its external validity., Methods: The study was designed as a retrospective cohort study that used a random sample of 2011-2012 Sanford Birth cohort (n = 595). Manual chart review was performed on the cohort for asthma ascertainment on the basis of the PAC. We then used half of the cohort as a training cohort (n = 298) and the other half as a blind test cohort to evaluate the adapted NLP-PAC algorithm. Association of known asthma-related risk factors with the Sanford-NLP algorithm-driven asthma ascertainment was tested., Results: Among the eligible test cohort (n = 297), 160 (53%) were males, 268 (90%) white, and the median age was 2.3 years (range, 1.5-3.1 years). NLP-PAC, after adaptation, and the human abstractor identified 74 (25%) and 72 (24%) subjects, respectively, with 66 subjects identified by both approaches. Sensitivity, specificity, positive predictive value, and negative predictive value for the NLP algorithm in predicting asthma status were 92%, 96%, 89%, and 97%, respectively. The known risk factors for asthma identified by NLP (eg, smoking history) were similar to the ones identified by manual chart review., Conclusions: Successful implementation of NLP-PAC for asthma ascertainment in 2 different practice settings demonstrates the feasibility of automated asthma ascertainment leveraging electronic health record data with a potential to enable large-scale, multisite asthma studies to improve asthma care and research., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Despite valvular heart diseases constituting a significant medical problem, the acquisition of information describing their pathophysiology remains difficult. Due to valvular size, role and location within the body, there is a need for in vitro systems that can recapitulate disease onset and progression. This study combines the development of an in vitro model and its application in the mechanical stimulation of valvular cell transformation. Specifically, porcine aortic valvular interstitial cells (PAVIC) were cultured on polydimethylsiloxane microfluidic devices with or without exposure to shear stresses. Mechanobiological responses of valvular interstitial cells were evaluated at shear stresses ranging from 0 to 4.26 dyn/cm 2 . When flow rates were higher than 0.78 dyn/cm 2 , cells elongated and aligned with the flow direction. In addition, we found that shear stress enhanced the formation of focal adhesions and up-regulated PAVIC transformation, assessed by increased expression of α-smooth muscle actin and transforming growth factor β. This study reveals a link between the action of shear forces, cell phenotype transformation and focal adhesion formation. This constitutes the first step towards the development of co-cultures (interstitial-endothelial cells) on organ-on-a-chip devices, which will enable studies of the signaling pathways regulating force-induced valvular degeneration in microtissues and potential discovery of valvular degeneration therapies.

Our search of the literature revealed no detailed case reports about drug fever induced by piperacillin/tazobactam in a patient with HIV infection although there were a few case reports about drug fever due to piperacillin/tazobactam with other comorbidities. A 63-year-old male patient with HIV positive was admitted for acute cholecystitis. He was started on piperacillin/tazobactam. For the next 8 days, he had intermittent fever up to 103°F (39.4°C) with relative bradycardia although he showed clinical improvement. There was no laboratory or imaging findings suggestive of another infectious source and drug fever was suspected. The antibiotics were stopped and after 48 hours no fever was observed until the day of discharge. Piperacillin/tazobactam can induce fever in patients with cystic fibrosis and in patients with other conditions. Drug fever may be more prevalent in patients with HIV infection. It has no characteristic pattern and may not be associated with eosinophilia., (2016 BMJ Publishing Group Ltd.)

The present studies were aimed at formulating AZD2811-loaded polylactic acid-polyethylene glycol (PLA-PEG) nanoparticles with adjustable release rates without altering the chemical structures of the polymer or active pharmaceutical ingredient (API). This was accomplished through the use of a hydrophobic ion pairing approach. A series of AZD2811-containing nanoparticles with a variety of hydrophobic counterions including oleic acid, 1-hydroxy-2-naphthoic acid, cholic acid, deoxycholic acid, dioctylsulfosuccinic acid, and pamoic acid is described. The hydrophobicity of AZD2811 was increased through formation of ion pairs with these hydrophobic counterions, producing nanoparticles with exceptionally high drug loading-up to five fold higher encapsulation efficiency and drug loading compared to nanoparticles made without hydrophobic ion pairs. Furthermore, the rate at which the drug was released from the nanoparticles could be controlled by employing counterions with various hydrophobicities and structures, resulting in release half-lives ranging from about 2 to 120h using the same polymer, nanoparticle size, and nanoemulsion process. Process recipe variables affecting drug load and release rate were identified, including pH and molarity of quench buffer. Ion pair formation between AZD2811 and pamoic acid as a model counterion was investigated using solubility enhancement as well as nuclear magnetic resonance spectroscopy to demonstrate solution-state interactions. Further evidence for an ion pairing mechanism of controlled release was provided through the measurement of API and counterion release profiles using high-performance liquid chromatography, which had stoichiometric relationships. Finally, Raman spectra of an AZD2811-pamoate salt compared well with those of the formulated nanoparticles, while single components (AZD2811, pamoic acid) alone did not. A library of AZD2811 batches was created for analytical and preclinical characterization. Dramatically improved preclinical efficacy and tolerability data were generated for the pamoic acid lead formulation, which has been selected for evaluation in a Phase 1 clinical trial (ClinicalTrials.gov Identifier NCT 02579226). This work clearly demonstrates the importance of assessing a wide range of drug release rates during formulation screening as a critical step for new drug product development, and how utilizing hydrophobic ion pairing enabled this promising nanoparticle formulation to proceed into clinical development., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Patients with sickle cell disease have high morbidity and healthcare utilization due to repeated painful crises. Some coexisting conditions which cause pain similar to sickle cell disease may go undiagnosed in these patients. We report two adults with concurrent hyperparathyroidism who experienced significant improvement in sickle cell pain following parathyroidectomy thereby pointing to hyperparathyroidism as the principal causative factor for their pain. Meticulous evaluation for parathyroid disorders can be rewarding in sickle cell disease.

Objectives: We designed this study to examine differences in receipt of mental health treatment between low-income uninsured nonelderly adults with serious mental illness (SMI) who were eligible for Medicaid under the Affordable Care Act (ACA) and their existing Medicaid counterparts. Assessing these differences might estimate the impact of the Medicaid expansion efforts under the ACA on receipt of mental health treatment among uninsured nonelderly adults with SMI., Methods: We examined data from 2000 persons aged 18 to 64 years who participated in the 2008 to 2013 National Survey on Drug Use and Health, had income below 138% of the federal poverty level, met SMI criteria, and either were uninsured (n = 1000) or had Medicaid-only coverage (n = 1000). We defined SMI according to the Alcohol, Drug Abuse, and Mental Health Administration Reorganization Act. We used descriptive analyses and logistic regression modeling., Results: In the 28 states currently expanding Medicaid, the model-adjusted prevalence (MAP) of receiving mental health treatment among Medicaid-only enrollees with SMI (MAP = 71.3%; 95% confidence interval [CI] = 65.74%, 76.29%) was 30.1% greater than their uninsured counterparts (MAP = 54.8%; 95% CI = 48.16%, 61.33%). In the United States, the MAP of receiving mental health treatment among Medicaid-only enrollees with SMI (MAP = 70.4%; 95% CI = 65.67%, 74.70%) was 35.9% higher than their uninsured counterparts (MAP = 51.8%; 95% CI = 46.98%, 56.65%)., Conclusions: Estimated increases in receipt of mental health treatment because of enrolling in Medicaid among low-income uninsured adults with SMI might help inform planning and implementation efforts for the Medicaid expansion under the ACA.

Background: The failure rate after gastric bypass surgery for weight loss has been reported at 10-20%. To date, no reliably safe and effective salvage operation is available. This pilot study was conducted to determine whether restriction of the Roux-en-Y gastric bypass (RYGB) pouch using the adjustable gastric band (AGB) is an effective revision operation., Methods: A prospectively accrued group of patients who underwent revisional surgery using the AGB placed around the RYGB pouch by our bariatric surgical group from October 2004 to October 2006 was analyzed., Results: Of the 10 patients accrued during this period, 2 were lost to follow-up, leaving 8 patients for analysis. Of the 8 patients, 1 was a man and 7 were women. The mean prerevision weight was 135.75 kg (range 105-165), and the body mass index was 48.42 kg/m(2) (range 38.92-55). The mean weight loss at 1 year of follow-up was 17.03 kg (range 0.2-42), with a mean percentage of excess weight loss of 24.29% (range 0.2-49.2%). The mean weight loss of the 5 patients with 2 years of follow-up was 36.4 kg (range 20-58), with a mean percentage of excess weight loss of 48.7% (range 21.8-98.1%). One patient with 3 years of follow-up had a weight loss of 56 kg and a percentage of excess weight loss of 66.2%. Three minor complications developed: 2 AGB port-related complications requiring port revision and 1 postoperative wound hematoma requiring evacuation. No band erosions or band slippages occurred, and no major complications developed., Conclusion: In our study, an AGB placed around the RYGB pouch was a safe and effective revision operation for a failed RYGB operation.

Purpose: It is proposed that local elastase inhibition could suppress the extracellular matrix (ECM) degradation and subsequent smooth muscle cell migration and limit subsequent in-stent restenosis. This study evaluated the effect of stent-based controlled elastase inhibition on restenosis after stent implantation in a rabbit model., Materials and Methods: Biodegradable microspheres containing the potent elastase inhibitor alpha-1-antitrypsin (AAT) were prepared. Daily release of AAT from the microspheres was confirmed in vitro. The microspheres were loaded into stents with an abluminal polymer reservoir. Implantation of the stent with AAT microspheres and blank microspheres (control) was performed in the abdominal aortae of six rabbits in each group. After stent deployment, all stents were overdilated to 125% diameter. Stent-implanted arteries were harvested after 7 days (n = 3 each) or 28 days (n = 3 each). To assess the effect of local delivery of AAT, elastase activity and elastin content of the stent-implanted aortae were analyzed. As an endpoint, intima-to-media (I/M) ratio was determined in the 7-day and 28-day specimens., Results: Significant inhibition of elastase was confirmed in treated vessels versus controls at 7 days after stent implantation (P < .05). This reduction in elastase activity was sufficient to afford early and late reduction of in-stent neointima. Plaque progression in the 28-day specimens decreased to 67% with elastase inhibition relative to controls (P < .05)., Conclusion: Stent-based controlled release of elastase inhibitor may significantly reduce ECM degradation and might limit in-stent restenosis.