Role of a Transient Receptor Potential Channels in Marfan Syndrome-induced Aortopathy and Cardiomyopathy

Marfan syndrome (MFS) represents a genetic disorder with variable phenotypic expression. The main cardiovascular sequelae of MFS include aortic aneurysm/dissection and cardiomyopathy. While significant advances in the understanding of TGF-β signaling have led to promising therapeutic targets for the treatment of aortopathy, clinical studies have tempered this optimism. In particular, these studies suggest additional signaling pathways that play a significant role in aortic disease progression. Furthermore, even less is known with respect to effectors involved in MFS-induced cardiomyopathy. To date, studies aimed at elucidating molecular mechanisms involved in MFS-induced disease progression have been hampered by the lack of an accelerated disease model. Meanwhile, transient receptor potential (TRP) channels have been implicated as key effectors in other vascular smooth muscle and cardiomyocyte pathologies, yet there is a paucity of investigation focused on their involvement in the aortopathy and cardiomyopathy of MFS. In these studies, we investigate the importance of TRP channels in the pathogenesis of MFS-induced aortopathy and cardiomyopathy by evaluating differential expression in a novel murine model of accelerated MFS etiolog

Automated Suturing For Pacemaker Lead Placement Via Video Guided Minimally Invasive Surgical Access

The placement of permanent and temporary cardiac epicardial pacemaker leads through minimally invasive cardiac surgery (MICS) access remains a challenge. A reliable ergonomic approach for remote lead placement requires improved technology. We present a novel means to enable the remote placement of epicardial leads using automated suturing devices and videoscopy

Serotonin and corticosterone rhythms in mice exposed to cigarette smoke and in patients with COPD:implication for COPD-associated neuropathogenesis

The circadian timing system controls daily rhythms of physiology and behavior, and disruption of clock function can trigger stressful life events. Daily exposure to cigarette smoke (CS) can lead to alteration in diverse biological and physiological processes. Smoking is associated with mood disorders, including depression and anxiety. Patients with chronic obstructive pulmonary disease (COPD) have abnormal circadian rhythms, reflected by daily changes in respiratory symptoms and lung function. Corticosterone (CORT) is an adrenal steroid that plays a considerable role in stress and anti-inflammatory responses. Serotonin (5-hydroxytryptamine; 5HT) is a neurohormone, which plays a role in sleep/wake regulation and affective disorders. Secretion of stress hormones (CORT and 5HT) is under the control of the circadian clock in the suprachiasmatic nucleus. Since smoking is a contributing factor in the development of COPD, we hypothesize that CS can affect circadian rhythms of CORT and 5HT secretion leading to sleep and mood disorders in smokers and patients with COPD. We measured the daily rhythms of plasma CORT and 5HT in mice following acute (3 d), sub-chronic (10 d) or chronic (6 mo) CS exposure and in plasma from non-smokers, smokers and patients with COPD. Acute and chronic CS exposure affected both the timing (peak phase) and amplitude of the daily rhythm of plasma CORT and 5HT in mice. Acute CS appeared to have subtle time-dependent effects on CORT levels but more pronounced effects on 5HT. As compared with CORT, plasma 5HT was slightly elevated in smokers but was reduced in patients with COPD. Thus, the effects of CS on plasma 5HT were consistent between mice and patients with COPD. Together, these data reveal a significant impact of CS exposure on rhythms of stress hormone secretion and subsequent detrimental effects on cognitive function, depression-like behavior, mood/anxiety and sleep quality in smokers and patients with COPD

Recurrent DNMT3A R882 Mutations in Chinese Patients with Acute Myeloid Leukemia and Myelodysplastic Syndrome

Somatic mutations of DNMT3A gene have recently been reported in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We examined the entire coding sequences of DNMT3A gene by high-resolution melting analysis and sequencing in Chinese patients with myeloid malignancies. R882 mutations were found in 12/182 AML and in 4/51 MDS, but not in either 79 chronic myeloid leukemia (CML), or 57 myeloproliferative neoplasms (MPNs), or 4 chronic monomyelocytic leukemia. No other DNMT3A mutations were detected in all patients. R882 mutations were associated with old age and more frequently present in monoblastic leukemia (M4 and M5, 7/52) compared to other subtypes (5/130). Furthermore, 14/16 (86.6%) R882 mutations were observed in patients with normal karyotypes. The overall survival of mutated MDS patients was shorter than those without mutation (median 9 and 25 months, respectively). We conclude that DNMT3A R882 mutations are recurrent molecular aberrations in AML and MDS, and may be an adverse prognostic event in MDS

Enhancement of PLA-PVA surface adhesion in bilayer assemblies by PLA aminolisation

Data Availability: The raw/processed data required to reproduce these findings cannot be shared at this time due to legal or ethical reasons.Poly(lactic acid) (PLA) and poly(vinyl alcohol) (PVA) present complementary barrier properties, and their combination in multilayer assemblies (laminates) could provide materials with more effective barrier capacity for food packaging purposes. However, their low chemical affinity compromises adequate polymer adhesion. Surface free energy modification of thermo-processed PLA films through treatment with 1,6-hexanediamine was used to enhance adhesion with polar PVA aqueous solutions. Treatments of 1 and 3 min increased the polar component of the solid surface tension, while treatments above 10 min provoked a corrosive effect in the films structure. Extensibility analyses of PVA solutions loaded with carvacrol (15 wt.%) and different Tween 85 ratios on PLA-activated surfaces allowed the selection of the 1-min aminolysed surface for obtaining PLA-PVA bilayers, by casting PVA solutions on the PLA films. This study revealed that despite aminolisation enhancing the PLA surface affinity for aqueous PVA solutions, casting-obtained bilayers presented limited oxygen barrier effectiveness due to heterogeneous thickness of PVA layer in the laminates.The authors acknowledge the financial support provided by the Ministerio de Economia y Competitividad (MINECO) of Spain (project AGL2016-76699-R). The author A. Tampau thanks MINECO for the pre-doctoral research grant #BES-2014-068100.info:eu-repo/semantics/publishedVersio

Treatments for people who use anabolic androgenic steroids: a scoping review.

BACKGROUND: A growing body of evidence suggests that anabolic androgenic steroids (AAS) are used globally by a diverse population with varying motivations. Evidence has increased greatly in recent years to support understanding of this form of substance use and the associated health harms, but there remains little evidence regarding interventions to support cessation and treat the consequences of use. In this scoping review, we identify and describe what is known about interventions that aim to support and achieve cessation of AAS, and treat and prevent associated health problems. METHODS: A comprehensive search strategy was developed in four bibliographic databases, supported by an iterative citation searching process to identify eligible studies. Studies of any psychological or medical treatment interventions delivered in response to non-prescribed use of AAS or an associated harm in any setting were eligible. RESULTS: In total, 109 eligible studies were identified, which included case reports representing a diverse range of disciplines and sources. Studies predominantly focussed on treatments for harms associated with AAS use, with scant evidence on interventions to support cessation of AAS use or responding to dependence. The types of conditions requiring treatment included psychiatric, neuroendocrine, hepatic, kidney, cardiovascular, musculoskeletal and infectious. There was limited evidence of engagement with users or delivery of psychosocial interventions as part of treatment for any condition, and of harm reduction interventions initiated alongside, or following, treatment. Findings were limited throughout by the case report study designs and limited information was provided. CONCLUSION: This scoping review indicates that while a range of case reports describe treatments provided to AAS users, there is scarce evidence on treating dependence, managing withdrawal, or initiating behaviour change in users in any settings. Evidence is urgently required to support the development of effective services for users and of evidence-based guidance and interventions to respond to users in a range of healthcare settings. More consistent reporting in articles of whether engagement or assessment relating to AAS was initiated, and publication within broader health- or drug-related journals, will support development of the evidence base