Left and right ventricular diastolic dysfunction and diastolic heart failure: does one lead to the other?

Background and Objective Diastolic dysfunction of the left ventricle is a mechanical abnormality diagnosed primarily by echocardiogram, and can be distinguished into three separate degrees based on the severity of reduction in passive compliance and active myocardial relaxation. Methods A literature search was performed for basic science studies, clinical studies and major practice guidelines on the subject of diastolic dysfunction and diastolic heart failure. Important findings were analyzed and correlated with regard to clinical relevance. Results Left ventricular diastolic dysfunction appears to compromise exercise tolerance and is believed to contribute to the pathophysiology in patients with diastolic heart failure. In the clinical setting, however, oftentimes no clear distinction is made between echocardiographically diagnosed diastolic dysfunction and diastolic heart failure, and adequate treatment recommendations are sparse and aimed to prevent worsening and progression of clinical symptoms. To date, there is a lack of high powered trials assessing the possible progression rate from echocardiographically diagnosed diastolic dysfunction to the clinical diagnosis of diastolic heart failure. Furthermore, there are no solid indices to assess the degree of severity of diastolic dysfunction or its progression. Pure right ventricular diastolic dysfunction appears to be even less understood and under-recognized, although it may play a role in the development of both right and left heart failure. Currently there are few but interesting data on the possible interaction between ventricles with diastolic dysfunction and the overall affect on the development of heart failure. Conclusions The timeline and progression of diastolic dysfunction to diastolic heart failure have not been well established and warrant further investigation.     

Unsteady simulation of distal blood flow in an end-to-side anastomosed coronary bypass graft with stenosis

In this paper, we report on the unsteady state modeling of blood flow in an end-to-side anastomosed bypass graft, which has a stenosis upstream from the junction. In coronary artery bypass grafting/surgery (CABG), new arteries are created in order to provide blood to the heart using other blood vessels as conduits to bypass the blocked section in the patient's coronary arteries. The failure of coronary artery bypass procedures has been attributed to both intimal hyperplasia (IH) and atherosclerosis. It is believed that these two phenomena are, in turn, related to the local hemodynamic factors. In this work, a three-dimensional computational fluid dynamics analysis is used to simulate the physiological blood flow through a model of a stenosed coronary bypass graft with the realistic assumption of non-Newtonian flow for human blood. For different flow repartitions and at different times of the cycle, both the recirculating areas and wall shear stress (WSS) are studied. Based on the different distribution of flow rates in the bypass graft and the host artery, the flow features are investigated and the influence of non-Newtonian behavior is discussed in terms of separation points, reattachment points, and the wall shear stresses. Various differences are observed based on the assumption of non-Newtonian behavior of blood, which have not been reported before when a simplified Newtonian approach is utilized.     

Comparative study of cryogen spray cooling with R-134a and R-404a: implications for laser treatment of dark human skin

Cutaneous laser treatment in dark skin patients is challenging due to significant light absorption by the melanin at the basal layer of epidermis, which can result in irreversible nonspecific thermal injury to the epidermis. Cryogen spray cooling (CSC) with R-134a (boiling point approximately -26.2 degrees C at 1 atm), which is currently used during cutaneous laser treatment, has shown poor efficacy in protecting dark human skin. We investigated the potential of CSC with R-404a (boiling point approximately -46.5 degrees C at 1 atm), which has a lower boiling point than R-134a, for improved therapeutic outcome in dark human skin at three levels: in vitro (epoxy resin skin phantom), ex vivo (normal dark human skin sample), and in vivo (skin of the rabbit external ear). The skin phantom was used to acquire the surface and internal temperature profiles in response to CSC with R-134a or R-404a at various spurt durations, based upon which CSC-induced heat removal from the skin phantom was estimated using an algorithm that solved a one-dimensional inverse heat conduction problem. CSC with R-404a increased the temperature reductions within the phantom and subsequently the amount of heat removal from the phantom in comparison to that with R-134a. Normal ex vivo Fitzpatrick types V-VI human skin samples were used to investigate the thermal response of dark human skin epidermis to CSC (R-134a or R-404a) at various spurt durations in conjunction with 595-nm pulsed dye laser irradiation at various radiant exposures. Cryogen R-404a increased the threshold radiant exposures for irreversible thermal injury to the epidermis in dark pigmentation skin. No obvious CSC-induced morphological changes to human skin was observed when sprayed with R404-a spurts using durations up to 300 ms. In vivo rabbit ear vasculature was used as a model of cutaneous anomalies to assess the influences of CSC (with R-134a or R-404a) on the photothermolysis of dermal blood vessels. CSC (R-134a or R-404a) with the spurt durations of 100 to 300 ms increased the most superficial depth of thermally damaged dermal blood vessel compared with the sites without CSC, implying possible nonspecific cooling of superficial dermal blood vessels by the cryogen spurts with the settings applied.     

Engineering Approaches Toward Deconstructing and Controlling the Stem Cell Environment

Stem cell-based therapeutics have become a vital component in tissue engineering and regenerative medicine. The microenvironment within which stem cells reside, i.e., the niche, plays a crucial role in regulating stem cell self-renewal and differentiation. However, current biological techniques lack the means to recapitulate the complexity of this microenvironment. Nano- and microengineered materials offer innovative methods to (1) deconstruct the stem cell niche to understand the effects of individual elements; (2) construct complex tissue-like structures resembling the niche to better predict and control cellular processes; and (3) transplant stem cells or activate endogenous stem cell populations for regeneration of aged or diseased tissues. In this article, we highlight some of the latest advances in this field and discuss future applications and directions of the use of nano- and microtechnologies for stem cell engineering.     

NOD2 exonic variations in Iranian Crohn's disease patients

Purpose

The NOD2 gene is known to have a strong association with Crohn??s disease, but different trends were reported in occurrence of NOD2 variants in distinct ethnicities. The aim of this study was to assess all exonic sequences of the NOD2 gene in Iranian Crohn's disease patients and healthy controls to identify any existing variation and evaluate their association with Crohn's disease.

Methods

A total of 90 non-related Crohn's disease patients and 120 sex- and age-matched healthy controls of Iranian origin were enrolled in this study. The participants were referred to a tertiary center in a 2-year period (2006?C2008). The exonic regions of the NOD2 gene were amplified by polymerase chain reaction and evaluated by direct sequencing.

Results

A total of 21 sequence variations were identified among all exonic regions of the NOD2 gene, of which eight had an allele frequency of more than 5%. Eight new mutations (one in exon 2 and seven in exon 4) were observed. The three main variants (R702W, G908R, and 1007fs) showed allele frequencies of 13.3%, 2.2%, and 1.7%, respectively. Three new variations (P371T, A794P, and Q908H) and R702W mutation were significantly more frequent in Crohn's disease patients compared to controls.

Conclusions

Eight novel mutations were identified in the NOD2 exons, but the pathophysiological importance of these variants remains unclear. Iranian patients with their different genetic reservoirs may demonstrate some novel characteristics for disease susceptibility.     

Improvement of kidney function in patients with chronic kidney disease and severe obesity after bariatric surgery: A systematic review and meta-analysis

The general management for chronic kidney disease (CKD) includes treating reversible causes, including obesity, which may be both a driver and comorbidity for CKD. Bariatric surgery has been shown to reduce the likelihood of CKD progression and improve kidney function in observational studies. We performed a systematic review and meta-analysis of patients with at least stage 3 CKD and obesity receiving bariatric surgery. We searched Embase, MEDLINE, CENTRAL and identified eligible studies reporting on kidney function outcomes in included patients before and after bariatric surgery with comparison to a medical intervention control if available. Risk of bias was assessed with the Newcastle-Ottawa Risk of Bias score. Nineteen studies were included for synthesis. Bariatric surgery showed improved eGFR with a mean difference (MD) of 11.64 (95%CI: 5.84 to 17.45, I² = 66%) ml/min/1.73m² and reduced SCr with MD of ?0.24 (95%CI ?0.21 to ?0.39, I² = 0%) mg/dl after bariatric surgery. There was no significant difference in the relative risk (RR) of having CKD stage 3 after bariatric surgery, with a RR of ?1.13 (95%CI: ?0.83 to ?2.07, I² = 13%), but there was reduced likelihood of having uACR >30 mg/g or above with a RR of ?3.03 (95%CI: ?1.44 to ?6.40, I² = 91%). Bariatric surgery may be associated with improved kidney function with the reduction of BMI and may be a safe treatment option for patients with CKD. Future studies with more robust reporting are required to determine the feasibility of bariatric surgery for the treatment of CKD.