Decorin inhibition of PDGF-stimulated vascular smooth muscle cell function: potential mechanism for inhibition of intimal hyperplasia after balloon angioplasty

Decorin is a small proteoglycan that binds to transforming growth factor-beta (TGF-beta) and inhibits its activity. However, its interaction with platelet-derived growth factor (PDGF), involved in arterial repair after injury, is not well characterized. The objectives of this study were to assess decorin-PDGF and decorin-PDGF receptor (PDGFR) interactions, the in vitro effects of decorin on PDGF-stimulated smooth muscle cell (SMC) functions and the in vivo effects of decorin overexpression on arterial repair in a rabbit carotid balloon-injury model. Decorin binding to PDGF was demonstrated by solid-phase binding and affinity cross-linking assays. Decorin potently inhibited PDGF-stimulated PDGFR phosphorylation. Pretreatment of rabbit aortic SMC with decorin significantly inhibited PDGF-stimulated cell migration, proliferation, and collagen synthesis. Decorin overexpression by adenoviral-mediated gene transfection in balloon-injured carotid arteries significantly decreased intimal cross-sectional area and collagen content by approximately 50% at 10 weeks compared to beta-galactosidase-transfected or balloon-injured, non-transfected controls. This study shows that decorin binds to PDGF and inhibits its stimulatory activity on SMCs by preventing PDGFR phosphorylation. Decorin overexpression reduces intimal hyperplasia and collagen content after arterial injury. Decorin may be an effective therapy for the prevention of intimal hyperplasia after balloon angioplasty.     

Evaluating mechanism and severity of injuries among trauma patients admitted to Sina Hospital, the National Trauma Registry of Iran

Purpose: Injuries are one of the leading causes of death and lead to a high social and financial burden. Injury patterns can vary significantly among different age groups and body regions. This study aimed to evaluate the relationship between mechanism of injury, patient comorbidities and severity of injuries. Methods: The study included trauma patients from July 2016 to June 2018, who were admitted to Sina Hospital, Tehran, Iran. The inclusion criteria were all injured patients who had at least one of the following: hospital length of stay more than 24 h, death in hospital, and transfer from the intensive care unit of another hospital. Data collection was performed using the National Trauma Registry of Iran minimum dataset. Results: The most common injury mechanism was road traffic injuries (49.0%), followed by falls (25.5%). The mean age of those who fell was significantly higher in comparison with other mechanisms (p < 0.001). Severe extremity injuries occurred more often in the fall group than in the vehicle collision group (69.0% vs. 43.5%, p < 0.001). Moreover, cases of severe multiple trauma were higher amongst vehicle collisions than injuries caused by falls (27.8% vs. 12.9%, p = 0.003). Conclusion: Comparing falls with motor vehicle collisions, patients who fell were older and sustained more extremity injuries. Patients injured by motor vehicle collision were more likely to have sustained multiple trauma than those presenting with falls. Recognition of the relationship between mechanisms and consequences of injuries may lead to more effective interventions.     

The cardiac atria are chambers of active remodeling and dynamic collagen turnover during evolving heart failure

OBJECTIVES: The role of atrial myocytes and extracellular matrix (ECM) changes in atrial chamber remodeling was studied in a canine model of heart failure (HF). BACKGROUND: Cardiac remodeling is a key process mediating the progression of HF. Studies of the structural mechanisms of cardiac remodeling have been limited to the left ventricle. The structural alterations associated with atrial chamber remodeling in evolving HF have not been studied. METHODS: Age- and weight-matched dogs were subjected to right ventricular pacing (240 beats/min) for one and three weeks to produce early and severe HF, respectively. Atrial tissues were assessed for myocyte and ECM changes. RESULTS: Right atrial and left atrial (LA) pressures were significantly increased in early and severe HF. The LA wall tension index was significantly increased at both HF stages by 116% and 443%, respectively. Atrial collagen synthesis and degradation were significantly increased in severe HF. Gelatinase activity was significantly increased at both early and severe stages of HF. Gelatin zymography showed increased matrix metalloproteinases (MMP)-9 with early HF and increased MMP-2 with severe HF. The LA wall tension index was significantly correlated with gelatinase activity and collagen synthesis. Although total atrial collagen content was not changed, disarray of collagen fibers was observed. Atrial myocyte hypertrophy without evidence of apoptosis was also present in severe HF. CONCLUSIONS: There is marked atrial chamber remodeling in canine pacing-induced HF, which is characterized by myocyte hypertrophy and dynamic collagen turnover. Atrial remodeling may contribute to the development of atrial arrhythmias and pulmonary hypertension and could offer a novel therapeutic target.     

Efficacy and safety of rituximab therapy in patients with systemic sclerosis disease (SSc): systematic review and meta-analysis

Clinical Rheumatology - The clinical benefits of rituximab in systemic sclerosis (SSc) are still contentious. The present meta-analysis aimed to systematically assess rituximab’s safety and...     

Characteristics,sources, and health risks of atmospheric PM10-bound heavy metals in a populated middle eastern city

ABSTRACT

This study reports on the characteristics, sources, and health risks of atmospheric PM₁₀-bound heavy metals (HMs) on citizenship living in different regions of Ahvaz, Southwest of Iran were investigated during 2016–2017. A total of 84 samples were analyzed from different regions: (S1) industrial, (S2) high traffic, and (S3) residential. Blood samples were collected from people who came to the east health center of Ahvaz. High volume air samplers, equipped with quartz fiber filters (8?×?10) were utilized for sampling in this study. Inductively coupled plasma optical emission spectroscopy (ICP-OES) was also used for HMs. Risk assessment and hazard index of these pollutants were estimated, using USEPA’s exposure parameters. Based on the results, the highest and the lowest concentration of HM were observed in industrial and residential areas. Blood’s HMs concentration for chromium (Cr), nickel (Ni), lead (Pb), and zinc (Zn) were 2.932, 4.199, 8.425, and 71.2?μg/dL, respectively. In conclusion, increasing exposure concentration of HMs would have a significant potential for increased cancer and risk of diseases. The results of this study show that increasing exposure concentration to HM in the studied scenarios have a significant potential for generating different health endpoints, although exposing to HMs led to generating diseases in individuals particularly in polluted and populated districts; so, environmental measures should be considered by urban air authorities to mitigate the concentration of these pollutants in ambient air.     

Oriented nanofibrous silk as a natural scaffold for ocular epithelial regeneration

The aim of this study was to develop nanofibrous silk substrates for limbal stem cell expansion that can serve as a potential alternative substrate to replace human amniotic membrane. The human limbal stem cell was used to evaluate the biocompatibility of substrates (random and oriented nanofibrous mats, and human amniotic membrane) based on their phenotypic profile, viability, proliferation, and attachment ability. Biocompatibility results indicated that all substrates were highly biocompatible, as limbal stem cells could favorably attach and proliferate on the nanofibrous surfaces. Microscopic figures showed that the human limbal stem cells were firmly anchored to the substrates and were able to retain a normal corneal stem cell phenotype. Microscopic analyses illustrated that cells infiltrated the nanofibers and successfully formed a three-dimensional corneal epithelium, which was viable for 15 days. Immunocytochemistry and real-time PCR results revealed no change in the expression profile of limbal stem cells grown on nanofibrous substrates when compared to those grown on human amniotic membrane. In addition, electrospun nanofibrous silk substrates especially oriented mat provides not only a milieu supporting limbal stem cells expansion, but also serve as a useful alternative carrier for ocular surface tissue engineering and could be used as an alternative substrate to amniotic membrane.     

Hip and knee muscle torque and its relationship with dynamic balance in chronic ankle instability,copers and controls

ObjectivesWe compared hip and knee isometric muscle torque between individuals with chronic ankle instability (CAI), those who have sustained one ankle sprain with no ongoing problems (copers) and healthy controls. Our secondary objective was to compare balance between groups and investigate the relationship between muscle torque and balance.DesignCross-sectional study.Methods22 CAI, 20 copers and 22 uninjured participants were tested. Isometric torque (normalised to body mass (Nm/kg)) was measured using a rigidly-fixated hand-held dynamometer. Balance was assessed with the Y-balance test.ResultsKnee and hip flexor and extensor, and hip adductor and abductor muscle torque was less in individuals with CAI compared to controls (standardised mean difference (SMD) >1.2). Hip and knee flexor and extensor muscle torque was less in CAI participants than copers (SMD: 0.69–1.1). Hip external and internal rotator torque did not differ between groups. There was no difference in hip or knee muscle torque between controls and copers (SMD: 0.01–0. 54). Balance was impaired in CAI participants compared to copers and controls in all directions. There was a strong positive correlation between posterolateral Y-balance test performance and torque of the hip adductors (r = 0.53), flexors (r = 0.52) and extensors (r = 0.50).ConclusionsIndividuals with CAI have weak knee and hip muscles compared to copers and controls. Hip strength was shown to be related to posterolateral balance performance. Future studies may investigate the effect of hip and knee strengthening exercise on ongoing ankle problems, such as episodic giving way in individuals with CAI.     

The associations between noise annoyance and psychological distress with blood pressure in children and adolescents: The CASPIAN‐V Study

Although blood pressure (BP) tracks from childhood to adulthood, and the prevalence of pediatric primary hypertension is increasing, related determinants are not well understood. The role of noise pollution and psychological distress in increasing BP is well documented in adults, but it remains elusive in children. This study aims to investigate the association of noise annoyance and psychological distress with BP in a pediatric population. This national cross‐sectional study was conducted in 2015 on a sample of 14400 Iranian students, aged 7‐18 years. Information regarding noise annoyance and psychological distress were assessed using questionnaires, and BP values were measured. Levels of noise annoyance and psychological distress were classified based on tertiles to no/low, moderate, and high. Data of 14274 students were completed. The mean age of participants was 12.28 (0.05), with 51% boys and 71.4% urban inhabitant. Diastolic BP and mean arterial BP (MAP) had positive correlations with noise annoyance (regression coefficient: 0.028, 95 % CI: 0.005 ‐ 0.05 and 0.025, 95 % CI: 0.002 – 0.04, respectively). Participants with higher psychological distress were 15 % more likely to experience abnormally high BP compared to those with normal psychological status or mild distresses (OR: 1.15, 95 % CI: 1.003 – 1.34). Here, we found significant positive relationships between the level of noise annoyance and values of diastolic BP and MAP. Moreover, high psychological distress showed to increase the chance of abnormally high BP. The clinical impact of these findings should be assessed in further longitudinal studies.     

The Evaluation of Leukocytes in Response to the In Vitro Testing of Ventricular Assist Devices

Infection is a clinically relevant adverse event in patients with ventricular assist device (VAD) support. The risk of infection could be linked to a reduced immune response resulting from damage to leukocytes during VAD support. The purpose of this study was to develop an understanding of leukocyte responses during the in vitro testing of VADs by analyzing the changes to their morphology and biochemistry. The VentrAssist implantable rotary blood pump (IRBP) and RotaFlow centrifugal pump (CP) were tested in vitro under constant hemodynamic conditions. Automated hematology analysis of samples collected regularly over 25‐h tests was undertaken. A new flow cytometric assay was employed to measure biochemical alteration, necrosis (7‐AAD) and morphological alteration (CD45 expression) of the circulating leukocytes during the pumping process. The results of hematology analysis show the total leukocyte number and subset counts decreased over the period of in vitro tests dependent on different blood pumps. The percentage of leukocytes damaged during 6‐h tests was 40.8 ± 5.7% for the VentrAssist IRBP, 17.6 ± 5.4% for the RotaFlow CP, and 2.7 ± 1.8% for the static control (all n = 5). Flow cytometric monitoring of CD45 expression and forward/side scatter characteristics revealed leukocytes that were fragmented into smaller pieces (microparticles). Scanning electron microscopy and imaging flow cytometry were used to confirm this. Device developers could use these robust cellular assays to gain a better understanding of leukocyte‐specific VAD performance.