Human Ovarian Tumor Cells Escape γδ T Cell Recognition Partly by Down Regulating Surface Expression of MICA and Limiting Cell Cycle Related Molecules

Background: Mechanisms of human Vc2Vd2 T cell-mediated tumor immunity have yet to be fully elucidated. Methods and Findings: At least some tumor cell recognition is mediated by NKG2D-MICA interactions. Herein, by using MTT assay and PI-BrdU co-staining and Western-blot, we show that these Vc2Vd2 T cells can limit the proliferation of ovarian tumor cells by down regulation of apoptosis and cell cycle related molecules in tumor cells. Cell-to-cell contact is critical. cd T cell-resistant, but not susceptible ovarian tumor cells escape cd T cell-mediated immune recognition by up-regulating pErk1/2, thereby decreasing surface MICA levels. Erk1/2 inhibitor pretreatment or incubation prevents this MICA decrease, while up-regulating key cell cycle related molecules such as CDK2, CDK4 and Cyclin D1, as well as apoptosis related molecules making resistant tumor cells now vulnerable to cd T cell-mediated lysis. Conclusion: These findings demonstrate novel effects of cdT cells on ovarian tumor cells

Human Umbilical Cord Blood-Derived CD34+ Cells Reverse Osteoporosis in NOD/SCID Mice by Altering Osteoblastic and Osteoclastic Activities

Osteoporosis is a bone disorder associated with loss of bone mineral density and micro architecture. A balance of osteoblasts and osteoclasts activities maintains bone homeostasis. Increased bone loss due to increased osteoclast and decreased osteoblast activities is considered as an underlying cause of osteoporosis.The cures for osteoporosis are limited, consequently the potential of CD34+ cell therapies is currently being considered. We developed a nanofiber-based expansion technology to obtain adequate numbers of CD34(+) cells isolated from human umbilical cord blood, for therapeutic applications. Herein, we show that CD34(+) cells could be differentiated into osteoblastic lineage, in vitro. Systemically delivered CD34(+) cells home to the bone marrow and significantly improve bone deposition, bone mineral density and bone micro-architecture in osteoporotic mice. The elevated levels of osteocalcin, IL-10, GM-CSF, and decreased levels of MCP-1 in serum parallel the improvements in bone micro-architecture. Furthermore, CD34(+) cells improved osteoblast activity and concurrently impaired osteoclast differentiation, maturation and functionality.These findings demonstrate a novel approach utilizing nanofiber-expanded CD34(+) cells as a therapeutic application for the treatment of osteoporosis

Mitral valve prolapse: «Much Ado About Nothing», or a real unsolved problem?

The paper discusses the modern state of the mitral valve prolapse (MVP) problem. Controversial and unresolved issues on terminology, diagnostics, and tactics for different MVP variants are considered on the basis of the “Heritable disorders of connective tissue” recommendations (2009) by Expert Committee, the Society of Cardiology of the Russian Federation (VNOK). The modern diagnostic criteria of MVP are discussed, as well as echocardiography-estimated MVP prevalence while using those diagnostic criteria, and the comparison of Framingham Heart Study results to the authors’ own data. The interrelation between autonomic dysfunction and MVP is assessed, and different approaches to the stratification of MVP complication risk are compared, based on the echocardiography results and clinical data. The modern methods of MVP treatment and management strategy are also described

SYSTEMIC INVOLVEMENT OF CONNECTIVE TISSUE AND THE HEART AS IMPORTANT CHARACTERISTICS OF PRIMARY MITRAL VALVE PROLAPSE

Aim. To evaluate systemic involvement of connective tissue (SICT) in young adultswith mitral valve prolapse (MVP) without significant mitral regurgitation (MR).Material and methods. We studied 78 asymptomatic young subjects (mean age19,7±1,6, 72% male) with MVP in comparison with 80 sex- and age-matchedhealthy subjects. We performed phenotypic examination of MVP patients andcontrol group subjects, and echocardiographic study to identify the minor heartanomalies. Longitudinal strain and strain rate (SR) were determined using spackletracking (Vivid 7 Dimension GE, EchoPAC’08).Results. We identified two clusters of patients with MVP. In the first cluster (17subjects, 28% of the MVP group) a significant reduction of longitudinal systolicstrain observed comparing to the control group and the second cluster (61 subjects,72%). Global strain in the second cluster did not differ significantly from the controlgroup. Echocardiographic study showed nonsignificant increase in the averagenumber of SICT points in the first cluster and highly significant increase of the minorheart anomalies’ number in this group of patients.Conclusion. Myocardial deformation assessment allowed to identify the signs ofcardiomyopathy in quarter of young asymptomatic patients with MVP. Increasingnumber of minor heart anomalies in the group with primary MVP and cardiomyopathyallows considering other valve prolapses, dilatation of major vessels, basal and thickLV chords as features of the SICT in primary MVP. A great number of minor heartanomalies in primary MVP may indicate a change in the heart extracellular matrixthat can cause the development of cardiomyopathy in primary MVP

Exposure to volatile organic compounds (VOCs) at gas stations: a probabilistic analysis

Gasoline evaporation and spills may cause high air pollution at gas stations. This study aimed to assess exposure to volatile organic compounds (VOCs) at gas stations among customers. Ambient air samples were collected in the fuel dispensing area of 51 gas stations in the Greater Memphis Area, USA, in summer 2017. For the comparison purpose, samples were collected in the ambient air at 20 community sites and in the indoor air of 30 homes, 11 offices, and 15 running vehicles in the same region. Air sampling used Tenax TA thermal desorption (TD) tubes and samples were analyzed by TD-gas chromatography/mass spectrometry (GC/MS) for 70 target compounds. Gasoline-related VOCs were identified using factor analysis, and exposure at gas stations was evaluated using Monte Carlo analysis. Benzene, toluene, ethylbenzene, and xylenes (BTEX) showed the highest concentrations ranging from 2 to 15 μg/m3, ten times higher than those in the community air. Factor analysis confirmed gasoline as the common source of aromatic compounds. VOC concentrations had no association with the number of cars present or environmental parameters. Exposure to aromatic compounds at gas stations represented 2% of the total exposure (i.e., the sum of indoor and outdoor exposures) but 38% of the outdoor exposure among customers. The exposure levels were below the acute health thresholds and presented 0.3 × 10−6 lifetime excess cancer risk. In conclusion, customers’ exposure to VOCs at gas stations has negligible non-cancer and cancer risks. It is also suggested that customers stand away from the nozzle to avoid high personal exposures during refueling

Autonomous dysfunction in young patients with mitral valve prolapse and Marfanoid habitus

Aim. To assess autonomous regulation status in young patients with mitral valve prolapse (MVP), Marfanoid habitus (MH), and signs of systemic connective tissue involvement (SCTP). Material and methods. The study included 59 young men with MVP, MH, and SCTP. All participants underwent phenotypical and clinical examination, anthropometry, electrocardiography (ECG), echocardiography (EchoCG), Holter monitoring (HM) of ECG and blood pressure (BP), treadmill test, heart rate variability (HRV) assessment, and additional cardiovascular tests. Results. In patients with MVP, MH, and particularly SCTI, a significant decrease in daytime parameters of sinus arrhythmia was observed. These individuals were also characterized by significantly reduced spectral HRV parameters. A pathologic reaction to active orthostatic test was registered in 50% of the participants with MVP and MH. The overall assessment of autonomous regulation tests demonstrated the presence of abnormalreactions in more than 50% of MH individuals and in 80% of MVP patients. Conclusion. Autonomous dysfunction is common among young patients with MVP, MH, and SCTI

MINOR HEART ANOMALIES

The paper attempts to revise the working classification of minor heart anomalies (MHA). It is proposed to exclude some syndromes and abnormalities which clearly have an independent clinical significance. The need for exclusion of prevalent normal variants, as well as anatomical and physiological characteristics of child’s heart, is justified. The inverse dynamics of selected MHA in older vs. younger age groups is demonstrated. The authors suggest that the current working classification should be modified