SDF1 Gene Variation Is Associated with Circulating SDF1 alpha Level and Endothelial Progenitor Cell Number-The Bruneck Study

BACKGROUND: Stromal cell-derived factor-1 (SDF1) and its receptor CXC chemokine receptor 4 (CXCR4) play a critical role in progenitor cell homing, mobilization and differentiation. It would be interesting to assess the predictive value of SDF-1alpha level for EPC number, and to ascertain whether there is a relationship between SDF1 gene variation, plasma SDF-1alpha level, and the number and function of circulating EPCs. We also tested whether EPC number and function was related to CXCR4 gene variation. METHODOLOGY AND PRINCIPAL FINDINGS: We genotyped a cohort of individuals who participated in the Bruneck Study for single nucleotide polymorphisms (SNPs) in the SDF1 and CXCR4 genes, and measured blood SDF1alpha level as well as EPC number and function. SDF1alpha levels were correlated with age, gender, alcohol consumption, circulating reticulocyte numbers, and concentrations of matrix metalloproteinase-9, C-reactive protein, cystatin C, fibrinogen and homocytein. In blood samples taken in 2005, EPC number was inversely associated with SDF1alpha level (p<0.001). EPC number in 2005 was also inversely associated with SDF1alpha level in 2000 (p = 0.009), suggesting a predictive value of plasma SDF1alpha level for EPC number. There was an association between the SDF1 gene rs2297630 SNP A/A genotype, increased SDF1alpha level (p = 0.002) and lower EPC number (p = 0.006). CONCLUSIONS: Our data indicate that a SDF1 gene variation (rs2297630) has an influence on SDF1alpha level and circulating EPC number, and that plasma SDF1alpha level is a predictor of EPC number

Multiworm algorithm quantum Monte Carlo

We review the path-integral quantum Monte Carlo method and discuss its implementation by multiworm algorithms. We analyze in details the features of the algorithms, and focus our attention on the computation of the $N$-body density matrix to study N-body correlations. Finally, we demonstrate the validity of the algorithms on a system of dipolar bosons trapped in a stack of $N$ one-dimensional layers in the case of zero and finite inter-layer hopping.Comment: 20 pages, 10 figure

Motion-Based Technical Skills Assessment in Transoesophageal Echocardiography

This paper presents a novel approach for evaluating technical skills in Transoesophageal Echocardiography (TEE). Our core assumption is that operational competency can be objectively expressed by specific motion-based measures. TEE experiments were carried out with an augmented reality simulation platform involving both novice trainees and expert radiologists. Probe motion data were collected and used to formulate various kinematic parameters. Subsequent analysis showed that statistically significant differences exist among the two groups for the majority of the metrics investigated. Experts exhibited lower completion times and higher average velocity and acceleration, attributed to their refined ability for efficient and economical probe manipulation. In addition, their navigation pattern is characterised by increased smoothness and fluidity, evaluated through the measures of dimensionless jerk and spectral arc length. Utilised as inputs to well-known clustering algorithms, the derived metrics are capable of discriminating experience levels with high accuracy (>84 %)

Nuclear localization of the mitochondrial factor HIGD1A during metabolic stress.

Cellular stress responses are frequently governed by the subcellular localization of critical effector proteins. Apoptosis-inducing Factor (AIF) or Glyceraldehyde 3-Phosphate Dehydrogenase (GAPDH), for example, can translocate from mitochondria to the nucleus, where they modulate apoptotic death pathways. Hypoxia-inducible gene domain 1A (HIGD1A) is a mitochondrial protein regulated by Hypoxia-inducible Factor-1α (HIF1α). Here we show that while HIGD1A resides in mitochondria during physiological hypoxia, severe metabolic stress, such as glucose starvation coupled with hypoxia, in addition to DNA damage induced by etoposide, triggers its nuclear accumulation. We show that nuclear localization of HIGD1A overlaps with that of AIF, and is dependent on the presence of BAX and BAK. Furthermore, we show that AIF and HIGD1A physically interact. Additionally, we demonstrate that nuclear HIGD1A is a potential marker of metabolic stress in vivo, frequently observed in diverse pathological states such as myocardial infarction, hypoxic-ischemic encephalopathy (HIE), and different types of cancer. In summary, we demonstrate a novel nuclear localization of HIGD1A that is commonly observed in human disease processes in vivo

Role of ADAMTS (A Disintegrin and Metalloproteinase With Thrombospondin Motifs)-5 in Aortic Dilatation and Extracellular Matrix Remodeling.

OBJECTIVE: Thoracic aortic aneurysm (TAA), a degenerative disease of the aortic wall, is accompanied by changes in the structure and composition of the aortic ECM (extracellular matrix). The ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family of proteases has recently been implicated in TAA formation. This study aimed to investigate the contribution of ADAMTS-5 to TAA development. APPROACH AND RESULTS: A model of aortic dilatation by AngII (angiotensin II) infusion was adopted in mice lacking the catalytic domain of ADAMTS-5 (Adamts5Δcat). Adamts5Δcat mice showed an attenuated rise in blood pressure while displaying increased dilatation of the ascending aorta (AsAo). Interestingly, a comparison of the aortic ECM from AngII-treated wild-type and Adamts5Δcat mice revealed versican as the most upregulated ECM protein in Adamts5Δcat mice. This was accompanied by a marked reduction of ADAMTS-specific versican cleavage products (versikine) and a decrease of LRP1 (low-density lipoprotein-related protein 1). Silencing LRP1 expression in human aortic smooth muscle cells reduced the expression of ADAMTS5, attenuated the generation of versikine, but increased soluble ADAMTS-1. A similar increase in ADAMTS-1 was observed in aortas of AngII-treated Adamts5Δcat mice but was not sufficient to maintain versican processing and prevent aortic dilatation. CONCLUSIONS: Our results support the emerging role of ADAMTS proteases in TAA. ADAMTS-5 rather than ADAMTS-1 is the key protease for versican regulation in murine aortas. Further studies are needed to define the ECM substrates of the different ADAMTS proteases and their contribution to TAA formation

Fate of the Aortic Arch Following Surgery on Aortic Root and Ascending Aorta in Bicuspid Aortic Valve.

BACKGROUND: Recent guidelines support more aggressive surgery for aneurysms of the ascending aorta and root in patients with bicuspid aortic valve. However, the fate of the arch after surgery of the root and ascending aorta is unknown. We set out to assess outcomes following root and ascending aortic surgery and subsequent growth of the arch. METHODS: Between 2005 and 2016, 536 consecutive patients underwent surgery for aneurysm of the root and ascending aorta. 168 had bicuspid aortic valve. Patients with dissection were excluded. Arch diameter was measured before and after surgery, at six months and then annually. RESULTS: Of 168 patients, 127 (75.6%) had aortic root replacement and 41 (24.4%) had ascending replacement. Mean age was 57±12.8 years, 82.7% were males and five operations were performed during pregnancy. There was one (0.6%) hospital death. One (0.6%) patient had a stroke and one (0.6%) had re-sternotomy for bleeding. Median ICU and hospital stays were 1 and 6 days respectively. Follow-up was complete for 94% at a median of 5.9 years (1-139 months). Aortic arch diameter was 2.9 cm preoperatively and 3.0 cm at follow-up. There was 97% freedom from reoperation and none of the patients required surgery on the arch. CONCLUSIONS: Prophylactic arch replacement during aortic root and ascending aortic surgery in patients with bicuspid aortic valve is not supported. Our data does not support long term surveillance of the rest of the aorta in this population

Handbook for Aboriginal Alcohol and Drug Work

The Handbook for Aboriginal Alcohol and Drug Work is a practical tool written for Aboriginal drug and alcohol workers, mental health workers and others working in this field. It offers a detailed look at alcohol and drug work from clinical, through to prevention, early intervention and harm reduction. This handbook is also likely to help people working to improve policy and those advocating for change. The idea for it came from workers all over Australia. They told us that they needed an easy to use handbook that can help them respond to the range of alcohol and drug issues they face every day. They also told us that such a book needs to take into account the complex challenges facing workers when helping clients, their families and, sometimes, whole communities

Individual variation in levels of haptoglobin-related protein in children from Gabon

Background: Haptoglobin related protein (Hpr) is a key component of trypanosome lytic factors (TLF), a subset of highdensity lipoproteins (HDL) that form the first line of human defence against African trypanosomes. Hpr, like haptoglobin (Hp) can bind to hemoglobin (Hb) and it is the Hpr-Hb complexes which bind to these parasites allowing uptake of TLF. This unique form of innate immunity is primate-specific. To date, there have been no population studies of plasma levels of Hpr, particularly in relation to hemolysis and a high prevalence of ahaptoglobinemia as found in malaria endemic areas. Methods and Principal Findings: We developed a specific enzyme-linked immunosorbent assay to measure levels of plasma Hpr in Gabonese children sampled during a period of seasonal malaria transmission when acute phase responses (APR), malaria infection and associated hemolysis were prevalent. Median Hpr concentration was 0.28 mg/ml (range 0.03-1.1). This was 5-fold higher than that found in Caucasian children (0.049 mg/ml, range 0.002-0.26) with no evidence of an APR. A general linear model was used to investigate associations between Hpr levels, host polymorphisms, parasitological factors and the acute phase proteins, Hp, C-reactive protein (CRP) and albumin. Levels of Hpr were associated with Hp genotype, decreased with age and were higher in females. Hpr concentration was strongly correlated with that of Hp, but not CRP

Factors affecting the technical efficiency of rural primary health care centers in Hamadan, Iran: data envelopment analysis and Tobit regression

Background: Studying and monitoring the efficiency of primary health care centers has a special place in the health system. Although studies have been conducted in the field of efficiency in Iran, few have focused on rural primary health care centers. In addition, previous studies have not used the child mortality rate and Behvarzes as input and output. Objective: The present study was conducted aimed to estimate the technical efficiency of rural primary health care centers and determinant factors in Hamadan using data envelopment analysis and Tobit regression. Methods: This is a Longitudinal study of rural primary health care centers in Hamadan province (2002�2016). Data Envelopment Analysis was employed to estimate technical efficiency of sampled health facilities while Panel Tobit Analysis was applied to predict factors associated with efficiency levels. The outputs were child mortality rate under 1 year of age and child mortality rate 1 year to 5 years of age. The input was Behvarzes (rural health workers). Results: The results of efficiency analysis showed that the average efficiency scores of the centers had a fluctuating trend during the period of the study, but the average performance scores generally decreased in 2016, as compared with 2002. The highest and lowest average performance scores were observed in 2003 (0.78) and 2013 (0.56), respectively. Number of physicians and rural primary healthcare centers per population had a positive statistically significant and the number of midwives and the total fertility per population had a negative statistically significant effect on efficiency. Conclusions: The findings suggest some level of wastage of health resources in primary health centers. Findings indicate a level of waste of health resources in primary health centers. Behvarz functions in providing primary care services can be considered in the reallocation and optimal use of available resources at the level of rural health centers. © 2020, The Author(s)