Monocyte Chemotactic Protein-1 (MCP-1) and Growth Factors Called into Question as Markers of Prolonged Psychosocial Stress

BACKGROUND:Psychosocial stress is becoming a major contributor to increased mental ill-health and sick leave in many countries. Valid markers of chronic stress would be valuable for diagnostic and prognostic purposes. A recent study suggested monocyte chemotactic protein-1 (MCP-1), epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) as markers of chronic stress. We aimed to confirm these potential biomarkers of prolonged psychosocial stress in female patients. METHODOLOGY/PRINCIPAL FINDINGS:Circulating levels of MCP-1, EGF and VEGF, along with several other cytokines, were measured in plasma from 42 female patients suffering from exhaustion due to prolonged psychosocial stress and 42 control subjects, using a protein biochip immunoassay. There were no significant differences between patients and controls in any of the cytokines or growth factors analyzed. Furthermore, when using a different protein bioassay and reanalyzing MCP-1 and VEGF in the same samples, markedly different levels were obtained. To further explore if inflammation is present in patients with exhaustion, the classical inflammatory marker C-reactive protein (CRP) was measured in another group of patients (n=89) and controls (n=88) showing a small but significant increase of CRP levels in the patients. CONCLUSIONS/SIGNIFICANCE:MCP-1, EGF and VEGF may not be suitable markers of prolonged psychosocial stress as previously suggested. Furthermore, significant differences were obtained when using two different protein assays measuring the same samples, indicating that comparing studies where different analytic techniques have been used might be difficult. Increased levels of CRP indicate that low-grade inflammation might be present in patients with exhaustion due to prolonged stress exposure but this inflammation does not seem to be reflected by increase in circulating MCP-1 or other cytokines measured

Carotid Plaque Age Is a Feature of Plaque Stability Inversely Related to Levels of Plasma Insulin

C-declination curve (a result of the atomic bomb tests in the 1950s and 1960s) to determine the average biological age of carotid plaques.C content by accelerator mass spectrometry. The average plaque age (i.e. formation time) was 9.6±3.3 years. All but two plaques had formed within 5–15 years before surgery. Plaque age was not associated with the chronological ages of the patients but was inversely related to plasma insulin levels (p = 0.0014). Most plaques were echo-lucent rather than echo-rich (2.24±0.97, range 1–5). However, plaques in the lowest tercile of plaque age (most recently formed) were characterized by further instability with a higher content of lipids and macrophages (67.8±12.4 vs. 50.4±6.2, p = 0.00005; 57.6±26.1 vs. 39.8±25.7, p<0.0005, respectively), less collagen (45.3±6.1 vs. 51.1±9.8, p<0.05), and fewer smooth muscle cells (130±31 vs. 141±21, p<0.05) than plaques in the highest tercile. Microarray analysis of plaques in the lowest tercile also showed increased activity of genes involved in immune responses and oxidative phosphorylation.C, can improve our understanding of carotid plaque stability and therefore risk for clinical complications. Our results also suggest that levels of plasma insulin might be involved in determining carotid plaque age

Multi-Organ Expression Profiling Uncovers a Gene Module in Coronary Artery Disease Involving Transendothelial Migration of Leukocytes and LIM Domain Binding 2: The Stockholm Atherosclerosis Gene Expression (STAGE) Study

Environmental exposures filtered through the genetic make-up of each individual alter the transcriptional repertoire in organs central to metabolic homeostasis, thereby affecting arterial lipid accumulation, inflammation, and the development of coronary artery disease (CAD). The primary aim of the Stockholm Atherosclerosis Gene Expression (STAGE) study was to determine whether there are functionally associated genes (rather than individual genes) important for CAD development. To this end, two-way clustering was used on 278 transcriptional profiles of liver, skeletal muscle, and visceral fat (n = 66/tissue) and atherosclerotic and unaffected arterial wall (n = 40/tissue) isolated from CAD patients during coronary artery bypass surgery. The first step, across all mRNA signals (n = 15,042/12,621 RefSeqs/genes) in each tissue, resulted in a total of 60 tissue clusters (n = 3958 genes). In the second step (performed within tissue clusters), one atherosclerotic lesion (n = 49/48) and one visceral fat (n = 59) cluster segregated the patients into two groups that differed in the extent of coronary stenosis (P = 0.008 and P = 0.00015). The associations of these clusters with coronary atherosclerosis were validated by analyzing carotid atherosclerosis expression profiles. Remarkably, in one cluster (n = 55/54) relating to carotid stenosis (P = 0.04), 27 genes in the two clusters relating to coronary stenosis were confirmed (n = 16/17, P<10−27and−30). Genes in the transendothelial migration of leukocytes (TEML) pathway were overrepresented in all three clusters, referred to as the atherosclerosis module (A-module). In a second validation step, using three independent cohorts, the A-module was found to be genetically enriched with CAD risk by 1.8-fold (P<0.004). The transcription co-factor LIM domain binding 2 (LDB2) was identified as a potential high-hierarchy regulator of the A-module, a notion supported by subnetwork analysis, by cellular and lesion expression of LDB2, and by the expression of 13 TEML genes in Ldb2–deficient arterial wall. Thus, the A-module appears to be important for atherosclerosis development and, together with LDB2, merits further attention in CAD research

Provenancing Archaeological Wool Textiles from Medieval Northern Europe by Light Stable Isotope Analysis (δ13C, δ15N, δ2H)

We investigate the origin of archaeological wool textiles preserved by anoxic waterlogging from seven medieval archaeological deposits in north-western Europe (c. 700-1600 AD), using geospatial patterning in carbon (δ13C), nitrogen (δ15N) and non-exchangeable hydrogen (δ2H) composition of modern and ancient sheep proteins. δ13C, δ15N and δ2H values from archaeological wool keratin (n = 83) and bone collagen (n = 59) from four sites were interpreted with reference to the composition of modern sheep wool from the same regions. The isotopic composition of wool and bone collagen samples clustered strongly by settlement; inter-regional relationships were largely parallel in modern and ancient samples, though landscape change was also significant. Degradation in archaeological wool samples, examined by elemental and amino acid composition, was greater in samples from Iceland (Reykholt) than in samples from north-east England (York, Newcastle) or northern Germany (Hessens). A nominal assignment approach was used to classify textiles into local/non-local at each site, based on maximal estimates of isotopic variability in modern sheep wool. Light element stable isotope analysis provided new insights into the origins of wool textiles, and demonstrates that isotopic provenancing of keratin preserved in anoxic waterlogged contexts is feasible. We also demonstrate the utility of δ2H analysis to understand the location of origin of archaeological protein samples

Cleft maxillary distraction versus orthognathic surgery: Clinical morbidities and surgical relapse

BACKGROUND: This is the first randomized controlled study aiming to compare the postoperative clinical morbidities in cleft lip and palate patients treated with distraction osteogenesis versus conventional orthognathic surgery. METHODS: Twenty-nine cleft lip and palate patients with moderate maxillary hypoplasia requiring a maxillary Le Fort I advancement of 4 to 10 mm were randomized into two groups for either internal maxillary distractors or immediate fragment transposition using miniplates and screw fixation. Clinical morbidities were recorded using standardized questionnaires. Skeletal and dental relapses were assessed using lateral cephalometric landmarks. RESULTS: In the distraction group, two of 15 patients developed infection around the distractors and one patient had an occlusal relapse. Among the 14 patients who received conventional orthognathic surgery, the complications included intraoperative hemorrhage (n = 1), plate exposure leading to sinusitis (n = 1), and occlusal relapse (n = 1). In the skeletal relapses of the osteotomy group, a statistically significant vertical relapse of the A point was noted during the second to twelfth weeks when compared with the distraction group. A statistically significant horizontal relapse of the A and P points during the eighth to twelfth weeks was noted when the osteotomy group was compared with the distraction group. CONCLUSIONS: There were no major differences in the clinical morbidities between the osteotomy and distraction groups. Distraction provided better skeletal stability, whereas there was a significant amount of skeletal relapse in the first 12 weeks after conventional cleft maxillary osteotomy. Copyright ©2006 by the American Society of Plastic Surgeons.link_to_subscribed_fulltex

Severity of psoriasis differs between men and women : a registry based study of the clinical outcome measure Psoriasis Area and Severity Index (PASI) in 5438 patients

Background: Psoriasis is a common skin disease and moderate to severe psoriasis is associated with a dose-dependent risk for metabolic and cardiovascular morbidity. It has previously been speculated that women have less severe psoriasis, as men are overrepresented in psoriasis registers and consume more care. Objective: The objective of this study was to investigate, for the first time, the sex differences in the severity of psoriasis using the gold standard of severity measurement, the Psoriasis Area and Severity Index (PASI), and the distinct elements of the PASI score. Design, Setting and Participants: This was a cross-sectional study based on the national registry for systemic treatment of psoriasis in Sweden (PsoReg), with 5438 patients experiencing moderate to severe psoriasis. Differences in the PASI score and its elements at enrolment were tested by multivariable ordinal logistic regressions. Main Outcome Measures: The different components of the PASI score were used to analyze the assessment of disease severity. For each body area (head, arms, trunk, and legs), the score of the plaque characteristics and degree of skin involvement were used as outcomes. Results: Women had statistically significantly lower median PASI scores (5.4) than men (7.3) [p &lt; 0.001], which was consistent across all ages. The difference remained statistically significant in a multivariable linear regression. The itemized PASI analyses from the Mann–Whitney–Wilcoxon tests and the adjusted ordinal logistic regressions confirmed that women had significantly lower scores than men in all areas of the body, except for the head. No differences in the use of medications prior to enrolment could be found that may cause this difference between the sexes. Conclusions: As the PsoReg contains the detailed disease measurement PASI, which was traditionally used for selected participants in clinical studies only, a nationwide unselected population could be investigated. The fact that women have less severe psoriasis can explain the dominance of males in the systemic treatment of psoriasis. These findings motivate a gender perspective in the management of psoriasis and in the prevention and management of its comorbidities