Influence of depression symptoms on serum tumor necrosis factor-α of patients with chronic low back pain

Introduction  

Patients with chronic low back pain (cLBP) have high rates of comorbid psychiatric disorders, mainly depression. Recent evidence suggests that depressive symptoms and pain, as interacting factors, have an effect on the circulating levels of inflammatory markers relevant to coronary artery disease. Our previous work showed a higher serum level of an inflammatory marker tumour necrosis factor-alpha (TNFα) in patients with cLBP, which did not correlate with intensity of low back pain alone. In the present study we investigated the cross-sectional associations of depressive symptoms, low back pain and their interaction with circulating levels of TNFα.     

How do we stand? Variations during repeated standing phases of asymptomatic subjects and low back pain patients

An irreproducible standing posture can lead to mis-interpretation of radiological measurements, wrong diagnoses and possibly unnecessary treatment. This study aimed to evaluate the differences in lumbar lordosis and sacrum orientation in six repetitive upright standing postures of 353 asymptomatic subjects (including 332 non-athletes and 21 athletes – soccer players) and 83 low back pain (LBP) patients using a non-invasive back-shape measurement device.In the standing position, all investigated cohorts displayed a large inter-subject variability in sacrum orientation (∼40°) and lumbar lordosis (∼53°). In the asymptomatic cohort (non-athletes), 51% of the subjects showed variations in lumbar lordosis of 10–20% in six repeated standing phases and 29% showed variations of even more than 20%. In the sacrum orientation, 53% of all asymptomatic subjects revealed variations of >20% and 31% of even more than 30%.It can be concluded that standing is highly individual and poorly reproducible. The reproducibility was independent of age, gender, body height and weight. LBP patients and athletes showed a similar variability as the asymptomatic cohort. The number of standing phases performed showed no positive effect on the reproducibility. Therefore, the variability in standing is not predictable but random, and thus does not reflect an individual specific behavioral pattern which can be reduced, for example, by repeated standing phases.     

Circular permutation in the Ω-loop of TEM-1 β-lactamase results in improved activity and altered substrate specificity

Generating diverse protein libraries that contain improved variants at a sufficiently high frequency is critical for improving the properties of proteins using directed evolution. Many studies have illustrated how random mutagenesis, cassette mutagenesis, DNA shuffling and similar approaches are effective diversity generating methods for directed evolution. Very few studies have explored random circular permutation, the intramolecular relocation of the N- and C-termini of a protein, as a diversity-generating step for directed evolution. We subjected a library of random circular permutations of TEM-1 β-lactamase to selections on increasing concentrations of a variety of β-lactam antibiotics including cefotaxime. We identified two circularly permuted variants that conferred elevated resistance to cefotaxime but decreased resistance to other antibiotics. These variants were circularly permuted in the Ω-loop proximal to the active site. Remarkably, one variant was circularly permuted such that the key catalytic residue Glu166 was located at the N-terminus of the mature protein.     

Electromyographic responses of erector spinae and lower limb’s muscles to dynamic postural perturbations in patients with adolescent idiopathic scoliosis

The aim of this study was to evaluate electromyographic (EMG) responses of erector spinae (ES) and lower limbs’ muscles to dynamic forward postural perturbation (FPP) and backward postural perturbation (BPP) in patients with adolescent idiopathic scoliosis (AIS) and in a healthy control group. Ten right thoracic AIS patients (Cobb = 21.6 ± 4.4°) and 10 control adolescents were studied. Using bipolar surface electrodes, EMG activities of ES muscle at T10 (ES_T10) and L3 (ES_L3) levels, biceps femoris (BF), gastrocnemius lateralis (G) and rectus femoris (RF) muscles in the right and the left sides during FPP and BPP were evaluated. Muscle responses were measured over a 1s time window after the onset of perturbation. In FPP test, the EMG responses of right ES_T10, ES_L3 and BF muscles in the scoliosis group were respectively about 1.40 (p = 0.035), 1.43 (p = 0.07) and 1.45 (p = 0.01) times greater than those in control group. Also, in BPP test, at right ES_L3 muscle of the scoliosis group the EMG activity was 1.64 times higher than that in the control group (p = 0.01). The scoliosis group during FPP displayed asymmetrical muscle responses in ES_T10 and BF muscles. This asymmetrical muscle activity in response to FPP is hypothesized to be a possible compensatory strategy rather than an inherent characteristic of scoliosis.     

Combination of ‘omics’ data to investigate the mechanism(s) of hydrazine-induced hepatotoxicity in Rats and to identify potential biomarkers

To gain novel insight into the molecular mechanisms underlying hydrazine-induced hepatotoxicity, mRNAs, proteins and endogenous metabolites were identified that were altered in rats treated with hydrazine compared with untreated controls. These changes were resolved in a combined genomics, proteomics and metabonomics study. Sprague–Dawley rats were assigned to three treatment groups with 10 animals per group and given a single oral dose of vehicle, 30 or 90 mg?kg^?1 hydrazine, respectively. RNA was extracted from rat liver 48 h post-dosing and transcribed into cDNA. The abundance of mRNA was investigated on cDNA microarrays containing 699 rat-specific genes involved in toxic responses. In addition, proteins from rat liver samples (48 and 120/168 h post-dosing) were resolved by two-dimensional differential gel electrophoresis and proteins with changed expression levels after hydrazine treatment were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry peptide mass fingerprinting. To elucidate how regulation was reflected in biochemical pathways, endogenous metabolites were measured in serum samples collected 48 h post-dosing by 600-MHz ¹H-NMR. In summary, a single dose of hydrazine caused gene, protein and metabolite changes, which can be related to glucose metabolism, lipid metabolism and oxidative stress. These findings support known effects of hydrazine toxicity and provide potential new biomarkers of hydrazine-induced toxicity.     

Lullabies and the memory of pain: Armenian women’s remembrance of the past in Turkey

Dialectical Anthropology -     

Effect of rosuvastatin on outcomes in chronic haemodialysis patients – design and rationale of the AURORA study

Background

Patients with end-stage renal disease (ESRD) are at high risk of cardiovascular events. Multiple risk factors for atherosclerosis are present in ESRD and may contribute to the increased risk of cardiovascular mortality in this population. In contrast to patients with normal renal function, the benefits of modifying lipid levels on cardiovascular outcomes in patients with ESRD on haemodialysis have yet to be confirmed in large prospective randomised trials. A study to evaluate the Use of Rosuvastatin in subjects On Regular haemodialysis: an Assessment of survival and cardiovascular events (AURORA) will be the first large-scale international trial to assess the effects of statin therapy on cardiovascular morbidity and mortality in ESRD patients on chronic haemodialysis.

Methods

More than 2,750 ESRD patients who have been receiving chronic haemodialysis treatment for at least 3 months have been randomised (1:1), irrespective of baseline lipid levels, to treatment with rosuvastatin 10 mg or placebo. The primary study endpoint is the time to a major cardiovascular event (first occurrence of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke). Secondary endpoints include all-cause mortality, major cardiovascular event-free survival time, time to cardiovascular death, time to non-cardiovascular death, cardiovascular interventions, tolerability of treatment and health economic costs per life-year saved. Study medication will be given until 620 subjects have experienced a major cardiovascular event.

Conclusion

Our hypothesis is that results from AURORA will establish the clinical efficacy and tolerability of rosuvastatin in patients with ESRD receiving chronic haemodialysis and guide the optimal management of this expanding population.     

Application of the 2013 ACR/EULAR classification criteria for systemic sclerosis to patients with Raynaud’s phenomenon

IntroductionWe investigated how many patients, who presented with Raynaud’s phenomenon (RP) and who had not been classified as systemic sclerosis (SSc), would be reclassified as SSc, if the 2013 American College of Rheumatology (ACR)/the European League Against Rheumatism (EULAR) classification criteria were used. We also analyzed the predictive values of the reclassification as SSc in those patients.MethodsWe consecutively enrolled 64 patients with RP and 60 patients with SSc. We applied the new classification criteria to them, reclassified them, and compared variables between those who were newly classified as SSc and those who were not or previously classified as SSc.ResultsSeventeen of 64 patients (26.5%), who presented with RP, but did not fulfill the 1980 ACR classification criteria, were newly classified as SSc by the 2013 ACR/EULAR classification criteria. The newly classified patients as SSc showed increased frequencies of sclerodactyly, digital tip ulcer, telangiectasia, abnormal nailfold capillaries and the presence of anti-centromere antibody, compared to those not and telangiectasia and anti-centromere antibody, compared to the previously classified patients. For the reclassification as SSc, the variables with independent predictive value were sclerodactyly (odds ratio (OR) 60.025), telangiectasia (OR 13.353) and the presence of anti-centromere antibody (OR 11.168).ConclusionsOverall, 26.5% of the patients, who presented with RP, but who did not fulfill the 1980 ACR classification criteria, were newly classified as SSc according to the 2013 ACR/EULAR classification criteria. Sclerodactyly, telangiectasia, and the presence of anti-centromere antibody had independent predictive value for reclassifying patients with RP as SSc.     

Surface electromyograph activity of submental muscles during swallowing and expiratory muscle training tasks in Huntington’s disease patients

IntroductionHuntington’s disease (HD) patients have difficulty in swallowing, leading to aspiration pneumonia, which is a major cause of death. It seems possible that submental muscles that are crucial for preventing an escape of a bolus into the airway, are affected by HD, but no previous studies have investigated this.ObjectiveTo assess surface electromyograph (sEMG) activity of submental muscles during swallowing and expiratory muscle training (EMT) tasks in HD patients in comparison to healthy volunteers.MethodssEMG activities of submental muscles during saliva, water swallowing, EMT tasks performed at 25% and 75% of maximum expiratory pressure were recorded and normalised by the sEMG activity during an effortful swallow in 17 early to mid stage HD patients and 17 healthy volunteers.ResultssEMG activity was greater (p < 0.05) during EMT tasks than saliva and water swallowing, but was not significantly different between groups for saliva, water swallowing and EMT at 25%. HD patients had lower sEMG activity for EMT at 75% (p < 0.05).ConclusionDecreases in submental muscle activity were not evident in HD patients except during EMT at 75%. This suggests that relative submental muscle weakness is observed only during a high intensity task in early to mid stage HD patients.     

Knockdown of PPAR δ Gene Promotes the Growth of Colon Cancer and Reduces the Sensitivity to Bevacizumab in Nude Mice Model

The role of peroxisome proliferator – activated receptor- δ (PPAR δ) gene in colon carcinogenesis remains highly controversial. Here, we established nude mice xenograft model using a human colon cancer cell line KM12C either with PPAR δ silenced or normal. The xenografts in PPAR δ-silenced group grew significantly larger and heavier with less differentiation, promoted cell proliferation, increased expression of vascular endothelial growth factor (VEGF) and similar apoptosis index compared with those of PPAR δ-normal group. After treated with the specific VEGF inhibitor bevacizumab, the capacities of growth and proliferation of xenografts were decreased in both groups while still significantly higher in PPAR δ-silenced group than in PPAR δ-normal group. Administration of PPAR δ agonist significantly decreased VEGF expression in PPAR δ-normal KM12C cells but not in PPAR δ-silenced cells. These findings demonstrate that, knockdown of PPAR δ promotes the growth of colon cancer by inducing less differentiation, accelerating the proliferation and VEGF expression of tumor cells in vivo, and reduces tumor sensitivity to bevacizumab. This study indicates that PPAR δ attenuates colon carcinogenesis.     

Influence of chronic exposure to low doses of γ-radiation and <Superscript>90</Superscript>Sr on the level of DNA breaks and cell sensitivity to hydrogen peroxide in the mouse spleen

Using comet assay, a statistically significant increase (p < 0.05) in the level of DNA breaks in spleen cells was revealed in male CBA/lac mice exposed to γ-radiation (1.7 mGy/day) or ⁹⁰Sr (150–250 Bq/day) for 210 days. The level of DNA breaks also increased under combined exposure to both γ-radiation and ⁹⁰Sr (p < 0.05), but to a lesser degree than under exposure to each of these factors alone. Upon additional in vitro treatment of spleen cells with hydrogen peroxide, the relative increase in the level of DNA breaks was smaller in cells of irradiated mice than in the control. The ratio of the level of DNA breaks after hydrogen peroxide treatment to that before this treatment in control mice was 4.2 ± 0.9, compared to 1.4 ± 0.6 in γ-irradiated mice, 1.9 ± 0.8 in ⁹⁰Sr-irradiated mice, and 2.3 ± 0.8 in mice exposed to both γ- and ⁹⁰Sr-irradiation.     

Arsenic concentration in the urine of patients with Blackfoot disease and Bowen’s disease

Extensive epidemiological study implicates that high arsenic content in artesian well water is the causal factor responsible for Blackfoot disease. We determine the arsenic concentration in urine samples of patients with Blackfoot and Bowen’s diseases and examine whether there exists any discrepancy of urinary arsenic concentrations among patients and the normal population. The analyses were made by hydride atomic absorption spectrophotometry (AAS) and the analytical reliability of the method was checked with a standard urine sample (ORTHO Bi-Level Urine Metal Control). The results show that the mean urinary arsenic concentration in 100 healthy adults is 63.4±29.7 μg/L, and those means for 23 and 11 patients with Blackfoot disease and Bowen’s disease are 75.7±39.1 μg/L (P vs controls >0.05) and 201±58 μg/L (P vs controls <0.001), respectively. From the analytical results obtained, we cannot conclude that urinary arsenic is associated with Blackfoot disease, as was disclosed from the epidemiological studies. However, urinary arsenic concentrations are possibly very closely associated with Bowen’s disease.     

Demonstration of extended field-of-view ultrasound’s potential to increase the pool of muscles for which in vivo fascicle length is measurable

Static, B-mode ultrasound is the most common method of measuring fascicle length in vivo. However, most forearm muscles have fascicles that are longer than the field-of-view of traditional ultrasound (T-US). As such, little work has been done to quantify in vivo forearm muscle architecture. The extended field-of-view ultrasound (EFOV-US) method, which fits together a sequence of B-mode images taken from a continuous ultrasound scan, facilitates direct measurements of longer, curved fascicles. Here, we test the validity and reliability of the EFOV-US method for obtaining fascicle lengths in the extensor carpi ulnaris (ECU). Fascicle lengths from images of the ECU captured in vivo with EFOV-US were compared to lengths from a well-established method, T-US. Images were collected in a joint posture that shortens the ECU such that entire fascicle lengths were captured within a single T-US image. Resulting measurements were not significantly different (p = 0.18); a Bland-Altman test demonstrated their agreement. A novice sonographer implemented EFOV-US in a phantom and in vivo on the ECU. The novice sonographer’s measurements from the ultrasound phantom indicate that the combined imaging and analysis method is valid (average error = 2.2 ± 1.3 mm) and the in vivo fascicle length measurements demonstrate excellent reliability (ICC = 0.97). To our knowledge, this is the first study to quantify in vivo fascicle lengths of the ECU using any method. The ability to define a muscle’s architecture in vivo using EFOV-US could lead to improvements in diagnosis, model development, surgery guidance, and rehabilitation techniques.     

Problems in application of the terms ‘blastic’ and ‘thallic’ to modes of conidiogenesis in some onygenalean fungi

A woman suffering from acute tubulo-interstitial nephritis was admitted to the hospital ten days after deliberate intoxication by ingestion of Cortinarius orellanus. Orellanine, the main toxin responsible for orellanine poisoning, was detected in biological fluids and renal biopsies. It was assayed by direct spectrofluorimetry on two-dimensional thin-layer chromatograms after specific photodecomposition into orelline. The orellanine concentration was 6.12 mg/l in the plasma (10 days after ingestion). Orellanine levels in renal biopsies were 7 g per 25 mm³ of the first biopsy (13 days after ingestion) and 24 g per 8 mm³ of the second biopsy (6 months later).Taken in part from the doctorate thesis of S. Rapior.