Age-dependent changes in CXC chemokine ligand 10 serum levels in euthyroid subjects.

Circulating levels of cytokines are deeply influenced by aging, and few data about serum chemokines are available. The aim of this study was to evaluate the influence of aging on circulating CXCL10. One hundred forty healthy subjects (70 males and 70 females), 10-79 years of age, underwent fasting plasma glucose, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride, and CXCL8 serum assay. Thyroid hormone testing for thyroid-stimulating hormone (TSH), antithyroglobulin (AbTg), and antithyroperoxidase (AbTPO) autoantibodies and thyroid ultrasonography were performed in all subjects to exclude the presence of clinical or subclinical thyroid disease. Serum CXCL10 levels were assayed in all subjects and found to be increased in 14 of 70 females (20%) and in 4 of 70 males (5.7%) (p = 0.01). In a multiple linear regression model including age, body mass index (BMI), systolic and diastolic blood pressure, glycemia, total cholesterol, HDL, LDL, triglycerides, TSH, AbTPO, AbTg, and CXCL8, only age was significantly related to CXCL10 [C.R. 1.30 (0.28-2.33), p = 0.001]. No relationship was present between CXCL8 serum levels and age, suggesting a specificity of CXCL10 elevation as a function of age. Results of this study, performed in healthy subjects on an age gradient, demonstrate an increase in serum CXCL10 with advancing age overall in females, supporting the hypothesis of enhanced Th1 immune responses in aging.     

Electrospinning of Poly (Acrylamide), Poly (Acrylic Acid) and Poly (Vinyl Alcohol) Nanofibers: Characterization and Optimization Study on the Effect of Different Parameters on Mean Diameter Using Taguchi Design of Experiment Method

In this study, nanofibers of poly (acrylic acid) (PAAc), polyacrylamide (PAAm) and poly (vinyl alcohol) (PVOH) were prepared using the electrospinning technique. Based on the Taguchi DOE (design of experiment) method, the effects of electrospinning parameters, i.e., needle tip to collector distance, polymer solution concentration, applied voltage, polymer solution feed rate and polymer type, on the diameter and morphology of polymer nanofibers were evaluated. Analyses of the experiments for the diameters of the polymer nanofibers showed that the type of polymer was the most significant factor. The optimal combination to obtain the smallest diameters with minimum deviations for electrospun polymer nanofibers was also determined. For this purpose, the appropriate factor levels were determined as follows: polymer PAAm, applied voltage 10 kV, delivery rate 0.1 mL/h, needle tip to collector distance 10 cm, and polymer solution concentration 8%, to obtain the thinnest nanofibers. This combination was further validated by conducting a confirmation experiment, and the average diameter of the polymer nanofibers was found to be close to the optimal conditions estimated by the Taguchi DOE method.     

Food insecurity,socio-economic factors and weight status in two Iranian ethnic groups

Objective. To study the association of weight status with food insecurity (FI) and socio-economic status (SES) in Azeri and Kurd ethnic groups living in Urmia city, North-Western Iran.

Design. In this cross-sectional study, 723 participants (427 women and 296 men) aged 20–64 years old, from two ethnic groups (445 Azeri and 278 Kurd), were selected through a combination of cluster, random and systematic sampling methods. Demographic and socio-economic characteristics were assessed by a valid questionnaire, and household food security status was analyzed using an adapted household food insecurity access scale through face-to-face interviews at homes. General and central obesities were measured and evaluated using standard methods.

Results. Based on the findings, moderate-to-severe FI, as well as low SES, was more dominant in Kurds, compared to Azeris. After adjusting for confounders, being female(OR?=?4.33, CI 95%: 2.35–7.97) and moderate-to-severe FI (OR?=?2.00, CI 95%: 1.01–3.97) in Azeris and being female (OR?=?5.39, CI 95%: 2.28–12.23) and higher total cost of household/capita (OR?=?1.005, CI 95%: 1.002–1.009) in Kurds were related to higher odds of general obesity while low (OR?=?0.41, CI 95%: 0.18–0.91) and moderate(OR?=?0.13, CI 95%: 0.02–0.60) education levels were linked to lower chance of general obesity. Furthermore, the chance of central obesity was lower in Azeris with high educational levels (OR?=?0.64, CI 95%: 0.21–0.94), females (OR?=?0.72, CI 95%: 0.34–0.86), home owners (OR?=?0.56, CI 95%: 0.31–0.91) and females Kurds (OR?=?0.60, CI 95%: 0.37–0.97) with moderate-to-severe FI and higher total income per capita. In contrast, the chance of central obesity increased in Kurds with increased age (OR?=?1.06, CI 95%: 1.02–1.10) and total cost of household per capita (OR?=?1.004, CI 95%: 1.000–1.008).

Conclusion. These findings show that the association between moderate-to-severe FI and risk of general/central obesity varies in Azeris, compared to Kurds. However, better SES decreased the chance of general/central obesity in both ethnic groups.     

Prevalence of thyroid dysfunctions in systemic lupus erythematosus

The association of systemic lupus erythematosus (SLE) and thyroid autoimmunity has been reported by several studies in a wide range of variability. However, from a review of the literature, discrepant results have been reported. The aim of the study was to evaluate the prevalence of clinical and subclinical thyroid disorders in patients with SLE vs sex- and age-matched controls. Thyroid hormones and the presence of antithyroid antibodies were tested and thyroid ultrasonography was performed in 213 patients with SLE vs 426 sex- and age-matched controls, from the same geographic area, with a well-defined status of iodine intake. The odds ratio for subclinical hypothyroidism for female patients with SLE with respect to controls was 4.5 (95% confidence interval [CI], 2.5-8.4); for antithyroid peroxidase antibody (AbTPO) positivity, it was 2.6 (95% CI, 1.7-4.1); and for thyroid autoimmunity, it was 2.9 (95% CI, 2.0-4.4). The mean values of thyroid-stimulating hormone and AbTPO were higher in female SLE patients than in controls (P < .01). A significantly (P < .01) higher prevalence of clinical hypothyroidism and Graves disease was observed in female SLE patients than in controls. No significant difference between SLE patients and controls was detected with regard to free triiodothyronine and thyroxine. In our series, 3% of SLE patients had “nonthyroidal illness syndrome” vs 0 control. Thyroid function and AbTPOs should be tested and ultrasonography should be performed as part of the clinical profile in SLE patients. Subjects at high risk (women, positive AbTPOs, hypoechoic, and small thyroid) should have thyroid function follow-up and appropriate treatment in due course.     

Simultaneous selection by object-based attention in visual and frontal cortex

Models of visual attention hold that top-down signals from frontal cortex influence information processing in visual cortex. It is unknown whether situations exist in which visual cortex actively participates in attentional selection. To investigate this question, we simultaneously recorded neuronal activity in the frontal eye fields (FEF) and primary visual cortex (V1) during a curve-tracing task in which attention shifts are object-based. We found that accurate performance was associated with similar latencies of attentional selection in both areas and that the latency in both areas increased if the task was made more difficult. The amplitude of the attentional signals in V1 saturated early during a trial, whereas these selection signals kept increasing for a longer time in FEF, until the moment of an eye movement, as if FEF integrated attentional signals present in early visual cortex. In erroneous trials, we observed an interareal latency difference because FEF selected the wrong curve before V1 and imposed its erroneous decision onto visual cortex. The neuronal activity in visual and frontal cortices was correlated across trials, and this trial-to-trial coupling was strongest for the attended curve. These results imply that selective attention relies on reciprocal interactions within a large network of areas that includes V1 and FEF.Visual scenes are usually too complex for all information to be analyzed at once. Selective attention selects a subset of the objects in the visual scene for detailed analysis at the expense of other items. Visual objects compete for selection, and the outcome of this competition depends on bottom-up cues such as saliency and perceptual organization and top-down cues that signal the objects’ behavioral relevance (1). It is not well understood how these different cues interact and which brain areas take the lead in visual selection.The top-down mechanisms for attentional selection are tightly linked to those for the selection of actions (2), and accordingly, cortical areas related to action planning influence the deployment of visual attention. The frontal eye fields (FEF) is one such area that is involved in visual processing, shifts of visual attention (2, 3), and also in the control of eye movements (4, 5). Area FEF contains different types of cells. Visual processing relies on visual and visuomovement cells, whereas the programming of eye movements relies on the activity of visuomovement and movement cells (6, 7). There are several lines of evidence that also implicate FEF in attentional control. First, FEF inactivation impairs attention shifts toward the contralateral visual field (8, 9). Second, subthreshold FEF microstimulation enhances neuronal activity in visual cortex in a manner that is reminiscent of selective attention (10, 11). Third, a role of FEF in the top-down guidance of attention is supported by studies on visual search. In search, selection signals in frontal cortex precede those in area V4 by 50 ms, suggesting that the frontal cortex determines selection and then provides feedback to visual cortex (12, 13). A comparable interareal delay in attentional effects was observed between the lateral intraparietal area and the motion sensitive middle temporal area (14). Thus, the parietal and frontal cortices appear to take the lead in attentional selection and to provide top-down signals to visual cortex. Within the visual cortex, such a reverse hierarchy (15) of attentional effects was observed in a task that required shifts of spatial attention (16) and also in a task demanding shifts between visual and auditory attention (17). Attentional signals in area V4 preceded signals in V2 by 50–250 ms, which in turn preceded attentional effects in the primary visual cortex (V1) by 50–400 ms.However, top-down factors are not the only ones that guide attention. Attention can be object-based, implying that the visual stimulus itself influences the distribution of attention too. If attention is directed to a feature, attention tends to coselect visually related features on the basis of perceptual grouping cues (18) so that entire objects rather than isolated features are attended (19, 20). The influence of perceptual grouping on attentional selection can be investigated with a curve-tracing task that requires grouping of the contour elements of a single curve (21, 22). Attention in this task is directed to the entire curve, implying that the curve’s shape itself influences the distribution of attention (22). Indeed, a traced curve evokes stronger activity in primary visual cortex than an irrelevant curve, revealing a neuronal correlate of object-based attention (23). However, it is not known if the coselection of all image elements of a single object is determined within early visual cortex or is guided by the frontal cortex, just as was shown for other tasks.Here we compare selection signals in areas FEF and V1 in the curve-tracing task with simultaneous recordings in the two areas. A priori, several possibilities exist for the interaction between V1 and FEF. First, the frontal cortex might select the relevant curve and then feed a guiding signal back to visual cortex (24, 25) as in the other tasks described above. If so, attentional selection signals in V1 might arise tens to hundreds of milliseconds later than in FEF. However, the chain of events in the curve-tracing task might differ because visual shape has a profound influence on the distribution of attention (26). Thus, a second possibility is that the visual cortex determines selection so that the attentional modulation in visual cortex precedes that in frontal cortex. A third possibility is that visual and frontal areas jointly determine what is relevant and what is not. In this situation, the selection signals are expected to occur in both areas at approximately the same time. It is also possible that the order of selection in different areas depends on the difficulty of the task. For example, the reverse hierarchy theory of visual perception (15) proposed that easy tasks are usually solved by higher visual areas, whereas lower visual areas are recruited when the picture has to be scrutinized. We therefore varied the difficulty of the curve-tracing task.     

Genetics and immunodysfunction underlying Behçet’s disease and immunomodulant treatment approaches

Behçet’s disease (BD) is a chronic autoimmune condition primarily prevalent in populations along the Mediterranean Sea. The exact etiology of BD has not been fully explained yet, but the disease occurrence is associated with a genetic factor, human leukocyte antigen (HLA)-B51 antigen. Among the various immunodysfunctions that are found in BD, patients are increased neutrophil motility and superoxide production, as well as elevated production of tumor necrosis factor (TNF)-α and decreased production of interleukin (IL)-10. Elevated levels of inflammatory cytokines like IL-1 and IL-17 in BD have been found associated with aberrant expression of microRNA. Gene polymorphisms in BD patients have been observed in molecules involved in responses to pathogens that can ultimately modulate the host antimicrobial response. Moreover, several single nucleotide polymorphisms (SNPs) have been reported in genes encoding chemokines and adhesion molecules; many of these changes manifest as increases in vascular inflammation and vascular damage. Lastly, genetic and epigenetic changes have been suggested as involved in the pathogenesis of BD. Modifications in DNA methylation have been found in BD patient monocytes and lymphocytes, leading to adverse function of these cells. This review presents a comprehensive compilation of the literature with regard to the immunodysfunction underlying BD, as well as of the genetics, newly described clinical specifications and novel treatment strategies using immunomodulants based on the current understanding of BD.     

Early goal-directed therapy reduces mortality in adult patients with severe sepsis and septic shock: Systematic review and meta-analysis

Introduction:

Survival sepsis campaign guidelines have promoted early goal-directed therapy (EGDT) as a means for reduction of mortality. On the other hand, there were conflicting results coming out of recently published meta-analyses on mortality benefits of EGDT in patients with severe sepsis and septic shock. On top of that, the findings of three recently done randomized clinical trials (RCTs) showed no survival benefit by employing EGDT compared to usual care. Therefore, we aimed to do a meta-analysis to evaluate the effect of EGDT on mortality in severe sepsis and septic shock patients.

Methodology:

We included RCTs that compared EGDT with usual care in our meta-analysis. We searched in Hinari, PubMed, EMBASE, and Cochrane central register of controlled trials electronic databases and other articles manually from lists of references of extracted articles. Our primary end point was overall mortality.

Results:

A total of nine trails comprising 4783 patients included in our analysis. We found that EGDT significantly reduced mortality in a random-effect model (RR, 0.86; 95% confidence interval [CI], 0.72–0.94; P = 0.008;   I² =50%). We also did subgroup analysis stratifying the studies by the socioeconomic status of the country where studies were conducted, risk of bias, the number of sites where the trials were conducted, setting of trials, publication year, and sample size. Accordingly, trials carried out in low to middle economic income countries (RR, 0.078; 95% CI, 0.67–0.91; P = 0.002; I² = 34%) significantly reduced mortality compared to those in higher income countries (RR, 0.93; 95% CI, 0.33–1.06; P = 0.28; I² = 29%). On the other hand, patients receiving EGDT had longer length of hospital stay compared to the usual care (mean difference, 0.49; 95% CI, –0.04–1.02; P = 0.07; I² = 0%).

Conclusion:

The result of our study showed that EGDT significantly reduced mortality in patients with severe sepsis and septic shock. Paradoxically, EGDT increased the length of hospital stay compared to usual routine care.     

Age-related differences in the response of the brain to dietary melatonin

The aged brain is prone to excessive levels of immune activity, not initiated by an acute response to an extrinsic agent. While dietary melatonin is reported to attenuate the extent of expression of proinflammatory genes, little is known about the extent to which these changes can be translated into altered levels of corresponding proteins. The baseline levels of the proinflammatory cytokines, tumor necrosis factor alpha (TNF-α) and interleukin-1 alpha, were greater in older (~29 months old) compared to younger (~7 months old) mouse brains. Acute (3 h) exposure to lipopolysaccharide (LPS) induced activation of nuclear factor kappa B (NF-κB), but not inflammatory cytokines in the brain. The serum level of TNF-α was increased after LPS injection, indicating a systemic immune response to the bacterial cell wall component. Dietary melatonin (40 ppm for 9.3 weeks) did not prevent LPS-induced changes in younger animals but caused an increased systemic TNF-α response in older mice. Melatonin did reduce markers of carbonyl formation in brain proteins of young animals and nitrosylative damage to peptide-bound amino acid residues, in the brains of older animals. Acute LPS challenge did not significantly affect these oxidative markers. Thus, despite lack of clear evidence of attenuation of the NF-κB–cytokine inflammatory trajectory within the CNS by melatonin, this agent did show a protective effect against free radical-initiated injury to amino acid residues within proteins. The results illustrate that previously reported changes in gene expression following melatonin treatment need not be closely paralleled by corresponding changes in protein content.