The clinical value of the delta finger to palm distance in systemic sclerosis.

Systemic sclerosis (SSc) is a collagen-vascular disorder characterized by fibrosis and vasculopathy. Delta finger to palm distance (delta FTP) is an index measuring the distance between the tip of the third finger to the distal palmar crease in the flexed and extended position. The present study aimed to evaluate the clinical value of delta FTP and to assess the correlation of delta FTP with modified Rodnan skin score (mRSS) and forced vital capacity (FVC) over the 12-month follow-up. This prospective longitudinal study began with 50 participants who were followed for twelve months. Lowess smoothing and linear regression were applied to detect and assess the relationship between delta FTP and mRSS. p-values were adjusted by the Benjamini-Hochberg method (BHM) as a control for false discovery rate. Delta FTP was lower among patients with higher disease duration (p-valueadj: 0.008), diffuse cutaneous SSc (p-valueadj: 0.006), digital ulcers (p-valueadj: 0.003), telangiectasia (p-valueadj: 0.006) and dysphagia (p-valueadj: 0.036). The mRSS has a significant negative linear effect on the delta FTP at the baseline and the end of the follow-up (r: -0.31 and -0.40, respectively). Moreover, changes of mRSS and delta FTP showed a negative linear association over time (r: -0.22). These linear effects remained significant after regrouping the patients based on their SSc subtype. Delta FTP and FVC were not correlated either at the baseline or at the end. It seems that the delta FTP can be a valuable clinical index, supported by its correlated changes with mRSS and other SSc clinical manifestations over the one-year follow-up.

Human lactoferrin attenuates the proinflammatory response of neonatal monocyte-derived macrophages.

Bioactive components of human milk, such as human lactoferrin (hLF), play an essential role in gut microbiome homeostasis and protection against neonatal inflammatory diseases. Neonatal intestinal macrophages display a proinflammatory profile that might contribute to inflammatory mucosal injury. Therefore, the aim of the study was to investigate the immunomodulatory effects of hLF on differentiation and activation of monocyte-derived macrophages (moMϕ). Monocytes isolated from umbilical cord blood of term neonates and peripheral blood of healthy adults were differentiated in the absence or presence of hLF, and differentiation, apoptosis and phagocytosis were evaluated. Cytokine production, Toll-like receptor (TLR) signalling and activation marker expression were investigated upon activation with lipopolysaccharide (LPS) and lipoteichoic acid (LTA) challenge. We demonstrate that hLF-differentiated moMϕ exhibit decreased TLR-4 expression, TLR signalling, proinflammatory cytokine secretion and intracellular tumour necrosis factor (TNF)-α production. Investigation of differentiation markers, morphology and induction of apoptosis showed no alteration in lactoferrin-differentiated moMϕ. Taken together, hLF promote anergic/anti-inflammatory effects by TLR expression and pathway interference, resulting in a diminished proinflammatory moMϕ phenotype. The anergic/anti-inflammatory properties of hLF might contribute to the prevention of harmful TLR-mediated inflammatory disorders in the developing gut of premature infants.

Monte Carlo methods for localization of cones given multielectrode retinal ganglion cell recordings.

It has recently become possible to identify cone photoreceptors in primate retina from multi-electrode recordings of ganglion cell spiking driven by visual stimuli of sufficiently high spatial resolution. In this paper we present a statistical approach to the problem of identifying the number, locations, and color types of the cones observed in this type of experiment. We develop an adaptive Markov Chain Monte Carlo (MCMC) method that explores the space of cone configurations, using a Linear-Nonlinear-Poisson (LNP) encoding model of ganglion cell spiking output, while analytically integrating out the functional weights between cones and ganglion cells. This method provides information about our posterior certainty about the inferred cone properties, and additionally leads to improvements in both the speed and quality of the inferred cone maps, compared to earlier "greedy" computational approaches.

Hepatitis E virus seroprevalence in haemodialysis patients in Zanjan Province, Islamic Republic of Iran.

Hepatitis E virus (HEV) infection is the most common form of acute hepatitis in adults in endemic regions of Asia. In a descriptive, cross-sectional study, anti-HEV antibody was measured in patients referred to the 2 haemodialysis centres in Zanjan city, Islamic Republic of Iran. Among 93 patients with chronic renal failure, mean age 57.0 (SD 18.5) years, antibodies against HEV were positive in 25 (26.9%) patients. HEV infection was not significantly associated with sex, age, educational level, residence or water source. The rate of HEV positivity was higher in patients with > 1 than < or = 1 year of haemodialysis (31.3% versus 15.4%) but this was not statistically significant. None of the patients had chronic hepatitis C or HIV infection, and only 2 were suffering from chronic hepatitis B infection. Given the high prevalence of HEV in haemodialysis patients in Zanjian, more attention is needed towards HEV epidemiology, control, prevention and training in the west of the Isalamic Republic of Iran and possibly neighbouring countries.

Suppressed ethanol intake by CER following the sucrose-fading initiation procedure.

Lever responding maintained with sweetened ethanol reinforcement (3% sucrose in 10% ethanol) was initiated in food- and water-sated rats with the sucrose-fading procedure. Four tone-shock pairings, one per session, were superimposed on this behavioral baseline [conditioned emotional response (CER) paradigm]. A profound and sustained ethanol response suppression was found. Baseline levels of ethanol responding were recovered by repeating the original initiation procedure. Subsequent exposure to the CS tone alone (no shock) led to a nonsignificant reduction in ethanol responding. These results were discussed in terms of anxiolytic action of ethanol.

Antagonism of ethanol-reinforced behavior by the benzodiazepine inverse agonists Ro15-4513 and FG 7142: relation to sucrose reinforcement.

The partial inverse benzodiazepine agonist Ro15-4513 has been shown to antagonize many of ethanol's actions, including the reduction of behavior reinforced with ethanol presentation. The studies reported here compared the effects of the Ro compound on sucrose reinforcement alone and concurrently available with ethanol reinforcement. Also, a second inverse agonist, FG 7142, was tested. The result indicated that ethanol reinforcement was more sensitive to the inverse agonists compared to sucrose reinforcement. This was seen as a graded effect upon ethanol responding at doses which failed to have any effect upon sucrose-reinforced behavior. The Ro compound was approximately three times more potent than the FG compound in suppressing ethanol-reinforced responding. Possible explanations for the greater sensitivity of ethanol reinforcement compared to sucrose reinforcement was discussed in terms of ethanol's potential actions at the benzodiazepine-GABA receptor complex.

Oral ethanol reinforcement in the rat: effect of the partial inverse benzodiazepine agonist RO15-4513.

The partial inverse benzodiazepine agonist RO15-4513 has been found to reverse the sedating and anti-conflict effects of acute ethanol administration. In non-food or fluid-deprived rats, orally self-administering 10% ethanol in an operant situation, RO15-4513 resulted in a dose-dependent suppression on ethanol intake. Doses of 0.3, 1.0 and 3.0 mg/kg suppressed responding from approximately 25% to 60% respectively. A dose of 0.1 mg/kg had no significant effect upon responding. These findings were discussed in terms of the potential independence of brain mechanisms related to ethanol reinforcement and sedation.

Ethanol preference following the sucrose-fading initiation procedure.

Lever responding maintained with ethanol reinforcement at concentrations up to 20% (v/v) was initiated in non-food and -water deprived rats via a sucrose-fading procedure. Home cage two-bottle preference tests between water and 10% ethanol were conducted before (pre) and after (post) the ethanol initiation procedure to determine the effect of initial ethanol preference on ethanol initiation and of initiation on later ethanol preference. Initial preference testing found that the rats could be divided into two groups, animals with low ethanol preference scores (preference below 25%) and those with moderate ethanol preference scores (preference between 25% and 50%). All animals were successfully initiated with the sucrose-fading procedure to lever press with ethanol reinforcement. Following initiation, home cage preference was markedly increased for the initially low-preferring rats (from 12% to 43%), while moderate-preferring rats showed only slight increases (from 37% to 47%). The shift in ethanol preference was discussed in terms of the relation between ethanol preference and behavioral history.

Relation of ethanol self-administration to feeding and drinking in a nonrestricted access situation in rats initiated to self-administer ethanol using the sucrose-fading technique.

Free-feeding male Long-Evans rats (N = 8) were initiated to self-administer 10% ethanol using a sucrose-fading procedure. Following initiation, they were placed into chambers which allowed for the continuous monitoring of feeding, water drinking and ethanol self-administration. All rats continued to daily self-administer ethanol in the continuous access situation. Ethanol drinking at certain times during the day appeared to be related to feeding bouts (prandial drinking). However, at other times, nonprandial ethanol self-administration occurred. These nonprandial ethanol drinking episodes, while not at levels of excessive ethanol intakes, were at levels well above water intake when water was substituted for ethanol. These findings suggest that ethanol intake in continuous access conditions is not solely a function of feeding behavior and that following initiation, ethanol-seeking behavior was maintained in a continuous access situation.

The accuracy of the Neosono Ultima EZ apex locator using files of different alloys: an in vitro study.

The purpose of this study was to compare the precision of one of the new generation of root canal measuring devices, Neosono Ultima EZ, while using files manufactured of different alloys. Fifty-four root canals of extracted teeth were chosen. They were placed in special tubes with roots immersed in 2 percent agar with phosphate buffered saline. The device was used to locate the apex of each canal in wet conditions at the zero digital reading, first using a stainless steel file and then using a nickel-titanium file. These values were compared to the actual lengths obtained by measuring the distance of the coronal reference point to the apical opening with a size 10 file minus 0.5 mm. The accuracy of the device was 94 percent with nickel-titanium files and 91 percent with stainless steel. No significant difference was noted between the results for either file. The accuracy of the Neosono Ultima EZ in wet conditions exceeded 90 percent regardless of the alloy used.

Preterm neonates display altered plasmacytoid dendritic cell function and morphology.

Bacterial and viral infections cause high rates of morbidity and mortality in premature newborns. In the setting of viral infection, pDCs play a key role as strong producers of IFN-α upon TLR9 activation. We analyzed pDC frequency, phenotype, morphology, and function in CB of preterm and term newborns in comparison with adults. Whereas all age groups show similar pDC numbers, BDCA-2, CD123, and TLR9 levels, the expression of BDCA-4 and capacity to produce IFN-α upon TLR9 challenge were decreased significantly in preterm neonates. Furthermore, we show by means of electron microscopy that pDCs from preterm newborns exhibit a distinct, "immature" morphology. Taken together, these findings suggest decreased functionality of pDCs in the premature newborn. The reduced capacity to produce IFN-α is likely to render such infants more susceptible to viral infections.

Cytomegalovirus hyperimmunoglobulin: mechanisms in allo-immune response in vitro.

BACKGROUND: Cytomegalovirus hyperimmunoglobulin (CMVIg) containing drugs are routinely administered in cardiac transplantation for prophylaxis against CMV disease. Yet little is known about their influence on transplant relevant immune functions. The aim of this study was to evaluate the effect of CMVIg on cellular immunity in in vitro experiments and to define their role in tolerance inducing mechanisms. MATERIALS AND METHODS/RESULTS: CMVIg reduces proliferation in mixed lymphocyte reactions and anti-CD3 blastogenesis assays and is related to decreased production of immune modulating cytokines interleukin (IL)-2, interferonr (IFNgamma), IL-10. This antiproliferative effect is associated with a cell-cycle arrest in the G0/G1 phase and induction of apoptosis in CD8+ and natural killer cells. Co-incubation with CMVIg causes down-regulation of cell bound immunoglobulin and FcgammaRIII surface expression on natural killer cells and leads to attenuation of antibody dependent cellular cytotoxicity effector functions. CONCLUSIONS: We conclude that CMVIg induces immunological features on leukocytes in vitro that are known to be related to tolerance induction. Our observations extend the current concept of CMVIg as passive CMV prophylaxis to a therapeutic drug compound capable of reducing allogeneic immune response.

The neurohormone melatonin inhibits cytokine, mitogen and ionizing radiation induced NF-kappa B.

Recently, the neurohormone melatonin was found to be a potent endogenous hydroxyl radical scavenger. Since the activation of an important transcriptional regulator, nuclear factor-kappa B (NF-kappa B) involves free radicals as second messengers, we investigated whether melatonin alters NF-kappa B expression if present during treatment of HeLa S3 cells with known activators. The results show that upon treatment of HeLa S3 cells with tumor necrosis factor-alpha or phorbol 12-myristate 13-acetate, or with ionizing radiation, there is a profound induction of NF-kappa B binding activity. If present at the time of treatment, exogenously added melatonin, at a concentration as low as 10 microM, was found to inhibit the activation of NF-kappa B by these agents. This results leads to the hypothesis that melatonin can play a role in many physiological functions through its modulation of NF-kappa B (and possibly other) transcriptional regulators.

Static tester for characterization of phase-change, dye-polymer, and magneto-optical media for optical data storage.

We have designed and built a static tester around a commercially available polarized light microscope. This device employs two semiconductor laser diodes (at 643- and 680-nm wavelengths) for the purpose of recording small marks on various media for optical data storage and for the simultaneous monitoring of the recording process. We use one of the lasers in the single-pulse mode to write a mark on the sample and operate the other laser in the cw mode to monitor the recording process. The two laser beams are brought to coincident focus on the sample through the objective lens of the microscope. The reflected beams are sent through a polarizing beam splitter and thus divided into two branches, depending on whether they are p or s polarized. In each branch the beam is further divided into two according to the wavelength. The four beams thus produced are sent to four high-speed photodetectors, and the resulting signals are used to monitor the reflectance as well as the polarization state of the beam on reflection from the sample. We provide a comprehensive description of the tester's design and operating principles. We also report preliminary results of measurements of phase-change, dye-polymer, and magneto-optical samples, which are currently of interest in the areas of writable and rewritable optical data storage.

Hepatitis E virus seroprevalence in haemodialysis patients in Zanjan province, Islamic Republic of Iran

Hepatitis E virus [HEV] infection is the most common form of acute hepatitis in adults in endemic regions of Asia. In a descriptive, cross-sectional study, anti-HEV antibody was measured in patients referred to the 2 haemodialysis centres in Zanjan city, Islamic Republic of Iran. Among 93 patients with chronic renal failure, mean age 57.0 [SD 18.5] years, antibodies against HEV were positive in 25 [26.9%] patients. HEV infection was not significantly associated with sex, age, educational level, residence or water source. The rate of HEV positivity was higher in patients with > 1 than </= 1 year of haemodialysis [31.3% versus 15.4%] but this was not statistically significant. None of the patients had chronic hepatitis C or HIV infection, and only 2 were suffering from chronic hepatitis B infection. Given the high prevalence of HEV in haemodialysis patients in Zanjan, more attention is needed towards HEV epidemiology, control, prevention and training in the west of the Islamic Republic of Iran and possibly neighbouring countries