Influence of blood flow velocity on arterial distensibility of carotid artery in healthy men

Decreased distensibility of carotid artery is independently associated with the incidence of cardiovascular and cerebrovascular events. Arterial distensibility is determined by vascular tone. Since shear stress is an important driving force of vasodilatory substances production form endothelial cells, we hypothesized that local basal (i.e., resting) arterial blood flow velocity is associated with regional arterial distensibility. To test this hypothesis, we determined the influence of local blood flow velocity on carotid arterial distensibility in cross-sectional study design. In a total of 73 apparent healthy men (18–64 years), carotid arterial properties, including measures of carotid arterial distensibility and BFV at rest, were evaluated via B-mode and Doppler ultrasound imaging and applanation tonometry system. Carotid arterial peak BFV and the absolute and normalized pulsatile BFV significantly correlated with age (r = ?0.453 to ?0.600, p < 0.0001), whereas mean and minimum BFV were not influenced by age. Distensibility coefficient of carotid artery correlated with peak BFV (r = 0.305, p < 0.01) and more strongly with pulsatile (i.e., systolic minus end-diastolic) BFV (r = 0.406, p < 0.0001) and the normalized pulsatile BFV by time-averaged velocity (r = 0.591, p < 0.0001). Multi-regression analysis revealed that age (β = ?0.57, p < 0.0001) was the primary independent determinant for distensibility coefficient. In addition with this, carotid lumen diameter (β = ?0.202, p < 0.01) and the normalized pulsatile BFV (β = 0.237, p < 0.05) were significant independent determinants of distensibility coefficient. Qualitatively similar results (although inverse in direction) were obtained by use of β-stiffness index. These results suggest that greater gradient of blood flow velocity during a cardiac cycle are favorably associated with distensibility of carotid artery.     

<Emphasis Type="Italic">CDKN1A</Emphasis> histone acetylation and gene expression relationship in gastric adenocarcinomas

CDKN1A is a tumor suppressor gene involved in gastric carcinogenesis and is a potential target for histone deacetylase inhibitor-based therapies. Upregulation of CDKN1A is generally observed in several cell lines after histone deacetylase inhibitor treatment; however, little is known about the histone acetylation status associated with this gene in clinical samples, including gastric tumor tissue samples. Therefore, our goal was to quantify the H3K9 and H4K16 acetylation levels associated with three CDKN1A regions in 21 matched pairs of gastric adenocarcinoma and corresponding adjacent non-tumor samples by chromatin immunoprecipitation and to correlate these data with the gene expression. Our results demonstrated that the ?402, ?20, and +182 CDKN1A regions showed a significantly increased acetylation level in at least one of the histones evaluated (p < 0.05, for all comparisons), and these levels were positively correlated in gastric tumors. However, an inverse correlation was detected between both H3K9 and H4K16 acetylation at the ?402 CDKN1A region and mRNA levels in gastric tumors (r = ?0.51, p = 0.02; r = ?0.60, p < 0.01, respectively). Furthermore, increased H4K16 acetylation at the ?20 CDKN1A region was associated with gastric tumors of patients without lymph node metastasis (p = 0.04). These results highlight the complexity of these processes in gastric adenocarcinoma and contribute to a better understanding of CDKN1A regulation in carcinogenesis.     

Influence of gaze distance and downward gazing on postural sway in hemiplegic stroke patients

Gaze distance and head flexion suppress postural sway in healthy subjects. However, the effects of these factors on stroke patients have not been fully elucidated. In this study, we aimed to evaluate the effects of gaze distance and downward gazing on postural sway in stroke patients. We examined 15 stroke patients and 14 elderly controls. Postural sway was measured in the subjects under the following 5 conditions: eyes fixed forward on a marker located 600 cm ahead (600-cm condition); eyes fixed forward on a marker located 150 cm ahead (150-cm condition); eyes fixed downward (downward condition); the subject facing straight ahead but with eyes closed (closed-forward condition); and the subject facing downward but with eyes closed (closed-downward condition). The root mean squares of the anteroposterior (A-P RMS) and the mediolateral (M-L RMS) directions were determined. The results showed that the short gaze distance decreased the M-L RMS in both the stroke patients and controls (p < 0.001, r = 0.66; p = 0.024, r = 0.43, respectively). In the control group, the downward condition increased the M-L RMS when compared with the 600-cm condition (p = 0.011, r = 0.48). The downward condition decreased the A-P and M-L RMS in the stroke patients when compared with the 600-cm condition (A-P RMS: p < 0.001; r = 0.66, M-L RMS: p = 0.001; r = 0.59). Our results showed that the short gaze distance decreased postural sway in both groups, and downward gazing decreased it only in the stroke group.     

Expression of <Emphasis Type="Italic">MIF</Emphasis> and <Emphasis Type="Italic">TNFA</Emphasis> in psoriatic arthritis: relationship with Th1/Th2/Th17 cytokine profiles and clinical variables

Psoriatic arthritis (PsA) is an autoimmune inflammatory disease associated with psoriasis. The cause of this pathology is still unknown, but research suggests the diseases are caused by a deregulated cytokine production. MIF is a cytokine associated with immunomodulation of Th1, Th2, and Th17 cytokine profiles in inflammatory diseases. Based on this knowledge, the aim of this study was to determine the association of MIF and TNFA expression with Th1, Th2, and Th17 cytokine profiles in serum levels of PsA patients. A cross-sectional study was performed in 50 PsA patients and 30 control subjects (CS). The cytokine profiles were quantified by BioPlex MagPix system and the mRNA expression levels by real-time PCR. TNFA mRNA expression was 138.81-folds higher in PsA patients than CS (p < 0.001). Regarding MIF mRNA expression, no significant differences were observed; however, a positive correlation was identified between MIF mRNA expression and PsA time of evolution (r = ? 0.53, p = 0.009). An increase of Th1 (IFNγ: PsA = 37.1 pg/mL vs. CS = 17 pg/mL, p < 0.05; TNFα: PsA = 24.6 pg/mL vs. CS = 9.8 pg/mL, p < 0.0001) and Th17 cytokine profiles (IL-17: PsA = 6.4 pg/mL vs. CS = 2.7 pg/mL, p < 0.05; IL-22: PsA = 8.4 pg/mL vs. CS = 1.8 pg/mL, p < 0.001), were found in PsA patients. Th2 cytokines were not significantly different in both groups. In conclusion, a high expression of TNFA mRNA, as well as an increase of Th1 and Th17 cytokine profiles evaluated by IFNγ, TNFα, IL-17, and IL-22 cytokines, was observed in PsA patients.     

The protective effect of α-hederin,the active constituent of <Emphasis Type="Italic">Nigella sativa</Emphasis>, on tracheal responsiveness and lung inflammation in ovalbumin-sensitized guinea pigs

Many investigations have demonstrated the prophylactic effect of Nigella sativa on asthma disease. One of its active constituents is α-hederin. In the present study, the preventive effect of two different concentrations of α-hederin on tracheal responsiveness and lung inflammation in ovalbumin-sensitized guinea pigs was examined. Forty male adult Dunkin-Hartley guinea pigs were randomly divided into the control (C), sensitized (S) and sensitized pretreated groups with thymoquinone (3 mg/kg i.p., S + TQ), low-dose α-hederin (0.3 mg/kg i.p., S + LAH) and high-dose α-hederin (3 mg/kg i.p., S + HAH). The responsiveness of tracheal smooth muscle (TR) to methacholine, histamine and ovalbumin was assessed. Moreover, total and differential white blood cell counts in lung lavage fluid were examined. Compared with the S group, the mean EC50 value in the S + LAH group increased significantly (p < 0.05). The mean EC50 value of histamine contraction in the S + LAH and S + HAH groups was significantly higher than in the S group (p < 0.05). In all pretreated groups, the TR to ovalbumin decreased in comparison to the S group (p < 0.001). Both the S + HAH and S + LAH groups showed significantly decreased TR compared to the S + TQ group (p < 0.01–p < 0.01). Total WBC and eosinophil counts in all pretreated groups decreased significantly in comparison with the S group (0.001–0.01). There was a significant increase in neutrophil, lymphocyte and monocyte counts in the pretreated groups compared to the S group (p < 0.001–p < 0.05). The basophil count in the S + TQ and S + HAH groups was significantly lower than in the S group (p < 0.01–p < 0.05). This study suggested that α-hederin has anti-inflammatory and bronchodilatory effects like thymoquinone.     

Testing a mobile mindful eating intervention targeting craving-related eating: feasibility and proof of concept

Theoretically driven smartphone-delivered behavioral interventions that target mechanisms underlying eating behavior are lacking. In this study, we administered a 28-day self-paced smartphone-delivered intervention rooted in an operant conditioning theoretical framework that targets craving-related eating using mindful eating practices. At pre-intervention and 1-month post-intervention, we assessed food cravings among adult overweight or obese women (N = 104; M age = 46.2 ± 14.1 years; M BMI = 31.5 ± 4.5) using ecological momentary assessment via text message (SMS), self-reported eating behavior (e.g., trait food craving), and in-person weight. Seventy-eight participants (75.0%) completed the intervention within 7 months (‘all completers’), and of these, 64 completed the intervention within 3 months (‘timely completers’). Participants experienced significant reductions in craving-related eating (40.21% reduction; p < .001) and self-reported overeating behavior (trait food craving, p < .001; other measures ps < .01). Reductions in trait food craving were significantly correlated with weight loss for timely completers (r = .30, p = .020), this pattern of results was also evident in all completers (r = .22, p = .065). Taken together, results suggest that smartphone-delivered mindful eating training targeting craving-related eating may (1) target behavior that impacts a relative metabolic pathway, and (2) represent a low-burden and highly disseminable method to reduce problematic overeating among overweight individuals. ClinicalTrials.gov registration: NCT02694731.     

Effect of Kalpaamruthaa on immunosuppression of both humoral and cell-mediated immunity in DMBA-induced mammary tumours of rats

The present study was carried out to elucidate the protective effect of Kalpaamruthaa on improving 7,12-dimethylbenz(a)anthracene (DMBA)-induced immunosuppression of both humoral and cell-mediated immunity in mammary carcinoma-induced rats. Breast cancer was induced in rats by administering DMBA orally (25 mg/rat) as a single dose. After 90 days of induction, SA (200 mg/kg body weight) and KA (300 mg/kg body weight) were administered for 14 days, by gastric intubation. Several immunotoxicological assays such as T cell rosette delayed type hypersensitivity (DTH) response, migration inhibition factor (MIF) assay, lymphocyte proliferation assay, plaque forming cell (PFC) assay and haemagglutination assay, plaque forming cell (PFC) assay, serum soluble immune complex and cytokine production, T and B cell mitogenesis induced by Con A and nonspecific cell-mediated immunity were evaluated using phagocytosis activity and NBT reduction. In cancer-induced animals (group II), the leukocyte migration inhibition declined markedly (p?<?0.001), the levels of cytokines IFN-γ and IL-2 were significantly decreased (p?<?0.001) and also the antibody titre level (p?<?0.001) was significantly reduced when compared with control rats. A marked decline in PFC (p?<?0.001) and serum soluble immune complex (PEG) formation (p?<?0.001) was also observed. Hence, the present study clearly demonstrates the immunoprotective effect of KA.     

Gasterophilosis in horses in Sardinia (Italy): effect of meteorological variables on adult egg-laying activity and presence of larvae in the digestive tract,and update of species

Gasterophilus larvae are common obligate parasites of the digestive tract of the equids. Horses become infected with this parasite by ingesting the larvae hatched from eggs laid by the female flies. In this study carried out monthly, we (i) counted the Gasterophilus eggs deposited by female flies on the coat of 30 grazing horses, (ii) counted and identified the Gasterophilus larvae retrieved from the digestive tract of 128 slaughtered horses, and (iii) compared these results to meteorological data. Eggs were deposited on all monitored horses, and were present from October to January and from May to September, whereas they were absent from February to April. The number of laid eggs was significantly different between the months, body regions, genders, and age classes (p?<?0.05). Larvae were recovered in 112 (87.5 %) horses, and 6 species of Gasterophilus were identified. The prevailing species were Gasterophilus intestinalis (recovered in 110 horses; 85.9 %) and Gasterophilus nasalis (69 horses; 53.9 %), recovered in all months. Gasterophilus inermis (5 horses; 3.9 %), Gasterophilus pecorum (3 horses; 2.3 %), Gasterophilus haemorrhoidalis (3 horses; 2.3 %)¸ and Gasterophilus meridionalis (2 horses; 1.6 %) larvae were also found. Significant differences were found among monthly larval burdens for both Gasterophilus spp. and G. intestinalis (p?<?0.05), but not for G. nasalis (p?>?0.05). Larval burdens and prevalences did not differed significantly between both genders and age classes (p?>?0.05). Monthly eggs and larvae trends were not significantly correlated (p?>?0.05). With regard to the meteorological variables, minimum air temperature was significantly correlated with the eggs trend (rho?=?1.000; p?<?0.001) and maximum air temperature with the Gasterophilus spp. (rho?=?0.972; p?<?0.001) and G. intestinalis (rho?=?0.972; p?<?0.001) larvae trends. In addition, the number of hours with a temperature below +10 °C was significantly correlated with G. intestinalis larvae trend (rho?=?0.602; p?<?0.05). Our findings confirmed that in Sardinia, Gasterophilosis is an important parasitosis in the horses, and it needs more attention and extensive and/or correct treatment to reduce its prevalence.     

Quantitative Volumetric K-Means Cluster Segmentation of Fibroglandular Tissue and Skin in Breast MRI

Mammographic breast density (MBD) is the most commonly used method to assess the volume of fibroglandular tissue (FGT). However, MRI could provide a clinically feasible and more accurate alternative. There were three aims in this study: (1) to evaluate a clinically feasible method to quantify FGT with MRI, (2) to assess the inter-rater agreement of MRI-based volumetric measurements and (3) to compare them to measurements acquired using digital mammography and 3D tomosynthesis. This retrospective study examined 72 women (mean age 52.4 ± 12.3 years) with 105 disease-free breasts undergoing diagnostic 3.0-T breast MRI and either digital mammography or tomosynthesis. Two observers analyzed MRI images for breast and FGT volumes and FGT-% from T1-weighted images (0.7-, 2.0-, and 4.0-mm-thick slices) using K-means clustering, data from histogram, and active contour algorithms. Reference values were obtained with Quantra software. Inter-rater agreement for MRI measurements made with 2-mm-thick slices was excellent: for FGT-%, r = 0.994 (95% CI 0.990–0.997); for breast volume, r = 0.985 (95% CI 0.934–0.994); and for FGT volume, r = 0.979 (95% CI 0.958–0.989). MRI-based FGT-% correlated strongly with MBD in mammography (r = 0.819–0.904, P < 0.001) and moderately to high with MBD in tomosynthesis (r = 0.630–0.738, P < 0.001). K-means clustering-based assessments of the proportion of the fibroglandular tissue in the breast at MRI are highly reproducible. In the future, quantitative assessment of FGT-% to complement visual estimation of FGT should be performed on a more regular basis as it provides a component which can be incorporated into the individual’s breast cancer risk stratification.     

Increased lipid and protein oxidation and lowered anti-oxidant defenses in systemic lupus erythematosus are associated with severity of illness,autoimmunity, increased adhesion molecules,and Th1 and Th17 immune shift

This study investigated nitro-oxidative stress in patients with systemic lupus erythematosus (SLE) in association with disease activity, immune-inflammatory biomarkers, and adhesion molecules. Two-hundred-four patients with SLE and 256 healthy volunteers were enrolled in this case-control study, which measured nitro-oxidative stress biomarkers, including lipid peroxides (LOOH), advanced oxidation protein products (AOPPs), nitric oxide metabolites (NO_x), sulfhydryl (?SH) groups, products of deoxyribonucleic acid (DNA)/ribonucleic acid (RNA) oxidative degradation, and total radical-trapping anti-oxidant parameter (TRAP). Also measured were anti-nuclear antibodies (ANAs), antibodies against double-stranded DNA (dsDNA), plasma levels of diverse cytokines, C-reactive protein, and adhesion molecules. LOOH (p < 0.001) and AOPP (p < 0.001) were significantly higher, while TRAP was significantly lower (p < 0.001) in SLE patients than in controls. AOPP and LOOH were significantly and positively associated with SLE disease activity index (SLEDAI) scores, anti-nuclear antibodies, and antibodies against double-stranded DNA (anti-dsDNA) levels, while TRAP was significantly and inversely correlated with SLEDAI, ANA, and dsDNA antibody levels. There were significant positive associations between AOPP and LOOH and immune-inflammatory markers, indicating T helper (Th)-17 and Th1 bias and Th1 + Th17/Th2 ratio (p = 0.002 and p = 0.001, respectively). AOPP and LOOH (positively) and TRAP (inversely) were associated with adhesion molecule expression. A model predicting SLE was computed showing that, using LOOH, AOPP, NO_x, adhesion molecules, and body mass index, 94.2% of the patients were correctly classified with a specificity of 91.5%. Increased nitro-oxidative stress takes part in the (auto)immune pathophysiology of SLE and modulates severity of illness and adhesion molecule expression.     

Haematological and acute-phase response of dogs with experimental skin <Emphasis Type="Italic">Pseudomonas aeruginosa</Emphasis> infection to treatment with antibiotic and parthenolide

Changes in white blood cells, leukogram patterns, the positive acute-phase protein (APP) fibrinogen and negative APPs (albumin and arylesterase) were monitored to evaluate their potential as sensitive indicators throughout the course of therapy in canine skin Pseudomonas aeruginosa infection. The study was performed on 15 male mixed-breed dogs, divided in three groups of 5 dogs each. Dogs from group A were injected subcutaneously with P. aeruginosa bacterial culture (1?×?10⁸ CFU/mL) at a dose of 0.3 mL/kg and treated with enrofloxacin (5 mg/kg, s.c.) on post infection hour 48 for 10 consecutive days. Dogs from group B were infected and treated with a combination of enrofloxacin (at above-mentioned dose and intervals) and parthenolide (feverfew extract 90 mg, 0.7 % parthenolide). The schedule consisted of daily oral intake of two capsules of feverfew beginning on post infection hour 4 and continued for 6 days. The control group C included healthy dogs, injected s.c. with 0.3 mL/kg physiological saline. The haematological indices and APPs were assayed before infection and on 4th, 24th, 48th and 72nd hours and on 7th, 10th and 14th days after infection. Infected and antibiotic-treated dogs responded with significant leukocytosis, left shift, eosinopaenia and lymphopaenia between hours 24 and 72. In this group, fibrinogen increased substantially by post infection hours 24 (p?<?0.01 vs 0 h; p?<?0.05 vs group C), 48 (p?<?0.001 vs 0 h; p?<?0.05 vs group C) and 72 (p?<?0.001 vs 0 h; p?<?0.01 vs group C) while albumin reduction was marked by hours 48 (p?<?0.05 vs 0 h) and 72 (p?<?0.05 vs 0 h; p?<?0.001 vs group C) and day 7 (p?<?0.01 vs 0 h; p?<?0.001 vs group C). The combination of enrofloxacin and parthenolide modified, at a significant extent, the deviations in studied parameters except for eosinophil percentage, which persisted low.     

Plasma clot formation and clot lysis to compare effects of different anticoagulation treatments on hemostasis in patients with atrial fibrillation

The effect of direct oral anticoagulants (DOACs) on turbidimetric measurements of plasma clot formation and susceptibility to fibrinolysis may facilitate a comparison between different classes of anticoagulants in plasma samples. We obtained 424 citrate plasma samples from 226 atrial fibrillation patients on anticoagulation and 24 samples without anticoagulation serving as controls. As comparators, we measured the international normalized ratio (INR) for phenprocoumon samples (N = 166), anti-Xa for low molecular weight heparin (LMWH) samples (N = 42), and DOAC levels with mass spectrometry (dabigatran N = 40, rivaroxaban N = 110, apixaban N = 42). Plasma clot formation and lysis were recorded continuously on a photometer after addition of an activation mix (tissue factor 2 pmol/l and tissue plasminogen activator 333 ng/ml). We used linear regression and ANCOVA for correlation analysis. Clot formation lag phase was prolonged in the presence of anticoagulants in a concentration-dependent manner for DOACs (dabigatran Spearman r = 0.74; rivaroxaban r = 0.78; apixaban r = 0.72, all p < 0.0001), INR dependent for phenprocoumon (r = 0.59, p < 0.0001), anti-Xa level dependent in LMWH samples (r = 0.90, p < 0.0001). Maximum rate of clot formation and peak clot turbidity were reduced in the presence of anticoagulants, but correlated only moderately with the comparator measures of anticoagulation. The clot lysis time was inversely correlated with DOAC concentrations in the presence of recombinant thrombomodulin. A direct ex vivo comparison between the effects of different classes of anticoagulants is possible with turbidimetric measurement of plasma clot formation and lysis. Anticoagulation inhibited clot formation in a plasma concentration manner for DOACs, INR dependent for phenprocoumon, and anti-Xa dependent for LMWH. Susceptibility to fibrinolysis increased with increasing DOAC concentrations.     

Telomere length in the gastric mucosa after <Emphasis Type="Italic">Helicobacter pylori</Emphasis> eradication and its potential role in the gastric carcinogenesis

The molecular mechanisms of gastric carcinogenesis after Helicobacter pylori (H. pylori) eradication remain unclear. We examined the telomere length of gastric mucosa samples after successful H. pylori eradication in patients without and those with gastric cancer. Telomere length was measured by the real-time PCR among four different groups of biopsies: gastric body from subjects without history of H. pylori infection (Hp-: n = 23), gastric body from cancer-free subjects after H. pylori eradication (cancer-free body: n = 24), gastric body from early gastric cancer patients diagnosed after H. pylori eradication (EGC body: n = 35) and its paired samples from adjacent mucosa of cancerous area (EGC ADJ: n = 35). The Hp-group presented the longest telomeres among the all groups (Hp- vs. all others, all P < 0.05). Samples from EGC body group showed shorter telomere length than the samples from cancer-free body groups (P < 0.05). Conversely, samples from EGC ADJ group showed rather longer telomere length compared to the EGC body group (P < 0.05), which was also confirmed by the comparison of 35 matched samples (P = 0.0007). Among the samples after H. pylori eradication, shorter telomere length was associated with higher expression of IL-1B and NF-kB (P < 0.0001, 0.0006, respectively). Longer telomere length was also associated with higher expression of TNF-A (P = 0.01). Telomere shortening seems to be important initial steps in gastric cancer predisposition after H. pylori eradication, while it might shift to lengthening to acquire more aggressive pathway to develop cancer.     

The correlation between <Emphasis Type="Italic">Toxoplasma gondii</Emphasis> infection and prenatal depression in pregnant women

Previous studies have demonstrated that latent toxoplasmosis is associated with neuropsychiatric disorders. We evaluated the correlation between Toxoplasma gondii infection and prenatal depression. In this case–control study, we enrolled 116 depressed pregnant women and 244 healthy controls. The Edinburgh Postpartum Depression Scale (EPDS) was used to evaluate the depression symptom severity in study participants. All participants were screened for the anti-Toxoplasma IgG by enzyme-linked immunosorbent assay. Seroprevalence of T. gondii did not significantly differ between the depressed pregnant women and healthy controls (OR?=?1.4; 95 % CI?=?0.9–2.19; P?=?0.142). T. gondii IgG titer was significantly higher in depressed women (18.6?±?10.9 IUs) than those in the control group (13.6?±?8.1 IUs) (z?= ?5.36, P?<?0.001). The T. gondii–positive depressed women showed a positive correlation of T. gondii IgG titer with the EPDS scores (r?=?0.52; P?<?0.01). The mean EPDS score was also significantly higher in the T. gondii–positive depressed women (20.7?±?2.7) compared with the controls (18.36?±?2.7) (P?<?0.001). The results obtained from the current study revealed that T. gondii infection might affect susceptibility to depression and severity of depressive symptoms in pregnant women, particularly in those patients who have high antibody titers. Further study is required to fully elucidate the characteristics and mechanisms of this association.     

Methylation status of <Emphasis Type="Italic">IGF2</Emphasis> DMR and <Emphasis Type="Italic">LINE1</Emphasis> in leukocyte DNA provides distinct clinicopathological features of gastric cancer patients

DNA methylation of leukocyte DNA has been proposed to be a biomarker for cancer that can be used to target patients for appropriate clinical implementation. We investigated IGF2 DMR and LINE1 methylation in the leukocyte DNA and their association with clinicopathological features and prognosis of gastric cancer (GC) patients. Methylation status of IGF2 DMR and LINE1 in the leukocyte DNA was quantified using bisulfite pyrosequencing in 207 GC patients. Methylation of both IGF2 DMR and the LINE1 was significantly higher in the undifferentiated histologic type compared to the differentiated histologic type (both P = 0.0002). Hypermethylation of both the IGF2 DMR and the LINE1 was associated with more aggressive features of GC such as advanced stage (IGF2 DMR, P = 0.0002; LINE1, P < 0.0001), lymphatic invasion positive (IGF2 DMR, P = 0.004; LINE1, P = 0.002), venous invasion positive (IGF2 DMR, LINE1, both P = 0.03), lymph node metastasis positive (IGF2 DMR, P = 0.01; LINE1, P = 0.001), peritoneal dissemination positive (IGF2 DMR, P = 0.04; LINE1, P = 0.002), liver metastasis positive (IGF2 DMR, P = 0.008; LINE1, P = 0.001), and other distant metastasis positive (IGF2 DMR, P = 0.04). Our data suggest that high LINE1 and IGF2 DMR methylation status would be a phenomenon that is observed with the progression of GC, supporting their potential utility as a biomarker in GC patients.     

Bilirubin in the early course of venovenous extracorporeal membrane oxygenation support for refractory ARDS

Bilirubin is known as a marker of hepatic dysfunction and is incorporated in scoring algorithms to assess prognosis in critically ill patients. No data are so far available on the prognostic role of hepatic dysfunction in patients with severe ARDS on venovenous extracorporeal membrane oxygenation (VV-ECMO) support. In 112 consecutive patients with severe ARDS treated with VV-ECMO, we aimed at assessing whether increased bilirubin during the first 72 h could affect early death. Increased serum bilirubin (≥1.2 mg/dl) was detectable in 29 patients (25.9%) who were older (p = 0.031), exhibited a higher SOFA score (p = 0.006), were more frequently given pre-ECMO muscular blockers (p = 0.001) and supported with ECMO for a longer period (p = 0.024), when compared to patients with normal bilirubin. No difference in in-ICU mortality rate was observed between the two subgroups. In survivors, bilirubin showed a progressive and significant decrease (p = 0.032) during the first 72 h of ECMO support, while it increased in dead patients (p = 0.007).The mortality rate was higher in patients with increased bilirubin at 24, 48 and 72 h after ECMO start in respect to that of patients with normal values. Pre-ECMO increased bilirubin values (≥1.2 mg/dl), being detectable in about one-fourth of the entire population, is not associated with increased in-ICU mortality, while the persistence of increased bilirubin values after 24 h of ECMO start and within the first 3 days identified a subgroup of patients at higher risk of death.     

Interleukin-28B TT genotype is frequently found in patients with hepatitis C virus cirrhosis but does not influence hepatocarcinogenesis

Persistent hepatitis C virus (HCV) infection is associated with progressive hepatic fibrosis and ultimately hepatocellular carcinoma. The interleukin-28B (IL28B) rs12979860 polymorphism is associated with fibrosis progression in chronic HCV infection. IL28B encodes interferon-λ, which has both antiviral and anti-proliferative properties. This study aimed to determine whether IL28B rs12979860 polymorphism is also associated with development of hepatocellular carcinoma both in chronic HCV infection and in non-viral-related cirrhosis. Real-time polymerase chain reaction and melting curve analyses were used to genotype 311 patients who underwent liver transplantation for HCV cirrhosis (n = 202) or alcoholic cirrhosis (n = 109). HCV patients were older (p = 0.012) and less likely males (p < 0.001) than patients with alcoholic cirrhosis. IL28B rs12979860 TT genotype [OR 6.08, 95 % CI 2.11–17.53; p < 0.001] and T allele carriage (CT + TT; OR 2.3, CI 95 % 1.42–3.72; p = 0.001) were more frequent among HCV patients and, among them, more common in patients infected with HCV genotype 1 (CT + TT; OR 1.79, CI 95 % 1.03–3.09; p = 0.009). Incidence of hepatocellular carcinoma was higher in HCV cirrhosis (OR 2.7, CI 95 % 1.5–4.7; p < 0.001), with no differences according to HCV genotype. IL28B genotype distribution was similar among patients with or without hepatocellular carcinoma, in both HCV patients regardless viral genotype (p = 0.84) and alcoholic patients (p = 0.91). Multivariate analysis showed that older age (OR 1.06, CI 95 % 1.02–1.1; p = 0.003) and male gender (OR 2.49, CI 95 % 1.24–5; p = 0.01) were independent risk factors for hepatocellular carcinoma in HCV patients. In summary, the current study did not find a significant association between IL28B rs12979860 polymorphism and hepatocarcinogenesis.     

Clinical Impact of <Emphasis Type="Italic">p27</Emphasis><Superscript><Emphasis Type="Italic">Kip1</Emphasis></Superscript> and CaSR Expression on Primary Hyperparathyroidism

We aimed to investigate the expressions of p27 kinase inhibitory protein 1 (p27^Kip1) and calcium sensing receptor (CaSR) in adenomas and normal parathyroid tissue and to evaluate the relationship of these molecules with clinical and biochemical parameters in primary hyperparathyroidism (PHPT). Fifty-one patients with histopathologically confirmed parathyroid adenomas and 20 patients with normal parathyroid glands (which were removed incidentally during thyroid resection) were included. Immunohistochemical stainings of CaSR and p27^Kip1 were performed in surgical specimens. Clinical features, biochemical parameters, and BMD measurements of patients with PHPT were evaluated retrospectively. Expressions of p27^Kip1 and CaSR were decreased in parathyroid adenomas, compared to normal glands (p <?0.05). High intensity of CaSR staining (3+) was more frequent in normal parathyroid tissue (75%) than adenomas (12%) (p <?0.01). Hypertension was not observed in patients with high staining intensity of CaSR (p =?0.032). There was a negative association between CaSR expression and body mass index (BMI) (p =?0.027, r =???0.313). There was no significant relationship between p27^Kip1 and CaSR expressions, serum calcium, plasma parathormone, 25-hydroxy vitamin D levels, and bone density (p >?0.05). The expressions of p27^Kip1 and CaSR were decreased in PHPT patients. This reduction may play an important role in the pathogenesis of PHPT. However, neither p27^Kip1 nor CaSR expression was found to be useful in predicting prognosis or severity of disease.     

<Emphasis Type="Bold">Risk Compensation Following Medical Male Circumcision: Results from a 1-Year Prospective Cohort Study of Young School-Going Men in KwaZulu-Natal,South Africa</Emphasis>

Purpose

This study sought to assess risk compensation following voluntary medical male circumcision of young school-going men. Risk compensation is defined as an inadvertent increase in sexual risk behaviors and a corresponding decrease in self-perceived risk for contracting HIV following the application of a risk reduction technology.

Methods

This study documented the sexual practices of circumcised (n = 485) and uncircumcised (n = 496) young men in 42 secondary schools at three time points (baseline and 6 and 12 months) in a sub-district of KwaZulu-Natal, South Africa. Study participants were aged from 16 to 24 years old.

Results

At the end of the study period, there was no significant difference between the two cohorts concerning learners’ perceptions of being at risk of contracting HIV (interaction effect: b = ?0.12, p = 0.40). There was also no significant difference in the number of sexual partners in the previous month (interaction effect: b = ?0.23, p = 0.15). The proportion of learners who have never used a condom decreased significantly over time (time effect: b = ?0.27, p = 0.01), and there was no difference between the circumcised and uncircumcised learners (interaction effect: b = ?0.09, p = 0.91).

Conclusions

Risk compensation, as evidenced in this study over a 1-year period, was not associated with undergoing voluntary medical male circumcision (VMMC) in our sample of young school-going men. However, it is of concern that at the end of this study, less than half of the sexually active sample in a high-HIV-prevalence community used condoms consistently in the previous month (39% for both study cohorts). The latter underscores the need to view VMMC as a potential entry point for planned HIV and sexuality education interventions targeting young men in this community.