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.     

Serum levels of P-glycoprotein and persistence of disease activity despite treatment in patients with systemic lupus erythematosus

Around 25% of patients with systemic lupus erythematosus (SLE) could be refractory to conventional therapies. P-glycoprotein expression on cell surface has been implied on drug resistance, however, to date, it is unknown if P-gp serum levels are associated with SLE disease activity. Evaluate the association of serum P-gp levels and SLE with disease activity despite treatment. A cross-sectional study was conducted on 93 female SLE patients, all receiving glucocorticoids at stable doses for the previous 6 months before to baseline. SLE patients were classified into two groups: (a) patients with active disease [SLE disease activity index (SLEDAI) ≥ 3] despite treatment, and (b) patients with inactive disease (SLEDAI < 3) after treatment. Forty-three healthy females comprised the control group. Serum P-gp, anti-DNA, and both anti-nucleosome antibody levels were measured using ELISA. Active-SLE patients despite treatment had higher P-gp levels compared with inactive-SLE after treatment (78.02 ng/mL ± 114.11 vs. 33.75 ng/mL ± 41.11; p = 0.018) or versus reference group subjects (30.56 ng/mL ± 28.92; p = 0.011). P-gp levels correlated with the scores of SLEDAI (r = 0.26; p = 0.01), Mexican-SLEDAI (MEX-SLEDAI) (r = 0.32; p = 0.002), SLICC/ACR damage index (r = 0.47; p < 0.001), and with prednisone doses (r = 0.33; p = 0.001). In the multivariate model, the high P-gp levels were associated with SLICC/ACR score (p = 0.001), and SLEDAI score (p = 0.014). Our findings support a relationship between serum P-gp levels and SLE with disease activity despite treatment, but it requires further validation in longitudinal studies.     

Association of serum bilirubin with oxidant damage of human atherosclerotic plaques and the severity of atherosclerosis

Bilirubin has protective effects against atherosclerotic cardiovascular diseases hypothetically due to its antioxidant–antilipoperoxidative properties. Thus, we investigated whether serum bilirubin is associated with oxidant damage, namely lipid peroxidation, of human atherosclerotic plaques and the severity of atherosclerosis. In this regard, we correlated the levels of serum total bilirubin (STB), direct (conjugated) bilirubin (SDB) and indirect (unconjugated) bilirubin (SIB) with those of fluorescent damage products of lipid peroxidation (FDPL) and lipid hydroperoxides (LOOH) of 32 endarterectomy-derived carotid atherosclerotic plaques. Moreover, we compared the levels of serum bilirubin and plaque lipoperoxides between two groups of patients of the study population with different severity of atherosclerosis as judged by the carotid stenosis degree, i.e., <90% (group A, n = 23) and ≥90% (group B, n = 9). Remarkably, the levels of STB were strongly inversely correlated with those of plaque FDPL (rS = ?0.70, P < 0.0001) and LOOH (rS = ?0.66, P < 0.0001), as were those of SIB (FDPL: rS = ?0.68, P < 0.0001; LOOH: rS = ?0.63, P < 0.0001). SDB had a weaker association with plaque FDPL (rS = ?0.41, P < 0.05) and LOOH (rS = ?0.35, P < 0.05). Moreover, the levels of STB, SDB and SIB were lower and those of plaque lipoperoxides higher in group B than in group A, pointing to the association of serum bilirubin and plaque oxidant burden with the severity of atherosclerosis. In conclusion, lowered serum bilirubin is associated with oxidant damage of human atherosclerotic plaques and the severity of atherosclerosis.     

The <Emphasis Type="Italic">PTPN22</Emphasis> R263Q polymorphism confers protection against systemic lupus erythematosus and rheumatoid arthritis,while <Emphasis Type="Italic">PTPN22</Emphasis> R620W confers susceptibility to Graves’ disease in a Mexican population

Objective

The functional PTPN22 R620W polymorphism (rs2476601) is clearly associated with susceptibility to several autoimmune diseases (ADs). However, the PTPN22 R263Q polymorphism (rs33996649) has been scarcely explored in different ADs. Here we aimed to examine the associations of the PTPN22 R620W and R263Q polymorphisms with susceptibility to or protection against rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Graves’ disease (GD) among Mexican patients.

Methods

We conducted a case–control study including 876 patients (405 with SLE, 388 with RA, and 83 with GD) and 336 healthy control individuals. PTPN22 genotypes were determined using the TaqMan 5′ allele discrimination assay.

Results

PTPN22 R620W was associated with GD susceptibility (OR 4.3, p = 0.004), but was not associated with SLE (OR 1.8, p = 0.19). We previously demonstrated that this polymorphism is associated with RA susceptibility (OR 4.17, p = 0.00036). Moreover, PTPN22 R263Q was associated with protection against SLE (OR 0.09, p = 004) and RA (OR 0.28, p = 0.045), but was not associated with GD.

Conclusions

Our data provide the first demonstration that PTPN22 R620W confers GD susceptibility among Latin-American patients. Moreover, this is the second report documenting the association of PTPN22 R263Q with protection against SLE and RA.

     

Changes of FibroScan,APRI, and FIB-4 in chronic hepatitis B patients with significant liver histological changes receiving 3-year entecavir therapy

Noninvasive fibrosis tests have been used widely for evaluation of liver fibrosis in patients with chronic hepatitis B (CHB). We aimed to investigate the influence of antiviral treatment on FibroScan, APRI, and FIB-4 in CHB patients with significant liver histological changes (SLHC) defined as inflammatory grade ≥ A2 and/or fibrosis stage ≥ F2. A total of 104 CHB patients with SLHC at the baseline were included. FibroScan, APRI, and FIB-4 values were compared before and after 3-year entecavir (ETV) treatment. Liver stiffness measurement values decreased significantly after 3-year ETV treatment in cirrhosis group (from 13.6 to 9.6 kPa, p = 0.018), significant fibrosis group (from 8.4 to 5.8 kPa, p = 0.001), and mild fibrosis group (from 5.5 to 4 kPa, p < 0.001). APRI decreased significantly after 3-year ETV treatment in patients with cirrhosis (from 0.80 to 0.25, p < 0.001), patients with significant fibrosis (from 0.54 to 0.24, p < 0.001), and those with mild fibrosis (from 0.35 to 0.23, p < 0.001). FIB-4 decreased significantly after 3-year ETV treatment in patients with cirrhosis (from 1.27 to 0.81, p = 0.007) and significant fibrosis (from 1.12 to 0.78, p < 0.001), while did not decrease significantly in patients with mild fibrosis (from 0.90 to 0.80, p = 0.389). FibroScan, APRI, and FIB-4 values decreased significantly after 3-year ETV treatment in CHB patients, which indicates that these noninvasive fibrosis tests might be useful for monitoring regression of liver fibrosis and assessing treatment efficacy during long-term ETV treatment.     

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.     

Outcome measures of extracorporeal life support (ECLS) in trauma patients versus patients without trauma: a 7-year single-center retrospective cohort study

This single-center retrospective study included a total of 99 extracorporeal life support (ECLS) cannulated patients assigned to a traumatic extracorporeal life-support cohort (TECLS) or a non-traumatic extracorporeal life-support cohort (NTECLS). Forty-nine TECLS patients and 50 NTECLS patients were compared. The TECLS patients were significantly younger [49.9 years 16.6–86.2 vs. 57.1 (21.4–78.6); p = 0.007] and had lower body mass indices (BMIs) [27.7 kg/m² (20–37) vs. 32.5 (19–88.5); p = 0.001] than the NTECLS patients. The intensive care unit (ICU) survival rate [n = 34 (69.4%) vs. n = 13 (26%); p ≤ 0.001] and the hospital survival rate [n = 32 (65.3%) vs. n = 13 (26%); p ≤ 0.001] were significantly higher for the TECLS cohort than for the NTECLS cohort. The lengths of stay (LOSs) in the ICU [24 days (4.8–71.1) vs. 11.3 (0–88.6); p = 0.001] and in the hospital [46.6 days (2.9–197.6) vs. 21 (0.1–213.8); p = 0.001] were significantly longer for the TECLS patients than for the NTECLS patients.     

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.     

Distribution of <Emphasis Type="Italic">PTPN22</Emphasis> polymorphisms in SLE from western Mexico: correlation with mRNA expression and disease activity

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune inflammatory disease characterized by loss of self-tolerance with hyperactivation of autoreactive T and B cells. Protein tyrosine phosphatase non-receptor type 22 (PTPN22) encodes for lymphoid-specific phosphatase (Lyp), which is a key negative regulator of T lymphocyte activation. The aim of this study was to evaluate the genetic contribution of PTPN22 ?1123G>C and +1858C>T polymorphisms and their haplotypes in SLE patients, as well as mRNA expression according to ?1123G>C promoter polymorphism and disease activity. One hundred and fifty SLE patients and 150 unrelated healthy controls (HC), both Mexican mestizos, were genotyped by PCR–RFLP technique for the PTPN22 ?1123G>C and +1858C>T polymorphisms. PTPN22 mRNA expression levels were determined by real-time PCR from PBMCs of thirty patients with SLE and fifteen HC carrying different genotypes. Distributions of genotype and allelic frequencies were similar between SLE and HC. The most frequent alleles were ?1123 G and +1858 C in both groups (69 vs. 66 % and 97 vs. 98 %, in SLE and HC, respectively). However, the recessive model of inheritance analysis showed a lower frequency of ?1123 CC genotype in SLE patients (7 vs. 15 %), suggesting a protection effect to develop SLE (OR 0.41, CI 1.10–5.28, p = 0.02). Haplotype analysis showed strong linkage disequilibrium D′ = 0.98 for PTPN22 ?1123G>C and +1858C>T polymorphisms, but haplotypes were not associated with SLE. The PTPN22 mRNA expression did not show differences among ?1123G>C genotypes; nevertheless, a significant negative correlation with disease activity was found (r = ?0.64, p < 0.01). SLE inactive patients showed similar PTPN22 mRNA expression levels to healthy controls, whereas in patients with severe flare, the expression was nearly depleted. In conclusion, we found a lack of association of PTPN22 ?1123G>C and +1858C>T polymorphisms with the risk of developing SLE in a Mexican population. Moreover, decreased or absent PTPN22 mRNA expression in SLE patients with severe flare suggests that Lyp plays an important regulatory role, and its absence contributes to the inflammatory response and disease activity in SLE. However, further analysis in a prospective study could help us determine its usefulness as a genetic marker of disease activity in SLE.     

The role of MSCT angiography in early detection of lower limb arterial lesions in patients with antiphospholipid syndrome

Antiphospholipid syndrome (APS) is an autoimmune disease which is characterized by arterial and venous thromboses, fetal loss, and the presence of antiphospholipid antibodies in the serum. It is characterized by accelerated atherosclerosis. Increased tendency towards thrombosis leads to the occurrence of various vascular events. The objective of our study was to determine if there are subclinical changes on lower limb arteries in APS patients and what the best diagnostic choice for their establishment is. In this study, we analyzed 50 patients with primary antiphospholipid syndrome (PAPS) and 50 patients, who have secondary antiphospholipid syndrome (SAPS). The results were compared to 50 controls. The groups were comparable with respect to age, gender, and traditional risk factors except for the lipid status, since controls had significantly higher levels of cholesterol and triglycerides. Study was conducted on 64-multi-slice computed tomography (64-MSCT), where we analyzed quantitative and morphological characteristics of blood vessel-detected lesions. Patients from the control group had statistically very significant elevated cholesterol and triglyceride levels in regard to the patients with SAPS and PAPS (p < 0.001 and p < 0.05). Analyzing percentage of diameter stenosis, we have established that lesions from group with 0–30% diameter stenosis (DS) in patients with PAPS (n = 47) and SAPS (n = 39) are more common than that in control group (n = 3, p < 0.001). The incidence of lesions higher than 70% DS in control group (n = 74) was statistically significant than that in patients with SAPS (n = 74, p < 0.05), while very statistically significant than that in patients with PAPS (n = 48, p < 0.001). Analyzing the qualitative characteristics of plaques, we have established significant higher frequency of soft tissue (n = 32) and mixed lesions (n = 36) in patients with PAPS than the calcified one (n = 7, p < 0.001). Our study showed that the subclinical manifestation of changes on lower extremity arteries is more common in patients with APS. Because of its safety and accuracy, the method of choice is 64-MSCT angiography in monitoring disease progression.     

The interplay between arms-only propelling efficiency,power output and speed in master swimmers

Purpose

To explore the interplay between arms-only propelling efficiency (η _p), mechanical power output (\(\dot W_{\text{tot}}\)) and swimming speed (V); these three parameters are indeed related through the following equation V ³ = 1/kη _p \(\dot W_{\text{tot}}\) (where k is the speed-specific drag; k = F/V ²); thus, the larger are η _p and \(\dot W_{\text{tot}}\) the larger is V. We furthermore wanted to test the hypothesis that a multiple linear regression between \(\dot W_{\text{tot}}\), η _p and V would have a stronger correlation coefficient than a linear regression between \(\dot W_{\text{tot}}\) and V alone.

Methods

To this aim we recruited 29 master swimmers (21 M/8F) who were asked to perform (1) an incremental protocol at the arm-ergometer (dry-land test) to determine \(\dot W_{\text{tot}}\) at \(\dot V\)O_2max (e.g. \(\dot V\) _max); (2) a maximal 200 m swim trial (with a pull buoy: arms only) during which V and η _p were determined.

Results

No relationship was found between \(\dot W_{\text{max}}\) and η _p (not necessarily the swimmers with the largest \(\dot W_{\text{max}}\) are those with the largest η _p and vice versa) whereas significant correlations were found between \(\dot W_{\text{max}}\) and V (R = 0.419, P = 0.024) and η _p and V (R = 0.741, P = 0.001); a multiple linear regression indicates that about 75 % of the variability of V can be explained by the variability of \(\dot W_{\text{max}}\) and η _p (R = 0.865, P < 0.001).

Conclusions

These findings indicate that η _p should be taken into consideration when the relationship between \(\dot W_{\text{max}}\) and V is investigated and that this allows to better explain the inter-subject variability in performance (swimming speed).

     

Replacing sedentary time with sleep,light, or moderate-to-vigorous physical activity: effects on self-regulation and executive functioning

Recent attention has highlighted the importance of reducing sedentary time for maintaining health and quality of life. However, it is unclear how changing sedentary behavior may influence executive functions and self-regulatory strategy use, which are vital for the long-term maintenance of a health behavior regimen. The purpose of this cross-sectional study is to examine the estimated self-regulatory and executive functioning effects of substituting 30 min of sedentary behavior with 30 min of light activity, moderate-to-vigorous physical activity (MVPA), or sleep in a sample of older adults. This study reports baseline data collected from low-active healthy older adults (N = 247, mean age 65.4 ± 4.6 years) recruited to participate in a 6 month randomized controlled exercise trial examining the effects of various modes of exercise on brain health and function. Each participant completed assessments of physical activity self-regulatory strategy use (i.e., self-monitoring, goal-setting, social support, reinforcement, time management, and relapse prevention) and executive functioning. Physical activity and sedentary behaviors were measured using accelerometers during waking hours for seven consecutive days at each time point. Isotemporal substitution analyses were conducted to examine the effect on self-regulation and executive functioning should an individual substitute sedentary time with light activity, MVPA, or sleep. The substitution of sedentary time with both sleep and MVPA influenced both self-regulatory strategy use and executive functioning. Sleep was associated with greater self-monitoring (B = .23, p = .02), goal-setting (B = .32, p < .01), and social support (B = .18, p = .01) behaviors. Substitution of sedentary time with MVPA was associated with higher accuracy on 2-item (B = .03, p = .01) and 3-item (B = .02, p = .04) spatial working memory tasks, and with faster reaction times on single (B = ?23.12, p = .03) and mixed-repeated task-switching blocks (B = ?27.06, p = .04). Substitution of sedentary time with sleep was associated with marginally faster reaction time on mixed-repeated task-switching blocks (B = ?12.20, p = .07) and faster reaction time on mixed-switch blocks (B = 17.21, p = .05), as well as reduced global reaction time switch cost (B = ?16.86, p = .01). Substitution for light intensity physical activity did not produce significant effects. By replacing sedentary time with sleep and MVPA, individuals may bolster several important domains of self-regulatory behavior and executive functioning. This has important implications for the design of long-lasting health behavior interventions. Trial Registration clinicaltrials.gov identifier NCT00438347.     

A Retrospective Study on the Efficacy of Trastuzumab in HER2-Positive and Tamoxifen-Refractory Breast Cancer with Brain Metastasis

Background and Objective

The role of trastuzumab in breast cancer with brain metastasis is still in discussion. This study was conducted to investigate the efficacy of trastuzumab in the management of human epidermal growth factor receptor 2 (HER2)–positive, tamoxifen-refractory breast cancer with brain metastasis.

Methods

This retrospective study was conducted between January 2008 and December 2012. A total of 33 patients receiving trastuzumab treatment for HER2-positive, tamoxifen-refractory breast cancer with brain metastasis were assigned to the experimental group, while a matched group of 35 patients who received systemic therapy without trastuzumab were assigned to the control group. Data on the patient characteristics and clinical outcomes were collected and evaluated.

Results

Patients in the trastuzumab group showed a significantly better response to treatment than those in the control group (p = 0.025). Univariate and multivariate Cox proportional regression analyses indicated that progression-free survival was significantly longer in patients receiving trastuzumab therapy than in the control group (hazard ratio [HR] 2.213 [p = 0.003] and HR 3.056 [p < 0.001], respectively) and significantly shorter in patients with two or more extracranial metastases (HR 0.417 [p = 0.002] and HR 0.317 [p < 0.001], respectively). Furthermore, patients on trastuzumab treatment experienced longer overall survival than patients in the control group (HR 2.844 [p < 0.001] and HR 4.017 [p < 0.001], respectively), while shorter overall survival was seen in patients with two or more extracranial metastases (HR 0.524 [p = 0.021] and HR 0.430 [p = 0.005], respectively) and in those receiving capecitabine-based therapy as compared with anthracycline-based therapy (HR 0.558 [p = 0.030] and HR 0.449 [p = 0.011], respectively).

Conclusion

Trastuzumab was found to benefit patients with HER2-positive, tamoxifen-refractory breast cancer with brain metastasis by improving progression-free and overall survival.

     

Comparing Clinicopathologic and Radiographic Findings Between TT-UMP,Classical, and Non-Encapsulated Follicular Variants of Papillary Thyroid Carcinomas

Thyroid tumors of uncertain malignant potential (TT-UMP) comprise an accepted subgroup of follicular-patterned thyroid tumors for which benignancy or malignancy cannot be precisely assessed. We aimed to evaluate the demographic characteristics, ultrasound (US) findings, and cytological results of patients with TT-UMP and compare these findings to a classical variant of papillary thyroid carcinoma (CV-PTC) and non-encapsulated follicular variant of PTC (NEFV-PTC) patients; we also evaluated the immunohistochemical characteristics of patients with TT-UMP. Twenty-four patients with TT-UMP, 672 with CV-PTC, and 132 with NEFV-PTC were included in the study. Mean longitudinal nodule size and median nodule volume were higher in the TT-UMP group than in the CV-PTC and NEFV-PTC groups (p?<?0.001 and p?<?0.001 for CV-PTC; p?<?0.001 and p?=?0.008 for NEFV-PTC). The presence of halo and peripheral vascularization was observed more frequently in the TT-UMP group than in the CV-PTC group (p?=?0.002 and p?=?0.024). Benign and follicular neoplasm/suspicious for follicular neoplasm cytological results were higher in the TT-UMP group than in the CV-PTC group (p?=?0.030 and p?=?0.001). US findings were similar between TT-UMP and NEFV-PTC groups (all, p?>?0.05). However, none of the patients with TT-UMP were called malignant; 105 patients (31.2 %) of CV-PTC and 11 patients (9.5 %) of NEFV-PTC (infiltrative FV) were classified as malignant cytologically. Tumor size was higher in the TT-UMP group than in the CV-PTC and NEFV-PTC groups (p?<?0.001 and p?=?0.006). In the TT-UMP group, positive expression of HBME-1, CK-19, and Gal-3 was found in 50, 33.3, and 25 % of patients, respectively. This study demonstrated that none of the TT-UMP patients were evaluated as malignant in preoperative cytology. However, patients with TT-UMP had higher nodule and tumor sizes than CV-PTC and NEFV-PTC patients; US features were similar between NEFV-PTC and TT-UMP patients.     

Bacterial vaginosis,aerobic vaginitis,vaginal inflammation and major Pap smear abnormalities

The purpose of this investigation was to evaluate the impact of the vaginal milieu on the presence of abnormal Pap smears and a positive human papilloma virus (HPV) test. A cross-sectional study was conducted between June 2014 and May 2015, evaluating the vaginal discharge by fresh wet mount microscopy and comparing these data with Pap smear findings. Wet mount slides were scored for bacterial vaginosis (BV), aerobic vaginitis (AV), presence of Candida and Trichomonas vaginalis. Cytologic evaluation was done on all Pap smears according to the Bethesda criteria. The cobas© HPV Test (Roche) was performed for HPV detection. A total of 622 cases were evaluated. The mean age of the patients was 41.6?±?10.65 years (range 21–75). Eighty-three women (13.3 %) had a cytology result worse than low-grade squamous intraepithelial lesion (LSIL). When comparing this group with the one with normal or minor [atypical squamous cells of undetermined significance (ASC-US) or LSIL] Pap smear abnormalities, there were no differences in the presence of Candida (32.5 % vs. 33.2 %, p?=?1.0), absence of lactobacilli (38.6 % vs. 32.5 %, p?=?0.32) or BV (20.5 % vs. 13.2 %, p?=?0.09). On the other hand, moderate or severe inflammation (msI) (41.0 % vs. 28.8 %, p?=?0,04), moderate or severe AV (msAV) (16.9 % vs. 7.2 %, p?=?0.009) and msAV/BV (37.3 % vs. 20.0 %, p?=?0.001) were more common in women with such major cervical abnormalities. No significant association was found between deviations of the vaginal milieu and high-risk HPV infection. The presence of msI or msAV, but not BV, is independently associated with an increased risk of major cervical cytological abnormalities, but not with HPV infection.     

Marijuana use and pregnancy: prevalence,associated characteristics,and birth outcomes

This study examines the prevalence, behaviors, and birth outcomes associated with marijuana use in pregnancy. This was a retrospective cohort from a university-based prenatal care clinic from July 1, 2009 to June 30, 2010. The primary exposure was marijuana use, defined by self-report or urine toxicology. Demographic and outcome data were determined by chart review and analyzed by chi-square test, Fisher’s exact test, ANOVA, and logistic regression. Three hundred and ninety-six patients initiated prenatal care during this time frame; 116 (29.3 %) of whom screened positive for marijuana at initial visit. Patients who used marijuana were less likely to have graduated high school (p?=?0.016) or be employed (p?=?0.015); they were more likely to use tobacco (p?<?0.001) or alcohol (p?=?0.032) and report a history of abuse (p?=?0.010) or depressed mood (p?=?0.023). When analyzed via logistic regression, only tobacco use remained associated with marijuana use (adjusted odds ratio (OR)?=?3.3; 95 % confidence interval (CI): 1.9–5.9). Birth outcomes were available for 170 (43.0 %) patients. Only 3 (1.9 %) tested positive for marijuana at the time of delivery. Marijuana use was not related to incidence of low birth weight (13.8 % vs 14.0 %, p?=?1.00), preterm delivery (17.7 % vs 12.0 %, p?=?0.325), or NICU admissions (25.5 % vs 15.8 %, p?=?0.139). Prenatal care utilization was equal between marijuana users and non-users. Although marijuana is common among obstetric patients at prenatal care initiation, most cease use by delivery. Marijuana is strongly correlated with cigarette use. We found no differences in birth outcomes or utilization of prenatal care by marijuana exposure.     

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.     

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.     

Association between dementia and reduced walking ability and 30-day mortality in patients with extended-spectrum beta-lactamase-producing <Emphasis Type="Italic">Escherichia coli</Emphasis> bacteremia

Previous studies have shown controversial results of factors associated with short-term mortality in patients with extended-spectrum beta-lactamase (ESBL)-producing E. coli bacteremia and no research has investigated the impact of the geriatric assessment criteria on short-term mortality. Our objective was to determine whether dementia and walking ability are associated with 30-day mortality in patients with ESBL-producing E. coli bacteremia. All blood bottle cultures, analyzed from January 2008 to April 2015, in the Bacteriology Department of a 2,600-bed, university-affiliated center, Nantes, France, were retrospectively extracted. Factors associated with short-term mortality in patients with ESBL-producing E. coli bacteremia: 140 patients with an ESBL-producing E. coli bloodstream infection were included; 22 (15.7%) patients died within 30 days following the first positive blood bottle culture of ESBL-producing E.coli. In multivariate analysis, a reduced ability to walk (OR = 0.30; p = 0.021), presence of dementia (OR = 54.51; p = 0.040), a high Sepsis-related Organ Failure Assessment (SOFA) score (OR = 1.69; p < 0.001), presence of neutropenia (OR = 12.94; p = 0.049), and presence of a urinary tract infection (OR = 0.07; p = 0.036), were associated with 30-day mortality. Our findings provide new data showing an independent association between 30-day mortality with dementia and reduced walking ability, in patients with ESBL-producing E. coli bacteremia. These criteria should be considered in the therapeutic management of patients with ESBL-producing E. coli bacteremia.     

Oxidative stress levels are correlated with <Emphasis Type="Italic">P15</Emphasis> and <Emphasis Type="Italic">P16</Emphasis> gene promoter methylation in myelodysplastic syndrome patients

Oxidative stress and abnormal DNA methylation have been implicated in some types of cancer, namely in myelodysplastic syndromes (MDS). Since both mechanisms are observed in MDS patients, we analyzed the correlation of intracellular levels of peroxides, superoxide anion, and glutathione (GSH), as well as ratios of peroxides/GSH and superoxide/GSH, with the methylation status of P15 and P16 gene promoters in bone marrow leukocytes from MDS patients. Compared to controls, these patients had lower GSH content, higher peroxide levels, peroxides/GSH and superoxide/GSH ratios, as well as higher methylation frequency of P15 and P16 gene promoters. Moreover, patients with methylated P15 gene had higher oxidative stress levels than patients without methylation (peroxides: 460 ± 42 MIF vs 229 ± 25 MIF, p = 0.001; superoxide: 383 ± 48 MIF vs 243 ± 17 MIF, p = 0.022; peroxides/GSH: 2.50 ± 0.08 vs 1.04 ± 0.34, p < 0.001; superoxide/GSH: 1.76 ± 0.21 vs 1.31 ± 0.10, p = 0.007). Patients with methylated P16 and at least one methylated gene had higher peroxide levels as well as peroxides/GSH ratio than patients without methylation. Interestingly, oxidative stress levels allow the discrimination of patients without methylation from ones with methylated P15, methylated P16, or at least one methylated (P15 or P16) promoter. Taken together, these findings support the hypothesis that oxidative stress is correlated with P15 and P16 hypermethylation.