Polymorphisms in DNA repair genes and breast cancer risk in Russian population: a case–control study

Genetic variation in DNA repair genes can alter an individual’s capacity to repair damaged DNA and influence the risk of cancer. We tested seven polymorphisms in DNA repair genes XRCC1, ERCC2, XRCC3, XRCC2, EXOI and TP53 for a possible association with breast cancer risk in a sample of 672 case and 672 control Russian women. An association was observed for allele A of the polymorphism XRCC1 (R399Q) rs25487 (co-dominant model AA vs. GG: OR 1.76, P = 0.003; additive model OR 1.28, P = 0.005; dominant model: OR 1.29, P = 0.03; recessive model OR 1.63, P = 0.008). Allele T of the polymorphism ERCC2 (D312N) rs1799793 was also associated with breast cancer risk (co-dominant model TT vs. CC: OR 1.43, P = 0.04; additive model OR 1.21, P = 0.02; dominant model: OR 1.30, P = 0.02), but the association became insignificant after applying Bonferroni correction. No association with breast cancer was found for the remaining SNPs. In summary, our study provides evidence that polymorphisms in DNA repair genes may play a role in susceptibility to breast cancer in the population of ethnical Russians.     

The Flip Side of NIFTP: an Increase in Rates of Unfavorable Histologic Parameters in the Remainder of Papillary Thyroid Carcinomas

The term noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was recently proposed to replace noninvasive follicular variant of papillary thyroid carcinoma (FVPTC) both to promote more conservative management of these tumors and spare patients the psychological burden of a cancer diagnosis. This reclassification will lower the incidence of papillary thyroid carcinoma (PTC). In addition, it could result in an increase in the rates of unfavorable histologic prognosticators for PTC overall because NIFTPs had previously accounted for many of the PTCs without these features. Our aim was to evaluate the potential impact of the reclassification of NIFTP on the rates of extrathyroidal extension, lymphovascular invasion, and lymph node metastases in PTC. We identified all PTCs clinically over 1 cm diagnosed on surgical resection between August 2010 and August 2012. The histopathologic characteristics, including PTC subtype, tumor size, presence of extrathyroidal extension and lymphovascular invasion, and surgical margin and lymph node status were all recorded. Based on these parameters, cases were classified according to the American Thyroid Association (ATA) risk stratification system for structural disease recurrence. Tumor slides for cases initially diagnosed as FVPTC were reviewed to identify tumors that would now be classified as NIFTPs. Our cohort included 348 cases of PTC, of which 94 (27%) would now be classified as NIFTPs. After excluding NIFTPs from the PTC category, there were increased rates of extrathyroidal extension (26% up from 19%, p = 0.046), lymphovascular invasion (37% up from 27%, p = 0.0099), and lymph node metastases (26% up from 19%, p = 0.045) among the remaining PTCs. Based on these changes in histologic features, 10% fewer cases were defined as ATA low risk (62% down from 72%, p = 0.0081). Our results indicate that the downgrading of some carcinomas to NIFTP will increase the rates of higher risk histologic parameters in the remaining PTCs by statistically significant margins. Although the overall survival for PTC is very high and would likely not be changed significantly by the introduction of NIFTP, additional studies evaluating the impact of the NIFTP shift are warranted.     

The effects of <Emphasis Type="Italic">SP110</Emphasis>’s associated genes on fresh cavitary pulmonary tuberculosis in Han Chinese population

SP110 is a promising anti-Mycobacterium tuberculosis (MTB) gene. To investigate the effects of SP110 and its associated genes, i.e., MYBBP1A and RELA, on pathological progression of MTB infection, an association study with 424 patients of fresh pulmonary tuberculosis (PTB) and 424 healthy controls was performed. Moreover, classification and regression tree and multifactor dimensionality reduction were employed to explore the effects of gene–gene interactions on cavitary PTB. The results indicated that both the heterozygous genotype GC and homozygous genotype CC in rs3809849 had significant effects on the risk of PTB (OR 1.42, 95 % CI 1.06–1.92, p 0.019; OR 1.55, 95 % CI 1.04–2.33, p = 0.033, respectively), and heterozygous genotype CT in rs9061 also had similar effects (OR 1.43, 95 % CI 1.07–1.90, p = 0.014). The rs3809849 and rs9905742 in MYBBP1A were also significantly associated with cavitary PTB (p = 0.00046 and 0.039, respectively), while rs9061 in SP110 had no such association (p = 0.06931) except its significant association with non-cavitary PTB (p = 0.0093). The interaction of MYBBP1A and RELA had significant effect on cavitary PTB (OR 4.24, 95 % CI 1.44–12.49, p = 0.005). These suggest that MYBBP1A instead of SP110 may be a genetic risk factor for cavitary PTB and play important effects on its whole progress.     

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.     

Differential role of Wnt signaling and base excision repair pathways in gastric adenocarcinoma aggressiveness

Aberrant activation of Wnt and base excision repair (BER) signaling pathways are implicated in tumor progression and chemotherapy resistance in gastric adenocarcinoma. This study was conducted to clarify the role of E2F6 and RhoA, components of the Wnt signaling pathway, and SMUG1, a component of the BER pathway in gastric adenocarcinoma. Expression levels and clinicopathological significance of three biomarkers, namely E2F6, RhoA, and SMUG1, as potential signaling molecules involved in tumorigenesis and aggressive behavior, were examined using tissue microarray. Our analysis showed a relative increase in the expression of E2F6 in gastric adenocarcinoma with no lymph node metastasis (χ ², P = 0.04 and OR, P = 0.08), while overexpression of RhoA and SMUG1 was found more often in the diffuse subtype of gastric adenocarcinoma as compared to the intestinal subtype (χ ², P = 0.05, OR, P = 0.08 and χ ², P = 0.001, OR, P = 0.009, respectively). Higher expression of RhoA was frequently seen in tumors with vascular invasion (χ ², P = 0.01 and OR, P = 0.01). In addition, increased expression of SMUG1 was found more often in poorly differentiated tumors (χ ², P = 0.01 and OR, P = 0.01). The distinct phenotype of E2F6^Low/SMUG1^High was more common in poorly differentiated tumors (P = 0.04) and with omental involvement (P = 0.01). The RhoA^High/SMUG1^High expression pattern was significantly more often found in diffuse subtype compared to the intestinal subtype (P = 0.001) as well as in poorly differentiated tumors (P = 0.004). The E2F6^Low/SMUG1^High and RhoA^High/SMUG1^High phenotypes can be considered as aggressive phenotypes of gastric adenocarcinoma. Our findings also demonstrated the synergistic effect of RhoA and SMUG1 in conferring tumor aggressiveness in diffuse subtype of gastric adenocarcinoma.     

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.     

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.     

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.     

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.

     

Glutathione S-transferases deletions may act as prognosis and therapeutic markers in breast cancer

Breast cancer (BC) is the main worldwide neoplasia in women. The metabolic balance between xenobiotic absorption and elimination rates plays an important role in preventing DNA damage and, consequently, tumor development. The glutathione S-transferases (GSTs), such as GSTM1 and GSTT1, and the NAD(P)H quinone oxidoreductase are important enzymes involved in phase II detoxification reactions. Deletions in GSTM1 and GSTT1, and single-nucleotide polymorphism (SNP) in NQO1 (rs1800655) have been investigated in cancer context, revealing conflicting results. The present study analyzed these genetic polymorphisms in 121 BC patients and 151 BC-free controls in order to verify if they could act as susceptibility modifiers and/or prognostic factors. Binary logistic regressions adjusted by age were performed to assess associations between allelic variants and interactions in polymorphisms combination with BC susceptibility, but no significant association was found. Genotypes distribution was also compared between BC subtypes, but no significant difference was observed (p > 0.05). GSTM1 deletion was significantly associated with histopathological grade, with a greater proportion of patients presenting grade III tumors (p = 0.007). Univariate analysis identified tumor size as the only clinicopathological parameter potentially associated with recurrence risk in patients that received adjuvant chemotherapy (p < 0.1). Thus, logistic regression analysis adjusted by tumor size revealed a positive association between GSTT1 deletion and recurrence risk in general BC (OR 4.25; p = 0.04), while GSTM1 was negatively associated with recurrence risk in ER/PR⁺HER2^? samples (OR 0.07; p = 0.03). In conclusion, the present study indicated that GSTT1 deletion was associated with increased recurrence risk, while GSTM1 correlated with worst prognosis parameters at diagnosis, but was negatively associated with recurrence risk in luminal subtype samples.     

Sporadic Gastric Well-Differentiated Neuroendocrine Tumors Have a Higher Ki-67 Proliferative Index

Well-differentiated neuroendocrine tumor (WDNET) of the stomach can arise in three distinct clinical settings: (1) in association with autoimmune atrophic gastritis, (2) in association with multiple neuroendocrine neoplasia type I (MEN I) or Zollinger-Ellison syndrome (ZES), or (3) sporadic. The Ki-67 proliferative index (PI) in gastric WDNETs in these three distinct clinical settings has not been evaluated in detail. Forty-five gastric WNETs underwent polypectomy (n = 4), endoscopic mucosal resection (n = 12), and surgical resection (n = 29) between 1994 and 2015 were included. H&E slides from each case were reviewed, and Ki-67 immunostain was performed on one representative tumor block. Ki-67 PI was determined by quantitative Aperio image analysis software in areas of strongest nuclear labeling (“hot spots”), and correlated with underlying clinical and pathological features. Twenty-one patients were male and 24 female with a median age of 57 years (range, 30–80 years). Tumors were classified as type I (n = 17), type II (n = 6), and type III (n = 22) WDNETs. Types II and III showed more advanced TNM stage compared to type I (p = 0.02, overall). WHO grade based on Ki-67 PI was higher in type III WDNETs [grade 1 (G1), n = 3; grade 2 (G2), n = 15; and grade 3 (G3), n = 4] than in type I WDNETs [G1, n = 5; G2, n = 12] and in type II WDNETs [G1, n = 2; G2, n = 4] (p = 0.050, overall). Ki-67 PI was significantly higher in type III WDNETs (mean ± SD = 13.0 ± 13.3 %) than in non-sporadic (type I and II) WDNETs (mean ± SD = 5.3 ± 3.3 %; p = 0.015). There was no difference in Ki-67 PI between type I WDNETs (mean ± SD = 5.2 ± 3.5 %) and type II WDNETs (mean ± SD = 5.6 ± 3.1%; p = 0.817). Higher Ki-67 PI was associated with higher tumor T stage (p = 0.003) and also tended to be associated with lymph node metastasis (p = 0.071). In the Kaplan-Meier survival analysis, type I was associated with a significantly longer disease-free survival (DFS) time compared to type II (p = 0.018) or III (0.010). Also, the WHO G3 group had a significantly shorter DFS time than the WHO G1 (p = 0.020) or G2 (p = 0.007) group. Gastric WDNET is a heterogeneous disease entity encompassing three clinical subtypes—type I, type II, and type III—having their own distinct clinicopathologic characteristics and prognosis. Our results showed that sporadic (type III) WDNET had a significantly higher Ki-67 PI than non-sporadic cases (type I or II); increased PI was associated with higher tumor stage. We also described four type III cases of morphologically WD gastric NET with WHO grade 3 on the basis of Ki-67 PI.     

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.     

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 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.     

Genetic association between TAP1 and TAP2 polymorphisms and ankylosing spondylitis: a systematic review and meta-analysis

Objectives

Ankylosing spondylitis (AS) is a chronic inflammatory joint disease. The transporter associated with antigen processing (TAP) has been identified to play an important role in immune response as well as the HLA-associated diseases. The aim of our meta-analysis was to investigate the contribution of TAP (TAP1 and TAP2) polymorphisms to the risk of AS.

Methods

Meta-analyses were performed between 2 polymorphisms in TAP1 (TAP1-333, -637) and 3 polymorphisms in TAP2 (TAP2-379, -565, and -665) and AS.

Results

The meta-analyses were involved with 6 studies with 415 cases and 659 controls. Significant association was found between TAP1-333Val, TAP1-637Gly, and TAP2-565Thr and AS compared with combined control group (TAP1-333Val: p = 0.009, OR = 1.40, 95% CI 1.09–1.80; TAP1-637Gly: p = 0.002, OR = 1.48, 95% CI 1.15–1.91; p = 0.03, OR = 1.38, 95% CI 1.04–1.84). Subgroup analysis shown that significant association was only found in AS when compared with HLA-B27-negative controls (TAP1-333Val: p = 0.004, OR = 1.53, 95% CI 1.14–2.06; TAP1-637Gly: p = 0.004, OR = 1.52, 95% CI 1.15–2.02; p = 0.02, OR = 1.56, 95% CI 1.09–2.24), but not in AS when compared with HLA-B27-positive controls (p > 0.05). Moreover, no significant associations were found between haplotypes in TAP1 and TAP2 in both the combined and the subgroup analyses (p > 0.05).

Conclusions

TAP1-333Val, TAP1-637Gly, and TAP2-565Thr were likely to be associated with AS.

     

<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.

     

Trunk Reaction Time and Kinematic Changes Following Slip Perturbations in Subjects with Recurrent Low Back Pain

Postural responses following slip perturbations are critical to fall prevention strategies. It is unclear how postural reactions with a handheld task can validly be transferred to treadmill-induced slip perturbations in subjects with recurrent low back pain (LBP). The purpose of this study was to investigate trunk reaction times and trunk flexion angle as well as velocity following the slips between subjects with and without LBP. There were 29 subjects with LBP and 40 control subjects who participated in the study. Three levels of consecutive treadmill-induced slip perturbations were introduced at level 1 (duration: 0.10 s, velocity: 0.24 m/s, displacement: 1.20 cm), level 2 (0.12 s, 0.72 m/s, 4.32 cm), and level 3 (0.12 s, 1.37 m/s, 8.22 cm). The trunk reaction time, swing/step times, and trunk flexion angle as well as velocity at heel strike/toe-off were compared between the groups. There were significantly longer trunk reaction times (t = ? 2.03, p = 0.04), swing times (t = ? 2.63, p = 0.01), and step times (t = ? 2.53, p = 0.01) in the LBP group at the level 1 slip perturbation. The groups demonstrated a significant interaction between the levels and trunk flexion angles (F = 4.72, p = 0.03), but there was no interaction between the levels and trunk flexion velocities (F = 0.07, p = 0.79). The LBP group demonstrated longer reaction times at the level 1 perturbation due to a possible pain recurrence. However, this compensatory tolerance was limited at the level 3 perturbation due to increased trunk flexion angle at heel strike and toe-off in the LBP group. Clinicians may consider a compensatory strategy to improve reaction time and minimize trunk flexion following slip perturbations in patients with LBP.     

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 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.     

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.