Heart Failure Induces Significant Changes in Nuclear Pore Complex of Human Cardiomyocytes

Aims

The objectives of this study were to analyse the effect of heart failure (HF) on several proteins of nuclear pore complex (NPC) and their relationship with the human ventricular function.

Methods and Results

A total of 88 human heart samples from ischemic (ICM, n = 52) and dilated (DCM, n = 36) patients undergoing heart transplant and control donors (CNT, n = 9) were analyzed by Western blot. Subcellular distribution of nucleoporins was analysed by fluorescence and immunocytochemistry. When we compared protein levels according to etiology, ICM showed significant higher levels of NDC1 (65%, p<0.0001), Nup160 (88%, p<0.0001) and Nup153 (137%, p = 0.004) than those of the CNT levels. Furthermore, DCM group showed significant differences for NDC1 (41%, p<0.0001), Nup160 (65%, p<0.0001), Nup153 (155%, p = 0.006) and Nup93 (88%, p<0.0001) compared with CNT. However, Nup155 and translocated promoter region (TPR) did not show significant differences in their levels in any etiology. Regarding the distribution of these proteins in cell nucleus, only NDC1 showed differences in HF. In addition, in the pathological group we obtained good relationship between the ventricular function parameters (LVEDD and LVESD) and Nup160 (r = −0382, p = 0.004; r = −0.290, p = 0.033; respectively).

Conclusions

This study shows alterations in specific proteins (NDC1, Nup160, Nup153 and Nup93) that compose NPC in ischaemic and dilated human heart. These changes, related to ventricular function, could be accompanied by alterations in the nucleocytoplasmic transport. Therefore, our findings may be the basis for a new approach to HF management.     

Long-Term Prognostic Value of Restitution Slope in Patients with Ischemic and Dilated Cardiomyopathies

Background

An action potential duration (APD) restitution curve with a steep slope ≥1 has been associated with increased susceptibility for malignant ventricular arrhythmias. We aimed to evaluate the “restitution hypothesis” and tested ventricular APD restitution slope as well as effective refractory period (ERP)/APD ratio for long-term prognostic value in patients with ischemic (ICM) or dilated cardiomyopathy (DCM).

Methodology/Principal Findings

Monophasic action potentials were recorded in patients with ICM (n = 32) and DCM (n = 42) undergoing routine programmed ventricular stimulation (PVS). Left ventricular ejection fraction was 32±7% and 28±9%, respectively. APD and ERP were measured at baseline stimulation (S₁) and upon introduction of one to three extrastimuli (S₂–S₄). ERP/APD ratios and the APD restitution curve were calculated and the maximum restitution slope was determined. After a mean follow-up of 6.1±3.0 years, the combined end-point of mortality and and/or implantable cardioverter-defibrillator shock was not predicted by restitution slope or ERP/APD ratios. Comparing S₂ vs. S₃ vs. S₄ extrastimuli for restitution slope (1.5±0.6 vs. 1.4±0.4 vs. 1.3±0.5; p = NS), additional extrastimuli did not lead to a steepening restitution slope. ERP/APD ratio decreased with additional extrastimuli (0.98±0.09 [S₁] vs. 0.97±0.10 [S₂] vs. 0.93±0.11 [S₃]; p = 0.03 S₁ vs. S₃). Positive PVS was strongly predictive of outcome (p = 0.006).

Conclusions/Significance

Neither ventricular APD restitution slope nor ERP/APD ratios predict outcome in patients with ICM or DCM.     

Heart Mitochondrial Proteome Study Elucidates Changes in Cardiac Energy Metabolism and Antioxidant PRDX3 in Human Dilated Cardiomyopathy

Background

Dilated cardiomyopathy (DCM) is a public health problem with no available curative treatment, and mitochondrial dysfunction plays a critical role in its development. The present study is the first to analyze the mitochondrial proteome in cardiac tissue of patients with DCM to identify potential molecular targets for its therapeutic intervention.

Methods and Results

16 left ventricular (LV) samples obtained from explanted human hearts with DCM (n = 8) and control donors (n = 8) were extracted to perform a proteomic approach to investigate the variations in mitochondrial protein expression. The proteome of the samples was analyzed by quantitative differential electrophoresis and Mass Spectrometry. These changes were validated by classical techniques and by novel and precise selected reaction monitoring analysis and RNA sequencing approach increasing the total heart samples up to 25. We found significant alterations in energy metabolism, especially in molecules involved in substrate utilization (ODPA, ETFD, DLDH), energy production (ATPA), other metabolic pathways (AL4A1) and protein synthesis (EFTU), obtaining considerable and specific relationships between the alterations detected in these processes. Importantly, we observed that the antioxidant PRDX3 overexpression is associated with impaired ventricular function. PRDX3 is significantly related to LV end systolic and diastolic diameter (r = 0.73, p value<0.01; r = 0.71, p value<0.01), fractional shortening, and ejection fraction (r = −0.61, p value<0.05; and r = −0.62, p value<0.05, respectively).

Conclusion

This work could be a pivotal study to gain more knowledge on the cellular mechanisms related to the pathophysiology of this disease and may lead to the development of etiology-specific heart failure therapies. We suggest new molecular targets for therapeutic interventions, something that up to now has been lacking.     

The Diverse Distribution of Risk Factors between Breast Cancer Subtypes of ER,PR and HER2: A 10-Year Retrospective Multi-Center Study in China

Introduction

Hormone receptors, human epidermal growth factor receptor 2 and some risk factors determine therapies and prognosis of breast cancer. The risk factors distributed differently between patients with receptors. This study aimed to investigate the distribution of risk factors between subtypes of breast cancer by the 3 receptors in Chinese native women with a large sample size.

Methods

The multi-center study analyzed 4211 patient medical records from 1999 to 2008 in 7 regions of China. Data on patients’ demographic information, risk factors (menopausal status, parity, body mass index) and receptor statuses were extracted. Breast cancer subtypes included ER (+/−), PR (+/−), HER2 (+/−), 4 ER/PR and 4 molecular subtypes. Wilcoxon and Chi-square tests were used to estimate the difference. The unconditional logistic regression model was used for analysis, and presented p-value after Bonferroni correction in the results.

Results

Compared to patients with negative progesterone receptor, the positive patients were younger at diagnosis, and reported less likely in postmenopausal status and lower parity (p<0.05). Comparing with the subtype of ER+/PR+, ER+/PR− subtype were 4-year older at diagnosis (OR = 1.02), more likely to be postmenopausal (OR = 1.91) and more likely to have >1 parity (OR = 1.36) (p<0.05); ER−/PR− subtype were more likely to be postmenopausal (OR = 1.33) and have >1 parity (OR = 1.19) (p<0.05). In contrast to the luminal A subtype, triple negative subtype had a lower BMI (OR = 0.96) and ORs of overweight and obesity reduced by >20% (p<0.05).

Conclusion

In this study, it was found that Chinese female patients did have statistically significant differences of age, menopausal status, parity and body mass index between breast cancer subtypes. Studies are warranted to further investigate the risk factors between subtypes, which was meaningful for prevention and treatment among Chinese females.     

Passive Smoking Exposure from Partners as a Risk Factor for ER+/PR+ Double Positive Breast Cancer in Never-Smoking Chinese Urban Women: A Hospital-Based Matched Case Control Study

Background

The relationship between passive smoking exposure (PSE) and breast cancer risk is of major interest.

Objective

To evaluate the relationship between PSE from partners and breast cancer risk stratified by hormone-receptor (HR) status in Chinese urban women population.

Design

Hospital-based matched case control study.

Setting

Chinese urban breast cancer patients without current or previous active smoking history in China Medical University 1st Hospital, Liaoning Province, China between Jan 2009 and Nov 2009.

Patients

Each breast cancer patient was matched 1∶1 with healthy controls by gender and age (±2 years) from the same hospital.

Measurements

The authors used unconditional logistic regression analyses to estimate odds ratio for women with PSE from partners and breast cancer risk.

Results

312 pairs were included in the study. Women who endured PSE had significantly increased risk of breast cancer (adjusted OR: 1.46; 95% CI: 1.05–2.03; P = 0.027), comparing with unexposed women. Women who exposed to >5 cigarettes/day also had significant increased risk (adjusted OR: 1.99; 95% CI: 1.28–3.10; P = 0.002), as were women exposed to passive smoke for 16–25 years (adjusted OR: 1.87 95% CI: 1.22–2.86; P = 0.004), and those exposed to > 4 pack-years (adjusted OR: 1.71 95% CI: 1.17–2.50; P = 0.004). Similar trends were significant for estrogen receptor (ER)/progesterone receptor (PR) double positive subgroup(adjusted OR: 1.71; 2.20; 1.99; 1.92, respectively), but not for ER+/PR−, ER−/PR+, or ER−/PR− subgroups.

Limitations

limitations of the hospital-based retrospective study, lack of information on entire lifetime PSE and low statistical power.

Conclusions

Our findings provide further evidence that PSE from partners contributes to increased risk of breast cancer, especially for ER/PR double positive breast cancer, in Chinese urban women.     

Gene Expression Signatures That Predict Outcome of Tamoxifen-Treated Estrogen Receptor-Positive,High-Risk,Primary Breast Cancer Patients: A DBCG Study

Background

Tamoxifen significantly improves outcome for estrogen receptor-positive (ER+) breast cancer, but the 15-year recurrence rate remains 30%. The aim of this study was to identify gene profiles that accurately predicted the outcome of ER+ breast cancer patients who received adjuvant Tamoxifen mono-therapy.

Methodology/Principal Findings

Post-menopausal breast cancer patients diagnosed no later than 2002, being ER+ as defined by >1% IHC staining and having a frozen tumor sample with >50% tumor content were included. Tumor samples from 108 patients treated with adjuvant Tamoxifen were analyzed for the expression of 59 genes using quantitative-PCR. End-point was clinically verified recurrence to distant organs or ipsilateral breast. Gene profiles were identified using a model building procedure based on conditional logistic regression and leave-one-out cross-validation, followed by a non-parametric bootstrap (1000x re-sampling). The optimal profiles were further examined in 5 previously-reported datasets containing similar patient populations that were either treated with Tamoxifen or left untreated (n = 623). Three gene signatures were identified, the strongest being a 2-gene combination of BCL2-CDKN1A, exhibiting an accuracy of 75% for prediction of outcome. Independent examination using 4 previously-reported microarray datasets of Tamoxifen-treated patient samples (n = 503) confirmed the potential of BCL2-CDKN1A. The predictive value was further determined by comparing the ability of the genes to predict recurrence in an additional, previously-published, cohort consisting of Tamoxifen-treated (n = 58, p = 0.015) and untreated patients (n = 62, p = 0.25).

Conclusions/Significance

A novel gene expression signature predictive of outcome of Tamoxifen-treated patients was identified. The validation suggests that BCL2-CDKN1A exhibit promising predictive potential.     

Blood Monocyte Chemotactic Protein-1 (MCP-1) and Adapted Disease Activity Score28-MCP-1: Favorable Indicators for Rheumatoid Arthritis Activity

Objective

We assessed blood pentraxin 3 (PTX3) and macrophage chemotactic factor-1 (MCP-1) levels as indicators of disease activity in rheumatoid arthritis (RA) patients, because data on disease activity score 28 (DAS28)-erythrocyte sedimentation rate (ESR) and DAS28-C-reactive protein (CRP) are still imperfect.

Methods

In 111 patients with RA, we examined longitudinal and cross-sectional correlations of blood PTX3, MCP-1, CRP, and ESR levels with measures of clinical arthritic activity, namely, swollen joint count (SJC), tender joint count (TJC), visual analog scale for general health (GH), DAS28, and adapted DAS28-MCP-1.

Results

Blood MCP-1, but not PTX3, was significantly correlated with SJC, TJC, DAS28, and DAS28-CRP. DAS28-MCP-1 was strongly correlated with DAS28 (r  = 0.984, P<0.001) and DAS28-CRP (r  = 0.971, P<0.001), and modestly correlated with CRP (r  = 0.350, P<0.001), and ESR (r  = 0.386, P<0.001). Similarly, the duration of arthritic symptoms, but not sex, was significantly correlated with variables of arthritic activity. In particular, DAS28-MCP-1 significantly correlated with DAS28 during a 6-month period (r  = 0.944, P<0.001; r  = 0.951, P<0.001; r  = 0.862, P<0.001; and r  = 0.865, P<0.001 for month 0, 1, 3, and 6, respectively).

Conclusion

Blood MCP-1 and adapted DAS28-MCP-1, but not blood PTX3, may be useful in monitoring RA activity.     

Expression of Autophagy-Related Proteins According to Androgen Receptor and HER-2 Status in Estrogen Receptor-Negative Breast Cancer

Purpose

The purpose of this study was to investigate the expression of autophagy-related proteins in relation to androgen receptor (AR) status in estrogen receptor (ER)-negative breast cancers.

Methods

We extracted 334 ER-negative breast cancer samples to construct tissue microarrays (TMAs), which were immunohistochemically stained for autophagy-related proteins (beclin-1, LC3A, LC3B, p62) and for AR and HER-2.

Results

There were 127 AR-positive cases and 207 AR-negative cases, and 140 HER-2-positive cases and 194 HER-2 negative cases. The AR-negative group was associated with tumoral LC3A expression (P<0.001), while the AR-positive group was associated with tumoral BNIP3 expression (P<0.001). Tumoral LC3A was most highly expressed in the AR-negative and HER-2 negative group, while stromal LC3A showed the highest expression in the AR-negative and HER-2-positive group. Tumoral BNIP3 and stromal BNIP3 were highest in the AR-positive and HER-2-negative group. In the AR-positive and HER-2-negative group, stromal p62 positivity was an independent factor that was statistically significant in its association with shorter disease-free survival (DFS) (Hazard ratio: 10.21, 95% CI: 1.130–92.31, P = 0.039). Shorter DFS was associated with tumoral LC3A positivity (Hazard ratio: 10.28, 95% CI: 2.068–51.19, P = 0.004) in the AR-negative and HER-2-positive group.

Conclusion

In ER-negative breast cancers, AR status was associated with expression of different types of autophagy-related proteins. Tumoral LC3A was most highly expressed in AR-negative breast cancers, while tumor BNIP3 was highest in AR-positive breast cancers.     

Long-Term Prognostic Performance of Ki67 Rate in Early Stage,pT1-pT2, pN0, Invasive Breast Carcinoma

Background

Molecular signatures may become of use in clinical practice to assess the prognosis of breast cancers. However, although international consensus conferences sustain the use of these new markers in the near future, concerns remain about their degree of discordance and cost-effectiveness in different international settings. The present study aims to validate Ki67 as prognostic factor in a large cohort of early-stage (pT1–pT2, pN0) breast cancer patients.

Methods

456 patients treated in 1995–1996 were identified in the Institut Curie database. Ki67 (MIB1) was retrospectively assessed by immunohistochemistry for all cases. The prognostic value of this index was compared to that of histological grade (HG), Estrogen receptor (ER) and HER2 status. Distant disease free interval, loco-regional recurrence, time-lapse from first metastatic diagnosis to death were analyzed.

Results

All 456 patients were treated by lumpectomy plus axillary dissection and radiotherapy. 27 patients (5.9%) received systemic treatment. Tumors were classified as HG1 in 35%, HG2 in 42% and HG3 in 23% of cases. ER was expressed in 86% of the tumors, HER2 in 5% and 14% were triple negative. The median follow-up was 151 [5–191] months. Distant and loco-regional disease recurrences were observed in 16% and 18%, respectively. High (>20%) Ki67 rate [HR = 3 (1.8–4.8), p<10e−06] and HG3 [HR = 4.4 (2.2–8.6), p = 0.00002] were associated with an increased rate of distant relapse. In multivariate analysis, the Ki67 remained the only significant prognostic factor in the subgroups of ER positive HER2 negative [HR = 2.6 (1.5–4.6), p = 0.0006] and ER positive HER2 negative HG2 tumors [HR = 2.2 (1.01–4.8), p = 0.04].

Conclusions

We validate the prognosis value of the Ki67 rate in small size node negative breast cancer. We conclude that Ki67 is a potential cost-effective decision marker for adjuvant therapy in early-stage HG2, pT1–pT2, pN0, breast cancers.     

Finger Position Alters the Median Nerve Properties within the Carpal Tunnel: A Pre-Post MRI Comparison Study

Purpose

The purpose of this study was to compare the properties of the median nerve and the flexor retinaculum within the carpal tunnel with Magnetic Resonance Imaging (MRI) under two conditions: (a) fingers extended, and (b) fingers in an isometric squeeze grip.

Methods

Thirty-Four volunteers participated in this experimental study. The flexor retinaculum and median nerve characteristics were measured during both conditions using MRI.

Results

The isometric squeeze grip condition resulted in significant palmar bowing of the flexor retinaculum (t = 7.67, p<.001), a significant flattening-ratio of the median nerve (t = 4.308, p<.001), and no significant decrease in the cross-sectional area of the median nerve (t = 2.508, p = 0.017).

Conclusion

The isometric squeeze grip condition resulted in anatomical deformations within the carpal tunnel, possibly explained by the lumbrical muscles incursion into the carpal tunnel during finger flexion.     

Radiation-Induced Temporal Lobe Injury for Nasopharyngeal Carcinoma: A Comparison of Intensity-Modulated Radiotherapy and Conventional Two-Dimensional Radiotherapy

Background

To compare the radiation-induced temporal lobe injury (TLI) in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT) or two-dimensional conventional radiotherapy (2D-CRT).

Patients and Methods

1276 cases of NPC treated with IMRT or 2D-CRT were retrospectively reviewed. A diagnosis of TLI was made on follow-up magnetic resonance imaging (MRI).

Results

The crude incidence of TLI was 7.5% and 10.8% (P = 0.048), and the actuarial 5-year incidence was 16% and 34.9% (P<0.001) for the IMRT and 2D-CRT groups, respectively. Multivariate analysis revealed both T stage (P<0.001) and radiation technique (P<0.001) as independent predictors. Patients with T1, T2 and T3 disease had a significantly higher risk when treated with 2D-CRT (P = 0.005, 0.016, <0.001, respectively). This trend was not evident for T4 patients (P = 0.680). The 2D-CRT group had a longer latency for the development of TLI (P<0.001). Those with T4 disease had a shorter median time to TLI (P = 0.006, 0.042, <0.001 when compared with T1, T2 and T3, respectively).

Conclusions

IMRT is superior to 2DRT for the management of T1-T3 NPC in terms of sparing the temporal lobe. The high incidence of TLI in T4 disease needs to be addressed.     

The Pretreatment Albumin to Globulin Ratio Has Predictive Value for Long-Term Mortality in Nasopharyngeal Carcinoma

Background

Low serum albumin is predictive of poor survival in nasopharyngeal carcinoma (NPC). We evaluated the ability of the pretreatment albumin/globulin ratio (AGR) to predict long-term mortality in patients with NPC.

Methods

This retrospective study examined an unselected cohort of 694 patients with NPC who had documented pretreatment total serum protein and serum albumin levels (ALB). AGR was calculated as [AGR = ALB/(total serum protein - ALB)]. Survival analysis was used to evaluate the predictive value of AGR.

Results

Multivariate analysis demonstrated that a low pretreatment serum AGR (<1.4) was an independent predictor of poor OS (P  = 0.029) and DMFS (P  = 0.033). A low AGR was significantly associated with advanced stage disease (P<0.001), high white blood cell count (P  = 0.033), high neutrophil count (P  = 0.047), high total serum protein (P<0.001) and low ALB (P<0.001).

Conclusion

The pretreatment AGR may represent a simple, potentially useful predictive biomarker for evaluating the long-term prognosis of patients with undifferentiated NPC.     

Association between MLH1 -93G>A Polymorphism and Risk of Colorectal Cancer

Background

The -93G>A (rs1800734) polymorphism located in the promoter of mismatch repair gene, MLH1, has been identified as a low-penetrance variant for cancer risk. Many published studies have evaluated the association between the MLH1 -93G>A polymorphism and colorectal cancer (CRC) risk. However, the results remain conflicting rather than conclusive.

Objective

The aim of this study was to assess the association between the MLH1 -93G>A polymorphism and the risk of CRC.

Methods

To derive a more precise estimation of the association, a meta-analysis of six studies (17,791 cases and 13,782 controls) was performed. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of the association. Four of these published studies were performed on subjects of known microsatellite instability (MSI) status. An additional analysis including 742 cases and 10,895 controls was used to assess the association between the MLH1 -93G>A polymorphism and the risk of MSI-CRC.

Results

The overall results indicated that the variant genotypes were associated with a significantly increased risk of CRC (AG versus GG: OR = 1.06, 95% CI = 1.01–1.11; AA/AG versus GG: OR = 1.06, 95% CI = 1.01–1.11). This increased risk was also found during stratified analysis of MSI status (AA versus GG: OR = 2.52, 95% CI = 1.94–3.28; AG versus GG: OR = 1.29, 95% CI = 1.10–1.52; AA/AG versus GG: OR = 1.45, 95% CI = 1.24–1.68; AA versus AG/GG: OR = 2.29, 95% CI = 1.78–2.96). Egger’s test did not show any evidence of publication bias.

Conclusion

Our results suggest that the MLH1 -93G>A polymorphism may contribute to individual susceptibility to CRC and act as a risk factor for MSI-CRC.     

Polymorphisms in ERCC1 and XPF Genes and Risk of Gastric Cancer in an Eastern Chinese Population

Background

Inherited functional single nucleotide polymorphisms (SNPs) in DNA repair genes may alter DNA repair capacity and thus contribute to cancer risk.

Methods

Three ERCC1 functional SNPs (rs2298881C>A, rs3212986C>A and rs11615G>A) and two XPF/ERCC4 functional SNPs (rs2276466C>G and rs6498486A>C) were genotyped for 1125 gastric adenocarcinoma cases and 1196 cancer-free controls by Taqman assays. Odds ratios (OR) and 95% confidence intervals (CI) were used to estimate risk associations, and false-positive report probabilities (FPRP) were calculated for assessing significant findings.

Results

ERCC1 rs2298881C and rs11615A variant genotypes were associated with increased gastric cancer risk (adjusted OR = 1.33, 95% CI = 1.05–1.67 for rs2298881 AC/CC and adjusted OR = 1.23, 95% CI = 1.05–1.46 for rs11615 AG/AA, compared with their common genotype AA and GG, respectively). Patients with 2–3 ERCC1 risk genotypes had significant increased risk (adjusted OR = 1.56, 95% CI = 1.27–1.93), compared with those with 0–1 ERCC1 risk genotypes, and this risk was more significantly in subgroups of never drinkers, non-gastric cardia adenocarcinoma (NGCA) and clinical stage I+II. All these risks were not observed for XPF SNPs.

Conclusions

These findings suggest that functional ERCC1 SNPs may contribute to risk of gastric cancer. Larger and well-designed studies with different ethnic populations are needed to validate our findings.     

miR-485-5p Binding Site SNP rs8752 in HPGD Gene Is Associated with Breast Cancer Risk

Background

Single nucleotide polymorphisms (SNPs) that reside in microRNA target sites may play an important role in breast cancer development and progression. To reveal the association between microRNA target site SNPs and breast cancer risk, we performed a large case-control study in China.

Methods

We performed a two-stage case-control study including 2744 breast cancer cases and 3125 controls. In Stage I, we genotyped 192 SNPs within microRNA binding sites identified from the “Patrocles” database using custom Illumina GoldenGate VeraCode assays on the Illumina BeadXpress platform. In Stage II, genotyping was performed on SNPs potentially associated with breast cancer risk using the TaqMan platform in an independent replication set.

Results

In stage I, 15 SNPs were identified to be significantly associated with breast cancer risk (P<0.05). In stage II, one SNP rs8752 was replicated at P<0.05. This SNP is located in the 3’ untranslated region (UTR) of the 15-hydroxyprostaglandin dehydrogenase (HPGD) gene at 4q34-35, a miR-485-5p binding site. Compared with the GG genotype, the combined GA+AA genotypes has a significantly higher risk of breast cancer (OR = 1.18; 95% CI: 1.06-1.31, P = 0.002). Specifically, this SNP was associated with estrogen receptor (ER) positive breast cancer (P = 0.0007), but not with ER negative breast cancer (P = 0.23), though p for heterogeneity not significant.

Conclusion

Through a systematic case-control study of microRNA binding site SNPs, we identified a new breast cancer risk variant rs8752 in HPGD in Chinese women. Further studies are warranted to investigate the underling mechanism for this association.     

Factors Associated with Lung Function Decline in Patients with Non-Tuberculous Mycobacterial Pulmonary Disease

Background

There is paucity of risk factors on lung function decline among patients with non-tuberculous mycobacteria (NTM) pulmonary disease in literature.

Methods

Patients with NTM pulmonary disease between January 2000 and April 2011 were retrospectively selected. Sixty-eight patients had at least two pulmonary function tests within a mean follow-up period of 47 months.

Results

Sixty-eight patients were included. They had a median age of 65 years and 65% had impaired lung function (Forced expiratory volume in 1 second [FEV₁] <80% of predicted value). The mean FEV₁ decline was 48 ml/year. By linear regression, younger age (beta: 0.472, p<0.001), initial FEV₁>50% of predicted value (beta: 0.349, p = 0.002), male sex (beta: 0.295, p = 0.018), bronchiectasis pattern (beta: 0.232, p = 0.035), and radiographic score >3 (beta: 0.217, p = 0.049) were associated with greater FEV₁ decline. Initial FEV₁>50% of predicted value (beta: 0.263, p = 0.032) was also associated with greater FVC annual decline, whereas M. kansasii pulmonary disease was marginally associated with greater annual FVC decline (beta: 0.227, p = 0.062).

Conclusions

NTM pulmonary disease is associated with greater decline in lung function in patients who are young, male, with bronchiectasis, and with a high radiographic score. Special attention should be given to patients with these risk factors.     

TERT-CLPTM1L Rs401681 C>T Polymorphism Was Associated with a Decreased Risk of Esophageal Cancer in a Chinese Population

Background

Esophageal cancer was the fifth most commonly diagnosed cancer and the fourth leading cause of cancer-related death in China in 2009. Esophageal squamous cell carcinoma (ESCC) accounts for more than 90 percent of esophageal cancers. Genetic factors probably play an important role in the ESCC carcinogenesis.

Methods

We conducted a hospital based case-control study to evaluate functional hTERT rs2736098 G>A and TERT-CLPTM1L rs401681 C>T single nucleotide polymorphisms (SNPs) on the risk of ESCC. Six hundred and twenty-nine ESCC cases and 686 controls were recruited. Their genotypes were determined using the ligation detection reaction (LDR) method.

Results

When the TERT-CLPTM1L rs401681 CC homozygote genotype was used as the reference group, the CT genotype was associated with a significantly decreased risk of ESCC (adjusted OR  = 0.74, 95% CI  = 0.58–0.94, p = 0.012); the CT/TT variants were associated with a 26% decreased risk of ESCC (adjusted OR  = 0.74, 95% CI  = 0.59–0.93, P = 0.009). The significantly decreased risk of ESCC associated with the TERT-CLPTM1L rs401681 C>T polymorphism was associated with male sex, young age (<63 years in our study) and alcohol consumption. No association between the hTERT rs2736098 G>A polymorphism and ESCC risk was observed.

Conclusion

TERT-CLPTM1L rs401681 CT and CT/TT genotypes were associated with decreased risk of ESCC, particularly among men, young patients and those reported to be drinkers. However, our results are preliminary conclusions. Larger studies with more rigorous study designs are required to confirm the current findings.     

Ex Vivo Effect of Varespladib on Secretory Phospholipase A2 Alveolar Activity in Infants with ARDS

Background

Secretory phospholipase A2 (sPLA2) plays a pivotal role in acute respiratory distress syndrome (ARDS). This enzyme seems an interesting target to reduce surfactant catabolism and lung tissue inflammation. Varespladib is a specifically designed indolic sPLA2 inhibitor, which has shown promising results in animals and adults. No specific data in pediatric ARDS patients are yet available.

Methods

We studied varespladib in broncho-alveolar lavage (BAL) fluids obtained ex vivo from pediatric ARDS patients. Clinical data and worst gas exchange values during the ARDS course were recorded. Samples were treated with saline or 10–40–100 µM varespladib and incubated at 37°C. Total sPLA2 activity was measured by non-radioactive method. BAL samples were subjected to western blotting to identify the main sPLA isotypes with different sensitivity to varespladib. Results was corrected for lavage dilution using the serum-to-BAL urea ratio and for varespladib absorbance.

Results

Varespladib reduces sPLA2 activity (p<0.0001) at 10,40 and 100 µM; both sPLA2 activity reduction and its ratio to total proteins significantly raise with increasing varespladib concentrations (p<0.001). IC₅₀ was 80 µM. Western blotting revealed the presence of sPLA2-IIA and –IB isotypes in BAL samples. Significant correlations exist between the sPLA2 activity reduction/proteins ratio and PaO₂ (rho = 0.63;p<0.001), PaO₂/FiO₂ (rho = 0.7; p<0.001), oxygenation (rho = −0.6; p<0.001) and ventilation (rho = −0.4;p = 0.038) indexes.

Conclusions

Varespladib significantly inhibits sPLA2 in BAL of infants affected by post-neonatal ARDS. Inhibition seems to be inversely related to the severity of gas exchange impairment.     

Salt-Restriction-Spoon Improved the Salt Intake among Residents in China

Objective

To evaluate the effect of an improved salt-restriction spoon on the attitude of salt-restriction, the using rate of salt-restriction-spoon, the actual salt intake, and 24-hour urinary sodium excretion (24HUNa).

Design

A community intervention study.

Setting

Two villages in Beijing.

Participants

403 local adult residents being responsible for home cooking.

Intervention

Participants were randomly assigned to the intervention group or the control group. Those in the intervention group were provided with an improved salt-restriction-spoon and health education, and were informed of their actual salt intake and 24HUNa. Not any intervention was given to those in the control group.

Main Outcome Measures

The scores on the variables of Health Belief Model, the using rate of salt-restriction-spoon, the actual salt intake, and 24HUNa.

Analysis

Covariance analyses, Chi-square tests, Student’s t tests, and repeated measures analyses of variance.

Results

After 6 months of intervention, the intervention group felt significantly less objective barriers, and got access to significantly more cues to action as compared to the control group. The using rate and the correctly using rate of salt-restriction-spoon were significantly higher in the intervention group. The daily salt intake decreased by 1.42 g in the intervention group and by 0.28 g in the control group, and repeated measures analysis of variance showed significant change over time (F = 7.044, P<0.001) and significant difference between groups by time (F = 2.589, P = 0.041). The 24HUNa decreased by 34.84 mmol in the intervention group and by 33.65 mmol in the control group, and repeated measures analysis of variance showed significant change over time (F = 14.648, P<0.001) without significant difference between groups by time (F = 0.222, P = 0.870).

Conclusions

The intervention effect was acceptable, therefore, the improved salt-restriction-spoon and corresponding health education could be considered as an alternative for salt reduction strategy in China and other countries where salt intake comes mainly from home cooking.