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Objectives: On December 1, 2015, the Japanese government launched the Stress Check Program, a new occupational health policy to screen employees for high psychosocial stress in the workplace. As only weak evidence exists for the effectiveness of the program, we sought to estimate the risk of stress-associated long-term sickness absence as defined in the program manual., Methods: Participants were 7356 male and 7362 female employees in a financial service company who completed the Brief Job Stress Questionnaire (BJSQ). We followed them for 1 year and used company records to identify employees with sickness absence of 1 month or longer. We defined high-risk employees using the BJSQ and criteria recommended by the program manual. We used the Cox proportional regression model to evaluate the prospective association between stress and long-term sickness absence., Results: During the follow-up period, we identified 34 male and 35 female employees who took long-term sickness absence. After adjustment for age, length of service, job type, position, and post-examination interview, hazard ratios (95% confidence intervals) for incident long-term sickness absence in high-stress employees were 6.59 (3.04-14.25) for men and 2.77 (1.32-5.83) for women. The corresponding population attributable risks for high stress were 23.8% (10.3-42.6) for men and 21.0% (4.6-42.1) for women., Conclusions: During the 1-year follow-up, employees identified as high stress (as defined by the Stress Check Program manual) had significantly elevated risks for long-term sickness absence.

Background: Lymph nodal (LN) metastasis, classified as pN1b, is considered as an independent poor prognostic factor for Papillary thyroid carcinoma (PTC) patients. However, whether LN metastasis can serve as a predictive factor for recurrence or disease-free survival of N1b PTC is still plagued by controversy., Methods: The N1b PTC patients who underwent total thyroidectomy and unilateral modified radical neck dissection (MRND) by the same surgical team in Ningbo NO.2 Hospital from March, 1998 to March, 2015 were included in this study. The clinical and pathological characteristics of each patient were recorded in detail. Univariate and multivariate Cox proportional hazards regression models were performed to analyze the associations between clinicopathological characteristics with recurrence. Kaplan-Meier analysis and log-rank test were used for the analysis of overall RFS and level V metastasis., Results: A total of 214 patients were eligible for the final analyses. Of the 214 finally included patients with N1b PTC, 39 patients were classified with recurrence and 175 without recurrence. The final univariate and multiple Cox proportional hazards analysis only suggested level V metastasis as the independent predictive factor of N1b PTC recurrence (HR: 4.11; 95% CI:1.22-11.05, P=0.028). The patients with level V metastasis showed a significantly lower 10-year RFS rate (P=0.031) as illustrated by Kaplan-Meier analysis and log-rank test., Conclusion: Level V metastasis is a novel indicator for tumor recurrence and 10-year RFS in patients with N1b PTC., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Developmental defects of the enamel (DDE) commonly occur in the primary dentition. Although several cross-sectional studies have shown the association of DDE with caries, there is a paucity of longitudinal studies demonstrating that teeth with DDE are at greater risk of caries than are normal teeth. Therefore, the aim of the present study was to longitudinally track a total of 14,220 primary teeth in 725 children from a large birth cohort study, who were interviewed by telephone or home visits at 6-mo intervals. There were 74 children with at least 1 tooth with DDE. We compared teeth with and without DDE by calculating hazard ratios for caries using a Cox proportional hazards model and by plotting caries-free probabilities by child's age for DDE categories in a Kaplan-Meier plot. Our results show that teeth with DDE had a much higher risk for caries and developed caries earlier than did teeth without DDE. The hazard ratios (95% confidence intervals) for caries were 6.0 (2.4 to 14.6; P < 0.001) for pits, 5.5 (3.8 to 7.8; P < 0.001) for missing enamel, and 4.5 (1.8 to 11.3; P < 0.002) for hypoplasia occurring with yellow-brown opacities. Kaplan-Meier survival plots of caries-free probabilities by age, depending on DDE type, suggest that all types of enamel hypoplasia are associated with a statistically significant increased risk for caries. The study provides longitudinal evidence that DDE are a strong determinant for caries in the primary dentition (ACTRN No. 012606000356561). Knowledge Transfer Statement: The study provides longitudinal evidence that developmental defects of enamel of the primary dentition are strongly associated with increased risk of early childhood caries.

Breast cancer is a heterogeneous disease associated with diverse clinical, biological and molecular features, presenting huge challenges for prognosis and treatment. Here we found that perilipin-1 (PLIN1) mRNA expression is significantly downregulated in human breast cancer. Kaplan-Meier analysis indicated that patients presenting with reduced PLIN1 expression exhibited poorer overall metastatic relapse-free survival (p = 0.03). Further Cox proportional hazard models analysis revealed that the reduced expression of PLIN1 is an independent predictor of overall survival in estrogen receptor positive (p < 0.0001, HR = 0.87, 95% CI = 0.81-0.92, N = 3,600) and luminal A-subtype (p = 0.02, HR = 0.88, 95% CI = 0.78-0.98, N = 1,469) breast cancer patients. We also demonstrated that the exogenous expression of PLIN1 in human breast cancer MCF-7 and MDA-MB-231 cells significantly inhibits cell proliferation, migration, invasion and in vivo tumorigenesis in mice. Together, these data provide novel insights into a prognostic significance of PLIN1 in human breast cancer and reveal a potentially new gene therapy target for breast cancer.

Approximately 90 % of head and neck cancers are squamous cell carcinomas (HNSCC), and the overall 5-year survival rate is not higher than 50 %. There is much evidence that human papillomavirus (HPV) infection may influence the expression of commonly studied HNSCC markers. Our study was focused on the possible HPV-specificity of molecular markers that could be key players in important steps of cancerogenesis (MKI67, EGF, EGFR, BCL-2, BAX, FOS, JUN, TP53, MT1A, MT2A, VEGFA, FLT1, MMP2, MMP9, and POU5F). qRT-PCR analysis of these selected genes was performed on 74 biopsy samples of tumors from patients with histologically verified HNSCC (22 HPV-, 52 HPV+). Kaplan-Meier analysis was done to determine the relevance of these selected markers for HNSCC prognosis. In conclusion, our study confirms the impact of HPV infection on commonly studied HNSCC markers MT2A, MMP9, FLT1, VEGFA, and POU5F that were more highly expressed in HPV-negative HNSCC patients and also shows the relevance of studied markers in HPV-positive and HPV-negative HNSCC patients.

Introduction: Lynch syndrome is known to cause an increased risk of malignancies, including bowel and endometrial cancers. However, the risk of breast cancer associated with mutations in the mismatch repair (MMR) genes that cause Lynch syndrome is still unclear., Materials and Methods: This study assesses the cumulative risk of breast cancer in 106 MLH1 and 118 MSH2 families. Families were referred on the basis of clinical criteria. Pedigree information was obtained, and tumour immunohistochemistry and microsatellite testing performed. Appropriate patients underwent sequencing and multiple ligation dependent probe amplification of all relevant exons of the MMR genes. Kaplan-Meier analysis of cumulative lifetime risk of breast cancer was made combining proven mutation carriers and their first-degree female relatives., Results: After allocation of mutation status, the cumulative risk of breast cancer to 70 years in MLH1 carriers was 18.6% (95% CI 11.3 to 25.9)). This is significantly higher than the cumulative risk for MSH2 which was 11.2% (95% CI 1.4 to 21.0) to age 70 years (p=0.014). The UK population risk is 7.5%-8% at the age of 70 years. Prospective analysis identified six breast cancers in 1120 years of follow-up with an OR of 3.41 (95% CI 1.53 to 7.59)., Discussions: Female MLH1 carriers would appear to be at moderate risk of breast cancer and should be considered for breast screening at ages earlier than national screening programmes., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Histone H2AX phosphorylation is a sensitive marker for DSB which contributes to both genomic instability and cancer treatment. Monitoring its formation may be a sensitive means to monitor cancer progression and treatment effect., Objective: To define the role of phospho-H2AX (pH2AX) expression in development and prognosis of epithelial ovarian cancer (EOC)., Methods: The expression of pH2AX in 87 EOC samples and 28 samples of normal ovarian tissues were examined by immunohistochemistry (IHC). The results were semi-quantitatively scored and analyzed by chi-square test. The overall survival time (OS) and disease free interval (DFI) were collected by follow-up and analyzed by Kaplan-Meier analysis., Results: The expression level of pH2AX protein in EOC were higher than that in normal tissues (P<0.001). Among the sensitive cases, high expression of pH2AX was found in 53.2% cases while for resistant cases, high expression rate was 80% (P=0.025). However, pH2AX expression was not significantly correlated with age, histopathological type, tumor differentiation, lymph node metastasis or FIGO stages. Kaplan-Meier analysis found that DFI was negatively correlated with the pH2AX expression, where higher expression of pH2AX resulted in shorter DFI while no OS difference was detected in our study., Conclusion: pH2AX may be used to detect EOC at an early stage and identify women at higher risk for relapse.

Purpose: To analyze factors affecting outcomes in breast cancer patients with brain metastases (BM) and characterize the role of HER2 status. Methods and Materials: We identified 264 breast cancer patients treated between 1999 and 2008 for BM. HER2 status was known definitively for 172 patients and was used to define cohorts in which survival and risk factors were analyzed. Results: Kaplan-Meier survival analysis demonstrated improved mean overall survival (105.7 vs. 74.3 months, p < 0.02), survival after diagnosis of BM (neurologic survival, NS) (32.2 vs. 18.9 months, p < 0.01), and survival after treatment with stereotactic radiosurgery (RS) (31.3 vs. 14.1, p < 0.01) in HER2+ patients relative to those with HER2− breast cancer. HER2+ status was an independent, positive prognostic factor for survival on univariate and multivariate hazard analysis (hazard ratio: overall survival = 0.66, 0.18; NS = 0.50, 0.34). Additionally, subgroup analysis suggests that stereotactic radiosurgery may be of particular benefit in patients with HER2+ tumors. Conclusions: Overall survival, NS, and RS are improved in patients with HER2+ tumors, relative to those with HER2− lesions, and HER2 amplification is independently associated with increased survival in patients with BM from breast cancer. Our findings suggest that the prognosis of HER2+ patients may be better than that of otherwise similar patients who are HER2− and that stereotactic radiosurgery may be beneficial for some patients with HER2+ lesions. [ABSTRACT FROM AUTHOR]

The article presents an abstract of the article titled "Pilot Study of Patient Responses to Multiple Impulse Therapy for Musculoskeletal Complaints," by Joseph M. Evans, Daniel L. Collins, and Reed H. Grundy.

Aim: To assess the expression of nuclear hepatoma-derived growth factor (HDGF) in benign and malignant gallbladder lesions and to determine its clinicopathological significance., Methods: We studied 40 patients with gallbladder cancer (GBC) and a control group of 40 patients with cholelithiasis. All diagnoses of GBC and cholelithiasis were confirmed by histopathological examination after surgery. None of the patients received chemotherapy or radiotherapy before surgery. All tissue samples were fixed in 4% formalin immediately after removal and embedded in paraffin for immunohistochemical staining. The HDGF expression in the GBC and cholelithiasis specimens was examined by immunohistochemical staining. The relationship between the HDGF expression and the clinicopathological parameters of GBC was analyzed., Results: Nuclear HDGF expression was significantly higher (77.5%) in GBC than in chronic cholelithiasis (21.5%, P < 0.001). High nuclear HDGF levels were associated with histopathological subtype (P < 0.05), clinical stage (P < 0.01), and perineural invasion (P < 0.01) but not with sex, age, history of gallstones, or lymph node metastasis. A univariate Kaplan-Meier analysis showed that positive nuclear HDGF expression was associated with decreased overall survival (P < 0.01). Multivariate Cox regression analysis showed that nuclear HDGF expression and lymph node metastasis were independent risk factors for disease-free survival., Conclusion: The expression of nuclear HDGF might be closely related to the carcinogenesis, clinical biological behaviors, and prognosis of gallbladder adenocarcinoma.

The cannabinoid system has been considered to be a potential target of colorectal carcinoma therapy. The aim of this study was to address the correlation between cannabinoid type 1 (CB1) receptor expression and disease severity/outcomes in patients with colorectal cancer (CRC). CB1 receptor expression was analyzed by immunohistochemistry using tissue microarrays in consecutive patients who underwent surgical resection (n=534). CB1 receptor expression was categorized as a high (≥66%) vs. low (<66%) immunopercentage as a median split, and was analyzed in relation to disease severity and overall survival. CB1 receptor expression was observed in 409 patients (76.6%). Low CB1 receptor expression was more frequently identified in stage IV than in stage I/II or III cancer (P<0.01 for both). In stage IV CRC, high vs. low CB1 expression was correlated with a statistically significant poorer overall survival (P=0.033) that was independent of age, R0 resection, tumor differentiation and chemotherapy [hazard ratio (HR), 1.805; 95% confidence interval (CI), 1.042-3.094; P=0.035]. However, CB1 expression was not observed to be correlated with patient survival following surgery in stage I/II or III cancer. The high immunoreactivity of the cannabinoid type 1 receptor is a significant prognostic factor following surgery in stage IV CRC.