Lifetime risks of hip fracture in patients with type 2 diabetic: Taiwan Diabetes Study.

This study is to estimate the lifetime risks of hip fracture in Chinese patients with type 2 diabetes. INTRODUCTION: The lifetime risks of hip fracture have not been reported across the age spectrum in male adults and female adults with type 2 diabetes. METHODS: A retrospective cohort study was conducted on 25275 men and 27953 women with type 2 diabetes aged 30-100 years old and participated in the National Diabetes Case Management Program in 2002-2004 in Taiwan. Sociodemographic factors, biomarkers, and comorbidity at the baseline and hip fracture events were analyzed with Cox proportional hazards regression models with age as the time scale. RESULTS: Significant differences in the lifetime risks of hip fracture were observed between men and women with type 2 diabetes. The cumulative lifetime incidences (%) of hip fracture at 50, 60, 65, 70, 75, 80, and 85 years old for men were 0.11, 0.40, 0.84, 1.84, 3.82, 8.53, and 16.72, respectively. The corresponding lifetime incidences (%) for women at 50, 60, 65, 70, 75, 80, and 85 years old were 0.05, 0.50, 1.36, 3.89, 9.56, 21.19, and 35.45, respectively. With competing risks, the significant multivariate-adjusted hazard ratio of developing hip fracture included smoking, alcohol drinking, duration of diabetes, type of oral hypoglycemic drugs use (no medication, sulfonylurea only, thiazolidinediones (TZD) only or TZD plus others, other single or multiple oral agents, insulin use, insulin plus oral hypoglycemic drug use), loop diuretics use, use of corticosteroids, normal weight or underweight, hyperlipidemia, and chronic obstructive pulmonary disease. CONCLUSIONS: The gender differences in lifetime hip fracture risk were significant. Thiazolidinediones and insulin use are factors with the greater magnitude of strength of association among those significantly associated with hip fracture.

Visit-to-visit blood pressure variability and hip fracture risk in older persons.

We investigated the association between blood pressure variability measured by the coefficient of variation (CV) of blood pressure and hip fracture in older persons with diabetes. After excluding patients with acute complications and comorbidities, a positive association with similar magnitude of strength was found between BP variability and hip fracture, compared with that in the original analysis. INTRODUCTION: Hypertension is a risk factor of osteoporosis and hip fracture, but studies have yet to investigate whether blood pressure variability measured by the CV of blood pressure can predict hip fracture in older persons with diabetes. METHODS: We conducted a retrospective cohort study on 21,160 patients who suffered from type 2 diabetes (age ≥ 50 years) and participated in the National Diabetes Care Management Program in Taiwan. The patients' 1-year variability in systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the baseline and subsequent hip fracture incidence for 8.2 years were analyzed. RESULTS: There were 937 recorded incident hip fractures. SBP-CV and DBP-CV were classified based on their tertiles. After multivariate adjustment was conducted, SBP-CV found to be a predictor of hip fracture, and its hazard ratio was 1.18 (95% CI 1.00-1.40) for the third tertile compared with the first tertile. CONCLUSIONS: Our study suggests SBP stability is a predictor for hip fracture incidence in older persons with type 2 diabetes.

Risk score prediction model for dementia in patients with type 2 diabetes.

BACKGROUND AND PURPOSE: No study has established a prediction dementia model in the Asian populations. This study aimed to develop a prediction model for dementia in Chinese type 2 diabetes patients. METHODS: The retrospective cohort study included 27 540 Chinese type 2 diabetes patients (aged 50-94 years) enrolled in the Taiwan National Diabetes Care Management Program. Participants were randomly allocated into derivation and validation sets at a 2:1 ratio. Cox proportional hazards regression models were used to identify risk factors for dementia in the derivation set. Steps proposed by the Framingham Heart Study were used to establish a prediction model with a scoring system. RESULTS: The average follow-up was 8.09 years, with a total of 853 incident dementia cases in the derivation set. The dementia risk score summed up the individual scores (from 0 to 20). The areas under the curve of 3-, 5- and 10-year dementia risks were 0.82, 0.79 and 0.76 in the derivation set and 0.84, 0.80 and 0.75 in the validation set, respectively. CONCLUSIONS: The proposed score system is the first dementia risk prediction model for Chinese type 2 diabetes patients in Taiwan.

Visit-to-visit variation of fasting plasma glucose is a predictor of hip fracture in older persons with type 2 diabetes: the Taiwan Diabetes Study.

We investigated the association between fasting plasma glucose variability (FPG-CV) and the risk of hip fracture in elderly diabetic patients. Our finding showed a temporal association between FPG-CV and hip fracture as patients categorized as FPG-CV greater than 25.4 % showed an increased risk in hip fractures. INTRODUCTION: Hip fracture is a major health burden in the population and is associated with high rates of mortality and morbidity especially in elderly. It is evident that diabetes mellitus is a risk factor of osteoporosis which is a significant risk factor of hip fracture. However, epidemiological studies exploring the risks of hip fracture among type 2 diabetic patients are limited. METHODS: A retrospective study of 26,501 ethnic Chinese older persons enrolled in the National Diabetes Care Management program in Taiwan was conducted; related factors were analyzed with extended Cox proportional hazards regression models to competing risk data on hip fracture incidence. RESULTS: The results show a temporal association between FPG-CV and hip fracture as patients categorized as FPG-CV greater than 25.4 % showed an increased risk in hip fractures, confirming a linear relationship between the two. After multivariate adjustment, the risk of hip fracture increased among patients with FPG-CV of 25.4-42.3 % and >42.3 % compared with patients with FPG-CV of ≦ 14.3 % (hazard ratio, 1.35; 95 % confidence interval 1.14-1.60 and 1.27; 1.07-1.52, respectively). Significant linear trends among various FPG-CV were observed. CONCLUSIONS: Thus, the present study demonstrated the importance of glucose stability for fracture prevention in older persons with type 2 diabetes. Future studies should be conducted to explore whether reduction in glucose oscillation in older adults with diabetes mellitus can reduce the risk of hip fracture.

Independent and joint effect of type 2 diabetes and gastric and hepatobiliary diseases on risk of pancreatic cancer risk: 10-year follow-up of population-based cohort.

BACKGROUND: Type 2 diabetes mellitus, gastric and hepatobiliary comorbidities, and cancer share common risk factors: for example, tobacco, obesity, physical inactivity, high calorie intake, and metabolic disorders. Prior studies find type 2 diabetes and gastric and hepatobiliary comorbidities heightening risk of pancreatic cancer. Yet joint association of type 2 diabetes mellitus and gastric and hepatobiliary comorbidities on pancreatic cancer risk has not been assessed. METHODS: This study rates independent/joint effects of type 2 diabetes as well as gastric and hepatobiliary comorbidity on pancreatic cancer risk for a retrospective population-based cohort of 166,850 type 2 diabetics identified in 1997-1998 and followed for 10-11 years, comparing their cancer incidence with that of 166,850 non-diabetics matched for age, gender, and locale. Time-dependent Cox's proportional hazards model evaluted joint association of type 2 diabetes and chronic conditions on pancreatic cancer risk. RESULTS: A total of 1178 subjects were newly diagnosed with pancreatic cancer during follow-up, with incidence rates of 0.49 per 1000 person-years in type 2 diabetes and 0.26 per 1000 person-years in the non-diabetics. We observed greater magnitude of hazard ratios (HRs) of pancreatic cancer for patients with type 2 diabetes along with acute alcoholic hepatitis, acute pancreatitis, cholecystitis, and gastric ulcer compared with patients without type 2 diabetes or counterpart comorbidity (HR: 1.36, 95% confidence interval (CI): 1.19-1.56; 1.74, 1.23-2.45; 9.18, 7.44-11.33; and 2.31, 1.98-2.70, respectively). Main effects of type 2 diabetes were all statistically with narrow 95% CI and remained similar across risk stratification with various comorbidities: range 1.59-1.80. CONCLUSIONS: Our study demonstrates that pre-existing type 2 diabetes, acute alcoholic hepatitis, acute pancreatitis, cholecystitis, and gastric ulcer independently or jointly predict subsequent pancreatic cancer risk. Clinicians must recognise burden of these gastric and hepatobiliary comorbidities and keep clinically vigilant for their diagnosis.

Vitamin D receptor variability and physical activity are jointly associated with low handgrip strength and osteoporosis in community-dwelling elderly people in Taiwan: the Taichung Community Health Study for Elders (TCHS-E).

UNLABELLED: We studied 472 elders to assess joint association of vitamin D receptor (VDR) variability and physical activity on low handgrip strength (LHS) and osteoporosis (OST). Our findings showed that higher risks of OST were associated with physically inactive elders with some specific VDR variations, highlighting the importance of promotion program for physical activity. INTRODUCTION: The aim of this study was to determine the joint association between VDR variability and physical activity on LHS and OST in community-dwelling elders. METHODS: Bone mineral density of the lumbar spine (LS), the femoral neck (FN), and the total hip were measured by dual-energy X-ray absorptiometry. Four single-nucleotide polymorphisms (SNPs) (rs7975232, rs1544410, rs2239185, and rs3782905) of the VDR gene were examined in 472 participants. RESULTS: Physical inactivity and each of the four SNPs were jointly associated with a significantly greater risk of LHS in people than that associated with each of the VDR SNPs or low physical activity alone. Physically inactive men with the AG or AA genotype of rs2239185 had a significantly greater risk of overall, LS, and FN OST than those of physically active men with the GG genotype [odds ratio (OR) 3.57, 95 % confidence interval (CI) 1.10-11.65; OR 4.74, 95 % CI 1.43-15.70; and OR 5.06, 95 % CI 1.08-23.71, respectively]. Similarly, physically inactive women with the CG or CC genotype of rs3782905 and the AG or AA genotype of rs1544410 had a significantly greater risk of FN OST than physically active women with the GG genotype (OR 5.33, 95 % CI 1.23-23.06 and OR 5.36, 95 % CI 1.11-25.94, respectively). CONCLUSIONS: VDR polymorphisms and physical activity are jointly associated with LHS and OST in elders. Health care programs should promote physical activity among elders as a cost-effective way to prevent LHS and OST, especially in those who may be genetically predisposed.

Evaluating environmental performance using new process capability indices for autocorrelated data.

Traditionally, the process capability index is developed by assuming that the process output data are independent and follow normal distribution. However, in most environmental cases, the process data are autocorrelated. The autocorrelated process, if unrecognized as an independent process, can lead to erroneous decision making and unnecessary quality loss. In this paper, three new capability indices with unbiased estimators are proposed to relieve the independence assumption for the-nominal-the-best and the-smaller-the-better cases. Furthermore, we use mean squared error (MSE) and mean absolute percent error (MAPE) to compare the accuracy of our proposed indices to previous autocorrelated indices. The results show that our proposed capability indices outperform the predecessors.

Gene expression array testing of FFPE archival breast tumor samples: an optimized protocol for WG-DASL sample preparation.

Archived formalin-fixed, paraffin embedded (FFPE) tissues constitute a vast, well-annotated, but underexploited resource for the molecular study of cancer progression, largely because degradation, chemical modification, and cross-linking, render FFPE RNA a suboptimal substrate for conventional analytical methods. We report here a modified protocol for RNA extraction from FFPE tissues which maximized the success rate (with 100% of samples) in the expression profiling of a set of 60 breast cancer samples on the WG-DASL platform; yielding data of sufficient quality such that in hierarchical clustering (a) 12/12 (100%) replicates correctly identified their respective counterparts, with a high self-correlation (r = 0.979), and (b) the overall sample set grouped with high specificity into ER+ (38/40; 95%) and ER- (18/20; 90%) subtypes. These results indicate that a large fraction of decade-old FFPE samples, of diverse institutional origins and processing histories, can yield RNA suitable for gene expression profiling experiments.

Competing risk analysis on visit-to-visit glucose variations and risk of depression: The Taiwan Diabetes Study.

AIM: Patients with diabetes have higher rates of depression than does the general population, but diabetes management mainly aims to maintain glucose stability. For this reason, our study assessed the relationship between 1-year variations in fasting plasma glucose (FPG) and risk of depression in Chinese patients with type 2 diabetes (T2D). METHODS: This retrospective cohort study was conducted on 32,829 patients aged ≥30 years who were diagnosed with T2D and who participated in the National Diabetes Case Management Program in Taiwan. Their 1-year FPG variation as a predictor was determined by coefficient of variation (CV), whereas depressive events were analyzed by Cox's proportional hazards models. RESULTS: During a mean 8.23 years of follow-up, 1041 new cases of depression were diagnosed. When patients were grouped based on quartiles of FPG-CV, incidence rates were 3.23, 3.49, 3.96 and 4.80 per 1000 person-years in the first, second, third and fourth quartile subgroups, respectively. After adjusting for traditional risk factors, baseline fasting glucose and HbA1c levels, and diabetes complications, FPG-CV was independently linked with incident depression. Hazard ratios of depression for FPG-CV in the fourth vs first quartile subgroups was 1.33 (95% CI: 1.11-1.59), respectively. CONCLUSION: Patients whose 1-year FPG variations were>42.6% had an increased risk of depression, thus suggesting that FPG variations may be a predictor of depression in patients with T2D. Also, glucose variation during outpatient visits may be an indicator for individualized diabetes management in clinical practice.

Differential patterns of allelic loss in estrogen receptor-positive infiltrating lobular and ductal breast cancer.

The two main histological types of infiltrating breast cancer, lobular (ILC) and the more common ductal (IDC) carcinoma are morphologically and clinically distinct. To assess the molecular alterations associated with these breast cancer subtypes, we conducted a whole-genome study of 166 archival estrogen receptor (ER)-positive tumors (89 IDC and 77 ILC) using the Affymetrix GeneChip(R) Mapping 10K Array to identify sites of loss of heterozygosity (LOH) that either distinguished, or were shared by, the two phenotypes. We found single nucleotide polymorphisms (SNPs) of high-frequency LOH (>50%) common to both ILC and IDC tumors predominately in 11q, 16q, and 17p. Overall, IDC had a slightly higher frequency of LOH events across the genome than ILC (fractional allelic loss = 0.186 and 0.156). By comparing the average frequency of LOH by chromosomal arm, we found IDC tumors with significantly (P < 0.05) higher frequency of LOH on 3p, 5q, 8p, 9p, 20p, and 20q than ILC tumors. We identified additional chromosomal arms differentiating the subtypes when tumors were stratified by tumor size, mitotic rate, or DNA content. Of 5,754 informative SNPs (>25% informativity), we identified 78 and 466 individual SNPs with a higher frequency of LOH (P < 0.05) in ILC and IDC tumors, respectively. Hierarchical clustering of these 544 SNPs grouped tumors into four major groups based on their patterns of LOH and retention of heterozygosity. LOH in chromosomal arms 8p and 5q was common in higher grade IDC tumors, whereas ILC and low-grade IDC grouped together by virtue of LOH in 16q.

Tamoxifen therapy for primary breast cancer and risk of contralateral breast cancer.

BACKGROUND: Women diagnosed with breast cancer have a twofold to sixfold greater risk of developing contralateral breast cancer than women in the general population have of developing a first breast cancer. Tamoxifen therapy reduces this risk, but it is unclear if this benefit exists for both estrogen receptor (ER)-positive and ER-negative contralateral tumors. METHODS: Using data from a population-based tumor registry that collects information on the ER status of breast tumors, we followed 8981 women residing in western Washington State who were diagnosed with a primary unilateral invasive breast cancer during the period from 1990 through 1998 to identify cases of contralateral breast cancer. We restricted our analyses to women who were at least 50 years old and whose first breast cancer had a localized or regional stage; women who received adjuvant hormonal therapy but not chemotherapy (n = 4654) were classified as tamoxifen users, while those who received neither adjuvant hormonal therapy nor chemotherapy (n = 4327) were classified as nonusers of tamoxifen. By reviewing selected patient abstracts, we estimated that 94% of the subjects were classified correctly with respect to tamoxifen use. The risk of contralateral breast cancer associated with tamoxifen use was estimated with the use of Cox regression. All statistical tests were two-sided. RESULTS: Of the 89 tamoxifen users and 100 nonusers of tamoxifen diagnosed with contralateral breast cancer, 112 had ER-positive tumors, 20 had ER-negative tumors, and 57 had tumors with an ER status that was unknown or had not been determined by an immunohistochemical assay. The risk of developing an ER-positive and an ER-negative contralateral tumor among tamoxifen users was 0.8 (95% confidence interval [CI] = 0.5 to 1.1) and 4.9 (95% CI = 1.4 to 17.4), respectively, times that of nonusers of tamoxifen. This difference in risk by ER status was statistically significant (P<.0001). CONCLUSIONS: Tamoxifen use appears to decrease the risk of ER-positive contralateral breast tumors, but it appears to increase the risk of ER-negative contralateral tumors.

Cue and context conditioning of defensive behaviors to cat odor stimuli.

Exposure of rats to a cat odor block in a previously familiarized situation was followed by three extinction days to the same or a different situation, and with or without an identical but odor-free block, and, testing in the original apparatus with an odor-free block (cue). Initial exposure produced risk assessment (stretch attend), avoidance of the block, and crouch/freeze with sniffing/head movements. Avoidance continued during extinction, but context-only exposed rats showed predominantly crouch/freeze with sniff/head movements, while rats exposed to the context+cue showed higher levels of stretch attend. During the test day, rats exposed to the cue during extinction showed reduced defensive responding compared to those not extinguished with the cue, but context extinction had less effect, possibly due in part to initial familiarization with the situation. These data indicate that both cue and context conditioning to cat odor did occur, and that the type of conditioned stimulus (context-only vs. context+cue) influenced the type of defensive behaviors elicited by this stimulus, although the all animals received the same conditioning protocol. Particular behaviors disappeared at different rates during extinction, with avoidance the most persistent. However, in this context there was no incentive for approach behaviors inconsistent with avoidance, and stretch attend behaviors could and did occur while subjects were located far from the block or the area in which it had been encountered. In addition, immobile crouch/freeze did not occur at higher than control levels, while the crouch/freeze activities that did increase incorporated sensory sampling in a relevant modality (sniffing/head movements). Thus, the behaviors seen to the conditioned stimulus appeared to reflect combinations of different defense strategies, appropriate to the type of conditioned stimulus and responsive to its extinction. Differences between these data and those from studies using fecal predator odorants suggest that the latter may not elicit a complete range of conditioned defenses.

Approaching healthy body mass index norms for children and adolescents from health-related physical fitness.

Current body mass index (BMI) norms for children and adolescents are developed from a reference population that includes obese and slim subjects. The validity of these norms is influenced by the observed secular increase in body weight and BMI. We hypothesized that the performance of children in health-related physical fitness tests would be negatively related to increased BMIs, and therefore fitness tests might be used as criteria for developing a more appropriate set of BMI norms. We evaluated the existing data from a nation-wide fitness survey for students in Taiwan (444 652 boys and 433 555 girls) to examine the relationship between BMI and fitness tests. The fitness tests used included: an 800/1600-m run/walk; a standing long jump; bent-leg curl-ups; and a sit-and-reach test. The BMI percentiles developed from the subgroup whose test scores were better than the 'poor' quartile in all four tests were compared with those of the whole population and linked to the adult criteria for overweight and obesity. The BMIs were significantly related to the results of fitness testing. A total of 43% of students had scores better than the poorest quartile in all of their tests. The upper BMI percentile curves of this fitter subgroup were lower than those of the total population. The 85th and 95th BMI percentile values of the fitter 18-year-old-students (23.7 and 25.5 kg m(-2) for boys; 22.6 and 24.6 kg m(-2) for girls) linked well with the adult cut-off points of 23 and 25 kg m(-2), which have been recommended as the Asian criteria for adult overweight and obesity. Hence, the BMI norms for children and adolescents could be created from selected subgroups that have better physical fitness. We expect that the new norms based on this approach will be used not only to assess the current status of obesity or overweight, but also to encourage activity and exercise.

Anthropometric variables in relation to risk of breast cancer in middle-aged women.

BACKGROUND: Many epidemiological studies have assessed the relationships between anthropometric variables and breast cancer risk. However, methodological approaches for analysing these factors differ appreciably. Also, age when maximum height is achieved has been identified as a potential risk factor for breast cancer in premenopausal women, but this issue has not been studied in postmenopausal women. METHODS: The participants in this population-based case-control study were postmenopausal women 50-64 years of age from the general female population of western Washington State. It included 479 women with incident primary breast cancer and 435 controls. RESULTS: This study found that: (i) women who gained over 70 pounds since age 18 had an increased risk of breast cancer relative to those who stayed within 10 pounds of their weight at age 18 (odds ratio [OR] = 2.7; 95% CI: 1.5-4.9), (ii) women with body mass indices (BMI) below what is considered healthy had a decreased risk (OR = 0.4; 95% CI: 0.2-1.1) while women with a BMI in the obese range had an increased risk of breast cancer (OR = 1.4; 95% CI: 1.0-2.1), and (iii) women who reached their maximum height at or after the age of 18 had a decreased risk of breast cancer compared to women who reached their maximum height at age 13 or younger (OR = 0.7; 95% CI: 0.5-1.0). CONCLUSIONS: By examining various anthropometric variables using clinically relevant strata, a clearer picture of how these variables relate to postmenopausal breast cancer risk was developed. Similar to younger women, postmenopausal women who reached their maximum height at later ages had a decreased risk of breast cancer.

Serum and tissue levels of estradiol during estrogen-induced renal tumorigenesis in the Syrian hamster.

The estrogen-induced renal tumor in the hamster has emerged as a major animal model in hormonal carcinogenesis. However, a fundamental aspect of this experimental model has as yet not been investigated. In the present study, comparisons between the serum and tissue 17 beta-estradiol (E2) levels in cyclic female hamsters and corresponding hormone levels in E2-treated castrated male hamsters have been made. Data is provided concerning the concentration of estrogenic hormones in the serum and target tissue typically required to elicit renal tumorigenesis in this species. Serum E2 levels in the cyclic female hamster average 79 pg/ml on days 1-2 and 311 pg/ml on days 3-4, attaining a maximum of 358 pg/ml on day 4 of the cycle. Elevation in uterine, renal and hepatic E2 tissue levels during days 3-4 of the cycle reflect increases in serum E2 levels which were 3.0-, 2.0-, and 2.6-fold higher when compared to day 1 of the cycle in these tissues. As expected, serum E2 levels of untreated castrated male hamsters did not appreciably vary over a 6 month period of aging and averaged about 32 pg/ml. Under conditions which produced essentially 100% renal tumor incidence, a rapid rise in serum E2 levels, averaging 71.0-fold higher than untreated castrated levels, was seen. A steady state serum E2 level of 2400 to 2700 pg/ml was maintained from 45-180 days of continuous estrogen treatment. Compared to kidneys of untreated hamsters, renal E2 levels in E2-treated hamsters rose only on average 5.4-fold between 15-180 days of hormone exposure. Serum levels of E2-treated hamsters were 5.7- to 8.0-fold higher than those observed in cyclic female hamsters on days 3 and 4. However, at these higher E2-treated serum levels there was no apparent effect either on weight loss or mortality of the animals.

Association between serum uric acid and cardiovascular risk factors among elderly people in Taiwan.

In order to understand the distribution of serum uric acid and the relationship between serum uric acid and the cardiovascular risk factor among elderly people, a cross-sectional study was conducted in Chung-Shing-Shin-Tseun community in Taiwan in May 1998. All individuals aged 65 and over were collected. A total of 1123 persons, out of 1774 registered residents, were contacted by face-to-face interview. The response rate was 63.3%. However, only 586 respondents had blood tests and completed questionnaires. Analysis in this study was based on these 586 subjects. The mean uric acid values were 7.4 +/- 1.8 mg/dl in men and 6.3 +/- 1.6 mg/dl in women, respectively (p < 0.001). Multivariate linear regression showed that serum uric acid was significantly correlated with sex and body mass index. Simple correlation showed that serum uric acid was significantly correlated with diastolic pressure, total cholesterol, triglyceride and creatinine. Age, systolic pressure and fasting glucose were not related to serum uric acid. In our conclusion, the uric acid values are high among elderly people. The serum uric acid levels are significantly associated with the cardiovascular risk factors among elderly people.

LRIG1 modulates aggressiveness of head and neck cancers by regulating EGFR-MAPK-SPHK1 signaling and extracellular matrix remodeling.

EGFR overexpression and chromosome 3p deletion are two frequent events in head and neck cancers. We previously mapped the smallest region of recurrent copy-number loss at 3p12.2-p14.1. LRIG1, a negative regulator of EGFR, was found at 3p14, and its copy-number loss correlated with poor clinical outcome. Inducible expression of LRIG1 in head and neck cancer TW01 cells, a line with low LRIG1 levels, suppressed cell proliferation in vitro and tumor growth in vivo. Gene expression profiling, quantitative RT-PCR, chromatin immunoprecipitation, and western blot analysis demonstrated that LRIG1 modulated extracellular matrix (ECM) remodeling and EGFR-MAPK-SPHK1 transduction pathway by suppressing expression of EGFR ligands/activators, MMPs and SPHK1. In addition, LRIG1 induction triggered cell morphology changes and integrin inactivation, which coupled with reduced SNAI2 expression. By contrast, knockdown of endogenous LRIG1 in TW06 cells, a line with normal LRIG1 levels, significantly enhanced cell proliferation, migration and invasiveness. Such tumor-promoting effects could be abolished by specific MAPK or SPHK1 inhibitors. Our data suggest LRIG1 as a tumor suppressor for head and neck cancers; LRIG1 downregulation in cancer cells enhances EGFR-MAPK-SPHK1 signaling and ECM remodeling activity, leading to malignant phenotypes of head and neck cancers.

Selenium is inversely associated with interleukin-6 in the elderly.

BACKGROUND: Selenium is an essential trace element with antioxidant property. Decreased serum selenium concentration with aging had been found in previous report. In this study, we aim to investigate the association between serum selenium and the inflammatory cytokine interleukin-6 in the elderly living in long-term care facilities in Taiwan. MATERIALS AND METHODS: A total of 336 subjects aged 65 years and older (range of age: 65 - 101 years) were recruited from eight long-term care facilities in 2002-2003. Baseline characteristics, anthropometric indices, and biochemical data were obtained. Selenium deficiency was defined as serum selenium concentration < 80 µg/L. Multiple logistic and linear regression analyses were used to examine the relationships between selenium deficiency and interleukin-6 (divided into quartiles). RESULTS: The prevalence of selenium deficiency was 35.6% in men and 43.2% in women, respectively. After adjusting for potential confounders using multiple logistic regression analysis, interleukin-6 quartiles were significantly associated with selenium deficiency. Compared to the interleukin-6 quartile I, the adjusted odds ratios of having selenium deficiency for interleukin-6 quartile II, III, IV were 1.00(0.50~2.01), 1.24 (0.62~2.50), and 2.35(1.15~4.83), respectively. The increasing odds ratios for selenium deficiency in higher interleukin-6 quartiles revealed dose-response effects (p < 0.05). Moreover, multiple linear regression analysis showed that serum selenium was significantly inversely associated with interleukin-6 after adjusting for potential confounders. CONCLUSIONS: Serum selenium was inversely associated with inflammatory cytokine interleukin-6 among elderly living in long-term care facilities in Taiwan. Monitoring serum selenium should be considered in these institutionalized elderly.

Relationship between interpregnancy interval and birth defects in Washington State.

OBJECTIVE: Interpregnancy interval (IPI) influences numerous adverse perinatal outcomes. IPI's impact on birth defects is unclear. STUDY DESIGN: We conducted a population-based case-control study, using 1998 to 2008 administrative data from Washington State. A total of 10, 772 cases, women whose second of two births resulted in an infant with a birth defect, were compared with 32 ,310 controls, women whose second of two births did not result in an infant with a birth defect. RESULT: Compared with mothers with an IPI between 18 to 23 months, those with an IPI <6 months or ≥60 months had elevated risks of delivering an infant with a birth defect (odds ratio=1.15, 95% confidence interval: 1.03 to 1.28, and odds ratio=1.15, 95% confidence interval: 1.04 to 1.26, respectively). CONCLUSION: We observed a J-shaped relationship between IPI and risk of having an infant with a birth defect. As this is one of the first studies to evaluate this association, confirmatory studies are needed.