Can weekend catch-up sleep decrease the risk of cognitive dysfunction in older adults?

PURPOSE: This study investigated whether weekend catch-up sleep was related to a decreased risk of cognitive dysfunction in older Taiwanese adults by using self-reported diaries and objective accelerometer measurements. METHODS: This cross-sectional study enrolled participants who were aged ≥ 65 years and had the capability to walk independently from a medical center in Taipei City, Taiwan, between September 2020 and December 2022. Self-reported sleep diaries and tri-axial accelerometers were used to record and measure sleep-related data for 7 consecutive nights. Weekend catch-up sleep was defined as the mean of weekend sleep time minus the mean of weekdays sleep time. Mini-Mental State Examination (MMSE) was evaluated the risk of cognitive dysfunction. The association between weekend catch-up sleep and the MMSE score was examined using a binary logistic regression model. RESULTS: A total of 215 older adults (53.0% female; 80.5 ± 7.1 years old; 11.6% at risk of cognitive dysfunction) were included. In the adjusted model (adjusted for sex, education level, moderate-to-vigorous physical activity and total accelerometer wear time), both the self-reported sleep diaries (odds ratio [OR] = 0.26, 95% confidence interval [CI] = 0.09-0.69, P = 0.007) and the accelerometer data (OR = 0.27, 95% CI = 0.10-0.70, P = 0.007) indicated that weekend catch-up sleep could decrease the risk of cognitive dysfunction by 73-74%. CONCLUSION: The study findings suggest that there is an association between weekend catch-up sleep and lower risk for cognitive decline. The causal relationship between weekend catch-up sleep and cognitive function in older adults should be further investigated in a study with longitudinal design.

Association of 24-Hour movement behavior and cognitive function in older Taiwanese adults.

OBJECTIVES: This study investigates how 24-hour movement behaviors (physical activity, sedentary time, sleep) relate to cognitive performance in older adults. METHODS: 213 adults (aged 65+) wore accelerometers to track activity. Cognitive function was assessed using the Mini-Mental State Examination (MMSE). Isotemporal substitution analysis examined how replacing one behavior with another affected cognition. RESULTS: Increased light physical activity was linked to better cognitive function, whereas longer sleep had a negative impact. Replacing 30 min of sedentary behavior or sleep with light physical activity improved orientation, attention, language, and short-term memory. Substituting moderate-to-vigorous physical activity did not have the same cognitive benefit. CONCLUSION: Encouraging older adults to replace sedentary time or excess sleep with light physical activity could support cognitive health and potentially help prevent dementia. These findings have implications for public health strategies promoting cognitive well-being in aging populations.

Fine particulate air pollution and outpatient department visits for headache in Taipei, Taiwan.

This study was undertaken to determine whether there was an association between fine particle matter (PM(2.5)) levels and daily outpatient department visits (OPD) for headaches in Taipei, Taiwan. Daily OPD visits for headaches and ambient air pollution data for Taipei were obtained for the period 2006-2011. The relative risk of visits for OPD headaches was estimated using a case-crossover approach, controlling for weather variables, day of the week, seasonality, and long-term time trends. For the single-pollutant model (without adjustment for other pollutants), increased OPD visits for headaches were significantly associated with levels of PM(2.5) both on warm days (>23°C) and cool days (<23°C), with an interquartile range rise associated with a 12% (95% CI = 10-14%) and 3% (95% CI = 1-5%) elevation in OPD visits for headaches, respectively. In the two-pollutant models, PM(2.5) remained significant after inclusion of sulfur dioxide (SO2) or ozone (O3) on both warm and cool days. This study provides evidence that higher levels of PM(2.5) increase the risk of OPD visits for headaches in Taipei, Taiwan.

Short-term effects of fine particulate air pollution on hospital admissions for cardiovascular diseases: a case-crossover study in a tropical city.

This study was undertaken to determine whether there was an association between fine particles (PM2.5) levels and hospital admissions for cardiovascular diseases (CVD) in Kaohsiung, Taiwan. Hospital admissions for CVD (including ischemic heart disease [IHD], stroke, congestive heart failure [CHF], and arrhythmias) and ambient air pollution data for Kaohsiung were obtained for the period from 2006-2010. The relative risk of hospital admissions for CVD was estimated using a case-crossover approach, controlling for weather variables, day of the week, seasonality, and long-term time trends. For the single-pollutant model (without adjustment for other pollutants), elevated number of admissions for CVD were significantly associated with higher PM2.5 levels only on cool days (<25°C), with an interquartile range rise associated with a 47% (95% CI = 39-56%), 48% (95% CI = 40-56%), 47% (95% CI = 34-61%), and 51% (95% CI = 34-70%) increase in IHD, stroke, CHF, and arrhythmias admissions, respectively. No significant associations between PM2.5 and hospital admissions for CVD were observed on warm days. In the two-pollutant models, PM2.5 levels remained significant even controlling for sulfur dioxide, nitrogen dioxide, carbon monoxide, or ozone on cool days. This study provides evidence that higher levels of PM2.5 enhance the risk of hospital admissions for CVD in Kaohsiung, Taiwan.

Relationship between hemorrhagic stroke hospitalization and exposure to fine particulate air pollution in Taipei, Taiwan.

This study was undertaken to determine whether there was a correlation between fine particle (PM2.5) levels and hospital admissions for hemorrhagic stroke (HS) in Taipei, Taiwan. Hospital admissions for HS and ambient air pollution data for Taipei were obtained for the period 2006-2010. The relative risk of hospital admissions was estimated using a case-crossover approach, controlling for weather variables, day of the week, seasonality, and long-term time trends. For the single-pollutant model (without adjustment for other pollutants), increased HS admissions were significantly associated with PM2.5 levels both on warm days (>23°C) and cool days (<23°C), with an interquartile range rise associated with a 12% (95% CI = 7-18%) and 4% (95% CI = 0-8%) elevation in admissions for HS, respectively. In the two-pollutant models, PM2.5 remained significantly high after inclusion of SO2 or O3 on both warm and cool days. This study provides evidence that higher levels of PM2.5 increase the risk of hospital admissions for HS.

Fine particulate air pollution and hospital admissions for myocardial infarction in a subtropical city: Taipei, Taiwan.

This study was undertaken to determine whether there was a correlation between fine particles (PM2.5) levels and hospital admissions for myocardial infarction (MI) in Taipei, Taiwan. Hospital admissions for MI and ambient air pollution data for Taipei were obtained for the period 2006-2010. The relative risk of hospital admissions for MI was estimated using a casecrossover approach, controlling for weather variables, day of the week, seasonality, and longterm time trends. For the single-pollutant model (without adjustment for other pollutants), increased numbers of MI admissions were significantly associated with higher PM2.5 levels both on warm days (>23°C) and on cool days (<23°C). This was accompanied by an interquartile range elevation correlated with a 10% (95% CI = 6-15%) and 5% (95% CI = 1-9%) rise in number of MI admissions, respectively. In the two-pollutant models, PM2.5 remained significant after inclusion of SO2 or O3 on both warm and cool days. This study provides evidence that higher levels of PM2.5 increase the risk of hospital admissions for MI.

Acute reactions after a homologous primary COVID-19 vaccination series: Analysis of Taiwan V-Watch data.

INTRODUCTION: The ChAdOx1 nCoV-19 (ChAd), mRNA-1273 (m1273), MVC-COV1901 (MVC), and BNT162b2 (BNT) COVID-19 vaccines received authorization for emergency use in Taiwan beginning in February 2021. We investigated acute reactions to homologous primary COVID-19 vaccination series in adults aged ≥ 18 years. METHODS: In this prospective observational study based on smartphone data (Taiwan V-Watch), we calculated the frequencies of self-reported local and systemic acute reactions within 7 days of a COVID-19 vaccination, and the health effects up to 3 weeks after each dose. Those who reported adverse reactions after both doses were assessed by the McNemar test. RESULTS: During 22 March 2021-13 December 2021, 77,468 adults were enrolled; 59.0 % were female and 77.8 % were aged 18-49 years. For both doses of all four vaccines, the local and systemic reactions were minor in severity and highest on days 1 and 2 after vaccination, and declined markedly until day 7. For 65,367 participants who provided data after the first and second doses, systemic reactions were more frequent after dose 2 of the BNT and m1273 vaccines (McNemar tests: both p < 0.001), while local reactions were more frequent after dose 2 of the m1273 and MVC vaccines (both p < 0.001), compared with dose 1 of the homologous vaccine. Among the participants aged 18-49 years, the percentage who missed work on the day after vaccination was slightly higher among women (9.3 %) than among men (7.0 %). CONCLUSIONS: Acute reactogenicity and impact of work absenteeism for the four COVID vaccines in the V-Watch survey were mild and of short duration.

Activation of HGF/c-Met signaling by ultrafine carbon particles and its contribution to alveolar type II cell proliferation.

Hepatocyte growth factor (HGF) is a potent mitogen and motogen for various epithelial cells. The present study aimed to explore the role of HGF and c-Met receptor in ultrafine carbon particle-induced alveolar type II epithelial (type II) cell proliferation. ICR mice were intratracheally instilled with 100 µg ultrafine carbon black (ufCB) and killed at 21, 48, and 72 days postexposure to examine type II cell proliferation, HGF release, and c-Met activation. In vivo and in vitro applications of neutralizing anti-HGF antibody were used to investigate the causal role of HGF in cell proliferation. The Met kinase inhibitor SU11274 and extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor PD98059 were used to delineate the involvement of c-Met/ERK1/2 in rat L2 pulmonary epithelial cell proliferation. The results demonstrated that in vivo exposure to 100 µg ufCB caused increased HGF in bronchoalveolar lavage fluid, as well as increased HGF production, c-Met phosphorylation, and cell proliferation in type II cells. In vitro study revealed that ufCB caused a dose-dependent increase in HGF release, c-Met phosphorylation, and cell proliferation. Importantly, treatment with the neutralizing anti-HGF antibody significantly blocked ufCB-induced in vivo and in vitro type II cell proliferation. Moreover, SU11274 and PD98059 significantly reduced ufCB-increased L2 cell proliferation. Results from Western blotting demonstrated that SU11274 successfully suppressed ufCB-induced phosphorylation of c-Met and ERK1/2. In summary, the activation of HGF/c-Met signaling is a major pathway involved in ufCB-induced type II cell proliferation.

Identification of Escherichia coli genes associated with urinary tract infections.

Escherichia coli is the most common cause of urinary tract infections (UTIs). E. coli genes epidemiologically associated with UTIs are potentially valuable in developing strategies for treating and/or preventing such infections as well as differentiating uropathogenic E. coli from nonuropathogenic E. coli. To identify E. coli genes associated with UTIs in humans, we combined microarray-based and PCR-based analyses to investigate different E. coli source groups derived from feces of healthy humans and from patients with cystitis, pyelonephritis, or urosepsis. The cjrABC-senB gene cluster, sivH, sisA, sisB, eco274, and fbpB, were identified to be associated with UTIs. Of these, cjrABC-senB, sisA, sisB, and fbpB are known to be involved in urovirulence in the mouse model of ascending UTI. Our results provide evidence to support their roles as urovirulence factors in human UTIs. In addition, the newly identified UTI-associated genes were mainly found in members of phylogenetic groups B2 and/or D.

Development of a Gd(III)-based receptor-induced magnetization enhancement (RIME) contrast agent for ß-glucuronidase activity profiling.

ß-Glucuronidase is a key lysosomal enzyme and is often overexpressed in necrotic tumor masses. We report here the synthesis of a pro receptor-induced magnetization enhancement (pro-RIME) magnetic resonance imaging (MRI) contrast agent ([Gd(DOTA-FPßGu)]) for molecular imaging of ß-glucuronidase activity in tumor tissues. The contrast agent consists of two parts, a gadolinium complex and a ß-glucuronidase substrate (ß-d-glucopyranuronic acid). The binding association constant (KA) of [Gd(DOTA-FPßGu)] is 7.42 × 10(2), which is significantly lower than that of a commercially available MS-325 (KA = 3.0 × 10(4)) RIME contrast agent. The low KA value of [Gd(DOTA-FPßGu)] is due to the pendant ß-d-glucopyranuronic acid moiety. Therefore, [Gd(DOTA-FPßGu)] can be used for detection of ß-glucuronidase through RIME modulation. The detail mechanism of enzymatic activation of [Gd(DOTA-FPßGu)] was elucidated by LC-MS. The kinetics of ß-glucuronidase catalyzed hydrolysis of [Eu(DOTA-FPßGu)] at pH 7.4 best fit the Miechalis-Menten kinetic mode with Km = 1.38 mM, kcat = 3.76 × 10(3), and kcat/Km = 2.72 × 10(3) M(-1) s(-1). The low Km value indicates high affinity of ß-glucuronidase for [Gd(DOTA-FPßGu)] at physiological pH. Relaxometric studies revealed that T1 relaxivity of [Gd(DOTA-FPßGu)] changes in response to the concentration of ß-glucuronidase. Consistent with the relaxometric studies, [Gd(DOTA-FPßGu)] showed significant change in MR image signal in the presence of ß-glucuronidase and HSA. In vitro and in vivo MR images demonstrated appreciable differences in signal enhancement in the cell lines and tumor xenografts in accordance to their expression levels of ß-glucuronidase.

Trihalomethanes in drinking water and the risk of death from kidney cancer: does hardness in drinking water matter?

The objectives of this study were to (1) examine the relationship between total trihalomethanes (TTHM) levels in public water supplies and risk of development of kidney cancer and (2) determine whether hardness levels in drinking water modify the effects of TTHM on risk of kidney cancer induction. A matched case-control study was used to investigate the relationship between the risk of death attributed to kidney cancer and exposure to TTHM in drinking water in 53 municipalities in Taiwan. All kidney cancer deaths in the 53 municipalities from 1998 through 2007 were obtained. Controls were deaths from other causes and were pair-matched to the cancer cases by gender, year of birth, and year of death. Each matched control was selected randomly from the set of possible controls for each cancer case. Data on TTHM levels and levels of hardness in drinking water were also collected. The municipality of residence for cancer cases and controls was presumed to be the source of the subject's TTHM and hardness exposure via drinking water. Relative to individuals whose TTHM exposure level was <4.9 ppb, the adjusted OR (95% CI) for kidney cancer was 0.98 (0.77-1.25) for individuals who resided in municipalities served by drinking water with a TTHM exposure ≥4.9 ppb. However, evidence of an interaction was noted between the use of soft water and drinking water TTHM concentrations. Increased knowledge of the interaction between hardness and TTHM levels in reducing risk of kidney cancer development will aid in public policy decision and establishing standards to prevent disease occurrence.

Top-Emitting Active-Matrix Quantum Dot Light-Emitting Diode Array with Optical Microcavity for Micro QLED Display.

An electroluminescent quantum-dot light-emitting diode (QLED) device and a micro QLED device array with a top-emitting structure were demonstrated in this study. The QLED device was fabricated in the normal structure of [ITO/Ag/ITO anode]/PEDOT:PSS/PVK/QDs/[ZnO nanoparticles]/Ag/MoO3, in which the semi-transparent MoO3-capped Ag cathode and the reflective ITO/metal/ITO (IMI) anode were designed to form an optical microcavity. Compared with conventional bottom-emitting QLED, the microcavity-based top-emitting QLED possessed enhanced optical properties, e.g., ~500% luminance, ~300% current efficiency, and a narrower bandwidth. A 1.49 inch micro QLED panel with 86,400 top-emitting QLED devices in two different sizes (17 × 78 µm2 and 74 × 40.5 µm2) on a low-temperature polysilicon (LTPS) backplane was also fabricated, demonstrating the top-emitting QLED with microcavity as a promising structure in future micro display applications.

Statins increase the risk of prostate cancer: a population-based case-control study.

BACKGROUND: Experimental studies have shown that statins have potential protective effects against cancer. The aim of this study was to investigate whether the use of statins was associated with prostate cancer risk. METHODS: We conducted a population-based case-control study in Taiwan. Data were retrospectively collected from the Taiwan National health Insurance Research Database. Cases consisted of all patients who were aged 50 years and older and had a first-time diagnosis of prostate cancer for the period between 2005 and 2008. The controls were matched to cases by age, sex, and index date. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by using multiple logistic regression. RESULTS: We examined 388 prostate cancer cases and 1,552 controls. We found that ever-use of any statin was associated with a significant increase in prostate cancer risk (OR = 1.55, 95%CI = 1.09-2.19). Compared with no use of statins, the adjusted ORs (95%CI) were 1.17 (0.60-2.28) for the group with cumulative dose ≤29.44 DDD, 1.59 (1.02-2.48) for the group with cumulative dose between 29.44 DDD and 321.33 DDD, and 1.86 (1.03-3.37) for the group with the highest cumulative dose (≥321.33 DDD). Also, there was a significant trend toward increasing prostate cancer risk with increasing cumulative dose (χ(2) for linear trend = 7.23, P = 0.007). CONCLUSIONS: The results of this case-control study suggest that statins may increase the risk of prostate cancer.

Sesamol attenuates isoproterenol-induced acute myocardial infarction via inhibition of matrix metalloproteinase-2 and -9 expression in rats.

BACKGROUND/AIMS: The protective role of sesamol and its possible action against isoproterenol-induced myocardial injury and infarction is unknown. We tested the hypothesis that sesamol's protection against myocardial infarction is associated with the inhibition of matrix metalloproteinase (MMP)-2 and MMP-9. METHODS: Four groups of experimental rats were subcutaneously injected with sesamol (0, 1, 3, or 10 mg/kg) and then, 2 h later, intraperitoneally injected with isoproterenol (100 mg/kg 24 h apart on 2 consecutive days) to induce myocardial infarction. Control rats were treated with saline only. Blood pressure (BP), heart rate (HR), and electrocardiography (ECG) wave durations, serum creatine phosphokinase isoenzymes (CKMB), lactate dehydrogenase (LDH), myocardial histology, MMP-2, and MMP-9 were assessed 24 h after the last dose of isoproterenol was given. RESULTS: BP was lower, and HR, ECG wave durations, CKMB, LDH, myocardial injury, MMP-2, and MMP-9 levels were higher in experimental rats than in control rats. BP was significantly higher, and all the other parameters were significantly lower in the rats treated with sesamol than in those treated with isoproterenol only. CONCLUSIONS: Sesamol effectively prevented myocardial infarction, at least in part, by controlling proteolytic activities and the expression of MMP-2 and -9 in isoproterenol-treated rats.

Statins are associated with a reduced risk of gastric cancer: a population-based case-control study.

OBJECTIVES: Experimental studies have shown that statins have potential protective effects against cancer. The aim of this study was to investigate whether the use of statins was associated with gastric cancer risk. METHODS: We conducted a population-based case-control study in Taiwan. Data were retrospectively collected from the Taiwan National health Insurance Research Database. Cases consisted of all patients who were aged ≥50 years and had a first-time diagnosis of gastric cancer for the period between 2005 and 2008. The controls were matched to cases by age, sex, and index date. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by using multiple logistic regression. RESULTS: We examined 337 gastric cancer cases and 1,348 controls. We found that ever-use of any statin was associated with a significant decrease in gastric cancer risk (OR=0.68, 95% CI=0.49-0.95). Compared with no use of statins, the adjusted ORs were 0.90 (95% CI=0.60-1.36) for the group having been prescribed statins with cumulative defined daily doses (DDDs) <134.25 and 0.49 (95% CI=0.30-0.79) for the group with cumulative statin use of ≥134.25 DDDs. Also, there was a significant trend toward decreasing gastric cancer risk with increasing cumulative dose (χ(2) for linear trend=7.42, P=0.006). CONCLUSIONS: The results of this study are the first to suggest that statins may reduce the risk of gastric cancer.

Calcium and magnesium in drinking water and risk of death from kidney cancer.

The possible association between the risk of kidney cancer development and the levels of calcium and magnesium in drinking water from municipal supplies was investigated in a matched cancer case-control study in Taiwan. All eligible kidney cancer deaths (1778 cases) of Taiwan residents from 1999 through 2008 were compared with deaths from other causes (1778 controls), and the levels of calcium and magnesium in drinking water of these residents were determined. Data on calcium and magnesium levels in drinking water throughout Taiwan were obtained from the Taiwan Water Supply Corporation (TWSC). The control group consisted of individuals who died from other causes, and the controls were pair-matched to the cancer cases by gender, year of birth, and year of death. The adjusted odd ratios for death attributed to kidney cancer for individuals with higher calcium levels in their drinking water, as compared to the lowest tertile, were 0.89 (95% CI = 0.72-1.11) and 0.78 (95% CI = 0.62-0.98), respectively. The adjusted odd ratios were not statistically significant for the relationship between magnesium levels in drinking water and kidney cancer development. The results of the present study demonstrate that there may be a significant protective effect of calcium intake from drinking water against the risk of death due to kidney cancer.

Elastases from inflammatory and dendritic cells mediate ultrafine carbon black induced acute lung destruction in mice.

CONTEXT: Exposure to ultrafine particles (<100 nm in diameter) is postulated to cause chronic obstructive pulmonary disease (COPD). However, the mechanism remains to be elucidated. OBJECTIVE: We aimed to evaluate whether ultrafine particle exposure causes the infiltration of inflammatory and dendritic cells (DCs) with increased elastase activity, contributing to lung parenchymal destruction. MATERIALS AND METHODS: C57BL/6 male mice were intratracheally instilled with 300 µg ultrafine carbon black (ufCB; 14 nm in diameter), and sacrificed at 1, 3, 7 and 14 d post-exposure. Differential cell counts, elastase activities, and desmosine and hydroxyproline in bronchoalveolar (BAL) fluid were determined. Immunofluorescent staining and flow cytometry analysis determined the cell origin of macrophage metalloelastase (MMP-12). Anti-neutrophil antibody was applied to assess the contribution of elastase in ufCB induced lung destruction. RESULTS: ufCB exposure led to significant increases in neutrophils, mononuclear cells and total proteins in BAL fluid. Desmosine and hydroxyproline were significantly increased in the ufCB group. Elastase activities were found to be significantly elevated, with both neutrophil elastase and MMP-12 peaking at 3 d post-exposure. Flow cytometry analysis demonstrated that pulmonary infiltrations of MMP-12 positive DCs, including Langerhans cells-derived DCs, occurred at 3 d and 7 d, while macrophage infiltration was obvious starting at 1 d. Anti-neutrophil antibody significantly reduced neutrophil elastase activity and prevented the increases in BAL desmosine and hydroxyproline following ufCB exposure. CONCLUSION: For the first time we demonstrate the infiltration of Langerhans and myeloid dendritic cells, and show that elastase production contributes to pulmonary destruction following exposure to ultrafine particles.

High-Flow Nasal Cannula Therapy in Children With Acute Respiratory Distress With Hypoxia in A Pediatric Intensive Care UnitA Single Center Experience.

Aim: High-flow nasal cannulas (HFNCs) show potential in the application of positive pressure, improving gas exchange, and decreasing work of breathing in patients with acute respiratory distress. The aims of this study were to elucidate the indications for HFNC therapy in children of all ages and diagnoses, and to evaluate the efficacy and risk factors for failure of HFNC therapy in children with acute respiratory distress with hypoxia in a pediatric intensive care unit. Methods: We conducted this retrospective cohort study at a tertiary pediatric intensive care unit between January 1, 2018 and December 31, 2020. All children, from 1 month to 18 years of age, with acute respiratory distress with hypoxia and HFNC therapy were eligible. The clinical data were reviewed. Results: One hundred and two children met the eligibility criteria for the study, of whom 57 (55.9%) were male, and the mean age was 7.00 6.79 years. Seventy-eight (76.5%) of the children had underlying disorders. The most common indications for the use of HFNC therapy were pneumonia (40, 39.2%), sepsis-related respiratory distress (17, 16.7%), and bronchiolitis (16, 15.7%). The failure rate was 15.7% (16 of 102 children). Higher initial and maximum fraction of inspiration O2 levels and lower initial and lowest SpO2/FiO2 (S/F) ratio were early and possible signs of failure requiring escalation of respiratory support. Conclusion: In our population, we found that HFNC therapy could be initiated as the first-line therapy for various etiologies of acute respiratory distress with hypoxia in a pediatric intensive care unit and for all age groups.

Use of proton pump inhibitors increased the risk of hip fracture: a population-based case-control study.

PURPOSE: To investigate whether the use of proton pump inhibitor (PPIs) was associated with an increased risk of hip fracture. METHODS: We conducted a population-based case-control study in Taiwan. Data were retrospectively collected from the Taiwan National health Insurance Research Database. Cases included all patients with a newly diagnosed of hip fracture in 2005 and 2006 (n = 1241). The controls were pair matched to cases by age, sex, and index date. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by using multiple logistic regression. RESULTS: Having been prescribed more than 28 defined daily dose (DDDs) of PPIs was associated with an increased risk for hip fracture in multivariate analyses (adjustments for matching variables and medication use) (at 29-70 DDDs, OR = 1.67, 95% CI = 1.11-2.51 and at >70 DDDs, OR = 2.51, 95% CI = 1.77-3.55). There was a significant trend toward increasing hip fracture risk with increasing cumulative DDDs of PPIs (p for trend <0.0001). CONCLUSIONS: This study provides evidence that PPIs use is associated with an increased risk of hip fracture in a dose-response manner.

Nitrates in drinking water and the risk of death from rectal cancer: does hardness in drinking water matter?

The objectives of this study were to (1) examine the relationship between nitrate levels in public water supplies and increased risk of death from rectal cancer and (2) determine whether calcium (Ca) and magnesium (Mg) levels in drinking water might modify the effects of nitrate on development of rectal cancer. A matched case-control study was used to investigate the relationship between the risk of death from rectal cancer and exposure to nitrate in drinking water in Taiwan. All rectal cancer deaths of Taiwan residents from 2003 through 2007 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to the cases by gender, year of birth, and year of death. Information on the levels of nitrate-nitrogen (NO(3)-N), Ca, and Mg in drinking water was collected from Taiwan Water Supply Corporation (TWSC). The municipality of residence for cancer cases and controls was presumed to be the source of the subject's NO(3)-N, Ca, and Mg exposure via drinking water. Relative to individuals whose NO(3)-N exposure level was <0.38 ppm, the adjusted odds ratio (OR) (95% CI) for rectal cancer occurrence was 1.15 (1.01-1.32) for individuals who resided in municipalities served by drinking water with a NO(3)-N exposure > or =0.38 ppm. There was no apparent evidence of an interaction between drinking water NO(3)-N levels with low Mg intake via drinking water. However, evidence of a significant interaction was noted between drinking-water NO(3)-N concentrations and Ca intake via drinking water. Our findings showed that the correlation between NO(3)-N exposure and risk of rectal cancer development was influenced by Ca in drinking water. This is the first study to report effect modification by Ca intake from drinking water on the association between NO(3)-N exposure and risk of rectal cancer occurrence. Increased knowledge of the mechanistic interaction between Ca and NO(3)-N in reducing rectal cancer risk will aid in public policymaking and setting threshold standards.