The impact of temperature on mortality in Tianjin, China : a case-crossover design with a distributed lag non-linear model

Background There has been increasing interest in assessing the impacts of temperature on mortality. However, few studies have used a case–crossover design to examine non-linear and distributed lag effects of temperature on mortality. Additionally, little evidence is available on the temperature-mortality relationship in China, or what temperature measure is the best predictor of mortality. Objectives To use a distributed lag non-linear model (DLNM) as a part of case–crossover design. To examine the non-linear and distributed lag effects of temperature on mortality in Tianjin, China. To explore which temperature measure is the best predictor of mortality; Methods: The DLNM was applied to a case¬−crossover design to assess the non-linear and delayed effects of temperatures (maximum, mean and minimum) on deaths (non-accidental, cardiopulmonary, cardiovascular and respiratory). Results A U-shaped relationship was consistently found between temperature and mortality. Cold effects (significantly increased mortality associated with low temperatures) were delayed by 3 days, and persisted for 10 days. Hot effects (significantly increased mortality associated with high temperatures) were acute and lasted for three days, and were followed by mortality displacement for non-accidental, cardiopulmonary, and cardiovascular deaths. Mean temperature was a better predictor of mortality (based on model fit) than maximum or minimum temperature. Conclusions In Tianjin, extreme cold and hot temperatures increased the risk of mortality. Results suggest that the effects of cold last longer than the effects of heat. It is possible to combine the case−crossover design with DLNMs. This allows the case−crossover design to flexibly estimate the non-linear and delayed effects of temperature (or air pollution) whilst controlling for season.

Gonadotropin-induced ovarian cancer cell migration and proliferation require extracellular signal-regulated kinase 1/2 activation regulated by calcium and protein kinase Cδ

The gonadotropin hypothesis proposes that elevated serum gonadotropin levels may increase the risk of epithelial ovarian cancer (EOC). We have studied the effect of treating EOC cell lines (OV207 and OVCAR-3) with FSH or LH. Both gonadotropins activated the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase 1/2 (ERK1/2) pathway and increased cell migration that was inhibited by the MAPK 1 inhibitor PD98059. Both extra- and intracellular calcium ion signalling were implicated in gonadotropin-induced ERK1/2 activation as treatment with either the calcium chelator EGTA or an inhibitor of intracellular calcium release, dantrolene, inhibited gonadotropin-induced ERK1/2 activation. Verapamil was also inhibitory, indicating that gonadotropins activate calcium influx via L-type voltage-dependent calcium channels. The cAMP/protein kinase A (PKA) pathway was not involved in the mediation of gonadotropin action in these cells as gonadotropins did not increase intracellular cAMP formation and inhibition of PKA did not affect gonadotropin-induced phosphorylation of ERK1/2. Activation of ERK1/2 was inhibited by the protein kinase C (PKC) inhibitor GF 109203X as well as by the PKCδ inhibitor rottlerin, and downregulation of PKCδ was inhibited by small interfering RNA (siRNA), highlighting the importance of PKCδ in the gonadotropin signalling cascade. Furthermore, in addition to inhibition by PD98059, gonadotropin-induced ovarian cancer cell migration was also inhibited by verapamil, GF 109203X and rottlerin. Similarly, gonadotropin-induced proliferation was inhibited by PD98059, verapamil, GF 109203X and PKCδ siRNA. Taken together, these results demonstrate that gonadotropins induce both ovarian cancer cell migration and proliferation by activation of ERK1/2 signalling in a calcium- and PKCδ-dependent manner.

Nitrone [2]rotaxanes: Simultaneous chemical protection and electrochemical activation of a functional group

We report on the use of the hydrogen bond accepting properties of neutral nitrone moieties to prepare benzylic-amide-macrocycle-containing [2]rotaxanes in yields as high as 70 %. X-Ray crystallography shows the presence of up to four intercomponent hydrogen bonds between the amide groups of the macrocycle and the two nitrone groups of the thread. Dynamic 1H NMR studies of the rates of macrocycle pirouetting in nonpolar solutions indicate that amide-nitrone hydrogen bonds are particularly strong, ~1.3 and ~0.2 kcal mol-1 stronger than similar amide-ester and amide-amide interactions, respectively. In addition to polarizing the N-O bond through hydrogen bonding, the rotaxane structure affects the chemistry of the nitrone groups in two significant ways: The intercomponent hydrogen bonding activates the nitrone groups to electrochemical reduction, a one electron reduction of the rotaxane being stablized by a remarkable 400 mV (8.1 kcal mol-1) with respect to the same process in the thread; encapsulation, however, protects the same functional groups from chemical reduction with an external reagent (and slows down electron transfer to and from the electroactive groups in cyclicvoltammetry experiments). Mechanical interlocking with a hydrogen bonding molecular sheath thus provides a route to an encapsulated polarized functional group and radical anions of significant kinetic and thermodynamic stability.

A large change in temperature between neighbouring days increases the risk of mortality

Background: Previous studies have found high temperatures increase the risk of mortality in summer. However, little is known about whether a sharp decrease or increase in temperature between neighbouring days has any effect on mortality. Method: Poisson regression models were used to estimate the association between temperature change and mortality in summer in Brisbane, Australia during 1996–2004 and Los Angeles, United States during 1987–2000. The temperature change was calculated as the current day’s mean temperature minus the previous day’s mean. Results: In Brisbane, a drop of more than 3 °C in temperature between days was associated with relative risks (RRs) of 1.157 (95% confidence interval (CI): 1.024, 1.307) for total non external mortality (NEM), 1.186 (95%CI: 1.002, 1.405) for NEM in females, and 1.442 (95%CI: 1.099, 1.892) for people aged 65–74 years. An increase of more than 3 °C was associated with RRs of 1.353 (95%CI: 1.033, 1.772) for cardiovascular mortality and 1.667 (95%CI: 1.146, 2.425) for people aged < 65 years. In Los Angeles, only a drop of more than 3 °C was significantly associated with RRs of 1.133 (95%CI: 1.053, 1.219) for total NEM, 1.252 (95%CI: 1.131, 1.386) for cardiovascular mortality, and 1.254 (95%CI: 1.135, 1.385) for people aged ≥75 years. In both cities, there were joint effects of temperature change and mean temperature on NEM. Conclusion : A significant change in temperature of more than 3 °C, whether positive or negative, has an adverse impact on mortality even after controlling for the current temperature.

Ambient temperature and morbidity: A review of epidemiological evidence

OBJECTIVE: This paper reviews the epidemiological evidence on the relationship between ambient temperature and morbidity. It assesses the methodological issues in previous studies, and proposes future research directions. DATA SOURCES AND DATA EXTRACTION: We searched the PubMed database for epidemiological studies on ambient temperature and morbidity of non-communicable diseases published in refereed English journals prior to June 2010. 40 relevant studies were identified. Of these, 24 examined the relationship between ambient temperature and morbidity, 15 investigated the short-term effects of heatwave on morbidity, and 1 assessed both temperature and heatwave effects. DATA SYNTHESIS: Descriptive and time-series studies were the two main research designs used to investigate the temperature–morbidity relationship. Measurements of temperature exposure and health outcomes used in these studies differed widely. The majority of studies reported a significant relationship between ambient temperature and total or cause-specific morbidities. However, there were some inconsistencies in the direction and magnitude of non-linear lag effects. The lag effect of hot temperature on morbidity was shorter (several days) compared to that of cold temperature (up to a few weeks). The temperature–morbidity relationship may be confounded and/or modified by socio-demographic factors and air pollution. CONCLUSIONS: There is a significant short-term effect of ambient temperature on total and cause-specific morbidities. However, further research is needed to determine an appropriate temperature measure, consider a diverse range of morbidities, and to use consistent methodology to make different studies more comparable.

P2-486 Environmental temperature variation and morbidity: a meta-analysis

Extreme temperatures have been shown to have a detrimental effect on health. Hot temperatures can increase the risk of mortality, particularly in people suffering from cardiorespiratory diseases. Given the onset of climate change, it is critical that the impact of temperature on health is understood, so that effective public health strategies can correctly identify vulnerable groups within the population. However, while effects on mortality have been extensively studied, temperature–related morbidity has received less attention. This study applied a systematic review and meta–analysis to examine the current literature relating to hot temperatures and morbidity.