Mitosis targeting in non-small lung cancer cells by inhibition of PAD4.

PAD4 expression and activity were significantly up-regulated in lung cancer tissues suggesting that PAD4 could be a possible target for lung cancer treatment. In this study we had demonstrated that PAD4 expression was higher in lung cancer patients whom with lymphnode metastasis and pleural invasion. Inhibiting PAD4 with a small molecular inhibitor could induce apoptosis and suppress growth in lung cancer cells. We used RNA-sequencing to further investigate transcriptional changes that induced by PAD4 inhibition, and results suggested its affected mostly on the cell cycle, mitotic cell cycle process, p53 signaling pathway. By using image flow cytometry analysis, we found that PAD4 inhibited by YW3-56 could accumulate cells in the G1/G0 phases and reducing the fraction of G2/M and S phase cells. Quantification of different phase of mitosis in cells treated with YW3-56 revealed an increasing trend of telophase and prophase cells. Taken together, our data indicated that PAD4 inhibitor could affect cell cycle and mitosis of lung cancer cells, and targeting PAD4 could be a promising strategy for discovery novel anti-NSCLC treatments.

CRP inhibits the osteoblastic differentiation of OPCs via the up-regulation of primary cilia and repression of the Hedgehog signaling pathway.

Inflammation disrupts bone metabolism and leads to bone damage. C-reactive protein (CRP) is a typical inflammation marker. Although CRP measurement has been conducted for many decades, how osteoblastic differentiation influences molecular mechanisms remains largely unknown. The present study attempted to investigate the effects of CRP on primary cultured osteoblast precursor cells (OPCs) while elucidating the underlying molecular mechanisms. OPCs were isolated from suckling Sprague-Dawleyrats. Fewer OPCs were observed after recombinant C-reactive protein treatment. In a series of experiments, CRP inhibited OPC proliferation, osteoblastic differentiation, and the OPC gene expression of the hedgehog (Hh) signaling pathway. The inhibitory effect of CRP on OPC proliferation occurred via blockade of the G1-S transition of the cell cycle. In addition, the regulation effect of proto cilium on osteoblastic differentiation was analyzed using the bioinformatics p. This revealed the primary cilia activation of recombinant CRP effect on OPCs through in vitro experiments. A specific Sonic Hedgehog signaling agonist (SAG) rescued osteoblastic differentiation inhibited by recombinant CRP. Moreover, chloral hydrate, which removes primary cilia, inhibited the Suppressor of Fused (SUFU) formation and blocked Gli2 degradation. This counteracted osteogenesis inhibition caused by CRP. Therefore, these data depict that CRP can inhibit the proliferation and osteoblastic differentiation of OPCs. The underlying mechanism could be associated with primary cilia activation and Hh pathway repression.

PDGF-BB/PDGFRß induces tumour angiogenesis via enhancing PKM2 mediated by the PI3K/AKT pathway in Wilms' tumour.

Platelet-derived growth factor receptor-ß (PDGFRß) is a critical type III receptor tyrosine kinase family member, which is involved in Wilms' tumour (WT) metastasis and aerobic glycolysis. The role of PDGFRß in tumour angiogenesis has not been fully elucidated. Here, we examined the effect of PDGFRß on angiogenesis in WT. First, the NCBI database integrated three datasets, GSE2712, GSE11151, and GSE73209, to screen differentially expressed genes. The R language was used to analyse the correlation between PDGFRB and vascular endothelial growth factor (VEGF). The results showed that PDGFRB, encoding PDGFRß, was upregulated in WT, and its level was correlated with VEGFA expression. Next, PDGFRß expression was inhibited by small interfering RNA (siRNA) or activated with the exogenous ligand PDGF-BB. The expression and secretion of the angiogenesis elated factor VEGFA in WT G401 cells were detected using Western blotting and ELISA, respectively. The effects of conditioned medium from G401 cells on endothelial cell viability, migration, invasion, the total length of the tube, and the number of fulcrums were investigated. To further explore the mechanism of PDGFRß in the angiogenesis of WT, the expression of VEGFA was detected after blocking the phosphatidylinositol-3-kinase (PI3K) pathway and inhibiting the expression of PKM2, a key enzyme of glycolysis. The results indicated that PDGFRß regulated the process of tumour angiogenesis through the PI3K/AKT/PKM2 pathway. Therefore, this study provides a novel therapeutic strategy to target PDGFRß and PKM2 to inhibit glycolysis and anti-angiogenesis, thus, developing a new anti-vascular therapy.

Prognostic value of miR-219-5p in relation to mortality in patients with small cell lung cancer: a retrospective, observational cohort study in China.

OBJECTIVES: Small cell lung cancer (SCLC) is a lethal human malignancy, and previous studies support the contribution of microRNA to cancer progression. The prognostic value of miR-219-5p in patients with SCLC remains unclear. This study aimed to evaluate the predictive value of miR-219-5p with respect to mortality in patients with SCLC and to incorporate miR-219-5p level into a prediction model and nomogram for mortality. DESIGN: Retrospective observational cohort study. SETTING AND PARTICIPANTS: Our main cohort included data from 133 patients with SCLC between 1 March 2010 and 1 June 2015 from the Suzhou Xiangcheng People's Hospital. Data from 86 patients with non-SCLC at Sichuan Cancer Hospital and the First Affiliated Hospital of Soochow University were used for external validation. OUTCOME MEASURES: Tissue samples were taken during admission and stored, and miR-219-5p levels were measured at a later date. A Cox proportional hazard model was used for survival analyses and for analysing risk factors to create a nomogram for mortality prediction. The accuracy of the model was evaluated by C-index and calibration curve. RESULTS: Mortality in patients with a high level of miR-219-5p (≥1.50) (n=67) was 74.6%, while mortality in the low-level group (n=66) was 100.0%. Based on univariate analysis, we included significant factors (p<0.05) in a multivariate regression model: patients with high level of miR-219-5p (HR 0.39, 95% CI 0.26-0.59, p<0.001), immunotherapy (HR 0.44, 95% CI 0.23-0.84, p<0.001) and prognostic nutritional index score >47.9 (HR=0.45, 95% CI 0.24-0.83, p=0.01) remained statistically significant factors for improved overall survival. The nomogram had good accuracy in estimating the risk, with a bootstrap-corrected C-index of 0.691. External validation indicated an area under the curve of 0.749 (0.709-0.788). CONCLUSIONS: The miR-219-5p level was associated with a reduced risk of mortality in patients with SCLC. A nomogram incorporating MiR-219-5p level and clinical factors demonstrated good accuracy in estimating the risk of overall mortality. Prospective validation of the prognostic nomogram is needed.

The Role of Peptidyl Arginine Deiminase IV(PADI4) in Cancers.

BACKGROUND: Peptidyl arginine deiminase IV (PADI4, also called PAD4), a Ca2+-dependent posttranslational modification enzyme, catalyzes the conversion of arginine residues to non-coded citrulline residues. Dysregulation of PADI4 is involved in a variety of diseases including rheumatoid arthritis (RA), multiple sclerosis (MS), Alzheimer's disease (AD) and many kinds of malignant tumors. OBJECTIVE: The roles of PADI4 in different tumors and the underlying molecular mechanisms are presented in this article. RESULTS: PADI4-mediated citrullination is associated with either transcriptional activation or repression in different contexts. Abnormal expression of PADI4 exists in a variety of malignant tumors and affects tumor progression and metastasis. Epithelial-to-mesenchymal transition (EMT), apoptosis, and neutrophil extracellular traps (NETs) may be the underlying molecular mechanisms. CONCLUSION: PADI4 plays crucial role in the occurrence, development, and metastasis of tumors, and PADI4 may be an effective biomarker for cancer prognosis and a potential target for cancer treatment.

Icariin Treatment Rescues Diabetes Induced Bone Loss via Scavenging ROS and Activating Primary Cilia/Gli2/Osteocalcin Signaling Pathway.

Diabetes-associated bone complications lead to fragile bone mechanical strength and osteoporosis, aggravating the disease burden of patients. Advanced evidence shows that chronic hyperglycemia and metabolic intermediates, such as inflammatory factor, reactive oxygen species (ROS), and advanced glycation end products (AGEs), are regarded as dominant hazardous factors of bone complications, whereas the pathophysiological mechanisms are complex and controversial. By establishing a diabetic Sprague-Dawley (SD) rat model and diabetic bone loss cell model in vitro, we confirmed that diabetes impaired primary cilia and led to bone loss, while adding Icariin (ICA) could relieve the inhibitions. Mechanistically, ICA could scavenge ROS to maintain the mitochondrial and primary cilia homeostasis of osteoblasts. Intact primary cilia acted as anchoring and modifying sites of Gli2, thereby activating the primary cilia/Gli2/osteocalcin signaling pathway to promote osteoblast differentiation. All results suggest that ICA has potential as a therapeutic drug targeting bone loss induced by diabetes.

Longitudinal Associations of Air Pollution With Body Size and Composition in Midlife Women: The Study of Women's Health Across the Nation.

OBJECTIVE: We examined longitudinal associations of air pollution exposure, including fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3), with weight, BMI, waist circumference, fat mass, lean mass, and proportion fat mass in midlife women. RESEARCH DESIGN AND METHODS: The study population included 1,654 White, Black, Chinese, and Japanese women from the Study of Women's Health Across the Nation, with the baseline median age of 49.6 years, followed from 2000 to 2008. Annual air pollution exposures were assigned by linking residential addresses with hybrid estimates of air pollutant concentrations at 1-km2 resolution. Body size was measured, and body composition was measured using DXA at approximately annual visits. Linear mixed effects models were used to examine the associations between air pollution and body size and composition measures and whether these associations differed by physical activity. RESULTS: After adjusting for potential confounders, an interquartile range increase in PM2.5 concentration (4.5 µg/m3) was associated with 4.53% (95% CI 3.85%, 5.22%) higher fat mass, 1.10% (95% CI 0.95%, 1.25%) higher proportion fat mass, and 0.39% (95% CI -0.77%, -0.01%) lower lean mass. Similar associations were also observed for NO2 and O3. Weaker associations of PM2.5 and NO2 with body composition were observed in participants who engaged in more physical activity. CONCLUSIONS: Our analyses provide evidence that exposure to PM2.5, NO2, and O3, is adversely associated with body composition, including higher fat mass, higher proportional fat mass, and lower lean mass, highlighting their potential contribution to obesity.

Role of micronutrients in Alzheimer's disease: Review of available evidence.

Alzheimer's disease (AD) is one of the most common age-related neurodegenerative disorders that have been studied for more than 100 years. Although an increased level of amyloid precursor protein is considered a key contributor to the development of AD, the exact pathogenic mechanism remains known. Multiple factors are related to AD, such as genetic factors, aging, lifestyle, and nutrients. Both epidemiological and clinical evidence has shown that the levels of micronutrients, such as copper, zinc, and iron, are closely related to the development of AD. In this review, we summarize the roles of eight micronutrients, including copper, zinc, iron, selenium, silicon, manganese, arsenic, and vitamin D in AD based on recently published studies.

Influence of Dichloroacetate on Wilms'Tumor in vitro.

OBJECTIVE: To investigate the effect of dichloroacetate (DCA) on Wilms' tumor (WT) G401 cells. METHODS: CCK-8 assay was used to detect the influence of DCA on G401 cells viability and 10 mmol/L DCA was selected for subsequent experiments. The expression of glycolysis-related enzymes, such as hexokinase 2 (HK2), pyruvate kinase M2 (PKM2), lactic acid dehydrogenase A (LDHA), pyruvate dehydrogenase kinase 1 (PDK1), and pyruvate dehydrogenase (PDH), were detected by qRT-PCR and western blot. The extracellular lactic acid and glucose concentrations were measured by the lactic acid assay kit and glucose oxidase method kit respectively. Flow cytometry was used to detect the effect of DCA on G401 cells apoptosis. The invasion and migration ability of G401 cells were detected by Transwell assay and wound-healing assay. RESULTS: The results showed that DCA reduced glycolysis-related enzymes expression, inhibited lactic acid production, and glucose consumption. DCA also suppressed cells growth, induced cells apoptosis and inhibited cells invasion and migration. CONCLUSION: Inhibition of aerobic glycolysis by DCA can reduce the viability of G401 cells, promote cells apoptosis and inhibit cells invasion and migration. Therefore, aerobic glycolysis may be a potential therapeutic target for Wilms' tumor.

PDGF-BB/PDGFRß promotes epithelial-mesenchymal transition by affecting PI3K/AKT/mTOR-driven aerobic glycolysis in Wilms' tumor G401 cells.

Wilms' tumor (WT) is the most common pediatric renal malignancy. PDGFRß belongs to the type III receptor tyrosine kinase family and is known to be involved in tumor metastasis and angiogenesis. Here, we studied the effect and underlying mechanism of PDGFRß on WT G401 cells. Transwell assay and wound-healing assay were used to detect the effect of PDGFRß on G401 cells invasion and migration. Western blot and immunofluorescence were used to detect the expression of EMT-related genes. The expression of PI3K/AKT/mTOR pathway proteins was detected by Western blot. The relationship between PDGFRß and aerobic glycolysis was studied by assessing the expression of glycolysis-related enzymes detected by qRT-PCR and Western blot. The activity of HK, PK, and LDH was detected by corresponding enzyme activity kits. The concentration of lactic acid and glucose was detected by Lactic Acid Assay Kit and Glucose Assay Kit-glucose oxidase method separately. To investigate the mechanism of PDGFRß in the development of WT, the changes of glucose and lactic acid were analyzed after blocking PI3K pathway, aerobic glycolysis, or PDGFRß. The key enzyme was screened by Western blot and glucose metabolism experiment after HK2, PKM2, and PDK1 were inhibited. The results showed that PDGFRß promoted the EMT process by modulating aerobic glycolysis through PI3K/AKT/mTOR pathway in which PKM2 plays a key role. Therefore, our study of the mechanism of PDGFRß in G401 cells provides a new target for the treatment of WT.

PDGFRß modulates aerobic glycolysis in osteosarcoma HOS cells via the PI3K/AKT/mTOR/c-Myc pathway.

Osteosarcoma is a malignant tumor abundant in vascular tissue, and its rich blood supply may have a significant impact on its metabolic characteristics. PDGFRß is a membrane receptor highly expressed in osteosarcoma cells and vascular wall cells, and its effect on osteosarcoma metabolism needs to be further studied. In this study, we discussed the effect and mechanism of action of PDGFRß on glucose metabolism in human osteosarcoma (HOS) cells. GSEA, Pearson's correlation test, and PPI correlation analysis indicated positive regulation of PDGFRß on aerobic glycolysis in osteosarcoma. The results of qPCR and western blot further confirmed the prediction of bioinformatics. Glucose metabolism experiments proved that PDGF/PDGFRß could effectively promote aerobic glycolysis in osteosarcoma cells. In addition, the mitochondrial membrane potential (ΔΨm) experiment proved that the metabolic change triggered by PDGFRß was not caused by mitochondrial damage. The PI3K pathway inhibitor LY294002, MEK pathway inhibitor U0126, or Warburg effect inhibitor DCA was used to perform western blot and glucose metabolism experiments, and the results showed that PDGFBB/PDGFRß mainly activated the PI3K/AKT/mTOR/c-Myc pathway to promote aerobic glycolysis in osteosarcoma HOS cells. The newly elucidated role of PDGFRß provides a novel metabolic therapeutic target for osteosarcoma.

Primary cilia regulate gastric cancer-induced bone loss via cilia/Wnt/ß-catenin signaling pathway.

Cancer-associated bone disease is a frequent occurrence in cancer patients and is associated with pain, bone fragility, loss, and fractures. However, whether primary or non-bone metastatic gastric cancer induces bone loss remains unclear. Here, we collected clinical evidence of bone loss by analyzing serum and X-rays of 25 non-bone metastatic gastric cancer patients. In addition, C57BL mice were injected with the human gastric cancer cell line HGC27 and its effect on bone mass was analyzed by Micro-CT, immunoblotting, and immunohistochemistry. Furthermore, the degree of the proliferation and osteogenic differentiation of mesenchymal stem cells (MSCs) co-cultured with HGC-27 or SGC-7901 cells was analyzed by colony-formation assay, alizarin red staining, immunofluorescence, qPCR, immunoblotting, and alkaline phosphatase activity assay. These indicated that gastric cancer could damage bone tissue before the occurrence of bone metastases. We also found that cilia formation of MSCs was increased in the presence of HGC27 cells, which was associated with abnormal activation of the Wnt/ß-catenin pathway. Expression of DKK1 inhibited the Wnt/ß-catenin signaling pathway and partially rescued osteogenic differentiation of MSCs. In summary, our results suggest that gastric cancer cells might cause bone damage prior to the occurrence of bone metastasis via cilia-dependent activation of the Wnt/ß-catenin signaling pathway.

Examining fine particulate matter and cause-specific morbidity during the 2017 North San Francisco Bay wildfires.

BACKGROUND: Recent increases in wildfire frequency and severity necessitate better understanding of health effects of wildfire smoke to protect affected populations. OBJECTIVES: We examined relationships between fine particulate matter (PM2.5) and morbidity during wildfires in California, and whether those relationships differed during the fire compared to a similar non-fire period. METHODS: For nine San Francisco Bay Area counties, daily county-level diagnosis-specific counts of emergency department visits (EDVs) and hospitalizations were linked with county-level estimates of daily mean PM2.5 during the October 2017 Northern California wildfires and similar October days in 2015, 2016, and 2017. Associations were estimated using Poisson regression. RESULTS: The median difference between county PM2.5 during the fire versus the non-fire period was 23.4 µg/m3, with days exceeding 80 µg/m3 in some counties. Over the entire study period, PM2.5 was most consistently linked to EDVs for respiratory disease (RREDV(lag0) per 23.4 µg/m3 increase: 1.25, 95% CI: 1.21, 1.30), asthma, chronic lower respiratory disease (CLRD; RREDV(lag0): 1.18, 95% CI: 1.10, 1.27), and acute myocardial infarction (RREDV(lag0): 1.14, 95% CI: 1.03, 1.25). Increases in acute upper respiratory infections and decreases in mental/behavioral EDVs were observed but were sensitive to model specification, specifically the inclusion of time-related covariates. Comparing fire and non-fire period EDV associations, we observed indications that PM2.5 during the fire was more strongly associated with asthma (RRlag0: 1.46, 95% CI: 1.38, 1.55) compared to non-fire period PM2.5 (RRlag0: 0.77, 95% CI: 0.55, 1.08), and the opposite observed for dysrhythmia, with the asthma difference being particularly robust to model choice. For hospitalizations, the most robust PM2.5 relationships were positive associations with respiratory, CLRD, and diabetes, and inverse associations with pneumonia. Respiratory and CLRD effect estimates were generally similar or smaller than for EDVs. CONCLUSIONS: Elevated short-term PM2.5 levels from wildfire smoke appears to impact respiratory and other health domains.

Complement sC5b-9 and CH50 increase the risk of cancer-related mortality in patients with non-small cell lung cancer.

Objectives: Immunologic dysfunction occurred in most of patients with non-small cell lung cancer (NSCLC), which worsened the overall survival (OS) of patients. Complement activation plays a significant role in abnormal activation of immune system. However, the prognostic value of complement components such as CH50 and sC5b-9 in NSCLC patients remains unclear. This study evaluated the risk factors of NSCLC and created a prediction model. Methods: A real-world study was conducted including data from 928 patients with NSCLC between April 1, 2005 and June 1, 2015. CH50 and sC5b-9 were recorded during the admission. Cox proportional hazard model was applied for survival analyses and for assessing risk factors of cancer-related mortality and to create a nomogram for prediction. The accuracy of the model was evaluated by C-index and calibration curve. Results: In this study, the mortality in group with high CH50 level (≥ 480.56 umol/L) was 92.0%. Based on univariate analysis, we put factors (P <0.05) into a multivariate regression model, patients with high CH50 level (P <0.001, HR=1.59) and sC5b-9 >1422.18 µmol/L (P <0.001, HR=2.28) remained statistically factors for worsened OS and regarded as independent risk factors. These independently associated risk factors were applied to establish an OS estimation nomogram. Nomogram revealed good accuracy in estimating the risk, with a bootstrap-corrected C index of 0.741. Conclusion: sC5b-9 and CH50 increased the risk of cancer-related mortality in patients with NSCLC. Nomogram based on multivariate analysis demonstrated good accuracy in estimating the risk of overall mortality.

Association between coarse particulate matter and inflammatory and hemostatic markers in a cohort of midlife women.

BACKGROUND: Exposure to particulate matter air pollution has been associated with cardiovascular disease (CVD) morbidity and mortality; however, most studies have focused on fine particulate matter (PM2.5) exposure and CVD. Coarse particulate matter (PM10-2.5) exposure has not been extensively studied, particularly for long-term exposure, and the biological mechanisms remain uncertain. METHODS: We examined the association between ambient concentrations of PM10-2.5 and inflammatory and hemostatic makers that have been linked to CVD. Annual questionnaire and clinical data were obtained from 1694 women (≥ 55 years old in 1999) enrolled in the longitudinal Study of Women's Health Across the Nation (SWAN) at six study sites from 1999 to 2004. Residential locations and the USEPA air monitoring network measurements were used to assign exposure to one-year PM10-2.5, as well as co-pollutants. Linear mixed-effects regression models were used to describe the association between PM10-2.5 exposure and markers, including demographic, health and other covariates. RESULTS: Each interquartile (4 µg/m3) increase in one-year PM10-2.5 exposure was associated with a 5.5% (95% confidence interval [CI]: 1.8, 9.4%) increase in levels of plasminogen activator inhibitor-1 (PAI-1) and 4.1% (95% CI: - 0.1, 8.6%) increase in high-sensitivity C-creative Protein (hs-CRP). Stratified analyses suggested that the association with PAI-1 was particularly strong in some subgroups, including women who were peri-menopausal, were less educated, had a body mass index lower than 25, and reported low alcohol consumption. The association between PM10-2.5 and PAI-1 remained unchanged with adjustment for PM2.5, ozone, nitrogen dioxide, and carbon monoxide. CONCLUSIONS: Long-term PM10-2.5 exposure may be associated with changes in coagulation independently from PM2.5, and thus, contribute to CVD risk in midlife women.

Capillary Electrophoresis with Detection by Laser-Induced Fluorescence.

Capillary zone electrophoresis (CZE) has been rising in its importance in structural analysis of plant cell walls, characterization of enzymes that degrade polysaccharides, and profiling of oligosaccharides to characterize cell wall mutants. CZE with laser-induced fluorescence detection provides high separation efficiencies, high-speed analysis, with extremely small sample requirements. Here we describe the instrumentation we use and methods for attaching fluorescent labels to oligosaccharides so that they can be detected.

Down-regulation of PDGFRß suppresses invasion and migration in osteosarcoma cells by influencing epithelial-mesenchymal transition.

Osteosarcoma (OS) is the most common malignant bone tumor primarily influencing children and adults. Approximately one-fifth of patients have micrometastasis in the lungs when OS is diagnosed. Platelet-derived growth factor receptor (PDGFR) beta (PDGFRß) is a subtype of PDGFR. PDGFRß has been noted to be highly expressed in OS cell lines and patient specimens, and is associated with metastasis and poor prognosis of OS. However, mechanistic insights into the exact role of PDGFRß in OS pathogenesis and development are still lacking. Here we assessed the effects of PDGFRß on invasive and migratory abilities, such as the epithelial-mesenchymal transition and phosphatidylinositol 3-kinase (PI3K), Akt and mammalian target of rapamycin (mTOR) pathways in HOS cells. Depleting PDGFRß resulted in reduced migration of HOS cells in the small interfering RNA duplexes specific for the PDGFRß group compared with the mock and scramble-treated groups in Transwell invasion assays. Using wound-healing assays, we demonstrate the rate of wound healing in the PDGF-BB-stimulated group was higher compared with the mock-treated group. Western blot showed that down-regulation of PDGFRß decreased the expression of stromal phenotype markers and phosphorylation pathway proteins (PI3K, AKT and mTOR), but the epithelial phenotype marker was increased in HOS cells. Treating HOS cells with PDGF-BB revealed a treatment time-dependent increase of phosphorylated, but not total, PI3K, AKT and mTOR. Taken together, we suggest that PDGFRß plays an important role in OS invasion, migration and epithelial-mesenchymal transition by influencing the PI3K, Akt and mTOR pathways, hence highlighting PDGFRß as a potential therapeutic target for OS.

Temperature and hand, foot and mouth disease in California: An exploratory analysis of emergency department visits by season, 2005-2013.

BACKGROUND: For the past decade, hand, foot and mouth disease (HFMD), caused by entero and coxsackie viruses, has been spreading in Asia, particularly among children, overloading healthcare settings and creating economic hardships for parents. Recent studies have found meteorological factors, such as temperature, are associated with HFMD in Asia. However, few studies have explored the relationship in the United States, although HFMD cases have steadily increased recently. As concerns of climate change grow, we explored the association between temperature and HFMD admissions to the Emergency Department (ED) in California. METHODS: Weekly counts of HFMD for 16 California climate zones were collected from 2005 to 2013. We calculated weekly temperature for each climate zone using an inverse distance-weighting method. For each climate zone stratified by season, we conducted a time-series using Poisson regression models. We adjusted models for weekly averaged relative humidity, average number of HFMD cases in previous weeks and long-term temporal trends. Climate zone estimates were combined to obtain an overall seasonal estimate. We attempted stratified analyses by region, race/ethnicity, and sex to identify sensitive subpopulations. RESULTS: Risk of ED visits for HFMD per 1 °F increase in mean temperature during the same week increased 2.00% (95% confidence intervals 1.15, 2.86%) and 2.35% (1.38, 3.33%) during the warm and cold seasons, respectively. The coastal region showed a higher, though not statistically different, association during the cold season [3.18% (1.99, 4.39)] than the warm season [1.64% (0.47, 2.82)]. CONCLUSIONS: Our findings indicated an association between temperature and ED visits for HFMD, with variation by season and region. Thus, the causative pathogen's ability to persist in the atmosphere may vary by season. Furthermore, the mild and wet winter in the coastal region of California may contribute to different results than studies in Asia. With the onset of climate change, HFMD cases will likely grow in California, warranting further investigation on this relationship, including new populations at-risk.

Wearable Sensor System to Monitor Physical Activity and the Physiological Effects of Heat Exposure.

Mobile health monitoring via non-invasive wearable sensors is poised to advance telehealth for older adults and other vulnerable populations. Extreme heat and other environmental conditions raise serious health challenges that warrant monitoring of real-time physiological data as people go about their normal activities. Mobile systems could be beneficial for many communities, including elite athletes, military special forces, and at-home geriatric monitoring. While some commercial monitors exist, they are bulky, require reconfiguration, and do not fit seamlessly as a simple wearable device. We designed, prototyped and tested an integrated sensor platform that records heart rate, oxygen saturation, physical activity levels, skin temperature, and galvanic skin response. The device uses a small microcontroller to integrate the measurements and store data directly on the device for up to 48+ h. continuously. The device was compared to clinical standards for calibration and performance benchmarking. We found that our system compared favorably with clinical measures, such as fingertip pulse oximetry and infrared thermometry, with high accuracy and correlation. Our novel platform would facilitate an individualized approach to care, particularly those whose access to healthcare facilities is limited. The platform also can be used as a research tool to study physiological responses to a variety of environmental conditions, such as extreme heat, and can be customized to incorporate new sensors to explore other lines of inquiry.