Impact of Ontario's Harmonized Heat Warning and Information System on emergency department visits for heat-related illness in Ontario, Canada: a population-based time series analysis.

INTERVENTION: Ontario's Harmonized Heat Warning and Information System (HWIS) brings harmonized, regional heat warnings and standard heat-health messaging to provincial public health units prior to periods of extreme heat. RESEARCH QUESTION: Was implementation of the harmonized HWIS in May 2016 associated with a reduction in emergency department (ED) visits for heat-related illness in urban locations across Ontario, Canada? METHODS: We conducted a population-based interrupted time series analysis from April 30 to September 30, 2012-2018, using administrative health and outdoor temperature data. We used autoregressive integrated moving average models to examine whether ED rates changed following implementation of the harmonized HWIS, adjusted for maximum daily temperature. We also examined whether effects differed in heat-vulnerable groups (≥65 years or <18 years, those with comorbidities, those with a recent history of homelessness), and by heat warning region. RESULTS: Over the study period, heat alerts became more frequent in urban areas (6 events triggered between 2013 and 2015 and 14 events between 2016 and 2018 in Toronto, for example). The mean rate of ED visits was 47.5 per 100,000 Ontarians (range 39.7-60.1) per 2-week study interval, with peaks from June to July each year. ED rates were particularly high in those with a recent history of homelessness (mean rate 337.0 per 100,000). Although rates appeared to decline following implementation of HWIS in some subpopulations, the change was not statistically significant at a population level (rate 0.04, 95% CI: -0.03 to 0.1, p=0.278). CONCLUSION: In urban areas across Ontario, ED encounters for heat-related illness may have declined in some subpopulations following HWIS, but the change was not statistically significant. Efforts to continually improve HWIS processes are important given our changing Canadian climate.

RéSUMé: INTERVENTION: Le système d'avertissement et d'information de chaleur harmonisé pour l'Ontario (SAIC) transmet des alertes régionales harmonisées sur la chaleur et des messages normalisés sur la chaleur et la santé aux unités de santé publique provinciales, avant les périodes de chaleur extrême. QUESTION DE RECHERCHE: La mise en œuvre du SAIC harmonisé en mai 2016 a-t-elle été associée à une réduction des visites aux urgences pour des maladies liées à la chaleur dans les zones urbaines de l'Ontario, au Canada? MéTHODES: Nous avons effectué une analyse de séries chronologiques interrompues basée sur la population du 30 avril au 30 septembre, 2012­2018, en utilisant des données administratives sur la santé et la température extérieure. Nous avons utilisé des modèles autorégressifs à moyenne mobile intégrée pour examiner si le taux de visites des urgences avait changé après la mise en œuvre du SAIC harmonisé, ajusté pour tenir compte de la température maximale quotidienne. Nous avons également examiné si les effets différaient pour les groupes vulnérables à la chaleur (≥65 ans ou <18 ans, les personnes ayant des comorbidités et les personnes avec un passé récent de sans-abri), et selon la région d'alerte de chaleur. RéSULTATS: Au cours de la période d'étude, les alertes de chaleur sont devenues plus fréquentes dans les zones urbaines (6 événements déclenchés entre 2013 et 2015 et 14 événements déclenchés entre 2016 et 2018 à Toronto, par exemple). Le taux moyen de visites aux urgences était de 47,5 pour 100 000 Ontariens (de 39,7 à 60,1) par intervalle de deux semaines, avec des pointes chaque année en juin et juillet. Le taux de visites aux urgences était particulièrement élevé chez les personnes avec un passé récent de sans-abri (taux moyen de 337,0 pour 100 000). Malgré une baisse du taux après la mise en œuvre du SAIC dans certaines sous-populations, le changement n'était pas statistiquement significatif au niveau de la population (taux 0,04, IC 95 % : -0,03 à 0,1, p=0,278). CONCLUSION: Dans les zones urbaines de l'Ontario, le nombre de consultations aux urgences pour des maladies liées à la chaleur a diminué dans certaines sous-populations après la mise en place du SAIC, mais le changement n'était pas statistiquement significatif. Les efforts visant à améliorer continuellement les processus du SAIC sont importants compte tenu de l'évolution du climat canadien.

Evaluating the association between extreme heat and mortality in urban Southwestern Ontario using different temperature data sources.

Urban areas have complex thermal distribution. We examined the association between extreme temperature and mortality in urban Ontario, using two temperature data sources: high-resolution and weather station data. We used distributed lag non-linear Poisson models to examine census division-specific temperature-mortality associations between May and September 2005-2012. We used random-effect multivariate meta-analysis to pool results, adjusted for air pollution and temporal trends, and presented risks at the 99th percentile compared to minimum mortality temperature. As additional analyses, we varied knots, examined associations using different temperature metrics (humidex and minimum temperature), and explored relationships using different referent values (most frequent temperature, 75th percentile of temperature distribution). Weather stations yielded lower temperatures across study months. U-shaped associations between temperature and mortality were observed using both high-resolution and weather station data. Temperature-mortality relationships were not statistically significant; however, weather stations yielded estimates with wider confidence intervals. Similar findings were noted in additional analyses. In urban environmental health studies, high-resolution temperature data is ideal where station observations do not fully capture population exposure or where the magnitude of exposure at a local level is important. If focused upon temperature-mortality associations using time series, either source produces similar temperature-mortality relationships.

The effect of sub-facet scale surface structure on wall brightness temperatures at multiple scales.

Wall surface temperatures are important components of urban climates but are under-sampled by satellite and airborne remote sensing and at the microscale are under-sampled in observational studies. In urban canopy models, they are represented with simplistic geometries. This study examines the effect of microscale (sub-facet) surface structure geometries on wall surface brightness temperature distributions at micro- to neighbourhood scales using mobile sampling traverses of two suburban neighbourhoods with different sub-facet geometries. Visible and thermal imagery were recorded simultaneously and combined and classified to create a database of temperatures with associated geographic and thermal attributes. This study investigates (1) if sub-facet scale geometries affect temperature distributions, (2) if these cause canyon scale biases, and (3) if there are therefore inter-neighbourhood biases. It is shown that sub-facet geometries modify wall surface temperatures predominantly by cooling due to self-shading. Surface-sun geometry thus leads to intra- and inter-neighbourhood temperature differences of several degrees Celsius. The observed effects have important implications for modelling of urban surface temperatures, where simplified geometries may overestimate wall surface temperatures.

Integrated urban hydrometeorological, climate and environmental services: Concept, methodology and key messages.

Integrated Urban hydrometeorological, climate and environmental Services (IUS) is a World Meteorological Organization (WMO) initiative to aid development of science-based services to support safe, healthy, resilient and climate friendly cities. Guidance for Integrated Urban Hydrometeorological, Climate and Environmental Services (Volume I) has been developed with the intent to provide an overview of the concept, methods and good practices for producing and providing these services to respond to urban hazards across a range of time scales (weather to climate). This involves combining (dense) heterogeneous observation networks, high-resolution forecasts, multi-hazard early warning systems and climate services to assist cities in setting and implementing mitigation and adaptation strategies for the management and building of resilient and sustainable cities. IUS includes research, evaluation and delivery with a wide participation from city governments, national hydrometeorological services, international organizations, universities, research institutions and private sector stakeholders. An overview of the IUS concept with key messages, examples of good practice and recommendations are provided. The research community will play an important role to: identify critical research challenges; develop impact forecasts and warnings; promote and deliver IUS internationally, and; support national and local communities in the implementation of IUS thereby contributing to the United Nations' Sustainable Development Goals at all scales.

Integrated urban services: Experience from four cities on different continents.

Rapid urbanization combined with climate change necessitates new types of urban services that make best use of science and technology. The Integrated Urban Hydro-Meteorological, Climate and Environmental Services and systems are a new initiative from the World Meteorological Organization (WMO) that seeks to provide science-based integrated urban services supporting safe, healthy and resilient cities. Various cities have already started development and implementation of such Integrated Urban Services and successfully test and use them following specific requirements of local stakeholders. This paper demonstrates the novel concept and approach of Integrated Urban Hydro-Meteorological, Climate and Environmental Services (IUS) from a set of four case study cities: Hong Kong, Toronto, Mexico City and Paris, that use different IUS configurations with good existing practice. These cities represent a range of countries, climates and geophysical settings. The aggregate main joint similarities of the IUS in these cities and synergy of the cities' experience, achievements and research findings are presented, as well as identification of existing gaps in knowledge and further research needs. A list of potential criteria for identifying and classifying IUS demonstration cities is proposed. It will aid future, more detailed analysis of the IUS experience, and selection of additional demonstration cities.

Effects of opioid antagonism on prolactin secretion and c-Fos/TH expression during lactation in rats.

Many studies have established that dopamine (DA) secreted by tuberoinfundibular dopaminergic (TIDA) neurons in the hypothalamus is the major inhibitory factor controlling prolactin (PRL) secretion from the anterior pituitary. Endogenous opioid peptides (EOPs), mainly the neuropeptide beta-endorphin, facilitate PRL secretion by decreasing TIDA neuronal inhibitory tone in a number of physiological conditions, including pregnancy and lactation. We have previously demonstrated that there are many more c-Fos-expressing neurons than TIDA neurons in the arcuate nucleus, and treatment with naloxone (NAL), an opioid antagonist, activated these neurons in pregnant rats. Our previous data also suggest that the rostral region of the arcuate nucleus is more important than the caudal region in regulating the nocturnal PRL surge in pregnant rats. The aim of this study was to investigate the effects of NAL in regulating TIDA neuronal activity and therefore facilitating PRL secretion during lactation in rats. NAL was continuously infused (0.2 mg/10 microL/min iv) for 1 h before the separated pups returned, and then for 2 or 5 h after the separated pups were returned. Radioimmunoassay (RIA) was used to measure plasma PRL levels, and the immunocytochemical (ICC) staining of c-Fos was performed to detect changes in transcriptional activity of neurons in the hypothalamus. ICC of tyrosine hydroxylase (TH), the rate-limiting enzyme for DA synthesis, was performed to visualize TIDA neurons in the arcuate nucleus. The results showed that the peak of the PRL response to suckling was markedly delayed and dampened in NAL-treated rats (p<0.05). The percentage of c-Fos positive TH neurons in the arcute nucleus increased in rats treated with NAL for 5 h after return of pups, but not in rats treated with NAL for 2 h.

Changes in estrogen receptor-alpha expression in hypothalamic dopaminergic neurons during proestrous prolactin surge.

A surge of prolactin (PRL) occurs in female rats during proestrus in response to elevated estradiol and progesterone levels. Dopamine is the primary hypothalamic inhibitor of PRL secretion from the pituitary. Using double-label immunocytochemistry, we investigated the pattern of estrogen receptor-alpha (ER-alpha) immunoreactivity in dopaminergic neurons in the arcuate nucleus (ARC) and the periventricular nucleus (PeVN) during the proestrous PRL surge and compared it to that during diestrus, when PRL levels are constantly low. Our results showed that during diestrus >80% of dopaminergic neurons in the ARC were also positive for ER-alpha, and this colocalization percentage decreased significantly during proestrus. By contrast, <15% of dopaminergic neurons in the PeVN expressed ER-alpha, and the low percentage of ER-alpha expression was unchanged throughout proestrus and diestrus. Results from estrogen plus progesterone treated ovariectomized rats showed similar patterns of ER-alpha expression within the ARC and the PeVN and, once again, compared with the control group, had a significant reduction in ER-alpha immunoreactivity in dopaminergic neurons in the ARC, but not in the PeVN. These results provide an anatomic basis that dopaminergic neurons in the ARC and the PeVN are functionally different regarding to ER-alpha expression. Our study also supports the hypothesis that dopaminergic neurons in the ARC are an important neuronal population responsive to estrogen by changing the expression of ER-alpha in those neurons. This modification of sensitivity of dopaminergic neurons in the ARC in response to ovarian steroids may be an important molecular mechanism involved in PRL regulation, including the regulation of the proestrous surge of PRL.

Promoter usage and estrogen regulation of prolactin receptor gene in the brain of the female rat.

Mechanisms underlying hormonal regulation of prolactin receptor (PRL-R) gene in the brain are unknown. The 5'-untranslated region of PRL-R mRNA in peripheral tissues contains at least three alternative first exons (1A, B, C) that are expressed as tissue-specific, suggesting the differential usage of PRL-R gene promoters. The present study aimed to investigate: (1). the possible regulation of PRL-R mRNA levels by estrogen in in vitro and in vivo tissues; (2). which exon (1A, or 1B, or 1C)-containing PRL-R mRNA transcript is expressed in the brain, and (3). how the specific exon 1-containing mRNA is affected by estrogen by using RT-PCR, Southern blot and 5'Race PCR techniques. The RT-PCR results showed that PRL-R mRNA was detected in the cerebral cortex and pons medulla in addition to the choroid plexus and hypothalamus in the female rat. The expression of PRL-R mRNA was up-regulated by estrogen treatment in the rat brain tissue and in the GT1-7 cell culture. Both exon 1A- and 1C-containing transcripts were expressed in all four regions, suggesting that promoters 1A and 1C for the PRL-R gene are utilized in the rat brain. Exon 1A-containing transcript was up-regulated by estrogen treatment in all four brain regions, whereas Exon 1C-containing transcript was up-regulated by estrogen treatment in 3 of the 4 brain regions, cerebral cortex being the exception. Exon 1B-containing transcript was neither detectable nor induced by estrogen treatment in any of the brain regions examined. The RT-PCR results were confirmed by partial isolation of 5'-untranslated regions of exon 1A- and 1C-containing PRL-R mRNA transcripts from brain tissue by using 5'Race PCR. The present result confirms the expression of PRL-R mRNA in the cerebral cortex and pons medulla in the female rat. The levels of PRL-R mRNA were up-regulated by estrogen in rat brain tissue and GT1-7 cell cultures. Detection of exon 1A- and 1C-containing transcripts implies that the promoter 1A and 1C are active in the female rat brain. Estrogen differentially regulates expression of the PRL-R mRNA in the different brain regions by increasing the utilization of PRL-R gene promoters 1A and 1C in the female rat.

Mating-activated nitric oxide-producing neurons in specific brain regions in the female rat.

Nitric oxide (NO)-containing neurons have been localized in various parts of the central nervous system including the hypothalamus. NO plays an important role in the regulation of reproductive activities including sexual behavior and pituitary hormone secretion. To test the hypothesis that NO-containing neurons in specific brain areas may respond to the stimulus of mating and participate in integrating the tactile information in the hypothalamus, this study used Fos as a marker of neuronal activity. Proestrous rats receiving intromissions (mated group) from males or mounts-without-intromission (mounted group) were sacrificed along with rats taken directly from their home cage (control group) 90 min after the beginning of mating or mounting. NOergic neurons were labeled by histochemical reaction for nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d). The presence of activated NO-producing (double-stained NADPH-d/Fos) neurons was quantitatively assessed in several brain areas before and after mating. The results showed that mating-with-intromissions induced a significant increase in the percentage of NADPH-d/Fos colabeled neurons in the medial preoptic area (mPOA) and the magnocellular component of the paraventricular nucleus (PVNm) compared to mounts-without-intromission or control treatment. Both mating and mounting induced Fos expression in NADPH-d-positive cells in the ventromedial nucleus of hypothalamus (VMN). In contrast, the expression of Fos in the NADPH-d-positive neurons in the supraoptic nucleus (SON) and the parvocellular portion of the paraventricular nucleus (PVNp) was not influenced by either mating or mounting although abundant NO-containing neurons were found in the two brain areas. The second experiment of the study examined whether NOergic neurons in these brain areas are influenced directly by estrogen by determining the number of NADPH-d-positive neurons that contained the estrogen receptor alpha (ERalpha), the classical ER. Double labeled NADPH-d/ERalpha neurons were observed in several brain areas including the mPOA and VMN while few, if any, NADPH-d-positive neurons in the SON, PVNm or PVNp contained ERalpha. The results suggest that the activated NOergic neurons in these brain areas may be involved in processing and integrating the mating stimulus. Further investigation is required to determine the physiological role of the mating-activated NOergic activity in specific mating-induced changes in reproductive neuroendocrinology.

Sex difference and estrous cycle: expression of prolactin receptor mRNA in rat brain.

The short and long forms of prolactin receptor (PRL-R) mRNA have been detected in the female rat brain. The present study aimed to investigate: (1) if the PRL-R mRNA is expressed in the male rat brain; (2) if expression levels in the female brain vary during the estrous cycle. All animals were sacrificed between 12:00 and 14:00 h. Radioactive RNase protection assay was used to measure mRNA levels. The results showed that both forms of PRL-R mRNA were expressed to varying degrees in the choroid plexus (ChP), preoptic area (POA), mediobasal hypothalamus (MBH), cerebral cortex (CTX) and pons-medulla PON) in both male and female rats. The average amount of both forms of PRL-R mRNA in the ChP, POA, MBH of cycling females was significantly higher than in the male rat. Among cycling female rats, the expression levels of both forms of PRL-R mRNA in the ChP, POA and MBH during proestrous were significantly greater than during diestrous or estrous. In proestrous females, the ChP expressed the highest levels of mRNA whereas the CTX contained the lowest. The ratios of short:long form mRNA were not significantly changed according to sex, estrous stage or brain regions although a slightly higher amount of the short form was observed. The detection of PRL-R mRNA in the male rat implicates that PRL may be involved in regulation of brain function in the male subject. The higher levels of PRL-R mRNA in female rats on proestrous suggest that PRL-R may be regulated by PRL or steroid hormones that show a surge on this day.

Progesterone induces dephosphorylation and inactivation of tyrosine hydroxylase in rat hypothalamic dopaminergic neurons.

After in vivo treatment, progesterone initially decreases tyrosine hydroxylase (TH) activity in the TIDA neurons, but subsequently increases TH activity with prolonged treatment. In order to explore the cellular mechanism for progesterone's effect, this study examined the acute inhibitory action of progesterone on TH activity in rat fetal hypothalamic dopaminergic neurons in vitro. Progesterone caused a rapid decrease in TH activity within 1 h, which was sustained for at least 6 h. However, the dopaminergic cells became refractory to progesterone with continuous treatment for 12 h to 10 days. Progesterone (10-100 nM) treatment suppressed TH activity in a concentration-dependent manner. The inhibitory effect of progesterone was dependent on prior exposure to estradiol. Whereas progesterone decreased TH activity, A ring-reduced metabolites of progesterone did not alter TH activity, suggesting that the response was specific to progesterone. Progesterone decreased radiolabeled phosphate incorporation into TH protein. Okadaic acid, a phosphoprotein phosphatase inhibitor, prevented the progesterone-induced suppression of TH activity and phosphate incorporation into TH, implicating dephosphorylation of TH as the cellular mechanism. In contrast, neither TH mRNA levels nor TH protein content was altered after 1 or 12 h of progesterone treatment. Progesterone decreased TH activity after pretreatment of the hypothalamic cells for 2 or 24 h with actinomycin D, an RNA synthesis inhibitor, suggesting that increased transcription does not mediate the effect. These data indicate that the acute progesterone-induced decline in TH activity is caused by dephosphorylation of TH.

Detection of prolactin receptor mRNA in the corpus striatum and substantia nigra of the rat.

The observation of prolactin modulation of the nigrostriatal dopaminergic system suggests the expression of prolactin receptor in the corpus striatum or substantia nigra. The present study investigated expression of prolactin receptor mRNA in tissues microdissected from the corpus striatum and substantia nigra of the rat. By using reverse transcription PCR combined with Southern hybridization, the long form of prolactin receptor mRNA was detected in the substantia nigra, caudate putamen, globus pallidus, and ventral pallidum in ovariectomized rats, whereas the short form was not detectable in any of these areas. Estrogen had no effect on expression of the long-form mRNA in the substantia nigra and corpus striatum. By using the RNase protection assay, the expression of both short and long forms of prolactin receptor mRNA was observed in the corpus striatum in ovariectomized rats. Again, levels of expression were not significantly altered by estrogen treatment. Both forms of prolactin receptor mRNA were clearly expressed in the choroid plexus and were up-regulated by estrogen treatment. The expression of both forms of prolactin receptor mRNA in nigrostriatal areas may help to support the hypothesis that prolactin has direct actions on these brain regions.