Trends and gaps in climate change and health research in North America.

The Intergovernmental Panel on Climate Change (IPCC) 5th Assessment Report (2014) assessed the state of climate change and health knowledge, globally through the Human Health: Impacts, Adaptation, and Co-Benefits Chapter and regionally through chapters, such as the North America Chapter. With IPCC's 6th Assessment Report scheduled to be released in 2021-22, we asked: how has climate change and health research in North America advanced since the IPCC's 5th Assessment Report in 2014? Specifically, we systematically identified and examined trends in the extent, range, and nature of climate-health research conducted in North America. We used a scoping review methodology to systematically identify literature and map publication trends. A search string was used to search five academic databases. Two independent reviewers first screened titles and abstracts, and then the full texts of articles for relevance. Research articles and reviews using systematic methods published since 2013 were eligible for inclusion, and no language restrictions were applied. To be included, articles had to measure and link climatic variables or hazards to health outcomes in North America. Relevant articles were analysed using descriptive statistics to explore publication trends. The number of climate-health articles has significantly increased since the last IPCC Assessment Report. Published research about climate change impacts, heat-related mortality and morbidity, and respiratory illness taking place in urban centres and in the USA continue to dominate the North American climate-health literature, reflected by the high proportion of articles published. Important research gaps on previously neglected climate-sensitive health outcomes, however, are beginning to be filled, including climate change impacts on mental health, nutrition, and foodborne disease. We also observed progress in research that included future projections of climate-health risks; however, projection research is still relatively nascent and under-studied for many climate-sensitive health outcomes in North America, and would benefit from considering social and demographic variables in models. Important research disparities in geographical coverage were noted, including research gaps in Canada and Mexico, and in rural and remote regions. Overall, these publication trends suggest an improved understanding of exposure-response relationships and future projections of climate-health risks for many climate-sensitive health outcomes in North America, which is promising and provides an evidence-base to inform the IPCC 6th Assessment Report. Despite these advancements and considering the urgent policy and practice implications, more research is needed to deepen our understanding of climate-sensitive health outcomes, as well as examine new arising issues that have limited evidence-bases. In particular, transdisciplinary and cross-sector research, that includes the social sciences, examining current and future climate-health adaptation, mitigation, and the adaptation-mitigation nexus should become a top priority for research, given the urgent need for this evidence to inform climate change policies, actions, and interventions.

Acute gastrointestinal illness in two Inuit communities: burden of illness in Rigolet and Iqaluit, Canada.

Food- and waterborne disease is thought to be high in some Canadian Indigenous communities; however, the burden of acute gastrointestinal illness (AGI) is not well understood due to limited availability and quality of surveillance data. This study estimated the burden of community-level self-reported AGI in the Inuit communities of Rigolet, Nunatsiavut, and Iqaluit, Nunavut, Canada. Cross-sectional retrospective surveys captured information on AGI and potential environmental risk factors. Multivariable logistic regression models identified potential AGI risk factors. The annual incidence of AGI ranged from 2·9-3·9 cases/person per year in Rigolet and Iqaluit. In Rigolet, increased spending on obtaining country foods, a homeless person in the house, not visiting a cabin recently, exposure to puppies, and alternative sources of drinking water were associated with increased odds of AGI. In Iqaluit, eating country fish often, exposure to cats, employment status of the person responsible for food preparation, not washing the countertop with soap after preparing meat, a homeless person in the house, and overcrowding were associated with increased odds of AGI. The results highlight the need for systematic data collection to better understand and support previously anecdotal indications of high AGI incidence, as well as insights into unique AGI environmental risk factors in Indigenous populations.

Projected decrease in trail access in the Arctic.

Transportation systems in northern Canada are highly sensitive to climate change. We project how access to semi-permanent trails on land, water, and sea ice might change this century in Inuit Nunangat (the Inuit homeland in northern Canada), using CMIP6 projections coupled with trail access models developed with community members. Overall trail access is projected to diminish, with large declines in access for sea ice trails which play a central role for Inuit livelihoods and culture; limits to adaptation in southern regions of Inuit Nunangat within the next 40 years; a lengthening of the period when no trails are accessible; and an unequal distribution of impacts according to the knowledge, skills, equipment, and risk tolerance of trail users. There are opportunities for adaptation through efforts to develop skillsets and confidence in travelling in more marginal environmental conditions, which can considerably extend the envelope of days when trails are accessible and months when this is possible. Such actions could reduce impacts across emissions scenarios but their potential effectiveness declines at higher levels of global warming, and in southern regions only delays when sea ice trails become unusable.

Improving Aboriginal health data capture: evidence from a health registry evaluation.

The lack of high-quality health information for accurately estimating burdens of disease in some Aboriginal populations is a challenge for developing effective and relevant public health programmes and for health research. We evaluated data from a health registry system that captured patient consultations, provided by Labrador Grenfell Health (Labrador, Canada). The goal was to evaluate the registry's utility and attributes using modified CDC guidelines for evaluating surveillance systems. Infectious gastrointestinal illness data were used as a reference syndrome to determine various aspects of data collection and quality. Key-informant interviews were conducted to provide information about system utility. The study uncovered limitations in data quality and accessibility, resulting in region-specific recommendations including conversion to an electronic system. More generally, this study emphasized how a systematic and standardized evaluation of health registry systems can help address challenges to obtaining quality health data in often remote areas where many Aboriginal communities are found.

Machine learning predictions of concentration-specific aggregate hazard scores of inorganic nanomaterials in embryonic zebrafish.

The possibility of employing computational approaches like nano-QSAR or nano-read-across to predict nanomaterial hazard is attractive from both a financial, and most importantly, where in vivo tests are required, ethical perspective. In the present work, we have employed advanced Machine Learning techniques, including stacked model ensembles, to create nano-QSAR tools for modeling the toxicity of metallic and metal oxide nanomaterials, both coated and uncoated and with a variety of different core compositions, tested at different dosage concentrations on embryonic zebrafish. Using both computed and experimental descriptors, we have identified a set of properties most relevant for the assessment of nanomaterial toxicity and successfully correlated these properties with the associated biological responses observed in zebrafish. Our findings suggest that for the group of metal and metal oxide nanomaterials, the core chemical composition, concentration and properties dependent upon nanomaterial surface and medium composition (such as zeta potential and agglomerate size) are significant factors influencing toxicity, albeit the ranking of different variables is sensitive to the exact analysis method and data modeled. Our generalized nano-QSAR ensemble models provide a promising framework for anticipating the toxicity potential of new nanomaterials and may contribute to the transition out of the animal testing paradigm. However, future experimental studies are required to generate comparable, similarly high quality data, using consistent protocols, for well characterized nanomaterials, as per the dataset modeled herein. This would enable the predictive power of our promising ensemble modeling approaches to be robustly assessed on large, diverse and truly external datasets.

Microvascular adaptation in the cerebral cortex of adult spontaneously hypertensive rats.

The purpose of this study was to determine the microvascular characteristics that cause cerebral cortical blood flow autoregulation to shift to a higher range of arterial pressures during established hypertension in spontaneously hypertensive rats (SHR). An open-skull technique with constant suffusion of artificial cerebrospinal fluid (PO2 = 40-45 mm Hg, PCO2 = 40-45 mm Hg, pH = 7.35-7.45) was used to view the parietal cortex of 18- to 21-week-old SHR and Wistar Kyoto (WKY) normotensive control rats. The resting inner diameters of first (1A)-, second (2A)-, and fourth (4a)-order arterioles were significantly (p less than 0.05) smaller, and the wall thickness/lumen diameter ratios were significantly (p less than 0.05) larger in SHR compared to WKY. Only 1A and 4A has significantly (p less than 0.05) increased vessel wall cross-sectional area in SHR. At the resting mean arterial pressures of WKY and SHR, the passive (10(-4) M adenosine, topical) diameters of comparable types of arterioles were not significantly different (p greater than 0.05). At reduced arterial pressures, however, the arterioles in SHR had smaller maximum diameters than in WKY. Cortical blood flow in WKY and SHR was constant at arterial pressures from 70-150 mm Hg and 100-200 mm Hg, respectively. Resting arteriolar pressures in 1A, 2A, and 3A of SHR were substantially and significantly (p less than 0.05) elevated, although pressures in the smallest arterioles and venules of WKY and SHR were similar. Therefore, it is possible that cerebral capillary pressure is only slightly elevated, if at all, in SHR as a result of the vasoconstriction. The number of arterioles per unit area of brain surface at rest was equal in WKY and SHR. In addition, the number of vessels was equal in WKY and SHR during maximal dilation, and neither type of rat demonstrated an opening of previously closed vessels upon maximum dilation. Therefore, the cerebral arteriolar constriction in SHR, which was probably potentiated by vessel wall hypertrophy of the largest and smallest arterioles, was the major contributor to an upward shift in the autoregulatory range, the protection of exchange vasculature pressures, and the increase in vascular resistance.

Amniotic membrane inlay and overlay grafting for corneal epithelial defects and stromal ulcers.

OBJECTIVES: To determine the effect of amniotic membrane transplantation (AMT) on persistent corneal epithelial defects (PEDs) and to compare the efficacy between inlay and overlay techniques. METHODS: Thirty patients (30 eyes) underwent AMT for PED. The use of AMT was restricted to patients in whom all previous measures, including bandage contact lens and tarsorrhaphy, had failed. The amniotic membrane was placed on the surface of the cornea in overlay (group A) or inlay (group B) fashion. RESULTS: The PED healed after the first AMT in 21 eyes (70%) within an average of 25.5 days after surgery and recurred in 6 eyes (29%). Among the 22 eyes treated with an overlay AMT (group A), the PED healed after the first AMT in 14 eyes (64%) within an average of 24.5 days and recurred in 4 eyes (29%). Among the 8 eyes treated with an inlay AMT (group B), the PED healed within an average of 27.4 days after AMT, which did not statistically significantly differ from group A (P = .72). The PED healed after the first AMT in 7 eyes (88%) and recurred in 2 (29%) of 7 eyes. CONCLUSIONS: The AMT can be helpful in the treatment of PED in which all other conventional management has failed. However, the success rate in our study was not as high as that previously reported, and our results showed a high incidence of recurrences of epithelial defects. We did not find any difference between overlay and inlay techniques in terms of healing time and recurrence rate.

Physiological development of the embryonic and larval crayfish heart.

The cardiovascular system is the first system to become functional in a developing animal and must perform key physiological functions even as it develops and grows. The ontogeny of cardiac physiology was studied throughout embryonic and larval developmental stages in the red swamp crayfish Procambarus clarkii using videomicroscopic dimensional analysis. The heart begins to contract by day 13 of development (at 25 degrees C, 20 kPa O(2)). Cardiac output is primarily regulated by changes in heart rate because stroke volume remains relatively constant throughout embryogenesis. Prior to eclosion, heart rate and cardiac output decreased significantly. Previous data suggest that the decrease in cardiac parameters prior to hatching may be due to an oxygen limitation to the embryo. Throughout development, metabolizing mass and embryonic oxygen consumption increased, while egg surface area remained constant. The surface area of the egg membrane is a constraint on gas exchange; this limitation, in combination with the increasing oxygen demand of the embryo, results in an inadequate diffusive supply of oxygen to developing tissues. To determine if the decrease in cardiac function was the result of an internal hypoxia experienced during late embryonic development, early and late-stage embryos were exposed to hyperoxic water (PO(2) = 40 kPa O(2)). Heart rate in late-stage embryos exposed to hyperoxic water increased significantly over control values, which suggests that the suppression in cardiac function observed in late-stage embryos is due to a limited oxygen supply.

Perspectives on cardiac physiological ontogeny in crustaceans.

Crustacean embryonic and larval systems offer a unique and valuable tool for furthering our understanding of both developmental processes and physiological regulatory mechanisms. The diverse array of developmental patterns exhibited by crustaceans allows species choice to be based on the specific questions being investigated, where defined larval forms are chosen based on their developmental pattern, degree of maturation or regulatory capabilities. However, this great diversity in developmental patterns, as well as crustacean diversity, can also confound ones ability to define or identify species for investigation. These issues are addressed and suggestions put forth to clarify some of the problems. The complexity and overlapping nature of adult cardio-regulatory systems makes teasing them apart difficult. Embryonic and larval systems exhibit varying degrees of regulatory complexity depending on developmental stage and ontogenetic pattern. This can allow complex adult regulatory systems to be teased apart temporally, as the developing animal builds regulatory pathways. Equally important is the nature of crustacean larvae; many undergo dramatic metamorphoses in cases where the larvae have adaptations to environments different to those of the adult. During environmental transitions physiological adaptations to immediate change should take precedence over long-term adult adaptations. It is therefore possible to look at physiological responses as a function of developmental/environmental adaptation, independent of adult functions.

The ocular manifestations of rheumatoid disease.

The inflammatory arthropathies that affect the eye most commonly are RA, JRA, and the seronegative spondyloarthropathies. These conditions not only cause devastating systemic findings but can be the source of damaging ocular disease. The inflammatory nature of these entities, with the accompanying liberation of mediators of inflammation, can result in a cycle of tissue destruction that culminates in blindness. The diseases reviewed can present first with systemic or ocular findings; thus, all physicians must be equipped with the appropriate knowledge to make accurate and timely diagnoses so that appropriate management strategies can be employed. The successful recognition and treatment of these conditions can prevent their associated systemic and ocular morbidity.

Intraocular lens explantation in uveitis.

Visual rehabilitation after cataract surgery has been improved with the development of IOLs. These lenses are well tolerated in many uveitis patients when complete control of preoperative inflammation is achieved. However, in some patients, IOL placement after cataract extraction results in chronic inflammation, deposition of inflammatory cells and debris on the IOL surface, and inflammatory membrane formation despite antiinflammatory coverage. Patients with systemic diseases characterized by chronic inflammation, such as sarcoidosis and JRA, and those with chronic ocular inflammatory conditions or inflammation involving the intermediate segment of the eye may be at high risk for these complications. In patients in whom antiinflammatory therapy fails, adequate control of inflammation may be achieved after lens explantation.

'Changing climate, changing health, changing stories' profile: using an EcoHealth approach to explore impacts of climate change on inuit health.

Global climate change and its impact on public health exemplify the challenge of managing complexity and uncertainty in health research. The Canadian North is currently experiencing dramatic shifts in climate, resulting in environmental changes which impact Inuit livelihoods, cultural practices, and health. For researchers investigating potential climate change impacts on Inuit health, it has become clear that comprehensive and meaningful research outcomes depend on taking a systemic and transdisciplinary approach that engages local citizens in project design, data collection, and analysis. While it is increasingly recognised that using approaches that embrace complexity is a necessity in public health, mobilizing such approaches from theory into practice can be challenging. In 2009, the Rigolet Inuit Community Government in Rigolet, Nunatsiavut, Canada partnered with a transdisciplinary team of researchers, health practitioners, and community storytelling facilitators to create the Changing Climate, Changing Health, Changing Stories project, aimed at developing a multi-media participatory, community-run methodological strategy to gather locally appropriate and meaningful data to explore climate-health relationships. The goal of this profile paper is to describe how an EcoHealth approach guided by principles of transdisciplinarity, community participation, and social equity was used to plan and implement this climate-health research project. An overview of the project, including project development, research methods, project outcomes to date, and challenges encountered, is presented. Though introduced in this one case study, the processes, methods, and lessons learned are broadly applicable to researchers and communities interested in implementing EcoHealth approaches in community-based research.

Metabolic, respiratory and cardiovascular responses to acute and chronic hypoxic exposure in tadpole shrimp Triops longicaudatus.

Hypoxic exposure experienced during sensitive developmental periods can shape adult physiological capabilities and define regulatory limits. Tadpole shrimp were reared under normoxic (19-21 kPa O(2)), moderate (10-13 kPa O(2)) or severe (1-3 kPa O(2)) hypoxic conditions to investigate the influence of developmental oxygen partial pressure (P(O(2))) on adult metabolic, respiratory and cardiovascular physiology. Developmental P(O(2)) had no effect on metabolic rate or metabolic response to hypoxic exposure in adults. All rearing groups decreased O(2) consumption as water P(O(2)) decreased. Heart rate, stroke volume and cardiac output were independent of P(O(2)) down to 5 kPa O(2) in all rearing groups. Below this, cardiac output was maintained only in tadpole shrimp reared under severe hypoxic conditions. The enhanced ability to maintain cardiac output was attributed to an increase in hemoglobin concentration and O(2)-binding affinity in those animals. Oxygen-delivery potential was also significantly higher in the group reared under severe hypoxic conditions (1,336 microl O(2) min(-1)) when compared with the group reared under normoxic conditions (274 microl O(2) min(-1)). Differences among the rearing groups that were dependent on hemoglobin were not considered developmental effects because hemoglobin concentration could be increased within seven days of hypoxic exposure independent of developmental P(O(2)). Hypoxia-induced hemoglobin synthesis may be a compensatory mechanism that allows tadpole shrimp to regulate O(2) uptake and transport in euryoxic (O(2) variable) environments. The results of this study indicate that increased hemoglobin concentration, increased O(2)-binding affinity and transient decreases in metabolic demand may account for tadpole shrimp hypoxic tolerance.

Cardiac development in crayfish: ontogeny of cardiac physiology and aerobic metabolism in the red swamp crayfish Procambarus clarkii.

The cardiovascular system performs key physiological functions even as it develops and grows. The ontogeny of cardiac physiology was studied throughout embryonic and larval development in the red swamp crayfish Procambarus clarkii using videomicroscopic dimensional analysis. The heart begins to contract by day 13 of development (at 25 degrees C, 20 kPa O2). Prior to eclosion, heart rate (fH) decreases significantly. Previous data suggests that the decrease in cardiac parameters prior to hatching may be due to an oxygen limitation of the embryo. Throughout development, metabolizing mass and embryonic oxygen consumption primarily increased while egg surface area remains constant. The limited area for gas exchange of the egg membrane, in combination with the increasing oxygen demand of the embryo could result in an inadequate diffusive supply of oxygen to developing tissues. To determine if the decrease in cardiac function was the result of an internal hypoxia experienced during late embryonic development, early and late stage embryos were exposed to hyperoxic water (PO2 = 40 kPa O2). The fH in late stage embryos increased significantly over control values when exposed to hyperoxic water suggesting that the suppression in cardiac function observed in late stage embryos is likely due to a limited oxygen supply.

Antihypertensive drug therapy prevents cerebral microvascular abnormalities in hypertensive rats.

Studies were performed on anesthetized 16-18 week old normotensive Wistar-Kyoto rats, spontaneously hypertensive rats, and Goldblatt two-kidney one clip renal hypertensive rats, treated from age 4-5 weeks with an oral antihypertensive regimen consisting of hydralazine, reserpine, and chlorothiazide. Measurements of flow and intravascular pressure in the cerebral microvasculature were made via a constantly suffused open cranial window using video microscopy. A significant upward shift was seen in the pressure range for cerebral blood flow autoregulation in both groups of untreated hypertensive animals. Following treatment, the autoregulatory range in both hypertensive models was restored to a level nearly identical to control. The prevention of this shift in treated animals was due primarily to the prevention of structural microvascular adaptations that occur in untreated hypertensive animals. By preventing elevations in microvascular pressure, treatment may have eliminated the major stimulus for development of hypertrophy in resistance vessels. However, a persistent increment of arteriolar wall mass in treated spontaneously hypertensive rats may represent a hyperplastic response not influenced by treatment. Likewise, a persistent constriction of the smallest arterioles in treated renal hypertensive rats may represent a differential sensitivity of microvessels to circulating vasoactive agents. It appears that treatment initiated in the prehypertensive state, or before significant sustained hypertension has occurred, can markedly reduce the cerebrovascular morbidity associated with two different forms of hypertension.

Effects of antihypertensive treatment on the cerebral microvasculature of spontaneously hypertensive rats.

Experiments were performed in anesthetized 18-19-week-old spontaneously hypertensive rats (SHR) to evaluate the effects of delayed antihypertensive treatment on cerebrovascular function. Animals were treated for 25 +/- 1 days with an oral antihypertensive regimen consisting of hydralazine, reserpine, and chlorothiazide, resulting in normotension within 2 weeks. Cerebral arterioles were examined via a constantly suffused open cranial window and video microscopy. Resting cerebral blood flow was measured using radioactive microspheres and the reference organ method. While untreated SHR exhibited reductions in arteriolar diameter compared with normotensive Wistar Kyoto rats (WKY), treatment restored arteriolar dimensions to normal. Increments in microvascular wall area, associated with medial hypertrophy in untreated SHR, were completely reversed in treated SHR to a magnitude not different from control. Resting cerebral blood flow was, however, decreased in treated SHR compared with both untreated SHR and WKY; this was due to an increase in total cerebrovascular resistance compared with WKY. Additionally, microvascular pressure in the largest arterioles in treated SHR was reduced compared with both WKY and untreated SHR. There was a significant increase in the relative pressure drop accounted for by the arterial vessels upstream from the cerebral microcirculation in treated SHR. These results suggest that 1) cerebral microvascular abnormalities induced by chronic hypertension are reversed by delayed antihypertensive therapy, and 2) there is a persistent elevation in cerebrovascular resistance upstream from the microcirculation representing large vessel adaptations that may not be readily reversible with treatment.

Evidence of myogenic vascular control in the rat cerebral cortex.

The potential presence of myogenic regulation in the cerebral microvasculature of the rat was investigated using a method which alters intravascular pressure without appreciably changing cerebral perfusion pressure (arterial minus venous pressure). The entire rat was placed in a sealed box, with the cranial cavity open to the atmosphere and prepared for in vivo microscopy. By increasing the ambient pressure in the box, both systemic arterial and venous pressure could be changed by nearly equal amounts (+/- 20 mm Hg). Heart and respiratory rates were not influenced by changing ambient pressure by +/- 20 mm Hg. At elevated ambient pressures, cortical arterioles constricted in linear proportion to the ambient pressure, whereas subatmospheric ambient pressures caused vasodilation whose magnitude was about equal at ambient pressures of -6 to -18 mm Hg. The calculated vessel wall tension typically remained within about +/- 10-15% of control during changes of transmural pressure of +/- 20-40%. In all cases, arteriolar responses to changes in ambient and intravascular pressure reached a new steady state within 10-15 seconds and were sustained for up to 30 minutes. These data are interpreted to indicate the presence of a myogenic vascular response in the brain vasculature of the rat.

Non-neoplastic ovarian cysts with ectopic pregnancy.

Thirty non-neoplastic ovarian cysts, discovered at laparotomy in association with 27 cases of tubal ectopic pregnancy, were examined to document changes seen in early pregnancy and possibly to identify precursor lesions to the luteinized cysts of later pregnancy. The ages of the patients ranged from 16 to 40 years, and length of gestation varied between 5 and 11 weeks. Of the 30 cysts, 12 were corpus luteum cysts; 10 were called lutein cysts, nonspecific, and had a lining of luteinized cells of a single cell type; three cysts were luteinized follicles; four cysts were unlined or lined by a single layer of cells. The origin of these four was not obvious, and they were called "simple cysts." The last was a granulosa-theca lutein cyst. Corpus luteum cysts are assumed to arise from the corpus luteum, and simple cysts appear to arise from both corpus luteum cysts and other follicular structures. The nonspecific lutein cysts appeared to arise from structures other than the corpus luteum or corpus luteum cysts; these nonspecific lutein cysts may be precursors to the so-called large solitary luteinized follicle cyst of pregnancy.

In vitro and in vivo measurement of red cell velocity with epi- and transillumination.

Measurement of red cell velocity with the dual-slit cross-correlation method in glass capillary tubes during transillumination indicates that the measured velocity must be divided by a correction factor of approximately 1.6 to equal the average velocity calculated from a known flow and inner diameter. Whether the same correction factor exists when red cell velocity is measured during epiillumination is questionable. Red cell velocity was measured with the dual-slit correlation method nearly simultaneously using epi- (EL) and transillumination (TL) while glass tubes (40-100 microns, i.d.) were pump perfused with whole human blood (hematocrit 39-42%). With TL, the measured velocity is 1.58 +/- 0.07 (SEM) times the calculated average velocity, whereas a factor of 2.04 +/- 0.04 (SEM) was obtained with epiillumination. When intestinal arterioles with approximately the same inner diameters and flow velocities as the glass tubes were used, the ratio of velocities measured with TL to EL was 1.21 +/- 0.02 (SEM) as compared to 1.31 +/- 0.09 (SEM) for glass tubes using TL and EL of the tube at the same pump flow. This similarity of TL to EL velocity ratios for glass tubes and microvessels may be fortuitous or indicate that comparable flow properties and measurement conditions exist for in vitro and in vivo situations. The major finding of the study is, however, that different velocity correction factors exist for EL and TL measurements when the dual-slit correlation method is used to estimate red cell velocities in tubes of an internal diameter of 40-100 microns at normal hematocrits.