Emergency Department Visits for Heat Stroke in the United States, 2009 and 2010

Background: The effect of extreme heat on health has become a growing public health concern due to climate change. We aimed to examine the epidemiological patterns of hospital-based emergency department (ED) visits for heat stroke in the United States. Findings: We analyzed data from the 2009 and 2010 Nationwide Emergency Department Sample, the largest ED data system sponsored by the Agency for Healthcare Research and Quality. ED visits for heat stroke were identified by screening the recorded diagnoses using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 992.0. Annual incidence rates of ED visits for heat stroke were computed according to demographic characteristics and geographic regions. In 2009 and 2010, there were an estimated 8,251 ED visits for heat stroke in the United States, yielding an annual incidence rate of 1.34 visits per 100,000 population (95% Confidence Interval [CI] = 1.23-1.45). Significantly higher incidence rates were found in males (1.99 per 100,000; 95% CI = 1.82-2.16), adults aged ≥ 80 years (4.45 per 100,000; 95% CI = 3.73-5.18), and residents living in the southern region (1.61 per 100,000; 95% CI = 1.43-1.79). The majority (63.1%) of ED visits for heat stroke occurred during the summer months of June, July and August. Over one-half (54.6%) of the ED visits for heat stroke required hospitalization and 3.5% of the patients died in the ED or hospital. Conclusions: Heat stroke results in approximately 4,100 ED visits each year in the United States, with the majority occurring in the summer months and requiring admission to the hospital. Men, the elderly, and people living in the south region are at heightened risk

Accuracy of the diagnosis of malignant hyperthermia in hospital discharge records

Background: In 1997, the International Classification of Diseases, 9th Revision Clinical Modification (ICD-9CM) coding system introduced the code for malignant hyperthermia (MH) (995.86). The aim of the current study was to estimate the accuracy of coding for MH in hospital discharge records. Materials and methods: A panel of anesthesiologists expert in MH, reviewed medical records for patients with a discharge diagnosis of MH based on ICD-9 or ICD-10 codes from January 1, 2006 to December 31, 2008 at six tertiary care medical centers in North America. All cases were categorized as possible, probable, or fulminant MH, history of MH (family or personal) or other. Results: A total of 47 medical records were identified and reviewed by three experts. The mean age of patients was 40 years and 49% were male. A surgical procedure with general anesthesia was documented in 68% of patients. However, only 23.4% were judged to have had a possible, probable, or fulminant MH event. Dantrolene was given in 81% of MH cases. Family and personal history of MH accounted for 46.8% of cases. High fever without evidence of MH during admission accounted for 23.4%, and in 6.4% cases the reason for the code was not apparent. All patients judged to have an incident MH event survived to discharge. Conclusions: Medical record coding for MH typically includes both incident cases as well as a history of MH. The positive predictive value of about 70% for MH in this study are consistent with other studies of ICD-9 accuracy in the US. However, epidemiologic studies based on coded diagnosis of MH should carefully distinguish between incident cases related to anesthesia, cases unrelated to anesthesia and diagnosis based on history only

Multi-Parametric Analysis and Modeling of Relationships between Mitochondrial Morphology and Apoptosis

Mitochondria exist as a network of interconnected organelles undergoing constant fission and fusion. Current approaches to study mitochondrial morphology are limited by low data sampling coupled with manual identification and classification of complex morphological phenotypes. Here we propose an integrated mechanistic and data-driven modeling approach to analyze heterogeneous, quantified datasets and infer relations between mitochondrial morphology and apoptotic events. We initially performed high-content, multi-parametric measurements of mitochondrial morphological, apoptotic, and energetic states by high-resolution imaging of human breast carcinoma MCF-7 cells. Subsequently, decision tree-based analysis was used to automatically classify networked, fragmented, and swollen mitochondrial subpopulations, at the single-cell level and within cell populations. Our results revealed subtle but significant differences in morphology class distributions in response to various apoptotic stimuli. Furthermore, key mitochondrial functional parameters including mitochondrial membrane potential and Bax activation, were measured under matched conditions. Data-driven fuzzy logic modeling was used to explore the non-linear relationships between mitochondrial morphology and apoptotic signaling, combining morphological and functional data as a single model. Modeling results are in accordance with previous studies, where Bax regulates mitochondrial fragmentation, and mitochondrial morphology influences mitochondrial membrane potential. In summary, we established and validated a platform for mitochondrial morphological and functional analysis that can be readily extended with additional datasets. We further discuss the benefits of a flexible systematic approach for elucidating specific and general relationships between mitochondrial morphology and apoptosis

Cataract-Causing Defect of a Mutant γ-Crystallin Proceeds through an Aggregation Pathway Which Bypasses Recognition by the α-Crystallin Chaperone

Background: The transparency of the eye lens depends upon maintenance of the native state of the γ- and β-crystallins, which is aided by the abundant chaperones αA- and αB-crystallin. Mature onset cataract, the leading cause of blindness worldwide, involves the polymerization of covalently damaged or partially unfolded crystallins into light-scattering aggregates. A number of single amino acid substitutions and truncations of γ-crystallins result in congenital cataract in both humans and mice, though in many cases the coupling between the protein alterations and the accumulation of aggregates is poorly defined. Methodology/Principal Findings: We have studied the aggregation properties and chaperone interactions of human γD-crystallin carrying substitutions of two buried core mutants, I90F and V75D, which cause congenital cataract in mice. The in vitro aggregation pathway competing with productive refolding was not altered by either substitution. Furthermore, this aggregation pathway for both mutant proteins–originating from a partially folded intermediate–was efficiently suppressed by αB-crystallin. Thus the cataract pathology was unlikely to be associated with a direct folding defect. The native state of wild-type human γD-crystallin exhibited no tendency to aggregate under physiological conditions. However both I90F and V75D native-like proteins exhibited slow (days) aggregation to high molecular weight aggregates under physiological conditions. The perturbed conformation of I90F was recognized and bound by both αA and αB chaperones. In contrast, the aggregation derived from the perturbed state of V75D was not suppressed by either chaperone, and the aggregating species were not bound by the chaperone. Conclusions/Significance: The cataract phenotype of I90F in mice may be due to premature saturation of the finite α- crystallin pool. The V75D aggregation pathway and its escape from chaperone surveillance and aggregation suppression can account for the congenital cataract pathology of this mutant. Failure of chaperone recognition may be an important source of pathology for many other protein folding defects.National Eye Institute (Grant no. EY015834 )National Institutes of Health (U.S.) (Grant no. GM17980

Friends with Benefits: Social Coupons as a Strategy to Enhance Customers’ Social Empowerment

Businesses often seek to leverage customers’ social networks to acquire new customers and stimulate word-of-mouth recommendations. While customers make brand recommendations for various reasons (e.g., incentives, reputation enhancement), they are also motivated by a desire for social empowerment—to feel an impact on others. In several multi-method studies, we show that facilitating sharing of social coupons (i.e., coupon sets that include one for self-use and one to be shared) is a unique marketing strategy that facilitates social empowerment. Firms benefit from social coupons because customers who share spend more and report greater purchase intentions than those who do not. Furthermore, we demonstrate that social coupons are most effective when the sharer’s brand relationship is new versus established. For customers with an established relationship, sharing with a receiver who also has an established relationship maximizes potential impact. Together, these studies connect social empowerment to relationship marketing and provide guidance to managers targeting social coupons

Variations in seasonal solar insolation are associated with a history of suicide attempts in bipolar I disorder

Background: Bipolar disorder is associated with circadian disruption and a high risk of suicidal behavior. In a previous exploratory study of patients with bipolar I disorder, we found that a history of suicide attempts was associated with differences between winter and summer levels of solar insolation. The purpose of this study was to confirm this finding using international data from 42% more collection sites and 25% more countries. Methods: Data analyzed were from 71 prior and new collection sites in 40 countries at a wide range of latitudes. The analysis included 4876 patients with bipolar I disorder, 45% more data than previously analyzed. Of the patients, 1496 (30.7%) had a history of suicide attempt. Solar insolation data, the amount of the sun’s electromagnetic energy striking the surface of the earth, was obtained for each onset location (479 locations in 64 countries). Results: This analysis confirmed the results of the exploratory study with the same best model and slightly better statistical significance. There was a significant inverse association between a history of suicide attempts and the ratio of mean winter insolation to mean summer insolation (mean winter insolation/mean summer insolation). This ratio is largest near the equator which has little change in solar insolation over the year, and smallest near the poles where the winter insolation is very small compared to the summer insolation. Other variables in the model associated with an increased risk of suicide attempts were a history of alcohol or substance abuse, female gender, and younger birth cohort. The winter/summer insolation ratio was also replaced with the ratio of minimum mean monthly insolation to the maximum mean monthly insolation to accommodate insolation patterns in the tropics, and nearly identical results were found. All estimated coefficients were significant at p < 0.01. Conclusion: A large change in solar insolation, both between winter and summer and between the minimum and maximum monthly values, may increase the risk of suicide attempts in bipolar I disorder. With frequent circadian rhythm dysfunction and suicidal behavior in bipolar disorder, greater understanding of the optimal roles of daylight and electric lighting in circadian entrainment is needed