Gene expression dynamics during temperature-dependent sex determination in a sea turtle.

Fifty years ago, researchers discovered a link between ambient temperature and the sex of turtle embryos. More recently, significant progress has been made in understanding the influence of temperature on freshwater turtles. However, our understanding of the key genetic factors in other turtle groups, such as sea turtles, remains limited. To address this gap, we conducted RNA-seq analyses on embryonic tissues from the sea olive ridley turtle during the thermosensitive period (stages 21-26) at temperatures known to produce males (26 °C) and females (33 °C). Our findings revealed that incubation temperatures primarily influence genes with broad expression across tissues due to differential cell division rates and later have an effect regulating gonad-specific transcripts. This effect is mostly related to gene activation rather than transcription repression. We performed transcriptome analyses following shifts in incubation temperatures of bi-potential gonads. This approach allowed us to identify genes that respond rapidly and may be closer to the beginning of the temperature-sensing pathway. Notably, we observed swift adaptations in the expression levels of chromatin modifiers JARID2 and KDM6B, as well as the splicing factor SRSF5, and transcription regulators THOC2, DDX3X and CBX3, but little impact in the overall gonad-specific pathways, indicating that temperature-sensing genes may change rapidly but the rewiring of the gonad's developmental fate is complex and resilient. AUTHOR SUMMARY: Sea turtles, one of the most iconic creatures of our oceans, confront a troubling reality of endangerment, a peril magnified by the looming specter of climate change. This climatic shift is gradually increasing the temperature of the nesting beaches thus causing dramatic male/female population biases. Conservation efforts will need genetic and molecular information to reverse the negative effects of climate change on the populations. In this study, we conducted the first transcriptomic analysis of embryonic tissues, including gonads, brain, liver, and mesonephros, in the olive ridley sea turtle during the critical thermosensitive period spanning stages 21-26. We examined both male-producing (26 °C) and female-producing (33 °C) temperatures and found that incubation temperatures influence temperature-sensitive genes that are either expressed globally or specifically associated with the gonads. These findings indicate that incubation temperatures predominantly sway genes with broad expression patterns due to differential cell division rates. This natural process was opted in the gonads to drive sex determination. We also identified genes that are rapidly capable of sensing temperature changes and that could play a role in the activation of the sex determination pathway. Overall, our study sheds light on the intricate interplay between temperature and gene expression during sea turtle development, revealing dynamic changes in the transcriptome and highlighting the involvement of key genetic players in sex determination.

Protocol: identifying policy, system, and environment change interventions to enhance availability of blood for transfusion in Kenya, a mixed-methods study.

BACKGROUND: Safe blood is essential for the care of patients with life-threatening anemia and hemorrhage. Low blood donation rates, inefficient testing procedures, and other supply chain disruptions in blood administration affect patients in low-resource settings across Sub-Saharan countries, including Kenya. Most efforts to improve access to transfusion have been unidimensional, usually focusing on only point along the blood system continuum, and have excluded community stakeholders from early stages of intervention development. Context-appropriate interventions to improve the availability of safe blood at the point of use in low-resource settings are of paramount importance. Thus, this protocol proposes a multifaceted approach to characterize the Kenyan blood supply chain through quantitative and qualitative analyses as well as an industrial engineering approach. METHODS: This study will use a mixed-methods approach in addition to engineering process mapping, modeling and simulation of blood availability in Kenya. It will be guided by a multidimensional three-by-three-by-three matrix: three socioeconomic settings, three components of the blood system continuum, and three levels of urgency of blood transfusion. Qualitative data collection includes one-on-one interviews and focus group discussions with stakeholders across the continuum to characterize ground-level deficits and potential policy, systems, and environment (PSE) interventions. Prospectively-collected quantitative data will be used to estimate blood collection and transfusion of blood. We will create a process map of the blood system continuum to model the response to PSE changes proposed by stakeholders. Lastly, we will identify those PSE changes that may have the greatest impact on blood transfusion availability, accounting for differences across socioeconomic settings and levels of urgency. DISCUSSION: Identifying and prioritizing community-driven interventions to improve blood supply in low-resource settings are of utmost importance. Varied constraints in blood collection, processing, delivery, and use make each socioeconomic setting unique. Using a multifaceted approach to understand the Kenyan blood supply and model the response to stakeholder-proposed PSE changes may lead to identification of contextually appropriate intervention targets to meet the transfusion needs of the population.

The BLOODSAFE program: Building the future of access to safe blood in Sub-Saharan Africa.

BACKGROUND: The supply of blood in many low- and middle-income nations in Sub-Saharan Africa (SSA) does not meet the patient care needs. Lack and delay of blood transfusion cause harm to patients and slow the rate of progress in other parts of the health system. Recognizing the power of implementation science, the BLOODSAFE Program was initiated which supports three SSA research study teams and one data coordinating center (DCC) with the goal to improve access to safe blood transfusion in SSA. STUDY DESIGN AND METHODS: The study team in Ghana is focusing on studying and decreasing iron deficiency in blood donors and evaluating social engagement of blood donors through different approaches. The study team in Kenya is building a "vein to vein" workflow model to elucidate and devise strategies to overcome barriers to blood donation and improve infrastructural components of blood product production and use. The Malawi team is studying the infectious disease ramifications of blood donation as well as blood donor retention strategies aimed at blood donors who commence their donation career in secondary schools. RESULTS AND DISCUSSION: Together the project teams and the DCC work as a consortium to support each other through a shared study protocol that will study donor motivations, outcomes, and adverse events across all three countries. The BLOODSAFE Program has the potential to lead to generalizable improvement approaches for increasing access to safe blood in SSA as well as mentoring and building the research capacity and careers of many investigators.

Disparities in Access to Postmastectomy Breast Reconstruction: Does Living in a Specific ZIP Code Determine the Patient's Reconstructive Journey?

BACKGROUND: Postmastectomy breast reconstruction (BR) has been shown to provide long-term quality of life and psychosocial benefits. Despite the policies initiated to improve access to BR, its delivery continues to be inequitable, suggesting that barriers to access have not been fully identified and/or addressed. The purpose of this study was to assess the influence of geographic location, socioeconomic status, and race in access to immediate BR (IBR). METHODS: An institutional review board-approved observational study was conducted. All patients who underwent breast cancer surgery from 2014 to 2019 were queried from our institutional Breast Cancer Registry. A geographical analysis was conducted using demographic characteristics and patient's ZIP codes. Euclidean distance from patient home ZIP code to UPMC Magee Women's Hospital was calculated, and χ2, Student t test, Mann-Whitney, and Kruskal-Wallis tests was used to evaluate differences between groups, as appropriate. Statistical significance was set at P < 0.05. RESULTS: Overall, 5835 patients underwent breast cancer surgery. A total of 56.7% underwent lumpectomy or segmental mastectomy, and 43.3% underwent modified, total, or radical mastectomy. From the latter group, 33.5% patients pursued BR at the time of mastectomy: 28.6% autologous, 48.1% implant-based, 19.4% a combination of autologous and implant-based, and 3.9% unspecified reconstruction. Rates of IBR varied among races: White or European (34.1%), Black or African American (27.7%), and other races (17.8%), P = 0.022. However, no difference was found between type of BR among races (P = 0.38). Moreover, patients who underwent IBR were significantly younger than those who did not pursue reconstruction (P < 0.0001). Patients who underwent reconstruction resided in ZIP codes that had approximately US $2000 more annual income, a higher percentage of White population (8% vs 11% non-White) and lower percentage of Black or African American population (1.8% vs 2.9%) than the patients who did not undergo reconstruction. CONCLUSIONS: While the use of postmastectomy BR has been steadily rising in the United States, racial and socioeconomic status disparities persist. Further efforts are needed to reduce this gap and expand the benefits of IBR to the entire population without distinction.

Peer mentorship to build research capacity among members of the International Student Surgical Network (InciSioN): a proof of concept study.

BACKGROUND: International Student Surgical Network (InciSioN) is the largest student and trainee global surgery interest group worldwide and its members have contributed significantly to global surgery research. The InciSioN Research Capacity-Building (IReCaB) program aimed to enhance the research skills and confidence of participants via a peer mentorship model. METHODS: After an open call to members of InciSioN to enroll, participants' knowledge of research methods and the process was evaluated through a test to assign mentor and mentee roles, with mentors being those who scored ≥ 20/25. Mentors then delivered a series of four webinars to help disseminate research methodology to mentees. Finally, mentees were tested on their knowledge of research and their satisfaction with the program was also evaluated. RESULTS: Fifty-two participants, mostly from LMICs (n = 23/52, 44.2%) were enrolled, and 36 completed the program. There was a significant improvement in the proportion of questions answered correctly on the post-program test (R = 0.755, p < 0.001). Post-IReCaB test scores were greater than pre-IReCaB scores (p < 0.001). The difference in confidence after the course was also significant (p < 0.001). IReCaB participants successfully designed, implemented, and published an international cross-sectional study. CONCLUSION: This study showed improvements in participants' understanding of theoretical components of scientific research. We offer a model for research capacity building that can be implemented, modeled, and further refined by similar organizations with academic research goals.

Impact of School Location on Children's Air Pollution Exposure.

The role of school location in children's air pollution exposure and ability to actively commute is a growing policy issue. Well-documented health impacts associated with near-roadway exposures have led school districts to consider school sites in cleaner air quality environments requiring school bus transportation. We analyze children's traffic-related air pollution exposure across an average Detroit school day to assess whether the benefits of reduced air pollution exposure at cleaner school sites are eroded by the need to transport students by bus or private vehicle. We simulated two school attendance scenarios using modeled hourly pollutant concentrations over the school day to understand how air pollution exposure may vary by school location and commute mode. We found that busing children from a high-traffic neighborhood to a school 19 km away in a low-traffic environment resulted in average daily exposures 2 to 3 times higher than children walking to a local school. Health benefits of siting schools away from high-volume roadways may be diminished by pollution exposure during bus commutes. School districts cannot simply select sites with low levels of air pollution, but must carefully analyze tradeoffs between location, transportation, and pollution exposure.

17ß-Estradiol modulates cell proliferation of medullary cords during ovarian differentiation of the Lepidochelys olivacea sea turtle.

In turtles undergoing temperature sex determination (TSD), bipotential gonads express Sox9 in medullary cords at both female- (FPT) and male-producing temperatures (MPT). Subsequently, when the sex fate of medullary cords becomes dimorphic, at FPT, Sox9 is downregulated, whereas at MPT, its expression is maintained. Medullary cords in the ovary turn into ovarian lacuna, whereas in the testis they differentiate as seminiferous cords. When embryos of Lepidochelys olivacea sea turtle are incubated at MPT and treated with estradiol, Sox9 expression persists in the medullary cords in the form of tiny ovotestis-like formations. The perturbed development of the treated gonads is due to a significant decrease in the number of proliferating cells. This suggests that the disturbed effect caused by exogenous estradiol may be due to a conflict between the gene networks regulated by temperature and the increased level of endogenous estrogens, induced by the treatment. Here, we decided to use fadrozole and fulvestrant, an aromatase inhibitor and an estrogen-receptor antagonist, respectively, to provide insights into the role played by endogenous estrogens in regulating the cell proliferation of the two main gonadal compartments: the medullary cords and the cortex. Comparing cell proliferation patterns, our current results suggest that the endogenous estrogens are involved in determining the sex fate of medullary cords, by repressing proliferation. Interestingly, our results showed that endogenous estradiol levels are unnecessary for the thickening of the ovarian cortex.

Development and Evaluation of the R-LINE Model Algorithms to Account for Chemical Transformation in the Near-road Environment.

With increased urbanization, there is increased mobility leading to higher amount of traffic-related activity on a global scale. Most NOx from combustion sources (about 90-95%) are emitted as NO, which is then readily converted to NO2 in the ambient air, while the remainder is emitted largely as NO2. Thus, the bulk of ambient NO2 is formed due to secondary production in the atmosphere, and which R-LINE cannot predict given that it can only model the dispersion of primary air pollutants. NO2 concentrations near major roads are appreciably higher than those measured at monitors in existing networks in urban areas, motivating a need to incorporate a mechanism in R-LINE to account for NO2 formation. To address this, we implemented three different approaches in order of increasing degrees of complexity and barrier to implementation from simplest to more complex. The first is an empirical approach based upon fitting a 4th order polynomial to existing near-road observations across the continental U.S., the second involves a simplified two-reaction chemical scheme, and the third involves a more detailed set of chemical reactions based upon the Generic Reaction Set (GRS) mechanism. All models were able to estimate more than 75% of concentrations within a factor of two of the near-road monitoring data and produced comparable performance statistics. These results indicate that the performance of the new R-LINE chemistry algorithms for predicting NO2 is comparable to other models (i.e. ADMS-Roads with GRS), both showing less than ±15% fractional bias and less than 45% normalized mean square error.

Attenuation of the physiological response to infection on adults over 65 years old admitted to the emergency room (ER).

It has been considered that the elderly have clinical manifestations different from the ones observed in middle-age adults during an injury event. This hypothesis has not been extensively explored in sepsis and bacterial infections. Secondary analysis of two prospective studies including 2611 patients over 18 years of age admitted to the emergency room with confirmed or probable bacterial infections and sepsis. The outcome measures were heart rate, respiratory rate, systolic blood pressure, temperature, Glasgow Coma Scale, creatinine, PaO2/FiO2 and platelets daily during the first week. Compared to survivors younger than 65, the deceased under 65 had an average heart rate of 12.5 beats per minute per day higher (95% CI 9.32; 15.61), while patients over 65 who died barely had an average 5.7 beats per minute per day higher than the same reference group (95% CI 3.45; 8.06). The systolic blood pressure had a significant decreased in those who died younger than 65, compared to survivors with the same age, in both cohorts (-5.2 mmHg, 95% CI -8.17; -2.23 and -8.5 mmHg, 95% CI -13.48; -3.54, respectively), while those older than 65 who died had a nonsignificant increase (+1.6 mmHg, 95% CI -1.33; 4.62 and +0.1, 95% CI -6.48; 6.72, respectively) compared to the same reference group. The behavior of most clinical and laboratory variables suggests a less pronounced response of subjects above 65 years of age who died 28 days after being diagnosed with sepsis.

Exogenous estradiol alters gonadal growth and timing of temperature sex determination in gonads of sea turtle.

Temperature sex determining species offer a model for investigating how environmental cues become integrated to the regulation of patterning genes and growth, among bipotential gonads. Manipulation of steroid hormones has revealed the important role of aromatase in the regulation of the estrogen levels involved in temperature-dependent sex determination. Estradiol treatment counteracts the effect of male-promoting temperature, but the resulting ovarian developmental pattern differs from that manifested with the female-promoting temperature. Hypoplastic gonads have been reported among estradiol-treated turtles; however the estradiol effect on gonadal size has not been examined. Here we focused on the sea turtle Lepidochelys olivacea, which develops hypoplastic gonads with estradiol treatment. We studied the effect of estradiol on cell proliferation and on candidate genes involved in ovarian pattern. We found this effect is organ specific, causing a dramatic reduction in gonadal cell proliferation during the temperature-sensitive period. Although the incipient gonads resembled tiny ovaries, remodeling of the medullary cords and down-regulation of testicular factor Sox9 were considerably delayed. Contrastingly, with ovarian promoting temperature as a cue, exogenous estradiol induced the up-regulation of the ovary factor FoxL2, prior to the expression of aromatase. The strong expression of estrogen receptor alpha at the time of treatment suggests that it mediates estradiol effects. Overall results indicate that estradiol levels required for gonadal growth and to establish the female genetic network are delicately regulated by temperature.

Dimorphic DNA methylation during temperature-dependent sex determination in the sea turtle Lepidochelys olivacea.

Sex determination in vertebrates depends on the expression of a conserved network of genes. Sea turtles such as Lepidochelys olivacea have temperature-dependent sex determination. The present work analyses some of the epigenetic processes involved in this. We describe sexual dimorphism in global DNA methylation patterns between ovaries and testes of L. olivacea and show that the differences may arise from a combination of DNA methylation and demethylation events that occur during sex determination. Irrespective of incubation temperature, 5-hydroxymethylcytosine was abundant in the bipotential gonad; however, following sex determination, this modification was no longer found in pre-Sertoli cells in the testes. These changes correlate with the establishment of the sexually dimorphic DNA methylation patterns, down regulation of Sox9 gene expression in ovaries and irreversible gonadal commitment towards a male or female differentiation pathway. Thus, DNA methylation changes may be necessary for the stabilization of the gene expression networks that drive the differentiation of the bipotential gonad to form either an ovary or a testis in L. olivacea and probably among other species that manifest temperature-dependent sex determination.

Severe Sinus Dysfunction in the Context of Chronic Lithium Intoxication and Poorly Controlled Hypothyroidism.

Cardiotoxicity associated with lithium is not a common event; however, it is potentially life-threatening, manifesting electrocardiographically with sinoatrial blocks, high-degree atrioventricular blocks, QT prolongation, and ventricular tachyarrhythmias. This case report presents a patient with severe sinus dysfunction in a clinically severe presentation secondary to cardiogenic shock. The patient sought medical attention for a one-week history of non-anginal chest pain, dizziness without syncope, generalized weakness, and somnolence progressing to bedridden status in the days preceding hospital admission. Laboratory findings revealed elevated blood levels of lithium and thyroid-stimulating hormone (TSH), along with concomitant Acute Kidney Injury Network (AKIN) II acute kidney injury. Subsequently, the patient was admitted to the intensive care unit, where persistent extreme sinus bradycardia of 30 bpm (beats per minute) with sinus pauses without ischemic changes was observed. The patient received supportive treatment, including renal replacement therapy, resulting in complete recovery of hemodynamic status without the need for long-term cardiac conduction devices.

Formation of the genital ridges is preceded by a domain of ectopic Sox9-expressing cells in Lepidochelys olivacea.

Bipotential gonads represent the structural framework from which alternative molecular sex determination networks have evolved. Maintenance of Sox9 expression in Sertoli cells is required for the structural and functional integrity of male gonads in mammals and probably in most amniote vertebrates. However, spatial and temporal patterns of Sox9 expression have diversified along evolution. Species with temperature sex determination are an interesting predictive model since one of two alternative developmental outcomes, either ovary or testis occurs under controlled laboratory conditions. In the sea turtle Lepidochelys olivacea, Sox9 is expressed in the medullary cords of bipotential gonads when incubated at both female- or male-promoting temperature (FT or MT). Sox9 is then turned off in presumptive ovaries, while it remains turned on in testes. In the current study, Sox9 was used as a marker of the medullary cell lineage to investigate if the medullary cords originate from mesothelial cells at the genital ridges where Sox9 is upregulated, or, if they derive from a cell population specified at an earlier developmental stage, which maintains Sox9 expression. Using immunofluorescence and in situ hybridization, embryos were analyzed prior to, during and after gonadal sex determination. A T-shaped domain (T-Dom) formed by cytokeratin (CK), N-cadherin (Ncad) and SOX9-expressing cells was found at the upper part of the hindgut dorsal mesentery. The arms of the T-Dom were extended to both sides towards the ventromedial mesonephric ridge before the thickening of the genital ridges, indicating that they contained gonadal epithelial cell precursors. Thereafter, expression of Sox9 was maintained in medullary cords while it was downregulated at the surface epithelium of bipotential gonads in both FT and MT. This result contrasts with observations in mammals and birds, in which Sox9 upregulation starts at a later stage in the inner cells underlying the Sox9-negative surface epithelium, suggesting that the establishment of a self-regulatory Sox9 loop required for Sertoli cell determination has evolved. The T-shaped domain at the upper part of the hindgut dorsal mesentery found in the current study may represent the earliest precursor of the genital ridges, previously unnoticed in amniote vertebrates.

A hyperlocal hybrid data fusion near-road PM2.5 and NO2 annual risk and environmental justice assessment across the United States.

Exposure to traffic-related air pollutants (TRAPs) has been associated with numerous adverse health effects. TRAP concentrations are highest meters away from major roads, and disproportionately affect minority (i.e., non-white) populations often considered the most vulnerable to TRAP exposure. To demonstrate an improved assessment of on-road emissions and to quantify exposure inequity in this population, we develop and apply a hybrid data fusion approach that utilizes the combined strength of air quality observations and regional/local scale models to estimate air pollution exposures at census block resolution for the entire U.S. We use the regional photochemical grid model CMAQ (Community Multiscale Air Quality) to predict the spatiotemporal impacts at local/regional scales, and the local scale dispersion model, R-LINE (Research LINE source) to estimate concentrations that capture the sharp TRAP gradients from roads. We further apply the Regionalized Air quality Model Performance (RAMP) Hybrid data fusion technique to consider the model's nonhomogeneous, nonlinear performance to not only improve exposure estimates, but also achieve significant model performance improvement. With a R2 of 0.51 for PM2.5 and 0.81 for NO2, the RAMP hybrid method improved R2 by ~0.2 for both pollutants (an increase of up to ~70% for PM2.5 and ~31% NO2). Using the RAMP Hybrid method, we estimate 264,516 [95% confidence interval [CI], 223,506-307,577] premature deaths attributable to PM2.5 from all sources, a ~1% overall decrease in CMAQ-estimated premature mortality compared to RAMP Hybrid, despite increases and decreases in some locations. For NO2, RAMP Hybrid estimates 138,550 [69,275-207,826] premature deaths, a ~19% increase (22,576 [11,288 - 33,864]) compared to CMAQ. Finally, using our RAMP hybrid method to estimate exposure inequity across the U.S., we estimate that Minorities within 100 m from major roads are exposed to up to 15% more PM2.5 and up to 35% more NO2 than their White counterparts.

The Association of Blood Banks per City with Mortality Due to Traumatic Hemorrhagic Shock in Colombia: A Population-Based Analysis.

Background: Hemorrhagic shock is the second leading cause of death for injured people and disproportionately affects low resource economies. The potential role of spatial allocation of blood banks and the unmet transfusion needs of patients are yet to be characterized. We aimed to estimate the effect of the number of blood banks in mortality due to traumatic hemorrhagic shock (THS) in Colombia. Methods: We performed a population-based cross-sectional study using secondary data from the Colombian Government: including annual reports from the Blood Bank Network, mortality, and population estimates for 2015-2016. International Classification of Disease 10th code T79.4 identified THS as the primary cause of death. A city-clustered multivariate negative binomial regression, weighted by violent deaths rate, was used to obtain incidence rate ratios (IRR) of death due to THS with 95% confidence intervals (95%CI). Results: Of the 59,030 violent deaths in Colombia in 2015-2016, 36.76% were due to THS. Only 3.13% of Colombian municipalities had a blood bank. THS incidence decreased as the number of blood banks in a city increased, and the lowest incidence was observed at ten banks (IRR:0.18, 95%CI:0.15-0.22). Receiving medical care in a city with blood banks had a more substantial impact on THS (IRR:0.85; 95%CI:0.76-0.96). Conclusion: The number of blood banks per city was associated with lower incidence of THS deaths. These findings may highlight the inequitable distribution of blood systems and their association with preventable deaths. Further studies with more focused clinical and geographical data might clarify the geographic determinants of blood products' availability.

Light and focused ion beam microscopy workflow for resin-embedded tissues.

Although the automated image acquisition with the focused ion beam scanning electron microscope (FIB-SEM) provides volume reconstructions, volume analysis of large samples remains challenging. Here, we present a workflow that combines a modified sample protocol of the classical transmission electron microscope with FIB-SEM volume imaging. The proposed workflow enables efficient 3D structural surveys of rabbit ovaries collected at consecutive developmental stages. The precise trimming of the region of interest adds the time dimension to the volume, constructing a virtual 4D electron microscopy. We found filopodia-like processes emitted by oocyte cysts allowing contact between oocytes not previously observed.

Development and Application of an Open Tool for Sharing and Analyzing Integrated Clinical and Environmental Exposures Data: Asthma Use Case.

BACKGROUND: The Integrated Clinical and Environmental Exposures Service (ICEES) serves as an open-source, disease-agnostic, regulatory-compliant framework and approach for openly exposing and exploring clinical data that have been integrated at the patient level with a variety of environmental exposures data. ICEES is equipped with tools to support basic statistical exploration of the integrated data in a completely open manner. OBJECTIVE: This study aims to further develop and apply ICEES as a novel tool for openly exposing and exploring integrated clinical and environmental data. We focus on an asthma use case. METHODS: We queried the ICEES open application programming interface (OpenAPI) using a functionality that supports chi-square tests between feature variables and a primary outcome measure, with a Bonferroni correction for multiple comparisons (α=.001). We focused on 2 primary outcomes that are indicative of asthma exacerbations: annual emergency department (ED) or inpatient visits for respiratory issues; and annual prescriptions for prednisone. RESULTS: Of the 157,410 patients within the asthma cohort, 26,332 (16.73%) had 1 or more annual ED or inpatient visits for respiratory issues, and 17,056 (10.84%) had 1 or more annual prescriptions for prednisone. We found that close proximity to a major roadway or highway, exposure to high levels of particulate matter ≤2.5 µm (PM2.5) or ozone, female sex, Caucasian race, low residential density, lack of health insurance, and low household income were significantly associated with asthma exacerbations (P<.001). Asthma exacerbations did not vary by rural versus urban residence. Moreover, the results were largely consistent across outcome measures. CONCLUSIONS: Our results demonstrate that the open-source ICEES can be used to replicate and extend published findings on factors that influence asthma exacerbations. As a disease-agnostic, open-source approach for integrating, exposing, and exploring patient-level clinical and environmental exposures data, we believe that ICEES will have broad adoption by other institutions and application in environmental health and other biomedical fields.

A High-Fat and High-Carbohydrate Diet Promotes Reminiscent Hallmarks of an Aging Ovary in the Rabbit Model.

The primary definition of ovarian aging refers to the loss of follicles. Moreover, the aging of the microenvironment in ovaries, specifically affecting the follicles, may reveal deterioration with advancing age. Besides aging, metabolic disorders associated with hypercaloric diets may affect ovarian health and manifest characteristics associated with premature aging. In this study, we used 10-week-old chinchilla rabbits fed with a high-fat and high-carbohydrate diet (HFCD) until 25 weeks of age to explore hallmarks of reminiscent ovarian aging. The HFCD diet appeared to affect the ovarian reserve, reflected in a significant decrease in primordial follicles. Likewise, Sudan black stain detection revealed substantial differences in the deposits of lipofuscin in the interstitial glands of HFCD-fed rabbits compared to controls, constituting a "hallmark" of aging. The HFCD showed no induced changes in the expression of SOD 2 in the interstitial gland; however, surface epithelium cells were greater expressed. Besides this, the HFCD induced nuclear translocation of NF-ΚΒ p65 factor transcription in surface epithelium cells. We conclude that an HFCD induces a greater accumulation of senescence cells in the interstitial gland, promoting characteristics reminiscent of ovarian aging. However, the activation mechanism of NF-KB caused by an HFCD, which may be stress-responsive and generated by the interstitial gland, requires further study.

Dynamic use of fibrinogen under viscoelastic assessment results in reduced need for plasma and diminished overall transfusion requirements in severe trauma.

BACKGROUND: Despite advances in trauma management, half of trauma deaths occur secondary to bleeding. Currently, hemostatic resuscitation strategies consist of empirical transfusion of blood products in a predefined fixed ratio (1:1:1) to both treat hemorrhagic shock and correct trauma-induced coagulopathy. At our hospital, the implementation of a resuscitation protocol guided by viscoelastic hemostatic assays (VHAs) with rotational thromboelastometry has resulted in a goal-directed approach. The objective of the study is twofold, first to analyze changes in transfusion practices overtime and second to identify the impact of these changes on coagulation parameters and clinical outcomes. We hypothesized that progressive VHA implementation results in a higher administration of fibrinogen concentrate (FC) and lower use of blood products transfusion, especially plasma. METHODS: A total of 135 severe trauma patients (January 2008 to July 2019), all requiring and initial assessment for high risk of trauma-induced coagulopathy based on high-energy injury mechanism, severity of bleeding and hemodynamic instability were included. After 2011 when we first modified the transfusion protocol, a progressive change in transfusional management occurred over time. Three treatment groups were established, reflecting different stages in the evolution of our strategy: plasma (P, n = 28), plasma and FC (PF, n = 64) and only FC (F, n = 42). RESULTS: There were no significant differences in baseline characteristics among groups. Progressive implementation of rotational thromboelastometry resulted in increased use of FC over time ( p < 0.001). Regression analysis showed that group F had a significant reduction in transfusion of packed red blood cells ( p = 0.005), plasma ( p < 0.001), and platelets ( p = 0.011). Regarding outcomes, F patients had less pneumonia ( p = 0.019) and multiorgan failure ( p < 0.001), without significant differences for other outcomes. Likewise, overall mortality was not significantly different. However, further analysis comparing specific mortality due only to massive hemorrhage in the F group versus all patients receiving plasma, it was significantly lower ( p = 0.037). CONCLUSION: Implementing a VHA-based algorithm resulted in a plasma-free strategy with higher use of FC and a significant reduction of packed red blood cells transfused. In addition, we observed an improvement in outcomes without an increase in thrombotic complications. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Improving emissions inputs via mobile measurements to estimate fine-scale Black Carbon monthly concentrations through geostatistical space-time data fusion.

Isolating air pollution sources in a complex transportation environment to quantify their contribution is challenging, particularly with sparse stationary measurements. Mobile measurements can add finer spatial resolution to support source apportionment, but they exhibit limitations when characterizing long term concentrations. Dispersion models can help overcome these limitations. However, they are only as reliable as their input emissions inventories. Herein, we developed an innovative method to revise emissions through inverse modeling and improve dispersion modeling predictions using stationary/mobile measurements. One specific revision estimated an adjustment factor of ~306 for warehouse emissions, indicating a significant underestimation of our initial estimates. This revised emission rate scaled up nationally would correspond to ~3.5% of the total Black Carbon emissions in the U.S. Nevertheless, domain-specific revisions only contribute to a 4% increase of area source emissions while improving R2 from monthly estimates at fixed sites by 38%. After revising emissions through inverse dispersion modeling, we combine this model with stationary/mobile measurements through Bayesian Maximum Entropy (I-DISP BME) to produce temporally coarse yet spatially fine data fusion. We compare this novel data fusion approach to BME using only measurements (Flat BME). A 10-fold conventional cross-validation (representative of months with mobile measurements) shows that all BME methods have R2 values that range from 0.787 to 0.798. A 2-fold cross-validation (representative of months with no mobile measurements) shows that the R2 for I-DISP BME increases by a factor 90 when compared to Flat BME. Furthermore, not only is our novel I-DISP BME method more accurate than the classic Flat BME method, but the area it detects as highly exposed can be up to 5 times larger than that detected by the less accurate Flat BME method.