APOL1 risk variants in individuals of African genetic ancestry drive endothelial cell defects that exacerbate sepsis.

The incidence and severity of sepsis is higher among individuals of African versus European ancestry. We found that genetic risk variants (RVs) in the trypanolytic factor apolipoprotein L1 (APOL1), present only in individuals of African ancestry, were associated with increased sepsis incidence and severity. Serum APOL1 levels correlated with sepsis and COVID-19 severity, and single-cell sequencing in human kidneys revealed high expression of APOL1 in endothelial cells. Analysis of mice with endothelial-specific expression of RV APOL1 and in vitro studies demonstrated that RV APOL1 interfered with mitophagy, leading to cytosolic release of mitochondrial DNA and activation of the inflammasome (NLRP3) and the cytosolic nucleotide sensing pathways (STING). Genetic deletion or pharmacological inhibition of NLRP3 and STING protected mice from RV APOL1-induced permeability defects and proinflammatory endothelial changes in sepsis. Our studies identify the inflammasome and STING pathways as potential targets to reduce APOL1-associated health disparities in sepsis and COVID-19.

"A ghost doesn't need insulin," Cotard's delusion leading to diabetic ketoacidosis and a body-mass index of 15: a case presentation.

BACKGROUND: Cotard's Syndrome (CS) is a rare clinical entity where patients can report nihilistic, delusional beliefs that they are already dead. Curiously, while weight loss, dehydration, and metabolic derangements have been described as discussed above, a review of the literature revealed neither a single case of a severely underweight patient nor a serious metabolic complication such as Diabetic Ketoacidosis. Further, a search on PubMed revealed no articles discussing the co-occurrence of Cotard's Delusion and eating disorders or comorbid metabolic illnesses such as diabetes mellitus. In order to better examine the association between Cotard's Delusion and comorbid eating disorders and metabolic illness, we will present and discuss a case where Cotard's delusion led to a severe metabolic outcome of DKA and a BMI of 15. CASE PRESENTATION: Mr. B is a 19 year old transgender man admitted to the hospital due to diabetic ketoacidosis secondary to Type 1 Diabetes Mellitus. Mr. B had a history of Obsessive-Compulsive Disorder, Major Depressive Disorder, and Post-Traumatic Stress Disorder. The primary pediatric team discovered that Mr. B had not been using his insulin appropriately and was severely underweight, and they believed this could be due to his underlying mental illness. The psychiatric consultation/liaison service found that Mr. B was suffering from Cotard's delusion leading him to be noncompliant with his insulin due to a belief that he was already dead. Cotard's delusion had in this case led to a severe metabolic outcome of DKA and a BMI of 15. CONCLUSIONS: This case provides clinical insight into the interactions of eating disorders and Cotard's delusion as well as the potential medical complications when Cotard's delusion is co-morbid with medical conditions such as Diabetes Mellitus. We recommend that clinicians routinely screen patients for Cotard's delusion and assess whether the presence of which could exacerbate any underlying medical illness. This includes clinicians taking special care in assessing patient's caloric and fluid intake as well as their adherence to medications both psychiatric and medical. Further research could be conducted to explore the potential overlap of Cotard's delusion and eating disorder phenomenology.

Cytomegalovirus Latent Infection is Associated with an Increased Risk of COVID-19-Related Hospitalization.

Some risk factors for severe coronavirus disease 2019 (COVID-19) have been identified, including age, race, and obesity. However, 20%-50% of severe cases occur in the absence of these factors. Cytomegalovirus (CMV) is a herpesvirus that infects about 50% of all individuals worldwide and is among the most significant nongenetic determinants of immune system. We hypothesized that latent CMV infection might influence the severity of COVID-19. Our analyses demonstrate that CMV seropositivity is associated with more than twice the risk of hospitalization due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Immune profiling of blood and CMV DNA quantitative polymerase chain reaction in a subset of patients for whom respiratory tract samples were available revealed altered T-cell activation profiles in absence of extensive CMV replication in the upper respiratory tract. These data suggest a potential role for CMV-driven immune perturbations in affecting the outcome of SARS-CoV-2 infection and may have implications for the discrepancies in COVID-19 severity between different human populations.

A consensus document on definition and diagnostic criteria for orthorexia nervosa.

PURPOSE: Since the term orthorexia nervosa (ON) was coined from the Greek (ὀρθός, right and ὄρεξις, appetite) in 1997 to describe an obsession with "correct" eating, it has been used worldwide without a consistent definition. Although multiple authors have proposed diagnostic criteria, and many theoretical papers have been published, no consensus definition of ON exists, empirical primary evidence is limited, and ON is not a standardized diagnosis. These gaps prevent research to identify risk and protective factors, pathophysiology, functional consequences, and evidence-based therapeutic treatments. The aims of the current study are to categorize the common observations and presentations of ON pathology among experts in the eating disorder field, propose tentative diagnostic criteria, and consider which DSM chapter and category would be most appropriate for ON should it be included. METHODS: 47 eating disorder researchers and multidisciplinary treatment specialists from 14 different countries across four continents completed a three-phase modified Delphi process, with 75% agreement determined as the threshold for a statement to be included in the final consensus document. In phase I, participants were asked via online survey to agree or disagree with 67 statements about ON in four categories: A-Definition, Clinical Aspects, Duration; B-Consequences; C-Onset; D-Exclusion Criteria, and comment on their rationale. Responses were used to modify the statements which were then provided to the same participants for phase II, a second round of feedback, again in online survey form. Responses to phase II were used to modify and improve the statements for phase III, in which statements that met the predetermined 75% of agreement threshold were provided for review and commentary by all participants. RESULTS: 27 statements met or exceeded the consensus threshold and were compiled into proposed diagnostic criteria for ON. CONCLUSIONS: This is the first time a standardized definition of ON has been developed from a worldwide, multidisciplinary cohort of experts. It represents a summary of observations, clinical expertise, and research findings from a wide base of knowledge. It may be used as a base for diagnosis, treatment protocols, and further research to answer the open questions that remain, particularly the functional consequences of ON and how it might be prevented or identified and intervened upon in its early stages. Although the participants encompass many countries and disciplines, further research will be needed to determine if these diagnostic criteria are applicable to the experience of ON in geographic areas not represented in the current expert panel. LEVEL OF EVIDENCE: Level V: opinions of expert committees.

Plasma sRAGE Acts as a Genetically Regulated Causal Intermediate in Sepsis-associated Acute Respiratory Distress Syndrome.

Rationale: Acute respiratory distress syndrome (ARDS) lacks known causal biomarkers. Plasma concentrations of sRAGE (soluble receptor for advanced glycation end products) strongly associate with ARDS risk. However, whether plasma sRAGE contributes causally to ARDS remains unknown.Objectives: Evaluate plasma sRAGE as a causal intermediate in ARDS by Mendelian randomization (MR), a statistical method to infer causality using observational data.Methods: We measured early plasma sRAGE in two critically ill populations with sepsis. The cohorts were whole-genome genotyped and phenotyped for ARDS. To select validated genetic instruments for MR, we regressed plasma sRAGE on genome-wide genotypes in both cohorts. The causal effect of plasma sRAGE on ARDS was inferred using the top variants with significant associations in both populations (P < 0.01, R2 > 0.02). We applied the inverse variance-weighted method to obtain consistent estimates of the causal effect of plasma sRAGE on ARDS risk.Measurements and Main Results: There were 393 European and 266 African ancestry patients in the first cohort and 843 European ancestry patients in the second cohort. Plasma sRAGE was strongly associated with ARDS risk in both populations (odds ratio, 1.86; 95% confidence interval [1.54-2.25]; 2.56 [2.14-3.06] per log increase). Using genetic instruments common to both populations, plasma sRAGE had a consistent causal effect on ARDS risk with a ß estimate of 0.50 (95% confidence interval [0.09-0.91] per log increase).Conclusions: Plasma sRAGE is genetically regulated during sepsis, and MR analysis indicates that increased plasma sRAGE leads to increased ARDS risk, suggesting plasma sRAGE acts as a causal intermediate in sepsis-related ARDS.

Nuclear war and public health: preparedness, protection and the case for prevention.

BACKGROUND: According to the Stockholm International Peace Research Institute, the year 2018 saw a continuing 'drift into global instability' in which 'both the USA and Russia are on a path of strategic nuclear (weapons) renewal' with 3750 nuclear bombs globally deployed 'ready to fire'. Treaties are being abrogated with increasingly aggressive language exchanged, and discredited tactics such as 'limited use' revived. These developments risk an amplifying cascade of nuclear weapon fire, whether started by intent, miscalculation or unintentionally. RESULTS: A nuclear war would cause immediate and massive loss of human life, unprecedented damage to societal infrastructures and climatic disruption resulting in a 'nuclear winter' or 'nuclear famine'. CONCLUSIONS: The systems defending national territory against nuclear warhead missiles do not guarantee protection, and neither would hastily erected domestic shelters. Any post-survival world would be utterly different and severely challenging. The only effective preventative measures require nuclear disarmament through treaty.

Plasma sTNFR1 and IL8 for prognostic enrichment in sepsis trials: a prospective cohort study.

BACKGROUND: Enrichment strategies improve therapeutic targeting and trial efficiency, but enrichment factors for sepsis trials are lacking. We determined whether concentrations of soluble tumor necrosis factor receptor-1 (sTNFR1), interleukin-8 (IL8), and angiopoietin-2 (Ang2) could identify sepsis patients at higher mortality risk and serve as prognostic enrichment factors. METHODS: In a multicenter prospective cohort study of 400 critically ill septic patients, we derived and validated thresholds for each marker and expressed prognostic enrichment using risk differences (RD) of 30-day mortality as predictive values. We then used decision curve analysis to simulate the prognostic enrichment of each marker and compare different prognostic enrichment strategies. MEASUREMENTS AND MAIN RESULTS: An admission sTNFR1 concentration > 8861 pg/ml identified patients with increased mortality in both the derivation (RD 21.6%) and validation (RD 17.8%) populations. Among immunocompetent patients, an IL8 concentration > 94 pg/ml identified patients with increased mortality in both the derivation (RD 17.7%) and validation (RD 27.0%) populations. An Ang2 level > 9761 pg/ml identified patients at 21.3% and 12.3% increased risk of mortality in the derivation and validation populations, respectively. Using sTNFR1 or IL8 to select high-risk patients improved clinical trial power and efficiency compared to selecting patients with septic shock. Ang2 did not outperform septic shock as an enrichment factor. CONCLUSIONS: Thresholds for sTNFR1 and IL8 consistently identified sepsis patients with higher mortality risk and may have utility for prognostic enrichment in sepsis trials.

Individuals who self-identify as having "orthorexia nervosa" score in the clinical range on the Eating Attitudes Test-26.

PURPOSE: In recent years, there has been growing interest in pathologically healthful eating, often called orthorexia nervosa (ON). Much of the literature in this area has been about point prevalence of ON in particular populations, which range from less than 1% to nearly 90% depending on the study. Despite this interest, there has been no extensive examination of whether those with pathologically healthful eating are detected by screening instruments that identify disordered eating. This study examines whether individuals who self-report suffering from ON score in the clinical range on the 26-item Eating Attitudes Test (EAT-26). METHOD: Individuals (n = 354) sampled from both clinical and non-clinical settings were administered the EAT-26 to determine whether those who self-identify as having ON scored in a range that suggests disordered eating. RESULTS: Participants who self-report suffering from ON had a mean EAT-26 score of 30.89 (SD 12.60) scoring in a range that urges individuals to seek additional advice on whether there is an eating disorder present (scores of 20 and higher fall in a range suggesting a possible eating disorder). Furthermore, those in the ON group scored no differently than those reporting other eating disorders, but significantly higher than a non-clinical control group. CONCLUSIONS: Our findings indicate that a screening instrument for a possible eating disorder is sensitive to pathologically healthful eating (but has no specificity). LEVEL OF EVIDENCE: Level III, case control analytic study.

Definition and diagnostic criteria for orthorexia nervosa: a narrative review of the literature.

AIM: In some cases, detrimental consequences on health are generated by self-imposed dietary rules intended to promote health. The pursuit of an "extreme dietary purity" due to an exaggerated focus on food may lead to a disordered eating behavior called "orthorexia nervosa" (ON). ON raises a growing interest, but at present there is no universally shared definition of ON, the diagnostic criteria are under debate, and the psychometric instruments used in the literature revealed some flaws. This narrative review of the literature aims at assessing state of the art in ON definition, diagnostic criteria and related psychometric instruments and provides research propositions and framework for future analysis. METHODS: The authors collected articles through a search into Pubmed/Medline, Scopus, Embase and Google Scholar (last access on 07 August 2018), using "orthorexia", "orthorexia nervosa" and "obsessive healthy eating" as search terms, and filled three tables including narrative articles (English), clinical trials (English), and articles in languages different from English. The data extrapolated from the revised studies were collected and compared. In particular, for each study, the diagnostic criteria considered, the specific psychometric instrument used, the results and the conclusions of the survey were analyzed. RESULTS: The terms employed by the different authors to define ON were fixation, obsession and concern/preoccupation. Several adjectives emphasized these expressions (e.g. exaggerated/excessive, unhealthy, compulsive, pathological, rigid, extreme, maniacal). The suitable food and the diet were defined in different ways. Most of the papers did not set the diagnostic criteria. In some cases, an attempt to use DSM (edition IV or 5) criteria for anorexia nervosa, or avoidant/restrictive food intake disorder, or body dysmorphic disorder, was done. Specific diagnostic criteria proposed by the authors were used in few studies. All these studies indicated as primary diagnostic criteria: (a) obsessional or pathological preoccupation with healthy nutrition; (b) emotional consequences (e.g. distress, anxieties) of non-adherence to self-imposed nutritional rules; (c) psychosocial impairments in relevant areas of life as well as malnutrition and weight loss. The ORTO-15 and the Orthorexia Self-Test developed by Bratman were the most used psychometric tools. CONCLUSIONS: The present review synopsizes the literature on the definition of ON, proposed diagnostic criteria and psychometric instruments used to assess ON attitudes and behaviors. This work represents a necessary starting point to allow a further progression of the studies on the possible new syndrome and to overcome the criticisms that have affected both research and clinical activity until now. LEVEL OF EVIDENCE: Level V, narrative review.

Mortality Benefit of Recombinant Human Interleukin-1 Receptor Antagonist for Sepsis Varies by Initial Interleukin-1 Receptor Antagonist Plasma Concentration.

OBJECTIVE: Plasma interleukin-1 beta may influence sepsis mortality, yet recombinant human interleukin-1 receptor antagonist did not reduce mortality in randomized trials. We tested for heterogeneity in the treatment effect of recombinant human interleukin-1 receptor antagonist by baseline plasma interleukin-1 beta or interleukin-1 receptor antagonist concentration. DESIGN: Retrospective subgroup analysis of randomized controlled trial. SETTING: Multicenter North American and European clinical trial. PATIENTS: Five hundred twenty-nine subjects with sepsis and hypotension or hypoperfusion, representing 59% of the original trial population. INTERVENTIONS: Random assignment of placebo or recombinant human interleukin-1 receptor antagonist × 72 hours. MEASUREMENTS AND MAIN RESULTS: We measured prerandomization plasma interleukin-1 beta and interleukin-1 receptor antagonist and tested for statistical interaction between recombinant human interleukin-1 receptor antagonist treatment and baseline plasma interleukin-1 receptor antagonist or interleukin-1 beta concentration on 28-day mortality. There was significant heterogeneity in the effect of recombinant human interleukin-1 receptor antagonist treatment by plasma interleukin-1 receptor antagonist concentration whether plasma interleukin-1 receptor antagonist was divided into deciles (interaction p = 0.046) or dichotomized (interaction p = 0.028). Interaction remained present across different predicted mortality levels. Among subjects with baseline plasma interleukin-1 receptor antagonist above 2,071 pg/mL (n = 283), recombinant human interleukin-1 receptor antagonist therapy reduced adjusted mortality from 45.4% to 34.3% (adjusted risk difference, -0.12; 95% CI, -0.23 to -0.01), p = 0.044. Mortality in subjects with plasma interleukin-1 receptor antagonist below 2,071 pg/mL was not reduced by recombinant human interleukin-1 receptor antagonist (adjusted risk difference, +0.07; 95% CI, -0.04 to +0.17), p = 0.230. Interaction between plasma interleukin-1 beta concentration and recombinant human interleukin-1 receptor antagonist treatment was not statistically significant. CONCLUSIONS: We report a heterogeneous effect of recombinant human interleukin-1 receptor antagonist on 28-day sepsis mortality that is potentially predictable by plasma interleukin-1 receptor antagonist in one trial. A precision clinical trial of recombinant human interleukin-1 receptor antagonist targeted to septic patients with high plasma interleukin-1 receptor antagonist may be worthy of consideration.

Prevalence of orthorexia nervosa is less than 1 %: data from a US sample.

PURPOSE: Orthorexia nervosa, or pathological dieting based on being "healthy," has been of growing interest. Clinical data are limited to less than a half-dozen case studies reporting instances of medical problems due to healthful eating. However, more than a dozen studies using a measure to identify orthorexia, the ORTO-15, report very high prevalence rates in non-clinical samples. Point prevalence rates are reported from 6 % to nearly 90 %. Such variability could be due to cultural issues or psychometric problems with the instrument. This study examines prevalence rate of orthorexia in a US sample. METHOD: The ORTO-15 was administered to 275 US college students along with other questions regarding diet, exercise, and health. RESULTS: While the ORTO-15 indicated a prevalence rate of 71 %, only 20 % of the sample endorsed a dietary practice of removing a particular food type (e.g. meat) from their diet. Those who endorsed following a vegan diet had the highest (less pathological) mean ORTO-15 score. Further, when classifying participants based on their seriousness about healthy eating and whether their diet had led to impairment in everyday activities and medical problems, less than 1 % of the sample fell into such a category. CONCLUSION: As in other countries, a large proportion of a non-clinical US sample scored in the orthorexia range on the ORTO-15. However, this instrument is likely unable to distinguish between healthy eating and pathologically healthful eating. Our estimate is that orthorexia nervosa like anorexia nervosa and bulimia nervosa, is not a common condition.

Physician Non-adherence to Colonoscopy Interval Guidelines in the Veterans Affairs Healthcare System.

BACKGROUND & AIMS: Colonoscopy can decrease colorectal cancer (CRC) mortality, although performing this procedure more frequently than recommended could increase costs and risks to patients. We aimed to determine rates and correlates of physician non-adherence to guidelines for repeat colonoscopy screening and polyp surveillance intervals. METHODS: We performed a multi-center, retrospective, observational study using administrative claims, physician databases, and electronic medical records (EMR) from 1455 patients (50-64 y old) who underwent colonoscopy in the Veterans Affairs healthcare system in fiscal year 2008. Patients had no prior diagnosis of CRC or inflammatory bowel disease, and had not undergone colonoscopy examinations in the previous 10 years. We compared EMR-documented, endoscopist-recommended intervals for colonoscopies with intervals recommended by the 2008 Multi-Society Task Force guidelines. RESULTS: The overall rate of non-adherence to guideline recommendations was 36% and ranged from 3% to 80% among facilities. Non-adherence was 28% for patients who underwent normal colonoscopies, but 45%-52% after colonoscopies that identified hyperplastic or adenomatous polyps. Most of all recommendations that were not followed recommended a shorter surveillance interval. In adjusted analyses, non-adherence was significantly higher for patients whose colonoscopies identified hyperplastic (odds ratio [OR] = 3.1; 95% CI, 1.7-5.5) or high-risk adenomatous polyps (OR = 3.0; 95% CI, 1.2-8.0), compared to patients with normal colonoscopy examinations, but not for patients with low-risk adenomatous polyps (OR = 1.8; 95% CI, 0.9-3.7). Nonadherence was also associated with bowel preparation quality, geographic region, Charlson comorbidity score, and colonoscopy indication. CONCLUSIONS: In a managed care setting with salaried physicians, endoscopists recommend repeat colonoscopy sooner than guidelines for more than one third of patients. Factors associated with non-adherence to guideline recommendations were colonoscopy findings, quality of bowel preparation, and geographic region. Targeting endoscopist about non-adherence to colonoscopy guidelines could reduce overuse of colonoscopy and associated healthcare costs.

Neutropenic sepsis is associated with distinct clinical and biological characteristics: a cohort study of severe sepsis.

BACKGROUND: Immunocompromised patients who develop sepsis while neutropenic are at high risk for morbidity and mortality; however, it is unknown if neutropenic sepsis is associated with distinct clinical and biological characteristics. METHODS: We conducted a prospective cohort study of patients admitted to the medical intensive care unit of an academic medical center with severe sepsis. Patients were followed for the development of acute respiratory distress syndrome (ARDS), acute kidney injury (AKI), and mortality. Plasma proteins, representing the host inflammatory response, anti-inflammatory response, and endothelial leak were measured in 30 % of subjects. Clinical characteristics and plasma protein concentrations of patients with neutropenia at enrollment were compared to patients without neutropenia. RESULTS: Of 797 subjects enrolled, 103 (13 %) were neutropenic at ICU admission. The neutropenic subjects were more often in shock, admitted from the hospital ward, had higher APACHE III scores, and more likely bacteremic. Neutropenia was an independent risk factor for AKI (RR 1.28; 95 % CI 1.04, 1.57; p = 0.03), but not ARDS (RR 0.90; 95 % CI 0.70, 1.17; p = 0.42) or 30-day mortality (RR 1.05; 95 % CI 0.85, 1.31; p = 0.65). Neutropenic subjects had higher plasma interleukin (IL)-6 (457 vs. 249 pg/ml; p = 0.03), IL-8 (581 vs. 94 pg/ml; p <0.001), and granulocyte colony-stimulating factor (G-CSF) (3624 vs. 99 pg/ml; p <0.001). Angiopoietin-2 and IL-1 receptor antagonist concentrations did not differ between groups. CONCLUSIONS: Neutropenic sepsis is associated with a higher AKI risk and concentrations of inflammatory mediators IL-6, IL-8, and G-CSF relative to non-neutropenic patients. These differences may have implications for future therapies targeting neutropenic sepsis.

Low Plasma Levels of Adiponectin Do Not Explain Acute Respiratory Distress Syndrome Risk: a Prospective Cohort Study of Patients with Severe Sepsis.

BACKGROUND: Obesity is associated with the development of acute respiratory distress syndrome (ARDS) in at-risk patients. Low plasma levels of adiponectin, a circulating hormone-like molecule, have been implicated as a possible mechanism for this association. The objective of this study was to determine the association of plasma adiponectin level at ICU admission with ARDS and 30-day mortality in patients with severe sepsis and septic shock. METHODS: This is a prospective cohort study of patients admitted to the medical ICU at the Hospital of the University of Pennsylvania. Plasma adiponectin was measured at the time of ICU admission. ARDS was defined by Berlin criteria. Multivariable logistic regression was used to determine the association of plasma adiponectin with the development of ARDS and mortality at 30 days. RESULTS: The study included 164 patients. The incidence of ARDS within 5 days of admission was 45%. The median initial plasma adiponectin level was 7.62 mcg/ml (IQR: 3.87, 14.90) in those without ARDS compared to 8.93 mcg/ml (IQR: 4.60, 18.85) in those developing ARDS. The adjusted odds ratio for ARDS associated with each 5 mcg increase in adiponectin was 1.12 (95% CI 1.01, 1.25), p-value 0.025). A total of 82 patients (51%) of the cohort died within 30 days of ICU admission. There was a statistically significant association between adiponectin and mortality in the unadjusted model (OR 1.11, 95% CI 1.00, 1.23, p-value 0.04) that was no longer significant after adjusting for potential confounders. CONCLUSIONS: In this study, low levels of adiponectin were not associated with an increased risk of ARDS in patients with severe sepsis and septic shock. This argues against low levels of adiponectin as a mechanism explaining the association of obesity with ARDS. At present, it is unclear whether circulating adiponectin is involved in the pathogenesis of ARDS or simply represents an epiphenomenon of other unknown functions of adipose tissue or metabolic alterations in sepsis.

An assessment of survey measures used across key epidemiologic studies of United States Gulf War I Era veterans.

Over the past two decades, 12 large epidemiologic studies and 2 registries have focused on U.S. veterans of the 1990-1991 Gulf War Era. We conducted a review of these studies' research tools to identify existing gaps and overlaps of efforts to date, and to advance development of the next generation of Gulf War Era survey tools. Overall, we found that many of the studies used similar instruments. Questions regarding exposures were more similar across studies than other domains, while neurocognitive and psychological tools were the most variable. Many studies focused on self-reported survey results, with a range of validation practices. However, physical exams, biomedical assessments, and specimen storage were not common. This review suggests that while research may be able to pool data from past surveys, future surveys need to consider how their design can yield data comparable with previous surveys. Additionally, data that incorporate recent technologies in specimen and genetic analyses would greatly enhance such survey data. When combined with existing data on deployment-related exposures and post-deployment health conditions, longitudinal follow-up of existing studies within this collaborative framework could represent an important step toward improving the health of veterans.

Exposure to ambient air pollutants and acute respiratory distress syndrome risk in sepsis.

PURPOSE: Exposures to ambient air pollutants may prime the lung enhancing risk of acute respiratory distress syndrome (ARDS) in sepsis. Our objective was to determine the association of short-, medium-, and long-term pollutant exposures and ARDS risk in critically ill sepsis patients. METHODS: We analyzed a prospective cohort of 1858 critically ill patients with sepsis, and estimated short- (3 days), medium- (6 weeks), and long- (5 years) term exposures to ozone, nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO), particulate matter < 2.5 µm (PM2.5), and PM < 10 µm (PM10) using weighted averages of daily levels from monitors within 50 km of subjects' residences. Subjects were followed for 6 days for ARDS by the Berlin Criteria. The association between each pollutant and ARDS was determined using multivariable logistic regression adjusting for preselected confounders. In 764 subjects, we measured plasma concentrations of inflammatory proteins at presentation and tested for an association between pollutant exposure and protein concentration via linear regression. RESULTS: ARDS developed in 754 (41%) subjects. Short- and long-term exposures to SO2, NO2, and PM2.5 were associated with ARDS risk (SO2: odds ratio (OR) for the comparison of the 75-25th long-term exposure percentile 1.43 (95% confidence interval (CI) 1.16, 1.77); p < 0.01; NO2: 1.36 (1.06, 1.74); p = 0.04, PM2.5: 1.21 (1.04, 1.41); p = 0.03). Long-term exposures to these three pollutants were also associated with plasma interleukin-1 receptor antagonist and soluble tumor necrosis factor receptor-1 concentrations. CONCLUSION: Short and long-term exposures to ambient SO2, PM2.5, and NO2 are associated with increased ARDS risk in sepsis, representing potentially modifiable environmental risk factors for sepsis-associated ARDS.

Universality of Hair as a Nucleant: Exploring the Effects of Surface Chemistry and Topography.

The ability to control crystal nucleation through the simple addition of a nucleating agent (nucleant) is desirable for a huge range of applications. However, effective nucleating agents are known for only a small number of systems, and many questions remain about the mechanisms by which they operate. Here, we explore the features that make an effective nucleant and demonstrate that the biological material hair-which naturally possesses a chemically and topographically complex surface structure-has excellent potential as an effective nucleating agent. Crystallization of poorly soluble compounds in the presence of hairs from a range of mammals shows that nucleation preferentially occurs at the cuticle step edges, while a novel microdroplet-based methodology was used to quantify the nucleating activities of different hairs. This showed that the activities of the hairs can be tuned over a wide range using chemical treatments. Analysis of the hair structure and composition using atomic force microscopy, scanning ion conductance microscopy, and X-ray photoelectron spectroscopy demonstrates that surface chemistry, surface topography, and surface charge all act in combination to create effective nucleation sites. This work therefore contributes to our understanding of heterogeneous nucleating agents and shows that surface topography as well as surface chemistry can be used in the design or selection of universal nucleating agents.