Dietary phenotype and advanced glycation end-products predict WTC-obstructive airways disease: a longitudinal observational study.

BACKGROUND: Diet is a modifier of metabolic syndrome which in turn is associated with World Trade Center obstructive airways disease (WTC-OAD). We have designed this study to (1) assess the dietary phenotype (food types, physical activity, and dietary habits) of the Fire Department of New York (FDNY) WTC-Health Program (WTC-HP) cohort and (2) quantify the association of dietary quality and its advanced glycation end product (AGE) content with the development of WTC-OAD. METHODS: WTC-OAD, defined as developing WTC-Lung Injury (WTC-LI; FEV1 < LLN) and/or airway hyperreactivity (AHR; positive methacholine and/or positive bronchodilator response). Rapid Eating and Activity Assessment for Participants-Short Version (REAP-S) deployed on 3/1/2018 in the WTC-HP annual monitoring assessment. Clinical and REAP-S data of consented subjects was extracted (7/17/2019). Diet quality [low-(15-19), moderate-(20-29), and high-(30-39)] and AGE content per REAP-S questionnaire were assessed for association with WTC-OAD. Regression models adjusted for smoking, hyperglycemia, hypertension, age on 9/11, WTC-exposure, BMI, and job description. RESULTS: N = 9508 completed the annual questionnaire, while N = 4015 completed REAP-S and had spirometry. WTC-OAD developed in N = 921, while N = 3094 never developed WTC-OAD. Low- and moderate-dietary quality, eating more (processed meats, fried foods, sugary drinks), fewer (vegetables, whole-grains),and having a diet abundant in AGEs were significantly associated with WTC-OAD. Smoking was not a significant risk factor of WTC-OAD. CONCLUSIONS: REAP-S was successfully implemented in the FDNY WTC-HP monitoring questionnaire and produced valuable dietary phenotyping. Our observational study has identified low dietary quality and AGE abundant dietary habits as risk factors for pulmonary disease in the context of WTC-exposure. Dietary phenotyping, not only focuses our metabolomic/biomarker profiling but also further informs future dietary interventions that may positively impact particulate matter associated lung disease.

Food Intake REstriction for Health OUtcome Support and Education (FIREHOUSE) Protocol: A Randomized Clinical Trial.

Fire Department of New York (FDNY) rescue and recovery workers exposed to World Trade Center (WTC) particulates suffered loss of forced expiratory volume in 1 s (FEV1). Metabolic Syndrome increased the risk of developing WTC-lung injury (WTC-LI). We aim to attenuate the deleterious effects of WTC exposure through a dietary intervention targeting these clinically relevant disease modifiers. We hypothesize that a calorie-restricted Mediterranean dietary intervention will improve metabolic risk, subclinical indicators of cardiopulmonary disease, quality of life, and lung function in firefighters with WTC-LI. To assess our hypothesis, we developed the Food Intake REstriction for Health OUtcome Support and Education (FIREHOUSE), a randomized controlled clinical trial (RCT). Male firefighters with WTC-LI and a BMI > 27 kg/m2 will be included. We will randomize subjects (1:1) to either: (1) Low Calorie Mediterranean (LoCalMed)-an integrative multifactorial, technology-supported approach focused on behavioral modification, nutritional education that will include a self-monitored diet with feedback, physical activity recommendations, and social cognitive theory-based group counseling sessions; or (2) Usual Care. Outcomes include reduction in body mass index (BMI) (primary), improvement in FEV1, fractional exhaled nitric oxide, pulse wave velocity, lipid profiles, targeted metabolic/clinical biomarkers, and quality of life measures (secondary). By implementing a technology-supported LoCalMed diet our FIREHOUSE RCT may help further the treatment of WTC associated pulmonary disease.

Acquired Coagulopathy and Hemorrhage Secondary to Subcutaneous Heparin Prophylaxis.

Unfractionated heparin and low-molecular-weight heparins are commonly used as thromboprophylaxis for hospitalized patients. Though generally considered safe at prophylactic doses, cases of catastrophic hemorrhage have been reported. The proposed mechanism involves bioaccumulation of heparin through saturation of the rapid-elimination pathway in its metabolism. We present an unusual case of an average-weight man with metastatic melanoma who suffered hemorrhage with syncope and end-organ damage while on prophylactic three times daily unfractionated heparin. Coagulation studies were consistent with heparin toxicity. Despite administration of protamine, the clearance of heparin was remarkably delayed, as demonstrated by serial coagulation studies. We review the suspected risk factors for heparin bioaccumulation and the emerging understanding of this unusual adverse event involving a nearly ubiquitous medication.

Changes in glomerular parietal epithelial cells in mouse kidneys with advanced age.

Kidney aging is accompanied by characteristic changes in the glomerulus, but little is known about the effect of aging on glomerular parietal epithelial cells (PECs), nor if the characteristic glomerular changes in humans and rats also occur in very old mice. Accordingly, a descriptive analysis was undertaken in 27-mo-old C57B6 mice, considered advanced age. PEC density was significantly lower in older mice compared with young mice (aged 3 mo), and the decrease was more pronounced in juxtamedullary glomeruli compared with outer cortical glomeruli. In addition to segmental and global glomerulosclerosis in older mice, staining for matrix proteins collagen type IV and heparan sulfate proteoglycan were markedly increased in Bowman's capsules of older mouse glomeruli, consistent with increased extracellular matrix production by PECs. De novo staining for CD44, a marker of activated and profibrotic PECs, was significantly increased in aged glomeruli. CD44 staining was more pronounced in the juxtamedullary region and colocalized with phosphorylated ERK. Additionally, a subset of aged PECs de novo expressed the epithelial-to-mesenchymal transition markers α-smooth muscle and vimentin, with no changes in epithelial-to-mesenchymal transition markers E-cadherin and ß-catenin. The mural cell markers neural/glial antigen 2, PDGF receptor-ß, and CD146 as well as Notch 3 were also substantially increased in aged PECs. These data show that mice can be used to better understand the aging kidney and that PECs undergo substantial changes, especially in juxtamedullary glomeruli, that may participate in the overall decline in glomerular structure and function with advancing age.

Glomerular parietal epithelial cells contribute to adult podocyte regeneration in experimental focal segmental glomerulosclerosis.

As adult podocytes cannot adequately proliferate following depletion in disease states, there has been interest in the potential role of progenitors in podocyte repair and regeneration. To determine whether parietal epithelial cells (PECs) can serve as adult podocyte progenitors following disease-induced podocyte depletion, PECs were permanently labeled in adult PEC-rtTA/LC1/R26 reporter mice. In normal mice, labeled PECs were confined to Bowman's capsule, whereas in disease (cytotoxic sheep anti-podocyte antibody) labeled PECs were found in the glomerular tuft in progressively higher numbers by days 7, 14, and 28. Early in disease, the majority of PECs in the tuft coexpressed CD44. By day 28, when podocyte numbers were significantly higher and disease severity was significantly lower, the majority of labeled PECs coexpressed podocyte proteins but not CD44. Neither labeled PECs on the tuft nor podocytes stained for the proliferation marker BrdU. The de novo expression of phospho-ERK colocalized to CD44 expressing PECs, but not to PECs expressing podocyte markers. Thus, in a mouse model of focal segmental glomerulosclerosis typified by abrupt podocyte depletion followed by regeneration, PECs undergo two phenotypic changes once they migrate to the glomerular tuft. Initially these cells are predominantly activated CD44 expressing cells coinciding with glomerulosclerosis, and later they predominantly exhibit a podocyte phenotype, which is likely reparative.

A contemporary analysis of parenteral nutrition-associated liver disease in surgical infants.

BACKGROUND/PURPOSE: Despite advances in pediatric nutritional support and a renewed focus on management of intestinal failure, there are limited recent data regarding the risk of parenteral nutrition (PN)-associated liver disease in surgical infants. This study investigated the incidence of cholestasis from PN and risk factors for its development in this population. METHODS: A retrospective review was performed of all neonates in our institution who underwent abdominal surgery and required postoperative PN from 2001 to 2006. Cholestasis was defined as 2 conjugated bilirubin levels greater than 2 mg/dL over 14 days. Nonparametric univariate analyses and multivariate logistic regression were used to model the likelihood of developing cholestasis. Median values with range are presented. RESULTS: One hundred seventy-six infants met inclusion criteria, and patients received PN for 28 days (range, 2-256 days). The incidence of cholestasis was 24%. Cholestatic infants were born at an earlier gestational age (34 vs 36 weeks; P < .01), required a 3-fold longer PN duration (76 vs 21 days; P < .001), had longer inpatient stays (86 vs 29 days; P < .001), and were more likely to be discharged on PN. The median time to cholestasis was 23 days. Cholestasis was an early development; 77% of cholestatic infants developed cholestasis by 5 weeks of PN exposure. On multivariate regression, only prematurity was significantly associated with development of cholestasis (P < .05). CONCLUSION: In this analysis, the development of PN-associated liver disease occurred early in the course of exposure to PN. These data help to define the time course and prognosis for PN-associated cholestasis in surgical infants.

Effects of body position on sleep related disordered breathing in a patient with steinert's disease

A observaçäo de mudanças abruptas do padräo respiratório durante estudo poligráfico do sono pode sugerir que estamos diante de síndrome de apnéia-hipopnéia ligada ao sono (SAHS) associada à postura adotada durante o sono pelo paciente. Relatamos o caso de um paciente de 37 anos com doença de Steinert e esta forma de SAHS. A respiraçäo durante o sono pode ser regularizada por simples controle postural