Search

Context: Most studies of the long-term effects of early childhood educational interventions are of demonstration programs rather than large-scale public programs. Previous studies of one of the oldest federally funded preschool programs have reported positive effects on school performance, but effects on educational attainment and crime are unknown.Objective: To determine the long-term effectiveness of a federal center-based preschool and school-based intervention program for urban low-income children.Design, Setting, and Participants: Fifteen-year follow-up of a nonrandomized, matched-group cohort of 1539 low-income, mostly black children born in 1980 and enrolled in alternative early childhood programs in 25 sites in Chicago, Ill.Interventions: The Chicago Child-Parent Center (CPC) Program (n = 989 children) provides comprehensive education, family, and health services and includes half-day preschool at ages 3 to 4 years, half- or full-day kindergarten, and school-age services in linked elementary schools at ages 6 to 9 years. The comparison group (n = 550) consisted of children who participated in alternative early childhood programs (full-day kindergarten): 374 in the preschool comparison group from 5 randomly selected schools plus 2 others that provided full-day kindergarten and additional instructional resources and 176 who attended full-day kindergartens in 6 CPCs without preschool participation.Main Outcome Measures: Rates of high school completion and school dropout by age 20 years, juvenile arrests for violent and nonviolent offenses, and grade retention and special education placement by age 18 years.Results: Relative to the preschool comparison group and adjusted for several covariates, children who participated in the preschool intervention for 1 or 2 years had a higher rate of high school completion (49.7 % vs 38.5%; P =.01); more years of completed education (10.6 vs 10.2; P =.03); and lower rates of juvenile arrest (16.9% vs 25.1%; P =.003), violent arrests (9.0% vs 15.3%; P =.002), and school dropout (46.7% vs 55.0%; P =.047). Both preschool and school-age participation were significantly associated with lower rates of grade retention and special education services. The effects of preschool participation on educational attainment were greater for boys than girls, especially in reducing school dropout rates (P =.03). Relative to less extensive participation, children with extended program participation from preschool through second or third grade also experienced lower rates of grade retention (21.9% vs 32.3%; P =.001) and special education (13.5% vs 20.7%; P =.004).Conclusions: Participation in an established early childhood intervention for low-income children was associated with better educational and social outcomes up to age 20 years. These findings are among the strongest evidence that established programs administered through public schools can promote children's long-term success. [ABSTRACT FROM AUTHOR]

Background: Screening for early detection of microalbuminuria signaling kidney disease should begin as early as the time of diagnosis of youth-onset type 2 diabetes. This quality improvement initiative aimed to standardize urine nephropathy screening in pediatric patients with type 2 diabetes at a tertiary academic medical center and increase a baseline screening rate of 56%-75% over 6 months (September 2022-February 2023) and sustain that increase for 6 months (March through August 2023)., Methods: A multi-disciplinary team used quality improvement methods and iterative Plan-Do-Study-Act cycles. Targeted interventions included previsit planning workflow, education, and a new-onset triage protocol. The team collected data at baseline and prospectively by reviewing electronic medical records. The primary outcome measure was pediatric type 2 diabetes clinic visits in diabetes clinic with urine nephropathy screening before or on the visit date., Results: A total of 121 youth were scheduled for T2D clinic visits between September 2021 and August 2023. The mean age was 14.5 years, and 60% were women, 40% were non-Hispanic Black, 28% were Hispanic/Latino, and 15% reported Spanish as their preferred language. Following the interventions of this project, urine nephropathy screening increased from 56% to 75%, and this change was sustained for 6 months., Conclusions: Interventions focused on efficient recognition of the population needing screening, coordinated internal processes around screening, a shared understanding between all stakeholders, and practical support in the healthcare system increased urine nephropathy screening with sustained improvement., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Urinary bladder organogenesis requires coordinated cell growth, specification, and patterning of both mesenchymal and epithelial compartments. Tcf21, a gene that encodes a helix-loop-helix transcription factor, is specifically expressed in the mesenchyme of the bladder during development. Here we show that Tcf21 is required for normal development of the bladder. We found that the bladders of mice lacking Tcf21 were notably hypoplastic and that the Tcf21 mutant mesenchyme showed increased apoptosis. There was also a marked delay in the formation of visceral smooth muscle, accompanied by a defect in myocardin (Myocd) expression. Interestingly, there was also a marked delay in the formation of the basal cell layer of the urothelium, distinguished by diminished expression of Krt5 and Krt14. Our findings suggest that Tcf21 regulates the survival and differentiation of mesenchyme cell-autonomously and the maturation of the adjacent urothelium non-cell-autonomously during bladder development., (© 2024 The Authors. Development, Growth & Differentiation published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Developmental Biologists.)

Objectives: We evaluated COVID-19 outcomes in children and young adults with type 1 diabetes (T1D) to determine if those with comorbidities are more likely to experience severe COVID-19 compared to those without., Research Design and Methods: This cross-sectional study included questionnaire data on patients <25 years of age with established T1D and laboratory-confirmed COVID-19 from 52 sites across the US between April 2020 and October 2021. We examined patient factors and COVID-19 outcomes between those with and without comorbidities. Multivariate logistic regression analysis examined the odds of hospitalization among groups, adjusting for age, HbA1c, race and ethnicity, insurance type and duration of diabetes., Results: Six hundred fifty-one individuals with T1D and COVID-19 were analyzed with mean age 15.8 (SD 4.1) years. At least one comorbidity was present in 31%, and more than one in 10%. Obesity and asthma were the most frequently reported comorbidities, present in 19% and 17%, respectively. Hospitalization occurred in 17% of patients and 52% of hospitalized patients required ICU level care. Patients with at least one comorbidity were almost twice as likely to be hospitalized with COVID-19 than patients with no comorbidities (Odds ratio 2.0, 95% CI: 1.3-3.1). This relationship persisted after adjusting for age, HbA1c, race and ethnicity (minority vs nonminority), insurance type (public vs. private), and duration of diabetes., Conclusions: Our findings show that comorbidities increase the risk for hospitalization with COVID-19 in children and young adults highlighting the need for tailored COVID-19 prevention and treatment strategies in T1D., (© 2022 The Authors. Pediatric Diabetes published by John Wiley & Sons Ltd.)

Total photoreducible mercury [Hg(II) RED ] and photoreduction rates in the surface waters of four lakes in Kejimkujik National Park, Nova Scotia were measured monthly over a summer. The percent of THg that was photoreducible [%Hg(II) RED ] decreased significantly in two of the four lakes from early to late summer: North Cranberry (maximum 42% to minimum 14%) and Big Dam East (maximum 51% to minimum 6%). Hg(II) RED was found to have a linear relationship with THg for all combined site data. THg and Hg(II) RED were found to have positive linear relationships with DOC concentrations (R 2  = 0.97; n = 36; p < 0.01 and R 2  = 0.75; n = 36; p < 0.01, respectively). A smaller proportion of THg was found to be photoreducible with increasing DOC concentration., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Competing Interests: CONFLICTS OF INTEREST: The authors have no conflict of interest to declare.

The human microbiome is a rich environment consisting of bacteria, fungi and other commensal microorganisms of the gut, mucosa and skin. The functional role of the gut microbiome includes facilitation in metabolism of macronutrients, maturation of the immune system, and production of pro- or anti-inflammatory signaling molecules and peptides. The identification of these resident organisms has brought about a new understanding of disease processes. Nevertheless, more questions remain regarding the interactions within the microbiome, its interactions with the host, and its contributions to the pathophysiology of disease. The purpose of this review is to examine the existing medical literature to highlight the role of the gut microbiome in human health, also paying attention to its role in several inflammatory skin diseases, namely atopic dermatitis, psoriasis, and rosacea., (Copyright © 2020 The Korean Dermatological Association and The Korean Society for Investigative Dermatology.)

None: In recent years, sleep-disordered breathing (SDB) has been recognized as a prevalent but under-diagnosed condition in adults and has prompted the need for new and better diagnostic and therapeutic options. To facilitate the development and availability of innovative, safe and effective SDB medical device technologies for patients in the United States, the US Food and Drug Administration collaborated with six SDB-related professional societies and a consumer advocacy organization to convene a public workshop focused on clinical investigations of SDB devices. Sleep medicine experts discussed appropriate definitions of terms used in the diagnosis and treatment of SDB, the use of home sleep testing versus polysomnography, clinical trial design issues in studying SDB devices, and current and future trends in digital health technologies for diagnosis and monitoring SDB. The panel's breadth of clinical expertise and experience across medical specialties provided useful and important insights regarding clinical trial designs for SDB devices., (© 2020 American Academy of Sleep Medicine.)

Aims: Identify the prevalence of health psychology use in children with type 1 diabetes (T1D) and evaluate how individual and contextual characteristics are associated with use., Methods: Children ages 8-16 years with T1D and their parents were recruited from two tertiary diabetes clinics. Cross-sectional data included parent and adolescent surveys and hemoglobin A1c. Parents self-reported the child's use of health psychology in the last year along with individual factors (e.g., predisposing factors including demographics, enabling factors including health insurance type, evaluated need including mental health diagnoses and perceived need including self-management barriers). Association of health psychology use with individual (e.g., demographics, enabling factors, evaluated and perceived need) and contextual (e.g., clinical site) characteristics was evaluated using logistic regression., Results: Of 363 eligible participants, 267 (74%) participated. Health psychology use was reported by only 8.2% (n = 22) of participants and was significantly associated with evaluated need factor of mental health diagnosis (OR 5.8; p < 0.001) and perceived need factor of parent-reported self-management barriers. Use was not associated with other individual or contextual factors., Conclusions: Though infrequent, health psychology use was positively associated with mental health diagnoses and self-management barriers., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Besides being regulated by G-protein-coupled receptors, the activity of heterotrimeric G proteins is modulated by many cytoplasmic proteins. GIV/Girdin and DAPLE ( D vl- a ssociating p rotein with a high frequency of le ucine) are the best-characterized members of a group of cytoplasmic regulators that contain a Gα-binding and -activating (GBA) motif and whose dysregulation underlies human diseases, including cancer and birth defects. GBA motif-containing proteins were originally reported to modulate G proteins by binding Gα subunits of the G i/o family (Gα i ) over other families (such as G s , G q/11 , or G 12/13 ), and promoting nucleotide exchange in vitro However, some evidence suggests that this is not always the case, as phosphorylation of the GBA motif of GIV promotes its binding to Gα s and inhibits nucleotide exchange. The G-protein specificity of DAPLE and how it might affect nucleotide exchange on G proteins besides Gα i remain to be investigated. Here, we show that DAPLE's GBA motif, in addition to Gα i , binds efficiently to members of the G s and G q/11 families (Gα s and Gα q , respectively), but not of the G 12/13 family (Gα 12 ) in the absence of post-translational phosphorylation. We pinpointed Met-1669 as the residue in the GBA motif of DAPLE that diverges from that in GIV and enables better binding to Gα s and Gα q Unlike the nucleotide-exchange acceleration observed for Gα i , DAPLE inhibited nucleotide exchange on Gα s and Gα q These findings indicate that GBA motifs have versatility in their G-protein-modulating effect, i.e. they can bind to Gα subunits of different classes and either stimulate or inhibit nucleotide exchange depending on the G-protein subtype., (© 2020 Marivin et al.)

Guanylyl cyclase C (GC-C) is found in brain regions where dopamine is expressed. We characterized a mouse in which GC-C was knocked out (KO) that was reported to be a model of attention deficit hyperactivity disorder (ADHD). We re-examined this model and controlled for litter effects, used 16 to 23 mice per genotype per sex and assessed an array of behavioral and neurochemical outcomes. GC-C KO mice showed no phenotypic differences from wild-type mice on most behavioral tests, or on striatal or hippocampal monoamines, and notably no evidence of an ADHD-like phenotype. KO mice were impaired on novel object recognition, had decreased tactile startle but not acoustic startle, and females had increased latency on cued training trials in the Morris water maze, but not hidden platform spatial learning trials. Open-field activity showed small differences in females but not males. The data indicate that the GC-C KO mouse with proper controls and sample sizes has a moderate cognitive and startle phenotype but has no ADHD-like phenotype., (© 2019 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.)

Aims: To establish the incidence and timing of hypoglycemia at a week-long residential diabetes camp for children. We hypothesized that hypoglycemia would occur more frequently during the first two days of camp and following evening all-camp games., Methods: 225 children (mean age 12.0 ± 2.3 years, 56% female, mean hemoglobin A1c 8.4% [71.6 mmol/mol]) had blood glucose (BG) levels obtained before meals, at bedtime, and as needed to detect hypoglycemia. Insulin adjustments were made by medical staff according to camp protocol and at the discretion of medical staff during camper check-in., Results: Mild hypoglycemia (BG 50-69 mg/dL [3.9 mmol/L]) occurred ≥ 1 time in 90% of campers while 43% had ≥ 1 episode of BG < 50 mg/dL (2.8 mmol/L). No episodes of hypoglycemia requiring glucagon occurred. More campers experienced ≥ 1 overnight hypoglycemia event during the first 48 hours of camp compared to later in the week (p = 0.01). Evening all-camp games did not impact hypoglycemia rates overnight., Conclusions: Nocturnal hypoglycemia occurred more frequently during the first two nights, establishing this period as high risk and supporting implementation of a standard protocol to lower insulin doses. Rates of hypoglycemia were unaffected by all-camp games, indicating current practices are effective at minimizing hypoglycemia., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Macrophages play a crucial role in maintaining homeostasis in the intestine, but the underlying mechanisms have not yet been elucidated fully. Here, we show for the first time that mature intestinal macrophages in mouse intestine express high levels of αvβ5 integrin, which acts as a receptor for the uptake of apoptotic cells and can activate molecules involved in several aspects of tissue homeostasis such as angiogenesis and remodeling of the ECM. αvβ5 is not expressed by other immune cells in the intestine, is already present on intestinal macrophages soon after birth, and its expression is not dependent on the microbiota. In adults, αvβ5 is induced during the differentiation of monocytes in response to the local environment and it confers intestinal macrophages with the ability to promote engulfment of apoptotic cells via engagement of the bridging molecule milk fat globule EGF-like molecule 8. In the absence of αvβ5, there are fewer monocytes in the mucosa and mature intestinal macrophages have decreased expression of metalloproteases and IL 10. Mice lacking αvβ5 on haematopoietic cells show increased susceptibility to chemical colitis and we conclude that αvβ5 contributes to the tissue repair by regulating the homeostatic properties of intestinal macrophages., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Mercury (Hg) in the Arctic is a significant concern due to its bioaccumulative and neurotoxic properties, and the sensitivity of Arctic environments. Previous research has found high levels of Hg in snowpacks with high chloride (Cl - ) concentrations. We hypothesised that Cl - would increase Hg retention by decreasing Hg photoreduction to Hg(0) in melted Arctic snow. To test this, changes in Hg photoreduction kinetics in melted Alert, NU snow were quantified with changing Cl - concentration and UV intensity. Snow was collected and melted in Teflon bottles in May 2014, spiked with 0-10μg/g Cl - , and irradiated with 3.52-5.78W·m -2 UV (280-400nm) radiation in a LuzChem photoreactor. Photoreduction rate constants (k) (0.14-0.59hr - 1 ) had positive linear relationships with [Cl - ], while photoreduced Hg amounts (Hg(II) red ) had negative linear relationships with [Cl - ] (1287-64pg in 200g melted snow). Varying UV and [Cl - ] both altered Hg(II) red amounts, with more efficient Hg stabilisation by Cl - at higher UV intensity, while k can be predicted by Cl - concentration and/or UV intensity, depending on experimental parameters. Overall, with future projections for greater snowpack Cl - loading, our experimental results suggest that more Hg could be delivered to Arctic aquatic ecosystems by melted snow (smaller Hg(II) red expected), but the Hg in the melted snow that is photoreduced may do so more quickly (larger k expected)., (Copyright © 2018. Published by Elsevier B.V.)

Mercury (Hg) is an important environmental contaminant, due to its neurotoxicity and ability to bioaccumulate. The Arctic is a mercury-sensitive region, where organisms can accumulate high Hg concentrations. Snowpack mercury photoredox reactions may control how much Hg is transported with melting Arctic snow. This work aimed to (1) determine the significance of temperature combined with UV irradiation intensity and snow age on Hg(0) flux from Arctic snow and (2) elucidate the effect of temperature on snowpack Hg photoreduction kinetics. Using a Teflon flux chamber, snow temperature, UV irradiation, and snow age were found to significantly influence Hg(0) flux from Arctic snow. Cross-correlation analysis results suggest that UV radiation has a direct effect on Hg(0)flux, while temperature may indirectly influence flux. Laboratory experiments determined that temperature influenced Hg photoreduction kinetics when snow approached the melting point (>-2 °C), where the pseudo-first-order reduction rate constant, k, decreased twofold, and the photoreduced Hg amount, Hg(II)red, increased 10-fold. This suggests that temperature influences Hg photoreduction kinetics indirectly, likely by altering the solid:liquid water ratio. These results imply that large mass transfers of Hg from snow to air may take place during the Arctic snowmelt period, altering photoreducible Hg retention and transport with snow meltwater.

Background: Voiding disorders in humans, particularly in children are associated with increased incidence of behavioral issues as well as past history of childhood abuse. We hypothesized that creating stress in mice, utilizing either a chronic social defeat model (SD) or restraint stress in shallow water model (RSSW) would engender changes in bladder function, morphology, and behavior, thereby enabling us to study the resultant voiding dysfunction., Methods: For SD stress (14 days), C57BL/6 male mice were exposed daily to a larger aggressive CD-1 male for 10 min, followed by sensory exposure in a barrier cage for 24h. Control mice were similarly housed with no exposure. For RSSW (21 days), C57BL/6 mice were put in a perforated conical tube with feet immersed in water daily for 4h, then returned to single housing cages. Control mice were also in single housing. After the stress period, voiding patterns were obtained on filter paper, followed by behavioral tests. At necropsy, blood was taken for corticosterone analysis, and bladder and body weights measured. Bladder cryosections were stained with hematoxylin and eosin (H&E) for morphological assessment. Sequential sections were immunostained with antibodies to Ki-67 as a proliferation marker, CD31 (endothelial cell marker), and uroplakin-II. ImageJ software was used to measure bladder wall thickness on blinded H&E photomicrographs as well as quantitate CD31 staining. Both Ki-67-positive and -negative nuclei were counted with Imaris software to obtain a proliferation index., Results: Only SD mice had a single large void pattern. Bladder-to-body weight ratios increased in SD mice (p≤0.02) but not in RSSW mice. Plasma corticosterone levels were elevated in all stressed mice. SD mice exhibited lower levels of locomotor activity compared with controls; RSSW mice were hyperactive. In SD mice, bladder wall thickness was increased (p ≤ 0.003) but no change was seen in Ki-67 proliferation index, consistent with hypertrophy. No difference with control mice was seen in vascularity as visualized by CD31 staining. Uniform uroplakin-II staining lined the urothelium of both SD and control mice., Conclusions: Mice exposed to repeated SD (14 days) respond with altered voiding indicative of urine retention, and exhibit bladder wall changes consistent with hypertrophy while the urothelial barrier is maintained. These changes were not observed with repeated RSSW. SD, in contrast to RSSW, provides a model of psychological stress to further study the interplay of behavior and bladder dysfunction, enabling an improved understanding of voiding dysfunction, and the ability to create innovative and more effective management pathways for children who present with voiding dysfunction., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Controlled experiments were performed with frozen and melted Arctic snow to quantify relationships between mercury photoreaction kinetics, ultra violet (UV) radiation intensity, and snow ion concentrations. Frozen (-10°C) and melted (4°C) snow samples from three Arctic sites were exposed to UV (280-400 nm) radiation (1.26-5.78 W · m(-2)), and a parabolic relationship was found between reduction rate constants in frozen and melted snow with increasing UV intensity. Total photoreduced mercury in frozen and melted snow increased linearly with greater UV intensity. Snow with the highest concentrations of chloride and iron had larger photoreduction and photooxidation rate constants, while also having the lowest Hg(0) production. Our results indicate that the amount of mercury photoreduction (loss from snow) is the highest at high UV radiation intensities, while the fastest rates of mercury photoreduction occurred at both low and high intensities. This suggests that, assuming all else is equal, earlier Arctic snow melt periods (when UV intensities are less intense) may result in less mercury loss to the atmosphere by photoreduction and flux, since less Hg(0) is photoproduced at lower UV intensities, thereby resulting in potentially greater mercury transport to aquatic systems with snowmelt., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Guanylate Cyclase C (GC-C; Gucy2c) is a transmembrane receptor expressed in intestinal epithelial cells. Activation of GC-C by its secreted ligand guanylin stimulates intestinal fluid secretion. Familial mutations in GC-C cause chronic diarrheal disease or constipation and are associated with intestinal inflammation and infection. Here, we investigated the impact of GC-C activity on mucosal immune responses., Methods: We utilized intraperitoneal injection of lipopolysaccharide to elicit a systemic cytokine challenge and then measured pro-inflammatory gene expression in colonic mucosa. GC-C(+/+) and GC-C(-/-) mice were bred with interleukin (IL)-10 deficient animals and colonic inflammation were assessed. Immune cell influx and cytokine/chemokine expression was measured in the colon of wildtype, IL-10(-/-), GC-C(+/+)IL-10(-/-) and GC-C(-/-)IL-10(-/-) mice. GC-C and guanylin production were examined in the colon of these animals and in a cytokine-treated colon epithelial cell line., Results: Relative to GC-C(+/+) animals, intraperitoneal lipopolysaccharide injection into GC-C(-/-) mice increased proinflammatory gene expression in both whole colon tissue and in partially purified colonocyte isolations. Spontaneous colitis in GC-C(-/-)IL-10(-/-) animals was significantly more severe relative to GC-C(+/+)IL-10(-/-) mice. Unlike GC-C(+/+)IL-10(-/-) controls, colon pathology in GC-C(-/-)IL-10(-/-) animals was apparent at an early age and was characterized by severely altered mucosal architecture, crypt abscesses, and hyperplastic subepithelial lesions. F4/80 and myeloperoxidase positive cells as well as proinflammatory gene expression were elevated in GC-C(-/-)IL-10(-/-) mucosa relative to control animals. Guanylin was diminished early in colitis in vivo and tumor necrosis factor α suppressed guanylin mRNA and protein in intestinal goblet cell-like HT29-18-N2 cells., Conclusions: The GC-C signaling pathway blunts colonic mucosal inflammation that is initiated by systemic cytokine burst or loss of mucosal immune cell immunosuppression. These data as well as the apparent intestinal inflammation in human GC-C mutant kindred underscore the importance of GC-C in regulating the response to injury and inflammation within the gut.

Background: Guanylate Cyclase C (GC-C) is an apically-oriented transmembrane receptor that is expressed on epithelial cells of the intestine. Activation of GC-C by the endogenous ligands guanylin or uroguanylin elevates intracellular cGMP and is implicated in intestinal ion secretion, cell proliferation, apoptosis, intestinal barrier function, as well as the susceptibility of the intestine to inflammation. Our aim was to determine if GC-C is required for host defense during infection by the murine enteric pathogen Citrobacter rodentium of the family Enterobacteriacea., Methods: GC-C+/+ control mice or those having GC-C genetically ablated (GC-C-/-) were administered C. rodentium by orogastric gavage and analyzed at multiple time points up to post-infection day 20. Commensal bacteria were characterized in uninfected GC-C+/+ and GC-C-/- mice using 16S rRNA PCR analysis., Results: GC-C-/- mice had an increase in C. rodentium bacterial load in stool relative to GC-C+/+. C. rodentium infection strongly decreased guanylin expression in GC-C+/+ mice and, to an even greater degree, in GC-C-/- animals. Fluorescent tracer studies indicated that mice lacking GC-C, unlike GC-C+/+ animals, had a substantial loss of intestinal barrier function early in the course of infection. Epithelial cell apoptosis was significantly increased in GC-C-/- mice following 10 days of infection and this was associated with increased frequency and numbers of C. rodentium translocation out of the intestine. Infection led to significant liver histopathology in GC-C-/- mice as well as lymphocyte infiltration and elevated cytokine and chemokine expression. Relative to naïve GC-C+/+ mice, the commensal microflora load in uninfected GC-C-/- mice was decreased and bacterial composition was imbalanced and included outgrowth of the Enterobacteriacea family., Conclusions: This work demonstrates the novel finding that GC-C signaling is an essential component of host defense during murine enteric infection by reducing bacterial load and preventing systemic dissemination of attaching/effacing-lesion forming bacterial pathogens such as C. rodentium.

Severe burn injury is accompanied by a systemic inflammatory response, making traditional indicators of sepsis both insensitive and nonspecific. To address this, the American Burn Association (ABA) published diagnostic criteria in 2007 to standardize the definition of sepsis in these patients. These criteria include temperature (>39°C or <36°C), progressive tachycardia (>110 beats per minute), progressive tachypnea (>25 breaths per minute not ventilated or minute ventilation >12 L/minute ventilated), thrombocytopenia (<100,000/μl; not applied until 3 days after initial resuscitation), hyperglycemia (untreated plasma glucose >200 mg/dl, >7 units of insulin/hr intravenous drip, or >25% increase in insulin requirements over 24 hours), and feed intolerance >24 hours (abdominal distension, residuals two times the feeding rate, or diarrhea >2500 ml/day). Meeting >3 of these criteria should "trigger" concern for infection. In this initial assessment of the ABA sepsis criteria correlation with infection, the authors evaluated the ABA sepsis criteria's correlation with bacteremia because bacteremia is not associated with inherent issues of diagnosis as occurs with pneumonia or soft tissue infections, and blood cultures are typically obtained due to concern for ongoing infections falling within the definition of "septic." A retrospective electronic records review was performed to evaluate episodes of bacteremia in the United States Army Institute of Research from 2006 through 2007. A total of 196 patients were admitted during the study period who met inclusion criteria. The first positive and negative cultures, if present, from each patient were evaluated. This totaled 101 positive and 181 negative cultures. Temperature, heart rate, insulin resistance, and feed intolerance criteria were significant on univariate analysis. Only heart rate and temperature were found to significantly correlate with bacteremia on multivariate analysis. The receiver operating characteristic curve area for meeting >3 ABA sepsis criteria is 0.638 (95% confidence interval 0.573-0.704; P < .001). Among severe burn patients, the ABA trigger for sepsis did not correlate strongly with bacteremia in this retrospective chart review.

The purpose of this study was to determine baseline user satisfaction for 2 computer decision support systems (DSSs) with demonstrated improvement in patient outcome used in a burn intensive care unit. We conducted a survey of staff members of a 16-bed burn intensive care unit (n = 82) using a written, anonymous questionnaire to determine satisfaction for 2 DSSs: a commercial glycemic management system and software program to guide initial burn fluid resuscitation. Staff members are not yet convinced of a positive correlation between DSS technology and patient outcomes. We suggest user satisfaction may be generally improved for DSS with concentration in the areas of interface, information, and communication.

The purpose of this systematic review of the literature was to determine the association of sepsis with mortality in the severely injured adult patient by means of a comparative analysis of sepsis in burn and trauma injury with other critically ill populations. The MEDLINE (PubMed), Cochrane Library, and ProQuest databases were searched. The following keywords and MeSH headings were used: "sepsis," septicemia," "septic shock," "epidemiology," "burns," "thermal injury," "trauma," "wounds and injuries," "critical care," "intensive care," "outcomes," and "mortality." Included studies were clinical studies of adult burn, trauma, and critically ill patients that reported survival data for sepsis. Thirty-eight articles were reviewed (9 burn, 11 trauma, 18 general critical care). The age of burn (<45 years) and trauma (34-49 years) groups was lower than the general critical care (57-64 years) population. Sepsis prevalence varied with trauma-injured patients experiencing fewer episodes (2.4%-16.9%) contrasted with burn patients (8%-42.5%) and critical care patients (19%-38%). Survival differed with trauma patients experiencing a lower rate of mortality associated with sepsis (7%-36.9%) compared with the burn (28%-65%) and critical care (21%-53%) groups. This study is the first to compare sepsis outcomes in three distinct patient populations: burn, trauma, and general critical care. Trauma patients tend to have relatively low sepsis-associated mortality; burn patients and the older critical care population have higher prevalence of sepsis with worse outcomes. Great variability of criteria to identify septic patients among studies compromises population comparisons.

Objective: Several formulas have been developed to guide resuscitation in severely burned patients during the initial 48 hrs after injury. These approaches require manual titration of fluid that may result in human error during this process and lead to suboptimal outcomes. The goal of this study was to analyze the efficacy of a computerized open-loop decision support system for burn resuscitation compared to historical controls., Design: Fluid infusion rates and urinary output from 39 severely burned patients with >20% total body surface area burns were recorded upon admission (Model group). A fluid-response model based on these data was developed and incorporated into a computerized open-loop algorithm and computer decision support system. The computer decision support system was used to resuscitate 32 subsequent patients with severe burns (computer decision support system group) and compared with the Model group., Setting: Burn intensive care unit of a metropolitan Level 1 Trauma center., Patients: Acute burn patients with >20% total body surface area requiring active fluid resuscitation during the initial 24 to 48 hours after burn., Measurements and Main Results: We found no significant difference between the Model and computer decision support system groups in age, total body surface area, or injury mechanism. Total crystalloid volume during the first 48 hrs post burn, total crystalloid intensive care unit volume, and initial 24-hr crystalloid intensive care unit volume were all lower in the computer decision support system group. Infused volume per kilogram body weight (mL/kg) and per percentage burn (mL/kg/total body surface area) were also lower for the computer decision support system group. The number of patients who met hourly urinary output goals was higher in the computer decision support system group., Conclusions: Implementation of a computer decision support system for burn resuscitation in the intensive care unit resulted in improved fluid management of severely burned patients. All measures of crystalloid fluid volume were reduced while patients were maintained within urinary output targets a higher percentage of the time. The addition of computer decision support system technology improved patient care.

Guanylate cyclase C (GUCY2C or GC-C) and its ligands, guanylin (GUCA2A or Gn) and uroguanylin (GUCA2B or Ugn), are expressed in intestinal epithelial cells and regulate ion secretion, intestinal barrier function, and epithelial monolayer homeostasis via cGMP-dependent signaling pathways. The aim of this study was to determine whether GC-C and its ligands direct the course of intestinal inflammation. In this article, we show that dextran sodium sulfate (DSS)-induced clinical disease and histological damage to the colonic mucosa were significantly less severe in GC-C(-/-) mice and moderately reduced in Gn(-/-) animals. Relative to wild-type controls, GC-C(-/-) and Gn(-/-) mice had reduced apoptosis and increased proliferation of intestinal epithelial cells during DSS colitis. Basal and DSS-induced production of resistin-like molecule β (RELMβ) was substantially diminished in GC-C(-/-) mice. RELMβ is thought to stimulate cytokine production in macrophages in this disease model and, consistent with this, TNF-α and IFN-γ production was minimal in GC-C(-/-) animals. RELMβ and cytokine levels were similar to wild-type in Gn(-/-) mice, however. Colonic instillation of recombinant RELMβ by enema into GC-C(-/-) mice restores sensitivity to DSS-mediated mucosal injury. These findings demonstrate a novel role for GC-C signaling in facilitating mucosal wounding and inflammation, and further suggest that this may be mediated, in part, through control of RELMβ production.

The purpose of this systematic review was to assess the evidence for use of routine procalcitonin testing to diagnose the presence of sepsis in the burn patient. The electronic databases MEDLINE, Cochrane, CINAHL, ProQuest, and SCOPUS were searched for relevant studies using the MeSH terms burn, infection, procalcitonin, and meta-analysis. The focus of the review was the adult burn population, but other relevant studies of critically ill patients were included as data specific to the patient with burns are limited. Studies were compiled in tabular form and critically appraised for quality and level of evidence. Four meta-analyses, one review of the literature, one randomized controlled trial, nine prospective observational, and three retrospective studies were retrieved. Six of these studies were specific to the burn population, with one specific to burned children. Only one meta-analysis, one adult burn and one pediatric burn study reported no benefit of procalcitonin testing to improve diagnosis of sepsis or differentiate sepsis from non-infectious systemic inflammatory response. The collective findings of the included studies demonstrated benefit of incorporating procalcitonin assay into clinical sepsis determination. Evaluation of the burn specific studies is limited by the use of guidelines to define sepsis and inconsistent results from the burn studies. Utility of the procalcitonin assay is limited due to the lack of availability of rapid, inexpensive tests. However, it appears procalcitonin assay is a safe and beneficial addition to the clinical diagnosis of sepsis in the burn intensive care unit., (Published by Elsevier Ltd.)

Automation and decision support systems are vital for improving critical patient care in the battlefield environment. However, advances in data management, sensor fusion, and decision support algorithms must be developed and incorporated into existing patient monitoring systems for this technology to improve battlefield patient care. This paper examines issues related to research and development of advanced monitoring and decision support systems for use both on the battlefield and in the civilian trauma environment.

The optimal method for glycemic control in the critically burned patient is unknown. The purpose of this randomized controlled study was to determine the safety and efficacy of computer decision support software (CDSS) to control serum glucose concentration in a burn intensive care unit. Eighteen adult burn/trauma patients receiving continuous insulin infusion were initially randomized to receive glucose management by a traditional paper protocol or a computer protocol (CP) for 72 hours and then crossed over to the alternate method for an additional 72 hours. Time in target glucose range (range: 80-110 mg/dl) was higher in the CP group (47 ± 17% vs 41 ± 16.6%; P ≤ .05); time over target range was not significantly reduced in the CP group (49 ± 17.8% vs 54 ± 17.1%; P = .08); and no difference was noted in time under target range of 80 mg/dl (CP: 4.5 ± 2.8%, paper protocol: 4.8 ± 3.3%; P = .8), less than 60 mg/dl (P = .7), and less than 40 mg/dl (P = 1.0). Severe hypoglycemic events (<40 mg/dl) did not differ from the CP group compared with historical controls for patients receiving no insulin (P = .6). More glucose measurements were performed in the CP group (P = .0003), and nursing staff compliance with CP recommendations was greater (P < .0001). Glycemic control using CDSS is safe and effective for the critically burned patient. Time in target range improved without increase in hypoglycemic events. CDSS enhanced consistency in practice, providing standardization among nursing staff.

Background: A relatively new technology in wound care, negative pressure wound therapy (NPWT), has become widely used for the management of open abdomens and soft tissue wounds and provides a means to collect wound exudate to quantify protein loss., Methods: A prospective observational study was conducted in surgical, trauma, or burn patients (8 patients with open abdomens and 9 patients with acute soft tissue wounds on NPWT). NPWT exudate was collected and assayed to characterize loss of protein, electrolyte, and immunoglobulins over multiple days of NPWT., Results: Total protein was present in open abdomen NPWT exudate, 2.9 ± 0.9 g/dL. In the soft tissue wound exudate, a similar mean concentration was found, 2.59 ± 0.6 g/dL (P = .34). Exudate concentrations of albumin, urea nitrogen, immunoglobulins, and electrolytes between wound types were also not significantly different. There were significant (P = .03) differences in the median volume of exudate, 1031 mL/d for open abdomens in contrast to 245 mL/d soft tissue wounds. Therefore, 24-hour losses of proteins and electrolytes were greater in patients with open abdomens than soft tissue wounds. Mean total protein loss was 25 ± 17 g/d for open abdomens and 8 ± 5 g/d for soft tissue wounds., Conclusion: There are significant losses of proteins in wound exudate. As there is no significant difference in the concentration of total protein between wound type, the rate of loss may be calculated as 2.9 g/dL times the volume of wound exudate. The rate of protein loss from wounds is similar to the presently assumed insensible loss rate of 12-25 g/d.

Background: Guanylate Cyclase C (GC-C) expression in the intestine plays a role in the regulation of fluid and ion transport, as well as epithelial cell apoptosis and proliferation. In the adult rat liver, GC-C expression is increased in response to injury. We hypothesized that GC-C is required for repair/recovery from liver injury., Methods: We subjected wild type (WT) and GC-C deficient mice to acute liver injury with a single injection of the hepatotoxin carbon tetrachloride. Changes in the level of expression of GC-C and its ligands uroguanylin and guanylin were quantified by real-time PCR. Liver morphology, and hepatocyte necrosis, apoptosis and proliferation, were examined at 1-3 days post-injury in mice on a mixed genetic background. Survival was followed for 14 days after carbon tetrachloride injection in wild type and GC-C deficient mice on both a mixed genetic background and on an inbred C57BL6/J background., Results: GC-C deficient mice on the mixed genetic background nearly all died (median survival of 5 days) following carbon tetrachloride injection while WT littermates experienced only 35% mortality. Elevated levels of TUNEL-positive hepatocyte death on post-injury day 1, increased apoptosis on day 2, and increased areas of centrilobular necrosis on days 2 and 3, were evident in livers from GC-C null mice compared to WT. Collectively these data suggest increased hepatocyte death in the GC-C null mice in the early time period after injury. This corresponds temporally with increased expression of GC-C and its ligands guanylin and uroguanylin in post-injury WT mouse liver. The hepatocyte proliferative response to injury was the same in both genotypes. In contrast, there was no difference in survival between GC-C null and WT mice on the inbred C57BL/6 J background in response to acute liver injury., Conclusions: Signalling via GC-C promotes hepatocyte survival in vivo and is required for effective recovery from acute toxic injury to the liver in a strain-specific manner.

Objective: Intensive insulin therapy in the critically ill reduces mortality but carries the risk of increased hypoglycemia. Point-of-care blood glucose analysis is standard; however, anemia causes falsely high values and potentially masks hypoglycemia. Permissive anemia is practiced routinely in most intensive care units. We hypothesized that point-of-care glucometer error due to anemia is prevalent, can be corrected mathematically, and correction uncovers occult hypoglycemia during intensive insulin therapy., Design: The study has both retrospective and prospective phases. We reviewed data to verify the presence of systematic error, determine the source of error, and establish the prevalence of anemia. We confirmed our findings by reproducing the error in an in vitro model. Prospective data were used to develop a correction formula validated by the Monte Carlo method. Correction was implemented in a burn intensive care unit and results were evaluated after 9 mos., Setting: Burn and trauma intensive care units at a single research institution., Patients/subjects: Samples for in vitro studies were taken from healthy volunteers. Samples for formula development were from critically ill patients who received intensive insulin therapy., Interventions: Insulin doses were calculated based on predicted serum glucose values from corrected point-of-care glucometer measurements., Measurements and Main Results: Time-matched point-of-care glucose, laboratory glucose, and hematocrit values. We previously found that anemia (hematocrit <34%) produces systematic error in glucometer measurements. The error was correctible with a mathematical formula developed and validated, using prospectively collected data. Error of uncorrected point-of-care glucose ranged from 19% to 29% (p < .001), improving to < or = 5% after mathematical correction of prospective data. Comparison of data pairs before and after correction formula implementation demonstrated a 78% decrease in the prevalence of hypoglycemia in critically ill and anemic patients treated with insulin and tight glucose control (p < .001)., Conclusions: A mathematical formula that corrects erroneous point-of-care glucose values due to anemia in intensive care unit patients reduces the prevalence of hypoglycemia during intensive insulin therapy.

Glycemic control with intensive insulin therapy (IIT) has received widespread adoption secondary to findings of improved clinical outcomes and survival in the burn population. Severe burn as a model for trauma is characterized by a hypermetabolic state, hyperglycemia, and insulin resistance. In this article, we review the findings of a burn center research facility in terms of understanding glucose management. The conferred benefits from IIT, our findings of poor outcomes associated with glycemic variability, advantages from preserved diurnal variation of glucose and insulin, and impacts of glucometer error and hematocrit correction factor are discussed. We conclude with direction for further study and the need for a reliable continuous glucose monitoring system. Such efforts will further the endeavor for achieving adequate glycemic control in order to assess the efficacy of target ranges and use of IIT.