Neutralization of Mitochondrial Superoxide by Superoxide Dismutase 2 Promotes Bacterial Clearance and Regulates Phagocyte Numbers in Zebrafish

Mitochondria are known primarily as the location of the electron transport chain and energy production in cells. More recently, mitochondria have been shown to be signaling centers for apoptosis and inflammation. Reactive oxygen species (ROS) generated as by-products of the electron transport chain within mitochondria significantly impact cellular signaling pathways. Because of the toxic nature of ROS, mitochondria possess an antioxidant enzyme, superoxide dismutase 2 (SOD2), to neutralize ROS. If mitochondrial antioxidant enzymes are overwhelmed during severe infections, mitochondrial dysfunction can occur and lead to multiorgan failure or death. Pseudomonas aeruginosa is an opportunistic pathogen that can infect immunocompromised patients. Infochemicals and exotoxins associated with P. aeruginosa are capable of causing mitochondrial dysfunction. In this work, we describe the roles of SOD2 and mitochondrial ROS regulation in the zebrafish innate immune response to P. aeruginosa infection. sod2 is upregulated in mammalian macrophages and neutrophils in response to lipopolysaccharide in vitro, and sod2 knockdown in zebrafish results in an increased bacterial burden. Further investigation revealed that phagocyte numbers are compromised in Sod2-deficient zebrafish. Addition of the mitochondrion-targeted ROS-scavenging chemical MitoTEMPO rescues neutrophil numbers and reduces the bacterial burden in Sod2-deficient zebrafish. Our work highlights the importance of mitochondrial ROS regulation by SOD2 in the context of innate immunity and supports the use of mitochondrion-targeted ROS scavengers as potential adjuvant therapies during severe infections.     

The longitudinal validity,reproducibility and responsiveness of the Brisbane Burn Scar Impact Profile (caregiver report for young children version) for measuring health-related quality of life in children with burn scars

BackgroundThe measurement of health-related quality of life (HRQoL) provides information about the perceived burden of the health condition and treatments from a lived experience. The Brisbane Burn Scar Impact Profile (caregiver report for young children, BBSIP^0–8), developed in 2013, is a proxy-report measure of burn scar-specific HRQoL. The aim of this study was to report its psychometric properties in line with an evaluative purpose.MethodsCaregivers of children up to 8 years of age at risk of burn scarring were recruited into a prospective, longitudinal cohort study. Caregivers completed the BBSIP^0–8, Pediatric Quality of Life Inventory and Patient Observer Scar Assessment Scale at baseline (approximately ≥85% of the total body surface area re-epithelialised), 1–2 weeks after baseline and 1-month after baseline. Psychometric properties measured included internal consistency, test–retest reliability, validity and responsiveness.ResultsEighty-six caregivers of mostly male children (55%), of a median age (IQR) of 1 year, 10 months (2 years, 1 month) and total body surface area burn of 1.5% (3.0%) were recruited. Over one third of participants were grafted and 15% had contractures or skin tightness at baseline. Internal consistency of ten item groups ranged from 0.73 to 0.96. Hypothesised correlations of changes in the BBSIP^0–8 items with changes in criterion measures supported longitudinal validity (ρ ranging from ?0.73 to 0.68). The majority of item groups had acceptable reproducibility (ICC = 0.65–0.83). The responsiveness of five item groups was supported (AUC = 0.71–0.90).ConclusionThe psychometric properties tested support the use of the BBSIP^0–8 as an evaluative measure of burn scar-related health-related quality of life for children aged below eight years in the early post-acute period of rehabilitation. Further investigation at longer time period after burn injury is indicated.     

Gender,race and socioeconomic influence on diagnosis and treatment of thyroid disorders in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

Thyroid diseases are common, and use of levothyroxine is increasing worldwide. We investigated the influence of gender, race and socioeconomic status on the diagnosis and treatment of thyroid disorders using data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), a multicenter cohort study of civil servants (35-74 years of age) from six Brazilian cities. Diagnosis of thyroid dysfunction was by thyrotropin (TSH), and free thyroxine (FT4) if TSH was altered, and the use of specific medications. Multivariate logistic regression models were constructed using overt hyperthyroidism/hypothyroidism and levothyroxine use as dependent variables and sociodemographic characteristics as independent variables. The frequencies of overt hyper- and hypothyroidism were 0.7 and 7.4%, respectively. Using whites as the reference ethnicity, brown, and black race were protective for overt hypothyroidism (OR=0.76, 95%CI=0.64-0.89, and OR=0.53, 95%CI=0.43-0.67, respectively, and black race was associated with overt hyperthyroidism (OR=1.82, 95%CI=1.06-3.11). Frequency of hypothyroidism treatment was higher in women, browns, highly educated participants and those with high net family incomes. After multivariate adjustment, levothyroxine use was associated with female gender (OR=6.06, 95%CI=3.19-11.49) and high net family income (OR=3.23, 95%CI=1.02-10.23). Frequency of hyperthyroidism treatment was higher in older than in younger individuals. Sociodemographic factors strongly influenced the diagnosis and treatment of thyroid disorders, including the use of levothyroxine.