Lethal metabolism of Candida albicans respiratory mutants.

The destructive impact of fungi in agriculture and animal and human health, coincident with increases in antifungal resistance, underscores the need for new and alternative drug targets to counteract these trends. Cellular metabolism relies on many intermediates with intrinsic toxicity and promiscuous enzymatic activity generates others. Fuller knowledge of these toxic entities and their generation may offer opportunities of antifungal development. From this perspective our observation of media-conditional lethal metabolism in respiratory mutants of the opportunistic fungal pathogen Candida albicans was of interest. C. albicans mutants defective in NADH:ubiquinone oxidoreductase (Complex I of the electron transport chain) exhibit normal growth in synthetic complete medium. In YPD medium, however, the mutants grow normally until early stationary phase whereupon a dramatic loss of viability occurs. Upwards of 90% of cells die over the subsequent four to six hours with a loss of membrane integrity. The extent of cell death was proportional to the amount of BactoPeptone, and to a lesser extent, the amount of yeast extract. YPD medium conditioned by growth of the mutant was toxic to wild-type cells indicating mutant metabolism established a toxic milieu in the media. Conditioned media contained a volatile component that contributed to toxicity, but only in the presence of a component of BactoPeptone. Fractionation experiments revealed purine nucleosides or bases as the synergistic component. GC-mass spectrometry analysis revealed acetal (1,1-diethoxyethane) as the active volatile. This previously unreported and lethal synergistic interaction of acetal and purines suggests a hitherto unrecognized toxic metabolism potentially exploitable in the search for antifungal targets.

Early Experience with High-density Electroanatomical Mapping Using the Rhythmia™ Mapping System in Congenital and Pediatric Heart Disease.

The Rhythmia™ system (Boston Scientific, Natick, MA, USA) facilitates the rapid acquisition of high-resolution electroanatomical and activation maps. However, there are limited data on its efficacy and safety in pediatric and adult congenital heart disease (CHD) patients. In a retrospective, observational cohort study, adult CHD and pediatric patients followed by pediatric cardiology underwent electrophysiologic study using the Rhythmia™ electroanatomic mapping system. Variables examined included the number of electroanatomical maps required, acquisition time, procedure time, fluoroscopy time, radiation dosage, and rate of recurrent arrhythmia. Twelve consecutive patients, including six male patients (50%), were included with an average age of 27.7 years (range: 11-64 years). Seven (58%) of these patients had a diagnosis of CHD [moderate complexity in two (17%) and great complexity in five patients (42%)] and 10 (83%) patients underwent ablation. A total of 37 high-density maps were created in 12 procedures, with a median of 8,140 mapping points, taking a median of 631 seconds. The median procedure time was 189.5 minutes. The median fluoroscopy time was 0.9 minutes, with eight (67%) patients receiving no fluoroscopy at all. Recurrence occurred in one patient (8%) over a median follow-up duration of 16 months (interquartile range: 12.8-17.3 months). No adverse periprocedural events were recorded. This study suggests the use of high-density electroanatomic mapping in adult CHD patients showed potential for rapid acquisition of highly detailed maps with minimal fluoroscopy time or risk of periprocedural events in the studied population.

Acute Tracheal Necrosis After Intubation in a Childhood Onset Systemic Lupus Erythematosus.

Upper airway involvement in systemic lupus erythematosus (SLE) disease process is uncommon. A 15-year-old girl, a known patient with class IVA lupus nephritis, presented in acute renal failure due to flare-up of SLE. She underwent an uneventful elective intubation procedure for placement of a hemodialysis catheter. After 36 hours of extubation, she developed biphasic stridor and severe shortness of breath that was unresponsive to multiple medications. Prompt airway evaluation by laryngoscopy and confirmation of acute tracheal necrosis by histopathology along with reintubation and high-dose steroid therapy resulted in good outcome and recovery.

Understanding Adolescent Expressions of Sadness: A Qualitative Exploration.

PURPOSE: Primary care providers are positioned to identify adolescents at risk for depression and prevent major depressive disorder. To identify subthreshold depression, we examined the language adolescents use to describe their symptoms. METHODS: Adolescents ages 13-18 with elevated levels on the Center for Epidemiologic Studies Depression (CES-D) scale and/or a history of depression who were part of a large randomized clinical trial to prevent depressive disorder were included. We used content analysis to analyze transcripts of semi-structured interviews. RESULTS: Saturation was reached at 37 interviews. Adolescents self-identified as African American (N = 15), Hispanic (N = 10), and White (N = 21). Three domains were revealed; external sources of stress, adolescent expressions of sadness, and seeking help and care. Within these domains, 12 distinct themes emerged contextualizing these domains. No variations in the expression of the themes identified for subthreshold depression were found between the three ethno-cultural groups. IMPLICATIONS FOR PRACTICE: Our study identifies, in adolescents' own words, how adolescents with subthreshold depression express feelings and cope with symptoms, and may guide primary care providers to recognize subthreshold depression early. These findings are a step toward filling the gap in the empirical literature needed to improve identification of adolescents at risk for depression in nonspecialist settings.

Fever without a source in children with congenital heart disease.

Two paediatric congenital heart disease patients presented with a brief history of low-grade fever without any focal symptoms. Their clinical features and laboratory tests were unremarkable; however, their blood cultures were positive that prompted further work-up. Infective endocarditis should be considered in any paediatric congenital heart disease patient who presents with fever without any other associated clinical features.

Long-term telemental health prevention interventions for youth: A rapid review.

INTRODUCTION: This rapid review identifies and summarizes the effectiveness of preventative telemental health interventions. It investigates studies conducted between 2010 and 2016 that improve mood and anxiety with long-term follow-up. METHODS: A literature search of three major databases was performed by four reviewers. After citation tracing, 3604 studies were discovered, and twenty of these met the inclusion criteria. Data from the papers were abstracted, assessed for quality, and effect sizes were calculated. RESULTS: Salient information was discussed using the Behavioural Vaccine Model of mental illness prevention. This included key concepts such as efficacy, duration of benefits, sociocultural relevance, professional guidance, peer-to-peer support, adherence, delivery and safety. CONCLUSION: This review suggests there are clear prolonged benefits to using technology in youth mental illness prevention. Although this is a rapidly growing area of investigation in countries around the globe, there is still a dearth of research with long-term follow-up. Future studies should aim to boost engagement by increasing motivational guidance in order to recruit at-risk youth of all demographics into these promising intervention programs.

Risk Factors for Interstage Mortality Following the Norwood Procedure: Impact of Sociodemographic Factors.

Interstage mortality remains significant for patients undergoing staged palliation for hypoplastic left heart syndrome and other related single right ventricle malformations (HLV). The purpose of this study was to identify factors related to demographics, socioeconomic position, and perioperative course associated with post-Norwood hospital discharge, pre-stage 2, interstage mortality (ISM). Medical record review was conducted for patients with HLV, born from 1/2000 to 7/2009 and discharged alive following the Norwood procedure. Sociodemographic and perioperative factors were reviewed. Patients were determined to have ISM if they died between Norwood procedure hospital discharge and stage 2 palliation. Univariable and multivariable logistic regressions were performed to identify risk factors associated with ISM. A total of 273 patients were included in the analysis; ISM occurred in 32 patients (12%). Multivariable analysis demonstrated that independent risk factors for interstage mortality included teen mothers [adjusted odds ratio (AOR) 6.6, 95% confidence interval (CI) 1.9-22.5], single adult caregivers (AOR 4.1, 95% CI 1.2-14.4), postoperative dysrhythmia (AOR 2.7, 95% CI 1.1-6.4), and longer ICU stay (AOR 2.7, 95% CI 1.2-6.1). Anatomic and surgical course variables were not associated with ISM in multivariable analysis. Patients with HLV are at increased risk of ISM if born to a teen mother, if they lived in a home with only one adult caregiver, suffered a postoperative dysrhythmia, or experienced a prolonged ICU stay. These risk factors are identifiable, and thus these infants may be targeted for interventions to reduce ISM.

Novel measurement of relative aortic size predicts rupture of thoracic aortic aneurysms.

BACKGROUND: Optimal operative decision making in thoracic aortic aneurysms requires accurate information on the risk of complications during expectant management. Cumulative and yearly risks of rupture, dissection, and death before operative repair increase with increasing aortic size, but previous work has not addressed the impact of relative aortic size on complication rates. METHODS: Our institutional database contains data on 805 patients followed up serially with thoracic aortic aneurysms. Body surface area information was obtained on 410 patients (257 male, 153 female). We calculated a new measure of relative aortic size, the "aortic size index," and examined its ability to predict complications in these patients. RESULTS: Increasing aortic size index was a significant predictor of increasing rates of rupture (p = 0.0014) as well as the combined endpoint of rupture, death, or dissection (p < 0.0001). Using aortic size index, patients were stratified into three risk groups: less than 2.75 cm/m2 are at low risk (approximately 4% per year), 2.75 to 4.24 cm/m2 are at moderate risk (approximately 8% per year), and those above 4.25 cm/m2 are at high risk (approximately 20% per year). CONCLUSIONS: This study confirms that (1) thoracic aortic aneurysm is a lethal disease, (2) relative aortic size is more important than absolute aortic size in predicting complications, and (3) a novel measurement of relative aortic size allows for the stratification of patients into three levels of risk, enabling appropriate surgical decision-making.