CT Imaging Assessment of Response to Treatment in Allergic Bronchopulmonary Aspergillosis in Adults With Bronchial Asthma.

Background: One of the major challenges in managing allergic bronchopulmonary aspergillosis remains consistent and reproducible assessment of response to treatment.

Research Question: What are the most relevant changes in CT scan parameters over time for assessing response to treatment?

Study Design And Methods: In this ancillary study of a randomized clinical trial (NebuLamB), patients with asthma with available CT scan and without exacerbation during a 4-month allergic bronchopulmonary aspergillosis exacerbation treatment period (corticosteroids and itraconazole) were included. Changed CT scan parameters were assessed by systematic analyses of CT scan findings at initiation and end of treatment.

Angiopoietin-like 3-derivative LNA043 for cartilage regeneration in osteoarthritis: a randomized phase 1 trial.

Osteoarthritis (OA) is a common, debilitating, chronic disease with no disease-modifying drug approved to date. We discovered LNA043-a derivative of angiopoietin-like 3 (ANGPTL3)-as a potent chondrogenesis inducer using a phenotypic screen with human mesenchymal stem cells. We show that LNA043 promotes chondrogenesis and cartilage matrix synthesis in vitro and regenerates hyaline articular cartilage in preclinical OA and cartilage injury models in vivo.

Nebulised liposomal amphotericin-B as maintenance therapy in allergic bronchopulmonary aspergillosis: a randomised, multicentre trial.

Background: In allergic bronchopulmonary aspergillosis (ABPA), prolonged nebulised antifungal treatment may be a strategy for maintaining remission.

Methods: We performed a randomised, single-blind, clinical trial in 30 centres. Patients with controlled ABPA after 4-month attack treatment (corticosteroids and itraconazole) were randomly assigned to nebulised liposomal amphotericin-B or placebo for 6 months.

Prognostic factors of severe community-acquired staphylococcal pneumonia in France.

Purpose: causes severe forms of community-acquired pneumonia (CAP), namely staphylococcal pleuropneumonia in young children and staphylococcal necrotising pneumonia in older patients. Methicillin resistance and the Panton-Valentine leukocidin (PVL) toxin, as well as less specific factors, have been associated with poor outcome in severe CAP, but their roles are unclear.

Methods: A prospective multicentre cohort study of severe staphylococcal CAP was conducted in 77 paediatric and adult intensive care units in France between January 2011 and December 2016.

Safety and pharmacokinetics of bimagrumab in healthy older and obese adults with body composition changes in the older cohort.

Background: Bimagrumab prevents activity of myostatin and other negative regulators of skeletal muscle mass. This randomized double-blind, placebo-controlled study investigated safety, pharmacokinetics (PK), and pharmacodynamics of bimagrumab in healthy older and obese adults.

Methods: A cohort of older adults (aged 70-85 years) received single intravenous infusions of bimagrumab 30 mg/kg (n = 6) or 3 mg/kg (n = 6) or placebo (n = 4) and was followed for 20 weeks.

Hyperpolarized C MRI of Tumor Metabolism Demonstrates Early Metabolic Response to Neoadjuvant Chemotherapy in Breast Cancer.

Purpose: To compare hyperpolarized carbon 13 (C) MRI with dynamic contrast material-enhanced (DCE) MRI in the detection of early treatment response in breast cancer.

Materials And Methods: In this institutional review board-approved prospective study, a woman with triple-negative breast cancer (age, 49 years) underwent C MRI after injection of hyperpolarized [1-carbon 13 {C}]-pyruvate and DCE MRI at 3 T at baseline and after one cycle of neoadjuvant therapy. The C-labeled lactate-to-pyruvate ratio derived from hyperpolarized C MRI and the pharmacokinetic parameters transfer constant ( ) and washout parameter ( ) derived from DCE MRI were compared before and after treatment.

Type 2 Diabetes Mellitus Is Independently Associated With Decreased Neural Baroreflex Sensitivity: The Paris Prospective Study III.

Objective: Impaired baroreflex function is an early indicator of cardiovascular autonomic imbalance. Patients with type 2 diabetes mellitus (T2D) have decreased baroreflex sensitivity (BRS), however, whether the neural BRS (nBRS) and mechanical component of the BRS is altered in those with high metabolic risk (HMR, impaired fasting glucose and metabolic syndrome) or with overt T2D, is unknown. We examined this in a community-based observational study, the Paris Prospective Study III (PPS3).

Association Between Occupational, Sport, and Leisure Related Physical Activity and Baroreflex Sensitivity: The Paris Prospective Study III.

Physical activity (PA) is a preventative behavior for noncommunicable disease. However, little consideration is given as to whether different domains of PA have differing associations with health outcomes. We sought to determine the association between occupational, sport, leisure, and total PA with baroreflex sensitivity (BRS), distinguishing between neural (nBRS) and mechanical (mBRS) BRS.

Body Silhouette Trajectories Across the Lifespan and Vascular Aging.

Vascular aging is a major contributor to cardiovascular disease and can be quantified by higher carotid stiffness, intima-media thickness and diameter, and hypertension. Weight gain across the lifetime may be an important, modifiable determinant of vascular aging. We therefore aimed to assess lifetime body silhouette trajectories (a marker of weight change across the lifespan) in relation to vascular aging in late adulthood.

Cerebral microbleeds and CSF Alzheimer biomarkers in primary progressive aphasias.

Objective: To reveal the prevalence and localization of cerebral microbleeds (CMBs) in the 3 main variants of primary progressive aphasia (PPA) (logopenic, semantic, and nonfluent/agrammatic), to identify the relationship with underlying Alzheimer pathology, and to explore whether CMBs contribute to language breakdown.

Methods: We used a cross-sectional design in a multicenter cohort of 82 patients with PPA and 19 similarly aged healthy controls. MRI allowed for rating CMBs (2-dimensional gradient recalled echo T2*, susceptibility weighted imaging sequences) and white matter hyperintensities.

Antagonist Anti-CD28 Therapeutics for the Treatment of Autoimmune Disorders.

The effector functions of T lymphocytes are responsible for most autoimmune disorders and act by directly damaging tissues or by indirectly promoting inflammation and antibody responses. Co-stimulatory and co-inhibitory T cell receptor molecules are the primary pharmacological targets that enable interference with immune-mediated diseases. Among these, selective CD28 antagonists have drawn special interest, since they tip the co-stimulation/co-inhibition balance towards efficiently inhibiting effector T cells while promoting suppression by pre-existing regulatory T-cells.

Preclinical Pharmacology and Pharmacokinetics of Inhaled Hexadecyl-Treprostinil (C16TR), a Pulmonary Vasodilator Prodrug.

This article describes the preclinical pharmacology and pharmacokinetics (PK) of hexadecyl-treprostinil (C16TR), a prodrug of treprostinil (TRE), formulated in a lipid nanoparticle (LNP) for inhalation as a pulmonary vasodilator. C16TR showed no activity (>10 M) in receptor binding and enzyme inhibition assays, including binding to prostaglandin E receptor 2, prostaglandin D receptor 1, prostaglandin I receptor, and prostaglandin E receptor 4; TRE potently bound to each of these prostanoid receptors. C16TR had no effect (up to 200 nM) on platelet aggregation induced by ADP in rat blood.

Hypothermia for Neuroprotection in Convulsive Status Epilepticus.

Background: Convulsive status epilepticus often results in permanent neurologic impairment. We evaluated the effect of induced hypothermia on neurologic outcomes in patients with convulsive status epilepticus.

Methods: In a multicenter trial, we randomly assigned 270 critically ill patients with convulsive status epilepticus who were receiving mechanical ventilation to hypothermia (32 to 34°C for 24 hours) in addition to standard care or to standard care alone; 268 patients were included in the analysis.

Ideal Cardiovascular Health and Subclinical Markers of Carotid Structure and Function: The Paris Prospective Study III.

Objective: We hypothesized that subclinical markers of vascular structure and function, which are independent predictors of cardiovascular disease, would be less frequent in subjects with ideal than poor cardiovascular health (CVH) as defined by the American Heart Association (AHA).

Approach And Results: Carotid parameters were measured using high-precision echotracking device in 9155 nonreferred participants attending a health checkup in a large health center in Paris (France) between 2008 and 2012. According to the AHA, participants with 0 to 2, 3 to 4, and 5 to 7 metrics (smoking, physical activity, body mass index, diet, blood glucose and total cholesterol, blood pressure) at the ideal level were categorized as having poor, intermediate, and ideal CVH.

Pharmacokinetics, Safety, and Efficacy of Intravitreal Digoxin in Preclinical Models for Retinoblastoma.

Purpose: To assess in vitro cytotoxic activity and antiangiogenic effect, ocular and systemic disposition, and toxicity of digoxin in rabbits after intravitreal injection as a potential candidate for retinoblastoma treatment.

Methods: A panel of two retinoblastoma and three endothelial cell types were exposed to increasing concentrations of digoxin in a conventional (72-hour exposure) and metronomic (daily exposure) treatment scheme. Cytotoxicity was defined as the digoxin concentration that killed 50% of the cells (IC50) and was assessed with a vital dye in all cell types.

Contribution of Rare and Common Genetic Variants to Plasma Lipid Levels and Carotid Stiffness and Geometry: A Substudy of the Paris Prospective Study 3.

Background: We assess the contribution of common and rare putatively functional genetic variants (most of them coding) present on the Illumina exome Beadchip to the variability of plasma lipids and stiffness of the common carotid artery.

Methods And Results: Measurements were obtained from 2283 men and 1398 women, and after filtering and exclusion of monomorphic variants, 32,827 common (minor allele frequency >0.01) and 68,770 rare variants were analyzed.

Treatment of sporadic inclusion body myositis with bimagrumab.

Objective: To study activin signaling and its blockade in sporadic inclusion body myositis (sIBM) through translational studies and a randomized controlled trial.

Methods: We measured transforming growth factor β signaling by SMAD2/3 phosphorylation in muscle biopsies of 50 patients with neuromuscular disease (17 with sIBM). We tested inhibition of activin receptors IIA and IIB (ActRII) in 14 patients with sIBM using one dose of bimagrumab (n = 11) or placebo (n = 3).

Locally advanced pancreatic adenocarcinoma: reassessment of response with CT after neoadjuvant chemotherapy and radiation therapy.

Purpose: To prospectively evaluate the utility of computed tomography (CT) for determination of tumor response and prediction of resectability after neoadjuvant combined chemotherapy and radiation therapy (CRT) in patients with nonmetastatic locally advanced pancreatic cancer.

Materials And Methods: This study received institutional review board approval, and all participants provided written informed consent. Consecutive patients with cephalic locally advanced pancreatic cancer who underwent surgical exploration and/or resection following neoadjuvant CRT were prospectively enrolled from June 2009 to May 2013.

Executive/attentional performance and measures of schizotypy in patients with schizophrenia and in their nonpsychotic first-degree relatives.

Previous studies of executive/attentional functions have found impairments in nonpsychotic first-degree relatives of patients with schizophrenia. The aims of this study were: (1) to replicate these findings by three laboratory measures of attention/information processing - a continuous performance test (DS-CPT), a forced-choice span of apprehension task (SPAN), and a digit symbol substitution test (DSST), and by a series of neuropsychological tests sensitive to prefrontal cortical damage - Trail Making A and B, verbal fluency (VFT), Stroop Color and Word Test (Stroop), and Wisconsin Card Sorting Test (WCST); (2) to investigate whether such executive/attentional deficits are associated with schizotypal traits assessed using the social anhedonia, physical anhedonia, perceptual aberration and magical ideation scales (Chapman, L.J.

Attentional deficits in patients with schizophrenia and in their non-psychotic first-degree relatives.

The aim of this study was to investigate whether non-psychotic relatives of schizophrenic probands have deficits in sustained attention as measured by the Continuous Performance Test, Identical Pairs version (CPT-IP) and whether such deficits are associated with negative schizotypal personality disorders. The study subjects were 23 schizophrenic probands, 45 of their first-degree relatives and 36 normal controls. For each subject, attention was assessed during five conditions (2 standard, 2 slow, 1 easy) of visual stimuli (numbers and shapes).

A quantitative approach for studying the effect of heat treatment conditions on resistance and recovery of Bacillus cereus spores.

When a bacterial population undergoes an unfavourable transient increase in temperature, a death phase followed by a lag and growth phase are observed for the surviving and cultivable population. The lag phase is of great interest in regard to food safety, but for bacterial spores, very few studies have been carried out on the evolution of lag time versus heat treatment duration. The experiments monitored on spores of two strains of Bacillus cereus showed a biphasic evolution of the lag time for germination of stressed spores with increase in heat treatment duration, at 90 degrees C, 95 degrees C and 100 degrees C and for different recovery conditions in laboratory medium.