Pathologic Substrates of Structural Brain Network Resilience and Topology in Parkinson Disease Decedents.

Background And Objectives: In Parkinson disease (PD), α-synuclein spreading through connected brain regions leads to neuronal loss and brain network disruptions. With diffusion-weighted imaging (DWI), it is possible to capture conventional measures of brain network organization and more advanced measures of brain network resilience. We aimed to investigate which neuropathologic processes contribute to regional network topologic changes and brain network resilience in PD.

Long-term benefits of physical activity in adult patients with late onset Pompe disease: a retrospective cohort study with 10 years of follow-up.

Background: In 2011 a 12 weeks personalized exercise training program in 23 mildly affected adult late onset Pompe patients (age 19.6-70.5 years) improved endurance, muscle strength and function.

Physical Training and Healthy Diet Improved Bowel Symptoms, Quality of Life, and Fatigue in Children With Inflammatory Bowel Disease.

Objectives: Physical activity programs have been suggested as adjunctive therapy in adult inflammatory bowel disease (IBD) patients. We assessed the effects of a 12-week lifestyle intervention in children with IBD.

Methods: This study was a randomized semi-crossover controlled trial, investigating a 12-week lifestyle program (3 physical training sessions per week plus personalized healthy dietary advice) in children with IBD.

Anti-C2 Antibody ARGX-117 Inhibits Complement in a Disease Model for Multifocal Motor Neuropathy.

Background And Objectives: To determine the role of complement in the disease pathology of multifocal motor neuropathy (MMN), we investigated complement activation, and inhibition, on binding of MMN patient-derived immunoglobulin M (IgM) antibodies in an induced pluripotent stem cell (iPSC)-derived motor neuron (MN) model for MMN.

Methods: iPSC-derived MNs were characterized for the expression of complement receptors and membrane-bound regulators, for the binding of circulating IgM anti-GM1 from patients with MMN, and for subsequent fixation of C4 and C3 on incubation with fresh serum. The potency of ARGX-117, a novel inhibitory monoclonal antibody targeting C2, to inhibit fixation of complement was assessed.

The novel TRPA1 antagonist BI01305834 inhibits ovalbumin-induced bronchoconstriction in guinea pigs.

Background: Asthma is a chronic respiratory disease in which the nervous system plays a central role. Sensory nerve activation, amongst others via Transient Receptor Potential Ankyrin 1 (TRPA1) channels, contributes to asthma characteristics including cough, bronchoconstriction, mucus secretion, airway hyperresponsiveness (AHR) and inflammation. In the current study, we evaluated the efficacy of the novel TRPA1 antagonist BI01305834 against AHR and inflammation in guinea-pig models of asthma.

Nine-year prospective efficacy and safety of brain-responsive neurostimulation for focal epilepsy.

Objective: To prospectively evaluate safety and efficacy of brain-responsive neurostimulation in adults with medically intractable focal onset seizures (FOS) over 9 years.

Methods: Adults treated with brain-responsive neurostimulation in 2-year feasibility or randomized controlled trials were enrolled in a long-term prospective open label trial (LTT) to assess safety, efficacy, and quality of life (QOL) over an additional 7 years. Safety was assessed as adverse events (AEs), efficacy as median percent change in seizure frequency and responder rate, and QOL with the Quality of Life in Epilepsy (QOLIE-89) inventory.

Relationship between β-amyloid and structural network topology in decedents without dementia.

Objective: To investigate the association between β-amyloid (Aβ) load and postmortem structural network topology in decedents without dementia.

Methods: Fourteen decedents (mean age at death 72.6 ± 7.

Cortical axonal loss is associated with both gray matter demyelination and white matter tract pathology in progressive multiple sclerosis: Evidence from a combined MRI-histopathology study.

Background: Neuroaxonal degeneration is one of the hallmarks of clinical deterioration in progressive multiple sclerosis (PMS).

Objective: To elucidate the association between neuroaxonal degeneration and both local cortical and connected white matter (WM) tract pathology in PMS.

Methods: 3T magnetic resonance imaging (MRI) and cortical tissue blocks were collected from 16 PMS donors and 10 controls.

Pharmacological Screening Identifies SHK242 and SHK277 as Novel Arginase Inhibitors with Efficacy against Allergen-Induced Airway Narrowing In Vitro and In Vivo.

Arginase is a potential target for asthma treatment. However, there are currently no arginase inhibitors available for clinical use. Here, a novel class of arginase inhibitors was synthesized, and their efficacy was pharmacologically evaluated.

Effects of the intake of white wheat bread added with garlic and resistant starch: action on calcium bioavailability and metabolic parameters of growing Wistar rats.

Wheat bread is a widely consumed food and is suitable for the introduction of functional ingredients. The aim of this work was to study the effects of bread with garlic and resistant starch as a fiber source on physiological, metabolic, and functional parameters using an in vivo Wistar rat model. Rats were fed with three diets: a control diet prepared according to the American Institute of Nutrition (C), and two semisynthetic diets containing wheat bread (B) and wheat bread with garlic, resistant starch and calcium citrate (BGR).

Search for a resonance decaying into WZ boson pairs in pp collisions.

We present the first search for an electrically charged resonance W' decaying to a WZ boson pair using 4.1 fb(-1) of integrated luminosity collected with the D0 detector at the Fermilab Tevatron pp collider. The WZ pairs are reconstructed through their decays into three charged leptons (l=e, mu).

Measurement of the WW production cross section with dilepton final states in pp collisions at square root(s) = 1.96 TeV and limits on anomalous trilinear gauge couplings.

We provide the most precise measurement of the WW production cross section in pp collisions to date at a center of mass energy of 1.96 TeV, and set limits on the associated trilinear gauge couplings. The WW-->lnul'nu (l, l' = e, mu) decay channels are analyzed in 1 fb(-1) of data collected by the D0 detector at the Fermilab Tevatron Collider.

Observation of ZZ production in p-p collisions at sqrt s=1.96 TeV.

We present an observation for ZZ-->l+l-l'+l'- (l, l'=e or mu) production in p[over]p collisions at a center-of-mass energy of sqrt[s]=1.96 TeV. Using 1.

Competitive inhibition of lipolytic enzymes. X. Further delineation of the active site of pancreatic phospholipases A2 from pig, ox and horse by comparing the inhibitory power of a number of (R)-2-acylamino phospholipid analogues.

Two series of (R)-phospholipid analogues, each containing a n-propyl group at the C-1 position and various acylamino functions at the C-2 position have been synthesized and their inhibitory properties towards three mammalian pancreatic phospholipases A2 have been determined. The members of the first series of analogues all contained the zwitter-ionic phosphocholine headgroup which in the second series was replaced by the anionic phosphoglycol function. In the saturated 2-acylamino phospholipids the length of the acyl chain ranged from 8 to 18 carbon atoms.

Competitive inhibition of lipolytic enzymes. IX. A comparative study on the inhibition of pancreatic phospholipases A2 from different sources by (R)-2-acylamino phospholipid analogues.

The inhibitory power (Z) of a number of (R)-1-alkyl-2-acylamino phospholipid analogues was determined for three mammalian phospholipases A2 from pig, ox and horse pancreas. All three enzymes display a clear preference for anionic (phosphoglycol) inhibitors over the zwitterionic (phosphocholine) derivatives; this effect is most pronounced for the bovine enzyme. Upon variation of the 1-alkyl chain length, the bovine and equine phospholipases, like the porcine enzyme in previous studies, show an optimum in Z for a six-carbon alkyl group.

Chimeric enkephalin-cystatins: opioid binding and structure-activity relationships of inhibitory domains.

A chimeric inhibitor of cysteine proteinases, YGGFLQVVAGK.amide, was synthesized for use in examining SAR of its cystatin and opioid domains. Analogs were prepared by solid-phase syntheses and evaluated for inhibition of rat brain cathepsin L (E.