Mitigation of zinc leaching from waste ground tire rubbers through polymer encapsulation.

The increasing disposal of waste tires is a growing environmental challenge requiring innovative recycling and reuse approaches. Crumb rubber, derived from end-of-life tires, has potential for various applications where resilience and elasticity are required. However, as highlighted by the upcoming ban on using crumb rubber granulate as infill for artificial turf in the EU, one of the most prominent issues, zinc leaching, urgently requires an effective solution.

Characterization of the central nervous system penetrant and selective purine P2X7 receptor antagonist JNJ-54175446 in patients with major depressive disorder.

JNJ-54175446 is a selective purine P2X7 receptor (P2X7R) antagonist that attenuates microglial IL-1β/IL-18 release. In healthy volunteers, JNJ-54175446 suppressed peripheral interleukin (IL)-1β release, and attenuated dexamphetamine-induced improvements of mood and (visuo)motor performance in a human dexamphetamine-challenge paradigm. In depression, P2X7R inhibition may dampen immune-related dysregulation of mood.

Pharmacological characterization of the selective orexin-1 receptor antagonist JNJ-61393215 in healthy volunteers.

Background: Up to 40% of patients suffering from anxiety disorders do not benefit from currently available pharmacological treatments. Overactivity of the orexin-1 receptor (OX1R) has been implicated in anxiety- and panic-related states.

Aim & Methods: We investigated the pharmacokinetics and characterized the pharmacodynamic (PD) profile of the OX1R antagonist JNJ-61393215 using a battery of central nervous system assessments investigating relevant functional domains such as alertness, attention, (visuo)motor coordination, balance, subjective effects and resting-state electroencephalography in a single ascending dose placebo-controlled study in doses from 1 to 90 mg inclusive, assessing PD up to 10 h after dosing, safety and pharmacokinetic in 48 healthy male subjects.

Profiling classical neuropsychiatric biomarkers across biological fluids and following continuous lumbar puncture: A guide to sample type and time.

Unlabelled: Identification of putative biomarkers for neuropsychiatric disorders has produced a diverse list of analytes involved in inflammation, hypothalamic-pituitary-adrenal axis (HPA) regulation, growth factor and metabolic pathways. However, translation of these findings to accurate and robust assays has been stalled, affecting objective diagnoses, tracking relapse/remission, and prediction/monitoring of drug affect. Two important factors to control are the sample matrix (e.

Time Trends of Cerebrospinal Fluid Biomarkers of Neurodegeneration in Idiopathic Normal Pressure Hydrocephalus.

Background: Longitudinal changes in cerebrospinal fluid (CSF) biomarkers are seldom studied. Furthermore, data on biomarker gradient between lumbar (L-) and ventricular (V-) compartments seems to be discordant.

Objective: To examine alteration of CSF biomarkers reflecting Alzheimer's disease (AD)-related amyloid-β (Aβ) aggregation, tau pathology, neurodegeneration, and early synaptic degeneration by CSF shunt surgery in idiopathic normal pressure hydrocephalus (iNPH) in relation to AD-related changes in brain biopsy.

Association of Hippocampal Subfields, CSF Biomarkers, and Cognition in Patients With Parkinson Disease Without Dementia.

Objective: To examine whether hippocampal volume loss is primarily associated with cognitive status or pathologic β-amyloid 1-42 (Aβ42) levels, this study compared hippocampal subfield volumes between patients with Parkinson disease (PD) with mild cognitive impairment (PD-MCI) and without cognitive impairment (PD-CN) and between patients with low and high Aβ42 levels, in addition exploring the relationship among hippocampal subfield volumes, CSF biomarkers (Aβ42, phosphorylated and total tau), neuropsychological tests, and activities of daily living.

Methods: Forty-five patients with PD without dementia underwent CSF analyses and MRI as well as comprehensive motor and neuropsychological examinations. Hippocampal segmentation was conducted using FreeSurfer image analysis suite 6.

The effects of inhibition of fatty acid amide hydrolase (FAAH) by JNJ-42165279 in social anxiety disorder: a double-blind, randomized, placebo-controlled proof-of-concept study.

JNJ-42165279 is a selective inhibitor of fatty acid amide hydrolase (FAAH), the enzyme responsible for the degradation of fatty acid amides (FAA) including anandamide (AEA), palmitoylethanolamide (PEA), and N-oleoylethanolamide (OEA). We assessed the efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics of treatment with JNJ-42165279 in subjects with social anxiety disorder (SAD). This was a multicenter, double-blind, placebo-controlled study randomizing subjects to 12 weeks of treatment with either JNJ-42165279 (25 mg daily) or placebo (PBO).

Translational evaluation of novel selective orexin-1 receptor antagonist JNJ-61393215 in an experimental model for panic in rodents and humans.

Orexin neurons originating in the perifornical and lateral hypothalamic area project to anxiety- and panic-associated neural circuitry, and are highly reactive to anxiogenic stimuli. Preclinical evidence suggests that the orexin system, and particularly the orexin-1 receptor (OX1R), may be involved in the pathophysiology of panic and anxiety. Selective OX1R antagonists thus may constitute a potential new treatment strategy for panic- and anxiety-related disorders.

Long-term safety and tolerability of atabecestat (JNJ-54861911), an oral BACE1 inhibitor, in early Alzheimer's disease spectrum patients: a randomized, double-blind, placebo-controlled study and a two-period extension study.

Background: Atabecestat, a potent brain-penetrable inhibitor of BACE1 activity that reduces CSF amyloid beta (Aβ), was developed for oral treatment for Alzheimer's disease (AD). The long-term safety and effect of atabecestat on cognitive performance in participants with predementia AD in two phase 2 studies were assessed.

Methods: In the placebo-controlled double-blind parent ALZ2002 study, participants aged 50 to 85 years were randomized (1:1:1) to placebo or atabecestat 10 or 50 mg once daily (later reduced to 5 and 25 mg) for 6 months.

Executive Function Is Related to the Urinary Urgency in Non-demented Patients With Parkinson's Disease.

: Evidence suggests urinary urgency is associated with cognitive impairment in a subtype of Parkinson's disease (PD) patients. This study investigates if cognitive impairment independently predicts the presence of urinary dysfunction. : We report data of 189 idiopathic PD patients, excluding those with concomitant diseases or medication interacting with bladder function.

Association of cognitive activities of daily living (ADL) function and nonmotor burden in nondemented Parkinson's disease patients.

Objective: In Parkinson's disease (PD), nonmotor symptoms (NMS) considerably influence disease progression and cognitive decline. Depression, anxiety, sleep disturbances, and hallucinations (DASH), may indicate a risk for dementia (PDD). Mild impairments in activities of daily living (ADL) caused by cognitive dysfunction are also present in the prodromal stage of PDD.

Neuroendocrine and Inflammatory Effects of Childhood Trauma Following Psychosocial and Inflammatory Stress in Women with Remitted Major Depressive Disorder.

The dysregulation of the inflammatory and neuroendocrine systems seen in major depressive disorder (MDD) may persist after remission and this is associated with a higher risk of relapse. This vulnerable subgroup may be characterized by a history of childhood trauma. In a single-blind randomized placebo-controlled crossover study, 21 women with remitted recurrent MDD and 18 healthy controls were exposed to psychosocial stress (Trier social stress test) or inflammatory stress (typhoid vaccine), or both, to investigate the effects of childhood trauma on the neuroendocrine and inflammatory responses.

Correction to: The selective orexin-2 antagonist seltorexant (JNJ-42847922/MIN-202) shows antidepressant and sleep-promoting effects in patients with major depressive disorder.

In the original Article, Tables two and three had formatting issues which affected their clarity. This has been corrected in the PDF and HTML versions of this Article.

The selective orexin-2 antagonist seltorexant (JNJ-42847922/MIN-202) shows antidepressant and sleep-promoting effects in patients with major depressive disorder.

Excessive arousal has a role in the pathophysiology of major depressive disorder (MDD). Seltorexant (JNJ-42847922/MIN-202) is a selective antagonist of the human orexin-2 receptor (OX2R) that may normalize excessive arousal and thereby attenuate depressive symptoms. In this study, the effects of night-time arousal suppression on depressive symptoms were investigated.

Relevance of the interplay between amyloid and tau for cognitive impairment in early Alzheimer's disease.

Amyloid β (Aβ) and tau are key hallmark features of Alzheimer's disease (AD) neuropathology. The interplay of Aβ and tau for cognitive impairment in early AD was examined with cross-sectional analysis, measured by cerebrospinal fluid biomarkers (Aβ, total tau [t-tau], and phosphorylated tau [p-tau181P]), and on cognitive performance by the repeatable battery for assessment of neuropsychological status (RBANS). Participants (n = 246) included cognitively normal (Aβ-), mild cognitively impaired (Aβ-), preclinical AD (Aβ+), and prodromal AD (Aβ+).

The selective orexin-2 receptor antagonist seltorexant improves sleep: An exploratory double-blind, placebo controlled, crossover study in antidepressant-treated major depressive disorder patients with persistent insomnia.

Background: Insomnia is common in patients with major depressive disorder. Although antidepressants improve mood, insomnia often persists as a result of physiological hyperarousal. The orexin-2 receptor is increasingly being recognized as a new target for the treatment of persistent insomnia in major depressive disorder .

Normative data from linear and nonlinear quantile regression in CANTAB: Cognition in mid-to-late life in an epidemiological sample.

Introduction: Normative cognitive data can help to distinguish pathological decline from normal aging. This study presents normative data from the Cambridge Neuropsychological Test Automated Battery, using linear regression and nonlinear quantile regression approaches.

Methods: Heinz Nixdorf Recall study participants completed Cambridge Neuropsychological Test Automated Battery tests: paired-associate learning, spatial working memory, and reaction time.

State-associated changes in longitudinal [F]-PBR111 TSPO PET imaging of psychosis patients: Evidence for the accelerated ageing hypothesis?

Objective: To determine whether state-associated changes in microglial activity, measured with translocator-protein positron emission tomography (TSPO PET), can be identified in psychosis patients through longitudinal evaluation of their regional tracer uptake over the clinical course from acute psychosis to post-treatment follow-up, and comparison to healthy controls. We also evaluated the relation between tracer uptake, clinical symptoms and peripheral immunological markers.

Method: Second-generation radioligand [F]-PBR111 TSPO PET-CT was used for longitudinal dynamic imaging in 14 male psychosis patients and 17 male age-matched healthy control subjects.

Assessment of cognitive-driven activity of daily living impairment in non-demented Parkinson's patients.

The core criterion for Parkinson's disease dementia (PDD) is the impairment in activities of daily living (ADL) function primarily caused by cognitive, not motor symptoms. There is evidence to assume that mild ADL impairments in mild cognitive impairment (PD-MCI) characterize those patients at high risk for dementia. Data of 216 Parkinson's disease (PD) patients assessed with comprehensive motor and neuropsychological assessments were analysed.

Clinical pharmacokinetics, pharmacodynamics, safety, and tolerability of JNJ-54175446, a brain permeable P2X7 antagonist, in a randomised single-ascending dose study in healthy participants.

Background: Central nervous system-derived interleukin-1β plays a role in mood disorders. P2X7 receptor activation by adenosine-triphosphate leads to the release of interleukin-1β.

Aims: This first-in-human study evaluated safety, tolerability, pharmacokinetics and pharmacodynamics of a novel central nervous system-penetrant P2X7 receptor antagonist, JNJ-54175446, in healthy participants.

Multiple daytime administration of the selective orexin-2 receptor antagonist JNJ-42847922 induces somnolence in healthy subjects without residual central effects.

Background: Pharmacokinetics, pharmacodynamics and general safety and tolerability of JNJ-42847922, a selective orexin-2 receptor antagonist, were assessed in healthy subjects.

Methods: Five consecutive cohorts of healthy subjects were enrolled and received doses of 5-60 mg orally once daily over 10 days of JNJ-42847922 ( n=6) or placebo ( n=2). Concentrations of drug in plasma and urine were measured over 24 h after dosing on Days 1, 5 and 10.

Pharmacodynamics of atabecestat (JNJ-54861911), an oral BACE1 inhibitor in patients with early Alzheimer's disease: randomized, double-blind, placebo-controlled study.

Background: β-Secretase enzyme (BACE) inhibition has been proposed as a priority treatment mechanism for Alzheimer's disease (AD), but treatment initiation may need to be very early. We present proof of mechanism of atabecestat (also known as JNJ-54861911), an oral BACE inhibitor for the treatment of AD, in Caucasian and Japanese populations with early AD who do not show signs of dementia.

Methods: In two similarly designed phase I studies, a sample of amyloid-positive elderly patients comprising 45 Caucasian patients with early AD diagnosed as preclinical AD (n = 15, Clinical Dementia Rating [CDR] = 0) or with mild cognitive impairment due to AD (n = 30, CDR = 0.

Validation of a novel Montreal Cognitive Assessment scoring algorithm in non-demented Parkinson's disease patients.

Introduction: The early diagnosis of mild cognitive impairment (PD-MCI) in Parkinson's disease (PD) is essential as it increases the future risk for PD dementia (PDD). Recently, a novel weighting algorithm for the Montreal Cognitive Assessment (MoCA) subtests has been reported, to best discriminate between those with and without cognitive impairment in PD. The aim of our study was to validate this scoring algorithm in a large sample of non-demented PD patients, hypothesizing that the weighted MoCA would have a higher diagnostic accuracy for PD-MCI than the original MoCA.