Adaptations to Postural Perturbations in Patients With Freezing of Gait

Introduction: Freezing of gait (FOG) is a powerful determinant of falls in Parkinson's disease (PD). Automatic postural reactions serve as a protective strategy to prevent falling after perturbations. However, differences in automatic postural reactions between patients with and without FOG in response to perturbation are at present unclear. Therefore, the present study aimed to compare the response patterns and neuromuscular control between PD patients with and without FOG and healthy controls (HCs) after postural perturbations.Methods: 28 PD patients (15 FOG+, 13 FOG−) and 22 HCs were included. Participants stood on a moveable platform while random perturbations were imposed. The first anterior platform translation was retained for analysis. Center of pressure (CoP) and center of mass (CoM) trajectories and trunk, knee and ankle angles were compared between the three groups using the Statistical Parametric Mapping technique, allowing to capture changes in time. In addition, muscle activation of lower leg muscles was measured using EMG.Results: At baseline, FOG+ stood with more trunk flexion than HCs (p = 0.005), a result not found in FOG−. Following a perturbation, FOG+ reacted with increased trunk extension (p = 0.004) in comparison to HCs, a pattern not observed in FOG−. The CoM showed greater backward displacement in FOG− and FOG+ (p = 0.008, p = 0.027). Both FOG+ and FOG− showed increased co-activation of agonist and antagonist muscles compared to HCs (p = 0.010), with no differences between FOG+ and FOG−.Conclusions: Automatic postural reactions after a sudden perturbation are similar between PD subgroups with and without FOG but different from HCs. Reactive postural control, largely regulated by brain stem centers, seems to be modulated by different mechanisms than those governing freezing of gait. Greater differences in initial stance position, enhanced by joint stiffening, could however underlie maladaptive postural responses and increase susceptibility for balance loss in FOG+ compared to FOG−

The Treatment of Hallucinations in Schizophrenia Spectrum Disorders

This article reviews the treatment of hallucinations in schizophrenia. The first treatment option for hallucinations in schizophrenia is antipsychotic medication, which can induce a rapid decrease in severity. Only 8% of first-episode patients still experience mild to moderate hallucinations after continuing medication for 1 year. Olanzapine, amisulpride, ziprasidone, and quetiapine are equally effective against hallucinations, but haloperidol may be slightly inferior. If the drug of first choice provides inadequate improvement, it is probably best to switch medication after 2-4 weeks of treatment. Clozapine is the drug of choice for patients who are resistant to 2 antipsychotic agents. Blood levels should be above 350-450 mu g/ml for maximal effect. For relapse prevention, medication should be continued in the same dose. Depot medication should be considered for all patients because nonadherence is high. Cognitive-behavioral therapy (CBT) can be applied as an augmentation to antipsychotic medication. The success of CBT depends on the reduction of catastrophic appraisals, thereby reducing the concurrent anxiety and distress. CBT aims at reducing the emotional distress associated with auditory hallucinations and develops new coping strategies. Transcranial magnetic stimulation (TMS) is capable of reducing the frequency and severity of auditory hallucinations. Several meta-analyses found significantly better symptom reduction for low-frequency repetitive TMS as compared with placebo. Consequently, TMS currently has the status of a potentially useful treatment method for auditory hallucinations, but only in combination with state of the art antipsychotic treatment. Electroconvulsive therapy (ECT) is considered a last resort for treatment-resistant psychosis. Although several studies showed clinical improvement, a specific reduction in hallucination severity has never been demonstrated

Fluorescent tagging of endogenous heme oxygenase-1 in human induced pluripotent stem cells for high content imaging of oxidative stress in various differentiated lineages

Tagging of endogenous stress response genes can provide valuable in vitro models for chemical safety assessment. Here, we present the generation and application of a fluorescent human induced pluripotent stem cell (hiPSC) reporter line for Heme oxygenase-1 (HMOX1), which is considered a sensitive and reliable biomarker for the oxidative stress response. CRISPR/Cas9 technology was used to insert an enhanced green fluorescent protein (eGFP) at the C-terminal end of the endogenous HMOX1 gene. Individual clones were selected and extensively characterized to confirm precise editing and retained stem cell properties. Bardoxolone-methyl (CDDO-Me) induced oxidative stress caused similarly increased expression of both the wild-type and eGFP-tagged HMOX1 at the mRNA and protein level. Fluorescently tagged hiPSC-derived proximal tubule-like, hepatocyte-like, cardiomyocyte-like and neuron-like progenies were treated with CDDO-Me (5.62-1000 nM) or diethyl maleate (5.62-1000 µM) for 24 h and 72 h. Multi-lineage oxidative stress responses were assessed through transcriptomics analysis, and HMOX1-eGFP reporter expression was carefully monitored using live-cell confocal imaging. We found that eGFP intensity increased in a dose-dependent manner with dynamics varying amongst lineages and stressors. Point of departure modelling further captured the specific lineage sensitivities towards oxidative stress. We anticipate that the newly developed HMOX1 hiPSC reporter will become a valuable tool in understanding and quantifying critical target organ cell-specific oxidative stress responses induced by (newly developed) chemical entities.Toxicolog

Perenosins: a new class of anion transporter with anti-cancer activity

A new class of anion transporter named ‘perenosins’ consisting of a pyrrole linked through an imine to either an indole, benzimidazole or indazole is reported. The indole containing members of the perenosin family function as effective transmembrane Cl?/NO3? antiporters and HCl cotransporters in a manner similar to the prodigiosenes. The compounds reduce the viability of MDA-MB-231 and MCF-7

La Abeja montañesa : Periódico de intereses locales: Año XI Número 2176 - 1867 marzo 12

Copia digital. Madrid : Ministerio de Educación, Cultura y Deporte. Subdirección General de Coordinación Bibliotecaria, 201

Anion transport and binding properties of N,N'-(phenylmethylene)dibenzamide based receptors

The anion transport and binding properties of a series of bis-amide based compounds have been studied in POPC lipid bilayers. The compounds display evidence of aggregation in solution with single crystal X-ray crystallographic analysis showing hydrogen bonding between the amide substituents of adjacent receptors in the solid state