Switch from oral pramipexole or ropinirole to rotigotine transdermal system in advanced Parkinson’s disease: an open-label study

Objective: Investigate safety, feasibility and efficacy of switching therapy in patients with advanced-stage Parkinson’s disease (PD) inadequately controlled with pramipexole (≤ 3.5 mg/day) or ropinirole (≤ 14 mg/day) to rotigotine transdermal system (≤ 14 mg/24 h; dose adjustments ≤ 16 mg/24 h permitted).

Methods: PD0009 (ClinicalTrials.gov: NCT01711866) was an open-label study in patients with advanced-stage PD receiving levodopa, and experiencing sleep disturbance or early-morning motor impairment. Pramipexole/ropinirole was switched to equivalent dose rotigotine overnight or in two stages. During the 4-week treatment period rotigotine dose adjustments were permitted (up to 16 mg/24 h). Primary variable: Clinical Global Impressions (CGI) item 4: side effects (assessing safety) at end of treatment.

Results: 79/87 (91%) patients completed the study; 2 (2%) withdrew due to adverse events (AEs). Most (84; 97%) had CGI item 4 score < 3 indicating switch did not interfere with functioning; three experienced drug-related AEs interfering with functioning (score = 3). 62% patients improved on Patient Global Impression of Change, assessing effectiveness. AEs occurring ≥ 5%: application site pruritus (10%), application site erythema (7%), dizziness (7%), dyskinesia (7%), erythema (6%), pruritus (6%). Unified Parkinson’s Disease Rating Scale II and III, Parkinson’s Disease Sleep Scale-2 and Pittsburgh Sleep Quality Index were unchanged. Numerical improvements in ‘off’ time, awakenings and nocturias were observed.

Conclusions: Switch from pramipexole or ropinirole to rotigotine (up to 14 mg/24 h) was feasible and possibly associated with some benefit.     

The Role of Muscarinic Receptors in the Pathophysiology of Mood Disorders: A Potential Novel Treatment?

The central cholinergic system has been implicated in the pathophysiology of mood disorders. An imbalance in central cholinergic neurotransmitter activity has been proposed to contribute to the manic and depressive episodes typical of these disorders. Neuropharmacological studies into the effects of cholinergic agonists and antagonists on mood state have provided considerable support for this hypothesis. Furthermore, recent clinical studies have shown that the pan-CHRM antagonist, scopolamine, produces rapid-acting antidepressant effects in individuals with either major depressive disorder (MDD) or bipolar disorder (BPD), such as bipolar depression, contrasting the delayed therapeutic response of conventional mood stabilisers and antidepressants. This review presents recent data from neuroimaging, post-mortem and genetic studies supporting the involvement of muscarinic cholinergic receptors (CHRMs), particularly CHRM2, in the pathophysiology of MDD and BPD. Thus, novel drugs that selectively target CHRMs with negligible effects in the peripheral nervous system might produce more rapid and robust clinical improvement in patients with BPD and MDD.     

Plasma dilution improves cognition and attenuates neuroinflammation in old mice

Our recent study has established that young blood factors are not causal, nor necessary, for the systemic rejuvenation of mammalian tissues. Instead, a procedure referred to as neutral blood exchange (NBE) that resets signaling milieu to a pro-regenerative state through dilution of old plasma, enhanced the health and repair of the muscle and liver, and promoted better hippocampal neurogenesis in 2-year-old mice (Mehdipour et al., Aging 12:8790–8819, 2020). Here we expand the rejuvenative phenotypes of NBE, focusing on the brain. Namely, our results demonstrate that old mice perform much better in novel object and novel texture (whisker discrimination) tests after a single NBE, which is accompanied by reduced neuroinflammation (less-activated CD68⁺ microglia). Evidence against attenuation/dilution of peripheral senescence-associated secretory phenotype (SASP) as the main mechanism behind NBE was that the senolytic ABT 263 had limited effects on neuroinflammation and did not enhance hippocampal neurogenesis in the old mice. Interestingly, peripherally acting ABT 263 and NBE both diminished SA-βGal signal in the old brain, demonstrating that peripheral senescence propagates to the brain, but NBE was more robustly rejuvenative than ABT 263, suggesting that rejuvenation was not simply by reducing senescence. Explaining the mechanism of the positive effects of NBE on the brain, our comparative proteomics analysis demonstrated that dilution of old blood plasma yields an increase in the determinants of brain maintenance and repair in mice and in people. These findings confirm the paradigm of rejuvenation through dilution of age-elevated systemic factors and extrapolate it to brain health and function.

     

The Impact of Economic Pressure on Parent Positivity,Parenting, and Adolescent Positivity into Emerging Adulthood

This study describes how positivity can be incorporated into the family stress model to explain resilience to disrupted family processes in the face of economic distress. Prospective, longitudinal data came from 451 mothers, fathers, and youth participating from their adolescence through early adulthood. Assessments included observational and self‐report measures. Information regarding economic pressure, parental positivity, and parenting were collected during early adolescence, positivity was collected in late adolescence and emerging adulthood. Results indicated that economic pressure was indirectly associated with adolescent positivity through parental positivity. Economic pressure was negatively associated with parent positivity, whereas parental positivity was positively associated with parenting. Moreover, parental positivity and parenting were related to positivity in adolescence. Results suggest that personal resources linked to a positive outlook can foster nurturant parenting, even in times of economic strain. Such parenting seems to positively influence adolescent development into emerging adulthood.     

Sonographic diagnosis of neuritis ossificans of the median nerve

We report the sonographic appearance of a rare case of neuritis ossificans of the median nerve at the wrist, which appeared as a hyperechoic lesion around the nerve. Diagnosis was confirmed with magnetic resonance imaging (MRI).     

Best Core Stabilization for Anticipatory Postural Adjustment and Falls in Hemiparetic Stroke

Objectives

To compare the effects of conventional core stabilization and dynamic neuromuscular stabilization (DNS) on anticipatory postural adjustment (APA) time, balance performance, and fear of falls in chronic hemiparetic stroke.

Virtual Reality Rehabilitation With Functional Electrical Stimulation Improves Upper Extremity Function in Patients With Chronic Stroke: A Pilot Randomized Controlled Study

Objective

To compare virtual reality (VR) combined with functional electrical stimulation (FES) with cyclic FES for improving upper extremity function and health-related quality of life in patients with chronic stroke.

Reliability and criterion validity of measurements using a smart phone-based measurement tool for the transverse rotation angle of the pelvis during single-leg lifting

Objective: The purposes of this study were to determine the intra-rater test–retest reliability of a smart phone-based measurement tool (SBMT) and a three-dimensional (3D) motion analysis system for measuring the transverse rotation angle of the pelvis during single-leg lifting (SLL) and the criterion validity of the transverse rotation angle of the pelvis measurement using SBMT compared with a 3D motion analysis system (3DMAS). Method: Seventeen healthy volunteers performed SLL with their dominant leg without bending the knee until they reached a target placed 20 cm above the table. This study used a 3DMAS, considered the gold standard, to measure the transverse rotation angle of the pelvis to assess the criterion validity of the SBMT measurement. Intra-rater test–retest reliability was determined using the SBMT and 3DMAS using intra-class correlation coefficient (ICC) [3,1] values. The criterion validity of the SBMT was assessed with ICC [3,1] values. Result: Both the 3DMAS (ICC = 0.77) and SBMT (ICC = 0.83) showed excellent intra-rater test–retest reliability in the measurement of the transverse rotation angle of the pelvis during SLL in a supine position. Moreover, the SBMT showed an excellent correlation with the 3DMAS (ICC = 0.99). Conclusion: Measurement of the transverse rotation angle of the pelvis using the SBMT showed excellent reliability and criterion validity compared with the 3DMAS.     

Hepatoprotective Effect of Herb Formula KIOM2012H against Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is a hepatic ailment with a rapidly increasing incidence due to dietary hypernutrition and subsequent obesity. Fatty liver disease can lead to steatohepatitis, fibrosis, cirrhosis, and even cancer, which is associated with various complications. Discovering effective natural materials and herbs can provide alternative and complementary medical treatments to current chemical pharmaceuticals. To develop an effective natural agent for NAFLD, we formulated a combination of four herb mixtures (KIOM2012H) and observed lipid-lowering efficacy. The inhibitory effects of KIOM2012H on free fatty acid-induced lipid accumulation, triglyceride contents, and gene expressions were analyzed in HepG2 cells. Using high fat diet-fed mice, body weight changes, gross liver appearances, hepatic triglyceride contents, and gene expressions were evaluated. KIOM2012H dose-dependently inhibited lipid accumulation and gene expressions involved in lipogenesis and related regulators. Experimental animals also showed a decrease in body weight changes and lipid-associated physiological parameters. This study shows that KIOM2012H has an alleviating effect on fatty acid and lipid accumulation, and therefore can be applied for development of new therapeutic pharmaceuticals for treatment of NAFLD using natural products and herbs.