Nationwide Retrospective Analysis of Combinations of Advanced Therapies in Patients With Parkinson Disease.

BACKGROUND AND OBJECTIVES: Advanced therapies (ATs; deep brain stimulation [DBS] or pump therapies: continuous subcutaneous apomorphine infusion [CSAI], levodopa/carbidopa intestinal gel [LCIG]) are used in later stages of Parkinson disease (PD). However, decreasing efficacy over time and/or side effects may require an AT change or combination in individual patients. Current knowledge about changing or combining ATs is limited to mostly retrospective and small-scale studies. The nationwide case collection Combinations of Advanced Therapies in PD assessed simultaneous or sequential AT combinations in Germany since 2005 to analyze their clinical outcome, their side effects, and the reasons for AT modifications. METHODS: Data were acquired retrospectively by modular questionnaires in 22 PD centers throughout Germany based on clinical records and comprised general information about the centers/patients, clinical (Mini-Mental Status Test/Montréal Cognitive Assessment, Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale [MDS-UPDRS], side effects, reasons for AT modification), and therapeutical (ATs with specifications, oral medication) data. Data assessment started with initiation of the second AT. RESULTS: A total of 148 AT modifications in 116 patients were associated with significantly improved objective (median decrease of MDS-UPDRS Part III 4.0 points [p < 0.001], of MDS-UPDRS Part IV 6.0 points [p < 0.001], of MDS-UPDRS Part IV-off-time item 1.0 points [p < 0.001]) and subjective clinical outcome and decreasing side effect rates. Main reasons for an AT modification were insufficient symptom control and side effects of the previous therapy. Subgroup analyses suggest addition of DBS in AT patients with leading dyskinesia, addition of LCIG for leading other cardinal motor symptoms, and addition of LCIG or CSAI for dominant off-time. The most long-lasting therapy-until requiring a modification-was DBS. DISCUSSION: Changing or combining ATs may be beneficial when 1 AT is insufficient in efficacy or side effects. The outcome of an AT combination is comparable with the clinical benefit by introducing the first AT. The added AT should be chosen dependent on dominant clinical symptoms and adverse effects. Furthermore, prospective trials are needed to confirm the results of this exploratory case collection. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that, in patients with PD, changing or combining ATs is associated with an improvement in the MDS-UPDRS or subjective symptom reporting.

Method to Measure Surface Tension of Microdroplets Using Standard AFM Cantilever Tips.

Surface tension is a physical property that is central to our understanding of wetting phenomena. One could easily measure liquid surface tension using commercially available tensiometers (e.g., Wilhelmy plate method) or by optical imaging (e.g., pendant drop method). However, such instruments are designed for bulk liquid volumes on the order of milliliters. In order to perform similar measurements on extremely small sample volumes in the range of femtoliters, atomic force microscope (AFM) is considered as a promising tool. It was previously reported that by fabricating a special "nanoneedle"-shaped cantilever probe, a Wilhelmy-like experiment can be performed with AFM. By measuring the capillary force between such special probes and a liquid surface, surface tension could be calculated. Here, we carried out measurements on microscopic droplets with AFM, but instead, using standard pyramidal cantilever tips. The cantilevers were coated with a hydrophilic polyethylene glycol-based polymer brush in a simple one-step process, which reduced its contact angle hysteresis for most liquids. Numerical simulations of a liquid drop interacting with a pyramidal or conical geometry were used to calculate surface tension from the experimentally measured force. The results on micrometer-sized drops agree well with bulk tensiometer measurement of three test liquids (mineral oil, ionic liquid, and glycerol), within a maximum error of 10%. Our method eliminates the need for specially fabricated "nanoneedle" tips, thus reducing the complexity and cost of measurement.

Association of age-related declined renal function and osteoporosis based on trabecular bone score in Bushehr Elderly Health (BEH) program.

PURPOSE: Osteoporosis is a systemic disease characterized by decreased bone strength and an increased risk of fracture in old age. Age and pathologic renal failure are independent risk factors for osteoporosis. However, it is not determined whether age-related decreased renal function, in the context of senescence, can be considered as an independent risk factor for osteoporosis. Therefore, this study was conducted to evaluate the effect of senescence-induced renal failure on bone quality and trabecular bone score. METHODS: This study used a cross-sectional design and was carried out based on data collected during the Bushehr Elderly Health (BEH) program, Phase II. A total of 2,125 elderly participants aged over 60 years old entered the study after meeting the inclusion criteria and providing informed consent. They underwent examinations for weight, height, abdominal and hip circumference, as well as blood pressure measurement. All participants also underwent DXA to assess bone mass density (BMD). Trabecular bone score (TBS) was calculated using the DXA apparatus software output. Univariate and adjusted multivariate linear regression analyses were used to evaluate the associations. RESULTS: In the univariate linear regression analysis, there was a direct correlation between age-related renal failure and TBS (ß = 0.038, p < 0.0001), neck of femur BMD (ß = 0.047, p < 0.0001), and lumbar BMD (ß = 0.055, p < 0.0001). However, after adjusting for BMI, age, sex, smoking, and physical activity, no significant association was observed for these variables. CONCLUSION: It is hypothesized that age-related renal failure cannot be considered as an independent risk factor for osteoporosis in elderly individuals aged over 60 years old.

Dynamic wetting properties of PDMS pseudo-brushes: Four-phase contact point dynamics case.

We investigate the wetting properties of PDMS (Polydimethylsiloxane) pseudo-brush anchored on glass substrates. These PDMS pseudo-brushes exhibit a significantly lower contact angle hysteresis compared to hydrophobic silanized substrates. The effect of different molar masses of the used PDMS on the wetting properties seems negligible. The surface roughness and thickness of the PDMS pseudo-brush are measured by atomic force microscopy and x-ray reflectivity. The outcome shows that these surfaces are extremely smooth (topologically and chemically), which explains the reduction in contact angle hysteresis. These special features make this kind of surfaces very useful for wetting experiments. Here, the dynamics of the four-phase contact point are studied on these surfaces. The four-phase contact point dynamics on PDMS pseudo-brushes deviate substantially from its dynamics on other substrates. These changes depend only a little on the molar mass of the used PDMS. In general, PDMS pseudo-brushes increase the traveling speed of four-phase contact point on the surface and change the associated power law of position vs time.

Ultrasound of the Biceps Muscle in Idiopathic Parkinson's Disease with Deep Brain Stimulation: Rigidity Can Be Quantified by Shear Wave Elastography.

Rigidity in Parkinson's disease (PD) is assessed by clinical scales, mostly the Unified Parkinson's Disease Rating Scale of the Movement Disorders Society (MDS-UPDRS). While the MDS-UPDRS-III ranges on an integer from 0 to 4, we investigated whether muscle ultrasound shear wave elastography (SWE) offers a refined assessment. Ten PD patients (five treated with deep brain stimulation (DBS) and levodopa, five with levodopa only) and ten healthy controls were included. Over a period of 80 min, both the SWE value and the item 22b-c of the MDS-UPDRS-III were measured at 5 min intervals. The measurements were performed bilaterally at the biceps brachii muscle (BB) and flexor digitorum profundus muscle in flexion and passive extension. Rigidity was modified and tracked under various therapeutic conditions (with and without medication/DBS). The feasibility of SWE for objective quantification was evaluated by correlation with the UPDRS-III: considering all positions and muscles, there was already a weak correlation (r = 0.01, p < 0.001)­in a targeted analysis, the BB in passive extension showed a markedly higher correlation (r = 0.494, p < 0.001). The application of dopaminergic medication and DBS resulted in statistically significant short-term changes in both clinical rigidity and SWE measurements in the BB (p < 0.001). We conclude that rigidity is reflected in the SWE measurements, indicating that SWE is a potential non-invasive quantitative assessment tool for PD.

Neuropharmaceutical Properties of Naringin Against Alzheimer's and Parkinson's Diseases: Naringin Protection Against AD and PD.

Neurological complications are considered the leading cause of disability and the second cause of death worldwide. Although the most common neurological disorders affecting a large population are Alzheimer's (AD) and Parkinson's diseases (PD), no definitive treatment has been propounded in the clinic. As in recent years, special attention has been paid to medicinal herbal products as one of the ways to meet the challenges of treating diseases. This review study aimed to introduce the naringin neuroprotective effects as an abundant flavonoid in grapes and citrus fruits on the most common neurological disorders, including AD and PD. For this purpose, the specified keywords were searched in PubMed, Web of Science, Scopus, Embase, and Google Scholar, and the results were entered into the study after a concise overview. The findings show naringin can confront neurological disorders through several mechanisms such as modulating stress response pathways, preventing apoptosis, oxidative stress, and neuroinflammation, excessive chelating amounts of metal ions, thereby improving cognitive impairment and memory loss induced by neurological disorders. However, further studies, particularly on human, are critical for the final confirmation of obtained findings. [GMJ.2022;11:e2337].

Case Report: Deep brain stimulation improves tremor in FGF-14 associated spinocerebellar ataxia.

Objectives: Spinocerebellar ataxia 27 (SCA 27) is a rare heredodegenerative disorder caused by mutations in the fibroblast growth factor 14 (FGF14) and characterized by early-onset tremor and progressive ataxia later during the disease course. We investigated the effect of deep brain stimulation (DBS) of the ventralis intermedius nucleus of the thalamus (VIM) and subthalamic projections on tremor and ataxia. Methods: At baseline, we studied the effects of high-frequency VIM stimulation and low-frequency stimulation of subthalamic projections on tremor and ataxia. The patient then adopted the best individual high-frequency stimulation programme at daytime and either 30 Hz-stimulation of the subthalamic contacts or StimOFF at night during two separate 5-weeks follow-up intervals. Both patient and rater were blinded to the stimulation settings. Results: High-frequency stimulation of the VIM effectively attenuated tremor. At follow-up, intermittent 30 Hz-stimulation at night resulted in a superior tremor response compared to StimOFF at night. Ataxia was not affected. Discussion: Stimulation of the VIM and adjacent subthalamic projections effectively attenuated tremor in a patient with confirmed SCA 27. Cycling between daytime high-frequency and night-time low-frequency stimulation led to a more sustained tremor response. This suggests to study in future if low-frequency stimulation of the subthalamic projection fibers may help overcome tolerance of tremor that is observed as a long-term limitation of VIM-DBS.

Evaluation of Mental Health and Related Factors among Patients with Beta-thalassemia Major in South East of Iran.

OBJECTIVE: Beta-thalassemia major (ß-TM) is a chronic, genetic and hematological disorder. Children and teenagers with chronic physical illnesses exemplified by thalassemia are vulnerable to emotional and behavioral problems. The aim of this study was to evaluate mental health and its related factors among young patients with beta-thalassemia major. METHODS: In this cross-sectional observational descriptive-analytic study, we studied 164 patients suffering from Beta-thalassemia major with age range of 15-24 years who referred for treatment to Ali Ebn-e Abitaleb (AS) University Hospital in Zahedan, a city in South East of Iran, during 2009-2010. The demographic data and pattern of mental health were collected by standard general health questionnaire (GHQ-28).Data was analyzed using statistical software SPSS (version 17.0); Student t test and Chi-square (χ2) were used. RESULTS: In this study, 96 (58.5%) patients were male; the mean age of all patients was 18.78 ±2.28. Based on data analysis, 83 patients (50.8%) suspected to have psychiatric disorders (58.8% of girls, 44.8% of boys). In addition, frequency of somatic symptoms, depression disorder, anxiety disorder and social dysfunction in all patients were 7.3%, 11.6%, 8.5% and 4.3% respectively. In illiterate patients, 70.4% suspected to have psychiatric disorder. Except for somatic disorder, other mental disorders were more frequent in girls. No significant association was found between mental state and gender, marital and literacy status and occupation. CONCLUSION: In this study, due to high prevalence of psychological disorders in young patients with Beta-thalassemia major, especially in girls, we suggest implementing further educational psychological programs to decrease the frequency of disorders. Moreover, conducting more quantitative and comprehensive researches is suggested to evaluate specific effective factors in psycho-social health.