Motor complications in Parkinson’s disease:results from 3,343 patients followed for up to 12 years

Background: Motor complications are well recognised in Parkinson’s disease (PD), but their reported prevalence varies and functional impact has not been well studied. Objectives: To quantify the presence, severity, impact and associated factors for motor complications in PD.Methods: Analysis of 3 large prospective cohort studies of recent-onset PD patients followed for up to 12 years. The MDS-UPDRS part 4 assessed motor complications and multivariable logistic regression tested for associations. Genetic risk score (GRS) for Parkinson’s was calculated from 79 single nucleotide polymorphisms. Results: 3,343 cases were included (64.7% male). Off periods affected 35.0% (95% CI 33.0, 37.0) at 4-6 years and 59.0% (55.6, 62.3) at 8-10 years. Dyskinesia affected 18.5% (95% CI 16.9, 20.2) at 4-6 years and 42.1% (38.7, 45.5) at 8-10 years. Dystonia affected 13.4% (12.1, 14.9) at 4-6 years and 22.8% (20.1, 25.9) at 8-10 years. Off periods consistently caused greater functional impact than dyskinesia. Motor complications were more common among those with higher drug doses, younger age at diagnosis, female gender, and greater dopaminergic responsiveness (in challenge tests), with associations emerging 2 to 4 years post-diagnosis. Higher Parkinson’s GRS was associated with early dyskinesia (0.026 ≤ P ≤ 0.050 from 2 to 6 years).Conclusions: Off periods are more common and cause greater functional impairment than dyskinesia. We confirm previously reported associations between motor 4 complications with several demographic and medication factors. Greater dopaminergic responsiveness and a higher genetic risk score are two novel and significant independent risk factors for the development of motor complications

Ultra-high-field arterial spin labeling MRI for non-contrast assessment of cortical lesion perfusion in multiple sclerosis

ObjectivesAssess the feasibility of using an optimised ultra-high-field high-spatial-resolution low-distortion ASL MRI acquisition to measure focal haemodynamic pathology in cortical lesions (CLs) in Multiple Sclerosis (MS).MethodsTwelve MS patients (8 female, mean age=50; range=35-64 years) gave informed consent and were scanned on a 7 Tesla Philips Achieva scanner. Perfusion data were collected at multiple post-labeling delay times using a single-slice flow-sensitive alternating inversion recovery ASL protocol with a balanced steady-state free precession readout scheme. CLs were identified using a high-resolution Phase-Sensitive Inversion Recovery (PSIR) scan. Significant differences in perfusion within CLs compared to immediately surrounding normal appearing grey matter (NAGMlocal) and total cortical normal appearing grey matter (NAGMcortical) were assessed using paired t-tests.Results40 CLs were identified in PSIR scans that overlapped with the ASL acquisition coverage. After excluding lesions due to size or intravascular contamination, 27 lesions were eligible for analysis. Mean perfusion was 40 ± 25 ml/100g/min in CLs, 53 ± 12 ml/100g/min in NAGMlocal, and 53±8 ml/100g/min in NAGMcortical. CL perfusion was significantly reduced by 23 ± 9% (mean±SE, p=0.013) and 26 ± 9% (mean±SE, p=0.006) relative to NAGMlocal and NAGMcortical perfusion, respectively.ConclusionThis is the first ASL MRI study quantifying CL perfusion in MS at 7T, demonstrating that an optimised ASL acquisition is sensitive to focal haemodynamic pathology previously observed using Dynamic Susceptibility Contrast MRI. ASL requires no exogenous contrast agent, making it a more appropriate tool to monitor longitudinal perfusion changes in MS, providing a new window to study lesion development

A Comparison Study on the Improved Operation Strategy for a Parabolic trough Solar Power Plant in Spain

The present work focuses on the development of a detailed dynamic model of an existing parabolic trough solar power plant (PTSPP) in Spain. This work is the first attempt to analyse the dynamic interaction of all parts, including solar field (SF), thermal storage system (TSS) and power block (PB), and describes the heat transfer fluid (HTF) and steam/water paths in detail. Advanced control circuits, including drum level, economiser water bypass, attemperator and steam bypass controllers, are also included. The parabolic trough power plant is modelled using Advanced Process Simulation Software (APROS). An accurate description of control structures and operation strategy is necessary in order to achieve a reasonable dynamic response. This model would help to identify the best operation strategy due to DNI (direct normal irradiation) variations during the daytime. The operation strategy used in this model has also been shown to be effective compared to decisions made by operators on cloudy periods by improving power plant performance and increasing operating hours

Ultra-high-field arterial spin labeling MRI for non-contrast assessment of cortical lesion perfusion in multiple sclerosis

Objectives Assess the feasibility of using an optimised ultra-high-field high-spatial-resolution low-distortion ASL MRI acquisition to measure focal haemodynamic pathology in cortical lesions (CLs) in Multiple Sclerosis (MS). Methods Twelve MS patients (8 female, mean age=50; range=35-64 years) gave informed consent and were scanned on a 7 Tesla Philips Achieva scanner. Perfusion data were collected at multiple post-labeling delay times using a single-slice flow-sensitive alternating inversion recovery ASL protocol with a balanced steady-state free precession readout scheme. CLs were identified using a high-resolution Phase-Sensitive Inversion Recovery (PSIR) scan. Significant differences in perfusion within CLs compared to immediately surrounding normal appearing grey matter (NAGMlocal) and total cortical normal appearing grey matter (NAGMcortical) were assessed using paired t-tests. Results 40 CLs were identified in PSIR scans that overlapped with the ASL acquisition coverage. After excluding lesions due to size or intravascular contamination, 27 lesions were eligible for analysis. Mean perfusion was 40 ± 25 ml/100g/min in CLs, 53 ± 12 ml/100g/min in NAGMlocal, and 53±8 ml/100g/min in NAGMcortical. CL perfusion was significantly reduced by 23 ± 9% (mean±SE, p=0.013) and 26 ± 9% (mean±SE, p=0.006) relative to NAGMlocal and NAGMcortical perfusion, respectively. Conclusion This is the first ASL MRI study quantifying CL perfusion in MS at 7T, demonstrating that an optimised ASL acquisition is sensitive to focal haemodynamic pathology previously observed using Dynamic Susceptibility Contrast MRI. ASL requires no exogenous contrast agent, making it a more appropriate tool to monitor longitudinal perfusion changes in MS, providing a new window to study lesion development

Adherence to antidiabetic medication during the month of Ramadan among diabetes mellitus patients in the kingdom of Saudi Arabia

Background: Ramadan may lead to reduced adherence to antidiabetic medications among Saudi diabetes patients due to fasting, changes in daily routine, social and cultural influences, health risks, and inadequate awareness. This study aimed to assess the Saudi population adherence to the diabetes management medication in Ramadan. Methodology: A convenience sampling method was used to recruit participants for the study. Participants were sourced from social media platforms, diabetes mellitus patient groups, and healthcare providers groups. The Medication Adherence Rating Scale (MARS), a tool, was used to assess medication compliance. Results: A total of 384 individuals were included in this study, 20.3% were from Riyadh, 52.3% were males, 35% aged 31-50 years, and 64.1% had type 2 diabetes mellitus of participants. Age between 31-50 years was negatively associated with compliance (β = -1.06, p = 0.002), while age between 51-65 years is positively associated ((β= 1.00, p = 0.003). Being male was negatively associated with compliance (β= -0.72, p = 0.001). Different fasting behaviors like non-fasting one day or more (β = -2.92, p < 0.001) and fasting all month (β = -2.90, p < 0.001), significantly affect compliance scores with negative associations indicating lower compliance during fasting periods. Various HbA1c levels were significant predictors of compliance. Higher HbA1c levels were associated with increased compliance. Conclusions: The study reveals that age, gender, fasting behaviors and HbA1c levels significantly impact medication compliance among patients with diabetes mellitus during Ramadan

J. Med. Genet.

Background: Primary microcephaly (MCPH) is a genetically heterogeneous disorder showing an autosomal recessive mode of inheritance. Affected individuals present with head circumferences more than three SDs below the age- and sex-matched population mean, associated with mild to severe mental retardation. Five genes (MCPH1, CDK5RAP2, ASPM, CENPJ, STIL) and two genomic loci, MCPH2 and MCPH4, have been identified so far. Methods and results: In this study, we investigated all seven MCPH loci in patients with primary microcephaly from 112 Consanguineous Iranian families. In addition to a thorough clinical characterisation, karyotype analyses were performed for all patients. For Homozygosity mapping, microsatellite markers were selected for each locus and used for genotyping. Our investigation enabled us to detect homozygosity at MCPH1 (Microcephalin) in eight families, at MCPH5 (ASPM) in thirtheen families. Three families showed homozygosity at MCPH2 and five at MCPH6 (CENPJ), and two families were linked to MCPH7 (STIL). The remaining 81 families were not linked to any of the seven known loci. Subsequent sequencing revealed eight, 10 and one novel mutations in Microcephalin, ASPM and CENPJ, respectively. In some families, additional features such as short stature, seizures or congenital hearing loss were observed in the microcephalic patient, which widens the spectrum of clinical manifestations of mutations in known microcephaly genes. Conclusion: Our results show that the molecular basis of microcephaly is heterogeneous; thus, the Iranian population may provide a unique source for the identification of further genes underlying this disorder

CD271-selected mesenchymal stem cells from adipose tissue enhance cartilage repair and are less angiogenic than plastic adherent mesenchymal stem cells

CD271 is a marker of bone marrow MSCs with enhanced differentiation capacity for bone or cartilage repair. However, the nature of CD271+ MSCs from adipose tissue (AT) is less well understood. Here, we investigated the differentiation, wound healing and angiogenic capacity of plastic adherent MSCs (PA MSCs) versus CD271+ MSCs from AT. There was no difference in the extent to which PA MSCs and CD271+ MSCs formed osteoblasts, adipocytes or chondrocytes in vitro. In contrast, CD271+ MSCs transplanted into athymic rats significantly enhanced osteochondral wound healing with reduced vascularisation in the repair tissue compared to PA MSCs and control animals; there was little histological evidence of mature articular cartilage formation in all animals. Conditioned medium from CD271+ MSC cultures was less angiogenic than PA MSC conditioned medium, and had little effect on endothelial cell migration or endothelial tubule formation in vitro. The low angiogenic activity of CD271+ MSCs and improved early stage tissue repair of osteochondral lesions when transplanted, along with a comparable differentiation capacity along mesenchymal lineages when induced, suggests that these selected cells are a better candidate than PA MSCs for the repair of cartilaginous tissue

Effects of L-asparginase administration on anticoagulant proteins and platelet function in patients with acute lymphoblastic leukemia

Introduction: Acute lymphoblastic leukemia is one the most common malignancies in children and adolescents. L-asparginase (L-ASP) is one of the leading medications in treatment of ALL. L.ASP interferes with the synthesis of some coagulation proteins and therefore causing disturbance in normal coagulation. In this study, the effects of L-ASP on anticoagulant proteins (protein C, protein S, and antithrombin III) and platelet function were assessed. Material and methods: This was a before-after study on 41 patients with ALL who refered to Mahak hospital (Tehran, Iran). Before and after the injection of L.ASP, a bleeding time test was performed based on Ivy method. Protein C and protein S performance was assessed by turbidometry and antithrombin III performance was evaluated by chromogenic method. Results: 48.8 of patients were female. Mean (±SD) of age was 4.0±7.2. A significant reduction in the mean amount of protein C, antithrombin III and bleeding time was recorded. However, the reduction in protein S was not significant. No patient showed the symptoms of thrombosis. Conclusion: The results of this study showed that L. ASP drug reduced coagulation proteins (except the protein S). This decrease along with other concomitant genetic factors can lead to thrombosis in some patients with ALL during induction therapy