Exploring Factors Associated with Falls in Multiple Sclerosis: Insights from a Scoping Review

Rachid Kaddoura,1,* Hanan Faraji,1,* Malek Othman,1 Amin Abu Hijleh,1 Tom Loney,2 Nandu Goswami,3,4 Hani T S Benamer5 1College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates; 2Department of Basic Sciences, College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates; 3Division of Physiology and Pathophysiology, Medical University of Graz, Graz, Austria; 4Center for Space and Aviation Health, College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates; 5Department of Clinical Sciences, College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates*These authors contributed equally to this workCorrespondence: Rachid Kaddoura, PO Box 505055, Dubai, United Arab Emirates, Tel +971 56 686 2555, Email [email protected] Nandu Goswami, Division of Physiology and Pathophysiology, Neue Stiftingtalstrasse 6, D05 Medical University of Graz, Graz, 8010, Austria, Tel +43 316 38573852, Email [email protected]: Multiple sclerosis (MS) is a chronic inflammatory condition that causes demyelination of the central nervous system accompanied by a wide range of symptoms. The high prevalence of falls among patients diagnosed with MS within the initial six months highlights the importance of this issue. The objective of this study is to identify factors associated with falls in MS patients in order to increase awareness and reduce the risk of falls. This scoping review used specific Mesh terms to formulate the literature search around falls and MS using Medline, Google Scholar, Scopus, and Embase search engines. English papers published between 2012 and 2022, studies with a clear definition of falls, McDonald’s diagnostic criteria for MS, and those with Expanded Disability Status Scale (EDSS) or Patient Determined Disease Steps (PDDS) scores were included. Critical data from the selected articles were extracted and classified according to the different factors associated with falls in MS patients. Eighteen articles were included in this review. The most important factors associated with falls in MS patients identified were the severity and progression of the disease, mobility and balance problems, bladder dysfunction, fear of falling, fatigue, and cognitive dysfunction. In conclusion, this scoping review yielded the most common factors associated with falls in patients with MS. Study findings can be used to develop future interventions focusing on improving mobility, proprioception, and balance to decrease fall risk and injury amongst MS patients.Keywords: multiple sclerosis, falls, causes, risk factors, neurological disorder

Clinical learning environments across two different healthcare settings using the undergraduate clinical education environment measure

Data availability: The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.Copyright © The Author(s) 2023. Background: The clinical placements of our medical students are almost equally distributed across private and public sectors. This study aims to assess medical students’ perceptions of their Clinical learning Environment (CLE) across these two different healthcare settings, using the Undergraduate Clinical Education Environment Measure (UCEEM). Methods: 76 undergraduate medical students (Year 5 and 6), were invited to participate. Data were collected using an online UCEEM with additional questions related to demographics and case load exposure. The UCEEM consists of two overarching domains of experiential learning and social participation, with four subdomains of learning opportunities, preparedness, workplace interaction, and inclusion. Results: 38 questionnaires were received. Of 225 responses to the individual UCEEM items, 51 (22.6%) scored a mean of ≥ 4 (range 4-4.5, representing strong areas), 31 (13.7%) scored a mean of ≤ 3 (range 2.1-3, needing attention) and 143 (63.6%) scored a mean of 3.1–3.9 (areas that could be improved). The majority (63%) of the case load exposure responses scored a mean of ≥ 4 (range 4-4.5). Compared to the private sittings, there is a significant reduction in total UCEEM (p = 0.008), preparedness for student entry (p = 0.003), and overarching dimension of social participation (p = 0.000) scores for the public sector. Similarly, both workplace interaction patterns and student inclusion and equal treatment scored significantly lower for the public sector (p = 0.000 and p = 0.011 respectively). Two out of three case load exposure items scored significantly higher for the public sector (p = 0.000). Discussion: The students’ CLE perceptions were generally positive. The lower UCEEM ratings in the public sector items were related to student entry preparedness, workplace interactions, student inclusiveness and workforce equity of treatment. In contrast the students were exposed to more variety and larger number of patients in the public sector. These differences indicated some significantly different learning environments between the two sectors.Not applicable

Generalisability of deep learning models in low-resource imaging settings: A fetal ultrasound study in 5 African countries

Most artificial intelligence (AI) research have concentrated in high-income countries, where imaging data, IT infrastructures and clinical expertise are plentiful. However, slower progress has been made in limited-resource environments where medical imaging is needed. For example, in Sub-Saharan Africa the rate of perinatal mortality is very high due to limited access to antenatal screening. In these countries, AI models could be implemented to help clinicians acquire fetal ultrasound planes for diagnosis of fetal abnormalities. So far, deep learning models have been proposed to identify standard fetal planes, but there is no evidence of their ability to generalise in centres with limited access to high-end ultrasound equipment and data. This work investigates different strategies to reduce the domain-shift effect for a fetal plane classification model trained on a high-resource clinical centre and transferred to a new low-resource centre. To that end, a classifier trained with 1,792 patients from Spain is first evaluated on a new centre in Denmark in optimal conditions with 1,008 patients and is later optimised to reach the same performance in five African centres (Egypt, Algeria, Uganda, Ghana and Malawi) with 25 patients each. The results show that a transfer learning approach can be a solution to integrate small-size African samples with existing large-scale databases in developed countries. In particular, the model can be re-aligned and optimised to boost the performance on African populations by increasing the recall to $0.92 \pm 0.04$ and at the same time maintaining a high precision across centres. This framework shows promise for building new AI models generalisable across clinical centres with limited data acquired in challenging and heterogeneous conditions and calls for further research to develop new solutions for usability of AI in countries with less resources

GluD1, linked to schizophrenia, controls the burst firing of dopamine neurons

Human mutations of the GRID1 gene encoding the orphan delta1 glutamate receptor-channel (GluD1) are associated with schizophrenia but the explicit role of GluD1 in brain circuits is unknown. Based on the known function of its paralog GluD2 in cerebellum, we searched for a role of GluD1 in slow glutamatergic transmission mediated by metabotropic receptor mGlu1 in midbrain dopamine neurons, whose dysfunction is a hallmark of schizophrenia. We found that an mGlu1 agonist elicits a slow depolarizing current in HEK cells co-expressing mGlu1 and GluD1, but not in cells expressing mGlu1 or GluD1 alone. This current is abolished by additional co-expression of a dominant-negative GluD1 dead pore mutant. We then characterized mGlu1-dependent currents in dopamine neurons from midbrain slices. Both the agonist-evoked and the slow postsynaptic currents are abolished by expression of the dominant-negative GluD1 mutant, pointing to the involvement of native GluD1 channels in these currents. Likewise, both mGlu1-dependent currents are suppressed in GRID1 knockout mice, which reportedly display endophenotypes relevant for schizophrenia. It is known that mGlu1 activation triggers the transition from tonic to burst firing of dopamine neurons, which signals salient stimuli and encodes reward prediction. In vivo recordings of dopamine neurons showed that their spontaneous burst firing is abolished in GRID1 knockout mice or upon targeted expression of the dominant-negative GluD1 mutant in wild-type mice. Our results de-orphanize GluD1, unravel its key role in slow glutamatergic transmission and provide insights into how GRID1 gene alterations can lead to dopaminergic dysfunctions in schizophrenia

Frequency and clinical patterns of stroke in Iran - Systematic and critical review

<p>Abstract</p> <p>Background</p> <p>Cerebrovascular disease is the second commonest cause of death, and over a third of stroke deaths occur in developing countries. To fulfil the current gap on data, this systematic review is focused on the frequency of stroke, risk factors, stroke types and mortality in Iran.</p> <p>Methods</p> <p>Thirteen relevant articles were identified by keyword searching of PubMed, Iranmedex, Iranian University index Libraries and the official national data on burden of diseases.</p> <p>Results</p> <p>The publication dates ranged from 1990 to 2008. The annual stroke incidence of various ages ranged from 23 to 103 per 100,000 population. This is comparable to the figures from Arab Countries, higher than sub-Saharan Africa, but lower than developed countries, India, the Caribbean, Latin America, and China. Similarly to other countries, ischaemic stroke was the commonest subtype. Likewise, the most common related risk factor is hypertension in adults, but cardiac causes in young stroke. The 28-day case fatality rate is reported at 19-31%.</p> <p>Conclusions</p> <p>Data on the epidemiology of stroke, its pattern and risk factors from Iran is scarce, but the available data highlights relatively low incidence of stroke. This may reflect a similarity towards the neighbouring nations, and a contrast with the West.</p

The Combination of Homocysteine and C-Reactive Protein Predicts the Outcomes of Chinese Patients with Parkinson's Disease and Vascular Parkinsonism

BACKGROUND: The elevation of plasma homocysteine (Hcy) and C-reactive protein (CRP) has been correlated to an increased risk of Parkinson's disease (PD) or vascular diseases. The association and clinical relevance of a combined assessment of Hcy and CRP levels in patients with PD and vascular parkinsonism (VP) are unknown. METHODOLOGY/PRINCIPAL FINDINGS: We performed a cross-sectional study of 88 Chinese patients with PD and VP using a clinical interview and the measurement of plasma Hcy and CRP to determine if Hcy and CRP levels in patients may predict the outcomes of the motor status, non-motor symptoms (NMS), disease severity, and cognitive declines. Each patient's NMS, cognitive deficit, disease severity, and motor status were assessed by the Nonmotor Symptoms Scale (NMSS), Mini-Mental State Examination (MMSE), the modified Hoehn and Yahr staging scale (H&Y), and the unified Parkinson's disease rating scale part III (UPDRS III), respectively. We found that 100% of patients with PD and VP presented with NMS. The UPDRS III significantly correlated with CRP (P = 0.011) and NMSS (P = 0.042) in PD patients. The H&Y was also correlated with Hcy (P = 0.002), CRP (P = 0.000), and NMSS (P = 0.023) in PD patients. In VP patients, the UPDRS III and H&Y were not significantly associated with NMSS, Hcy, CRP, or MMSE. Strong correlations were observed between Hcy and NMSS as well as between CRP and NMSS in PD and VP. CONCLUSIONS/SIGNIFICANCE: Our findings support the hypothesis that Hcy and CRP play important roles in the pathogenesis of PD. The combination of Hcy and CRP may be used to assess the progression of PD and VP. Whether or not anti-inflammatory medication could be used in the management of PD and VP will produce an interesting topic for further research

The Arab world's contribution to solid waste literature: a bibliometric analysis

BACKGROUND: Environmental and health-related effects of solid waste material are considered worldwide problems. The aim of this study was to assess the volume and impact of Arab scientific output published in journals indexed in the Science Citation Index (SCI) on solid waste. METHODS: We included all the documents within the SCI whose topic was solid waste from all previous years up to 31 December 2012. In this bibliometric analysis we sought to evaluate research that originated from Arab countries in the field of solid waste, as well as its relative growth rate, collaborative measures, productivity at the institutional level, and the most prolific journals. RESULTS: A total of 382 (2.35 % of the overall global research output in the field of solid waste) documents were retrieved from the Arab countries. The annual number of documents published in the past three decades (1982–2012) indicated that research productivity demonstrated a noticeable rise during the last decade. The highest number of articles associated with solid waste was that of Egypt (22.8 %), followed by Tunisia (19.6), and Jordan (13.4 %). the total number of citations over the analysed years at the date of data collection was 4,097, with an average of 10.7 citations per document. The h-index of the citing articles was 31. Environmental science was the most researched topic, represented by 175 (45.8 %) articles. Waste Management was the top active journal. The study recognized 139 (36.4 %) documents from collaborations with 25 non-Arab countries. Arab authors mainly collaborated with countries in Europe (22.5 %), especially France, followed by countries in the Americas (9.4 %), especially the USA. The most productive institution was the American University of Beirut, Lebanon, with 6.3 % of total publications. CONCLUSIONS: Despite the expected increase in solid waste production from Arab world, research activity about solid waste is still low. Governments must invest more in solid waste research to avoid future unexpected problems. Finally, since solid waste is a multidisciplinary science, research teams in engineering, health, toxicology, environment, geology and others must be formulated to produce research in solid waste from different scientific aspects

Blood transcriptomics of drug-na\uefve sporadic Parkinson's disease patients

BACKGROUND: Parkinson's disease (PD) is a chronic progressive neurodegenerative disorder that is clinically defined in terms of motor symptoms. These are preceded by prodromal non-motor manifestations that prove the systemic nature of the disease. Identifying genes and pathways altered in living patients provide new information on the diagnosis and pathogenesis of sporadic PD. METHODS: Changes in gene expression in the blood of 40 sporadic PD patients and 20 healthy controls ("Discovery set") were analyzed by taking advantage of the Affymetrix platform. Patients were at the onset of motor symptoms and before initiating any pharmacological treatment. Data analysis was performed by applying Ranking-Principal Component Analysis, PUMA and Significance Analysis of Microarrays. Functional annotations were assigned using GO, DAVID, GSEA to unveil significant enriched biological processes in the differentially expressed genes. The expressions of selected genes were validated using RT-qPCR and samples from an independent cohort of 12 patients and controls ("Validation set"). RESULTS: Gene expression profiling of blood samples discriminates PD patients from healthy controls and identifies differentially expressed genes in blood. The majority of these are also present in dopaminergic neurons of the Substantia Nigra, the key site of neurodegeneration. Together with neuronal apoptosis, lymphocyte activation and mitochondrial dysfunction, already found in previous analysis of PD blood and post-mortem brains, we unveiled transcriptome changes enriched in biological terms related to epigenetic modifications including chromatin remodeling and methylation. Candidate transcripts as CBX5, TCF3, MAN1C1 and DOCK10 were validated by RT-qPCR. CONCLUSIONS: Our data support the use of blood transcriptomics to study neurodegenerative diseases. It identifies changes in crucial components of chromatin remodeling and methylation machineries as early events in sporadic PD suggesting epigenetics as target for therapeutic intervention