Longitudinal clinical study of patients with iron rim lesions in multiple sclerosis.

BACKGROUND: Iron rims (IRs) surrounding white matter lesions (WMLs) are suggested to predict a more severe disease course. Only small longitudinal cohorts of patients with and without iron rim lesions (IRLs) have been reported so far. OBJECTIVE: To assess whether the presence and number of IRLs in patients with clinically isolated syndrome (CIS) and multiple sclerosis (MS) are associated with long-term disability or progressive disease. METHODS: Ninety-one CIS/MS patients were recruited between 2008 and 2013 and scanned with 7 T magnetic resonance imaging (MRI). Expanded Disability Status Scale (EDSS) was used to calculate Age-related Multiple Sclerosis Severity Score (ARMSS) at the time of scan and at the latest clinical follow-up after 9 years. WMLs were assessed for the presence of IRL using Susceptibility weighted imaging (SWI)-filtered phase images. RESULTS: In all, 132 IRLs were detected in 42 patients (46%); 9% of WMLs had IRs; 54% of the cohort had no rims, 30% had 1-3 rims and 16% had ⩾4. Patients with IRL had a higher EDSS and ARMSS. Presence of IRL was also a predictor of long-term disability, especially in patients with ⩾4 IRLs. IRLs have a greater impact on disability compared to the WML number and volume. CONCLUSION: The presence and number of perilesional IR on MRI hold prognostic value for long-term clinical disability in MS.

Effects of Gingival Retraction Paste and Subsequent Cleaning with Hydrogen Peroxide on the Polymerization of Three Elastomeric Impression Materials: An In Vitro Study.

PURPOSE: It has been hypothesized that there are no effects of Expasyl and subsequent cleaning with hydrogen peroxide on polymerization of selected commonly used impression materials. Therefore, the aim of this study was to evaluate the effect of Expasyl paste on the polymerization of three impression materials with and without subsequent cleaning using 3% hydrogen peroxide (H2 O2 ). MATERIALS AND METHODS: Nine standardized stainless steel specimens were fabricated. One hundred and eighty impressions were made using 3 materials (60 each) as follows: group I: poly(vinyl siloxane) (PVS) (Virtual); group II: polyether (Monophase); group III: polyether (Impregum). Groups were subdivided into 3 categories: control without intervention (n = 20), pre-application of Expasyl and subsequent 1-minute washing with water and air-drying (n = 20), and pre-application of Expasyl and subsequent cleaning with 3% H2 O2 for 10 seconds (n = 20). All impressions were made by one operator using auto-mixing cartridges under standardized conditions at room temperature. Evaluation of the polymerization inhibition was blindly and independently performed by three practitioners with comparable experience using a visual scale. The observation was subjectively categorized as noninhibited or inhibited. Data were tabulated and analyzed using Fisher's exact test with significance level set at p ˂ 0.05. RESULTS: Significant differences were found between the control group and the impressions made after contamination with Expasyl (p < 0.001). Polymerization inhibition of PVS and Impregum was similar (in 85% and 90% of the specimens, respectively) when washed with water. There was a statistically significant reduction in polymerization inhibition in both upon cleaning with H2 O2 (p < 0.001); however, polymerization inhibition occurred in 100% of Monophase specimens when contaminated with Expasyl despite the washing technique used. CONCLUSIONS: Under these in vitro conditions, it can be concluded that the remnants of Expasyl on specimens caused a significant polymerization inhibition of the 3 impression materials tested. Subsequent cleaning with 3% H2 O2 significantly reduced this inhibitory effect on polymerization. Expasyl should not be used with Monophase polyether material.

Effectiveness of Partial Body Weight-Supported Treadmill Training on Various Outcomes in Different Contexts among Children and Adolescents with Cerebral Palsy: A Systematic Review and Meta-Analysis.

The efficiency of partial body weight-supported treadmill training (PBWSTT) for treating various conditions in children and adolescents with cerebral palsy (CP) in diverse contexts of rehabilitation, households, or schools is unknown. The major objective of this systematic review and meta-analysis was to analyze the effectiveness of PBWSTT on various outcomes in different contexts among children and adolescents with CP. We incorporated full-text, randomized controlled trial studies that specifically assessed the effects of PBWSTT walking, motor function, stride, balance, and endurance in children and adolescents aged 3 to 18 years with CP. The literature search was carried out using Google Scholar, PubMed, Web of Science, CINAHL Plus, Scopus, PEDro, and ResearchGate databases. The methodological quality was evaluated using a Cochrane risk of bias instrument. A meta-analysis of pooled data from 10 studies with 255 participants demonstrated that PBWSTT for 4-12 weeks in rehabilitation (mean difference [MD] = 1.94, 95% confidence interval [CI] = 1.40-2.48, p < 0.0001), at home or in a school context (MD = 13.5, 95% CI = 13.9-16.0, p < 0.0001), was significantly effective for treating various conditions in children and adolescents suffering with CP. The period of 4-12 weeks of PBWSTT in rehabilitation and at-home/school settings is effective on various outcomes in children or adolescents with CP.

Predictors of long-term disability in multiple sclerosis patients using routine magnetic resonance imaging data: A 15-year retrospective study.

INTRODUCTION: Early identification of patients at high risk of progression could help with a personalised treatment strategy. Magnetic resonance imaging (MRI) measures have been proposed to predict long-term disability in multiple sclerosis (MS), but a reliable predictor that can be easily implemented clinically is still needed. AIM: Assess MRI measures during the first 5 years of the MS disease course for the ability to predict progression at 10+ years. METHODS: Eighty-two MS patients (53 females), with ≥10 years of clinical follow-up and having two MRI scans, were included. Clinical data were obtained at baseline, follow-up and at ≥10 years. White matter lesion (WML) counts and volumes, and four linear brain sizes were measured on T2/FLAIR 'Fluid-Attenuated-Inversion-Recovery' and T1-weighted images. RESULTS: Baseline and follow-up inter-caudate diameter (ICD) and third ventricular width (TVW) measures correlated positively with Expanded Disability Status Scale, ≥10 or more of WMLs showed a high sensitivity in predicting progression, at ≥10 years. A steeper rate of lesion volume increase was observed in subjects converting to secondary progressive MS. The sensitivity and specificity of both ICD and TVW, to predict disability at ≥10 years were 60% and 64%, respectively. CONCLUSION: Despite advances in brain imaging and computerised volumetric analysis, ICD and TVW remain relevant as they are simple, fast and have the potential in predicting long-term disability. However, in this study, despite the statistical significance of these measures, the clinical utility is still not reliable.

Investigating the Effect of Cigarette Smoking on Serum Uric Acid Levels in Multiple Sclerosis Patients: A Cross Sectional Study.

OBJECTIVES: The present study is aimed at determining the effect of cigarette smoking (CS) on serum uric acid (UA) levels quantitatively before and after smoking cessation among people with MS (pwMS). Additionally, a possible correlation between UA levels and both disability progression and disease severity was also investigated. A retrospective cross-sectional study was conducted using the Nottingham University Hospitals MS Clinics database. It involves 127 people with definite MS recorded when reporting the latest smoking status and the clinical diagnosis. All necessary demographics and clinical characteristics were collected. We found that smoker pwMS had significantly lower serum UA levels than non-smoker pwMS (p-value = 0.0475), and this reduction was recovered after smoking cessation (p-value = 0.0216). However, the levels of disability or disease severity were not correlated with the levels of serum UA in current smoker pwMS, measured by the expanded disability status scale (EDSS; r = -0.24; p-value = 0.38), multiple sclerosis impact scale 29 (MSIS-29; r = 0.01; p-value = 0.97) and MS severity score (MSSS; r = -0.16; p-value = 0.58), respectively. Our result suggests that the reduction in UA levels is more likely a consequence of oxidative stress triggered by many risk factors, including CS, and could be considered a potential indicator of smoking cessation. In addition, the absence of a correlation between UA levels and disease severity and disability suggests that UA is not an optimal biomarker for disease severity and disability prediction among current smoker, ex-smoker or non-smoker pwMS.

Linagliptin and Empagliflozin Inhibit Microtubule Affinity Regulatory Kinase 4: Repurposing Anti-Diabetic Drugs in Neurodegenerative Disorders Using In Silico and In Vitro Approaches.

Type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) are significant public health burdens. Many studies have revealed the possibility of common pathophysiology between T2DM and AD. Thus, in recent years, studies deciphering the action mechanism of anti-diabetic drugs with their future use in AD and related pathologies are on high demand. Drug repurposing is a safe and effective approach owing to its low cost and time-saving attributes. Microtubule affinity regulating kinase 4 (MARK4) is a druggable target for various diseases and is found to be linked with AD and diabetes mellitus. MARK4 plays a vital role in energy metabolism and regulation and thus serves as an irrefutable target to treat T2DM. The present study was intended to identify the potent MARK4 inhibitors among FDA-approved anti-diabetic drugs. We performed structure-based virtual screening of FDA-approved drugs to identify the top hits against MARK4. We identified five FDA-approved drugs having an appreciable affinity and specificity toward the binding pocket of MARK4. Among these identified hits, two drugs, linagliptin, and empagliflozin, favorably bind to the MARK4 binding pocket, interacting with its critical residues and thus subjected to detailed analysis. All-atom detailed molecular dynamics (MD) simulations revealed the dynamics of binding of linagliptin and empagliflozin with MARK4. Kinase assay showed significant inhibition of MARK4 kinase activity in the presence of these drugs, implying them as potent MARK4 inhibitors. In conclusion, linagliptin and empagliflozin may be promising MARK4 inhibitors, which can further be exploited as potential lead molecules against MARK4-directed neurodegenerative diseases.

Exploratory Analysis of Survival and Mortality Rates among Older Lung Cancer Patients Utilizing Different Treatment Modalities.

Objective: To explore the impact of different lung cancer treatment modalities on survival time and mortality rates in older patients. Methods: The Surveillance Epidemiology and End Results (SEER) database was used to identify lung cancer patients aged ≥50 years old in the United States. Descriptive statistics and trend charts from 2000 to 2016 were generated. Regression analysis was performed among lung cancer patients to explore the association between survival time and treatment utilization (chemotherapy, radiation, and surgery). A regression model was also applied to explore the association between treatment modalities and odds of dying. Results: A total of 826,217 patients were diagnosed with lung cancer between 2000-2016. The number of lung cancer cases increased by 7%, and the average annual frequency was 48,529 cases per year. Survival, mortality, and treatment utilization varied over the years based on demographic, clinical characteristics, and social status. Five-year survival rate was less than 10% among the study population, and 84% of included lung cancer patients died. Chemotherapy was more commonly used (62%), followed by radiation (35%) and surgical interventions (22%). Chemotherapy and surgery showed a survival advantage. The odds of dying were two times higher among patients treated with surgery than those who were not (OR: 2.62, 95%Cl: 2.58-2.67). Conclusion: This study highlighted the importance of considering treatment modalities and individual patient characteristics, which may impact survival times and mortality rates among older lung cancer patients.

Magnetic Resonance Imaging as a Prognostic Disability Marker in Clinically Isolated Syndrome and Multiple Sclerosis: A Systematic Review and Meta-Analysis.

To date, there are no definite imaging predictors for long-term disability in multiple sclerosis (MS). Magnetic resonance imaging (MRI) is the key prognostic tool for MS, primarily at the early stage of the disease. Recent findings showed that white matter lesion (WML) counts and volumes could predict long-term disability for MS. However, the prognostic value of MRI in the early stage of the disease and its link to long-term physical disability have not been assessed systematically and quantitatively. A meta-analysis was conducted using studies from four databases to assess whether MS lesion counts and volumes at baseline MRI scans could predict long-term disability, assessed by the expanded disability status scale (EDSS). Fifteen studies were eligible for the qualitative analysis and three studies for meta-analysis. T2 brain lesion counts and volumes after the disease onset were associated with disability progression after 10 years. Four or more lesions at baseline showed a highly significant association with EDSS 3 and EDSS 6, with a pooled OR of 4.10 and 4.3, respectively. The risk increased when more than 10 lesions were present. This review and meta-analysis confirmed that lesion counts and volumes could be associated with disability and might offer additional valid guidance in treatment decision making. Future work is essential to determine whether these prognostic markers have high predictive potential.

Investigating Microstructural Changes in White Matter in Multiple Sclerosis: A Systematic Review and Meta-Analysis of Neurite Orientation Dispersion and Density Imaging.

Multiple sclerosis (MS) is characterised by widespread damage of the central nervous system that includes alterations in normal-appearing white matter (NAWM) and demyelinating white matter (WM) lesions. Neurite orientation dispersion and density imaging (NODDI) has been proposed to provide a precise characterisation of WM microstructures. NODDI maps can be calculated for the Neurite Density Index (NDI) and Orientation Dispersion Index (ODI), which estimate orientation dispersion and neurite density. Although NODDI has not been widely applied in MS, this technique is promising in investigating the complexity of MS pathology, as it is more specific than diffusion tensor imaging (DTI) in capturing microstructural alterations. We conducted a meta-analysis of studies using NODDI metrics to assess brain microstructural changes and neuroaxonal pathology in WM lesions and NAWM in patients with MS. Three reviewers conducted a literature search of four electronic databases. We performed a random-effect meta-analysis and the extent of between-study heterogeneity was assessed with the I2 statistic. Funnel plots and Egger's tests were used to assess publication bias. We identified seven studies analysing 374 participants (202 MS and 172 controls). The NDI in WM lesions and NAWM were significantly reduced compared to healthy WM and the standardised mean difference of each was -3.08 (95%CI -4.22 to (-1.95), p ≤ 0.00001, I2 = 88%) and -0.70 (95%CI -0.99 to (-0.40), p ≤ 0.00001, I2 = 35%), respectively. There was no statistically significant difference of the ODI in MS WM lesions and NAWM compared to healthy controls. This systematic review and meta-analysis confirmed that the NDI is significantly reduced in MS lesions and NAWM than in WM from healthy participants, corresponding to reduced intracellular signal fraction, which may reflect underlying damage or loss of neurites.

Investigating Brain Microstructural Alterations in Type 1 and Type 2 Diabetes Using Diffusion Tensor Imaging: A Systematic Review.

Type 1 and type 2 diabetes mellitus have an impact on the microstructural environment and cognitive functions of the brain due to its microvascular/macrovascular complications. Conventional Magnetic Resonance Imaging (MRI) techniques can allow detection of brain volume reduction in people with diabetes. However, conventional MRI is insufficiently sensitive to quantify microstructural changes. Diffusion Tensor Imaging (DTI) has been used as a sensitive MRI-based technique for quantifying and assessing brain microstructural abnormalities in patients with diabetes. This systematic review aims to summarise the original research literature using DTI to quantify microstructural alterations in diabetes and the relation of such changes to cognitive status and metabolic profile. A total of thirty-eight published studies that demonstrate the impact of diabetes mellitus on brain microstructure using DTI are included, and these demonstrate that both type 1 diabetes mellitus and type 2 diabetes mellitus may affect cognitive abilities due to the alterations in brain microstructures.

Effects of Plyometric Exercises versus Flatfoot Corrective Exercises on Postural Control and Foot Posture in Obese Children with a Flexible Flatfoot.

BACKGROUND: Obesity contributes to the acquired flatfoot deformity which in turn impairs balance. AIM: The purpose of the current study was to compare the effect of plyometric exercises with flatfoot corrective exercises on balance, foot posture, and functional mobility in obese children with a flexible flatfoot. METHODS: Forty-seven children participated in the study. Their age ranged from 7 to 11 years. Participants were randomly divided into 3 groups: experimental group I (EGI), experimental group II (EGII), and the control group (CG). The EGI received plyometric exercises and the EGII received corrective exercises, 2 sessions weekly for 10 weeks. The control group did not perform any planned physical activities. The Prokin system was used to assess balance, the timed up and go test (TUG) was used to assess functional mobility, and the navicular drop test (NDT) was used to assess foot posture. RESULTS: EGI showed significant improvement in all balance parameters, foot posture, and TUG. EGII showed improvement in the ellipse area and perimeter in addition to foot posture and TUG. CONCLUSION: Plyometric exercises and foot correction exercises had a positive effect on foot posture, balance, and functional mobility in obese children with flatfeet.

Parental Attitude and Awareness toward Preventive Dentistry in Riyadh, Saudi Arabia: A Cross-Sectional Study.

INTRODUCTION: Preventive oral health of a child is dependent on the parental knowledge toward caries control, care of deciduous tooth, use of space maintainers for malocclusion, and utilization of various procedures available for preventing oral diseases by oral health professionals. This study was aimed to assess the attitude and awareness of preventive dentistry among parents residing in Riyadh city, Kingdom of Saudi Arabia. METHODOLOGY: A cross-sectional, questionnaire study was conducted among 300 male parents. Questionnaire was sent through the use of social media, and responses were collected. RESULTS: Seventy-four percent of male Saudi parents were aware of prevention of oral diseases. 38.45% of male parents were aware of preventive dentistry procedure, but preventive dentistry utilization rate was seen among 6% population only. Attitude toward the prevention of oral disease was statistically not significant according to the age group and income but statistically significant according to education. The utilization of preventive procedures was significant according to education and income (P < 0.05). CONCLUSION: Awareness about preventive dentistry was more among Saudi parents but utilization rate was directly correlated to their education and income. After The utilization of preventive procedures was significant according to education and income (P < 0.05).

Iron Rims as an Imaging Biomarker in MS: A Systematic Mapping Review.

BACKGROUND: Multiple sclerosis (MS) is an autoimmune, inflammatory, demyelinating and degenerative disease of the central nervous system (CNS). To date, there is no definitive imaging biomarker for diagnosing MS. The current diagnostic criteria are mainly based on clinical relapses supported by the presence of white matter lesions (WMLs) on MRI. However, misdiagnosis of MS is still a significant clinical problem. The paramagnetic, iron rims (IRs) around white matter lesions have been proposed to be an imaging biomarker in MS. This study aimed to carry out a systematic mapping review to explore the detection of iron rim lesions (IRLs), on clinical MR scans, and describe the characteristics of IRLs presence in MS versus other MS-mimic disorders. METHODS: Publications from 2001 on IRs lesions were reviewed in three databases: PubMed, Web of Science and Embase. From the initial result set 718 publications, a final total of 38 papers were selected. RESULTS: The study revealed an increasing interest in iron/paramagnetic rims lesions studies. IRs were more frequently found in periventricular regions and appear to be absent in MS-mimics. Conclusions IR is proposed as a promising imaging biomarker for MS.

Cross-Cultural Adaptation and Validation of the Arabic Version of Musculoskeletal Health Questionnaire (MSK-HQ-Ar).

BACKGROUND: Musculoskeletal disorders (MSD) affect millions of people worldwide. Musculoskeletal Health Questionnaire (MSK-HQ) is a valid and reliable tool to assess the health of patients with MSD. However, this scale is not available in the Arabic language. The purpose of this study was to translate and cross-culturally adapt the Musculoskeletal Health Questionnaire (MSK-HQ) into Arabic (MSK-HQ-Ar) and evaluate its validity and reliability among participants with MSD. METHODS: This cross-sectional study used guidelines from the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) to translate as well as validate the psychometric properties of MSK-HQ-Ar. Patients with MSD (n = 149) living in Taif participated in the study. Cronbach's alpha and the intraclass correlation coefficient (ICC) were used to assess internal consistency and test-retest reliability of MSK-HQ-Ar respectively. Spearman's correlation was used to assess the correlation between MSK-HQ-Ar and the European quality of life five-dimension, five-level scale (EQ-5D-5L). RESULTS: Out of 149 participants, 119 completed the MSK-HQ-Ar twice. The scale showed good internal consistency, Cronbach's alpha (0.88), and reliability (ICC 0.92-0.95). A strong association was found with the EQ-5D-5L scores. CONCLUSION: The adapted MSK-HQ-Arabic version revealed acceptable psychometric properties and is a valid and reliable outcome measure to assess MSK health among Arabic speaking patients with MSD.

Awareness of diabetic retinopathy among Saudis with diabetes type 2 in Riyadh city.

OBJECTIVE: To assess awareness of diabetic retinopathy (DR) for Saudis with diabetes mellitus (DM) type 2 in Riyadh City. METHODS: A cross-sectional study that used self-administered questionnaires conducted in primary healthcare centers in Riyadh City between October and December 2019. RESULTS: There were 267 Saudi participants with diabetes mellitus type 2 visiting primary healthcare clinics. (52.4%) were aged 40 years or above at time of diagnosis with diabetes. (73%) had diabetes for at least 5 years. Most of the participants have a good blood glucose control and they do home measurements. In regard to DR, (64.4%) of participants had no subjective or objective indicators of retinopathy, and (70%) had visited ophthalmology clinics. Majority of the participants were advised about DR or referred to an ophthalmologist by their primary physician, with the percentages being (64.8%) and (59.6%), respectively. Regarding other risk factors of DR, (19.5%) had a family history of DR, (23.2%) of participant are smokers and (41.6%) were hypertensives. Majority of the participants were aware about all the aspects of DR, its consequences, and appropriate management except the laser therapy. In terms of area of living and education respondents, who lived in the center of Riyadh City and the secondary level or less educated participants had the lowest level of education. CONCLUSIONS: Awareness of DR is acceptable but should not lead this information to reduced awareness and educational programs. Outreach researchers' efforts should cover other directions instead awareness of DR.

Awareness of cardiovascular disease associated risk factors among Saudis in Riyadh City.

OBJECTIVE: The aim of this study was to estimate the awareness of Saudi population in Riyadh regarding cardiovascular diseases (CVDs) and their risk factors. METHODS: This was a cross-sectional study that used self-administered questionnaires conducted in universities, primary care centers, and electronic copies distributed in social media websites. RESULTS: Overall, 47.1% of the respondents had a good awareness of CVD and associated risk factors. However, awareness of the symptoms of stroke and heart attack was low. Pulmonary embolism and deep vein thrombosis were the most commonly identified types of CVD, with 39.2% aware of these conditions. The most well-known symptom of heart attack was shortness of breath (known by 54.4% of the respondents). In relation to stroke, the most commonly recognized symptom was "sudden dizziness, trouble walking, or loss of balance" (45.4%). Respondents' awareness of CVD risk factors was moderate. The most common factors-identified by over two-thirds of participants-were unhealthy diet, smoking, dyslipidemia, and physical inactivity. Independent predictors of good CVD awareness were age 35-44 years, living in the north of Riyadh and following a healthy diet. CONCLUSIONS: The awareness of CVD and associated risk factors is insufficient among Saudis in Riyadh City. This study emphasizes the necessity for effective education to increase the awareness about CVD in Saudi Arabia. High awareness may lead to early recognition of the risk factors and lead to early implementation of primary prevention which the cornerstone of family medicine practice.

Prevalence, Attitude, Knowledge, and Practice of Anabolic Androgenic Steroid (AAS) Use Among Gym Participants.

BACKGROUND: Anabolic steroids (AS) are synthetic testosterone derivatives that last longer than physiological androgens in the body. Anabolic-androgenic steroid (AAS) abuse is spreading among athletes. The aim of this study is to assess the knowledge, attitudes, and practices of gym participants in Saudi Arabia. METHODS: A cross-sectional survey was carried out among gym users from February 2017 to May 2017. The questionnaire included information on demographics related to the use of AAS and lifestyle habits. Any willing male gym participant could be included. RESULTS: A total of 4860 male gym participants with a mean age of 28.6 ± 6.2 years were included. A majority were single, with a bachelor's degree or higher. Moreover, 9.8% of the participants used AAS, of which 76.7% reported improved fitness. Friends were the main source of AAS-related information, but only 38.0% of AAS users sought medical consults. The oral route was most common, and testosterone enanthate was the AAS most used. CONCLUSION: Also, 9.8% of gym participants used AAS and were more likely to be involved in risky habits, such as smoking and growth hormone abuse. They were less aware of potential complications of AAS, with gym trainers being the predominant source of AAS substances.