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Mesenchymal stem cell (MSC) therapies for the treatment of diseases associated with inflammation and oxidative stress employ primarily bone marrow MSCs (BMMSCs) and other MSC types such as MSC from the chorionic villi of human term placentae (pMSCs). These MSCs are not derived from microenvironments associated with inflammation and oxidative stress, unlike MSCs from the decidua basalis of the human term placenta (DBMSCs). DBMSCs were isolated and then extensively characterized. Differentiation of DBMSCs into three mesenchymal lineages (adipocytes, osteocytes, and chondrocytes) was performed. Real-time polymerase chain reaction (PCR) and flow cytometry techniques were also used to characterize the gene and protein expression profiles of DBMSCs, respectively. In addition, sandwich enzyme-linked immunosorbent assay (ELISA) was performed to detect proteins secreted by DBMSCs. Finally, the migration and proliferation abilities of DBMSCs were also determined. DBMSCs were positive for MSC markers and HLA-ABC. DBMSCs were negative for hematopoietic and endothelial markers, costimulatory molecules, and HLA-DR. Functionally, DBMSCs differentiated into three mesenchymal lineages, proliferated, and migrated in response to a number of stimuli. Most importantly, these cells express and secrete a distinct combination of cytokines, growth factors, and immune molecules that reflect their unique microenvironment. Therefore, DBMSCs could be attractive, alternative candidates for MSC-based therapies that treat diseases associated with inflammation and oxidative stress. [ABSTRACT FROM AUTHOR]

Background: We have previously shown headache to be highly prevalent among adults in Saudi Arabia. Here we estimate associated symptom burden and impaired participation (impaired use of time, lost productivity and disengagement from social activity), and use these estimates to assess headache-related health-care needs in Saudi Arabia., Methods: A randomised cross-sectional survey included 2,316 adults (18-65 years) from all 13 regions of the country. It used the standardised methodology of the Global Campaign against Headache with a culturally mandated modification: engagement by cellphone using random digit-dialling rather than door-to-door visits. Enquiry used the HARDSHIP questionnaire, with diagnostic questions based on ICHD-3 beta, questions on symptom burden, enquiries into impaired participation using the HALT index and questions about activity yesterday in those reporting headache yesterday (HY). Health-care "need" was defined in terms of likelihood of benefit. We counted all those with headache on ≥ 15 days/month, with migraine on ≥ 3 days/month, or with migraine or TTH and meeting either of two criteria: a) proportion of time in ictal state (pTIS) > 3.3% and intensity ≥ 2 (moderate-severe); b) ≥ 3 lost days from paid work and/or household chores during 3 months., Results: For all headache, mean frequency was 4.3 days/month, mean duration 8.4 h, mean intensity 2.3 (moderate). Mean pTIS was 3.6%. Mean lost days from work were 3.9, from household chores 6.6, from social/leisure activities 2.0. Of participants reporting HY, 37.3% could do less than half their expected activity, 19.8% could do nothing. At population-level (i.e., for every adult), 2.5 workdays (potentially translating into lost GDP), 3.6 household days and 1.3 social/leisure days were lost to headache. According to HY data, mean total impaired participation (not distinguishing between work, household and social/leisure) was 6.8%. A total of 830 individuals (35.8%) fulfilled one or more of our needs assessment criteria., Conclusion: A very high symptom burden is associated with a commensurately high burden of impaired participation. The economic cost appears to be enormous. Over a third of the adult population are revealed to require headache-related health care on the basis of being likely to benefit, demanding highly efficient organization of care., (© 2024. The Author(s).)

Background: Spinal Muscular Dystrophy (SMA) is one of the leading causes of death in infants and young children from heritable diseases. Although no large-scale popultion-based studies have been done in Saudi Arabia, it is reported that the incidence of SMA is higher in the Saudi population partly because of the high degree of consanguineous marriages., Methods: The final analysis included 4198 normal volunteers aged between 18 and 25 years old, 54.7% males, and 45.3% females. Whole blood was spotted directly from finger pricks onto IsoCode StixTM and genomic DNA was isolated using one triangle from the machine. To discern the SMN1 copy number independently from SMN2, Multiplex PCR with Dral restriction fragment analysis was completed. We used the carrier frequency and population-level data to estimate the prevalence of SMA in the population using the life-table method., Results: This data analysis showed the presence of one copy of the SMN1 gene in 108 samples and two copies in 4090 samples, which resulted from a carrier frequency of 2.6%. The carrier frequency was twofold in females reaching 3.7% compared to 1.6% in males. 27% of participants were children of first-cousin marriages. We estimated the birth incidence of SMA to be 32 per 100,000 birth and the total number of people living with SMA in the Kingdom of Saudi Arabia to be 2265 of which 188 are type I, 1213 are type II, and 8,64 are type III., Conclusion: The SMA carrier rate of 2.6% in Saudi control subjects is slightly higher than the reported global frequency of 1.25 to 2% with links to the high degree of consanguinity., (© 2022 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Patients with multiple sclerosis (MS) should be vaccinated against COVID-19. All COVID-19 vaccines are effective and do not appear to carry any additional risk for patients with MS. Patients with MS should get a COVID-19 vaccine as soon as it becomes available. The risks of COVID-19 disease outweigh any potential risks from the vaccine. Even if vaccinated, patients with MS should continue to practice standard and recommended precautions against COVID-19, such as wearing a face mask, social distancing and washing hands. There is no evidence that patients with MS are at higher risk of complications from the mRNA, non-replicating viral vector, inactivated virus or protein COVID-19 vaccines, compared to the general population. COVID-19 Vaccines are safe to use in patients with MS treated with disease-modifying therapies (DMTs). The effectiveness of vaccination may be affected by few of the DMTs but yet some protection is still provided. For certain DMTs we may consider coordinating the timing of the vaccine with the timing of the DMT dose to increase vaccine efficacy., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In countries where headache services exist at all, their focus is usually on specialist (tertiary) care. This is clinically and economically inappropriate: most headache disorders can effectively and more efficiently (and at lower cost) be treated in educationally supported primary care. At the same time, compartmentalizing divisions between primary, secondary and tertiary care in many health-care systems create multiple inefficiencies, confronting patients attempting to navigate these levels (the "patient journey") with perplexing obstacles.High demand for headache care, estimated here in a needs-assessment exercise, is the biggest of the challenges to reform. It is also the principal reason why reform is necessary.The structured headache services model presented here by experts from all world regions on behalf of the Global Campaign against Headache is the suggested health-care solution to headache. It develops and refines previous proposals, responding to the challenge of high demand by basing headache services in primary care, with two supporting arguments. First, only primary care can deliver headache services equitably to the large numbers of people needing it. Second, with educational supports, they can do so effectively to most of these people. The model calls for vertical integration between care levels (primary, secondary and tertiary), and protection of the more advanced levels for the minority of patients who need them. At the same time, it is amenable to horizontal integration with other care services. It is adaptable according to the broader national or regional health services in which headache services should be embedded.It is, according to evidence and argument presented, an efficient and cost-effective model, but these are claims to be tested in formal economic analyses., (© 2021. The Author(s).)

Disease-modifying therapies (DMT) for relapsing-remitting MS (RRMS) act on the immune system, suggesting a need for caution during the SARS-CoV2/Covid-19 pandemic. A group of experts in MS care from Saudi Arabia convened to consider the impact of Covid-19 on MS care in that country, and to develop consensus recommendations on the current application of DMT therapy. Covid-19 has led to disruption to the care of MS in Saudi Arabia as elsewhere. The Expert Panel considered a DMT's overall tolerability/safety profile to be the most important consideration on whether or not to prescribe at this time. Treatment can be started or continued with interferon beta, teriflunomide, dimethyl fumarate, or natalizumab, as these DMTs are not associated with increased risk of infection (there was no consensus on the initiation of other DMTs). A consensus also supported continuing treatment regimens with fingolimod (or siponimod) and cladribine tablets for a patient without active Covid-19. No DMT should be imitated in a patient with active Covid-19, and (only) interferon beta could be continued in the case of Covid-19 infection. Vaccination against Covid-19 is a therapeutic priority for people with MS. New treatment should be delayed for 2-4 weeks for vaccination. Where treatment is already ongoing, vaccination against Covid-19 should be administered immediately without disruption of treatment (first-line DMTs, natalizumab, fingolimod), when lymphocytes have recovered sufficiently (cladribine tablets, alemtuzumab) or 4 months after the last dose (ocrelizumab). These recommendations will need to be refined and updated as new clinical evidence in this area emerges., (Copyright © 2021. Published by Elsevier B.V.)

Few studies examine health-related quality of life (HRQoL) in Arabic-speaking multiple sclerosis (MS) patients. However, HRQoL tools such as the Short Form-36 QoL instrument (SF-36) and the Multiple Sclerosis International QoL (MusiQoL) questionnaire have been validated in other languages. The primary objective of this study was to prospectively assess HRQoL using the MusiQoL questionnaire among Arabic-speaking MS patients treated with subcutaneous interferon (sc IFN β -1a) over 12 months, as part of a prospective, multinational, multicenter cohort study. Patients' clinical parameters and HRQoL were assessed at baseline, 6 months, and 12 months. Changes in MusiQoL total and subdomain scores were compared using a Friedman test. Correlation between MusiQoL total score and Expanded Disability Status Score (EDSS) was also evaluated. In total, 439 patients from four Arabic-speaking countries were included. The mean age was 32.44 (±0.34) years, 71.5% were female, and 63.1% had an education level of university or above. The mean MS duration was 4.13 (±0.12) years, mean age at first attack was 27.35 (±0.26) years, and mean baseline EDSS score was 2.05 (±0.04). MusiQoL total score significantly improved at 6 months; however, this diminished at 12 months (65.67 ± 0.8 at baseline vs. 67.21 ± 0.79 at 6 months and 65.75 ± 0.8 at 12 months; p = 0.0015). Several aspects of patients' HRQoL including activity of daily living, physical well-being, symptoms, and coping improved. Overall HRQoL measured using SF-36 remained generally unchanged over time ( p = 0.215). There was a statistically significant inverse relationship between change in EDSS score over time and change in overall MusiQoL score over time. In summary, findings confirm the utility of using MusiQoL for assessing changes in HRQoL during treatment with sc IFN β -1a in Arabic-speaking patients with MS., Competing Interests: Mohammed Al Jumah has received honoraria as a consultant to and speaker for Merck KGaA, Darmstadt, Germany. Suleiman Kojan, Raed Alroughani, Saeed Bohlega, Abdulkader Daif, Mousa Al Mujalli, Talal Al Harbi, Mohamed El Tamawy, Samia Ashour, Chokri Mhiri, Ayah Jawhary, and Mohamed Hussein have no conflicts of interest to disclose. Edward Cupler reports personal fees from Merck KGaA (Darmstadt, Germany), outside the submitted work. Riadh Gouider reports personal fees from Biogen, Hikma, Merck KGaA (Darmstadt, Germany), Roche, and Sanofi, outside the submitted work. Ahmed El Boghdady is an employee of Merck Serono, Jeddah, Saudi Arabia, an affiliate of Merck KGaA, Darmstadt, Germany., (Copyright © 2021 Mohammed Al Jumah et al.)

More than half of all patients with multiple sclerosis (MS) in the Kingdom of Saudi Arabia (KSA) are women of childbearing age. Raising a family is an important life goal for women in our region of the world. However, fears and misconceptions about the clinical course of relapsing-remitting MS (RRMS) and the effects of disease-modifying drugs (DMDs) on the foetus have led many women to reduce their expectations of raising a family, sometimes even to the point of avoiding pregnancy altogether. The increase in the number of DMDs available to manage RRMS and recent studies on their effects in pregnancy have broadened management options for these women. Interferon beta now has an indication in Europe for use during pregnancy (according to clinical need) and can be used during breastfeeding. Glatiramer acetate is a further possible option for women with lower levels of RRMS disease activity who are, or about to become, pregnant; natalizumab may be used up to 30 weeks in patients with higher levels of disease activity. Where possible, physicians need to support and encourage women to pursue their dream of a fulfilling family life, supported where necessary by active interventions for RRMS that are increasingly evidence based., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Mohammed Al Jumah et al.)

Background: The large geographical gaps in our knowledge of the prevalence and burden of headache disorders include most of Eastern Mediterranean Region (EMR). Following a nationwide population-based study in Pakistan, we present here a similar study from Kingdom of Saudi Arabia (KSA). Both were conducted as projects within the Global Campaign against Headache The two purposes of this study were to inform national health policy and contribute to global knowledge of headache disorders., Methods: We surveyed Arabic-speaking adults aged 18-65 years in all 13 regions of KSA. While previous Global Campaign studies have engaged participants by calling at randomly selected households, the culture of KSA made this unacceptable. Participants were, instead, contacted by cell-phone (since cell-phone coverage exceeded 100% in KSA), using random-digit dialling. Trained interviewers used a culturally adapted version of the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire, with diagnostic enquiry based on ICHD-II. We estimated 1-year prevalences of the headache disorders of public-health importance (migraine, tension-type headache [TTH] and probable medication-overuse headache [pMOH]) and examined their associations with demographic variables., Results: A total of 2316 participants (mean age of 32.2 ± 10.7 years; 62.3% male; 37.7% female) were included (participation proportion 86.5%). Gender and age distributions imperfectly matched those of the national population, requiring adjustments for these to prevalence estimates. Observed 1-year prevalence of all headache was 77.2%, reducing to 65.8% when adjusted. For headache types, adjusted 1-year prevalences were migraine 25.0%, TTH 34.1%, pMOH 2.0% and other headache on ≥15 days/month 2.3%. Adjusted 1-day prevalence of any headache was 11.5%. Migraine and pMOH were associated with female gender (ORs: 1.7 and 4.7; p < 0.0001). Migraine was negatively associated with age > 45 years (OR: 0.4; p = 0.0143) while pMOH was most prevalent in those aged 46-55 years (OR: 2.7; p = 0.0415). TTH reportedly became more common with increasing level of education., Conclusion: Prevalences of migraine and TTH in KSA are considerably higher than global averages (which may be underestimated), and not very different from those in Pakistan. There is more pMOH in KSA than in Pakistan, reflecting, probably, its higher-income status and greater urbanisation (facilitating access to medication).

Background: Multiple sclerosis (MS) is the most common non-traumatic condition that leads to disability among young individuals. It is associated with demyelination, inflammation, and neurodegeneration within the central nervous system. Information on risk factors of multiple sclerosis is crucial for the prevention and control of the disease. The aim of this study was to determine risk factors of MS among adults in Saudi Arabia., Methods: A matched multicenter case-control study, including 307 MS patients and 307 healthy controls, was conducted in MS clinics and wards in 3 main cities of Saudi Arabia. Age, gender, and hospital were matched. Information on demographics, family history of MS, past medical and family history, sun exposure at different age periods, tobacco use, diet, consanguinity, and coffee consumption was obtained from self-administered questionnaires. ORs and 95% confidence intervals (CIs) were calculated. A conditional logistic regression model was used to control for potential confounding factors., Results: The conditional logistic regression adjusted for age and gender showed that being the first child in the family (Adjusted Odds Ratio (AOR) 1.68, 95% CI: 1.03-2.74), having a family history of MS (AOR 5.83, 95% CI: 2.83-12), eating fast food ≥5 times weekly (AOR 2.05, 95% CI: 1.03-4.08), and having had measles (AOR 3.77, 95% CI: 2.05-6.96), were independently associated with an increased risk of MS. In contrast, eating ≥5 servings of fruit per week (AOR 0.25, 95% CI: 0.16-0.38), drinking coffee daily (AOR 0.46, 95% CI: 0.31-0.68), and having a high level of sun exposure at the primary school level and university level (AOR 0.57, 95% CI: 0.38-0.85 and AOR 0.48, 95% CI: 0.30-0.76, respectively) were independently associated with a decreased risk of MS., Conclusions: Our study suggested that high levels of sun exposure during primary school and university, consumption of fruits and drinking coffee protect against MS. In contrast, eating fast food was associated with an increased risk of the disease. Encouraging outdoor activity and healthy diets in school, especially for females, is highly recommended.

Mesenchymal stem/stromal cells derived from chorionic villi of human term placentae (pMSCs) produce a unique combination of molecules, which modulate important cellular functions of their target cells while concurrently suppressing their immune responses. These properties make MSCs advantageous candidates for cell-based therapy. Our first aim was to examine the effect of high levels of oxidative stress on pMSC functions. pMSCs were exposed to hydrogen peroxide (H 2 O 2 ) and their ability to proliferate and adhere to an endothelial cell monolayer was determined. Oxidatively stressed pMSCs maintained their proliferation and adhesion potentials. The second aim was to measure the ability of pMSCs to prevent oxidative stress-related damage to endothelial cells. Endothelial cells were exposed to H 2 O 2 , then co-cultured with pMSCs, and the effect on endothelial cell adhesion, proliferation and migration was determined. pMSCs were able to reverse the damaging effects of oxidative stress on the proliferation and migration but not on the adhesion of endothelial cells. These data indicate that pMSCs are not only inherently resistant to oxidative stress, but also protect endothelial cell functions from oxidative stress-associated damage. Therefore, pMSCs could be used as a therapeutic tool in inflammatory diseases by reducing the effects of oxidative stress on endothelial cells., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objectives: To estimate JCV seroprevalence and risk of seroconversion against JCV among MS patients in the Middle East., Methods: This multicenter study was conducted by implementing a cross-sectional design to assess JCV seroprevalence, and a longitudinal design to assess the risk of JCV seroconversion. Multivariable logistic and Poisson regression analyses were used to assess the relationship between clinical variables and JCV seropositivity and risk of seroconversion., Results: Of 581 MS patients, 64.9% patients were females. Mean age and mean disease duration were 33.9 and 8.4years respectively. JCV seroprevalence was 48.7%. Male gender (p=0.002), age at onset (p=0.001) and disease duration of 20 or more years (p=0.007) were significantly associated with JCV seropositivity. Among patients (n=125), followed longitudinally, the risk of JCV seroconversion was 17.6% (95% CI: 11.4%-25.4%) during a median follow-up of 18months. The proportion of seroreverted and pseudoconverted patients was 4% and 3.2% respectively., Conclusions: JCV seroprevalence among MS patients in the Middle East was lower than international figures. Male gender, age at onset and disease duration were significantly associated with JCV seropositivity. Risk of JCV seroconversion was higher than previously reported figures. Observed JCV sero-reversion or pseudo-conversion entail watchful period before embarking on a clinical decision., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The burden of multiple sclerosis (MS) in women of childbearing potential is increasing, with peak incidence around the age of 30 years, increasing incidence and prevalence, and growing female : male ratio. Guidelines recommend early use of disease-modifying therapies (DMTs), which are contraindicated or recommended with considerable caution, during pregnancy/breastfeeding. Many physicians are reluctant to prescribe them for a woman who is/is planning to be pregnant. Interferons are not absolutely contraindicated during pregnancy, since interferon- β appears to lack serious adverse effects in pregnancy, despite a warning in its labelling concerning risk of spontaneous abortion. Glatiramer acetate, natalizumab, and alemtuzumab also may not induce adverse pregnancy outcomes, although natalizumab may induce haematologic abnormalities in newborns. An accelerated elimination procedure is needed for teriflunomide if pregnancy occurs on treatment or if pregnancy is planned. Current evidence supports the contraindication for fingolimod during pregnancy; data on other DMTs remains limited. Increased relapse rates following withdrawal of some DMTs in pregnancy are concerning and require further research. The postpartum period brings increased risk of disease reactivation that needs to be carefully addressed through effective communication between treating physicians and mothers intending to breastfeed. We address the potential for use of the first- and second-line DMTs in pregnancy and lactation., Competing Interests: The authors declare that they have no competing interests.

Background: Pompe disease is a rare autosomal recessive disorder caused by a deficiency of the lysosomal enzyme alpha-glucosidase responsible for degrading glycogen. Late-onset Pompe disease has a complex multisystem phenotype characterized by a range of symptoms., Methods: An expert panel from the Middle East and North Africa (MENA) region met to create consensus-based guidelines for the diagnosis and treatment of late-onset Pompe disease for the MENA region, where the relative prevalence of Pompe disease is thought to be high but there is a lack of awareness and diagnostic facilities., Results: These guidelines set out practical recommendations and include algorithms for the diagnosis and treatment of late-onset Pompe disease. They detail the ideal diagnostic workup, indicate the patients in whom enzyme replacement therapy should be initiated, and provide guidance on appropriate patient monitoring., Conclusions: These guidelines will serve to increase awareness of the condition, optimize patient diagnosis and treatment, reduce disease burden, and improve patient outcomes.

Ethical issues regarding research biobanks continue to be a topic of intense debate, especially issues of confidentiality, informed consent, and child participation. Although considerable empirical literature concerning research biobank ethics exists, very little information is available regarding the opinions of medical professionals doing genetics research from the Middle East, especially Arabic speaking countries. Ethical guidelines for research biobanks are critically needed as some countries in the Middle East are starting to establish national research biobanks. Islam is the dominant religion in these countries, and it affects people's behavior and influences their positions. Moreover, communities in these countries enjoy a set of customs, traditions and social norms, and have social and familial structures that must be taken into account when developing research policies. We interviewed 12 medical professionals from the Middle East currently working with stored tissue samples to document their opinions. We found general agreement. Participants' primary concerns were similar to the views of researchers internationally. Since children tend to represent a high percentage of Middle Eastern populations, and because children's bodies are not just small adult bodies, the interviewed professionals strongly believed that it is imperative to include children in biobank research. Participants generally believed that protecting confidentiality is socially very important and that informed consent/assent must be obtained from both adult and child participants. This study provides a starting point for additional studies.