Correction: Ashraf et al. Inhibition of Microtubule Affinity Regulating Kinase 4 by Metformin: Exploring the Neuroprotective Potential of Antidiabetic Drug through Spectroscopic and Computational Approaches. Molecules 2022, 27, 4652.

The updated affiliation information can be seen in the affiliation part of this correction [...].

Inhibition of Microtubule Affinity Regulating Kinase 4 by Metformin: Exploring the Neuroprotective Potential of Antidiabetic Drug through Spectroscopic and Computational Approaches.

Microtubule affinity regulating kinase 4 (MARK4) regulates the mechanism of microtubules by its ability to phosphorylate the microtubule-associated proteins (MAP's). MARK4 is known for its major role in tau phosphorylation via phosphorylating Ser262 residue in the KXGS motif, which results in the detachment of tau from microtubule. In lieu of this vital role in tau pathology, a hallmark of Alzheimer's disease (AD), MARK4 is a druggable target to treat AD and other neurodegenerative disorders (NDs). There is growing evidence that NDs and diabetes are connected with many pieces of literature demonstrating a high risk of developing AD in diabetic patients. Metformin (Mtf) has been a drug in use against type 2 diabetes mellitus (T2DM) for a long time; however, recent studies have established its therapeutic effect in neurodegenerative diseases (NDs), namely AD, Parkinson's disease (PD) and amnestic mild cognitive impairment. In this study, we have explored the MARK4 inhibitory potential of Mtf, employing in silico and in vitro approaches. Molecular docking demonstrated that Mtf binds to MARK4 with a significant affinity of -6.9 kcal/mol forming interactions with binding pocket's critical residues. Additionally, molecular dynamics (MD) simulation provided an atomistic insight into the binding of Mtf with MARK4. ATPase assay of MARK4 in the presence of Mtf shows that it inhibits MARK4 with an IC50 = 7.05 µM. The results of the fluorescence binding assay demonstrated significant binding of MARK4 with a binding constant of 0.6 × 106 M-1. The present study provides an additional axis towards the utilization of Mtf as MARK4 inhibitor targeting diabetes with NDs.

Consanguinity in patients with mesial temporal lobe epilepsy due to hippocampal sclerosis in a Saudi population.

OBJECTIVE: To investigate if there is an association between consanguinity and hippocampal sclerosis (HS) in the Saudi population. METHODS: A retrospective case-control study was conducted by assessing the prevalence of consanguinity in patients with pathologically proven HS, who underwent epilepsy surgery at King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia, between January 2004 and December 2015. We reviewed the medical records to extract data, which included; age, gender, duration of epilepsy, history of febrile seizure, family history of epilepsy in a first or second-degree relative, and pathology reports. RESULTS: A total of 120 patients, out of which 40 patients (65% male) having mesial temporal lobe epilepsy due to HS, and 80 controls (56% male) with cryptogenic epilepsy, were identified. Twenty-two patients (53.5%) in the HS group had a history of consanguinity. In the control group, 30 patients (37.5%) had a history of consanguinity. The odds ratio was 2.04 (95% confidence interval = 0.94 - 4.4, p=0.052). A family history of epilepsy was found in 28% of the patients with HS and 32.5% cryptogenic epilepsy. Only 8 patients (19.5%) with HS reported a history of febrile seizure. CONCLUSION: Our retrospective case-control study suggests that consanguinity might increase the likelihood of developing HS.

Infratentorial immature teratoma of congenital origin can be associated with a 20-year survival outcome: a case report and review of literature.

BACKGROUND: Congenital intracranial tumors are very rare and account for less than 2% of all childhood brain tumors. Teratomas constitute about one third to one half of these, predominantly located midline in the supratentorial region. Posterior fossa location rarely occurs and, based on the cases reported in the literature, commonly has a poor prognosis. CASE PRESENTATION: A newborn female, diagnosed prenatally with hydrocephalus, is presented at birth with increasing head circumference and Parinaud's syndrome. Magnetic resonance imaging scans demonstrated a huge posterior fossa tumor with obstructive hydrocephalus. At surgery, through a suboccipital craniotomy, complete excision was achieved of a histological-proven immature teratoma. The infant received adjuvant chemotherapy for 1 year. She had normal neurological development and remained tumor-free through her 20-year follow-up. CONCLUSION: The authors report this rare case of congenital posterior fossa teratoma with long-term outcome, and the literature is reviewed.

Intracranial Dystrophic Calcification of Ventriculoperitoneal Shunt: A Case Report.

Ventriculoperitoneal (VP) shunting is one of the most common simple neurosurgical procedures. VP shunt catheters are made of silicone-coated Silastic tubes, which are made to be inert and hardly induce any reaction in normal tissue. We report a rare case of an extensive intracranial calcification of a VP shunt. This is a very rare case of a documented extensive calcification around the ventricular catheter of a VP shunt. We review the previously reported cases in the literature and present our management of the case. We discuss the possible mechanisms for such a dystrophic calcification around a VP shunt.

Physician awareness of decompressive hemicraniectomy for malignant middle cerebral artery infarction in Saudi Arabia and the Gulf countries.

OBJECTIVE: To explore the perspective on Decompressive craniectomy (DH) of each of these specialties to establish common grounds for improved clinical practice. METHODS: An electronic survey was distributed via email and social media groups to members of these specialties in Kingdom of Saudi Arabia and the Gulf countries. Local practices, common triggers for referral for DH, perceived outcomes of these procedures, individual impression of what constitutes good clinical outcomes were explored. RESULTS: There are 89 physicians participated: 41 (46.1%) neurologists, 34 (38.2%) neurosurgeons, and 14 (15.7%) intensivests. Participants are mostly practicing in intermediate volume centers or high volume centers. Half of the neurosurgeons preferred to be consulted immediately on candidates with large middle cerebral artery (MCA) strokes. The most important referral trigger for DH was clinical changes. The modified Rankin Scale (mRS) cutoff for good clinical outcome was 3 for 73.6% of respondents. There was agreement that DH only improves survival (64.4%). A third of the neurologists considered it to improve functional outcome compared to 15.4% of intensivests and 14.8% of neurosurgeons. There was agreement (66.7%) that patients older than 60 years with involvement of more than one territory should be excluded from DH. Only 7.7% of neurosurgeons excluded patients with dominant hemispheric strokes. CONCLUSION: Our physicians` views are variable in what`s called acceptable outcome, and further studies are needed to to test the characteristics that helps in decision making such as hemisphere dominancy, time onset of stroke and vital radiological signs. This is seen despite the literature being full of data that supports the DC over medical management in malignant MCA infarction. Better multidisciplinary education initiatives are needed to unify the understanding and help improve the practices in this challenging subset of patients.

Public awareness of central nervous system tumors in the Kingdom of Saudi Arabia.

OBJECTIVE: To investigate individuals` knowledge about central nervous system tumors (CNST) signs and symptoms and risk factors, as well as their readiness to seek medical advice. The signs and symptoms associated with CNSTs are often vague, and failure to recognize them could lead to delays in seeking help and possibly fatal results. METHODS: This was a cross-sectional survey that utilized 2 delivery methods. A total of 1,500 personally delivered and 1,500 online self-administered questionnaires were completed in parallel between June 2015 and June 2016 for the occupants of the Kingdom of Saudi Arabia. RESULTS: Significant differences were observed for the sociodemographic characteristics of participants recruited via the 2 methods. The most recognized symptom was "Headaches" (45.2%), and the most recognized risk factor was "Radioactive location/occupation" (84.1%). Overall knowledge scores were low, significantly predicted by employment and cancer contact (p<0.05), while the scores significantly higher for participants who were willing to see their doctors within a week (p<0.005). The most recognized barrier to seeking help was "Worry about what the doctor might find" (74.0%). CONCLUSION: The level of awareness of CNSTs was low. Using a questionnaire delivered in 2 different ways enabled the recruitment of sample pools with different sociodemographic characteristics.

Comprehensive molecular biomarker identification in breast cancer brain metastases.

BACKGROUND: Breast cancer brain metastases (BCBM) develop in about 20-30% of breast cancer (BC) patients. BCBM are associated with dismal prognosis not at least due to lack of valuable molecular therapeutic targets. The aim of the study was to identify new molecular biomarkers and targets in BCBM by using complementary state-of-the-art techniques. METHODS: We compared array expression profiles of three BCBM with 16 non-brain metastatic BC and 16 primary brain tumors (prBT) using a false discovery rate (FDR) p < 0.05 and fold change (FC) > 2. Biofunctional analysis was conducted on the differentially expressed probe sets. High-density arrays were employed to detect copy number variations (CNVs) and whole exome sequencing (WES) with paired-end reads of 150 bp was utilized to detect gene mutations in the three BCBM. RESULTS: The top 370 probe sets that were differentially expressed between BCBM and both BC and prBT were in the majority comparably overexpressed in BCBM and included, e.g. the coding genes BCL3, BNIP3, BNIP3P1, BRIP1, CASP14, CDC25A, DMBT1, IDH2, E2F1, MYCN, RAD51, RAD54L, and VDR. A number of small nucleolar RNAs (snoRNAs) were comparably overexpressed in BCBM and included SNORA1, SNORA2A, SNORA9, SNORA10, SNORA22, SNORA24, SNORA30, SNORA37, SNORA38, SNORA52, SNORA71A, SNORA71B, SNORA71C, SNORD13P2, SNORD15A, SNORD34, SNORD35A, SNORD41, SNORD53, and SCARNA22. The top canonical pathway was entitled, role of BRCA1 in DNA damage response. Network analysis revealed key nodes as Akt, ERK1/2, NFkB, and Ras in a predicted activation stage. Downregulated genes in a data set that was shared between BCBM and prBT comprised, e.g. BC cell line invasion markers JUN, MMP3, TFF1, and HAS2. Important cancer genes affected by CNVs included TP53, BRCA1, BRCA2, ERBB2, IDH1, and IDH2. WES detected numerous mutations, some of which affecting BC associated genes as CDH1, HEPACAM, and LOXHD1. CONCLUSIONS: Using complementary molecular genetic techniques, this study identified shared and unshared molecular events in three highly aberrant BCBM emphasizing the challenge to detect new molecular biomarkers and targets with translational implications. Among new findings with the capacity to gain clinical relevance is the detection of overexpressed snoRNAs known to regulate some critical cellular functions as ribosome biogenesis.

Decompressive hemicraniectomy for malignant middle cerebral artery infarction. Experience from the Western Province of Saudi Arabia.

OBJECTIVE: To describe our experience implementing decompressive hemicraniectomy (DH) for eligible patients with malignant middle cerebral artery (MCA) infarcts. METHODS: We retrospectively collected data of malignant MCA infarction patients requiring DH at King Abdulaziz University Hospital & King Faisal Specialist Hospital & Research Center, Jeddah, Kingdom of Saudi Arabia between October 2010 and July 2015. Clinical outcome was assessed immediately postoperatively using Glasgow Coma Score (GCS), and at 12 months using the modified Rankin scale (mRS) and Barthel index. Survival was evaluated at thirty-days and one year after surgery. RESULTS: Six out of 10 patients diagnosed with malignant MCA infarction underwent DH. Among the surgically treated patients (n=6), 4 were males (66%), and the median age was 22.5 years. The median time from admission to surgery was 35.5 hours. The median post-operative GCS was 6.5. Three patients (50%) died within 30 days of DH. In those who survived, the median mRS was 4.5 and BI was 7.5. CONCLUSION: Decompressive hemicraniectomy saves life and has the potential of improving survival functional outcome when done fast and in carefully selected patients. We call for national awareness of the management of such cases and early intervention.

Publications pattern of clinical epilepsy research in Saudi Arabia.

OBJECTIVE: To assess the progress in the field clinical epilepsy in Saudi Arabia, by analyzing in depth the research output productivity and publication pattern, and to identify the current situation of epilepsy research and offer solutions. METHODS: Literature search strategy was designed to retrieve accessible articles that are related to epilepsy utilizing PubMed, Google Scholar, and Embase. The retrieved articles were analyzed with several parameters, then evaluated using Oxford Center of Evidence Based Medicine level of evidence scale. RESULTS: Of all identified articles, 90 were conducted in Kingdom of Saudi Arabia and therefore were included. The included articles had a frequency of only 3.5 publications per year, and growth of 24.4% between the periods of 1990-2003 and 2004-2016. Only 13.3% of the articles were related to surgical epilepsy but the majority (86.7%) were related to medical epilepsy. Many articles (53.3%) were level III studies. The most common study design was retrospective studies in 35.6%, and the citations number ranged from 1-289 (Mean=7). CONCLUSION: Pattern of publications in clinical epilepsy researches revealed a slow growth rate in the frequency and a lower significance in the quality throughout the past 26 years. Active institutional and national promotion of clinical research is needed to help assess and therefore improve the quality of the provided epilepsy services.