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Neuronal hyperexcitability is a key element of many neurodegenerative disorders including the motor neuron disease Amyotrophic Lateral Sclerosis (ALS), where it occurs associated with elevated late sodium current (I NaL ). I NaL results from incomplete inactivation of voltage-gated sodium channels (VGSCs) after their opening and shapes physiological membrane excitability. However, dysfunctional increases can cause hyperexcitability-associated diseases. Here we reveal the atypical binding mechanism which explains how the neuroprotective ALS-treatment drug riluzole stabilises VGSCs in their inactivated state to cause the suppression of I NaL that leads to reversed cellular overexcitability. Riluzole accumulates in the membrane and enters VGSCs through openings to their membrane-accessible fenestrations. Riluzole binds within these fenestrations to stabilise the inactivated channel state, allowing for the selective allosteric inhibition of I NaL without the physical block of Na + conduction associated with traditional channel pore binding VGSC drugs. We further demonstrate that riluzole can reproduce these effects on a disease variant of the non-neuronal VGSC isoform Nav1.4, where pathologically increased I NaL is caused directly by mutation. Overall, we identify a model for VGSC inhibition that produces effects consistent with the inhibitory action of riluzole observed in models of ALS. Our findings will aid future drug design and supports research directed towards riluzole repurposing., (© 2024. The Author(s).)

Aims: In the literature, it is still unclear if the decisions for selecting the type of implant crown-retaining system are based on scientific-based research or if the Universities' choices, Implant marketing trends, or finances could have a major influence on the private dentists' decisions., Objectives: Therefore, this study aimed to evaluate the crown-retaining system (cement- or screw-retained) used in dental schools and private dental practices., Methods: A 13-item questionnaire was sent to Canadian dental schools (n = 10) and dental offices in London (n = 298), Canada. The questionnaire included demographic questions and questions to reveal the dentists' perspectives on prosthetic implant treatment between the two-retaining systems. Results were analyzed using descriptive statistics and multinomial logistic regression (p = 0.05)., Results: Twenty-four private dentists and five dental schools responded to the survey - 62.5% of private practitioners and 60% of universities reported using both systems. A trend was observed in using screw-retained systems by dentists who graduated 5-10 years ago. Straumann, Astra, and Nobel Biocare were the private practices and dental schools' preferred implant systems. The use of platform switching for all cases was selected by 54.2% of the private practitioners and 40% of the dental schools. Resin cement was the private practice's preferred cementation method; the dental schools used glass ionomer and zinc phosphate cement. The multinomial logistic regressions showed no statistical difference between the crown-retaining system chosen and the decision factors. The laboratory technician's recommendations and cost influenced the decision-making process for private dentists. For the universities, perio-restorative outcome, implant position, survival rates, institute preferences, and evidence-based research influenced the crown-retaining system's decision-making process.  CONCLUSION: The Canadian dental schools and private practice reported using both screw- and cement-retaining systems. However, there was a difference in the selection criteria as the universities showed a tendency towards a more research-based approach in their decision, while for the private practices, the technicians' recommendations and cost played a major role in the decision process. It was noted that the implant systems preconized by the Universities were observed to be used in private practices., (© 2024 The Authors. Journal of Dental Education published by Wiley Periodicals LLC on behalf of American Dental Education Association.)

Meningiomas are the most common intracranial tumors, predominantly affecting adults, with a higher incidence in female and elderly populations. Despite their prevalence, research on neurocognitive impairment in meningioma patients remains limited compared to intra-axial tumors such as gliomas. We conducted a comprehensive systematic review of the current literature on neurocognitive outcomes in meningioma patients pre- and post-surgery. Our review revealed significant disparities in reported neurocognitive outcomes, with prospective studies suggesting tumor-related factors as the primary contributors to postoperative deficits, while retrospective studies imply surgical intervention plays a significant role. Regardless of study design or specifics, most studies lack baseline preoperative neurocognitive assessments and standardized protocols for evaluating neurocognitive function. To address these gaps, we advocate for standardized neurocognitive assessment protocols, consensus on neurocognitive domains to be targeted in this population by tailored test batteries, and more prospective studies to elucidate correlations between tumor characteristics, patient attributes, surgical interventions, neurocognitive status, and planning for implementing tailored neurocognitive rehabilitation strategies early in the postoperative course which is crucial for achieving optimal long-term neurocognitive outcomes and enhancing patients' quality of life., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Distraction osteogenesis is utilized to increase intracranial volume in the treatment of restrictive pathologies, most commonly syndromic synostosis. Children too young for open calvarial vault expansion or other systemic or local contraindications to a direct reconstructive approach benefit greatly from distraction osteogenesis, typically addressing posterior vault expansion. Wound infection, cerebrospinal fluid (CSF) leak, device failure, need for a second surgery for removal, and cost, are issues that can limit the use of this approach. These challenges are more pronounced in low- and middle-income countries (LMICs) due to lack of access to the device, the financial burden of the need for a second surgery, and the severity of the implications of infection and CSF leak. Over the last five decades, there has been an increased acceptance of bioresorbable instrumentation in craniofacial surgery. Poly L-lactic acid, polyglycolic acid, and polydioxanone are the most commonly used polymers. New resorbable fixation tools such as ultrasound-activated pins and heat-activated pins are superior to conventional bioresorbable screws in allowing attachment to thinner bone plates. In this paper, we present a review of the literature on cranial vault distraction and the use of bioresorbable materials and propose a novel design of a fully absorbable cranial distractor system using external magnetic distraction control, eliminating the need for external activation ports and a second surgery to remove the hardware. The application of this technology in LMIC settings could advance access to care and treatment options for patients with syndromic synostosis., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Cranial irradiation is associated with several adverse events such as endocrinopathy, growth retardation, neurocognitive impairment, secondary malignancies, cerebral vasculopathy, and potential stroke. The better side effects profile of proton beam therapy compared with that of photon radiation therapy is due to its physical properties, mainly the sharp dose fall-off after energy deposition in the Bragg peak. Despite the better toxicity profile of proton beam therapy, the risk of  moyamoya syndrome still exists. We conducted a systematic review of the existing literature on moyamoya syndrome after receiving cranial radiation therapy for pediatric brain tumors to investigate the incidence of moyamoya syndrome after receiving photon versus proton radiation therapy. In this review, we report that the incidence of moyamoya syndrome after receiving proton beam therapy is almost double that of photon-induced moyamoya syndrome. Patients who received proton beam therapy for the management of pediatric brain tumors are more likely to develop moyamoya syndrome at the age of less than 5 years. Meanwhile, most patients with proton-induced moyamoya are more likely to be diagnosed within the first 2 years after the completion of their proton beam therapy., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Thousands of videos are posted on websites and social media every day, including Twitter, Facebook, WhatsApp, Instagram, and YouTube. Newspapers, law enforcement publications, criminal investigations, surveillance systems, Banking, the museum, the military, imaging in medicine, insurance claims, and consumer photography are just a few examples of places where important visual data may be obtained. Thus, the emergence of powerful processing tools that can be easily made available online poses a huge threat to the authenticity of videos. Therefore, it's vital to distinguish between true and fake data. Digital video forgery detection techniques are used to validate and check the realness of digital video content. Deep learning algorithms lately sparked a lot of interest in the field of digital forensics, such as Recurrent Neural Networks (RNN), Deep Convolutional Neural Networks (DCNN), and Adaptive Neural Networks (ANN). In this paper, we give a soft taxonomy as well as a thorough overview of recent research on multimedia falsification detection systems. First, the basic knowledge needed to comprehend video forgery is provided. Then, a summary of active and passive video manipulation detection approaches is provided. Anti-forensics, compression video methods, datasets required for video forensics, and challenges of video detection approaches are also addressed. Following that, we presented an overview of deepfake, and the datasets required for detection were also provided. Also, helpful software packages and forensics tools for video detection are covered. In addition, this paper provides an overview of video analysis tools that are used in video forensic applications. Finally, we highlight research difficulties as well as interesting research avenues. In short, this survey provides detailed information and a broader investigation to extract data and detect fraud video contents under one umbrella., Competing Interests: Conflict of interestWe declare that we have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

The Saudi Osteoporosis Society (SOS) has updated its guidelines for the diagnosis and management of osteoporosis in Saudi Arabia (SA), with emphasis on postmenopausal women. This document is relevant to all healthcare professionals in SA involved in the care of patients with osteoporosis and osteoporosis-related fractures., Introduction: The SOS launched the first national osteoporosis guidelines in 2015 and spearheaded the Gulf Cooperation Council Countries (GCC) osteoporosis consensus report in 2020 which was under the auspices of the European Society for Clinical and Economic Aspects of Osteoporosis (ESCEO). This paper highlights a major update of the guidelines in the SA setting., Methods: This guideline is an adaptation of the current guidelines derived from ESCEO, the American Association of Clinical Endocrinologists (AACE), and the GCC osteoporosis consensus report and studies on osteoporosis done in SA. Where accessible, the timeliest systematic review, meta-analysis, and randomized controlled trials were used as evidence., Results: The present update includes new recommendations for the assessment of osteoporosis taking into consideration the Saudi model of FRAX for fracture probabilities, appropriate doses for the maintenance of vitamin D status and calcium, the use of representative blood analytes for therapy monitoring, the use of romosozumab and sequential therapy in the pharmacological management strategies, and the establishment of fracture liaison services to prevent secondary fractures., Conclusion: This updated guideline is for all healthcare professionals involved in osteoporosis and post-fracture care and management in SA and harmonized the most up-to-date changes in the field based on evidence-based medicine for use in the local setting., (© 2023. The Author(s).)

Background: Children with chronic kidney disease (CKD), particularly those who require hemodialysis (HD), are at high risk of hepatitis B virus (HBV) infection. The HBV vaccine non-/hypo-response rate among HD children remains high, and it is critical to investigate the influencing factors and their linkages. The aim of this study was to identify the pattern of HB vaccination response in HD children and to analyze the interference of various clinical and biomedical factors with the immunological response to HB vaccination. Methods: This cross-sectional study included 74 children on maintenance hemodialysis, aged between 3 and 18 years. These children were subjected to complete clinical examination and laboratory investigations. Results: Out of a total of 74 children with HD, 25 (33.8%) were positive for the HCV antibody. Regarding the immunological response to hepatitis B vaccine, 70% were non-/hypo-responders (≤100 IU/mL) and only 30% mounted a high-level response (more than 100 IU/mL). There was a significant relation between non-/hypo-response and sex, dialysis duration, and HCV infection. Being on dialysis for more than 5 years and being HCV Ab-positive were independent variables for non-/hypo-response to HB vaccine. Conclusions: Children with CKD on regular HD have poor seroconversion rates in response to the HBV vaccine, which were influenced by dialysis duration and HCV infection.

The aim of this study was to examine the feasibility and effectiveness of telemedicine care provided to osteoporotic patients in Saudi Arabia. Our results show that this service was effective and feasible, and patients had a good rate of satisfaction with it., Purpose: To investigate the efficacy and feasibility of telemedicine care in osteoporotic patients during the COVID-19 lockdown period in Saudi Arabia compared to in-person patients, as well as their satisfaction with this service., Methods: This observational retrospective study was conducted between March 2021 and September 2021 in King Saud University Medical City, Saudi Arabia. A survey was used to compare patients attending telemedicine clinics with in-person patients in terms of access and adherence to medications, occurrence of new fractures, and overall satisfaction with this service., Results: 195 patients attended the telemedicine clinic, while 63 attended the in-person clinic. Exercise frequency was similar in both groups, although exercise intensity was greater in the in-person group. 25(OH)D levels were stable in both groups. The availability and delay of supply of osteoporosis medications were not statistically different between both groups while adherence to treatment did not differ significantly between the two groups. The majority of patients in the telemedicine group were satisfied., Conclusions: Telemedicine care was feasible and effective in managing osteoporotic patients during the COVID-19 epidemic. Such service could be considered in the future for managing disabled patients and those living in remote areas., (© 2022. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Background: Sepsis, caused by a dysregulated response to infections, can lead to cardiac arrhythmias. However, the mechanisms underlying sepsis-induced inflammation, and how inflammation provokes cardiac arrhythmias, are not well understood. We hypothesized that cannabidiol (CBD) may ameliorate lipopolysaccharide (LPS)-induced cardiotoxicity, via Toll-like receptors (TLR4) and cardiac sodium channels (Na V 1.5)., Methods and Results: We incubated human immune cells (THP-1 macrophages) with LPS for 24 h, then extracted the THP-1 incubation media. ELISA assays showed that LPS (1 or 5 μg·ml -1 ), in a concentration-dependent manner, or MPLA (TLR4 agonist, 5 μg·ml -1 ) stimulated the THP-1 cells to release inflammatory cytokines (TNF-α and IL-6). Prior incubation (4 h) with CBD (5 μM) or C34 (TLR4 antagonist: 5 μg·ml -1 ) inhibited LPS and MPLA-induced release of both IL-6 and TNF-α. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) were subsequently incubated for 24 h in the media extracted from THP-1 cells incubated with LPS, MPLA alone, or in combination with CBD or C34. Voltage-clamp experiments showed a right shift in the voltage dependence of Na V 1.5 activation, steady state fast inactivation (SSFI), increased persistent current and prolonged in silico action potential duration in hiSPC-CMs incubated in the LPS or MPLA-THP-1 media. Co-incubation with CBD or C34 rescued the biophysical dysfunction caused by LPS and MPLA., Conclusion: Our results suggest that CBD may protect against sepsis-induced inflammation and subsequent arrhythmias through (i) inhibition of the release of inflammatory cytokines, antioxidant and anti-apoptotic effects and/or (ii) a direct effect on Na V 1.5., (© 2022 British Pharmacological Society.)

Acquired and inherited dysfunction in voltage-gated sodium channels underlies a wide range of diseases. In addition to defects in trafficking and expression, sodium channelopathies are caused by dysfunction in one or several gating properties, for instance activation or inactivation. Disruption of channel inactivation leads to increased late sodium current, which is a common defect in seizure disorders, cardiac arrhythmias skeletal muscle myotonia and pain. An increase in late sodium current leads to repetitive action potentials in neurons and skeletal muscles, and prolonged action potential duration in the heart. In this Topical Review, we compare the effects of late sodium current in brain, heart, skeletal muscle and peripheral nerves., (© 2022 The Authors. The Journal of Physiology © 2022 The Physiological Society.)

Nav1.5 is the pore forming α-subunit of the cardiac voltage-gated sodium channel that initiates cardiac action potential and regulates the human heartbeat. A normal level of Nav1.5 is crucial to cardiac function and health. Over- or under-expression of Nav1.5 can cause various cardiac diseases ranging from short PR intervals to Brugada syndromes. An assay that can directly quantify the protein amount in biological samples would be a priori to accurately diagnose and treat Nav1.5-associated cardiac diseases. Due to its large size (>200 KD), multipass transmembrane domains (24 transmembrane passes), and heavy modifications, Nav1.5 poses special quantitation challenges. To date, only the relative quantities of this protein have been measured in biological samples. Here, we describe the first targeted and mass spectrometry (MS)-based quantitative assay that can provide the copy numbers of Nav1.5 in cells with a well-defined lower limit of quantification (LLOQ) and precision. Applying the developed assay, we successfully quantified transiently expressed Nav1.5 in as few as 1.5 million Chinese hamster ovary (CHO) cells. The obtained quantity was 3 ± 2 fmol on the column and 3 ± 2 × 104 copies/cell. To our knowledge, this is the first absolute quantity of Nav1.5 measured in a biological sample.

Rhombencephalosynapsis is a rare congenital anomaly, characterized by partial or total agenesis of the cerebellar vermis with midline fusion of the cerebellar hemispheres, dentate nuclei, and the superior cerebellar peduncles, creating the distinctive keyhole appearance of the fourth ventricle. Rhombencephalosynapsis can be isolated or can occur in association with other congenital anomalies and syndromes such as Gómez-López-Hernández syndrome (GLHS) or VACTERL: vertebral anomalies (V), anal atresia (A), cardiovascular defects (C), esophageal atresia and/or tracheoesophageal fistula (TE), and renal (R) and limb/radial (L) anomalies. Recent advances in prenatal imaging have resulted in an increasing rate of prenatal diagnosis of abnormalities of the posterior fossa including rhombencephalosynapsis. Patients with rhombencephalosynapsis may present with motor developmental delay, ataxia, swallowing difficulties, muscular hypotonia, spastic quadriparesis, abnormal eye movements, and a characteristic "figure-of-eight" head shaking. Cognitive outcome varies from severe intellectual disability to normal intellectual function. Rhombencephalosynapsis with VACTERL is often associated with severe cognitive disabilities, whereas patients with GLHS may have better cognitive function. The most common associated findings with rhombencephalosynapsis include hydrocephalus, mesencephalosynapsis, holoprosencephaly, pontocerebellar hypoplasia, corpus callosum dysgenesis, and absence of septum pellucidum. Patients can be categorized into 4 groups: 1) rhombencephalosynapsis associated with GLHS; 2) rhombencephalosynapsis with VACTERL; 3) rhombencephalosynapsis with atypical holoprosencephaly, and 4) isolated rhomboencephalosynapsis. The etiology of rhombencephalosynapsis is unknown. Here, we discuss several hypotheses about its etiology., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Metabolic syndrome (MetS) is a serious health condition that is becoming extremely threatening in Saudi Arabia. The link between vitamin D receptor (VDR) gene polymorphisms and maternal MetS has been observed in several ethnic groups, but is yet to be clarified in the Arabian population. This study aims to investigate the relationship between the FokI VDR genotype and the risk of MetS and its components in pregnant Saudi women. A cross-sectional study was conducted using 368 pregnant Saudi women on first trimester screened for MetS (44 with MetS and 324 without MetS). Measurements included anthropometrics, glycemic and lipid profile and 25(OH)D. TaqMan genotyping assay was used to determine Fokl VDR genotype of participants. Vitamin D deficiency (25(OH)D <50nmol/l) was seen in 85% of the participants. An estimated 12% of participants had MetS. In the MetS group, the FokI VDR genotyping frequencies for FF, Ff , and ff genotypes were 50%, 36.4% and 13.6%, respectively. In controls, the frequencies were 62.7%, 31.4% and 5.9%, respectively. No significant association between the individual MetS components and FokI VDR genotypes were observed. Nevertheless, carriers of the ff allele had a significant risk for full maternal MetS [Odds Ratio 4.2 (95% Confidence Interval 1.4-12.2; adjusted p =0.009). The study suggests that the ff FokI VDR genotype is a genetic marker of maternal MetS in pregnant Arabian women. Prospective studies that include neonatal outcomes may confirm present findings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Alzaim, Al-Daghri, Sabico, Fouda, Al-Musharaf, Khattak, Mohammed, Al-Ajlan, Binjawhar and Wood.)

Cerebral palsy (CP) is the most common cause of physical disability for children worldwide. Many infants and toddlers are not diagnosed with CP until they fail to achieve obvious motor milestones. Currently, there are no effective pharmacologic interventions available for infants and toddlers to substantially improve their trajectory of neurodevelopment. Because children with CP from preterm birth also exhibit a sustained immune system hyper-reactivity, we hypothesized that neuro-immunomodulation with a regimen of repurposed endogenous neurorestorative medications, erythropoietin (EPO) and melatonin (MLT), could improve this trajectory. Thus, we administered EPO + MLT to rats with CP during human infant-toddler equivalency to determine whether we could influence gait patterns in mature animals. After a prenatal injury on embryonic day 18 (E18) that mimics chorioamnionitis at ∼25 weeks human gestation, rat pups were born and raised with their dam. Beginning on postnatal day 15 (P15), equivalent to human infant ∼1 year, rats were randomized to receive either a regimen of EPO + MLT or vehicle (sterile saline) through P20. Gait was assessed in young adult rats at P30 using computerized digital gait analyses including videography on a treadmill. Results indicate that gait metrics of young adult rats treated with an infantile cocktail of EPO + MLT were restored compared to vehicle-treated rats (p < 0.05) and similar to sham controls. These results provide reassuring evidence that pharmacological interventions may be beneficial to infants and toddlers who are diagnosed with CP well after the traditional neonatal window of intervention., (© 2022 S. Karger AG, Basel.)

Genetic differences among individuals could affect the clinical presentations and outcomes of COVID-19. Human Leukocyte Antigens are associated with COVID-19 susceptibility, severity, and prognosis. This study aimed to identify HLA-B and -C genotypes among 69 Egyptian patients with COVID-19 and correlate them with disease outcomes and other clinical and laboratory data. HLA-B and -C typing was performed using Luminex-based HLA typing kits. Forty patients (58%) had severe COVID-19; 55% of these patients died, without reported mortality in the moderate group. The alleles associated with severe COVID-19 were HLA-B*41, -B*42, -C*16, and -C*17, whereas HLA-B*15, -C*7, and -C*12 were significantly associated with protection against mortality. Regression analysis showed that HLA-B*15 was the only allele associated with predicted protection against mortality, where the likelihood of survival increased with HLA-B*15 (P < 0.001). Patient survival was less likely to occur with higher total leukocytic count, ferritin, and creatinine levels. This study provides interesting insights into the association between HLA class I alleles and protection from or severity of COVID-19 through immune response modulation. This is the first study to investigate this relationship in Egyptian patients. More studies are needed to understand how HLA class I alleles interact and affect Cytotoxic T lymphocytes and natural killer cell function., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

Breast cancer is a heterogeneous disease, and new biomarkers are needed for more accurate classification and prediction of prognosis. The goal of this study is to assess the expression of breast cancer classification genes, to identify new molecular signatures in different intrinsic subtypes of breast cancer and to correlate their expression with different clinical variables. The study included 84 female patients newly diagnosed with non-metastatic breast cancer at the outpatient clinic at the National Cancer Institute, Cairo University, Egypt. Detection of 17 breast cancer classification genes was done using RT-PCR in tumor and normal tissues. Estrogen receptor (ER), progesterone receptor (PR), HER2, and Ki67 expression were assessed using IHC assay for intrinsic subtyping. Combined expression of FOXA1 and GATA3 was statistically higher in luminal subtypes in comparison to non-luminal subtypes. In Luminal A subtype; GRB7, EGFR, PTGS2, ID1, and KRT5 were significantly downregulated. FOXA1 and GATA3 were significantly upregulated in luminal B subtype, where EGFR and PTGS2 were significantly downregulated. While ESR1, EGFR, KRT5 and PTGS2 showed significantly low expression in tumor tissue in Her2 enriched subtype, TFF3 was significantly downregulated in triple negative subtype. GATA3 and FOXA1 expression exhibited significant correlation with tumor grade. Furthermore, GATA3, FOXA1, ESR1, and ID1 were also correlated significantly with staging of the tumor. Combined expression of ESR1, FOXA1 and GATA3 represents a molecular signature of luminal subtypes. Long term follow-up is needed to investigate the prognostic effect of breast cancer classification genes found in this study., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Osteoporosis and its complications are a major health concern in Saudi Arabia, and the prevalence of osteoporosis is on the rise. The aim of this study was to estimate the direct healthcare cost for patients with osteoporosis. A retrospective study was carried out among adult patients with osteoporosis in a teaching hospital in Saudi Arabia. A bottom-up approach was conducted to estimate the healthcare resources used and the total direct medical cost for the treatment of osteoporosis and related fractures. The study included 511 osteoporosis patients, 93% of whom were female. The average (SD) age was 68.5 years (10.2). The total mean direct medical costs for patients without fractures were USD 975.77 per person per year (PPPY), and for those with osteoporotic fractures, the total direct costs were USD 9716.26 PPPY, of which 56% of the costs were attributable to surgery procedures. Prior to fractures, the main cost components were medication, representing 61%, and physician visits, representing 18%. The findings of this study indicated the economic impact of osteoporosis and related fractures. With the aging population in Saudi Arabia, the burden of disease could increase significantly, which highlights the need for effective prevention strategies to minimize the economic burden of osteoporosis.

Evidence suggests that immunosuppressant therapies protect against harmful effects of endotoxaemia. In this study, we tested whether calcineurin-dependent (cyclosporine/tacrolimus) and -independent (sirolimus) immunosuppressants variably influence nephrotoxicity induced by endotoxaemia and whether this interaction is modulated by testosterone. We investigated the effects of immunosuppressants on renal histopathological, biochemical and inflammatory profiles in endotoxic male rats and the role of androgenic state in the interaction. Six-hour treatment of rats with lipopolysaccharide (LPS, 3 mg/kg) increased (i) serum urea/creatinine, (ii) width of proximal/distal tubules, (iii) tubular degeneration and vacuolation, (iv) Western protein expressions of renal toll-like receptor 4, monocyte chemoattractant protein-1, and NADPH oxidase-2, and (v) serum tumour necrosis factor-α and myeloperoxidase. These endotoxic manifestations were intensified and eliminated upon concurrent exposure to cyclosporine and sirolimus, respectively. The cyclosporine actions appear to be a class rather than a drug effect because similar exacerbation of LPS nephrotoxicity was observed in rats treated with tacrolimus, another calcineurin inhibitor (CNI). Moreover, the deteriorated renal outcomes in LPS/tacrolimus-treated rats were reduced after castration or androgen receptor blockade by flutamide. The data suggest opposite effects for calcineurin-dependent (exaggeration) and -independent immunosuppressants (amelioration) on renal defects of endotoxaemia and implicate androgenic pathways in the worsened endotoxic renal profile induced by CNIs., (© 2021 John Wiley & Sons Australia, Ltd.)

Background: The advancement of endoscopic techniques in the past decade has improved the surgical management of cerebellopontine angle (CPA) tumors. Endoscope-assisted microsurgery improves the ability to evaluate the extent of resection, achieve safe tumor resection and reduce the risk of surgery-related morbidity., Methods: In this study, we used a cadaveric model to demonstrate a step by step endoscope-assisted microsurgery of the retrosigmoid approach to the lateral posterior fossa., Results: Retrosigmoid craniotomies were performed on four latex-injected cadaver heads (eight CPAs). Microsurgical exposures were performed to identify neurovascular structures in each segment. 0° and 30° rigid endoscope lenses were subsequently introduced into each corridor and views were compared in this manner. The endoscopic images were compared with the standard microscopic views to determine the degree of visualization with each technique. In each case, better visualization was provided by both the 0° and 30° endoscope lenses. Endoscopic views frequently clarified neurovascular relationships in obscured anatomic regions., Conclusion: Endoscope-assisted microsurgery could allow better visualization of various regions of the posterior fossa. Surgical planning for posterior fossa lesions should include consideration of this combined approach., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Surgical Neurology International.)

Introduction Systemic lupus erythematosus (SLE) is a systemic disease with clinically heterogeneous outcomes. Lupus nephritis (LN) is a common complication of SLE. LN impacts clinical SLE outcomes both directly, in the form of target organ damage, and indirectly, through the adverse effects of immunosuppressive therapy. Patients & methods The study included 402 SLE cases with biopsy-proven lupus nephritis who were under follow-up for the past 13 years at Mansoura Urology and Nephrology Center, Egypt. We studied the differences in outcome among various LN classes and between 275 proliferative cases and 102 non-proliferative cases. Results Class IV was the main LN class in our series with renal survival of 60% at 10 years. The major induction regimen after the first biopsy was cyclophosphamide. Mycophenolate mofetil was the main induction and adjunctive regimen after the second biopsy. The mean follow-up period was 6.7 + 5.2 years. Higher serum creatinine, proteinuria, activity, and chronicity indices were noted in proliferative LN. Patients suffering from proliferative lesions received higher immunosuppression and demonstrated higher morbidity than those with non-proliferative lesions. Remission was higher among the non-proliferative compared to the proliferative group. Conclusions Serum creatinine, proteinuria, and LN class were the most relevant prognostic factors for renal survival among Egyptian LN patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Zahab et al.)

Objective: The goal in this study was to outline unique differences between radiation-induced and nonradiation-induced pediatric meningiomas and to identify independent risk factors of tumor recurrence/progression., Methods: This is a retrospective cohort study of all pediatric meningiomas diagnosed and surgically treated at the authors' institution between 1993 and 2017. Multivariable Cox regression was applied to identify independent risk factors for tumor recurrence/progression., Results: Thirty-five patients were identified. The primary etiology was nonradiation-induced (n = 24: n = 3 with neurofibromatosis type 2) or radiation-induced (n = 11: acute lymphoblastic leukemia [n = 5], medulloblastoma [n = 4], germ cell tumor [n = 1], and primitive neuroectodermal tumor [n = 1]) meningioma. The mean age at time of diagnosis was 10.7 ± 5.7 years for nonradiation-induced and 17.3 ± 3.5 years for radiation-induced meningiomas. Overall, 8/24 patients with nonradiation-induced meningioma experienced either recurrence or progression of the tumor. Of the 8 patients with tumor recurrence or progression, the pathological diagnosis was clear cell meningioma (n = 3: 2 recurrent and 1 progressive); grade I (n = 2 progressive); grade I with atypical features (n = 2: 1 recurrent and 1 progressive); or atypical meningioma (n = 1 recurrent). None of the patients with radiation-induced meningioma experienced recurrence or progression. Predictors of tumor recurrence/progression by univariate analysis included age at time of diagnosis ≤ 10 years (p = 0.002), histological subtype clear cell meningioma (p = 0.003), and primary etiology nonradiation-induced meningioma (p = 0.04), and there was a notable trend with elevated MIB-1 staining index (SI) (p = 0.09). There was no significant difference between nonradiation-induced and radiation-induced meningiomas (p = 0.258), although there was a trend between recurrent and nonrecurrent meningiomas (p = 0.09). Multivariate Cox regression, adjusted for length of follow-up, identified younger age at diagnosis (p = 0.004) and a higher MIB-1 SI (p = 0.044) as independent risk factors for recurrence. Elevated MIB-1 SI statistically correlated with atypia (p < 0.001). However, there was no significant statistical correlation between tumor recurrence/progression and atypia (p = 0.2)., Conclusions: Younger patient age and higher MIB-1 SI are independent risk factors for recurrence. Atypia was not a predictor of recurrence.

Cannabidiol (CBD) is the primary nonpsychotropic phytocannabinoid found in Cannabis sativa, which has been proposed to be therapeutic against many conditions, including muscle spasms. Among its putative targets are voltage-gated sodium channels (Navs), which have been implicated in many conditions. We investigated the effects of CBD on Nav1.4, the skeletal muscle Nav subtype. We explored direct effects, involving physical block of the Nav pore, as well as indirect effects, involving modulation of membrane elasticity that contributes to Nav inhibition. MD simulations revealed CBD's localization inside the membrane and effects on bilayer properties. Nuclear magnetic resonance (NMR) confirmed these results, showing CBD localizing below membrane headgroups. To determine the functional implications of these findings, we used a gramicidin-based fluorescence assay to show that CBD alters membrane elasticity or thickness, which could alter Nav function through bilayer-mediated regulation. Site-directed mutagenesis in the vicinity of the Nav1.4 pore revealed that removing the local anesthetic binding site with F1586A reduces the block of INa by CBD. Altering the fenestrations in the bilayer-spanning domain with Nav1.4-WWWW blocked CBD access from the membrane into the Nav1.4 pore (as judged by MD). The stabilization of inactivation, however, persisted in WWWW, which we ascribe to CBD-induced changes in membrane elasticity. To investigate the potential therapeutic value of CBD against Nav1.4 channelopathies, we used a pathogenic Nav1.4 variant, P1158S, which causes myotonia and periodic paralysis. CBD reduces excitability in both wild-type and the P1158S variant. Our in vitro and in silico results suggest that CBD may have therapeutic value against Nav1.4 hyperexcitability., (© 2021 Ghovanloo et al.)

Background: De novo malignancy is a worrying complication after kidney transplantation; the type of which may vary due to factors such as the prevalence of viral infection and race. Kaposi sarcoma used to be the most common malignancy among our patients constituting more than one-third of cancers. Nevertheless, we noticed that Kaposi sarcoma has not been observed for a long period. Therefore, we conducted this study to explore such observation., Methods: Data of all kidney transplant recipients were retrieved and retrospectively analyzed. Their total number was 3126 patients. Their mean age was 28.71 ± 10.97 years and of them, 823 (26.3%) were females. The pattern of Kaposi sarcoma throughout the last decade as well as the preceding three decades was studied. The possible relation between the disappearance of Kaposi sarcoma and three paradigm shifts in our practice, namely the use of mTOR inhibitors, steroid-free regimen and CMV prophylaxis was explored., Results: Since 2010, no new cases of Kaposi sarcoma have been observed. In addition, patients who have been transplanted after 2006 did not develop such malignancy. Patients who received CMV prophylaxis and/or were maintained on mTOR inhibitor or steroid-free regimens have not developed Kaposi sarcoma. Moreover, CMV prophylaxis had a statistically significant difference when compared to a homogenous group without CMV prophylaxis. However, Kaplan-Meier analysis of patients of the three policies and their counterpart groups showed comparable results., Conclusion: Kaposi sarcoma, which was previously the most common malignancy, is no longer observed for almost a decade among our kidney transplant recipients. m-TOR inhibitors, steroid-free regimen and CMV prophylaxis policy are possible contributing factors. Nevertheless, only CMV prophylaxis policy had a statistically significant relation to the disappearance of Kaposi sarcoma.

Background: Cardiovascular anomalies are predisposing factors for diabetes-induced morbidity and mortality. Recently, we showed that high glucose induces changes in the biophysical properties of the cardiac voltage-gated sodium channel (Nav1.5) that could be strongly correlated to diabetes-induced arrhythmia. However, the mechanisms underlying hyperglycemia-induced inflammation, and how inflammation provokes cardiac arrhythmia, are not well understood. We hypothesized that inflammation could mediate the high glucose-induced biophyscial changes on Nav1.5 through protein phosphorylation by protein kinases A and C. We also hypothesized that this signaling pathway is, at least partly, involved in the cardiprotective effects of cannabidiol (CBD) and 17β-estradiol (E 2 ). Methods and Results: To test these ideas, we used Chinese hamster ovarian (CHO) cells transiently co-transfected with cDNA encoding human Nav1.5 α-subunit under control, a cocktail of inflammatory mediators or 100 mM glucose conditions (for 24 h). We used electrophysiological experiments and action potential modeling. Inflammatory mediators, similar to 100 mM glucose, right shifted the voltage dependence of conductance and steady-state fast inactivation and increased persistent current leading to computational prolongation of action potential (hyperexcitability) which could result in long QT3 arrhythmia. We also used human iCell cardiomyocytes derived from inducible pluripotent stem cells (iPSC-CMs) as a physiologically relevant system, and they replicated the effects produced by inflammatory mediators observed in CHO cells. In addition, activators of PK-A or PK-C replicated the inflammation-induced gating changes of Nav1.5. Inhibitors of PK-A or PK-C, CBD or E 2 mitigated all the potentially deleterious effects provoked by high glucose/inflammation. Conclusion: These findings suggest that PK-A and PK-C may mediate the anti-inflammatory effects of CBD and E 2 against high glucose-induced arrhythmia. CBD, via Nav1.5, may be a cardioprotective therapeutic approach in diabetic postmenopausal population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Fouda and Ruben.)

Background: Saudi Arabia has a high burden of diabetes mellitus and vitamin D deficiency. The objective of this study was to explore the association between glycosylated hemoglobin and 25-hydroxyvitamin D in patients with type 2 diabetes mellitus (T2DM) in Riyadh, Saudi Arabia., Methods: An interview based cross-sectional study was conducted on 606 patients with type 2 diabetes, aged 30-75 years, visiting primary health care centers. Blood samples were collected for measuring HbA1c, 25(OH)D and bone and lipid markers. Multivariable linear regression analysis was conducted to explore the association between HbA1c and 25(OH)D., Results: The mean (±SD) levels for HbA1c and 25(OH) D were 7.69 (±1.77) and 44.28 (±23.06), respectively. Around 55% of patients had uncontrolled HbA1c (>7.0), whereas vitamin D deficiency (<50 nmol/L) was found in 52.3% (=317). Multiple linear regression analysis found that a unit increase in vitamin D levels and parathyroid hormone levels was associated with -0.17 (-0.02, -0.01, p < 0.001) and -0.20 (-2.66, -1.18, p < 0.001) unit decrease in levels of HbA1c, respectively. Similarly, increasing age was associated with -0.15 (-0.01, -0.04, p = 0.002) unit decrease in HbA1c levels, whereas unit increases in serum alkaline phosphatase, calcium and diabetes duration were associated with 0.22 (0.01, 0.02, p < 0.001), 0.14 (1.03, 3.88, p = 0.001) and 0.26 (0.42, 0.78, p < 0.001) unit increase in HbA1c levels, respectively., Conclusion: HbA1c levels are associated with 25-hydroxyvitamin D levels. For better control of HbA1c levels, it is important to maintain 25-hydroxyvitamin D level and bone markers within normal range.

Objective: The goal of this study was to identify the independent risk factors for recurrence or progression of pediatric craniopharyngioma and to establish predictors of the appropriate timing of intervention and best management strategy in the setting of recurrence/progression, with the aim of optimizing tumor control., Methods: This is a retrospective cohort study of all pediatric patients with craniopharyngioma who were diagnosed and treated at Boston Children's Hospital between 1990 and 2017. This study was approved by the institutional review board at Boston Children's Hospital. All statistical analyses were performed using Stata software., Results: Eighty patients (43 males and 37 females) fulfilled the inclusion criteria. The mean age at the time of diagnosis was 8.6 ± 4.4 years (range 1.2-19.7 years). The mean follow-up was 10.9 ± 6.5 years (range 1.3-24.6 years). Overall, 30/80 (37.5%) patients developed recurrence/progression. The median latency to recurrence/progression was 12.75 months (range 3-108 months). Subtotal resection with no adjuvant radiotherapy (p < 0.001) and fine calcifications (p = 0.008) are independent risk factors for recurrence/progression. An increase (%) in the maximum dimension of the tumor at the time of recurrence/progression was considered a statistically significant predictor of the appropriate timing of intervention., Conclusions: Based on the identified independent risk factors for tumor recurrence/progression and the predictors of appropriate timing of intervention in the setting of recurrence/progression, the authors propose an algorithm for optimal management of recurrent pediatric craniopharyngioma to increase the likelihood of tumor control.

Purpose: To develop postoperative surveillance protocols that yield efficient detection rates of tumor recurrence or progression using fewer imaging studies and less cost., Method: This is a retrospective cohort study of all pediatric craniopharyngioma patients who have been diagnosed and treated at Boston Children's Hospital (BCH) between 1990 and 2017. All statistical analyses were performed using Stata., Results: Eighty patients (43 males and 37 females) fulfilled the inclusion criteria. The mean age at time of diagnosis was 8.6 ± 4.4 years. The mean follow-up period was 10.9 ± 6.5 years. Overall 30/80 (37.5%) patients experienced tumor recurrence/progression. The median latency to recurrence/progression was 12.75 months (range 3 to 108 months), with 76.6% of the recurrences/progressions taking place within the first 2 years postoperatively. Given the lack of any clinical symptoms/signs associated with the vast majority of the recurrent/progressed cases, we propose postoperative MR imaging surveillance protocols that are substantially less intensive than the current practice. Therefore, we recommend the following postoperative MR imaging surveillance protocols, stratified by management strategies; 0, 9, 15, 36, 48, and 60 months for patients who underwent GTR, 0, 3, 6,12, 18, and 24 months for patients who underwent STR alone and 0, 3, 12, 72, 96, and 120 months for patients who underwent STR followed by subsequent XRT., Conclusion: The proposed postoperative MR imaging surveillance protocols would provide a potential 50% decrement of healthcare costs. It may also minify the psychological burden of frequent MR scanning for these patients and their families.

Purpose: To identify the independent risk factors for developing morbid hypothalamic obesity, to propose a predictive scoring system for morbid hypothalamic obesity, and to propose an algorithm for management in order to minimize the risk of developing morbid hypothalamic obesity in patients with pediatric craniopharyngioma., Methods: A retrospective analysis of all pediatric craniopharyngioma patients diagnosed and treated at Boston Children's Hospital (BCH) between 1985 and 2017. Analysis of the data was conducted using IBM SPSS Statistics., Results: We identified 105 patients, 90 (47 males and 43 females) fulfilled the inclusion criteria. The median age of patients at time of diagnosis was 8.4 years. The median follow-up was 10.6 years. Morbid hypothalamic obesity was evident in 28 (31.1%) patients at the last follow-up visit. Age of patients at time of diagnosis > 10 years (P = 0.023), preoperative body mass index (BMI) > 95th percentile (P = 0.006), and preoperative papilledema (P < 0.001) were the independent risk factors for developing morbid hypothalamic obesity., Conclusion: We developed a unique predictive scoring system in order to differentiate between patients with and without high risk for developing morbid hypothalamic obesity.

Endotoxic manifestations are diminished in female populations due to immune boosting actions of sex steroids. Considering that tobacco constituents including nicotine inhibit estrogen synthesis, we tested the hypothesis that nicotine exposure unveils cardiovascular anomalies of endotoxemia in female rats. Studies were undertaken in conscious female rats treated with i.v. lipopolysaccharide (LPS, 10 mg/kg) in absence and presence of nicotine. In contrast to no effects for LPS when used alone, dose-related decreases in blood pressure (BP) and serum estrogen were noted in endotoxic rats treated consequently with nicotine (25, 50, or 100 μg/kg i.v.). Signs of cardiac autonomic dysfunction appeared in LPS/nicotine-treated rats such as (i) decreased time-domain indices of heart rate variability (HRV), e.g. standard deviation of R-R intervals (SDNN) and root mean square of successive differences in R-R interval durations (rMSSD), and (ii) reduced total power of the frequency spectrum and shifted cardiac sympathovagal balance toward sympathetic dominance. Nicotine reversed the LPS-evoked modest rises in serum TNFα and IL-1β while had no effect on associated arterial baroreflex dysfunction, inferring no roles for inflammation or baroreflexes in LPS-nicotine interaction. Estrogen or aminoguanidine (iNOS inhibitor), but not pentoxifylline (TNFα inhibitor), abolished LPS/nicotine hypotension. Together, nicotine acts probably via reducing estrogen availability to uncover nitric oxide-dependent hypotension and autonomic dysregulation in endotoxic female rats., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: To recognize the national trends in management of pediatric craniopharyngioma and to address the significant predictors of discharge disposition., Methods: We utilized the Kids' Inpatient Database (KID), a pediatric inpatient sample generated by the Healthcare Cost and Utilization Project (HCUP) triennially from 1997 to 2016., Results: KID contains 2141 pediatric craniopharyngioma admissions. Patient demographics had no effect on discharge disposition. Based on the multivariable logistic regression analysis, we confirmed a significantly higher non-routine discharge rate among patients with hydrocephalus (P = 0.01). Patients who developed diabetes insipidus were at higher risk for non-routine discharge (P = 0.02). Admission of patients to a freestanding children's hospital increased the likelihood of routine discharge (P = 0.001)., Conclusion: Hydrocephalus, diabetes insipidus, and admission to a freestanding children's hospital are significant independent predictors of discharge disposition.

Background and Purpose: Cardiovascular complications are the major cause of mortality in diabetic patients. However, the molecular mechanisms underlying diabetes-associated arrhythmias are unclear. We hypothesized that high glucose could adversely affect Na v 1.5, the major cardiac sodium channel isoform of the heart, at least partially via oxidative stress. We further hypothesized that cannabidiol (CBD), one of the main constituents of Cannabis sativa, through its effects on Na v 1.5, could protect against high glucose-elicited oxidative stress and cytotoxicity., Experimental Approach: To test these ideas, we used CHO cells transiently co-transfected with cDNA encoding human Na v 1.5 α-subunit under control and high glucose conditions (50 or 100 mM for 24 hr). Several experimental and computational techniques were used, including voltage clamp of heterologous expression systems, cell viability assays, fluorescence assays and action potential modelling., Key Results: High glucose evoked cell death associated with elevation in reactive oxygen species (ROS) right shifted the voltage dependence of conductance and steady-state fast inactivation, and increased persistent current leading to computational prolongation of action potential (hyperexcitability) which could result in long QT3 arrhythmia. CBD mitigated all the deleterious effects provoked by high glucose. Perfusion with lidocaine (a well-known sodium channel inhibitor with antioxidant effects) or co-incubation of Tempol (a well-known antioxidant) elicited protection, comparable to CBD, against the deleterious effects of high glucose., Conclusion and Implications: These findings suggest that, through its favourable antioxidant and sodium channel inhibitory effects, CBD may protect against high glucose-induced arrhythmia and cytotoxicity., (© 2020 The British Pharmacological Society.)

Aims: To investigate if autonomic dysregulation is exacerbated in female rats, subjected to diabetes mellitus (DM), via a paradoxical estrogen (E 2 )-evoked provocation of neuroinflammation/injury of the hypothalamic paraventricular nucleus (PVN)., Main Methods: We measured cardiac autonomic function and conducted subsequent PVN neurochemical studies, in DM rats, and their respective controls, divided as follows: male, sham operated (SO), ovariectomized (OVX), and OVX with E 2 supplementation (OVX/E 2 )., Key Findings: Autonomic dysregulation, expressed as sympathetic dominance (higher low frequency, LF, band), only occurred in DM E 2 -replete (SO and OVX/E 2 ) rats, and was associated with higher neuronal activity (c-Fos) and higher levels of TNFα and phosphorylated death associated protein kinase-3 (p-DAPK3) in the PVN. These proinflammatory molecules likely contributed to the heightened PVN oxidative stress, injury and apoptosis. The PVN of these E 2 -replete DM rats also exhibited upregulations of estrogen receptors, ERα and ERβ, and proinflammatory adenosine A1 and A2a receptors., Significance: The E 2 -dependent autonomic dysregulation likely predisposes DM female rats and women to hypersensitivity to cardiac dysfunction. Further, upregulations of proinflammatory mediators including adenosine A1 and A2 receptors, TNFα and DAPK3, conceivably explain the paradoxical hypersensitivity of DM females to PVN inflammation/injury and the subsequent autonomic dysregulation in the presence of E 2 ., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The female gender is protected against immunological complications of endotoxemia. Here we investigated whether gonadal hormone depletion by ovariectomy (OVX) uncovers inflammatory and cardiovascular effects of endotoxemia and whether these effects are reversed by hormone replacement therapies. Changes in inflammatory cytokines, blood pressure (BP), left ventricular (LV) function, and cardiac autonomic activity caused by lipopolysaccharide (LPS) in conscious female rats with different hormonal states were determined. In contrast to no effects in sham-operated females, treatment of OVX rats with LPS (i) decreased BP, (ii) increased spectral low-frequency/high-frequency ratio of HRV, denoting enhanced cardiac sympathetic dominance, (iii) attenuated reflex tachycardic responses to sodium nitroprusside, and (iv) increased systolic contractility (dP/dt max ). The developed hypotension was (i) fully eliminated in estrogen (E 2 )-pretreated OVX rats, (ii) partially counteracted after selective activation of estrogen receptor-α (PPT) or β (DPN). All estrogenic compounds abrogated LPS enhancement of cardiac sympathetic drive. However, PPT was more successful than E2 or DPN in compromising LPS depression in baroreflex activity and elevation in dP/dt max . Molecular studies showed that PPT was most effective in attenuating the upregulated myocardial expressions of NF-κB and iNOS in endotoxic OVX rats. Myocardial expression of the defensive HSP70 was comparably increased by all estrogenic products. Except for improved cardiac spectral activity, none of these functional or molecular entities was affected by medroxyprogesterone acetate (MPA). Overall, our data suggest diverse therapeutic advantages for gonadal hormones in the worsened endotoxic complications in rats with surgical menopause, with probably more favorable role for ERα agonism within this context., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: A summary of recommendations is given within the Gulf Cooperation Council (GCC) setting on the assessment and management of vitamin D deficiency in the region., Methods: An assembly of 11 regional experts gathered to formulate an all-inclusive approach to vitamin D deficiency within GCC., Results and Conclusion: Several gaps were identified before regional guidelines could be developed. These include adequacy and standardization of vitamin D testing, frequency of repeated testing and reference ranges, distinguishing prevention from the treatment of vitamin D deficiency, quality assurance of vitamin D products sold within GCC including contents and origins of products, and cut-points for vitamin D levels in local populations. A platform is created that can be further developed for overall regional implementation.

Introduction: This study aimed to investigate the association between components of metabolic syndrome (MetS) at first trimester and development of Gestational diabetes mellitus (GDM) in 498 Saudi pregnant women. Materials and Methods: Biochemical and anthropometric parameters were determined at the first trimester and MetS components were defined. Participants were screened for GDM at follow up according to International Association of Diabetes and Pregnancy Study Group (IADPSG) criteria. The main outcome measures were development of GDM and GDM risk vs. MetS components at first trimester. Results: One hundred twenty three (24.7%) were diagnosed with GDM according to IADPSG criteria. GDM risk was significantly higher for participants with hypertriglyceridemia at 1st trimester even after adjusting for age, BMI and parity (OR: 1.82; CI: 1.1-3.7, p = 0.04). Furthermore, the odds of hyperglycemia at 1st trimester was significantly higher in GDM than in non-GDM participants even after adjustments (OR: 2.13, 95% CI: 1.1 to 4.3, p = 0.038). The receiver operating characteristic (ROC) for predicting GDM revealed an area under the curve (AUC) of 0.69 (95% CI: 0.64 to 0.74, p < 0.001) and 0.71 (95% CI: 0.65 to 0.77, p < 0.001) for first-trimester hyperglycemia and hypertriglyceridemia respectively. Conclusions: The incidence of GDM in Saudi pregnant women was strongly associated with hyperglycemia and hypertriglyceridemia at first trimester. These findings are of clinical importance, as an assessment of MetS in early pregnancy can identify women at higher risk of developing GDM., (Copyright © 2020 Wani, Sabico, Alnaami, Al-Musharaf, Fouda, Turkestani, Al-Ajlan, Alshingetti, Alokail and Al-Daghri.)

Studies involving oncology especially diagnosis, prognosis and therapeutic monitoring are increasingly relying on molecular analyses. These analyses require high quality biomolecules to get accurate and precise results and this requires among others, monitoring for pre-analytical variables. The purpose of our study was to validate the SOPs of the newly established Egyptian National Cancer Institute (ENCI) biobank. We used a panel of 91 fresh frozen breast cancer tissue samples and their matched normal tissues and have investigated the overall quality (integrity and yield) of RNA extracted from fresh frozen breast tumor tissues and matched normal breast tissues. We investigated the effect of several factors including seasonal temperature variation, cold ischemia time, transportation method, and RNA extraction method. The RNA yield and quality were significantly increased with tumor samples collected in winter, transported on wet ice and using an automated RNA extraction platform. No significant effect was observed due to increased cold ischemia time >30 min. The effect of delay in time to cryopreservation on RNA degradation in fresh tissue samples may vary according to the type of tissue, temperature during tissue collection and transportation, and the use of stabilizing agents as RNA later., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose. This research was funded by the Egyptian Science and Technology Development Fund (STDF) Grant No. CSE5232., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To demonstrate the paradigm shift in management strategies of pediatric craniopharyngioma at our institution over the past six decades., Methods: Retrospective analysis of all pediatric patients with craniopharyngioma treated at Boston Children's Hospital between 1960 and 2017., Results: One hundred seventy-eight patients with craniopharyngioma were treated between 1960 and 2017; 135 (70 males and 65 females) fulfilled the inclusion criteria. Forty-five patients were treated in the old era (1960-1984) and 90 patients were treated in the new era (1985-2017). Gross total resection (GTR) was achieved in 4% and 43% of patients in old and new eras respectively. Sub-total resection (STR) and radiotherapy (XRT) were performed in 27% and 28% of patients in old and new eras respectively. STR without XRT was performed in 20% and 29% of patients in old and new era respectively. Cyst drainage and adjuvant radiotherapy were performed in 49% of patients in the old era while no patients in the new era underwent such conservative management. Aggressive surgical resection was associated with a higher risk of worsening visual outcomes (20% vs 16%), panhypopituitarism and diabetes insipidus (86% vs 53%), psycho-social impairment (42% vs 26%), and new-onset obesity (33% vs 22%). The mortality rate was higher in the old era in comparison with that of the new one (9% vs 2%)., Conclusion: There was a paradigm shift in management strategies of pediatric craniopharyngioma over the past six decades which in turn affected the long-term outcomes and quality of life of patients.

The onset of vascular impairment precedes that of diagnostic hyperglycemia in diabetic patients suggesting a vascular insult early in the course of metabolic dysfunction without a well-defined mechanism. Mounting evidence implicates adipose inflammation in the pathogenesis of insulin resistance and diabetes. It is not certain whether amelioration of adipose inflammation is sufficient to preclude vascular dysfunction in early stages of metabolic disease. Recent findings suggest that antidiabetic drugs, metformin, and pioglitazone, improve vascular function in prediabetic patients, without an indication if this protective effect is mediated by reduction of adipose inflammation. Here, we used a prediabetic rat model with delayed development of hyperglycemia to study the effect of metformin or pioglitazone on adipose inflammation and vascular function. At the end of the metabolic challenge, these rats were neither obese, hypertensive, nor hyperglycemic. However, they showed increased pressor responses to phenylephrine and augmented aortic and mesenteric contraction. Vascular tissues from prediabetic rats showed increased Rho-associated kinase activity causing enhanced calcium sensitization. An elevated level of reactive oxygen species was seen in aortic tissues together with increased Transforming growth factor β1 and Interleukin-1β expression. Although, no signs of systemic inflammation were detected, perivascular adipose inflammation was observed. Adipocyte hypertrophy, increased macrophage infiltration, and elevated Transforming growth factor β1 and Interleukin-1β mRNA levels were seen. Two-week treatment with metformin or pioglitazone or switching to normal chow ameliorated adipose inflammation and vascular dysfunction. Localized perivascular adipose inflammation is sufficient to trigger vascular dysfunction early in the course of diabetes. Interfering with this inflammatory process reverses this early abnormality., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Nicotine improves endotoxic manifestations of hypotension and cardiac autonomic dysfunction in rats. Here, we test the hypothesis that brainstem antiinflammatory pathways of α7/α4β2 nicotinic acetylcholine receptors (nAChRs) modulate endotoxic cardiovascular derangements. Pharmacologic and molecular studies were performed to determine the influence of nicotine or selective α7/α4β2-nAChR ligands on cardiovascular derangements and brainstem neuroinflammation caused by endotoxemia in conscious rats. The i.v. administration of nicotine (50 μg/kg) abolished the lipopolysaccharide (LPS, 10 mg/kg i.v.)-evoked: (i) falls in blood pressure and spectral measure of cardiac sympathovagal balance (ratio of the low-frequency to high-frequency power, LF/HF), (ii) elevations in immunohistochemical protein expressions of NFκB and α4β2-nAChR in medullary neurons of the nucleus tractus solitarius (NTS) and rostral ventrolateral medulla (RVLM), and (iii) decreases in medullary α7-nAChR protein expression. These favorable nicotine influences were replicated in rats treated intracisternally (i.c.) with PHA-543613 (selective α7-nAChR agonist) or 5-iodo-A-85380 (5IA, selective α4β2-nAChRs agonist). Measurement of arterial baroreflex activity by the vasoactive method revealed that nicotine, PHA, or 5IA reversed the LPS depression of reflex bradycardic, but not tachycardic, activity. Moreover, the counteraction by nicotine of LPS hypotension was mostly inhibited after treatment with i.c. methyllycaconitine (MLA, α7-nAChR antagonist) in contrast to a smaller effect for dihydro-β-erythroidine (DHβE, α4β2-nAChR antagonist), whereas the associated increases in LF/HF ratio remained unaltered. The data signifies the importance of brainstem α7, and to a lesser extent α4β2, receptors in the nicotine counteraction of detrimental cardiovascular and neuroinflammatory consequences of endotoxemia., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Biobanking is a relatively new concept in Egypt. Building a good relationship with different stakeholders is essential for the social sustainability of biobanks. To establish this relationship, it is necessary to assess the attitude of different groups towards this concept. The objective of this work is to assess the knowledge, attitude, and opinions of Egyptian patients towards biobanking issues., Methods: We designed a structured survey to be administered to patients coming to the outpatient clinics in 3 university hospitals in Egypt. The survey included questions estimating the level of knowledge about the term "Biobank", together with questions about the attitudes and opinions about related issues., Results: Two hundred and fifty-nine patients participated in the survey. Eighty-one percent of participants reported that they never heard about the term before. About 85% expressed that they would be willing to donate their samples for research and about 87% thought that sample donation did not contradict their religious beliefs. Fifty eight percent were willing to participate in a genetic research project, 27.8% supported sharing their sample with pharmaceutical companies, and 32.4% agreed to share their samples with institutions abroad., Conclusion: Although there is limited knowledge about biobanking among Egyptian patients, many had a positive attitude towards sample donation and didn't show religious concerns against it. However, they showed concerns regarding participation in genetic research and with sharing their samples across borders or with pharmaceutical companies. Public education about biobanking is possible, taking into consideration the specific cultural and legal framework in Egypt.

In May 2016, highly pathogenic avian influenza virus of the subtype A/H5N1 was detected in Cameroon in an industrial poultry farm at Mvog-Betsi, Yaoundé (Centre region), with a recorded sudden increase of deaths among chickens, and an overall mortality rate of 75%. The virus spread further and caused new outbreaks in some parts of the country. In total, 21 outbreaks were confirmed from May 2016 to March 2017 (six in the Centre, six in the West, eight in the South and one in the Adamaoua regions). This resulted in an estimated total loss of 138,252 birds (44,451 deaths due to infection and 93,801 stamped out). Only domestic birds (chickens, ducks and geese) were affected in farms as well as in poultry markets. The outbreaks occurred in three waves, the first from May to June 2016, the second in September 2016 and the last wave in March 2017. The topology of the phylogeny based on the haemagglutinin gene segment indicated that the causative H5N1 viruses fall within the genetic clade 2.3.2.1c, within the same group as the A/H5N1 viruses collected in Niger in 2015 and 2016. More importantly, the gene constellation of four representative viruses showed evidence of H5N1/H9N2 intra-clade reassortment. Additional epidemiological and genetic data from affected countries in West Africa are needed to better trace the origin, spread and evolution of A/H5N1 in Cameroon. RESEARCH HIGHLIGHTS HPAI A/H5N1 was detected in May 2016 in domestic chickens in Yaoundé-Cameroon. Twenty-one outbreaks in total were confirmed from May 2016 to March 2017. The causative H5N1 viruses fall within the genetic clade 2.3.2.1c. The viral gene constellation showed evidence of H5N1/H9N2 intra-clade reassortment.

Background: Chronic nicotine administration impairs reflex chronotropic responses that follow arterial baroreceptor unloading in female rats with repleted, but not depleted (ovariectomized, OVX), estrogen (E 2 ). This study investigated whether products of nitric oxide synthase (NOS) and/or heme oxygenase (HO) and related soluble guanylate cyclase (sGC)/phosphatidylinositol 3-kinase (PI3K)/mitogen-activated protein kinases (MAPKs) signaling mediate the E 2 -sensitive depressant effect of nicotine on reflex tachycardia., Methods: Baroreflex curves relating reflex tachycardic responses to falls in blood pressure (BP) generated by sodium nitroprusside (SNP) were established in conscious female rats and slopes of the curves were taken as measures of baroreflex sensitivity (BRS)., Results: Nicotine (2 mg/kg/day ip, 14 days) reduced BRS in OVX rats treated with E 2 but not vehicle. Baroreceptor dysfunction in nicotine-treated OVXE 2 rats was abolished after iv treatment with hemin (HO inducer) but not l-arginine (NOS substrate) denoting the importance of reduced availability of carbon monoxide, but not NO, in the nicotine effect. The favorable BRS effect of hemin was abolished after intracisternal (ic) administration of L-NAME (NOS inhibitor) or wortmannin (PI3 K inhibitor). Central circuits of MAPKs do not seem to contribute to the baroreflex facilitatory effect of hemin because the latter was preserved after central inhibition of MAPK ERK (PD98059), MAPK p38 (SB203580) or MAPK JNK (SP600125). Likewise, sGC inhibition (ODQ) or E 2 receptor blockade (ICI182780) failed to alter the hemin effect., Conclusion: The activation of central NOS/PI3K signaling following HO upregulation improves the E 2 -dependent depressant effect of nicotine on reflex tachycardia., (Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.)

Data regarding the prevalence and predictors of vitamin D deficiency during early pregnancy are limited. This study aims to fill this gap. A total of 578 Saudi women in their 1 st trimester of pregnancy were recruited between January 2014 and December 2015 from three tertiary care antenatal clinics in Riyadh, Saudi Arabia. Information collected includes socio-economic, anthropometric, and biochemical data, including serum vitamin D (25(OH)D) levels, intake of calcium and vitamin D, physical activity, and sun exposure indices. Pregnant women with 25(OH)D levels <50 nmol/L were considered vitamin D deficient. The majority of participants ( n = 468 (81%)) were vitamin D deficient. High levels of indoor activity, whole body clothing, multiparity, total cholesterol/HDL ratio(>3.5), low HDL-cholesterol, and living in West Riyadh were significant independent predictors for vitamin D deficiency, with odds ratios (ORs) (95% confidence interval) of 25.4 (5.5&ndash;117.3), 17.8 (2.3&ndash;138.5), 4.0 (1.7&ndash;9.5), 3.3 (1.4&ndash;7.9), 2.8 (1.2&ndash;6.4), and 2.0 (1.1&ndash;3.5), respectively. Factors like increased physical activity, sun exposure at noon, sunrise or sunset, high educational status, and residence in North Riyadh were protective against vitamin D deficiency with ORs 0.2 (0.1&ndash;0.5); 0.2 (0.1&ndash;0.6); 0.3 (0.1&ndash;0.9); and 0.4 (0.2&ndash;0.8), respectively. All ORs were adjusted for age, BMI, sun exposure, parity, summer season, vitamin D intake, multivitamin intake, physical activity, education, employment, living in the north, and coverage with clothing. In conclusion, the prevalence of vitamin D deficiency among Saudi women during early pregnancy was high (81%). Timely detection and appropriate supplementation with adequate amounts of vitamin D should reduce the risks of vitamin D deficiency and its complications during pregnancy.

Background: Gestational diabetes mellitus (GDM) has serious consequences such as increased risks of preeclampsia, macrosomia and cesarean delivery. Even though the mechanistic basis of GDM has not been completely understood, several risk factors have been identified and one of these is vitamin D. However, the link between vitamin D deficiency and development of GDM is yet to be proven with certainty., Methods: This study aimed to investigate the link between the incidence of GDM and serum vitamin D level in pregnant women of Saudi Arabia. 515 Saudi women (ages 18-46) in their 24-28th week of pregnancy, visiting various hospitals of Riyadh, participated in this study. Serum vitamin D and various biochemical and anthropometric parameters were determined in the first trimester and the recruits were screened for GDM by OGTT according to IADPSG criteria in their 2nd trimester. The association between vitamin D deficiency and development of GDM was calculated based on odds ratio of the incidence of GDM among vitamin D deficient and normal women., Results: In this study cohort of 515 pregnant women, in the first trimester vitamin D deficiency (< 50 nmol/l) was detected in 425 (82.5%). On their 2nd visit (2nd trimester), 116 (27.7%) were diagnosed with GDM out of 419 with OGTT, according to IADPSG criteria. GDM risk was significantly higher among vitamin D deficient than non-deficient women (Odds Ratio: 2.87; Confidence Interval: 1.32-6.25; P = 0.008) even after adjusting for season, sun exposure and vitamin D intake (OR: 2.9; CI: 1.07-7.89). Of the various anthropometric and biochemical parameters, the GDM women differed significantly from non-GDM women with respect to serum levels of triglycerides (in mmol/l) (1.3 ± 0.6; 1.5 ± 0.6, p = 0.018) and fasting glucose (in mmol/l) [4.7 (4.3-5.2); 5.1 (4.6-5.6), p < 0.01]. Also, fasting glucose level in the 2nd trimester correlated inversely to serum vitamin D level determined during the 1st trimester (r = - 0.121; p = 0.014)., Conclusions: Results of our study reveal a significantly higher risk of development of GDM among pregnant women having deficient vitamin D status.

Objectives: Renal transplant is the criterion standard for treatment of end-stage renal disease. The effects of disparities between men and women on renal transplant outcomes have been evaluated in many studies but with debatable results. It has been suggested that female kidney donors have poor outcomes after transplant compared with male kidney donors, especially when implanted in a male recipient. The aim of the study was to evaluate the effects of sex on living-donor kidney transplant outcome., Materials and Methods: The data of 979 patients who underwent living-donor kidney transplant from January 2000 to December 2010 at a single center were reviewed retrospectively. The patients were divided into 4 groups according to recipient and donor sex: male donor-to-male recipient (n = 307), male donor-to-female recipient (n = 132), female donor-to-male recipient (n = 411), and female donor-to-female recipient (n = 129). We compared the demographic characteristics, posttransplant rejection and complications, and graft and patient survival rates among the groups., Results: Male recipients were older than female recipients, whereas male donors were younger than female donors (P < .001). No statistically significant differences were shown regarding recipient body mass index, ischemia time and time to diuresis, and acute and chronic rejection rates between the groups. Graft (P = .947) and patient (P = .421) survival rates were comparable between groups., Conclusions: Donor and recipient sex had no significant effect on outcomes of living-donor renal allograft recipients.

The male gender is more vulnerable to immunological complications of sepsis. Here, we tested the hypotheses that female rats are protected against endotoxemia-evoked hypotension and cardiac autonomic dysfunction, and that gonadal hormone receptors account for such protection. Changes in blood pressure, heart rate, and cardiac sympathovagal balance caused by i.v. lipopolysaccharide (LPS) were determined. In male rats, LPS elevated serum TNFα together with falls in blood pressure and rises in heart rate. The spectral index of cardiac sympathovagal balance (low-frequency/high-frequency ratio, LF/HF) was reduced by LPS, suggesting an enhanced parasympathetic dominance. Remarkably, none of these LPS effects was evident in female rats. We also report that pretreatment of female rats with fulvestrant (nonselective estrogen receptor blocker), PHTPP (estrogen receptor β blocker), or mifepristone (progesterone receptor blocker) uncovered clear inflammatory (increased serum TNFα), hypotensive and tachycardic responses to LPS. However, these female rats, contrary to their male counterparts, exhibited increases in LF/HF ratio. On the other hand, LPS failed to modify inflammatory or cardiovascular states in rats pretreated with MPP (estrogen receptor α blocker). In females treated with formestane (aromatase inhibitor), LPS increased LF/HF ratio but had no effect on blood pressure. In male rats, the hypotensive and cardiac autonomic effects of LPS were (i) eliminated after treatment with estrogen, and (ii) intensified and inhibited, respectively, in flutamide (androgen receptor blocker)-pretreated rats. These findings highlight important roles for female gonadal hormones and functional estrogen receptor β and progesterone receptors in offsetting inflammatory and cardiovascular derangements caused by endotoxemia in female rats., (Copyright © 2018 Elsevier B.V. All rights reserved.)