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Hussain Al Dera1,2 1Department of Basic Medical Sciences, College of Medicine, King Saud Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Kingdom of Saudi Arabia; 2King Abdullah International Medical Research Center (KAIMRC), Riyadh, Kingdom of Saudi ArabiaCorrespondence: Hussain Al Dera Email derah@KSAU-HS.edu.saBackground: Curriculum mapping and alignment are complex processes essential for the improvement of curriculum and serve as guidelines for students, faculty, and college administrators. This project aims to map different components of the curriculum in a comprehensive manner to ensure smooth running of the curriculum for the end users.Materials and Methods: The project addressed the neuroscience block of the undergraduate medicine program. Eight parameters were investigated: competencies (learning outcomes), curriculum themes, block objectives, weekly problems, and objectives of weekly problems, disciplines, delivery, and assessment. The Delphi method was used by ten experts to assess the importance of these parameters. Focus interviews were then conducted with faculty members.Results: The panel of ten experts reached consensus by agreeing that the eight parameters are important for aligning and mapping the neuroscience block and can be helpful for smooth operation of the curriculum. Mapping and alignment were performed electronically using eight parameters over 8 weeks. Majority of the faculty members appreciated the use of curriculum mapping.Conclusion: Curriculum mapping using electronic software helps in identifying gaps and redundancies and facilitating alignment between learning and assessment and learning objectives and competencies (learning outcomes). Training programs for faculty members and encouragement from leaders are suggested.Keywords: curriculum alignment, curriculum mapping, neuroscience block, electronic mapping, Delphi method

This study was conducted to examine if modulating transporters like transient receptor potential cation channels, subfamily M, member 7 (TRPM7) underlies the hippocampal neuroprotection afforded by melatonin (Mel) in rats exposed to cerebral hypoperfusion (CHP). Experimental groups included control, Mel-treated (1.87 g/kg), CHP, and CHP + Mel (1.87 g/kg)-treated rats. CHP was induced by the permanent bilateral occlusion of the common carotid arteries (2VO) method and treatments were conducted for 7 days, orally. Mel prevented the damage of the dental gyrus and memory loss in CHP rats and inhibited the hippocampal reactive oxygen species (ROS), lipid peroxidation levels of tumor necrosis factor-α (TNF-α), interleukine-6 (IL-6), interleukine-1 beta (IL-1β), and prostaglandin E2 (PGE2). It also reduced the hippocampal transcription of the TRPM7 channels and lowered levels of calcium (Ca

This study investigated the expression pattern, regulation of expression, and the role of hippocampal small-conductance Ca2+-activated K+ (SK) channels in memory deficits after cerebral hypoperfusion (CHP) with or without melatonin treatment, in rats. Adults male Wistar rats (n = 20/group) were divided into (1) a sham (2) a sham + melatonin (3) a two-vessel occlusion (2-VO) model, and (4) a 2-VO + melatonin. Melatonin was administered (i.p.) to all rats at a daily dose of 10 mg kg−1 for 7 days starting at the time of 2-VO-induction. In contrast to 2-VO rats, melatonin increased the latency of the passive avoidance learning test and decreased time to find the hidden platform in Water Morris Test in all tested rats. In addition, it concomitantly downregulated SK1, SK2, and SK3 channels, downregulated mRNA levels of TNFα and IL-1β, enhanced BDNF levels and activity of PKA levels, and restored the levels of cholinergic markers in the hippocampi of the treated-rats. Mechanistically, melatonin significantly prevented CHP-induced activation of ERK1/2, JNK, and P38 MAPK at least by inhibiting ROS generation and enhancing the total antioxidant potential. In cultured hypoxic hippocampal neurons, individual blockage of MAPK signaling by the MEK1/2 inhibitor (U0126), but not by the P38 inhibitor (SB203580) or JNK inhibitor (SP600125), completely prevented the upregulation of all three kinds of SK channels. These data clearly confirm that upregulation of SK channels plays a role in CHP-induced memory loss and indicate that melatonin reverses memory deficits after CHP in rats, at least by, downregulation of SK1, SK2, and SK3 channels in their hippocampi.

It is proposed that gluten- and casein-rich diets (GRD and CRD) can synergistically exacerbate dysbiosis as comorbidity in autism by worsening leaky gut that affects the brain through the gut–brain axis. In this study, 35 young male rats were divided into 7 groups, Group 1 serves as control; Group 2, clindamycin (CL)-treated; and Group 3, propionic acid (PPA)-induced rodent model of autism. These three groups were fed standard diet until the end of the experiment. Groups 4–7 are rats treated similarly with CL and PPA, then fed on CRD or GRD until the end of the experiment. Serum zonulin, glutathione (GSH), lipid peroxides, and gut microbial composition were measured in the seven studied groups. Data demonstrate the significant increase in serum zonulin as marker of leaky gut in the CL-treated groups fed on CRD or GRD. Lipid peroxides were significantly higher in the serum of GRD-fed rats compared to CRD-fed or normal diet-fed rats. GSH was much lower in CL-treated groups fed on CRD or GRD compared to PPA-treated rats fed on both diets. Both diets differentially affected the diversity of the gut microbiota. This study demonstrates that CRD and GRD exacerbates leaky gut, according to serum zonulin, which was used as marker for increased gut permeability.

Background: Not many randomized controlled trials (RCTs) have explored the effects of melatonin and melatonin products on sleep parameters such as sleep latency (SL) and total sleep time (TST). This importance magnifies when we speak of children with autism who are susceptible to sleep disturbances with no currently approved intervention. Therefore, this meta-analysis was conducted to gather available data describing the influence of melatonin on these parameters. Methods: A computer-aided search of Google Scholar, PubMed, CINAHL, Cochrane complete, Medline Complete, EMBASE, Scopus, and ERIC databases from their inception to November 2020. We included all published (RCTs) studies that provided data on the relevant use of melatonin and melatonin products in children diagnosed with autism in adherence with the Diagnostic and Statistical Manual of Mental Disorders (DSM-V). The risk of bias within the included (RCTs) was assessed using the Cochrane risk of bias tool for the prevalence studies. All statistical analysis was performed using the Review Manager software. Findings: The present meta-analysis included 6 (RCTs) that reported the influence of melatonin and melatonin products on (SL) and (TST) in children with autism with a total sample size of 600 patients with an overall low risk of bias. The primary outcomes are sleep latency (SL) and total sleep time (TST). The main comparison for this study is melatonin VS. placebo for sleep problems in autistic pediatric patients. Melatonin has significantly reduced the sleep latency (SL) with a p-value of

Objectives: KSA has the highest prevalence of diabetes mellitus among Middle Eastern countries with a prevalence range of 21%–24%. Gestational diabetes (GDM) is a well-known risk factor for type 2 diabetes mellitus (T2DM). GDM is associated with a 7-fold increased risk of T2DM. Thus, this research assessed the prevalence and risk factors associated with the development T2DM in a cohort of patients with GDM in KSA. Methods: The medical records of patients with GDM who visited the outpatient clinics of a tertiary care hospital from 2011 to 2014 were included in this study. Patients with a prior diagnosis of diabetes mellitus before pregnancy and those with GDM who did not have postpartum diabetes screening were excluded. Results: A total of 123 women with GDM and underwent postpartum diabetes screening, 82 (67%) developed T2DM based on follow-up records. Approximately 45% (37/82) of patients who developed T2DM were screened ≤6 months after delivery, whereas 55%(45/82) were screened >6 months after delivery. Older patients, patients who had a higher number of pregnancies (gravidity and parity), and patients with previous GDM were more likely to develop T2DM. Conclusion: In KSA, women who developed GDM, particularly those who are older, multigravid, and multiparous and who have a prior history of GDM, are at an increased risk of developing T2DM. Postpartum diabetes screening of patients with GDM within the recommended period need to be improved. Keywords: Gestational diabetes, Postpartum, Risk factors, Screening, Type 2 diabetes

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that can cause significant social, communication and behavioral challenges. Environmental contribution to ASD is due in large part to the sensitivity of the developing brain to external exposures such as lead (Pb), and mercury (Hg) as toxic heavy metals or due to a poor detoxification ability as the phenotype of this disorder. Selenium (Se) as an antioxidant element that counteracts the neurotoxicity of Hg, and Pb, presumably through the formation of nontoxic complexes. In the present study, Pb, Hg, and Se were measured in red blood cells (RBCs) of 35 children with ASD and 30 age- and gender-matched healthy control children using atomic absorption spectrometry. Receiver Operating Characteristics (ROC) analysis of the obtained data was performed to measure the predictive value of their absolute and relative concentrations. The obtained data demonstrates a significant elevation of Hg and Pb together with a significant decrease in the Se levels in RBCs of patients with ASD when compared to the healthy controls. The ratios of Se to both Pb and Hg were remarkably altered, being indicative of heavy metal neurotoxicity in patients with ASD. In conclusion, the present study indicates the importance of Se for prevention and/or therapy of heavy metal neurotoxicity.

This study investigated the expression pattern, regulation of expression, and the role of hippocampal small-conductance Ca

Objectives: To investigate the potential protective effect of resveratrol (RES) on aluminum chloride (AlCl3)-induced nephrotoxicity in rats. Methods: This experimental study was conducted from April to June 2015 at the Medical College of King Khalid University, Abha, Kingdom of Saudi Arabia. The experiments were performed on 24 male Wistar rats. The rats were randomly allocated into 4 groups; 1) group A: control rats received only normal saline, 2) group B: received RES dissolved in normal saline, 3) group C: model group and received AlCl3 dissolved in normal saline and 4) group D: RES treated group and received concomitant doses of RES+AlCl3. All treatments were administered for consecutive 40 days. After 40 days of treatments, kidney function tests, oxidative stress parameters and histopathological assay were evaluated. Results: all findings clearly showed significant deteriorations in kidney function and architectures after AlCl3 exposure. This was accompanied by increased renal oxidative stress and inflammation suggesting strong pro-oxidant activity of AlCl3 in spite of its non-redox status. Resveratrol co-treatment with AlCl3 to the rats showed significant improvement in all biochemical and histological parameters related to kidney function and structure. Conclusion: The findings of the current study showed that RES pre-administration to rats ameliorates renal damage and improves renal function in AlCl3 intoxicated rats in a mechanism related to its antioxidant potential. Saudi Med J 2016; Vol. 37 (4): 369-378 doi: 10.15537/smj.2016.4.13611 How to cite this article: Al Dera HS. Protective effect of resveratrol against aluminum chloride induced nephrotoxicity in rats. Saudi Med J 2016; 37: 369-378.

Autism characteristics in sixty children (aged from 2 to 8) were assed. Their behavioral symptoms were evaluated using the Autism Treatment Evaluation Checklist (ATEC). ATEC has four main domains of autistic disorders (Speech/Language/Communication, Sociability, Sensory/Cognitive Awareness, and Health/Physical/Behavior) in children with clinical diagnosis by Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and Childhood Autism Rating Scale (CARS) of autism spectrum disorder (ASD). Utilizing ATEC checklist, our study describes significant behavioral observations between autistic children which could effectively contribute to better understanding and treatment during their early intervention stage.

The gut microbiota is a complex ecosystem that makes a great contribution toward the health of its host. One of the recent findings is the importance of the gut–brain axis as a bidirectional pathway through which the microbiota in the gut has potential influence on behavior and mental states. Gastrointestinal disorders are commonly reported in autistic patients, which may be due to altered composition of the gut microbiota, promoting the overgrowth of pathogenic bacteria. This can support the role of dysbiosis in the development of persistent autistic features. It is well known that diet plays an important role in the etiology of autism. Understanding the mechanism of diet–microbiota interaction may help to avoid the increasing prevalence of this disorder. Strategies to decrease the overgrowth of pathogenic bacteria and thus improve the composition of gut microbiota of autistic patients through dietary intervention may help to ameliorate gastrointestinal disorders commonly seen in autistic patients.

This study was designed to investigate the role of the liver in lowering fasting blood glucose levels (FBG) in rats native to high (HA) and low altitude (LA) areas. As compared with LA natives, besides the improved insulin and glucose tolerance, HA native rats had lower FBG, at least mediated by inhibition of hepatic gluconeogenesis and activation of glycogen synthesis. An effect that is mediated by the enhancement of hepatic insulin signaling mediated by the decreased phosphorylation of TSC induced inhibition of mTOR function. Such effect was independent of activation of AMPK nor stabilization of HIF1α, but most probably due to oxidative stress induced REDD1 expression. However, under insulin stimulation, and in spite of the less activated mTOR function in HA native rats, LA native rats had higher glycogen content and reduced levels of gluconeogenic enzymes with a more enhanced insulin signaling, mainly due to higher levels of p-IRS1 (tyr612).

The effects of spinal cord injury (SCI) on sympathetic neurovascular transmission have generally been ignored. This review describes changes in sympathetic nerve-mediated activation of arterial vessels to which ongoing sympathetic activity has been reduced or silenced following spinal cord transection in rats. In all vessels studied in rats, SCI markedly enhanced their contractile responses to nerve activity. However, the mechanisms that augment neurovascular transmission differ between the rat tail artery and mesenteric artery. In tail artery, the enhancement of neurovascular transmission cannot be attributed to changes in sensitivity of the vascular muscle to α1- or α2-adrenoceptor agonists. Instead the contribution of L-type Ca2+ channels to activation of the smooth muscle by nerve-released noradrenaline is greatly increased following SCI. By contrast, mesenteric arteries from SCI rats had increased sensitivity to phenylephrine but not to methoxamine. While both phenylephrine and methoxamine are α1-adrenoceptor agonists, only phenylephrine is a substrate for the neuronal noradrenaline transporter. Therefore the selective increase in sensitivity to phenylephrine suggests that the activity of the neuronal noradrenaline transporter is reduced. While present evidence suggests that sympathetic vasoconstrictor neurons do not contribute to the normal regulation of peripheral resistance below a complete SCI in humans, the available evidence does indicate that these experimental findings in animals are likely to apply after SCI in humans and contribute to autonomic dysreflexia.

Background Autism is neurodevelopmental disorder that is characterized by developmental, behavioral, social and sensory abnormalities. Researchers have focused in last years in immunological alteration and inflammation as a hot subject in autism field. This work aims to study the alteration in phospholipids (PE, PS, and PC) together with the change in cPLA2 concentration as the main phospholipid hydrolytic enzyme in autistic patients compared to control. It was also extended to find a correlation between these biomarkers and severity of autism measured as childhood autism rating scale (CARS), Social responsiveness scale (SRS), and Short sensory profile (SSP). Methods Phospholipids (PE, PS, PC) and cPLA2 as biochemical parameters were determined in the plasma of 48 Saudi autistic male patients, categorized as mild-moderate and severe as indicated by their Childhood Autism Rating Scale (CARS), social responsiveness scale (SRS) and short sensory profile (SSP) and compared to 40 age- and gender-matched control samples. Results The reported data demonstrate significantly lower levels of PE, PS, and PC together with a significant increase in cPLA2. While association between severity of autism and impaired phospholipid concentration was completely lacked, an association between cPLA2 and impaired sensory processing was observed. Conclusions The impaired phospholipid level and remarkable increased in cPLA2 concentration asserted their roles in the etiology of autism. Receiver operating characteristic analysis together with predictiveness diagrams proved that the measured parameters could be used as predictive biomarkers of clinical symptoms and provide significant guidance for future therapeutic strategy to re-establish physiological homeostasis.

Studies in individuals with spinal cord injury (SCI) suggest the vasculature is hyperreactive to angiotensin II (Ang II). In the present study, the effects of SCI on the reactivity of the rat tail and mesenteric arteries to Ang II have been investigated. In addition, the effects of SCI on the facilitatory action of Ang II on nerve-evoked contractions of these vessels were determined. Isometric contractions of artery segments from T11 (tail artery) or T4 (mesenteric arteries) spinal cord-transected rats and sham-operated rats were compared 6-7 weeks postoperatively. In both tail and mesenteric arteries, SCI increased nerve-evoked contractions. In tail arteries, SCI also greatly increased Ang II-evoked contractions and the facilitatory effect of Ang II on nerve-evoked contractions. By contrast, SCI did not detectably change the responses of mesenteric arteries to Ang II. These findings provide the first direct evidence that SCI increases the reactivity of arterial vessels to Ang II. In addition, in tail artery, the findings indicate that Ang II may contribute to modifying their responses following SCI.

In rat tail artery (RTA), spinal cord injury (SCI) increases nerve-evoked contractions and the contribution of L-type Ca2+ channels to these responses. In RTAs from unoperated rats, these channels play a minor role in contractions and Bay K8644 (L-type channel agonist) mimics the effects of SCI. Here we investigated the mechanisms underlying the facilitatory actions of SCI and Bay K8644 on nerve-evoked contractions of RTAs and the hypothesis that Ca2+ entering via L-type Ca2+ channels is rapidly sequestered by the sarcoplasmic reticulum (SR) limiting its role in contraction. In situ electrochemical detection of noradrenaline was used to assess if Bay K8644 increased noradrenaline release. Perforated patch recordings were used to assess if SCI changed the Ca2+ current recorded in RTA myocytes. Wire myography was used to assess if SCI modified the effects of Bay K8644 and of interrupting SR Ca2+ uptake on nerve-evoked contractions. Bay K8644 did not change noradrenaline-induced oxidation currents. Neither the size nor gating of Ca2+ currents differed between myocytes from sham-operated (control) and SCI rats. Bay K8644 increased nerve-evoked contractions in RTAs from both control and SCI rats, but the magnitude of this effect was reduced by SCI. By contrast, depleting SR Ca2+ stores with ryanodine or cyclopiazonic acid selectively increased nerve-evoked contractions in control RTAs. Cyclopiazonic acid also selectively increased the blockade of these responses by nifedipine (L-type channel blocker) in control RTAs, whereas ryanodine increased the blockade produced by nifedipine in both groups of RTAs. These findings suggest that Ca2+ entering via L-type channels is normally rapidly sequestered limiting its access to the contractile mechanism. Furthermore, the findings suggest SCI reduces the role of this mechanism.

In patients with spinal cord injury (SCI), somatosympathetic reflexes produce exaggerated decreases in skin blood flow below the lesion. This hypoperfusion appears to result from an increased responsiveness of cutaneous arterial vessels to neural activation. Here we investigated the mechanisms that underlie SCI-induced enhancement of neurovascular transmission in a cutaneous vessel, the rat tail artery. Isometric contractions of arterial segments from T11 spinal cord transected and sham-operated rats were compared 6 wk postoperatively. SCI more than doubled the amplitudes of contractions of arteries in response to moderate frequencies of nerve stimulation (0.1 to 1 Hz). In arteries from SCI rats, but not those from sham-operated rats, the L-type Ca2+ channel blocker nifedipine (1 μM) reduced the amplitudes of nerve-evoked contractions. Furthermore, while the sensitivity to the agonists phenylephrine (α1-adrenoceptor selective) and clonidine (α2-adrenoceptor selective) did not differ significantly between arteries from SCI and sham-operated rats, nifedipine had a greater inhibitory effect on contractions to both agents in arteries from SCI rats. Although sensitivity to clonidine was unchanged, SCI selectively reduced the contribution of postjunctional α2-adenceptors to nerve-evoked contractions. In arteries from unoperated rats, the L-type channel agonist BAY K 8644 (0.1 μM) produced a similar enhancement of nerve-evoked contraction to that produced by SCI and also selectively reduced the contribution of α2-adrenceptors to these responses. Together the findings demonstrate that the SCI-induced enhancement of neurovascular transmission in the rat tail artery can largely be accounted for by an increased contribution of L-type Ca2+ channels to activation of the vascular smooth muscle.

Introduction: Studies suggest that exercise therapy may enhance heart rate variability in myocardial infarction, chronic heart failure and revascularization patients by increasing vagal tone and decreasing sympathetic activity. This review addressed the impact of cardiac rehabilitation programs (CRPs) in post CABG patients on the quality of life, in terms of physical function and cardiac risk factors. Methods: OVID, Science direct, Embase, AMED and Cochrane controlled Trial Register were searched for studies published from 2005 up to 2015. Two reviewers assessed the eligibility of each study based on predefined inclusion criteria. Results: Of 35 abstracts reviewed, 9 studies met the inclusion criteria. All studies compared CRPs of different interventions to a control (non-intervention) group. From the selected 9 studies, 6 studies included interventions compared with control groups (usual or standard care) while 3 studies compared two different intervention strategies with groups and included a no-intervention control group. Conclusion: This systematic review concludes that all types of CRPs lead to improvements in the quality of life and reduction of cardiac risk factors in post CABG patients. However, these improvements were quite varied between the 9 studies according to variations in the components of CRPs.