Oxidative Stress: Mechanistic Insights into Inherited Mitochondrial Disorders and Parkinson's Disease

Oxidative stress arises when cellular antioxidant defences become overwhelmed by a surplus generation of reactive oxygen species (ROS). Once this occurs, many cellular biomolecules such as DNA, lipids, and proteins become susceptible to free radical-induced oxidative damage, and this may consequently lead to cellular and ultimately tissue and organ dysfunction. Mitochondria, as well as being a source of ROS, are vulnerable to oxidative stress-induced damage with a number of key biomolecules being the target of oxidative damage by free radicals, including membrane phospholipids, respiratory chain complexes, proteins, and mitochondrial DNA (mt DNA). As a result, a deficit in cellular energy status may occur along with increased electron leakage and partial reduction of oxygen. This in turn may lead to a further increase in ROS production. Oxidative damage to certain mitochondrial biomolecules has been associated with, and implicated in the pathophysiology of a number of diseases. It is the purpose of this review to discuss the impact of such oxidative stress and subsequent damage by reviewing our current knowledge of the pathophysiology of several inherited mitochondrial disorders together with our understanding of perturbations observed in the more commonly acquired neurodegenerative disorders such as Parkinson’s disease (PD). Furthermore, the potential use and feasibility of antioxidant therapies as an adjunct to lower the accumulation of damaging oxidative species and hence slow disease progression will also be discussed

Simulation of ion behavior in an open three-dimensional Paul trap using a power series method

Simulations of the dynamics of ions trapped in a Paul trap with terms in the potential up to the order 10 have been carried out. The power series method is used to solve numerically the equations of motion of the ions. The stability diagram has been studied and the buffer gas cooling has been implemented by a Monte Carlo method. The dipole excitation was also included. The method has been applied to an existing trap and it has shown good agreement with the experimental results and previous simulations using other methods

Old World cutaneous leishmaniasis treatment response varies depending on parasite species, geographical location and development of secondary infection

Background: In the Kingdom of Saudi Arabia (KSA), Leishmania major and L. tropica are the main causative agents of Old World cutaneous leishmaniasis (CL). The national CL treatment regimen consists of topical 1% clotrimazole/2% fusidic acid cream followed by 1–2 courses of intralesional sodium stibogluconate (SSG); however, treatment efficacy is highly variable and the reasons for this are not well understood. In this study, we present a complete epidemiological map of CL and determined the efficacy of the standard CL treatment regime in several endemic regions of KSA.Results: Overall, three quarters of patients in all CL-endemic areas studied responded satisfactorily to the current treatment regime, with the remaining requiring only an extra course of SSG. The majority of unresponsive cases were infected with L. tropica. Furthermore, the development of secondary infections (SI) around or within the CL lesion significantly favoured the treatment response of L. major patients but had no effect on L. tropica cases.Conclusions: The response of CL patients to a national treatment protocol appears to depend on several factors, including Leishmania parasite species, geographical location and occurrences of SI. Our findings suggest there is a need to implement alternative CL treatment protocols based on these parameters

Mitochondrial Function, Oxidative Stress and Parkinson's Disease

The loss of the activity of mitochondrial respiratory chain (MRC) complexes, particularly complex I, has been implicated in Parkinson’s disease (PD) pathogenesis. However, it is still uncertain whether altered MRC activity is an early event in the pathophysiology of PD, or a late consequence of cellular stress. Therefore, this thesis contributes differently from other studies as to the ongoing investigations about MRC activity in PD post-mortem brain based on pathological severity. This study demonstrates that loss of complex I activity occurs in regions with both moderate and mild pathology in PD brain. Furthermore, multiple complex defects were noted in the moderate pathology region. However, the activity of complex II which is entirely encoded by nuclear DNA appeared to be preserved. The exact mechanism of multiple complex defects remain elusive. However, the possibility arises that impairment of complex I results in secondary damage to the other complexes. Here, neuroblastoma cells were employed to study the effect of pharmacologically induced MRC complex I deficiency upon the activity of the other complexes. In this model, rotenone-treated (100 nM; 24-48 hours) SH-SY5Y cells induced an inhibition of complex I. At 24 hours no effect was observed on the other complexes. However at 48 hours, multiple complex defects were noted, but the activity of complex II appeared to be preserved. Additionally, bioenergetics and glutathione status were compromised. By utilizing this model, the effectiveness of antioxidants in alleviating the progression of complex I deficiency on other complexes were also evaluated. Furthermore, the use of the Oxygraph-2K® instrument together with a step-wise protocol was developed to assess the integrated mitochondrial function in cultured SH-SY5Y cells. Additionally, the focus of attention was also to validate the fibroblast growth factor-21 ELISA assay. Based on the results, this assay appears to be a useful as a biomarker for mitochondrial dysfunction

Access and utilisation of primary health care services comparing urban and rural areas of Riyadh Providence, Kingdom of Saudi Arabia

The Kingdom of Saudi Arabia (KSA) has seen an increase in chronic diseases. International evidence suggests that early intervention is the best approach to reduce the burden of chronic disease. However, the limited research available suggests that health care access remains unequal, with rural populations having the poorest access to and utilisation of primary health care centres and, consequently, the poorest health outcomes. This study aimed to examine the factors influencing the access to and utilisation of primary health care centres in urban and rural areas of Riyadh province of the KSA

Genetic and phenotypic characterization of NKX6‐2‐related spastic ataxia and hypomyelination

Background and purpose Hypomyelinating leukodystrophies are a heterogeneous group of genetic disorders with a wide spectrum of phenotypes and a high rate of genetically unsolved cases. Bi‐allelic mutations in NKX6‐2 were recently linked to spastic ataxia 8 with hypomyelinating leukodystrophy. Methods Using a combination of homozygosity mapping, exome sequencing, and detailed clinical and neuroimaging assessment a series of new NKX6‐2 mutations in a multicentre setting is described. Then, all reported NKX6‐2 mutations and those identified in this study were combined and an in‐depth analysis of NKX6‐2‐related disease spectrum was provided. Results Eleven new cases from eight families of different ethnic backgrounds carrying compound heterozygous and homozygous pathogenic variants in NKX6‐2 were identified, evidencing a high NKX6‐2 mutation burden in the hypomyelinating leukodystrophy disease spectrum. Our data reveal a phenotype spectrum with neonatal onset, global psychomotor delay and worse prognosis at the severe end and a childhood onset with mainly motor phenotype at the milder end. The phenotypic and neuroimaging expression in NKX6‐2 is described and it is shown that phenotypes with epilepsy in the absence of overt hypomyelination and diffuse hypomyelination without seizures can occur. Conclusions NKX6‐2 mutations should be considered in patients with autosomal recessive, very early onset of nystagmus, cerebellar ataxia with hypotonia that rapidly progresses to spasticity, particularly when associated with neuroimaging signs of hypomyelination. Therefore, it is recommended that NXK6‐2 should be included in hypomyelinating leukodystrophy and spastic ataxia diagnostic panels

Diagnostic challenge of intestinal obstruction secondary to Henoch–Schonlein purpura

Henoch–Schonlein purpura is the most common form of vasculitis in pediatric age group. Gastrointestinal manifestations have been long recognized as part of the disease, but usually preceded by other manifestations. We present a case of a boy whose  initial manifestation of the disease was bowel obstruction and ischemia requiring surgical intervention twice with diagnostic  dilemma prior to diagnosis of Henoch–Schonlein purpura. Although common surgical diseases prove to be the culprit in most cases, a surgeon should always keep an open mind for possibility beyond surgical diseases. Multidisciplinary approach to  situations where ambiguities in diagnosis exist proves to be a valuable tool aiding surgical decision.Keywords: gastrointestinal, henochscholine, intestinal ischemia, intussusception, purpur

Diagnostic challenge of intestinal obstruction secondary to Henoch–Schonlein purpura

Henoch–Schonlein purpura is the most common form of vasculitis in pediatric age group. Gastrointestinal manifestations have been long recognized as part of the disease, but usually preceded by other manifestations. We present a case of a boy whose initial manifestation of the disease was bowel obstruction and ischemia requiring surgical intervention twice with diagnostic dilemma prior to diagnosis of Henoch–Schonlein purpura. Although common surgical diseases prove to be the culprit in most cases, a surgeon should always keep an open mind for possibility beyond surgical diseases. Multidisciplinary approach to situations where ambiguities in diagnosis exist proves to be a valuable tool aiding surgical decision.Keywords: gastrointestinal, henochscholine, intestinal ischemia, intussusception, purpur

Perception of Faculty Members of Regional Medical School Toward Faculty Development Program

Introduction: Any types or process of activities that are performed by a group or an individual to enhance, promote, and improve the performance, competencies or skills of a health professional at an institute level are defined as faculty development which has many other names like staff development, academic development, and educational development. The importance of faculty development stressed by Harden is equivalent to curriculum development, which is a very difficult assignment. Objectives: To determine the pattern of faculty members’ perception toward their weekly faculty development program. Methodology: Enrolling the faculty members of the College of Medicine, University of Bisha, Kingdom of Saudi Arabia ( COM/UB,KSA). COM/UB adopting the innovative curriculum (problem-based learning, team-based learning, interactive lectures, and case-based learning and seminars. Each Tuesday, faculty members gather in the faculty development academic program (FDAP) room to discuss issues related to medical education and quality. Usually, there is a presentation on the selected topic over 25 min, followed by a discussion and workshop, and finally, a recommendation is drawn. The inclusion criterion is those staying in the college for a period of more than one year. New joiners and those staying for a period of less than one year were excluded. Faculty members were enrolled optionally and requested to fill a validated questionnaire. Results: The response rate was 92% of total staff. More than 89%, 87%, 86% and 74% thought that the FDAP is useful to them, helps them in addressing academic issues in the faculty, is an enriching experience, and thought that it helps them in constructing high-quality multiple choice questions (MCQs). Finally, 84% were interested in presenting topics in FDP. Conclusion: FDAP was positively perceived by the faculty members of the University Bisha/College of Medicine, since it enriches their experience and satisfies their academic job. Keywords: faculty, development, academic, program, MCQ

Effect of Admission Type on the Risk of Bloodstream Infections among Critically Ill Patients with Peripherally Inserted Central Catheters in a Tertiary Center in Saudi Arabia

The purpose of the study was to evaluate the association between type of admission (medical versus surgical) with risk of central line associated bloodstream infection (CLABSI) in a university hospital setting. A retrospective analysis was performed on critically ill patients who had peripherally inserted central catheters (PICC) during the period between January 2010 and October 2012. Demographic data, duration of catheterization and type of admission were obtained from patien