Adaptive leadership during challenging times: Effective strategies for health professions educators: AMEE Guide No. 148.

Leadership and management are becoming increasingly recognised as vital for high-performing organisations and teams in health professions education. It is often difficult for those embarking on leadership activities (as well as more experienced leaders) to find their way through the volume of literature and generic information on the topic. This guide aims to provide a framework for developing educators' understanding of leadership, management, and followership in the context of health professions education. It explains many relevant approaches to leadership and suggests various strategies through which educators can develop their practice to become more effective.

Model for utilizing distance learning post COVID-19 using (PACT)™ a cross sectional qualitative study.

BACKGROUND: COVID - 19 pandemic pressured medical schools globally to shift to Distance learning (DL) as an alternative way to ensure that the content delivered is satisfactory for student progression. AIM OF THE WORK: This work aims at mapping priorities for post-COVID planning for better balance between distance learning and face to face learning. METHODS: This qualitative study aimed to develop a model for utilizing DL using The Polarity Approach for Continuity and Transformation (PACT)™. A virtual mapping session was held with 79 faculty from 19 countries. They worked in small groups to determine upsides and downsides of face-to-face and DL subsequently. An initial polarity map was generated identifying five tension areas; Faculty, Students, Curriculum, Social aspects and Logistics. A 63-item assessment tool was generated based on this map, piloted and then distributed as a self-administered assessment. The outcomes of this assessment were utilized for another mapping session to discuss warning signs and action steps to maintain upsides and avoid downsides of each pole. RESULTS: Participants agreed that face-to-face teaching allows them to inspire students and have meaningful connections with them. They also agreed that DL provides a good environment for most students. However, students with financial challenges and special needs may not have equal opportunities to access technology. As regards social issues, participants agreed that face-to-face learning provides a better chance for professionalism through enhanced team-work. Cognitive, communication and clinical skills are best achieved in face-to-face. Participants agreed that logistics for conducting DL are much more complicated when compared to face-to-face learning. Participants identified around 10 warning signs for each method that need to be continuously monitored in order to minimize the drawbacks of over focusing on one pole at the expense of the other. Action steps were determined to ensure optimized use of in either method. CONCLUSION: In order to plan for the future, we need to understand the dynamics of education within the context of polarities. Educators need to understand that the choice of DL, although was imposed as a no-alternative solution during the COVID era, yet it has always existed as a possible alternative and will continue to exist after this era. The value of polarity mapping and leveraging allows us to maximize the benefit of each method and guide educators' decisions to minimize the downsides for the good of the learning process.

Students' perception of portfolio as a learning tool at King Abdulaziz University Medical School.

BACKGROUND: Medical education has a longstanding tradition of using logbooks to record activities. The portfolio is an alternative tool to document competence and promote reflective practice. This study assessed the acceptance of portfolio use among Saudi undergraduate medical students. METHODS: Portfolios were introduced in the 2nd through 5th years at King Abdulaziz University over a two-year period (2013-2015). At the end of each academic year, students completed a mixed questionnaire that included a self-assessment of skills learned through the use of portfolio. RESULTS: The results showed a difference in focus between basic and clinical years: in basic years students' focus was on acquiring practical skills, but in clinical years they focused more on acquiring complex skills, including identifying and managing problems. The questionnaire responses nonetheless revealed a positive trend in acceptance (belief in the educational value) of portfolios among students and their mentors, across the years of the program. CONCLUSIONS: Using portfolios as a developmental learning and formative assessment tool in the early undergraduate years was found to contribute to students' ability to create their own clinical skills guidelines in later years, as well as to engage in and appreciate reflective learning.

Ginsenoside Rb1 inhibits fibrillation and toxicity of alpha-synuclein and disaggregates preformed fibrils.

Compelling evidence indicates that α-synuclein (α-syn) aggregation plays a central role in the pathogenesis of Parkinson's disease (PD) and other synucleinopathies. Identification of compounds that inhibit or reverse the aggregation process may thus represent a viable therapeutic strategy against PD and related disorders. Ginseng is a well-known medicinal plant that has been used in East Asia for more than two thousand years to treat several conditions. It is now understood that the pharmacological properties of ginseng can be attributed to its biologically active components, the ginsenosides, which in turn have been shown to have neuroprotective properties. We therefore sought to determine for the first time, the potential of the most frequently used and studied ginsenosides, namely Rg1, Rg3 and Rb1, as anti-amyloidogenic agents. The effect of Rg1, Rg3 and Rb1 on α-syn aggregation and toxicity was determined by an array of biophysical, biochemical and cell-culture-based techniques. Among the screened ginsenosides, only Rb1 was shown to be a potent inhibitor of α-syn fibrillation and toxicity. Additionally, Rb1 exhibited a strong ability to disaggregate preformed fibrils and to inhibit the seeded polymerization of α-syn. Interestingly, Rb1 was found to stabilize soluble non-toxic oligomers with no ß-sheet content, that were susceptible to proteinase K digestion, and the binding of Rb1 to those oligomers may represent a potential mechanism of action. Thus, Rb1 could represent the starting point for designing new molecules that could be utilized as drugs for the treatment of PD and related disorders.

Origin of profunda femoris artery and its circumflex femoral branches: anatomical variations and clinical significance.

BACKGROUND: Knowledge of the anatomical variations of the profunda femoris artery and its circumflex branches is important during angiographic diagnostic procedures as well as during performing surgery in the femoral region. The aim of this study was to examine the original sites, distances and variations of the profunda femoris artery and its circumflex branches. MATERIALS AND METHODS: The study was conducted in the Department of Anatomy, Faculty of Medicine, King Abdulaziz University from October, 2011 to May, 2013 after the approval of the medical ethical committee. Dissections of 90 femoral triangles of 25 male and 20 female adult human cadavers were performed to demonstrate the origin and distribution of the profunda femoris artery and its circumflex branches. RESULTS: The profunda femoris artery mostly originated from the posterolateral aspect of the femoral artery in 42% of male limbs and in 42.5% of female limbs, from the posterior side in 24% of male and 27.5% of female limbs, from the lateral side in 20% of males and female limbs and from the posteromedial aspect in 14% of male limbs and in 7.5% of female limbs. The mean distance of origin of profunda femoris artery from the midpoint of inguinal ligament was 51.5 ± 1.9 mm in right male, 49.7 ± 1.9 mm in left male, 48.5 ± 2.2 mm in right female and 48.9 ± 2.2 mm in left female limbs. The medial and lateral circumflex arteries originated mostly from the profunda femoris artery (60% in males; 57.7% in females) at a mean distance of 18.6 ± 2.1 mm and 20.2 ± 2.2 mm in right male, 19.6 ± 1.9 mm and 22.5 ± 2.3 mm in left male, 18.8 ± 2.7 mm and 21 ± 2.6 mm in right female and 19.1 ± 2.1 mm and 21.7 ± 2.6 mm in left female limbs, respectively. The original incidence of the medial and lateral circumflex femoral arteries from the femoral artery including the common trunk was 40% in male and 42.3% in female limbs. CONCLUSIONS: Awareness of the original sites and distances of the profunda femoris artery and its circumflex femoral branches will allow the surgeon to define the vascular pattern before performing any invasive procedure and to avoid unexpected iatrogenic injuries.

Neurofascin as a novel target for autoantibody-mediated axonal injury.

Axonal injury is considered the major cause of disability in patients with multiple sclerosis (MS), but the underlying effector mechanisms are poorly understood. Starting with a proteomics-based approach, we identified neurofascin-specific autoantibodies in patients with MS. These autoantibodies recognize the native form of the extracellular domains of both neurofascin 186 (NF186), a neuronal protein concentrated in myelinated fibers at nodes of Ranvier, and NF155, the oligodendrocyte-specific isoform of neurofascin. Our in vitro studies with hippocampal slice cultures indicate that neurofascin antibodies inhibit axonal conduction in a complement-dependent manner. To evaluate whether circulating antineurofascin antibodies mediate a pathogenic effect in vivo, we cotransferred these antibodies with myelin oligodendrocyte glycoprotein-specific encephalitogenic T cells to mimic the inflammatory pathology of MS and breach the blood-brain barrier. In this animal model, antibodies to neurofascin selectively targeted nodes of Ranvier, resulting in deposition of complement, axonal injury, and disease exacerbation. Collectively, these results identify a novel mechanism of immune-mediated axonal injury that can contribute to axonal pathology in MS.

Healthcare leadership development during a pandemic: do not stop, adapt.

Research carried out in 2016 by two of the authors of this article investigated the role that leadership 'theory' plays within an individual's leadership development and identified other components of clinical leadership programmes that are key to enabling the development of future leaders. While early career doctors identified leadership theories and concepts as important within their development as clinical leaders, these must be closely tied to real-life practices and coupled with activities that aim to develop an increased self-awareness, understanding of others, clinical exposure and leadership tools that they can use in practice. During a healthcare crisis, such as a global pandemic, maintaining a focus on leadership development (particularly for more junior clinicians) might not be seen as important, but leadership is needed to help people and organisations 'get through' a crisis as well as help develop leadership capacity for the longer term. This article, drawing from contemporary literature, the authors' own research and reflections, discusses how leadership development needs to continually adapt to meet new demands and sets out tips for those involved with clinical leadership development.

Leadership in a crisis: doing things differently, doing different things.

This article summarises the findings from a review of publications related to healthcare leadership that were published during the first wave of the COVID-19 crisis in 2020. The review discusses a range of strategies for leaders to adopt in challenging situations and identifies three aspects of leadership which are considered essential when leading teams during a crisis: 1) communication, 2) decision making and 3) mental health and wellbeing. This article identifies key principles for each of these three aspects and provides practical tips for how leaders can use the lessons learned from the pandemic in their own contexts.

Electron microscopic study of the myelinated nerve fibres and the perineurial cell basement membrane in the diabetic human peripheral nerves.

OBJECTIVE: To study the quantitative and ultrastructural changes in myelinated nerve fibers and the basement membranes of the perineurial cells in diabetic nerves. METHODS: The study was performed at the Department of Anatomy, Faculty of Medicine, King Abdul-Aziz University, Jeddah, Saudi Arabia from 2003 to 2005. Human sural nerves were obtained from 15 lower limbs and 5 diabetic nerve biopsies. The total mean and density of myelinated nerve fibers per fascicle were calculated, with density of microtubules and mitochondria in the axoplasm. The number of the perineurial cell basement membrane layers was counted, and thickness of the basement membrane was measured. RESULTS: Among the 15 diabetic and 5 normal human sural nerves, the average diameters, number and surface area of myelinated nerve fibers and axonal microtubules density were found to be less in diabetic nerves. Mitochondrial density was higher in diabetic axons. Thickness of the perineurial cell basement membrane had a greater mean, but the number of perineurial cell layers was less than that of the diabetic group. The inner cellular layer of the perineurium of the diabetic nerves contained large vacuoles containing electron-dense degenerated myelin. A few specimens showed degenerated myelinated nerve fibers, while others showed recovering ones. Retracted axoplasms were encountered with albumin extravasation. CONCLUSION: Diabetes caused an increase in perineurial permeability. The diabetic sural nerve showed marked decrease in the myelinated nerve fibres, increase degenerated mitochondria, and decreased microtubules.

Ultrastructural changes of compressed lumbar ventral nerve roots following decompression.

OBJECTIVE: To study whether there will be a permanent lumbar nerve root scarring or degeneration secondary to continuous compression followed by decompression on the nerve roots, which can account for postlaminectomy leg weakness or back pain. METHODS: The study was performed at the Department of Anatomy, Faculty of Medicine, King Abdul-Aziz University, Jeddah, Kingdom of Saudi Arabia during 2003-2005. Twenty-six adult male New Zealand rabbits were used in the present study. The ventral roots of the left fourth lumbar nerve were clamped for 2 weeks then decompression was allowed by removal of the clips. The left ventral roots of the fourth lumbar nerve were excised for electron microscopic study. RESULTS: One week after nerve root decompression, the ventral root peripheral to the site of compression showed signs of Wallerian degeneration together with signs of regeneration. Schwann cells and myelinated nerve fibers showed severe degenerative changes. Two weeks after decompression, the endoneurium of the ventral root showed extensive edema with an increase in the regenerating myelinated and unmyelinated nerve fibers, and fibroblasts proliferation. Three weeks after decompression, the endoneurium showed an increase in the regenerating myelinated and unmyelinated nerve fibers with diminution of the endoneurial edema, and number of macrophages and an increase in collagen fibrils. Five and 6 weeks after decompression, the endoneurium showed marked diminution of the edema, macrophages, mast cells and fibroblasts. The endoneurium was filled of myelinated and unmyelinated nerve fibers and collagen fibrils. CONCLUSION: Decompression of the compressed roots of a spinal nerve is followed by regeneration of the nerve fibers and nerve recovery without endoneurial scarring.

The blood and nerve supply of the long head of the biceps femoris muscle; its possible use in dynamic neoanal sphincter.

OBJECTIVES: Dynamic graciloplasty is used commonly as a neoanal sphincter to reconstruct the damaged anal sphincter. However, infection of the transposed gracilis and consequent failure of anal reconstruction has been recorded in some cases. An alternative to gracilis muscle should be searched for to reconstruct and replace the anal sphincter. STUDY DESIGN: 30 fresh cadavers (20 adult, 10 stillborns) had been used in this study. MATERIALS AND METHODS: The external and common iliac arteries were injected with a mixture of 50% lead oxide and 50% red latex. The long head of biceps femoris was exposed to identify its neurovascular bundle and estimate the whole length of the thigh, the whole length of the long head of biceps and the dominant neurovascular pedicles of the long head of biceps muscle. The functional length of the biceps muscle that is used during the muscle rotation was also calculated. The diameter of the arteries supplying the muscle was measured at their proximal and distal ends using a Swiss mechanic caliber. The thighs of both sides of each cadaver were X-rayed in order to study the vascular architecture of the muscle, and then the biceps muscle was dissected and removed then X-rayed to study the internal vasculature and anastomosis. RESULTS: The study showed that there were four dominant arterial pedicles to the long head of biceps femoris muscle in addition to several minor arterial branches in 90% of the studied cases. In all cases, the inferior gluteal artery gave one major arterial pedicle to the proximal end of the muscle. The radiological study of the vasculature of the long head of biceps muscle during the current study showed the presence of anastomosing arterial loops between the internal iliac, external iliac, femoral and profunda femoris arteries. It also showed the presence of extensive intramuscular anastomosis between the intramuscular branches of the major arterial pedicles inside the long head of biceps femoris muscle. During the present study, it was found that the muscle received a single nerve supply in 97% of the dissected cadavers. This means that about in 58% of the cases, the muscle is available for transposition to wrap the anal canal. The available length of the muscle for rotation was about 57% of the length of the thigh. CONCLUSION: It can be concluded that, the long head of the biceps muscle can be safely rotated to wrap around the anal canal without serious effect on the main vascular pedicles and its nerve supply.

Anticonvulsant action of anandamide in an in vitro model of epilepsy.

OBJECTIVE: In both in vitro and in vivo models of epilepsy, cannabinoids had anti-convulsant properties, which have been shown to be mediated through activation of central cannabinoid type 1 receptors (CB1). The current study used 24 adult Sprague Dawley rats to investigate the effects of endogenously occurring cannabinoids (endocannabinoids) on epileptiform activity induced by picrotoxin. METHODS: We carried out the study at King Fahad Medical Research Center, Jeddah, Kingdom of Saudi Arabia in September 2004. We made extracellular recordings from stratum pyramidale of the CA1 region of hippocampal slices maintained in a submersion type recording chamber. Stimulation with single pulses, evoked population spikes of approximately equal amplitude. RESULTS: Using single pulse stimulation, perfusion of 0.5 uM picrotoxin caused a small increase in the amplitude of the first population spike, and caused epilepsy by introducing a second or multiple population spikes. In the presence of picrotoxin, anandamide reduced the amplitude of both the first population spike (PS1) and the second population spike (PS2), thus reducing the epilepsy. The CB1 receptor antagonist, AM281 (500 nM) had no effect on responses recorded in the presence of picrotoxin, but totally blocked the effect of subsequently perfused anandamide. CONCLUSION: The results showed that anandamide caused an anti-convulsant effect. Furthermore, these results implicate the cannabinoid CB1 receptor as a major endogenous site of seizure modulation.

CREATING: a sustainable plan for biomedical higher education in Saudi Arabia. Phase I.

Biomedical higher education has been acquiring increasing importance worldwide, including the Kingdom of Saudi Arabia, and effective strategies to improve outcomes and competitiveness are key for academic success. The plan presented here is divided into two major phases. Phase 1 (Communication, Research governance, Education planning, Accreditation) deals mainly with adopting a systematic approach to academic activities according to the current international standards. In other words, the aim is to re-organise what is already in place, taking into account current guidelines and strategies that help improve quality of education and research. It is suggested that this is not necessarily to be achieved by major investments but, rather, by a more imaginative and structured work plan. In Phase 2 (Translational practice, Implementation, Networking, Growth), higher education institutions are expected to invest in new strategic resources, to establish strong reciprocal links with international academic partners and industry, and to shift their attention to the hot topics and current academic challenges, leading the way in translational education models and pioneering cutting-edge research.

Effect of cannabinoids on synaptic transmission in the rat hippocampal slice is temperature-dependent.

We have previously reported that the synthetic cannabinoid R-(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazin-yl]-(1-naphthalenyl)methanone mesylate (WIN55,212-2) causes a selective inhibition of paired pulse depression of population spikes recorded from the CA1 region of rat hippocampal slices maintained at 28-30 degrees C. We now show that this effect is highly temperature-dependent and that WIN55,212-2 actually increases paired pulse depression of population spikes recorded from slices maintained at 35 degrees C. This temperature dependence was found to correlate with the effects of the known gamma-amino butyric acid (GABA)-uptake inhibitors, nipecotic acid and guvacine, which were without effect at 28-30 degrees C, but increased paired pulse depression at 35 degrees C. The results show that the effects of cannabinoids on synaptic transmission in the hippocampal slice are highly temperature-dependent and it is suggested that this is due to the presence of increased GABA uptake at higher temperatures.

The innovative safe fixative for histology, histopathology, and immunohistochemistry techniques: "pilot study using shellac alcoholic solution fixative".

The concerns over health and workplace hazards of formalin fixative, joined to its cross-linking of molecular groups that results in suboptimal immunohistochemistry, led us to search for an innovative safe fixative. Shellac is a natural material which is used as a preservative in foods and pharmaceutical industries. This study was undertaken to evaluate the fixation adequacy and staining quality of histopathological specimens fixed in the "shellac alcoholic solution" (SAS), and also to determine the validity of immunohistochemical staining of SAS-fixed material in comparison to those fixed in formalin. Fresh samples from 26 cases from various human tissues were collected at the frozen section room of King Abdulaziz University Hospital, and fixed in SAS fixative or in neutral buffered formaldehyde (NBF) for 12, 18, 24, and 48 h, and processed for paraffin sectioning. Deparaffinized sections were stained with hematoxylin and eosin (H&E) and immunostained for different antigens. The tissues fixed in SAS for >18 h showed best staining quality of H&E comparable to NBF-fixed tissues. Comparison of the immunohistochemical staining of different tissues yielded nearly equivalent readings with good positive nuclear staining quality in both fixatives. These findings support the fixation and preservation adequacy of SAS. Furthermore, it was concluded that the good staining quality obtained with SAS-fixed tissues, which was more or less comparable with the quality obtained with the formalin fixed tissues, supports the validity of this new solution as a good innovative fixative.

Levels of cerebrospinal fluid α-synuclein oligomers are increased in Parkinson's disease with dementia and dementia with Lewy bodies compared to Alzheimer's disease.

INTRODUCTION: The objective was to study whether α-synuclein oligomers are altered in the cerebrospinal fluid (CSF) of patients with dementia, including Parkinson disease with dementia (PDD), dementia with Lewy bodies (DLB), and Alzheimer disease (AD), compared with age-matched controls. METHODS: In total, 247 CSF samples were assessed in this study, including 71 patients with DLB, 30 patients with PDD, 48 patients with AD, and 98 healthy age-matched controls. Both total and oligomeric α-synuclein levels were evaluated by using well-established immunoassays. RESULTS: The levels of α-synuclein oligomers in the CSF were increased in patients with PDD compared with the controls (P < 0.05), but not in patients with DLB compared with controls. Interestingly, the levels of α-synuclein oligomers in the CSF were also significantly higher in patients with PDD (P < 0.01) and DLB (P < 0.05) compared with patients with AD. The levels of CSF α-synuclein oligomers and the ratio of oligomeric/total-α-synuclein could distinguish DLB or PDD patients from AD patients, with areas under the curves (AUCs) of 0.64 and 0.75, respectively. In addition, total-α-synuclein alone could distinguish DLB or PDD patients from AD patients, with an AUC of 0.80. CONCLUSIONS: The levels of α-synuclein oligomers were increased in the CSF from α-synucleinopathy patients with dementia compared with AD cases.

Elevated levels of cerebrospinal fluid α-synuclein oligomers in healthy asymptomatic LRRK2 mutation carriers.

Mutations in the leucine-rich repeat kinase 2 gene are the most common cause of autosomal dominant Parkinson's disease (PD). To assess the cerebrospinal fluid (CSF) levels of α-synuclein oligomers in symptomatic and asymptomatic leucine-rich repeat kinase 2 mutation carriers, we used enzyme-linked immunosorbent assays (ELISA) to investigate total and oligomeric forms of α-synuclein in CSF samples. The CSF samples were collected from 33 Norwegian individuals with leucine-rich repeat kinase 2 mutations: 13 patients were clinically diagnosed with PD and 20 patients were healthy, asymptomatic leucine-rich repeat kinase 2 mutation carriers. We also included 35 patients with sporadic PD (sPD) and 42 age-matched healthy controls. Levels of CSF α-synuclein oligomers were significantly elevated in healthy asymptomatic individuals carrying leucine-rich repeat kinase 2 mutations (n = 20; P < 0.0079) and in sPD group (n = 35; P < 0.003) relative to healthy controls. Increased α-synuclein oligomers in asymptomatic leucine-rich repeat kinase 2 mutation carriers showed a sensitivity of 63.0% and a specificity of 74.0%, with an area under the curve of 0.66, and a sensitivity of 65.0% and a specificity of 83.0%, with an area under the curve of 0.74 for sPD cases. An inverse correlation between CSF levels of α- synuclein oligomers and disease severity and duration was observed. Our study suggests that quantification of α-synuclein oligomers in CSF has potential value as a tool for PD diagnosis and presymptomatic screening of high-risk individuals.

Structure activity relationship of phenolic acid inhibitors of α-synuclein fibril formation and toxicity.

The aggregation of α-synuclein (α-syn) is considered the key pathogenic event in many neurological disorders such as Parkinson's disease (PD), dementia with Lewy bodies and multiple system atrophy, giving rise to a whole category of neurodegenerative diseases known as synucleinopathies. Although the molecular basis of α-syn toxicity has not been precisely elucidated, a great deal of effort has been put into identifying compounds that could inhibit or even reverse the aggregation process. Previous reports indicated that many phenolic compounds are potent inhibitors of α-syn aggregation. The aim of the present study was to assess the anti-aggregating effect of gallic acid (GA) (3,4,5-trihydroxybenzoic acid), a benzoic acid derivative that belongs to a group of phenolic compounds known as phenolic acids. By employing an array of biophysical and biochemical techniques and a cell-viability assay, GA was shown not only to inhibit α-syn fibrillation and toxicity but also to disaggregate preformed α-syn amyloid fibrils. Interestingly, GA was found to bind to soluble, non-toxic oligomers with no ß-sheet content, and to stabilize their structure. The binding of GA to the oligomers may represent a potential mechanism of action. Additionally, by using structure activity relationship data obtained from fourteen structurally similar benzoic acid derivatives, it was determined that the inhibition of α-syn fibrillation by GA is related to the number of hydroxyl moieties and their position on the phenyl ring. GA may represent the starting point for designing new molecules that could be used for the treatment of PD and related disorders.

The role of α-synuclein in neurodegenerative diseases: from molecular pathways in disease to therapeutic approaches.

Parkinson disease (PD) is the second most prevalent neurodegenerative disorder after Alzheimer's disease (AD). The formation of the cytoplasmic inclusions named "Lewy bodies" in the brain, considered to be a marker for neuronal degeneration in PD and dementia with Lewy bodies. However, Lewy bodies (LBs) are also observed in approximately 60 percent of both sporadic and familial cases with AD. LBs consist of fibrils mainly formed by post-translational modified α-synuclein (α-syn) protein. The modifications can be truncation, phosphorylation, nitration and mono-, di-, or tri-ubiquitination. Development of disease seems to be linked to events that increase the concentration of α-syn or cause its chemical modification, either of which can accelerate α-syn aggregation. Examples of such events include increased copy number of genes, decreased rate of degradation via the proteasome or other proteases, or modified forms of α-syn. As the aggregation of α-syn in the brain has been strongly implicated as a critical step in the development of several neurodegenerative diseases, the current search for disease-modifying drugs is focused on modification of the process of α-syn deposition in the brain. Recently researchers have screened and designed various molecules that are selectively focused on inhibiting or preventing α-syn aggregation and toxicity. Another strategy that has emerged is to target α-syn expression as a potential therapy for neurodegenerative diseases associated with LBs.

Structural alterations induced by botulinum toxin injection in juvenile versus adult rat muscle.

OBJECTIVE: To investigate whether botulinum neurotoxin type A (BoNT-A) injections produce the same structural changes in juvenile and adult muscle. METHODS: The present study was carried out in the Department of Anatomy, Faculty of Medicine, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia from October 2010 to May 2011. A total of 32 adult and 32 juvenile rats were used. Electron microscopy and immuno-histochemical techniques were used to conduct the morphological study. Neurofilament immunohistochemistry method was used. RESULTS: The results indicate that the use of BoNT-A injections induced morphological changes in the form of muscle fiber atrophy, disorganization of the muscle fiber structure, extension of nerve terminal sprouts, and formation of new neuromuscular junctions. The same set of structural changes took place in both groups. However, the time scale of these changes occurred earlier in juvenile rats than adult muscle. CONCLUSION: The injection of BoNT-A leads to morphological changes in juvenile and adult rat muscle. These changes were the same in both groups.