The number of risk factors increases the recurrence events in ischemic stroke.

PURPOSE: Stroke is a significant cause of disability worldwide and is considered a disease caused by long-term exposure to lifestyle-related risk factors. These risk factors influence the first event of stroke and recurrent stroke events, which carry more significant risks for more severe disabilities. This study specifically compared the risk factors and neurological outcome of patients with recurrent ischemic stroke to those who had just experienced their first stroke among patients admitted to the Hospital. PATIENTS AND METHODS: We observed and analyzed 300 patients' data who met the inclusion and exclusion criteria. This retrospective observational study was conducted on consecutive acute ischemic stroke patients admitted to the top referral hospital, West Java, Indonesia. The data displayed are epidemiological characteristics, NIHSS score at admission and discharge, and the type and number of risk factors. Data were then analyzed using appropriate statistical tests. RESULTS: Most patients had more than one risk factor with hypertension as the most frequent (268 subjects or 89.3%). In patients who experienced ischemic stroke for the first time, the average National Institutes of Health Stroke Scale (NIHSS) score was lower (6.52 ± 3.55), and the alteration of NIHSS score was higher (1.22 ± 2.26) than those with recurrent stroke (6.96 ± 3.55) for NIHSS score and 1.21 ± 1.73 for alteration of NIHSS score). We processed the data with statistical analysis and showed a positive correlation between age (P < 0.05) and the number of risk factors (P < 0.001) in the recurrent ischemic stroke group. CONCLUSIONS: Age and the number of risk factors correlate with recurrent ischemic strokes.

Benefits of gamification in medical education.

Medical education is changing at a fast pace. Students attend medical school with a high degree of technological literacy and a desire for a diverse educational experience. As a result, a growing number of medical schools are incorporating technology-enhanced active learning and multimedia education tools into their curriculum. Gamified training platforms include educational games, mobile medical apps, and virtual patient scenarios. We provide a systematic review of what is meant by gamification in this era. Specific educational games, mobile apps, and virtual simulations that may be used for preclinical and clinical training have been discovered and classified. The available data were presented in terms of the recognized platforms for medical education's possible benefits. Virtual patient simulations have been shown to enhance learning results in general. Gamification could improve learning, engagement, and cooperation by allowing for real-world application. They may also help with promoting risk-free healthcare decision-making, remote learning, learning analytics, and quick feedback. We account for Preclinical training which included 5 electronic games and 4 mobile apps, while clinical training included 5 electronic games, 10 mobile applications, and 12 virtual patient simulation tools. There were additionally nine more gamified virtual environment training products that were not commercially accessible. Many of these studies have shown that utilizing gamified media in medical education may confer advantages. This collection of hyperlinked resources may be utilized by medical students, practitioners, and instructors at all levels.

The panniculus carnosus muscle: a missing link in the chronicity of heel pressure ulcers?

Chronic and recurring pressure ulcers (PUs) create an unmet need for predictive biomarkers. In this work, we examine the panniculus carnosus, a thin cutaneous muscle, traditionally considered vestigial in humans, and ask whether the panniculus may play a role in the chronicity and reinjury of heel PUs. To determine whether humans have a panniculus muscle layer at the heel, we dissected eight cadavers. To assess the influence of the panniculus layer on PU, we performed computational simulations of supine weight bearing. Finally, we assessed panniculus regeneration in fluorescent mice. Results show a panniculus layer present in all cadavers examined. Simulations show a thin layer of panniculus muscle causes a dramatic decrease in the volume of soft tissue experiencing high strain and stress, compared to a heel without a panniculus. Importantly, in the mouse model, the panniculus fails to regenerate after PU, even when other cutaneous layers had fully regenerated. Our work shows that the panniculus is able to redistribute load around the heel bone, which might allow it to prevent PUs. Moreover, it is highly susceptible to incomplete regeneration after PU. Poor panniculus regeneration after PU might be a predictive anatomical biomarker for recurrence, and this biomarker should be evaluated prospectively in future clinical trials.

The Lymphocyte Depletion in Patients with Acute Ischemic Stroke Associated with Poor Neurologic Outcome.

PURPOSE: Inflammation plays an important role and is involved in all stages of acute ischemic stroke. One of these stages involves the recruitment of leukocytes from the peripheral circulation into the ischemic tissue. Lymphocytes as a subtype of leukocytes are important mediators and can become a predictor of neurological outcome. Several studies have been conducted regarding the correlation between differential lymphocyte counts and acute ischemic stroke. Most of these studies analyzed lymphocyte ratio to other leukocyte subtypes such as neutrophils and monocytes. This study specifically observed the role of lymphocytes as an indicator of the inflammatory response in patients with acute ischemic stroke. This study aimed to observe the correlation among risk factors, infarct location, leukocyte counts, lymphocyte value and neurologic output in acute ischemic stroke patients. PATIENTS AND METHODS: We observed and analyzed 193 patients' data from medical record which met the inclusion and exclusion criteria with a diagnosis of acute ischemic stroke at the Department of Neurology of Dr. Hasan Sadikin General Bandung. Data were then analysed using appropriate statistical tests. RESULTS: Most patients have more than one risk factor with a leukocyte count of less than 10,000 cell/mm3. Infarct was mostly located in subcortical area (basal ganglia), with moderate average NIHSS values at admission and at discharge. The number of lymphocytes decreased in the subject group with more than 10,000 cell/mm3 leukocytes. Subsequently, data were analyzed using Spearman's test and there was a correlation between NIHSS on admission and lymphocyte depletion. CONCLUSION: The lymphocyte depletion in patients with leukocytosis is a predictor of poor NIHSS.

Scan and Learn: Quick Response Code Enabled Museum for Mobile Learning of Anatomy and Pathology.

In the past, medical museums played a significant role in anatomy and pathology training. The attraction of medical museums has declined recently due to the emergence of information technology and innovative medical curricula. An innovative mobile learning platform has been developed using quick response (QR) codes for the museum specimens at the Lee Kong Chain School of Medicine, Singapore. High-quality images of the potted specimens were captured and combined into an album and a video using Adobe Acrobat Pro 9 and Windows Movie Maker, respectively. Subsequently, QR codes were generated linking to PDF documents with annotations, pathology, and clinical history concerning the specimens. Quick response codes were piloted in gastrointestinal teaching module for Year 2 medical students. Survey responses were obtained from students to verify the efficacy of QR as a learning tool. The majority of students either agreed or strongly agreed that it was easy to access the information about the specimen with QR codes (4.47 ± 0.84), while 96% of students agreed that they are able to correlate the specimen with the annotated images (4.56 ± 0.56). The majority of students (78%) agreed that QR codes are useful for their learning (4.22 ± 0.87), while 75% of students felt QR codes motivate them to visit Anatomy Resource Centre. Most of the students agreed that QR codes are useful for revision of materials (4.13 ± 1.07) and independent learning (4.38 ± 0.87). These findings suggest that QR codes are not only effective for students learning but also enhance their exploration experience with the museum specimens.

Gamifying anatomy education.

The objective of our research is to find out if gamification increases motivation for self-directed learning (SDL) of human anatomy among year 1 medical students, and more importantly, their academic grades (n = 120). At the NUS Yong Loo Lin School of Medicine, anatomy teaching has traditionally been delivered via didactic means. To encourage more active learning, suitable games (non-digital) and the script concordance test were utilized to enhance the process. The flipped classroom approach was also introduced to further trigger active learning. In addition, the use of mobile apps (digital) was also initiated as supplements for SDL. Feedback was collected based on the previously validated PRO-SDL scale. Results from the research yielded inconclusive evidence to support enhanced motivation among our students due to gamification (P > 0.05). However, it did help to encourage active participation for a "fun learning" experience supported by numerous positive comments. More importantly, the participant's continuous assessment (CA1, CA2, and CA3) and objective specific practical exam results were better than the cohort's average (P < 0.05), suggesting that enhanced meta-cognition, and factual recall had taken place. While it is positive, there are some caveats to note with gamification, first and foremost, that it is tutor dependent. Taken together, gamification could represent a new paradigm for anatomy education, and also an opportune time to change the prevailing culture in the healthcare and education industry. Clin. Anat. 31:997-1005, 2018. © 2018 Wiley Periodicals, Inc.

Transgenic Mice Overexpressing the Divalent Metal Transporter 1 Exhibit Iron Accumulation and Enhanced Parkin Expression in the Brain.

Exposure to divalent metals such as iron and manganese is thought to increase the risk for Parkinson's disease (PD). Under normal circumstances, cellular iron and manganese uptake is regulated by the divalent metal transporter 1 (DMT1). Accordingly, alterations in DMT1 levels may underlie the abnormal accumulation of metal ions and thereby disease pathogenesis. Here, we have generated transgenic mice overexpressing DMT1 under the direction of a mouse prion promoter and demonstrated its robust expression in several regions of the brain. When fed with iron-supplemented diet, DMT1-expressing mice exhibit rather selective accumulation of iron in the substantia nigra, which is the principal region affected in human PD cases, but otherwise appear normal. Alongside this, the expression of Parkin is also enhanced, likely as a neuroprotective response, which may explain the lack of phenotype in these mice. When DMT1 is overexpressed against a Parkin null background, the double-mutant mice similarly resisted a disease phenotype even when fed with iron- or manganese-supplemented diet. However, these mice exhibit greater vulnerability toward 6-hydroxydopamine-induced neurotoxicity. Taken together, our results suggest that iron accumulation alone is not sufficient to cause neurodegeneration and that multiple hits are required to promote PD.

Detectability of secretagogin in human erythrocytes.

Secretagogin is a six EF-hand calcium-binding protein that can identify granule cells in the dentate gyrus of hippocampus. The aim of this study was to determine if secretagogin can be detected in human blood cells. Eight adult males were recruited for blood analysis. Whole blood was separated into plasma, peripheral mononuclear cells and erythrocytes with Ficoll-Paque and probed for secretagogin using reverse-transcription polymerase chain reaction and Western blot. While secretagogin mRNA was detected in both peripheral mononuclear cells and erythrocytes using reverse-transcription polymerase chain reaction, SCGN protein was only detected in erythrocytes. Interestingly, peripheral mononuclear cells secretagogin mRNA expression levels showed significant negative correlation with age. This begets the question on the function of secretagogin in blood cells and if it is correlated to neurodegeneration associated with ageing. This remains our impetus for further research.

Singapore's anatomical future: quo vadis?

The disciplines of anatomy and surgery are not dichotomous since one is dependent on the other. Traditionally, surgeons predominantly taught gross and clinical anatomy. In this review, we examine the context of how human anatomy is taught nowadays. In essence, we discovered that there are certain discernable trends consistently observable between the American and British systems. In Singapore, the British Russell Group first influenced its education landscape but now more so by the American Ivy League. Singapore now has three medical schools all offering differing anatomy curricula, which serves as an opportune time for it to consider if there is a best approach given that the practice of surgery is also evolving in parallel. This review discusses the various pedagogies and issues involved, and will serve as a forum and stimulus for discussion. By tweaking the curriculum correctly and the lessons learnt, future doctors and surgeons in training will receive a better anatomical education, not just in Singapore but the world in general. Key recommendations include the use of body painting, clay, plasticine to facilitate the learning of anatomy, and the implementation of a body donation program. Furthermore, strategic mergers with key stakeholders will also ensure the survival of the discipline.

Enhanced autophagy from chronic toxicity of iron and mutant A53T α-synuclein: implications for neuronal cell death in Parkinson disease.

Parkinson disease (PD), a prevalent neurodegenerative motor disorder, is characterized by the rather selective loss of dopaminergic neurons and the presence of α-synuclein-enriched Lewy body inclusions in the substantia nigra of the midbrain. Although the etiology of PD remains incompletely understood, emerging evidence suggests that dysregulated iron homeostasis may be involved. Notably, nigral dopaminergic neurons are enriched in iron, the uptake of which is facilitated by the divalent metal ion transporter DMT1. To clarify the role of iron in PD, we generated SH-SY5Y cells stably expressing DMT1 either singly or in combination with wild type or mutant α-synuclein. We found that DMT1 overexpression dramatically enhances Fe(2+) uptake, which concomitantly promotes cell death. This Fe(2+)-mediated toxicity is aggravated by the presence of mutant α-synuclein expression, resulting in increased oxidative stress and DNA damage. Curiously, Fe(2+)-mediated cell death does not appear to involve apoptosis. Instead, the phenomenon seems to occur as a result of excessive autophagic activity. Accordingly, pharmacological inhibition of autophagy reverses cell death mediated by Fe(2+) overloading. Taken together, our results suggest a role for iron in PD pathogenesis and provide a mechanism underlying Fe(2+)-mediated cell death.

Neurodegenerative diseases: exercising toward neurogenesis and neuroregeneration.

Currently, there is still no effective therapy for neurodegenerative diseases (NDD) such as Alzheimer's disease (AD) and Parkinson's disease (PD) despite intensive research and on-going clinical trials. Collectively, these diseases account for the bulk of health care burden associated with age-related neurodegenerative disorders. There is therefore an urgent need to further research into the molecular pathogenesis, histological differentiation, and clinical management of NDD. Importantly, there is also an urgency to understand the similarities and differences between these two diseases so as to identify the common or different upstream and downstream signaling pathways. In this review, the role iron play in NDD will be highlighted, as iron is key to a common underlying pathway in the production of oxidative stress. There is increasing evidence to suggest that oxidative stress predisposed cells to undergo damage to DNA, protein and lipid, and as such a common factor involved in the pathogenesis of AD and PD. The challenge then is to minimize elevated and uncontrolled oxidative stress levels while not affecting basal iron metabolism, as iron plays vital roles in sustaining cellular function. However, overload of iron results in increased oxidative stress due to the Fenton reaction. We discuss evidence to suggest that sustained exercise and diet restriction may be ways to slow the rate of neurodegeneration, by perhaps promoting neurogenesis or antioxidant-related pathways. It is also our intention to cover NDD in a broad sense, in the context of basic and clinical sciences to cater for both clinician's and the scientist's needs, and to highlight current research investigating exercise as a therapeutic or preventive measure.

Motor axonal sprouting and neuromuscular junction loss in an animal model of Charcot-Marie-Tooth disease.

Muscle weakness in Charcot-Marie-Tooth Type 1A disease (CMT1A) caused by mutations in peripheral myelin protein 22 (PMP22) has been attributed to an axonopathy that results in denervation and muscle atrophy. The underlying pathophysiological mechanisms involved are not understood. We investigated motor performance, neuromuscular junctions (NMJs), physiological parameters, and muscle morphometry of PMP22 transgenic mice. Neuromuscular junctions were progressively lost in hindlimb muscles of PMP22 transgenic mice, but their motor performance did not completely deteriorate during the observation period. There was considerable variability, including in laterality, in deficits among the animals. Cross-sectional areas and mean fiber size measurements indicated variable myofiber atrophy in hindlimb muscles. There was substantial concomitant axonal sprouting, and loss of neuromuscular junctions was inversely correlated with the accumulated length of axonal branches. Synaptic transmission studied in isolated nerve/muscle preparations indicated variable partial muscle denervation. Acetylcholine sensitivity was higher in the mutant muscles, and maximum tetanic force evoked by direct or indirect stimulation, specific force, and wet weights were markedly reduced in some mutant muscles. In summary, there is partial muscle denervation, and axons may retain some regenerative capacity but fail to reinnervate muscles in PMP22 transgenic mice.

Alterations in spatial learning and memory after forced exercise.

Exercise has been shown to influence learning and memory. Most studies were performed with a voluntary running paradigm (e.g. running wheel) in mice. However, such effects of exercise on learning and memory are less well demonstrated using a forced running paradigm (e.g. treadmill). The present study was designed to examine the effects of 12 weeks of forced treadmill running on learning and memory performance in rats. We have previously shown that forced running resulted in qualitative and quantitative changes in the cholinergic neurons of the horizontal diagonal band of Broca (HDB) in the septum. This study was conducted in order to determine whether or not these changes occur simultaneously with enhanced learning and memory. The one-day version of the Morris water maze (MWM) test [Frick, K.M., Stillner, E.T., Berger-Sweeney, J., 2000. Mice are not little rats: species differences in a one-day water maze task. NeuroReport 11, 3461-3465] was used to test spatial learning and memory after the exercise period. Our data showed that runners displayed better spatial learning and memory when compared to nonrunners. This was evidently shown by a reduction in the time required for spatial acquisition (p<0.05) and superior probe trial performance (p<0.05). A shorter distance swam by the runners also suggested improved learning over the nonrunners (p<0.05). In an attempt to revalidate our earlier quantitative results, we used design-based stereology (DBS) to estimate the number of cholinergic neuronal profile population in the medial septum and diagonal band (MSDB). We confirmed that forced running increased the cholinergic neuronal profile subpopulation in the HDB (Coefficient of Error<0.2). Taken together, these results indicate that forced exercise could influence learning and memory with a concomitant increase in the number of cholinergic neurons in the HDB.