Hyperglycaemia does not increase perfusion deficits after focal cerebral ischaemia in male Wistar rats

Background: Hyperglycaemia is associated with a worse outcome in acute ischaemic stroke patients; yet the pathophysiological mechanisms of hyperglycaemia-induced damage are poorly understood. We hypothesised that hyperglycaemia at the time of stroke onset exacerbates ischaemic brain damage by increasing the severity of the blood flow deficit. Methods: Adult, male Wistar rats were randomly assigned to receive vehicle or glucose solutions prior to permanent middle cerebral artery occlusion. Cerebral blood flow was assessed semi-quantitatively either 1 h after middle cerebral artery occlusion using 99mTc-D, L-hexamethylpropyleneamine oxime (99mTc-HMPAO) autoradiography or, in a separate study, using quantitative pseudo-continuous arterial spin labelling for 4 h after middle cerebral artery occlusion. Diffusion weighted imaging was performed alongside pseudo-continuous arterial spin labelling and acute lesion volumes calculated from apparent diffusion coefficient maps. Infarct volume was measured at 24 h using rapid acquisition with refocused echoes T2-weighted magnetic resonance imaging. Results: Glucose administration had no effect on the severity of ischaemia when assessed by either 99mTc-HMPAO autoradiography or pseudo-continuous arterial spin labelling perfusion imaging. In comparison to the vehicle group, apparent diffusion coefficient–derived lesion volume 2–4 h post-middle cerebral artery occlusion and infarct volume 24 h post-middle cerebral artery occlusion were significantly greater in the glucose group. Conclusions: Hyperglycaemia increased acute lesion and infarct volumes but there was no evidence that the acute blood flow deficit was exacerbated. The data reinforce the conclusion that the detrimental effects of hyperglycaemia are rapid, and that treatment of post-stroke hyperglycaemia in the acute period is essential but the mechanisms of hyperglycaemia-induced harm remain unclear

Plasma exosomes from children with juvenile dermatomyositis are taken up by human aortic endothelial cells and are associated with altered gene expression in those cells

BACKGROUND: The pathology of juvenile dermatomyositis (JDM) is characterized by prominent vessel wall and perivascular inflammation. This feature of the disease has remained unexplained and under-investigated. We have hypothesized that plasma exosomes, which play an important role in inter-cellular communication, may play a role in the vascular injury associated with JDM. OBJECTIVE: To characterize the circulating exosomes of children with JDM and determine whether the small RNA cargoes within those exosomes are capable of altering transcriptional programs within endothelial cells. DESIGN/METHODS: We purified exosomes from plasma samples of children with active, untreated JDM (n = 6) and healthy controls (n = 9). We characterized the small RNA cargoes in JDM and control exosomes by RNA sequencing using the Illumina HiSeq 2500 platform. We then incubated isolated exosomes from healthy controls and children with JDM with cultured human aortic endothelial cells (HAEC) for 24 h. Fluorescence microscopy was used to confirm that both control and JDM exosomes were taken up by HAEC. RNA was then purified from HAEC that had been incubated with either control or JDM exosomes and sequenced on the Illumina platform. Differential expression of mRNAs from HAEC incubated with control or JDM exosomes was ascertained using standard computational methods. Finally, we assessed the degree to which differential gene expression in HAEC could be attributed to the different small RNA cargoes in JDM vs control exosomes using conventional and novel analytic methods. RESULTS: We identified 10 small RNA molecules that showed differential abundance when we compared JDM and healthy control exosomes. Fluorescence microscopy of labeled exosomes confirmed that both JDM and control exosomes were taken up by HAEC. Differential gene expression analysis revealed 59 genes that showed differential expression between HAEC incubated with JDM exosomes vs HAEC incubated with exosomes from controls. Statistical analysis of gene expression data demonstrated that multiple miRNAs exerted transcriptional control on multiple genes with HAEC. CONCLUSIONS: Plasma exosomes from children with active, untreated JDM are taken up by HAEC and are associated with alterations in gene expression in those cells. These findings provide new insight into potential mechanisms leading to the targeting of vascular tissue by the immune system in JDM

Anisamide-targeted gold nanoparticles for siRNA delivery in prostate cancer - synthesis, physicochemical characterisation and in vitro evaluation

Metastatic prostate cancer is a leading cause of cancer-related death in men and current chemotherapies are largely inadequate in terms of efficacy and toxicity. Hence improved treatments are required. The application of siRNA as a cancer therapeutic holds great promise. However, translation of siRNA into the clinic is dependent on the availability of an effective delivery system. Gold nanoparticles (AuNPs) are known to be effective and non-toxic siRNA delivery agents. In this study, a stable gold nanosphere coated with poly(ethylenimine) (PEI) was prepared to yield PEI capped AuNPs (Au-PEI). The PEI was further conjugated with the targeting ligand anisamide (AA, is known to bind to the sigma receptor overexpressed on the surface of prostate cancer cells) to produce an anisamide-targeted nanoparticle (Au-PEI-AA). The resulting untargeted and targeted nanoparticles (Au-PEI and Au-PEI-AA respectively) were positively charged and efficiently complexed siRNA. Au-PEI-AA mediated siRNA uptake into PC3 prostate cancer cells via binding to the sigma receptor. In addition, the Au-PEI-AA·siRNA complexes resulted in highly efficient knockdown of the RelA gene (∼70%) when cells were transfected in serum-free medium. In contrast, no knockdown was observed in the presence of serum, suggesting that adsorption of serum proteins inhibits the binding of the anisamide moiety to the sigma receptor. This study provides (for the first time) proof of principle that anisamide-labelled gold nanoparticles can target the sigma receptor. Further optimisation of the formulation to increase serum stability will enhance its potential to treat prostate cancer

Smart & Savvy Students: Year 2

Smart & Savvy Students\u27 (SSS) main goal is to convert scientific psychological articles to understandable pieces of information for general audiences. We have a Twitter feed, Facebook page, and Instagram to spread the information to Clemson\u27s student body and other audiences that we post to 3 to 5 times a week. Each tweet contains a 140-character tip written in a dialogue format. The tweets include links to the Facebook page, which has more information. The Facebook page provides links to scientific sources that support our claims. These links provide students with the opportunity to learn more about the topics. In addition, we post to an Instagram account that links back to Facebook and Twitter, which allows us to spread our information to the largest audience possible. Using popular social media, SSS targets students by including information on topics such as study skills, exercise and diet, and healthy habits, which can be applied in day-to-day life for more positive lifestyles

SHAPS-C: the Snaith-Hamilton pleasure scale modified for clinician administration

Anhedonia, a diminished or lack of ability to experience and anticipate pleasure represents a core psychiatric symptom in depression. Current clinician assessment of anhedonia is generally limited to one or two all-purpose questions and most well-known psychometric scales of anhedonia are relatively long, self-administered, typically not state sensitive, and are unsuitable for use in clinical settings. A user-friendly tool for a more in-depth clinician assessment of hedonic capacity is needed. The present study assessed the validity and reliability of a clinician administered version of the Snaith-Hamilton Pleasure Scale, the SHAPS-C, in 34 depressed subjects. We compared total and specific item scores on the SHAPS-C, SHAPS (self-report version), Montgomery-Åsberg Depression Rating Scale (MADRS), and the Inventory of Depressive Symptomatology-Self Rating version (IDS-SR). We also examined construct, content, concurrent, convergent, and discriminant validity, internal consistency, and split-half reliability of the SHAPS-C. The SHAPS-C was found to be valid and reliable. The SHAPS and the SHAPS-C were positively correlated with one another, with levels of depression severity, as measured by the MADRS, and the IDS-SR total scores, and with specific items of the MADRS and IDS-SR sensitive to measuring hedonic capacity. Our investigation indicates that the SHAPS-C is a user friendly, reliable, and valid tool for clinician assessment of hedonic capacity in depressed bipolar and unipolar patients

Biomimetic gold nanocomplexes for gene knockdown - will gold deliver dividends for siRNA nanomedicines?

RNA interference (RNAi) effectors such as small interfering RNA (siRNA) and micro RNA (miRNA) can selectively downregulate any gene implicated in the pathology of a disease. Therefore, RNAi-based therapies have immense potential for the treatment of a wide range of diseases. However, pharmacokinetic and pharmacodynamic studies have revealed that these therapeutic agents have poor bioactivity due to a number of factors, including insufficient plasma drug levels, short plasma half-lives, renal clearance, and hepatic metabolism. Non-viral delivery may facilitate the clinical application of siRNA-based therapeutics by helping to overcome these barriers. Recently, the potential of gold nanoparticles (AuNPs) as multifunctional carriers for transporting drugs, proteins, and genetic materials has been demonstrated. In this review, some of the key properties of AuNPs relevant to siRNA delivery, such as physical properties and surface chemistry have been described. In addition, the ability of AuNP-based formulation strategies to successfully overcome delivery barriers associated with siRNA, and the potential for this material to translate into safe and effective nanomedicines are critically discussed

Interobserver Agreement in the Clinical Assessment of Children With Blunt Abdominal Trauma

Objectives The objective was to determine the interobserver agreement of historical and physical examination findings assessed during the emergency department (ED) evaluation of children with blunt abdominal trauma. Methods This was a planned substudy of a multicenter, prospective cohort study of children younger than 18 years of age evaluated for blunt abdominal trauma. Patients were excluded if injury occurred more than 24 hours prior to evaluation or if computed tomography (CT) imaging was obtained at another hospital prior to transfer to a study site. Two clinicians independently recorded their clinical assessments of a convenience sample of patients onto data collection forms within 60 minutes of each other and prior to CT imaging (if obtained) or knowledge of laboratory results. The authors categorized variables as either subjective symptoms (i.e., patient history) or objective findings (i.e., physical examination). For each variable recorded by the two observers, the agreement beyond that expected by chance was estimated, using the kappa (κ) statistic for categorical variables and weighted κ for ordinal variables. Variables with 95% lower confidence limits (LCLs) κ ≥ 0.4 (moderate agreement or better) were considered to have acceptable agreement. Results A total of 632 pairs of physician observations were obtained on 23 candidate variables. Acceptable agreement was achieved in 16 (70%) of the 23 variables tested. For six subjective symptoms, κ ranged from 0.48 (complaint of shortness of breath) to 0.90 (mechanism of injury), and only the complaint of shortness of breath had a 95% LCL κ < 0.4. For the 17 objective findings, κ ranged from –0.01 (pelvis instability) to 0.82 (seat belt sign present). The 95% LCL for κ was <0.4 for flank tenderness, abnormal chest auscultation, suspicion of alcohol or drug intoxication, pelvis instability, absence of bowel sounds, and peritoneal irritation. Conclusions Observers can achieve at least acceptable agreement on the majority of historical and physical examination variables in children with blunt abdominal trauma evaluated in the ED. Those variables are candidates for consideration for development of a clinical prediction rule for intra‐abdominal injury in children with blunt trauma. Resumen Concordancia Interobservador en la Valoración Clínica de los Niños con Traumatismo Abdominal Cerrado Objetivos Determinar la concordancia interobservador de los hallazgos de la historia clínica y la exploración física obtenidos durante la valoración de los niños con traumatismo abdominal de alta energía en el servicio de urgencias (SU). Metodología Se diseñó un subestudio de un estudio de cohorte prospectivo y multicéntrico de niños de 18 años o menos evaluados por traumatismo abdominal cerrado. Se excluyeron los pacientes si el traumatismo había ocurrido más de 24 horas antes de la primera valoración, o si las imágenes de la tomografía computarizada (TC) se obtuvieron en otro hospital previamente a trasladarse al lugar del estudio. Dos clínicos recogieron de forma independiente su valoración clínica en un formulario de datos, de una muestra de conveniencia de pacientes, en los primeros 60 minutos, y previamente a las imágenes de la TC (si ésta se realizó) o al conocimiento de los resultados del laboratorio. Se clasificaron las variables como síntomas subjetivos (ej.: historia del paciente) o hallazgos objetivos (ej.: exploración física). Para cada variable recogida por los dos observadores, se estimó la concordancia más allá de la esperada por el azar usando el índice kappa (κ) para las variables categóricas y índice κ ponderado para las variables ordinales. Se consideró que existía una concordancia aceptable para las variables con una κ ≥ 0,4 (concordancia moderada o buena) en el límite inferior del intervalo de confianza del 95% (IC 95%). Resultados Se obtuvieron 632 pares de observaciones clínicas en 23 variables candidatas. Se alcanzó la concordancia aceptable en 16 (70%) de ellas. Para los seis síntomas subjetivos, el rango de κ fue de 0,48 (queja de dificultad respiratoria) a 0,90 (mecanismo de la lesión), y sólo la queja de dificultad respiratoria tuvo una κ < 0,4 en el límite inferior del IC 95%. Para los 17 hallazgos objetivos, el rango de κ fue desde ‐0,01 (inestabilidad pelvis) a 0,82 (presencia del signo del cinturón de seguridad). El dolor en el flanco, la auscultación torácica alterada, la sospecha de intoxicación por alcohol o tóxicos, la inestabilidad de pelvis, la ausencia de ruidos intestinales y la irritación peritoneal tuvieron una κ < 0,4 en el límite inferior del IC 95%. Conclusiones Los observadores pueden alcanzar al menos una concordancia aceptable en la mayoría de las variables de la historia clínica y la exploración física en los niños con traumatismo abdominal cerrado evaluado en el SU. Estas variables son candidatas para considerarse en el desarrollo de una regla de predicción clínica para la lesión intrabdominal en los niños con traumatismo de cerrado.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98339/1/acem12132.pd

A Communicating Branch Between the Musculocutaneous Nerve and the Median Nerve: A Case Report

Anatomical variations of peripheral nerves are commonly reported in the literature.&nbsp; While typically benign, they are of clinical importance as they can contribute to atypical clinical presentations, cause difficulty with imaging and nerve conduction studies, and lead to surgical challenges for surgeons.&nbsp; We report here a communicating branch between the musculocutaneous nerve and median nerve found during cadaveric dissection in a Doctor of Nursing Practice course in the Department of Nurse Anesthesia at Samford University.&nbsp; Although the case described here is among the most common anatomical variations of the peripheral nerves, there are classification systems for this variation that need to be recognized and applied by anatomists, clinicians, and surgeons

Bilateral Long Head of the Triceps Brachii Muscle Innervation via Axillary Nerve: A Case Report

The radial nerve has traditionally been considered the innervation of the long head of the triceps brachii (LHT). However, cadaveric studies have discovered LHT innervation via the axillary nerve in roughly 6-15 % of shoulders. A cadaver with exclusive axillary nerve innervation to the LHT bilaterally was discovered during cadaveric dissection in a graduate course at Samford University. This anatomical variation may have clinical implications for surgeries, shoulder dislocations, and quadrilateral space syndrome. Axillary nerve injuries may additionally present with shoulder extension and elbow extension weakness if this variation is present.&nbsp

Post-diagnosis dietary factors and survival after invasive breast cancer.

Little is known about the effects of diet after breast cancer diagnosis on survival. We prospectively examined the relation between post-diagnosis dietary factors and breast cancer and all-cause survival in women with a history of invasive breast cancer diagnosed between 1987 and 1999 (at ages 20-79 years). Diet after breast cancer diagnosis was measured using a 126-item food frequency questionnaire. Among 4,441 women without a history of breast cancer recurrence prior to completing the questionnaire, 137 subsequently died from breast cancer within 7 years of enrollment. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated for intake of macronutrients as well as selected micronutrients and food groups from Cox proportional hazards regression models. After adjustment for factors at diagnosis (age, state of residence, menopausal status, smoking, breast cancer stage, alcohol, history of hormone replacement therapy), interval between diagnosis and diet assessment, and at follow-up (energy intake, breast cancer treatment, body mass index, and physical activity), women in the highest compared to lowest quintile of intake of saturated fat and trans fat had a significantly higher risk of dying from any cause (HR = 1.41, 95% CI = 1.06-1.87, P trend = 0.03) for saturated fat; (HR = 1.78, 95% CI = 1.35-2.32, P trend = 0.01) for trans fat intake. Associations were similar, though did not achieve statistical significance, for breast cancer survival. This study suggests that lower intake of saturated and trans fat in the post-diagnosis diet is associated with improved survival after breast cancer diagnosis