Significance and implications of FHIT gene expression and promoter hypermethylation in acute lymphoblastic leukemia (ALL).

BACKGROUND: Fragile histidine triad (FHIT) has been documented to play a vital role in various cancers including acute lymphoblastic leukemia (ALL). Keeping in view the plausible role of FHIT gene, we aimed to examine DNA promoter hypermethylation and mRNA expression in ALL cases in Kashmir (North India). METHODS: A total of 66 cases of ALL were analyzed for FHIT mRNA expression and promoter methylation by qRT-PCR and Methylation Specific-PCR (MS-PCR) respectively. RESULTS: FHIT mRNA expression showed significantly decreased expression in ALL cases with mean fold change of 9.24 ± 5.44 as compared to healthy controls (p = 0.01). The pattern of FHIT deregulation in ALL cases differed significantly between decreased and increased expression (p < 0.0001). A threefold decreased expression was observed in 75% of ALL cases than healthy controls (- 3.58 ± 2.32). ALL patients with FHIT gene promoter hypermethylation presented significantly higher in 80% (53/66) of cases (p = 0.0005). The association of FHIT gene hypermethylation and its subsequent expression showed FHIT mRNA expression as significantly lower in ALL cases with hypermethylation (p = 0.0008). B-ALL cases exhibited a highly significant association between the methylation pattern and its mRNA expression (p = 0.000). In low range WBC group, a significant association was found between increased expression (26%) of the cases and methylated (4%)/unmethylated group 86% (p = 0.0006). CONCLUSION: The present study conclude that FHIT gene hypermethylation and its altered expression may be linked in the pathogenesis of ALL and provide an evidence for the role of FHIT in the development of ALL.

EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) POLYMORPHIC VARIATIONS (-216G/T & -191 C/A) POSE A HIGH RISK TO PATIENTS WITH MALIGNANT GLIOMA.

BACKGROUND: Malignant gliomas are the most frequent and lethal brain tumors. Their molecular aspects remain intangible but current studies have pointed to certain genetic polymorphic loci that pose the risk. The polymorphic sequence variations of the epidermal growth factor receptor gene (EGFR) pathway play a vital role in the glioma risk, and the EGFR variants (216G>T and 191C>A) are identified to affect the risk for the development of different tumors including glioma. AIM: To examine genetic variations of EGFR T rs712829 (216G/T) and rs712830 (191C>A) with respect to glioma risk. MATERIALS AND METHODS: 129 confirmed glioma cases were genotyped against 180 malignancy-free healthy controls by polymerase chain reaction-restriction fragment length polymorphism technique (RFLP). RESULTS: The frequency of the TT homozygous variant of the EGFR -216 G/T genotype differed significantly between cases and controls (49.6% vs. 23.0%) (p < 0.0001). The EGFR -216 G>T allele 'T' was found significantly more frequently in cases (0.56 vs. 0.33 in controls; p < 0.0001). The EGFR -191C>A homozygous 'AA' genotype was implicated significantly more frequently in cases than in controls (p < 0.0001). The distribution of the 'A' variant allele was also more frequent in cases (41.9%) than in controls (14.0%) (0.55 vs. 0.30; p < 0.0001). TC and TA haplotypes showed varied frequency in cases and controls. CONCLUSION: EGFR -216 G>T and -191 C>A variants and haplotypes (TA and TC) of the EGFR gene are very strong risk factors in the development of glioma in the Kashmiri population.

A 32-Bit Single Quadrant Angle-Controlled Chipless Tag for Radio Frequency Identification Applications.

A 32-bit chipless RFID tag operating in the 4.5-10.9 GHz band is presented in this paper. The tag has a unique multiple-arc-type shape consisting of closely packed 0.2 mm wide arcs of different radii and lengths. The specific tag geometry provides multiple resonances in frequency domain of an RCS plot. A frequency domain coding technique has also been proposed to encode the tag's RCS signature into a 32-bit digital identification code. The tag has an overall dimension of 17.9 × 17.9 mm2, resulting in a high code density of 9.98 bits/cm2 and spectral efficiency of 5 bits/GHz. The proposed tag is built on a low loss substrate bearing a very small footprint, thereby making it extremely suitable for large-scale product identification purposes in future chipless RFID tag systems.

The effect of gender dyads on the quality of narrative assessments of general surgery trainees.

BACKGROUND: Prior studies have shown that gender can influence how learners are assessed and the feedback they receive. We investigated the quality of faculty narrative comments in general surgery trainee evaluation using trainee-assessor gender dyads. METHODS: Narrative assessments of surgical trainees at the University of British Columbia were collected and rated using the McMaster Narrative Comment Rating Scale (MNCRS). Variables from the MNCRS were inputted into a generalized linear mixed model to explore the impact of gender dyads on the quality of narrative feedback. RESULTS: 2,469 assessments were collected. Women assessors tended to give higher-quality comments (p's < 0.05) than men assessors. Comments from men assessors to women trainees were significantly more positive than comments from men assessors to men trainees (p = 0.02). Men assessors also tended to give women trainees more reinforcing than corrective comments than to men trainees (p < 0.01). CONCLUSIONS: There are significant differences in the quality of faculty feedback to trainees by gender dyads. A range of solutions to improve and reduce differences in feedback quality are discussed.

Seroprevalence of Toxoplasma gondii and associated hematological alterations in small ruminants of D.G. Khan district of Southern Punjab, Pakistan / [Soroprevalência de Toxoplasma gondii e alterações hematológicas associadas em pequenos ruminantes no distrito de D.G. Khan no sul de Punjab, Paquistão]

The present study was carried out to evaluate the prevalence and hematological effects of Toxoplasma gondii in sheep and goat in district Dera Ghazi Khan. Blood samples (n=204) were collected comprise goats (n=101) and sheep (n=103) alongwith age, gender and breeds of animals. Samples were collected randomly from 25 flocks of 7 different union council Viz. Vehova, Tibbi Qaisrani, Lakhani, Kohar, Tuman Qaisrani, Nutkani and Kot Qaisrani of Tehsil Taunsa Sharif at least 4 animals from each flock. All ruminants divide into three groups based on age, breed and gender. The prevalence was detected through two different kits Viz. LAT and ELISA kit. The overall prevalence suspected in goats through LAT and ELISA kit was (35.64%), (32.67%) and in sheep was (25.24%), (23.30%) respectively. The Toxoplasma gondii had a significant effect on goats in age groups and non-significant all other groups of goats and sheep. Toxoplasma gondii had a significant effect on all hematological parameters like Hemoglobin, total leukocyte cells, granulocytes, lymphocytes, platelets, and red blood cells, except monocytes. In conclusion of the current study, toxoplasmosis is prevalent among ruminants, reveals the possibility of transmission to humans on the use of host animals as protein source.(AU)

O objetivo do presente estudo foi avaliar a prevalência e efeitos hematológicos de Toxoplasma gondii em ovelhas e cabras no distrito Dera Ghazi Khan. Amostras de sangue (n=204) foram coletadas para incluir cabras (n=101) e ovelhas (n=103), além de idade, gênero e raça dos animais. Amostras foram coletadas aleatoriamente de 25 rebanhos de 7 conselhos sindicais: Vehova, Tibbi Qaisrani, Lakhani, Kohar, Tuman Qaisrani, Nutkani e Kot Qaisrani of Tehsil Taunsa Sharif com pelo menos 4 animais em cada rebanho. Todos os ruminantes foram divididos em três grupos baseados em idade, raça e gênero. A prevalência foi detectada usando dois kits, LAT e ELISA. A prevalência total suspeita em cabras através dos kits LAT e ELISA foi (35.64%), (32.67%) e em ovelhas foi (25.24%), (23.30%) respectivamente. O Toxoplasma gondii teve efeito significativo em cabras em grupos de idade e não significativo em todos os outros grupos de cabras e ovelhas. Toxoplasma gondii teve efeito significativo em todos os parâmetros hematológicos como hemoglobina, células totais de leucócitos, granulócitos, linfócitos, plaquetas e glóbulos vermelhos, exceto monócitos. O presente estudo conclui que toxoplasmose é prevalente entre ruminantes, e revela a possibilidade de transmissão para humanos com o uso de animais hospedeiros como fonte de proteína.(AU)

Long-term safety and efficacy of closed-loop spinal cord stimulation to treat chronic back and leg pain (Evoke): a double-blind, randomised, controlled trial.

BACKGROUND: Spinal cord stimulation has been an established treatment for chronic back and leg pain for more than 50 years; however, outcomes are variable and unpredictable, and objective evidence of the mechanism of action is needed. A novel spinal cord stimulation system provides the first in vivo, real-time, continuous objective measure of spinal cord activation in response to therapy via recorded evoked compound action potentials (ECAPs) in patients during daily use. These ECAPs are also used to optimise programming and deliver closed-loop spinal cord stimulation by adjusting the stimulation current to maintain activation within patients' therapeutic window. We aimed to examine pain relief and the extent of spinal cord activation with ECAP-controlled closed-loop versus fixed-output, open-loop spinal cord stimulation for the treatment of chronic back and leg pain. METHODS: This multicentre, double-blind, parallel-arm, randomised controlled trial was done at 13 specialist clinics, academic centres, and hospitals in the USA. Patients with chronic, intractable pain of the back and legs (Visual Analog Scale [VAS] pain score ≥60 mm; Oswestry Disability Index [ODI] score 41-80) who were refractory to conservative therapy, on stable pain medications, had no previous experience with spinal cord stimulation, and were appropriate candidates for a spinal cord stimulation trial were screened. Eligible patients were randomly assigned (1:1) to receive ECAP-controlled closed-loop spinal cord stimulation (investigational group) or fixed-output, open-loop spinal cord stimulation (control group). The randomisation sequence was computer generated with permuted blocks of size 4 and 6 and stratified by site. Patients, investigators, and site staff were masked to the treatment assignment. The primary outcome was the proportion of patients with a reduction of 50% or more in overall back and leg pain with no increase in pain medications. Non-inferiority (δ=10%) followed by superiority were tested in the intention-to-treat population at 3 months (primary analysis) and 12 months (additional prespecified analysis) after the permanent implant. This study is registered with ClinicalTrials.gov, NCT02924129, and is ongoing. FINDINGS: Between Feb 21, 2017, and Feb 20, 2018, 134 patients were enrolled and randomly assigned (67 to each treatment group). The intention-to-treat analysis comprised 125 patients at 3 months (62 in the closed-loop group and 63 in the open-loop group) and 118 patients at 12 months (59 in the closed-loop group and 59 in the open-loop group). The primary outcome was achieved in a greater proportion of patients in the closed-loop group than in the open-loop group at 3 months (51 [82·3%] of 62 patients vs 38 [60·3%] of 63 patients; difference 21·9%, 95% CI 6·6-37·3; p=0·0052) and at 12 months (49 [83·1%] of 59 patients vs 36 [61·0%] of 59 patients; difference 22·0%, 6·3-37·7; p=0·0060). We observed no differences in safety profiles between the two groups. The most frequently reported study-related adverse events in both groups were lead migration (nine [7%] patients), implantable pulse generator pocket pain (five [4%]), and muscle spasm or cramp (three [2%]). INTERPRETATION: ECAP-controlled closed-loop stimulation provided significantly greater and more clinically meaningful pain relief up to 12 months than open-loop spinal cord stimulation. Greater spinal cord activation seen in the closed-loop group suggests a mechanistic explanation for the superior results, which aligns with the putative mechanism of action for spinal cord stimulation and warrants further investigation. FUNDING: Saluda Medical.

Differentiation of Autoimmune Pancreatitis from Pancreatic Cancer Remains Challenging.

BACKGROUND: Autoimmune pancreatitis (AIP) is an uncommon form of chronic pancreatitis. Whilst being corticosteroid responsive, AIP often masquerades radiologically as pancreatic neoplasia. Our aim is to appraise demographic, radiological and histological features in our cohort in order to differentiate AIP from pancreatic malignancy. METHODS: Clinical, biochemical, histological and radiological details of all AIP patients 1997-2016 were analysed. The initial imaging was re-reviewed according to international guidelines by three blinded independent radiologists to evaluate features associated with autoimmune pancreatitis and pancreatic cancer. RESULTS: There were a total of 45 patients: 25 in type 1 (55.5%), 14 type 2 (31.1%) and 6 AIP otherwise not specified (13.3%). The median (IQR) age was 57 (51-70) years. Thirty patients (66.6%) were male. Twenty-six patients (57.8%) had resection for suspected malignancy and one for symptomatic chronic pancreatitis. Three had histologically proven malignancy with concurrent AIP. Two patients died from recurrent pancreatic cancer following resection. Multidisciplinary team review based on radiology and clinical history dictated management. Resected patients (vs. non-resected group) were older (64 vs. 53, p = 0.003) and more frequently had co-existing autoimmune pathologies (22.2 vs. 55.6%, p = 0.022). Resected patients also presented with less classical radiological features of AIP, which are halo sign (0/25 vs. 3/17, p = 0.029) and loss of pancreatic clefts (18/25 vs. 17/17, p = 0.017). There were no differences in demographic features other than age. CONCLUSION: Despite international guidelines for diagnosing AIP, differentiation from pancreatic cancer remains challenging. Resection remains an important treatment option in suspected cancer or where conservative treatment fails.

Identification of Cystic Lesions by Secondary Screening of Familial Pancreatic Cancer (FPC) Kindreds Is Not Associated with the Stratified Risk of Cancer.

OBJECTIVES: Intraductal papillary mucinous neoplasms (IPMNs) are associated with risk of pancreatic ductal adenocarcinoma (PDAC). It is unclear if an IPMN in individuals at high risk of PDAC should be considered as a positive screening result or as an incidental finding. Stratified familial pancreatic cancer (FPC) populations were used to determine if IPMN risk is linked to familial risk of PDAC. METHODS: This is a cohort study of 321 individuals from 258 kindreds suspected of being FPC and undergoing secondary screening for PDAC through the European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer (EUROPAC). Computerised tomography, endoscopic ultrasound of the pancreas and magnetic resonance imaging were used. The risk of being a carrier of a dominant mutation predisposing to pancreatic cancer was stratified into three even categories (low, medium and high) based on: Mendelian probability, the number of PDAC cases and the number of people at risk in a kindred. RESULTS: There was a median (interquartile range (IQR)) follow-up of 2 (0-5) years and a median (IQR) number of investigations per participant of 4 (2-6). One PDAC, two low-grade neuroendocrine tumours and 41 cystic lesions were identified, including 23 IPMN (22 branch-duct (BD)). The PDAC case occurred in the top 10% of risk, and the BD-IPMN cases were evenly distributed amongst risk categories: low (6/107), medium (10/107) and high (6/107) (P = 0.63). CONCLUSIONS: The risk of finding BD-IPMN was independent of genetic predisposition and so they should be managed according to guidelines for incidental finding of IPMN.

Spontaneous transitions of actin-bound tropomyosin toward blocked and closed states.

After muscle contraction, myosin cross-bridge heads detach from thin actin filaments during relaxation. Structural and kinetic data of cross-bridge-thin filament interactions have shown that tropomyosin's position on F-actin is biased toward the blocked or closed states when myosin detaches. It is not clear if structural linkages between tropomyosin and myosin cross-bridge heads, or tropomyosin and Ca2+-free troponin, drive the process or whether tropomyosin movement is energetically independent of myosin and troponin influence. Here we provide in silico data about tropomyosin dynamics on troponin/myosin-free F-actin indicating that tropomyosin moves from the open state toward blocked- or closed-state positions on actin. To follow transitions inherent to tropomyosin itself on F-actin, we performed MD simulations initiated from the blocked-, open-, and intermediate-state models and followed tropomyosin over the surface of F-actin in the absence of myosin and troponin. These MD simulations maintain tropomyosin in a cable-like conformation, including the tropomyosin overlap domain, while allowing tropomyosin to retain most of its motional freedom. Tropomyosin shows considerable azimuthal movement away from the open state toward the surrounds of a more energetically favorable blocked B-state position over F-actin. In contrast, little movement away from the B-state location is observed. Our results are consistent with previous predictions based on electrostatic interaction energy landscapes determined by rigid-body translocation of tropomyosin. They support the view that in the absence of myosin, i.e., when myosin cross-bridges detach from actin, the blocked- or closed-state positions of tropomyosin are energetically favored, while the open state is not.

Latent myopathy is more pronounced in patients with low flow versus normal flow aortic stenosis with normal left ventricular ejection fraction who are undergoing surgical aortic valve replacement: Multicenter study with a brief review of the literature.

BACKGROUND: Midwall fibrosis and low stroke volume are independent predictors of mortality in severe aortic stenosis (AS) with preserved LV ejection fraction (LVEF). The role of speckle tracking echocardiography (STE) to identify latent myopathy pre- and post- aortic valve replacement (AVR) in high risk AS patients with normal LVEF is limited. METHODS: Demographic, 2D echocardiographic, and STE data were analyzed in patients with severe AS and preserved LVEF who underwent tissue AVR. Velocity vector imaging (VVI) was used to assess regional and global peak systolic longitudinal strain (GLS). Low flow (LF) was defined as an indexed LV stroke volume <35 mL/m2 . RESULTS: Between December 2008 and May 2011, 37 patients (75 ± 9 years, 51% male) had both pre- and post-AVR echos within 6.6 ± 6.5 months (median = 4 months; range = 2.5-9.5) of surgery. Compared with pre-AVR, GLS (-6.9 ± 4.9% vs -11.1 ± 4.1%; P < .001) and strain rate (-0.72 ± 0.3s-1 vs -0.87 ± 0.3s-1 ; P = .01) improved post-AVR. Pre-AVR mid-segments showed a similar myopathy as the basal segments (-9.5 ± 4.3% vs -9.0 ± 4.2%;P = .3). The 16 (43%) LF patients in this study had lower pre- and post-AVR strain compared to NF patients (GLS Pre-AVR:LF vs NF: -5.1 ± 4.1% vs -8.4 ± 4.9% (P = .04) and GLS Post-AVR:LF vs NF: -9.2 ± 3.7% vs -12.5 ± 3.9% (P = .01)). However, there was no difference in absolute and %change improvement in GLS post-AVR (LF vs NF:∆ -4.2 ± 3.5% vs ∆-4.1 ± 5.3% (P = .90) and 193 ± 214% vs 143 ± 230% change (P = .5)). The lowest GLS was seen in LF/HG AS followed by LF/LG, NF/LG and NF/HG AS; P = .03. CONCLUSIONS: Latent myopathy is more pronounced in LF AS both pre- and post-AVR. Our study provides evidence of improvement in myopathy in LF AS despite a persistent worse myopathy compared to NF patients post-AVR.

Tropomyosin Must Interact Weakly with Actin to Effectively Regulate Thin Filament Function.

Elongated tropomyosin, associated with actin-subunits along the surface of thin filaments, makes electrostatic interactions with clusters of conserved residues, K326, K328, and R147, on actin. The association is weak, permitting low-energy cost regulatory movement of tropomyosin across the filament during muscle activation. Interestingly, acidic D292 on actin, also evolutionarily conserved, lies adjacent to the three-residue cluster of basic amino acids and thus may moderate the combined local positive charge, diminishing tropomyosin-actin interaction and facilitating regulatory-switching. Indeed, charge neutralization of D292 is connected to muscle hypotonia in individuals with D292V actin mutations and linked to congenital fiber-type disproportion. Here, the D292V mutation may predispose tropomyosin-actin positioning to a myosin-blocking state, aberrantly favoring muscle relaxation, thus mimicking the low-Ca2+ effect of troponin even in activated muscles. To test this hypothesis, interaction energetics and in vitro function of wild-type and D292V filaments were measured. Energy landscapes based on F-actin-tropomyosin models show the mutation localizes tropomyosin in a blocked-state position on actin defined by a deeper energy minimum, consistent with augmented steric-interference of actin-myosin binding. In addition, whereas myosin-dependent motility of troponin/tropomyosin-free D292V F-actin is normal, motility is dramatically inhibited after addition of tropomyosin to the mutant actin. Thus, D292V-induced blocked-state stabilization appears to disrupt the delicately poised energy balance governing thin filament regulation. Our results validate the premise that stereospecific but necessarily weak binding of tropomyosin to F-actin is required for effective thin filament function.

Important Clinical Rehabilitation Principles Unique to People with Non-traumatic Spinal Cord Dysfunction.

Background: Non-traumatic spinal cord dysfunction (SCDys) is caused by a large range of heterogeneous etiologies. Although most aspects of rehabilitation for traumatic spinal cord injury and SCDys are the same, people with SCDys have some unique rehabilitation issues. Purpose: This article presents an overview of important clinical rehabilitation principles unique to SCDys. Methods: Electronic literature search conducted (January 2017) using MEDLINE and Embase (1990-2016) databases for publications regarding SCDys. The focus of the literature search was on identifying publications that present suggestions regarding the clinical rehabilitation of SCDys. Results: The electronic search of MEDLINE and Embase identified no relevant publications, and the publications included were from the authors' libraries. A number of important clinical rehabilitation principles unique to people with SCDys were identified, including classification issues, general rehabilitation issues, etiology-specific issues, and a role for the rehabilitation physician as a diagnostic clinician. The classification issues were regarding the etiology of SCDys and the International Standards for Neurological Classification of Spinal Cord Injury. The general rehabilitation issues were predicting survival, improvement, and rehabilitation outcomes; admission to spinal rehabilitation units, including selection decision issues; participation in rehabilitation; and secondary health conditions. The etiology-specific issues were for SCDys due to spinal cord degeneration, tumors, and infections. Conclusions: Although there are special considerations regarding the rehabilitation of people with SCDys, such as the potential for progression of the underlying condition, functional improvement is typically significant with adequate planning of rehabilitation programs and special attention regarding the clinical condition of patients with SCDys.

Realistic and interactive high-resolution 4D environments for real-time surgeon and patient interaction.

BACKGROUND: Remote consultations that are realistic enough to be useful medically offer considerable clinical, logistical and cost benefits. Despite advances in virtual reality and vision hardware and software, these benefits are currently often unrealised. METHOD: The proposed approach combines high spatial and temporal resolution 3D and 2D machine vision with virtual reality techniques, in order to develop new environments and instruments that will enable realistic remote consultations and the generation of new types of useful clinical data. RESULTS: New types of clinical data have been generated for skin analysis and respiration measurement; and the combination of 3D with 2D data was found to offer potential for the generation of realistic virtual consultations. CONCLUSION: An innovative combination of high resolution machine vision data and virtual reality online methods, promises to provide advanced functionality and significant medical benefits, particularly in regions where populations are dispersed or access to clinicians is limited. Copyright © 2016 John Wiley & Sons, Ltd.

Disposable, Paper-Based, Inkjet-Printed Humidity and H2S Gas Sensor for Passive Sensing Applications.

An inkjet-printed, fully passive sensor capable of either humidity or gas sensing is presented herein. The sensor is composed of an interdigitated electrode, a customized printable gas sensitive ink and a specialized dipole antenna for wireless sensing. The interdigitated electrode printed on a paper substrate provides the base conductivity that varies during the sensing process. Aided by the porous nature of the substrate, a change in relative humidity from 18% to 88% decreases the electrode resistance from a few Mega-ohms to the kilo-ohm range. For gas sensing, an additional copper acetate-based customized ink is printed on top of the electrode, which, upon reaction with hydrogen sulphide gas (H2S) changes, both the optical and the electrical properties of the electrode. A fast response time of 3 min is achieved at room temperature for a H2S concentration of 10 ppm at a relative humidity (RH) of 45%. The passive wireless sensing is enabled through an antenna in which the inner loop takes care of conductivity changes in the 4-5 GHz band, whereas the outer-dipole arm is used for chipless identification in the 2-3 GHz band.

Knowledge Regarding Basic Facts of Stroke Among Final Year MBBS Students and House Officers: A Cross-Sectional Survey of 708 Respondents from Pakistan.

INTRODUCTION: Stroke is the leading cause of neurological disability in the world. In Pakistan, house officers (HOs) are usually the first contact for a stroke patient in the emergency department. Sometimes they need to make quick decisions regarding diagnosis and management without specialist supervision. Thousands of current final year MBBS (Bachelor of Medicine, Bachelor of Surgery) students will be performing the duties of HOs soon. This study documents the knowledge and confidence levels of final year students and HOs in Pakistan regarding basic facts related to initial diagnosis and management of stroke. MATERIALS AND METHODS: A questionnaire was developed using two standard textbooks of medicine and current stroke guidelines of the American Heart Association. The pre-tested self-administered questionnaire was distributed among 800 final year MBBS students and HOs in 14 medical colleges and hospitals in four different cities. The response rate was 88.5%. Data analysis was done using SPSS V.21. The CMH Lahore Medical College Ethics Review Committee approved this project. RESULTS: Respondents included medical students (n=496) and HOs (N= 212); most were female (n = 452, 63.9%). Of these, 31.4% had managed or assisted in the management of a patient with a stroke and had a higher confidence level in its diagnosis (p< 0.001) and management (p <0.001). Having a family member with stroke was associated with higher confidence in the diagnosis of stroke (p < 0.05) but not with confidence in its management (p = 0.41). Most correctly defined stroke (60.6%), identified the CT scan as the initial diagnostic modality (88.1%), knew the dosage of aspirin (64.9%), knew the time limit for thrombolysis (67.4%), and were familiar with the risk of deep vein thrombosis in immobilized stroke patients (85.4%). Less than half (44.5%) chose tissue plasminogen activator (t-PA) as the preferred initial intervention for acute ischemic stroke. CONCLUSION: This multicenter survey shows that the knowledge and confidence of medical students and HOs in Pakistan regarding initial diagnosis and management of stroke are inadequate in most domains. There is a need to improve the medical training for stroke in emergency departments for optimal outcomes. Public education campaigns about stroke should be conducted to increase the general awareness of the population about the prevention, signs, symptoms, and emergency steps to be taken when encountering a case of stroke.

Guidelines for the Use of Echocardiography in the Evaluation of a Cardiac Source of Embolism.

Embolism from the heart or the thoracic aorta often leads to clinically significant morbidity and mortality due to transient ischemic attack, stroke or occlusion of peripheral arteries. Transthoracic and transesophageal echocardiography are the key diagnostic modalities for evaluation, diagnosis, and management of stroke, systemic and pulmonary embolism. This document provides comprehensive American Society of Echocardiography guidelines on the use of echocardiography for evaluation of cardiac sources of embolism. It describes general mechanisms of stroke and systemic embolism; the specific role of cardiac and aortic sources in stroke, and systemic and pulmonary embolism; the role of echocardiography in evaluation, diagnosis, and management of cardiac and aortic sources of emboli including the incremental value of contrast and 3D echocardiography; and a brief description of alternative imaging techniques and their role in the evaluation of cardiac sources of emboli. Specific guidelines are provided for each category of embolic sources including the left atrium and left atrial appendage, left ventricle, heart valves, cardiac tumors, and thoracic aorta. In addition, there are recommendation regarding pulmonary embolism, and embolism related to cardiovascular surgery and percutaneous procedures. The guidelines also include a dedicated section on cardiac sources of embolism in pediatric populations.

Vascular geometry of the extracranial carotid arteries: an analysis of length, diameter, and tortuosity.

BACKGROUND: Stable access is essential for successful intracranial interventions. Quantifying variations in extracranial carotid arteries may help in the selection and development of access catheters. This study describes the vascular dimensions from the aortic arch to the skull base. METHODS: CT angiography analysis was performed on 100 patients. The lengths, diameters, and tortuosity of the common carotid artery (CCA) and internal carotid artery (ICA) were measured from the aortic arch to the skull base. RESULTS: The mean±SD length of the carotid artery from the aortic arch to the skull base was 22.2±2.2 cm for the right side and 20.8±1.9 cm for the left side (p<0.0001). The length of the right CCA was 13.6±1.2 cm and the length of the left CCA was 12.4±1.4 cm (p<0.0001). The length of the right ICA was 8.6±1.4 cm compared with 8.4±1.4 cm for the left ICA (p=0.3). The ICA length in men and women was 8.9±1.3 cm and 8.2±1.3 cm, respectively (p=0.0001), and the CCA length in men and women was 13.6±1.5 cm and 12.3±1.6 cm, respectively (p<0.0001). The lengths of the CCA and ICA in patients aged ≥60 years were 13.3±1.7 cm and 8.9±1.5 cm, respectively compared with 12.8±1.7 cm and 8.2±1.1 cm, respectively, for patients aged <60 years (p=0.04 for CCA, p=0.0002 for ICA). Tortuosity of the CCA and ICA was 1.2±0.2 and 1.3±0.1, respectively, in patients aged ≥60 years compared with 1.1±0.1 for both the ICA and CCA in patients aged <60 years (p<0.0001 for both). There was a consistent ratio of CCA/ICA length of 1.6±0.3 on the right and 1.5±0.3 on the left (p<0.0001). The arterial diameters did not show any significant difference. CONCLUSIONS: The distance from the aortic arch to the skull base is longer on the right than on the left side. Both the CCA and ICA are longer in men and in patients aged ≥60 years. The tortuosity of both segments significantly increases with age.

Design, synthesis, and delivery studies of organotin(IV) based HCV inhibitor.

Tributylstannic[3-(3,5 -dimethylphenylamido)propionate] is synthesized and characterized by elemental analysis, FT-IR, multinuclear NMR ((1)H, (13)C and (119)Sn) and mass spectrometry. The organic anion was found to act as monodentate O-bound ligand in solution. The compound was screened for the anti-HCV potency by the Gaussia luciferase Assay using infected Huh 7.5 cells (human hepatocellular cell) and is found active against HCV with logIC50 1.2nM in the cell-based assay. Cationic surfactant cetyl N,N,N-trimethylammoniumbromide (CTAB) was used to study the interactions of the organotin(IV) complex with positively charged micelles of the surfactant acting as a model cell membrane. The thermodynamics parameters of complex- CTAB interaction concluded that the complex is located in the palisade layer of CTAB micelles. The increase in absorbance of visible spectra of the compound confirmed its solubilization into micelles. The two carbonyl oxygen's were found to be binding sites of the complex with CTAB.