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Shankar Prasad Nagaraju, Srinivas Vinayak Shenoy, Indu Ramachandra Rao, Mohan V Bhojaraja, Dharshan Rangaswamy, Ravindra Attur Prabhu Department of Nephrology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Udupi, Karnataka, 576104, IndiaCorrespondence: Mohan V Bhojaraja, Email mohan.vb@manipal.eduAbstract: Chronic kidney disease (CKD) is extremely common all over the world and is strongly linked to cardiovascular disease (CVD). The great majority of CKD patients have hypertension, which raises the risk of cardiovascular disease (CVD), end-stage kidney disease, and mortality. Controlling hypertension in patients with CKD is critical in our clinical practice since it slows the course of the disease and lowers the risk of CVD. As a result, accurate blood pressure (BP) monitoring is crucial for CKD diagnosis and therapy. Three important guidelines on BP thresholds and targets for antihypertensive medication therapy have been published in the recent decade emphasizing the way we measure BP. For both office BP and out-of-office BP measuring techniques, their clinical importance in the management of hypertension has been well defined. Although BP measurement is widely disseminated and routinely performed in most clinical settings, it remains unstandardized, and practitioners frequently fail to follow the basic recommendations to avoid measurement errors. This may lead to misdiagnosis and wrong management of hypertension, especially in CKD patients. Here, we review presently available all BP measuring techniques and their use in clinical practice and the recommendations from various guidelines and research gaps emphasizing CKD patients.Keywords: ambulatory BP, office BP, chronic kidney disease, out-of-office BP, standardized BP

Shankar Prasad Nagaraju,1 Mohan V Bhojaraja,1 Ganesh Paramasivam,2 Ravindra Attur Prabhu,1 Dharshan Rangaswamy,1 Indu Ramachandra Rao,1 Srinivas Vinayak Shenoy1 1Department of Nephrology, Kasturba Medical College, Manipal, Manipal Academy Higher Education, Manipal, Karnataka, 576104, India; 2Department of Cardiology, Kasturba Medical College, Manipal, Manipal Academy Higher Education, Manipal, Karnataka, 576104, IndiaCorrespondence: Mohan V Bhojaraja Email mohan.vb@manipal.eduIntroduction: Pulmonary hypertension (PH) is an underestimated cardiovascular consequence and a mortality predictor in patients on hemodialysis (HD). Thus, we studied its prevalence, risk factors, association with inflammation/oxidative stress, and cardiac changes in HD patients.Methods: This was a single-center cross-sectional observational study conducted at a tertiary care hospital. Patients aged > 18 years on hemodialysis for at least three months were included and divided into those with and without PH; patients with secondary causes for PH were excluded. Clinical characteristics, HD-related factors, lab parameters (C-reactive protein and malondialdehyde with thiol assay were used as markers of inflammation and oxidative stress, respectively), and echocardiography details were compared. PH was defined as a mean pulmonary artery pressure of > 25 mmHg at rest, and it was further divided as mild (25– 40 mmHg), moderate (40– 60 mmHg), and severe (> 60 mmHg).Results: Of 52 patients, 28 patients had PH (mild 24, moderate 4, and none had severe PH) with prevalence of 54%. No difference was found in clinical characteristics, dialysis-related factors, biochemical parameters including inflammation (C-reactive protein; p=0.76), or oxidative stress (thiol; p=0.36 and MDA; p=0.46) between the groups. When compared to individuals without PH, HD patients with PH exhibited significantly more mitral regurgitation (p=0.002).Conclusion: Hemodialysis patients have a high prevalence of PH. PH was significantly associated with the presence of mitral regurgitation on echocardiography. Our study did not find differences in traditional risk factors, HD-related factors, and inflammation/oxidative markers between the groups with and without PH.Keywords: chronic kidney disease, hemodialysis, inflammation, oxidative stress, pulmonary hypertension

Ravindra Attur Prabhu,1 Srinivas V Shenoy,1 Shankar Prasad Nagaraju,1 Dharshan Rangaswamy,1 Indu Ramachandra Rao,1 Mohan V Bhojaraja,1 Deepak Nayak M,2 Sindhura Lakshmi Koulmane Laxminarayana,2 Karan Saraf,1,3 Ashok Ramaswamy1,4 1Department of Nephrology, Kasturba Medical College Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India; 2Department of Pathology, Kasturba Medical College Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India; 3Department of Nephrology, Excelcare Hospitals, Guwahati, Assam, India; 4Department of Nephrology, Saveetha Medical College, Chennai, Tamil Nadu, IndiaCorrespondence: Srinivas V ShenoyDepartment of Nephrology, Kasturba Medical College Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, IndiaTel +91 9844374705Email shenoy.srinivas@manipal.eduPurpose: Diabetic kidney disease (DKD) represents a unique subset of patients with chronic kidney disease (CKD). Acute kidney injury (AKI) is implicated in DKD progression; however, their interplay is not studied well. We studied risk factors for AKI and the effect of AKI on disease progression in a homogeneous group of patients with DKD.Patients and Methods: We conducted a retrospective open cohort study of patients with DKD at a single tertiary care centre between August 2016 – August 2019. Patients with a minimum follow-up of 2 years were included in the study. The incidence, etiology and risk factors for AKI were studied. The primary outcome studied was the effect of AKI on reduction in estimated glomerular filtration rate (eGFR) in DKD. Loss in eGFR by 50% and need for renal replacement therapy or reaching CKD stage V were studied as secondary outcomes.Results: Two hundred and ninety-two DKD patients meeting the study criteria with a follow-up of 29.57 (± 4.3) months were included. The incidence of AKI was 31.1%. Sepsis was the most common etiology (61%). Proteinuria was an independent risk factor for AKI after adjusting for covariates (adjusted OR - 1.158; 95% CI (1.018– 1.316); p=0.025). In patients with AKI, median decline in eGFR was 10.29 mL/min/1.73m2/year (IQR-5.58– 13.84) which was significantly higher compared to patients with no AKI [eGFR 7.25 (IQR 5.06– 11.38); p-0.014]. On subgroup analysis, sepsis-induced AKI (versus non-sepsis AKI; p< 0.001) and higher AKI stage (stage 2/3 versus stage 1; p=0.019) were associated with a faster decline in eGFR.Conclusion: AKI is common in patients with DKD with sepsis being the most common etiology. AKI in diabetic kidney disease is associated with a faster decline in eGFR. Baseline proteinuria is an independent risk factor for AKI.Keywords: diabetic kidney disease, acute kidney injury, GFR decline, proteinuria, sepsis

Abstract Phonon antibunching, a phenomenon arising from the quantum statistics of mechanical vibrations, has attracted significant attention due to its potential applications in quantum information processing, sensing, and energy harvesting. Here, we present a comprehensive investigation of phonon antibunching in a system consisting of three weakly nonlinear coupled nanomechanical resonators. We analytically derive and study the antibunching behavior of phonons in the proposed system and bring insight into the underlying mechanisms. The optimal phonon blockade results from destructive quantum interference due to distinct two-phonon excitation pathways. Due to this quantum interference, these unconventional phonon blockade systems can achieve antibunched statistics even in weakly nonlinear regimes, in contrast to conventional phonon blockade systems that require strong nonlinearity. We show that with the inclusion of an additional resonator, there are multiple additional two-phonon excitation pathways compared to two resonator cases, which results in stronger phonon antibunching and supports single phonon for longer duration. These findings are interesting for practical phononics using coupled-resonator systems.

Abstract An extraordinary resolution down to 50 microns is demonstrated for the first time for bulk ultrasonics, using novel micro-fabricated metamaterial lenses. The development and performance of the silicon-based Fabry–Perot type metalenses with an array of 10 micrometre square holes are discussed. Challenges in wave reception are addressed by a custom-developed micro-focal laser with a sub-micron spot size and an innovative experimental set-up together with physics based signal processing. The results provide a pathway for material diagnostics at greater depths with high resolution using micro-metalens-enhanced ultrasound as an alternative to expensive and radiation prone electromagnetic techniques.

Alveolar macrophages (AMs) are a fully differentiated lung-resident immune cell population and are a critical component of lung immunity. AMs can be easily isolated from mice via bronchoalveolar lavage fluid (BALF) collection. The quality and quantity of AMs in BALF isolation are critical for generating reliable and high-quality data for ex vivo studies. Traditional techniques use ice-cold (4°C) buffer to collect AMs in BALF and result in low yield. Hence, a new method that consistently gives a higher yield of AMs is needed. We demonstrate here an optimized method that significantly increases the quantity of AM recovery in BALF (>2.8 times than the traditional method). Our method uses a warm-buffer (37°C) containing EDTA. We compared the viability and functional parameters (cytokine/chemokine expression, phagocytosis) of AMs isolated by our new and traditional methods. Our study revealed that AMs collected using our method have similar viability and functional characteristics to those collected using traditional method. Hence, our new method can be used for the collection of a higher number of AMs without altering their function. This protocol might also be useful for isolating tissue-resident immune cells from other anatomical sites for ex vivo and other downstream applications.

Breast cancer (BC) is the leading cause of female cancer mortality and is a type of cancer that is a major threat to women's health. Deep learning methods have been used extensively in many medical domains recently, especially in detection and classification applications. Studying histological images for the automatic diagnosis of BC is important for patients and their prognosis. Owing to the complication and variety of histology images, manual examination can be difficult and susceptible to errors and thus needs the services of experienced pathologists. Therefore, publicly accessible datasets called BreakHis and invasive ductal carcinoma (IDC) are used in this study to analyze histopathological images of BC. Next, using super-resolution generative adversarial networks (SRGANs), which create high-resolution images from low-quality images, the gathered images from BreakHis and IDC are pre-processed to provide useful results in the prediction stage. The components of conventional generative adversarial network (GAN) loss functions and effective sub-pixel nets were combined to create the concept of SRGAN. Next, the high-quality images are sent to the data augmentation stage, where new data points are created by making small adjustments to the dataset using rotation, random cropping, mirroring, and color-shifting. Next, patch-based feature extraction using Inception V3 and Resnet-50 (PFE-INC-RES) is employed to extract the features from the augmentation. After the features have been extracted, the next step involves processing them and applying transductive long short-term memory (TLSTM) to improve classification accuracy by decreasing the number of false positives. The results of suggested PFE-INC-RES is evaluated using existing methods on the BreakHis dataset, with respect to accuracy (99.84%), specificity (99.71%), sensitivity (99.78%), and F1-score (99.80%), while the suggested PFE-INC-RES performed better in the IDC dataset based on F1-score (99.08%), accuracy (99.79%), specificity (98.97%), and sensitivity (99.17%).

Abstract Obesity has been associated with increased risk of adult asthma, however, not all studies have found a clear association between overweight and the incidence of asthma, and data on other adiposity measures have been limited. Hence, we aimed to summarize evidence on association between adiposity and adult asthma. Relevant studies were retrieved through searches conducted in PubMed, and EMBASE up to March 2021. A total of sixteen studies (63,952 cases and 1,161,169 participants) were included in the quantitative synthesis. The summary RR was 1.32 (95% CI 1.21–1.44, I2 = 94.6%, pheterogeneity

Abstract Tau is an intrinsically disordered neuronal protein in the central nervous system. Aggregated Tau is the main component of neurofibrillary tangles observed in Alzheimer’s disease. In vitro, Tau aggregation can be triggered by polyanionic co-factors, like RNA or heparin. At different concentration ratios, the same polyanions can induce Tau condensates via liquid–liquid phase separation (LLPS), which over time develop pathological aggregation seeding potential. Data obtained by time resolved Dynamic Light Scattering experiments (trDLS), light and electron microscopy show that intermolecular electrostatic interactions between Tau and the negatively charged drug suramin induce Tau condensation and compete with the interactions driving and stabilizing the formation of Tau:heparin and Tau:RNA coacervates, thus, reducing their potential to induce cellular Tau aggregation. Tau:suramin condensates do not seed Tau aggregation in a HEK cell model for Tau aggregation, even after extended incubation. These observations indicate that electrostatically driven Tau condensation can occur without pathological aggregation when initiated by small anionic molecules. Our results provide a novel avenue for therapeutic intervention of aberrant Tau phase separation, utilizing small anionic compounds.

Highlights A novel computational approach was adopted for the development of a vaccine model against lymphatic filariasis. The potential epitopes were screened to test their antigenicity, toxicity, immunogenicity, and allergenicity. The prophylactic vaccine model was constructed with appropriate peptide linkers and the adjuvant—50 s ribosomal protein L7/L12. The tertiary structure of the vaccine model was validated with Ramachandran plot, ProSA, etc. Molecular docking against TLR4 receptor and immune simulation studies were performed to test the efficacy of the vaccine.

Abstract Over the past decade, targeted therapy for oncogene-driven NSCLC and immune checkpoint inhibitors for non-oncogene-driven NSCLC, respectively, have greatly improved the survival and quality of life for patients with unresectable NSCLC. Increasingly, these biomarker-guided systemic therapies given before or after surgery have been used in patients with early-stage NSCLC. In March 2022, the US FDA granted the approval of neoadjuvant nivolumab and chemotherapy for patients with stage IB-IIIA NSCLC. Several phase II/III trials are evaluating the clinical efficacy of various neoadjuvant immune checkpoint inhibitor combinations for non-oncogene-driven NSCLC and neoadjuvant molecular targeted therapies for oncogene-driven NSCLC, respectively. However, clinical application of precision neoadjuvant treatment requires a paradigm shift in the biomarker testing and multidisciplinary collaboration at the diagnosis of early-stage NSCLC. In this comprehensive review, we summarize the current diagnosis and treatment landscape, recent advances, new challenges in biomarker testing and endpoint selections, practical considerations for a timely multidisciplinary collaboration at diagnosis, and perspectives in emerging neoadjuvant precision systemic therapy for patients with resectable, early-stage NSCLC. These biomarker-guided neoadjuvant therapies hold the promise to improve surgical and pathological outcomes, reduce systemic recurrences, guide postoperative therapy, and improve cure rates in patients with resectable NSCLC.

Abstract Hyperlenses for ultrasonic imaging in nondestructive evaluation and non-invasive diagnostics have not been widely discussed, likely due to the lack of understanding on their performance, as well as challenges with reception of the elastic wavefield past fine features. This paper discusses the development and application of a cylindrical hyperlens that can magnify subwavelength features and achieve super-resolution in the far-field. A radially symmetric structure composed of alternating metal and water layers is used to demonstrate the hyperlens. Numerical simulations are used to study the performance of cylindrical hyperlenses with regard to their geometrical parameters in imaging defects separated by a subwavelength distance, gaining insight into their construction for the ultrasonic domain. An elegant extension of the concept of cylindrical hyperlens to flat face hyperlens is also discussed, paving the way for a wider practical implementation of the technique. The paper also presents a novel waveguide-based reception technique that uses a conventional ultrasonic transducer as receiver to capture waves exiting from each fin of the hyperlens discretely. A metallic hyperlens is then custom-fabricated, and used to demonstrate for the first time, a super-resolved image with 5X magnification in the ultrasonic domain. The proposed hyperlens and the reception technique are among the first demonstrations in the ultrasonic domain, and well-suited for practical inspections. The results have important implications for higher resolution ultrasonic imaging in industrial and biomedical applications.

Introduction: Idiopathic adhesive capsulitis is characterised by gradual onset of pain in shoulder and its limited mobility of motion due to a thickened capsule with an unknown cause. The peak incidence rate is between the ages of 40 and 60 years with less chances of occurrence in the younger group and individuals, who engage in physical labour are far less likely to experience it. In order to determine whether the kinetic chain approach is more effective, researchers tested it on individuals with adhesive capsulitis. Aim: To assess effectiveness of the kinetic chain approach for treating primary adhesive capsulitis. Materials and Methods: This pre and postexperimental study was conducted at the Department of Physiotherapy, Santosh Medical College and Hospital, Ghaziabad, Uttar Pradesh, India, for a period of one year from January 2020 to December 2020. A total of 60 patients with primary adhesive capsulitis were included in the trial and were divided into Group-A and Group-B using a systematic random sampling process. Group A received traditional physiotherapy in addition to the Kinetic chain technique. In Group B, regular physiotherapy was the only treatment provided to patients. The Range of Motion (ROM), Visual Analog Scale (VAS) and the Shoulder Pain and Disability Index (SPADI) were measured in both groups pre, mid and post-treatment groups. Non parametric statistical techniques were used to analyse the data owing its originality. Results: A total of 30 patients in each Group (A and B) were provided with Kinetic chain approach (mean age=53.93 years) and conventional physiotherapy (mean age=55.40 years), respectively. For comparing data within the same group, Wilcoxon signed-ranks test was used for this. Mann Whitney U-test was used to compare the data between groups. The p-values for the VAS, SPADI, and ROM showed statistical significance at the 0.001 level. In terms of pain, functional impairment, and range of motion, with Group A showing greater strides than Group B. Conclusion: The combination of kinetic chain technique and traditional physiotherapy was more beneficial than either group when used singularly to reduce discomfort, increase the range of motion, and enhance functional capacity in adhesive capsulitis patients.

Introduction: Adhesive Capsulitis of Shoulder (ACS) is a common self-limiting disorder characterised by painful, progressive loss of active and passive shoulder motion due to fibrosis and rigidity of the joint capsule. ACS occurs in 2-5% of the population overall and up to 20% of those with diabetes. Women between the ages of 40 and 60 are at increased risk, and one in four patients may have bilateral illness. Several studies have been done to prove the effectiveness of electro-therapeutic modalities and manual mobilisation techniques on Adhesive Capsulitis, but very few studies have been done to find out and compare the effectiveness of Niel-Asher technique and Positional Release Technique (PRT) on adhesive capsulitis. Aim: To compare effect of Niel-Asher technique and positional release technique on pain, active Range of Motion (ROM) and functional disability in patients with adhesive capsulitis Materials and Methods: This was a pre and post-experimental design conducted at Santosh Medical College and Hospital, Ghaziabad, India, for a duration of two years conducted on 110 patients with a diagnosis of stage II primary adhesive capsulitis. The patients were divided into group A and group B using a systematic random sampling procedure. Conventional physiotherapy and the Niel-Asher technique were used on patients in group A. Patients in group B received conventional physiotherapy and Positional Release Technique. The therapy was given to patients, three times weekly for a total of six weeks. The Shoulder Pain and Disability Index (SPADI), Range of Motion (ROM) and Visual Analogue Scale (VAS) were measured in both groups in pre, mid and post-therapy. The analysis of the collected data was done by Statistical Package for Social Sciences (SPSS) software version 17.0. Results: A total of 110 patients with adhesive capsulitis patients, 55 in each group A (mean age: 51.78±7.810 years) and group B (mean age: 52.33±7.794 years) were included in the study and the mean age of total study subjects was 52.05±7.80 years. On analysis of the collected data, statistically significant outcomes across all three measures (VAS, SPADI, and ROM) were observed with a p-value of less than 0.001. In pain, functional impairment and restricted ROM, group A, outperformed group B in this comparison. Conclusion: Both conventional physiotherapy along with Niel-Asher technique group and conventional physiotherapy along with PRT group were individually effective in relieving pain and improving Range of Motion and Functional ability in patients with Adhesive capsulitis, but among these two groups, the group that received Niel-Asher technique in addition to conventional physiotherapy reported more significant improvements when compared to PRT group, in pain, range of motion and functional ability.

This paper discusses designing and implementing an adaptive thrust distribution algorithm on the already robust control system for serial split-hull underwater vehicles to maximise operational efficiency. Split-hull underwater vehicles are gaining popularity in subsea operations due to their flexible hyper-redundant design and enhanced manoeuvrability. These features facilitate them to replace conventional solutions, including torpedo-shaped Autonomous Underwater Vehicles (AUVs) and Remotely Operated Vehicles (ROVs). The field of research is currently undergoing a considerable transition toward operations on subsea activities that are more economical and efficient. Thus, implementing a robust and energy-efficient control system is of utmost importance. The robust Super Twisting Algorithm (STA) based control system is used on the vehicle, and an adaptive thrust distribution algorithm is proposed and implemented to optimise the energy efficiency further. The work involves modelling the vehicle, fluid forces, torque effects, and thruster configuration matrix and implementing the adaptive weight distribution on the STA-based control system. With the help of simulations, the improvements in the control system are proved.

Abstract Background Granulomatosis with polyangiitis (GPA) previously known as Wegener's granulomatosis is a rare complex immune-mediated disease and a multisystem disorder with varying presentations where many of the imaging features of GPA overlap with those of other diseases, and hence its diagnosis can be challenging. Case presentation Here we report a case of a 48-year-old female who presented with complaints of hemoptysis, difficulty in speech, bilateral progressive hearing loss and, a palpable lump in the right breast. The case was initially misdiagnosed as breast carcinoma but biopsy proved to be GPA. Here we present the multisystem manifestations of GPA involving the head and neck, breast, lungs, spleen with involvement of the breast being very rare. The breast lesion showed improvement with steroids on follow-up. Conclusions GPA is a multisystem disease and though breast lesions in GPA are rare, a thorough knowledge about this uncommon manifestation is required and clinical, radiological, and histopathological correlation is of utmost importance in the evaluation of a breast lesion in cases of multisystem involvement to avoid unnecessary surgeries. The differential diagnosis of breast tumors should include such rare conditions that can sometimes mimic breast cancer. Early diagnosis and initiation of the immunosuppressive treatment help in a better prognosis of the disease.

Abstract Background The prevalence of antimicrobial resistance (AMR) among Gram-negative bacteria is alarmingly high. Reintroduction of colistin as last resort treatment in the infections caused by drug-resistant Gram-negative bacteria has led to the emergence and spread of colistin resistance. This study was designed to determine the prevalence of drug-resistance among beta-lactamase-producing strains of Escherichia coli and Klebsiella pneumoniae, isolated from the clinical specimens received at a tertiary care centre of Kathmandu, Nepal during the period of March to August, 2019. Methods A total of 3216 different clinical samples were processed in the Microbiology laboratory of Kathmandu Model Hospital. Gram-negative isolates (E. coli and K. pneumoniae) were processed for antimicrobial susceptibility test (AST) by using modified Kirby-Bauer disc diffusion method. Drug-resistant isolates were further screened for extended-spectrum beta-lactamase (ESBL), metallo-beta-lactamase (MBL), carbapenemase and K. pneumoniae carbapenemase (KPC) production tests. All the suspected enzyme producers were processed for phenotypic confirmatory tests. Colistin resistance was determined by minimum inhibitory concentration (MIC) using agar dilution method. Colistin resistant strains were further screened for plasmid-mediated mcr-1 gene using conventional polymerase chain reaction (PCR). Results Among the total samples processed, 16.4% (529/3216) samples had bacterial growth. A total of 583 bacterial isolates were recovered from 529 clinical samples. Among the total isolates, 78.0% (455/583) isolates were Gram-negative bacteria. The most predominant isolate among Gram-negatives was E. coli (66.4%; 302/455) and K. pneumoniae isolates were 9% (41/455). In AST, colistin, polymyxin B and tigecycline were the most effective antibiotics. The overall prevalence of multidrug-resistance (MDR) among both of the isolates was 58.0% (199/343). In the ESBL testing, 41.1% (n = 141) isolates were confirmed as ESBL-producers. The prevalence of ESBL-producing E. coli was 43% (130/302) whereas that of K. pneumoniae was 26.8% (11/41). Similarly, 12.5% (43/343) of the total isolates, 10.9% (33/302) of E. coli and 24.3% of (10/41) K. pneumoniae were resistant to carbapenem. Among 43 carbapenem resistant isolates, 30.2% (13/43) and 60.5% (26/43) were KPC and MBL-producers respectively. KPC-producers isolates of E. coli and K. pneumoniae were 33.3% (11/33) and 20% (2/10) respectively. Similarly, 63.6% (21/33) of the E. coli and 50% (5/10) of the K. pneumoniae were MBL-producers. In MIC assay, 2.2% (4/179) of E. coli and 10% (2/20) of K. pneumoniae isolates were confirmed as colistin resistant (MIC ≥ 4 µg/ml). Overall, the prevalence of colistin resistance was 3.1% (6/199) and acquisition of mcr-1 was 16.6% (3/18) among the E. coli isolates. Conclusion High prevalence of drug-resistance in our study is indicative of a deteriorating situation of AMR. Moreover, significant prevalence of resistant enzymes in our study reinforces their roles in the emergence of drug resistance. Resistance to last resort drug (colistin) and the isolation of mcr-1 indicate further urgency in infection management. Therefore, extensive surveillance, formulation and implementation of effective policies, augmentation of diagnostic facilities and incorporation of antibiotic stewardship programs can be some remedies to cope with this global crisis.

Abstract Ciclopirox (CPX) is an FDA-approved topical antifungal agent that has demonstrated preclinical anticancer activity in a number of solid and hematologic malignancies. Its clinical utility as an oral anticancer agent, however, is limited by poor oral bioavailability and gastrointestinal toxicity. Fosciclopirox, the phosphoryloxymethyl ester of CPX (Ciclopirox Prodrug, CPX-POM), selectively delivers the active metabolite, CPX, to the entire urinary tract following parenteral administration. We characterized the activity of CPX-POM and its major metabolites in in vitro and in vivo preclinical models of high-grade urothelial cancer. CPX inhibited cell proliferation, clonogenicity and spheroid formation, and increased cell cycle arrest at S and G0/G1 phases. Mechanistically, CPX suppressed activation of Notch signaling. Molecular modeling and cellular thermal shift assays demonstrated CPX binding to γ-secretase complex proteins Presenilin 1 and Nicastrin, which are essential for Notch activation. To establish in vivo preclinical proof of principle, we tested fosciclopirox in the validated N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) mouse bladder cancer model. Once-daily intraperitoneal administration of CPX-POM for four weeks at doses of 235 mg/kg and 470 mg/kg significantly decreased bladder weight, a surrogate for tumor volume, and resulted in a migration to lower stage tumors in CPX-POM treated animals. This was coupled with a reduction in the proliferation index. Additionally, there was a reduction in Presenilin 1 and Hes-1 expression in the bladder tissues of CPX-POM treated animals. Following the completion of the first-in-human Phase 1 trial (NCT03348514), the pharmacologic activity of fosciclopirox is currently being characterized in a Phase 1 expansion cohort study of muscle-invasive bladder cancer patients scheduled for cystectomy (NCT04608045) as well as a Phase 2 trial of newly diagnosed and recurrent urothelial cancer patients scheduled for transurethral resection of bladder tumors (NCT04525131).

Abstract Osteosarcoma (OS) is the most common primary bone tumor that primarily affects children and adolescents. Studies suggested that dysregulation JAK/STAT signaling promotes the development of OS. Cells treated with pimozide, a STAT5 inhibitor suppressed proliferation and colony formation and induced sub G0/G1 cell cycle arrest and apoptosis. There was a reduction in cyclin D1 and CDK2 expression and Rb phosphorylation, and activation of Caspase-3 and PARP cleavage. In addition, pimozide suppressed the formation of 3-dimensional osteospheres and growth of the cells in the Tumor in a Dish lung organoid system. Furthermore, there was a reduction in expression of cancer stem cell marker proteins DCLK1, CD44, CD133, Oct-4, and ABCG2. More importantly, it was the short form of DCLK1 that was upregulated in osteospheres, which was suppressed in response to pimozide. We further confirmed by flow cytometry a reduction in DCLK1+ cells. Moreover, pimozide inhibits the phosphorylation of STAT5, STAT3, and ERK in OS cells. Molecular docking studies suggest that pimozide interacts with STAT5A and STAT5B with binding energies of −8.4 and −6.4 Kcal/mol, respectively. Binding was confirmed by cellular thermal shift assay. To further understand the role of STAT5, we knocked down the two isoforms using specific siRNAs. While knockdown of the proteins did not affect the cells, knockdown of STAT5B reduced pimozide-induced necrosis and further enhanced late apoptosis. To determine the effect of pimozide on tumor growth in vivo, we administered pimozide intraperitoneally at a dose of 10 mg/kg BW every day for 21 days in mice carrying KHOS/NP tumor xenografts. Pimozide treatment significantly suppressed xenograft growth. Western blot and immunohistochemistry analyses also demonstrated significant inhibition of stem cell marker proteins. Together, these data suggest that pimozide treatment suppresses OS growth by targeting both proliferating cells and stem cells at least in part by inhibiting the STAT5 signaling pathway.

Abstract Background Various abdominal vessels can compress the adjacent structures or in turn can get compressed by them. Most of these compression syndromes present with non-specific symptoms. Unlike the common causes of acute abdomen, the various vascular compression syndromes have bizarre clinical presentations and subtle imaging findings, which can easily be missed by the physicians as well as the radiologists. Main body of the abstract This is a retrospective study which was done for a period of 3 years from April 2015 to April 2018 using a 64-slice CT scanner. Among 2412 cases that came for evaluation, 114 patients were diagnosed to have one of the various vascular compression syndromes. These 114 cases were further managed either conservatively or surgically depending on the pathology and the severity of the compression. The syndromes discussed in this article include median arcuate ligament syndrome (29 cases), superior mesenteric artery syndrome (23 cases), portal biliopathy (3 cases), nutcracker syndrome (6 cases), pelvi-ureteric junction obstruction due to crossing of vessels (8 cases), and retrocaval ureter and May-Thurner syndrome (45 cases). Conclusions The primary goal of this article is to reinforce the knowledge of the radiologists of the various vascular compression syndromes and to make them possess a high degree of vigilance to detect them. This article elaborates the imaging findings of these syndromes and the role of multidetector CT angiography in diagnosing them.

Abstract The focusing of ultrasound using topographic lenses, typically made of plates with step changes that cause an interaction between forward- and backward-propagating guided waves, has been widely studied in recent years. However, such ‘step-change’ lenses require precise machining and moreover, the thick-thin structure can be unstable during deployment in practical inspection applications. The work reported here follows from the insight that perhaps any approach to induce a mismatch in acoustical impedance as achieved by the step-change can also lead to focusing of ultrasonic guided waves. By carefully choosing the impedance pairing, a novel material contrast lens stacking Aluminium and Molybdenum plates in series is shown to achieve focusing of ultrasound through negative refraction. The interface between the two metals causes the interaction of the forward-propagating second symmetric Lamb mode S2 into the backward- propagating first symmetric S2b. The focusing of Lamb waves is demonstrated using numerical simulations validated by experiments. Comparison with a simple Aluminium-Aluminium plate combination brings out the underlying physics of focusing using the proposed material contrast lens. Simulation results showing super-resolution imaging using the proposed material contrast lens are also presented, demonstrating the power of the proposed approach. This report opens up the possibilities of developing new lensing devices for use in medical imaging and nondestructive evaluation, among other possible applications.

Fascioliasis is a re-emerging food-borne parasitic zoonosis which presents with nonspecific clinical symptoms. Definitive diagnosis requires demonstration of parasitic ova in stool which may often be elusive. Imaging plays a crucial role in raising the possibility of this diagnosis early in the disease course. Contrast-Enhanced Computed Tomography (CECT) of the abdomen was performed in a 44-year-old male with fever, right upper quadrant pain and dyspepsia. The patient later underwent an ultrasound-guided biopsy of liver lesions. The stool examination for ova was negative. Biopsy of the liver lesions showed ill-defined granulomas. Imaging plays a crucial role in establishing the early diagnosis of hepatic fascioliasis especially in nonendemic regions where the clinical suspicion for this diagnosis is low. This article places emphasis on the description of typical imaging features of this condition and the usage of additional investigative/testing techniques recommended by the Center for Disease Control and Prevention (CDC).

This paper proposes a novel design for a hermetically sealable device, consisting of charged linear and nonlinear membranes driven in the gigahertz range in vacuum setting, as a source of antibunched single phonons. Constraints for effecting phonon antibunching are found using the stationary Liouville–von Neumann master equation. Using analytical calculations and material and geometry optimization, we show that sizes of the proposed system can be upscaled to the near-micrometer range in a trade-off with the system operating temperature. The results are significant to realize quantum phononics, which has much promise as a modality for sensing and computing applications.

Experimental results on deep subwavelength resolution of defects are presented for the first time in the context of guided ultrasonic wave inspection of defects, using novel “structured channel” metamaterials. An Aluminum bar with side-drilled holes is used as a test sample, interrogated by the fundamental bar-guided symmetric mode. Simulations were conducted to optimize dimensional parameters of the metamaterial structure. Experiments using metamaterials fabricated accordingly demonstrate a resolution down to 1/72 of the operating wavelength, potentially bringing the resolution of guided wave inspection to the same range as that of bulk ultrasonics. This work has much promise for remote inspection in industry and biomedicine.

Congenital and acquired vascular pathologies of the gastrointestinal system may be diagnosed at any age and a detailed knowledge of the normal anatomy and their imaging findings is very important for surgical or interventional procedures. The aim of this review is to discuss clinical and imaging findings of the rare vascular pathologies that we encountered in patients undergoing abdominal computed tomography. Keywords: Aneurysm, Dissection, Fistula

This cross-sectional study was designed to identify information on the frequency, antimicrobial resistance and species diversity of methicillin-resistant coagulase negative staphylococci (MRCoNS) among pet dogs and humans within households. Fifty five nasal swabs each from dogs and their owners were collected. MRCoNS were identified based on gram staining, culture on mannitol salt agar, biochemical tests, and mecA gene amplification. The antibiotic susceptibility of the isolates was assessed by a disc diffusion test. Uniplex and multiplex polymerase chain reaction (PCR) were employed for the species identification of MRCoNS and SCCmec typing, respectively. Species were further confirmed by MALDI-TOF-MS. The prevalence of MRCoNS was 29% in dog owners and 23.6% in dogs. Four different species of MRCoNS, Staphylococci saprophyticus (48.3%), S. haemolyticus (24.1%), S. warneri (17.2%), and S. epidermidis (10.3%), were detected. Two isolates each from dog owners and dogs showed a constitutive resistance to macrolide-lincosamide-streptogramin B (cMLSB) resistance, eight isolates each from dogs and their owners showed a macrolide-streptogramin B (MSB) resistance, and only two isolates from dog owners revealed an inducible resistance to macrolide-lincosamide-streptogramin B (iMLSB) resistance. SCCmec types were SCCmec type IV (55.2%), SCCmec type V (24.1%), SCCmec III (10.3%), SCCmec II (3.4%); two isolates were non-typable. MRCoNS are prevalent and genetically diverse in companion animals and humans. Different species of MRCoNS were found in dogs and their owners.

Abstract This paper reports the experimental demonstration of deep subwavelength ultrasonic imaging of defects in metallic samples with a feature size of λ/25 using holey-structured metamaterial lenses. Optimal dimensions of the metamaterial’s geometric parameters are determined using numerical simulation and the physics of wave propagation through holey lenses. The paper also shows how the extraordinary transmission capacity of holey structured metamaterials comes about by the coupling of higher frequencies in the incident ultrasonic wave field to resonant modes of the lens.

Objective: To investigate the molecular epidemiology and antimicrobial resistance patterns of methicillin-resistant Staphylococcus aureus (MRSA) among healthcare workers and patients. Methods: MRSA isolates were recovered from nasal swabs collected at a tertiary care hospital of Nepal and confirmed on the basis of Gram staining, conventional biochemical tests, and PCR amplification of mecA gene. PCRs were also used for detection of the different resistance genes and staphylococcal cassette chromosome (SCC) mec types. Antibiotic susceptibility patterns of isolates were assessed by disc diffusion method and minimum inhibitory concentrations were determined by E-test. Results: A total of 29 MRSA were isolated from 536 nasal swabs (5.4%) of health care workers and patients at a tertiary care hospital in Nepal. All isolates were susceptible to amikacin, gentamicin, vancomycin (minimal inhibitory concentrations 1 024 μg/mL). Fourteen isolates were found harboring the mupA gene and one isolate was found carrying the novel mupB gene. High prevalence (68%) of SCCmec I type was found, followed by SCCmec V (13%) and SCCmec III (3%) among all the MRSA isolates. Conclusions: We found the emergence of SCCmec type I with high-level mupirocin resistance among MRSA in Nepal. Data also suggest that MRSA SCCmec type V strain has spread from the community to the hospital.

Abstract Background Molecular analysis of carbapenem-resistant genes in Acinetobacter baumannii, an emerging pathogen, is less commonly reported from Nepal. In this study we determined the antibiotic susceptibility profile and genetic mechanism of carbapenem resistance in clinical isolates of A. baumannii. Methods A. baumannii were isolated from various clinical specimens and identified based on Gram staining, biochemical tests, and PCR amplification of organism specific 16S rRNA and bla OXA-51 genes. The antibiotic susceptibility testing was performed using disc diffusion and E-test method. Multiplex PCR assays were used to detect the following β-lactamase genes: four class D carbapenem hydrolyzing oxacillinases (bla OXA-51, bla OXA-23, bla OXA-24 and bla OXA-58). Uniplex PCRs were used to detect three class B metallo-β-lactamases genes (bla IMP, bla VIM and bla NDM-1), class C cephalosporin resistance genes (bla ADC), aminoglycoside resistance gene (aphA6), and ISAba1 of all isolates. Insertion sequence ISAba125 among NDM-1 positive strains was detected. Clonal relatedness of all isolates were analyzed using repetitive sequence-based PCR (rep-PCR). Results Of total 44 analyzed isolates, 97.7% (n = 43) were carbapenem-resistant A. baumannii (CR-AB) and 97.7% (n = 43) were multidrug resistant A. baumannii (MDR-AB). One isolate was detected to be extremely drug resistant A. baumannii (XDR-AB). All the isolates were fully susceptible to colistin (MICs

This study looked at 227 saliva samples from Rhesus macaques (Macaca mulatta) and 218 samples from the surrounding environments. From these samples, MRSA isolates were collected from Rhesus saliva samples (n = 13) and environmental samples (n = 19) near temple areas in Kathmandu, Nepal. For comparison, selected MRSA isolates (n = 5) were obtained from patients with wound infections from a Kathmandu hospital. All isolates were characterized using Abbott StaphyType® DNA microarrays. Eighteen isolates (62%) from monkeys (n = 4; 31%) and environmental samples (n = 14; 74%), were CC22-MRSA-IV. Most (n = 16) of them carried both, the PVL locus and toxic shock toxin gene (tst1), an unusual combination which is the same as in previously characterized strain from Nepalese macaques and pigs. The five human isolates also belonged to that strain type. Eight monkey MRSA isolates were CC361-MRSA-IV. One MRSA from a monkey and one from an environmental sample, were CC88-MRSA-V. Other environmental MRSA included one each, CC121-MRSA-VT, and CC772 -MRSA-V. Two were CC779-MRSA-VT, potentially a novel clone. All MRSA carried the blaZ gene. The aacA–aphD, dfrA, and erm (C) genes were very common in isolates from all sources. One macaque MRSA carried the resistance genes aphA3 and sat, neither previously identified in primate MRSA isolates. This current study suggests that humans could be a potential source of the MRSA in the macaques/environment and transmission may be linked to humans feeding the primates and/or living in close proximity to each other.

Triple negative breast cancer (TNBC) is observed in ~15% of breast cancers and results in poor survival and increased distant metastases. Within the tumor are present a small portion of cancer stem cells that drive tumorigenesis and metastasis. In this study, we aimed to elucidate whether the two natural compounds, celastrol and triptolide, inhibit stemness in TNBC. MDA-MB-231, BT20, and a patient-derived primary cells (PD-TNBC) were used in the study. Mammosphere assay was performed to assess the stemness. Both celastrol and triptolide treatment suppressed mammosphere formation. Furthermore, the compound suppressed expression of cancer stem cell marker proteins DCLK1, ALDH1, and CD133. Notch signaling plays a critical role in stem cells renewal. Both celastrol or triptolide reduced Notch -1 activation and expression of its downstream target proteins HES-1 and HEY-1. However, when NICD 1 was ectopically overexpressed in the cells, it partially rescued proliferation and mammosphere formation of the cells, supporting the role of notch signaling. Together, these data demonstrate that targeting stem cells and the notch signaling pathway may be an effective strategy for curtailing TNBC progression.

Numerical models based on the Semi Analytical Finite-Element method are used to study the characteristics of guided wave modes supported by bone-like multi-layered tubular structures. The method is first validated using previous literature and experimental studies on phantoms mimicking healthy and osteoporotic conditions of cortical bone, and later used to study a trilayer marrow–bone–tissue system at varying mechanical degradation levels. The results show that bone condition strongly affects the modal properties of axially propagating guided waves and indicates that L(0,3) and F(1,6) are suitable modes for assessing the mechanical condition of the bone. The work here reports suitable modal selection and their dispersion properties which would the aid in development of a transduction mechanism for mechanical assessment of bones.

Staphylococcus aureus is a ubiquitous pathogen and colonizer in humans and animals. There are few studies on the molecular epidemiology of S. aureus in wild monkeys and apes. S. aureus carriage in rhesus macaques (Macaca mulatta) and Assam macaques (Macaca assamensis) is a species that has not previously been sampled and lives in remote environments with limited human contact. Forty Staphylococcus aureus isolates including 33 methicillin-susceptible S. aureus (MSSA) and seven methicillin-resistant S. aureus (MRSA) were characterized. Thirty-four isolates were from rhesus macaques and six isolates (five MSSA, one MRSA) were from Assam macaques. Isolates were characterized using StaphyType DNA microarrays. Five of the MRSA including one from Assam macaque were CC22 MRSA-IV (PVL+/tst+), which is a strain previously identified in Nepalese rhesus. One MRSA each were CC6 MRSA-IV and CC772 MRSA-V (PVL+). One MSSA each belonged to CC15, CC96, and CC2990. Six MRSA isolates carried the blaZ, while ten known CC isolates (seven MRSA, three MSSA) carried a variety of genes including aacA-aphD, aphA3, erm(C), mph(C), dfrA, msrA, and/or sat genes. The other 30 MSSA isolates belonged to 17 novel clonal complexes, carried no antibiotic resistance genes, lacked Panton–Valentine Leukocidin (PVL), and most examined exotoxin genes. Four clonal complexes carried egc enterotoxin genes, and four harbored edinB, which is an exfoliative toxin homologue.

MnFe2O4 thin films were pulsed laser deposited on to quartz substrate from room temperature (RT) to 650 °C in a pure argon environment. Temperature dependence of spontaneous magnetization (4πMS) was measured on these films from 10 K to 350 K using a vibrating sample magnetometer. Ferromagnetic resonance (FMR) study was also carried out at 300 K. The exchange stiffness constant (D) values were obtained by fitting the 4πMS data to the Bloch’s equation. The D values of the films thus found decreases while the 4πMS value increases, though non-monotonically, with the increase in TS and tend to reach bulk values at TS = 650 °C. The variation in D and 4πMS values of the films are explained based on the degree of inversion and oxidation state of cations in thin films.

This paper studies the propagation of ultrasound in spiral waveguides, towards distributed temperature measurements on a plane. Finite Element (FE) approach was used for understanding the velocity behaviour and consequently designing the spiral waveguide. Temperature measurements were experimentally carried out on planar surface inside a hot chamber. Transduction was performed using a piezo-electric crystal that is attached to one end of the waveguide. Lower order axisymmetric guided ultrasonic modes L(0,1) and T(0,1) were employed. Notches were introduced along the waveguide to obtain ultrasonic wave reflections. Time of fight (TOF) differences between the pre-defined reflectors (notches) located on the waveguides were used to infer local temperatures. The ultrasonic temperature measurements were compared with commercially available thermocouples.

OBJECTIVES/SPECIFIC AIMS: Drug repositioning has the potential to accelerate translation of novel cancer chemotherapeutics from bench to bedside. The goal of this study was to determine the effects of ciclopirox olamine (CPX) on esophageal tumor cells. METHODS/STUDY POPULATION: We tested the effect of CPX on four esophageal cancer cell lines, assessing cell proliferation and viability by hexosaminidase and clonogenicity assay, respectively. We analyzed the effects of CPX on three-dimensional (3D) esophageal tumor cell spheroids. We also analyzed effects on cell cycle by flow cytometry. For mechanism, we performed western blots for proteins involved in cell cycle regulation, apoptosis and the Wnt/β-catenin pathway. For in vivo effects, we performed a murine xenograft model with intraperitoneal administration of CPX (100 mg/Kg body weight daily). RESULTS/ANTICIPATED RESULTS: CPX inhibited growth of all cell lines in a time and concentration-dependent manner. CPX also inhibited growth of esophageal spheroids. Cell cycle analysis demonstrated G0/G1 arrest in cells treated with CPX. Western blot analyses demonstrated decreased expression of cyclinD1, CDK4, CDK6, and transcriptionally active β-catenin, supporting the role of CPX in cell cycle inhibition and decreased β-catenin activity. Finally, treatment of nude mice with CPX significantly decreased tumor xenograft volume. DISCUSSION/SIGNIFICANCE OF IMPACT: CPX demonstrates anti-tumor properties in esophageal cancer cell lines. The current results justify further research into the mechanism of this inhibition. Additionally, given its established safety in humans, CPX is a potential candidate for repositioning as an adjunct treatment for esophageal cancer.

This paper introduces an ultrasonic torsional mode based technique, configured in the form of a helical “spring-like” waveguide, for multi-level temperature measurement. The multiple sensing levels can be repositioned by stretching or collapsing the spring to provide simultaneous measurements at different desired spacing in a given area/volume. The transduction is performed using piezo-electric crystals that generate and receive T(0,1) mode in a pulse echo mode. The gage lengths and positions of measurements are based on machining multiple reflector notches in the waveguide at required positions. The time of fight (TOF) measurements between the reflected signals from the notches provide local temperatures that compare well with co-located thermocouples.

Splenectomy has been the conventional surgical treatment for patients with Immune Thrombocytopenic Purpura (ITP). Aim: To define response to surgical therapy, pre operative factors influencing outcome and tolerability of surgery in adult patients undergoing splenectomy for ITP. Method: We analyzed prospectively maintained data of 33 patients who were diagnosed as ITP and underwent splenectomy over the last 10 years. The age, presenting complaints, bleeding manifestations, clinical details and other investigations were noted. Details of immediate pre-operative administration of blood transfusions, platelet transfusions and other forms of therapy were also recorded. Operative details with regards to blood loss and the presence of accessory spleens were obtained. Postoperative course in terms of clinical improvement, rates of complications and platelet counts was also noted. Results: Skin petechiae and menorhhagia were common presenting symptoms in patients (mean age 26.5±10.5 yrs) with ITP. Eighteen patients underwent splenectomy for failure of therapy and fifteen for relapse on medical treatment. Mean platelet bags transfused in immediate pre-operative period were 2.8±0.8. Mean intra-operative blood loss was 205±70.5 ml. Accessory spleens were removed in 1 case (3.03%). The immediate postoperative response was complete in 19 cases (57.58%) and partial in 13 cases (39.39%). The platelet counts increased significantly from 23142±12680/ µL (Microliter) (mean ± SD) preoperatively to 170000±66000/µL (Microliter) within 24-48 hours after splenectomy ( P < 0.05). The mean platelet count was 165000+66000/µL (Microliter) at the end of one month when steroids were tapered off gradually. Four patients (12.12%) had complications (one each of wound hematoma, wound infection, splenic fossa collection and upper GI hemorrhage) in postoperative period but all responded to therapy. One relapsed patient was detected with accessory spleen and responded after re-surgery. Response to splenectomy was better in young patients and in those patients who had higher immediate post-splenectomy thrombocytosis. Conclusions: Splenectomy is safe and effective therapy in ITP patients with no response to steroids and relapse after medical therapy. Response to splenectomy was more in young patients and in those patients who had higher immediate post-splenectomy thrombocytosis.

Rationale and Objectives: Various devices are used to aid in the education of laparoscopic skills ranging from simple box trainers to sophisticated virtual reality trainers. Virtual reality system is an advanced and effective training method, however it is yet to be adopted in India due to its cost and the advanced technology required for it. Therefore, box trainers are being used to train laparoscopic skills. Hence this study was undertaken to assess the overall effectiveness of the box-training course. Study Procedure: The study was conducted during six-day laparoscopic skills training workshops held during 2006. Twenty five surgeons; age range of 26 to 45 years, of either sex, who had not performed laparoscopic surgery before; attending the workshop were evaluated. Each participant was given a list of tasks to perform before beginning the box-training course on day one and was evaluated quantitatively by rating the successful completion of each test. Evaluation began when the subject placed the first tool into the cannula and ended with task completion. Two evaluation methods used to score the subject, including a global rating scale and a task-specific checklist. After the subject completed all sessions of the workshop, they were asked to perform the same tasks and were evaluated in the same manner. For each task completed by the subjects, the difference in the scores between the second and first runs were calculated and interpreted as an improvement as a percentage of the initial score. Statistical Analysis: Wilcoxon matched-paired signed-ranks test was applied to find out the statistical significance of the results obtained. Results: The mean percentage improvement in scores for both the tasks, using global rating scale, was 44.5% + 6.930 (Mean + SD). For task 1, using the global rating scale mean percentage improvement was 49.4% + 7.948 (Mean + SD). For task 2, mean percentage improvement using global rating scale was 39.6% + 10.4 (Mean + SD). Using Wilcoxon matched-paired signed-ranks test, 2-tailed P -value< 0.0001 which is extremely significant. Conclusion: This study confirms that a short-term, intensive, focused course does improve laparoscopic skills of trainees. Box-trainers can be used to change the present day didactic training into objective and competency-based. Global rating scale and checklist provide an inexpensive and effective way of objective assessment of performance of laparoscopic skills.

Angiomatous malformation is the most common vascular abnormality, accounting for 30-40% cases of obscure GI bleeding from small bowel. Surgical resection is the treatment of choice in severe or recurrent hemorrhage requiring multiple blood transfusions. However, the diffuse nature of the lesions poses a challenge to localize them accurately preoperatively, for exact resection. We present a case in which we have used selective mesenteric angiography with selective cannulation and exact localization of the lesion by injecting dye such as methylene blue, indigo carmine, and fluorescein, to localize the angiomatous malformation before surgical resection and also to determine the exact resection to be done.