Search results for: punch biopsy

Authors: W. Ling, Mohamed Saufi Bin Awang

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Introduction: Mycobacterium tuberculosis post a major health problem worldwide. Central nervous system (CNS) infection by mycobacterium tuberculosis is one of the most devastating complications of tuberculosis. Although with advancement in medical fields, we are yet to understand the pathophysiology of how mycobacterium tuberculosis was able to cross the blood-brain barrier (BBB) and infect the CNS. CNS TB may present with nonspecific clinical symptoms which can mimic other diseases/conditions; this is what makes the diagnosis relatively difficult and challenging. Public health has to be informed and educated about the spread of TB, and early identification of TB is important as it is a curable disease. Case Report: A young 21-year-old Malay gentleman was initially presented to us with symptoms of ear discharge, tinnitus, and right-sided headache for the past one year. Further history reveals that the symptoms have been mismanaged and neglected over the period of 1 year. Initial investigation reveals features of inflammation of the ear. Further imaging showed the feature of chronic inflammation of the otitis media and atypical right cerebral abscess, which has the same characteristic features and consistency. He further underwent a biopsy, and results reveal positive Mycobacterium tuberculosis of the otitis media. With the results and the available imaging, we were certain that this is likely a case of disseminated tuberculosis causing CNS TB. Conclusion: We aim to highlight the challenge and difficult face in our health care system and public health in early identification and treatment.

Keywords: central nervous system tuberculosis, intracranial tuberculosis, tuberculous encephalopathy, tuberculous meningitis

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Authors: Leila Noori, Rosario Barone, Francesca Rappa, Antonella Marino Gammazza, Alessandra Maria Vitale, Giuseppe Donato Mangano, Giusy Sentiero, Filippo Macaluso, Kathryn H. Myburgh, Francesco Cappello, Federica Scalia

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The neuromuscular system controls, directs, and allows movement of the body through the action of neural circuits, which include motor neurons, sensory neurons, and skeletal muscle fibers. Protein homeostasis of the involved cytotypes appears crucial to maintain the correct and prolonged functions of the neuromuscular system, and both neuronal cells and skeletal muscle fibers express significant quantities of protein chaperones, the molecular machinery responsible to maintain the protein turnover. Genetic mutations or defective post-translational modifications of molecular chaperones (i.e., genetic or acquired chaperonopathies) may lead to neuromuscular disorders called as neurochaperonopathies. The limited knowledge of the effects of the defective chaperones on skeletal muscle fibers and neurons impedes the progression of therapeutic approaches. A distinct genetic variation of CCT5 gene encoding for the subunit 5 of the chaperonin CCT (Chaperonin Containing TCP1; also known as TRiC, TCP1 Ring Complex) was recently described associated with severe distal motor neuropathy by our team. In this study, we investigated the histopathological abnormalities of the skeletal muscle biopsy of the pediatric patient affected by the mutation Leu224Val in the CCT5 subunit. We provide molecular and structural features of the diseased skeletal muscle tissue that we believe may be useful to identify undiagnosed cases of this rare genetic disorder. We investigated the histological abnormalities of the affected tissue via hematoxylin and eosin staining. Then we used immunofluorescence and qPCR techniques to explore the expression and distribution of CCT5 in diseased and healthy skeletal muscle tissue. Immunofluorescence and immunohistochemistry assays were performed to study the sarcomeric and structural proteins of skeletal muscle, including actin, myosin, tubulin, troponin-T, telethonin, and titin. We performed Western blot to examine the protein expression of CCT5 and some heat shock proteins, Hsp90, Hsp60, Hsp27, and α-B crystallin, along with the main client proteins of the CCT5, actin, and tubulin. Our findings revealed muscular atrophy, abnormal morphology, and different sizes of muscle fibers in affected tissue. The swollen nuclei and wide interfiber spaces were seen. Expression of CCT5 had been decreased and showed a different distribution pattern in the affected tissue. Altered expression, distribution, and bandage pattern were detected by confocal microscopy for the interested muscular proteins in tissue from the patient compared to the healthy control. Protein levels of the studied Hsps normally located at the Z-disk were reduced. Western blot results showed increased levels of the actin and tubulin proteins in the diseased skeletal muscle biopsy compared to healthy tissue. Chaperones must be expressed at high levels in skeletal muscle to counteract various stressors such as mechanical, oxidative, and thermal crises; therefore, it seems relevant that defects of molecular chaperones may result in damaged skeletal muscle fibers. So far, several chaperones or cochaperones involved in neuromuscular disorders have been defined. Our study shows that alteration of the CCT5 subunit is associated with the damaged structure of skeletal muscle fibers and alterations of chaperone system components and paves the way to explore possible alternative substrates of chaperonin CCT. However, further studies are underway to investigate the CCT mechanisms of action to design applicable therapeutic strategies.

Keywords: molecular chaperones, neurochaperonopathy, neuromuscular system, protein homeostasis

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Authors: Zohra Salim

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Objective: To access the relationship of primary tumor thickness with cervical lymphadenopathy in squamous cell carcinoma of buccal mucosa. Methodology: A cross-sectional observational study was carried out on 80 Patients with biopsy-proven oral squamous cell carcinoma of buccal mucosa at Dow University of Health Sciences. All the study participants were treated with wide local excision of the primary tumor with elective neck dissection. Patients with prior head and neck malignancy or those with prior radiotherapy or chemotherapy were excluded from the study. Data was entered and analyzed on SPSS 21. Chi-squared test with 95% C.I and 80% power of the test was used to evaluate the relationship of tumor depth with cervical lymph nodes. Results: 50 participants were male, and 30 patients were female. 30 patients were in the age range of 20-40 years, 36 patients in the range of 40-60 years, while 14 patients were beyond age 60 years. Tumor size ranged from 0.3cm to 5cm with a mean of 2.03cm. Tumor depth ranged from 0.2cm to 5cm. 20% of the participants reported with tumor depth greater than 2.5cm, while 80% of patients reported with tumor depth less than 2.5cm. Out of 80 patients, 27 reported with negative lymph nodes, while 53 patients reported with positive lymph nodes. Conclusion: Our study concludes that relationship exists between the depth of primary tumor and cervical lymphadenopathy in squamous cell carcinoma of buccal mucosa.

Keywords: squamous cell carcinoma, tumor depth, cervical lymphadenopathy, buccal mucosa

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Authors: Jemal Ebrahim Dessie, Lukács Zsolt

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High-strength aluminum alloys have drawn a lot of attention because of the expanding demand for lightweight vehicle design in the automotive sector. Due to poor formability at room temperature, warm and hot forming have been advised. However, warm and hot forming methods need more steps in the production process and an advanced tooling system. In contrast, since ordinary tools can be used, forming sheets at room temperature in the W temper condition is advantageous. However, springback of supersaturated sheets and their thinning are critical challenges and must be resolved during the use of this technique. In this study, AA6082-T6 aluminum alloy was solution heat treated at different oven temperatures and times using a specially designed and developed furnace in order to optimize the W-temper heat treatment temperature. A U-shaped bending test was carried out at different time periods between W-temper heat treatment and forming operation. Finite element analysis (FEA) of U-bending was conducted using AutoForm aiming to validate the experimental result. The uniaxial tensile and unload test was performed in order to determine the kinematic hardening behavior of the material and has been optimized in the Finite element code using systematic process improvement (SPI). In the simulation, the effect of friction coefficient & blank holder force was considered. Springback parameters were evaluated by the geometry adopted from the NUMISHEET ’93 benchmark problem. It is noted that the change of shape was higher at the more extended time periods between W-temper heat treatment and forming operation. Die radius was the most influential parameter at the flange springback. However, the change of shape shows an overall increasing tendency on the sidewall as the increase of radius of the punch than the radius of the die. The springback angles on the flange and sidewall seem to be highly influenced by the coefficient of friction than blank holding force, and the effect becomes increases as increasing the blank holding force.

Keywords: aluminum alloy, FEA, springback, SPI, U-bending, W-temper

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Authors: C. Gallottini, W. Di Mari, A. Amaddeo, K. Barbaro, A. Dolci, G. Dolci, L. Gallottini, G. Barraco, S. Eramo

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A group of 10 dogs (group A) with Periodontal Disease in the third stage, were subjected to regenerative therapy of periodontal tissues, by use of nano hydroxy apatite (NHA). These animals induced by general anesthesia, where treated by ultrasonic scaling, root planning, and at the end by a mucogingival flap in which it was applied NHA. The flap was closed and sutured with simple steps. Another group of 10 dogs (group B), control group, was treated only by scaling and root planning. No patient was subjected to antibiotic therapy. After three months, a check was made by inspection of the oral cavity, radiography and bone biopsy at the alveolar level. Group A showed a total restitutio ad integrum of the periodontal structures, and in group B still mild gingivitis in 70% of cases and 30% of the state remains unchanged. Numerous experimental studies both in animals and humans have documented that the grafts of porous hydroxyapatite are rapidly invaded by fibrovascular tissue which is subsequently converted into mature lamellar bone tissue by activating osteoblast. Since we acted on the removal of necrotic cementum and rehabilitating the root tissue by polishing without intervention in the ligament but only on anatomical functional interface of cement-blasts, we can connect the positive evolution of the clinical-only component of the cement that could represent this perspective, the only reason that Periodontal Disease become a Cement Disease, while all other clinical elements as nothing more than a clinical pathological accompanying.

Keywords: nanoidroxiaphatite, parodontal disease, cement disease, regenerative therapy

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Authors: Raju Ranjha, Surbhi Aggarwal

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Background: Inflammation plays an important role in infectious and non-infectious diseases. MiRNA is also reported to play role in inflammation and associated cancers. Chemokine CXCL12 is also known to play role in inflammation and various cancers. CXCL12/CXCR4 chemokine axis was involved in pathogenesis of IBD specially UC. Supplementation of CXCL12 induces homing of dendritic cells to spleen and enhances control of plasmodium parasite in BALB/c mice. We looked at the regulation of CXCL12β by miRNA in UC colitis. Prolonged inflammation of colon in UC patient increases the risk of developing colorectal cancer. We looked at the expression differences of CXCl12β and its targeting miRNA in cancer susceptible area of colon of UC patients. Aim: Aim of this study was to find out the expression regulation of CXCL12β by miRNA in inflammation. Materials and Methods: Biopsy samples and blood samples were collected from UC patients and non-IBD controls. mRNA expression was analyzed using microarray and real-time PCR. CXCL12β targeting miRNA were looked by using online target prediction tools. Expression of CXCL12β in blood samples and cell line supernatant was analyzed using ELISA. miRNA target was validated using dual luciferase assay. Results and conclusion: We found miR-200a regulate the expression of CXCL12β in UC. Expression of CXCL12β was increased in cancer susceptible part of colon and expression of its targeting miRNA was decreased in the same part of colon. miR-200a regulate CXCL12β expression in inflammation and may be an important therapeutic target in inflammation associated cancer.

Keywords: inflammation, miRNA, regulation, CXCL12

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Authors: Waqas Ahmad, Eisha Tahir, Shahper Aqeel, Imran Khalid Niazi, Amjad Iqbal

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Background: Breast conservation surgery applies a number of techniques for accurate localization of lesions. Wire localization remains the method of choice in non-palpable breast cancers post-neoadjuvant chemotherapy. Objective: The aim of our study was to determine the accuracy of wire localization procedures in our department and compare it with internationally set protocols as per the Royal College of Radiologists. Post wire mammography, as well as the margin status of the postoperative specimen, assessed the accuracy of the procedure. Methods: We retrospectively reviewed the data of 225 patients who presented to our department from May 2014 to June 2015 post neoadjuvant chemotherapy with non-palpable cancers. These patients are candidates for wire localized lumpectomies either under ultrasound or stereotactic guidance. Metallic marker was placed in all the patients at the time of biopsy. Post wire mammogram was performed in all the patients and the distance of the wire tip from the marker was calculated. The presence or absence of the metallic clip in the postoperative specimen, as well as the marginal status of the postoperative specimen, was noted. Results: 157 sonographic and 68 stereotactic wire localization procedures were performed. 95% of the wire tips were within 1 cm of the metallic marker. Marginal status was negative in 94% of the patients in histopathological specimen. Conclusion: Our audit report declares more than 95% accuracy of image guided wire localization in successful excision of non-palpable breast lesions.

Keywords: breast, cancer, non-palpable, wire localization

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Authors: Inseon Ryoo, Soo Chin Kim, Hyena Jung, Sangil Suh

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Objectives: The purpose of this study is to evaluate the clinical significance of hyper-intense signal thyroid incidentalomas on the time of flight magnetic resonance angiography (TOF-MRA) using correlation study with ultrasound (US). Methods: We retrospectively reviewed 3,505 non-contrast TOF-MRA performed at an institution between September 2014 and May 2017. Two radiologists correlated the thyroid incidentalomas detected on TOF-MRA with US features which was obtained within three months interval between MRA and US examinations in consensus method. Results: The prevalence of hyper-intense signal thyroid nodules incidentally detected on TOF-MRA was 1.2% (43/3505). Among them, 35 people (81.4%) underwent US examinations, and total 45 hyper-intense signal thyroid nodules were detected on US exams. Of these 45 nodules, 35 nodules (72.9%) were categorized as benign (K-TIRADS category 2) on US exams. Fine needle aspiration was performed on 9 nodules according to the indications recommended by Korean Society of Thyroid Radiology. All except one high-suspicious thyroid nodule were confirmed as benign (Bethesda 2) on cytologic exams. One high-suspicious nodule on US showed a non-diagnostic result (Bethesda 1) on cytologic exam. However, this nodule collapsed after aspiration of thick colloid material. Conclusions: Our study showed that the most hyper-intense signal thyroid nodules detected on TOF-MRA were benign. Therefore, if a hyper-intense signal incidentaloma is found on TOF-MRA, further evaluation, especially invasive biopsy of the nodules could be suspended unless the patient had other symptoms or clinical factors suggesting the need for further evaluation.

Keywords: incidentaloma, thyroid nodule, TOF MR angiography, ultrasound

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Authors: Huajuan Shi

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Background: The biopsy of the preimplantation embryo may increase the potential risk and concern of embryo viability. Clinically discarded spent embryo medium (SEM) has entered the view of researchers, sparking an interest in noninvasive embryo screening. However, one of the major restrictions is the extremelty low quantity of cf-RNA, which is difficult to efficiently and unbiased amplify cf-RNA using traditional methods. Hence, there is urgently need to an efficient and low bias amplification method which can comprehensively and accurately obtain cf-RNA information to truly reveal the state of SEM cf-RNA. Result: In this present study, we established an agarose PCR amplification system, and has significantly improved the amplification sensitivity and efficiency by ~90 fold and 9.29 %, respectively. We applied agarose to sequencing library preparation (named AG-seq) to quantify and characterize cf-RNA in SEM. The number of detected cf-RNAs (3533 vs 598) and coverage of 3' end were significantly increased, and the noise of low abundance gene detection was reduced. The increasing percentage 5' end adenine and alternative splicing (AS) events of short fragments (< 400 bp) were discovered by AG-seq. Further, the profiles and characterizations of cf-RNA in spent cleavage medium (SCM) and spent blastocyst medium (SBM) indicated that 4‐mer end motifs of cf-RNA fragments could remarkably differentiate different embryo development stages. Significance: This study established an efficient and low-cost SEM amplification and library preparation method. Not only that, we successfully described the characterizations of SEM cf-RNA of preimplantation embryo by using AG-seq, including abundance features fragment lengths. AG-seq facilitates the study of cf-RNA as a noninvasive embryo screening biomarker and opens up potential clinical utilities of trace samples.

Keywords: cell-free RNA, agarose, spent embryo medium, RNA sequencing, non-invasive detection

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Authors: Pejman Taghibeikzadehbadr

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Muscle contraction stimulates a transient change of myogenic factors, partly related to the mode of contractions. Here, we assessed the response of Insulin-like growth factor 1Ea (IGF-1Ea), Insulin-like growth factor 1Eb (IGF-1Eb), Insulin-like growth factor 1Ec (IGF-1Ec), Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α-1), Peroxisome proliferator-activated receptor gamma coactivator 4-alpha (PGC1α-4), and myostatin to the eccentric Vs the concentric contraction in human skeletal muscle. Ten healthy males were performed an acute eccentric and concentric exercise bout (n = 5 per group). For each contraction type, participants performed 12 sets of 10 repetitions knee extension by the dominant leg. Baseline and post-exercise muscle biopsy were taken 4 weeks before and immediately after experimental sessions from Vastus Lateralis muscle. Genes expression was measured by real-time PCR technique. There was a significant increase in PGC1α-1, PGC1α-4, IGF-1Ea and, IGF-1Eb mRNA after concentric contraction (p ≤ 0.05), while the PGC1α-4 and IGF-1Ec significantly increased after eccentric contraction (p ≤ 0.05). It is intriguing to highlight that; no significant differences between groups were evident for changes in any variables following exercise bouts (p ≥ 0.05). Our results found that concentric and eccentric contractions presented different responses in PGC1α-1, IGF-1Ea, IGF-1Eb, and IGF-1Ec mRNA. However, a similar significant increase in mRNA content was observed in PGC1α-4. Further, no apparent differences could be found between the response of genes to eccentric and concentric contraction.

Keywords: eccentric contraction, concentric contraction, gene expression, PGC-1 alpha, IGF-1 Myostatin

Procedia PDF Downloads 138

Authors: Huajuan Shi

Abstract:

Background: The biopsy of the preimplantation embryo may increase the potential risk and concern of embryo viability. Clinically discarded spent embryo medium (SEM) has entered the view of researchers, sparking an interest in noninvasive embryo screening. However, one of the major restrictions is the extremelty low quantity of cf-RNA, which is difficult to efficiently and unbiased amplify cf-RNA using traditional methods. Hence, there is urgently need to an efficient and low bias amplification method which can comprehensively and accurately obtain cf-RNA information to truly reveal the state of SEM cf-RNA. Result: In this present study, we established an agarose PCR amplification system, and has significantly improved the amplification sensitivity and efficiency by ~90 fold and 9.29 %, respectively. We applied agarose to sequencing library preparation (named AG-seq) to quantify and characterize cf-RNA in SEM. The number of detected cf-RNAs (3533 vs 598) and coverage of 3' end were significantly increased, and the noise of low abundance gene detection was reduced. The increasing percentage 5' end adenine and alternative splicing (AS) events of short fragments (< 400 bp) were discovered by AG-seq. Further, the profiles and characterizations of cf-RNA in spent cleavage medium (SCM) and spent blastocyst medium (SBM) indicated that 4‐mer end motifs of cf-RNA fragments could remarkably differentiate different embryo development stages. Significance: This study established an efficient and low-cost SEM amplification and library preparation method. Not only that, we successfully described the characterizations of SEM cf-RNA of preimplantation embryo by using AG-seq, including abundance features fragment lengths. AG-seq facilitates the study of cf-RNA as a noninvasive embryo screening biomarker and opens up potential clinical utilities of trace samples.

Keywords: cell-free RNA, agarose, spent embryo medium, RNA sequencing, non-invasive detection

Procedia PDF Downloads 33

Authors: Rajendra N. Ghosh, Paramjeet Singh, Niranjan Khandelwal, Sameer Vyas, Pratibha Singhi, Naveen Sankhyan

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Background: Tuberculoma and neurocysticercosis (NCC) are two most common intracranial infections in developing country. They often simulate on neuroimaging and in absence of typical imaging features cause significant diagnostic dilemmas. Differentiation is extremely important to avoid empirical exposure to antitubercular medications or nonspecific treatment causing disease progression. Purpose: Better characterization and differentiation of CNS tuberculoma and NCC by using morphological and multiple advanced functional MRI. Material and Methods: Total fifty untreated patients (20 tuberculoma and 30 NCC) were evaluated by using conventional and advanced sequences like CISS, SWI, DWI, DTI, Magnetization transfer (MT), T2Relaxometry (T2R), Perfusion and Spectroscopy. rCBV,ADC,FA,T2R,MTR values and metabolite ratios were calculated from lesion and normal parenchyma. Diagnosis was confirmed by typical biochemical, histopathological and imaging features. Results: CISS was most useful sequence for scolex detection (90% on CISS vs 73% on routine sequences). SWI showed higher scolex detection ability. Mean values of ADC, FA,T2R from core and rCBV from wall of lesion were significantly different in tuberculoma and NCC (P < 0.05). Mean values of rCBV, ADC, T2R and FA for tuberculoma and NCC were (3.36 vs1.3), (1.09x10⁻³vs 1.4x10⁻³), (0.13 x10⁻³ vs 0.09 x10⁻³) and (88.65 ms vs 272.3 ms) respectively. Tuberculomas showed high lipid peak, more choline and lower creatinine with Ch/Cr ratio > 1. T2R value was most significant parameter for differentiation. Cut off values for each significant parameters have proposed. Conclusion: Quantitative MRI in combination with conventional sequences can better characterize and differentiate similar appearing tuberculoma and NCC and may be incorporated in routine protocol which may avoid brain biopsy and empirical therapy.

Keywords: advanced functional MRI, differentiation, neurcysticercosis, tuberculoma

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Authors: John M. Kimani, Joseph K. N. Kuria, Stephen G. Kiama

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The spiny mouse (Acomys species) is a precocial rodent that has emerged as an interesting mammal model for various organ regeneration studies due to its remarkable ability to restore all tissues in punched ear holes and injured skin. There is a scarcity of information regarding neonatal and postnatal skin development in precocial mammals in comparison to other close relatives in the altricial-precocial spectrum. The varying developmental degrees of neonates and how they relate to adults are the focus of this study. The study compares neonatal characteristics and postnatal skin development in Acomys Percival to its close relative Lophuromys zena (Lophuromys flavipunctatus group) in the Deomyinae subfamily to establish their neonatal maturity status and growth pattern. Breeding colonies of A. percivali, L. zena and Mus musculus were established. The off-springs postnatal stages of structural dorsal and auricular skin development were studied where manifesting external features established through gross examination were used to unravel histogenesis of skin in neonates and aged groups. Skin specimens from the different rodents showed striking differences between the neonatal and aged groups. Moreover, the skin structure also exhibited considerable inter-species differences at the same postnatal time points but followed similar development patterns to maturity. The integument of the newborn A. Percival was the most advanced in development compared to the in-between nidicolous semi-precocial young of L. zena with a rapid postnatal development pattern and the altricial M. musculus, where most maturation of the integumentary system occurred in a prolonged postnatal period. We then utilized a 4-mm ear punch assay to compare the ability to replace auricular tissue and the rate of pinnal hole closure. L. zena closed the pinnal hole at a faster rate compared A. percivali. Taken together, our findings support the conclusion that neonatal maturity status and developmental patterns are not directly related to regenerative ability. This study deepens the understanding of skin morphogenesis across developmental, regenerative and evolutionary levels in mammals.

Keywords: altricial, intermediate, precocial, skin development, regeneration

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Authors: Joseph George, Anne Kotteswara Roa

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Skin disease is one of the most common and popular kinds of health issues faced by people nowadays. Skin cancer (SC) is one among them, and its detection relies on the skin biopsy outputs and the expertise of the doctors, but it consumes more time and some inaccurate results. At the early stage, skin cancer detection is a challenging task, and it easily spreads to the whole body and leads to an increase in the mortality rate. Skin cancer is curable when it is detected at an early stage. In order to classify correct and accurate skin cancer, the critical task is skin cancer identification and classification, and it is more based on the cancer disease features such as shape, size, color, symmetry and etc. More similar characteristics are present in many skin diseases; hence it makes it a challenging issue to select important features from a skin cancer dataset images. Hence, the skin cancer diagnostic accuracy is improved by requiring an automated skin cancer detection and classification framework; thereby, the human expert’s scarcity is handled. Recently, the deep learning techniques like Convolutional neural network (CNN), Deep belief neural network (DBN), Artificial neural network (ANN), Recurrent neural network (RNN), and Long and short term memory (LSTM) have been widely used for the identification and classification of skin cancers. This survey reviews different DL techniques for skin cancer identification and classification. The performance metrics such as precision, recall, accuracy, sensitivity, specificity, and F-measures are used to evaluate the effectiveness of SC identification using DL techniques. By using these DL techniques, the classification accuracy increases along with the mitigation of computational complexities and time consumption.

Keywords: skin cancer, deep learning, performance measures, accuracy, datasets

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Authors: Francis Zerd, Brian E. Moore, Atuganile E. Malango, Patrick W. Hosokawa, Kevin O. Lillehei, Laurence Lemery Mchome, D. Ryan Ormond

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Introduction: Since neuropathologic diagnosis in the developing world is hampered by limitations in technical infrastructure, trained laboratory personnel, and subspecialty-trained pathologists, the use of telepathology for diagnostic support, second-opinion consultations, and ongoing training holds promise as a means of addressing these challenges. This research aims to assess the utility of static teleneuropathology in improving neuropathologic diagnoses in low- and middle-income countries. Methods: Consecutive neurosurgical biopsy and resection specimens obtained at Muhimbili National Hospital in Tanzania between July 1, 2018, and June 30, 2019, were selected for retrospective, blinded static-image neuropathologic review followed by on-site review by an expert neuropathologist. Results: A total of 75 neuropathologic cases were reviewed. The agreement of static images and on-site glass diagnosis was 71% with strict criteria and 88% with less stringent criteria. This represents an overall improvement in diagnostic accuracy from 36% by general pathologists to 71% by a neuropathologist using static telepathology (or 76% to 88% with less stringent criteria). Conclusions: Telepathology offers a suitable means of providing diagnostic support, second-opinion consultations, and ongoing training to pathologists practicing in resource-limited countries. Moreover, static digital teleneuropathology is an uncomplicated, cost-effective, and reliable way to achieve these goals.

Keywords: neuropathology, resource-limited settings, static image, Tanzania, teleneuropathology

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Authors: Laila Seada, Ashraf Ibrahim, Amjad Al Shammari

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Background and Objectives: Breast carcinoma is the most common cancer of females in Hail region, accounting for 31% of all diagnosed cancer cases followed by thyroid carcinoma (25%) and colorectal carcinoma (13%). Methods: In the present retrospective study, all cases of breast lesions received at the histopathology department in King Khalid Hospital, Hail, during the period from May 2011 to April 2016 have been retrieved from department files. For all cases, a trucut biopsy, lumpectomy, or modified radical mastectomy was available for histopathologic diagnosis, while 105/140 (75%) had, as well, preoperative fine needle aspirates (FNA). Results: 49 cases out of 140 (35%) breast lesions were carcinomas: 44/49 (89.75%) was invasive ductal, 2/49(4.1%) invasive lobular carcinomas, 1/49(2.05%) intracystic low grade papillary carcinoma and 2/49 (4.1%) ductal carcinoma in situ (DCIS). Mean age for malignant cases was 45.06 (+/-10.58): 32.6% were below the age of 40 and 30.6 below 50 years, 18.3% below 60 and 16.3% below 70 years. For the benign group, mean age was 32.52 (+/10.5) years. Benign lesions were in order of frequency: 34 fibroadenomas, 14 fibrocystic disease, 12 chronic mastitis, five granulomatous mastitis, three intraductal papillomas, and three benign phyllodes tumor. Tubular adenoma, lipoma, skin nevus, pilomatrixoma, and breast reduction specimens constituted the remaining specimens. Conclusion: Breast lesions are common in our series and invasive carcinoma accounts for more than 1/3^rd of the lumps, with 63.2% incidence in pre-menopausal ladies, below the age of 50 years. FNA as a non-invasive procedure, proved to be an effective tool in diagnosing both benign and malignant/suspicious breast lumps and should continue to be used as a first assessment line of palpable breast masses.

Keywords: age incidence, breast carcinoma, fine needle aspiration, hail region

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Authors: Ishani Majumdar, Jaishree Paul

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Introduction: Ulcerative Colitis (UC) is an inflammatory disease of the colon resulting from an autoimmune response towards individual’s own microbiota. Excessive inflammation is characterized by hyper-activation of NFkB, a transcription factor regulating expression of various pro-inflammatory genes. The ubiquitin editing complex consisting of TNFAIP3, ITCH, RNF11 and TAX1BP1 maintains homeostatic levels of active NFkB through feedback inhibition and assembles in response to various stimuli that activate NFkB. TNFAIP3 deubiquitinates key signaling molecules involved in NFkB activation pathway. ITCH, RNF11 and TAX1BP1 provide substrate specificity, acting as adaptors for TNFAIP3 function. Aim: This study aimed to find expression of members of the ubiquitin editing complex at the transcript level in inflamed colon tissues of UC patients. Materials and Methods: Colonic biopsy samples were collected from 30 UC patients recruited at Department of Gastroenterology, AIIMS (New Delhi). Control group (n= 10) consisted of individuals undergoing examination for functional disorders. Real Time PCR was used to determine relative expression with GAPDH as housekeeping gene. Results: Expression of members of the ubiquitin editing complex was significantly altered during active disease. Expression of TNFAIP3 was upregulated while concomitant decrease in expression of ITCH, RNF11, TAX1BP1 was seen in UC patients. Discussion: This study reveals that increase in expression of TNFAIP3 was unable to control inflammation during active UC. Further, insufficient upregulation of ITCH, RNF11, TAX1BP1 may limit the formation of the ubiquitin complex and contribute to pathogenesis of UC.

Keywords: altered expression, inflammation, ubiquitin editing complex, ulcerative colitis

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Authors: Abhimanyu Thakur, Youngjin Lee

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Glioma is a lethal brain cancer whose early diagnosis and prognosis are limited due to the dearth of a suitable technique for its early detection. Current approaches, including magnetic resonance imaging (MRI), computed tomography (CT), and invasive biopsy for the diagnosis of this lethal disease, hold several limitations, demanding an alternative method. Recently, extracellular vesicles (EVs) have been used in numerous biomarker studies, majorly exosomes and microvesicles (MVs), which are found in most of the cells and biofluids, including blood, cerebrospinal fluid (CSF), and urine. Remarkably, glioma cells (GMs) release a high number of EVs, which are found to cross the blood-brain-barrier (BBB) and impersonate the constituents of parent GMs including protein, and lncRNA; however, biophysical properties of EVs have not been explored yet as a biomarker for glioma. We isolated EVs from cell culture conditioned medium of GMs and regular primary culture, blood, and urine of wild-type (WT)- and glioma mouse models, and characterized by nano tracking analyzer, transmission electron microscopy, immunogold-EM, and differential light scanning. Next, we measured the biophysical parameters of GMs-EVs by using atomic force microscopy. Further, the functional constituents of EVs were examined by FTIR and Raman spectroscopy. Exosomes and MVs-derived from GMs, blood, and urine showed distinction biophysical parameters (roughness, adhesion force, and stiffness) and different from that of regular primary glial cells, WT-blood, and -urine, which can be attributed to the characteristic functional constituents. Therefore, biophysical features can be potential diagnostic biomarkers for glioma.

Keywords: glioma, extracellular vesicles, exosomes, microvesicles, biophysical properties

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Authors: Chih Jou Hsiao, Chung Ming Lo, Li Chun Hsieh

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Brain tumor is not the cancer having high incidence rate, but its high mortality rate and poor prognosis still make it as a big concern. On clinical examination, the grading of brain tumors depends on pathological features. However, there are some weak points of histopathological analysis which can cause misgrading. For example, the interpretations can be various without a well-known definition. Furthermore, the heterogeneity of malignant tumors is a challenge to extract meaningful tissues under surgical biopsy. With the development of magnetic resonance imaging (MRI), tumor grading can be accomplished by a noninvasive procedure. To improve the diagnostic accuracy further, this study proposed a computer-aided diagnosis (CAD) system based on MRI features to provide suggestions of tumor grading. Gliomas are the most common type of malignant brain tumors (about 70%). This study collected 34 glioblastomas (GBMs) and 73 lower-grade gliomas (LGGs) from The Cancer Imaging Archive. After defining the region-of-interests in MRI images, multiple quantitative morphological features such as region perimeter, region area, compactness, the mean and standard deviation of the normalized radial length, and moment features were extracted from the tumors for classification. As results, two of five morphological features and three of four image moment features achieved p values of <0.001, and the remaining moment feature had p value <0.05. Performance of the CAD system using the combination of all features achieved the accuracy of 83.18% in classifying the gliomas into LGG and GBM. The sensitivity is 70.59% and the specificity is 89.04%. The proposed system can become a second viewer on clinical examinations for radiologists.

Keywords: brain tumor, computer-aided diagnosis, gliomas, magnetic resonance imaging

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Authors: Shreya Ghosh, Akansha Garg, Chayanika Kala, Ashwani Kumar Thakur

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Background: Granuloma formation is one of the characteristic features of tuberculosis. Besides, chronic inflammation underlying tuberculosis is often indicated by an increase in the concentration of serum amyloid A (SAA) protein. The connection between tuberculosis and SAA-driven secondary amyloidosis is well documented. However, SAA-derived amyloid deposition start sites are not well understood in tuberculosis and other chronic inflammatory conditions. It was hypothesized that granuloma could be a potential site for an amyloid deposition because both SAA protein and proteases that cleave SAA into aggregation-prone fragments are reported to be present in the granuloma. Here the authors have shown the presence of SAA-derived amyloid deposits in the granuloma of tuberculosis patients. Methodology: Over a period of two years, tuberculosis patients were screened, and biopsies were collected from the affected organs of the patients. The gold standard, Congo red dye staining, was used to identify amyloid deposits in the tissue sections of tuberculosis patients containing granulomatous structure. Results: 11 out of 150 FFPE biopsy specimens of tuberculosis patients showed eosinophilic hyaline-rich deposits surrounding granuloma. Upon Congo red staining, these deposits exhibited characteristic apple-green birefringence under polarized light, confirming amyloid deposits. Further, upon immunohistochemical staining with anti-SAA, the amyloid enriched areas showed positive immunoreactivity. Conclusion: In this pilot study, we have shown that granuloma can be a potential site for serum amyloid A-derived amyloid formation in tuberculosis patients. Moreover, the presence of amyloid gave significant cues that granuloma might be a probable amyloid deposition start in tuberculosis patients. This study will set a stage to expand the clinical and fundamental research in the understanding of amyloid formation in granuloma underlying tuberculosis and chronic inflammatory conditions.

Keywords: amyloid, granuloma, periphery, serum amyloid A, tuberculosis

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Authors: Eldar Mammadov, Konul Mammadova, Aytaj Ilyaszada

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Background: According to many studies, it is known that H. pylori transform into the coccoid form, which cannot be cultured and has poor metabolic activity.In this study, we succeeded in preserving the spiral shape of H.pylori for a long time by preparing a biphase transport medium with a hard bottom (Muller Hinton with 7% HRBC (horse red blood cells) agar 5ml) and liquid top part (BH (brain heart) broth + HS (horse serum)+7% HRBC+antibiotics (Vancomycin 5 mg, Trimethoprim lactate 25 mg, Polymyxin B 1250 I.U.)) in cell culture flasks with filter caps. For comparison, we also used a BH broth medium with 7% HRBC used for the transport of H.pylori. Methods: Rapid urease test positive 7 biopsy specimens were also inoculated into biphasic and BH broth medium with 7% HRBC, then put in CO2 Gaspak packages and sent to the laboratory. Then both mediums were kept in the thermostat at 37 °C for 1 day. After microscopic, PCR and urease test diagnosis, they were transferred to Columbia Agar with 7% HRBC. Incubated at 37°C for 5-7 days, cultures were examined for colony characteristics and bacterial morphology. E-test antimicrobial susceptibility test was performed. Results: There were 3 growths from biphasic transport medium passed to Columbia agar with 7% HRBC and only 1 growth from BH broth medium with 7% HRBC. It was also observed that after the first 3 days in BH broth medium with 7%, H.pylori passed into coccoid form and its biochemical activity weakened, while its spiral shape did not change for 2-3 weeks in the biphase transport medium. Conclusions: By using the biphase transport medium we have prepared; we can culture the bacterium by preventing H.pylori from spiraling into the coccoid form. In our opinion, this may result in the wide use of culture method for diagnosis of H.pylori, study of antibiotic susceptibility and molecular genetic analysis.

Keywords: clinical trial, H.pylori, coccoid form, transport medium

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Authors: Deependra Prasad Sarraf, Ashish Shrestha, Mehul Rajesh Jaisani, Gajendra Prasad Rauniar

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Background: Honey is the worlds’ oldest known wound dressing. Its wound healing properties are not fully established till today. Concerns about antibiotic resistance, and a renewed interest in natural remedies have prompted the resurgence in the antimicrobial and wound healing properties of Honey. Evidence from animal studies and some trials has suggested that honey may accelerate wound healing in burns, infected wounds and open wounds. None of these reports have documented the effect of honey on the healing of socket after tooth extraction. Therefore, the present experimental study was planned to evaluate the efficacy of honey on the healing of socket after tooth extraction in rabbits. Materials and Methods: An experimental study was conducted in six New Zealand White rabbits. Extraction of first premolar tooth on both sides of the lower jaw was done under anesthesia produced by Ketamine and Xylazine followed by application of honey on one socket (test group) and normal saline (control group) in the opposite socket. The intervention was continued for two more days. On the 7th day, the biopsy was taken from the extraction site, and histopathological examination was done. Student’s t-test was used for comparison between the groups and differences were considered to be statistically significant at p-value less than 0.05. Results: There was a significant difference between control group and test group in terms of fibroblast proliferation (p = 0.0019) and bony trabeculae formation (p=0.0003). Inflammatory cells were also observed in both groups, and it was not significant (p=1.0). Overlying epithelium was hyperplastic in both the groups. Conclusion: The study showed that local application of honey promoted the rapid healing process particularly by increasing fibroblast proliferation and bony trabeculae.

Keywords: honey, extraction wound, Nepal, healing

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Authors: Aly Kassem, Eman A. Sabet, Hanaa A. El-Hady, Doha S. Mohamed, Abeer Sheneef, Mona Fattouh, Mamdouh M. Esmat

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Objective: Giardia lamblia parasite is the most common protozoal infection in human. Concomitant Helecobacter Pylori (H. pylori) and Giardia lamblia infection is common for their similar mode of transmission and strong correlation to socioeconomic levels. Only few reports had described gastric giardiasis. Our aim was to detect H. pylori and Giardia in gastric antral mucosal biopsies from patients with dyspepsia. The impact of both pathogens on clinical, endoscopic and histopathogical changes was studied. Methods: 48 patients with dyspepsia (group1) and 28 control patients (patients undergoing esophagogastroduodenoscopy EGD for reasons other than dyspepsia), (group 2) were studied. Endoscopic data were reported and gastric biopsy specimens were obtained for subsequent PCR assay for both organisms and for histopathological and electron microscopic examination. Results: Endoscopic antral gastritis and duodenal lesions were found in both groups, however, they were significantly more frequently in group 1 (p= 0.002 and P= 0.0005 respectively). Esophageal lesions, nodular antral gastritis, gastric ulcers and superficial corpal gastritis were found only in group 1. PCR detected H. pylori infection in 58% Vs 64 % for group 1 and group 2 respectively (P: NS). Giardia infection was present in 67 % Vs 42 % for group 1 and group 2 respectively (P=0.0003, Odd ratio=2.6). Co-infection with H. pylori and Giardia was present in 33% of group 1 Vs 36% for group 2 (P:NS). Abnormal histologic findings were found in both groups, however, intestinal metaplasia was found in group 1 only. Cellular abnormalities in the form of cytoplasmic vacuoles, mitochondrial destruction or nuclear abnormalities were found by Electron microscopic study in infected subjects of both groups. Conclusion: H. pylori is not the only gastric pathogen in our community, gastric giardiasis is another pathogen. Its contribution might be a factor in persistent dyspepsia after H. pylori eradication.

Keywords: dyspepsia, gastritis, Giardia lamblia, H. pylori

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Authors: H. Hadjeris, R. B. Ghoul, Lekhlaf, M. Nebbal

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Introduction: Adenoid cystic carcinomas of the lacrimal gland or orbital cylindroma constitute the second cause of epithelial tumors of this gland. It is a malignant tumor usually developed at the expense of the salivary glands; its orbital location is exceptional. It is a rare clinical entity, formidable by its malignancy and local aggressiveness; the recurrence rate is high. Materials and methods: Clinical case: 63 years old woman who presents with irreducible no pulsatile painful left exophthalmos with inflammatory chemosis and a decrease in visual acuity with a moderate intracranial hypertension syndrome that has been evolving for 03 months. Antecedent; a biopsy of the tumor was made; the histological examination was in favor of an adenoid cystic carcinoma of the lacrimal gland. Lesion assessment: computed tomography and brain MRI: show an intra and extra-conical mass; with sinus (ethmoido-frontal) and cerebral (left frontal) extension strongly enhanced after injection of contrast product surrounded by edema around the lesion, associated with left frontal bone lysis extension assessment: unremarkable treatment: Patient operated by left frontotemporal approach, a total exenteration was performed with macroscopically complete excision of the frontal lesion and wide frontal craniectomy with craniofacial reconstruction, followed by complementary radiotherapy. Results: The patient was seen again after 3 months in consultation; she does not present any signs in favor of a recurrence. Conclusion: Adenoid cystic carcinomas of the lacrimal gland are rare malignant tumors; they are very infiltrating and invasive. The prognosis is strongly linked to the treatment time.

Keywords: adenoid cystic, lacrimal gland, orbital location, fronto-temporal approac

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Authors: K. M. Pratap Shankar, Dattatreya Rao, Sai Prasad

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Background: Skin diseases are among the most common health problems worldwide and are associated with a considerable burden. Eczema is such a skin ailment which cause psychological, social and financial burden on the patient and their families. Management of eczema with antibiotics, antihistamines, steroids etc., are available but even after their use relapses, recurrences and other complications are very common. Aim: The aim of this study was to assess the efficacy of leech application in the management of vicarcikā (Eczema) with Histopathological study. Methods: For the present study 10 patients having the classical symptoms of Vicarcikā, were randomly selected as per the inclusion and exclusion criteria from O.P.D. & I.P.D. sections of Śalya department, S.V. Āyurvedic Hospital, Tirupati. Minimum 4 sittings of Leech application was carried out with seven days interval. Total duration of treatment was 6 weeks. Biopsy samples were collected from the lesion site before and after treatment. Histopathological examination was done by the pathologist. Results: In eczema (dermatitis) the leech application therapy gives excellent response by reducing the inflammatory component, hyperkeratosis, spongiosis, irregular acanthosis and by evoking a granulation tissue response in the dermis and in most of the cases with complete recovery from the lesion. Most of the cases in the study were chronic dermatitis and sebhoric keratosis, almost all local/focal pigmented lesions is totally relieved by leech therapy especially in cases of sebhoric keratosis. Conclusion: In the present study it was found that, leech application evokes significant changes at histological level specifically in reduction of inflammatory component, hyperkeratosis, spongiosis and irregular acanthosis. It was also found that there was a considerable formation of granulation tissue, which helps in formation of healthy new tissues.

Keywords: acanthosis, eczema, hyperkeratosis, leech application, spongiosis

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Authors: Aniqa Jabeen

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The aim of this study was to evaluate the effectiveness of Tc-99m MIBI (Technetium 99-methoxy-iso-butyl-isonitrile) scintigraphy to differentiate malignancies from benign lesions, which were detected on planar bone scans. Materials and Methods: 59 patients with bone lesions were enrolled in the study. The scintigraphic findings were compared with the clinical, radiological and the histological findings. Each patient initially underwent a three-phase bone scan with Tc-99m MDP (Methylene Diphosphonate) and if evidence of lesion found, the patient then underwent a dynamic and static MIBI scintigraphy after three to four days. The MDP and MIBI scans were evaluated visually and quantitatively. For quantitative analysis count ratios of lesions and contralateral normal side (L/C) were taken by region of interests drawn on scans. The Student T test was applied to assess the significant difference between benign and malignant lesions p-value < 0.05 was considered significant. Result: The MDP scans showed the increase tracer uptake, but there was no significant difference between benign and malignant uptake of the radiotracer. However significant difference (p-value 0.015), in uptake was seen in malignant (L/C = 3.51 ± 1.02) and benign lesion (L/C = 2.50±0.42) on MIBI scan. Three of thirty benign lesions did not show significant MIBI uptake. Seven malignant appeared as false negatives. Specificity of the scan was 86.66%, and its Negative Predictive Value (NPV) was 81.25% whereas the sensitivity of scan was 79.31%. In excluding the axial metastasis from the lesions, the sensitivity of MIBI scan increased to 91.66% and the NPV also increased to 92.85%. Conclusion: MIBI scintigraphy provides its usefulness by distinguishing malignant from benign lesions. MIBI also correctly identifies metastatic lesions. The negative predictive value of the scan points towards its ability to accurately diagnose the normal (benign) cases. However, biopsy remains the gold standard and a definitive diagnostic modality in musculoskeletal tumors. MIBI scan provides useful information in preoperative assessment and in distinguishing between malignant and benign lesions.

Keywords: benign, malignancies, MDP bone scan, MIBI scintigraphy

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Authors: Soumaya Mrabet, Imen Akkari, Amira Atig, Elhem Ben Jazia

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Introduction: Primary biliary cirrhosis (PBC) is a cholestatic cholangitis of unknown etiology. It is frequently associated with autoimmune diseases, which explains their systematic screening. The aim of our study was to determine the prevalence and the type of autoimmune disorders associated with PBC and to assess their impact on the prognosis of the disease. Material and methods: It is a retrospective study over a period of 16 years (2000-2015) including all patients followed for PBC. In all these patients we have systematically researched: dysthyroidism (thyroid balance, antithyroid autoantibodies), type 1 diabetes, dry syndrome (ophthalmologic examination, Schirmer test and lip biopsy in case of Presence of suggestive clinical signs), celiac disease(celiac disease serology and duodenal biopsies) and dermatological involvement (clinical examination). Results: Fifty-one patients (50 women and one men) followed for PBC were collected. The Mean age was 54 years (37-77 years). Among these patients, 30 patients(58.8%) had at least one autoimmune disease associated with PBC. The discovery of these autoimmune diseases preceded the diagnosis of PBC in 8 cases (26.6%) and was concomitant, through systematic screening, in the remaining cases. Autoimmune hepatitis was found in 12 patients (40%), defining thus an overlap syndrome. Other diseases were Hashimoto's thyroiditis (n = 10), dry syndrome (n = 7), Gougerot Sjogren syndrome (n=6), celiac disease (n = 3), insulin-dependent diabetes (n = 1), scleroderma (n = 1), rheumatoid arthritis (n = 1), Biermer Anemia (n=1) and Systemic erythematosus lupus (n=1). The two groups of patients with PBC with or without associated autoimmune disorders were comparable for bilirubin levels, Child-Pugh score, and response to treatment. Conclusion: In our series, the prevalence of autoimmune diseases in PBC was 58.8%. These diseases were dominated by autoimmune hepatitis and Hashimoto's thyroiditis. Even if their association does not seem to alter the prognosis, screening should be systematic in order to institute an early and adequate management.

Keywords: autoimmune diseases, autoimmune hepatitis, primary biliary cirrhosis, prognosis

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Authors: W. Mohammedsaeed, A. J. Mcbain, S. M. Cruickshank, C. A. O’Neill

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Many studies have demonstrated the importance of probiotics and their potential therapeutic effects within the gut. Recently, the possible therapeutic effects of probiotics in other tissues have also begun to be investigated. Comparatively few studies have evaluated the use of topical probiotics in relation to the skin. In this study, we have conducted preliminary investigations into whether a well-known probiotic, Lactobacillus rhamnosus GG (LGG), can increase the rate of re-epithelialization in a model wound. Full-thickness skin was obtained from individuals undergoing elective cosmetic surgery. This skin was wounded using excisional punch and cultured using a serum-free medium, either in the presence or absence of L. rhamnosus GG lysate. Histological staining of the sections was performed with Haematoxylin& Eosin E to quantify “epithelial tongue length”. This is the length of the new epithelial ‘tongue’ that grows and covers the exposed dermis at the inner wound edges. The length of the new epithelial ‘tongue’ was compared in untreated section and section treated with and L. rhamnosus GG made using108CFU/ml bacterial cells. L. rhamnosus GG lysate enhanced significantly the re-epithelialisation of treated wounds compared with that of untreated wounds (P=0.005, n=3). Tongue length, at day 1 was 7.55μm 0.15, at day 3 it was 18.5μm 0.25 and at day 7 was 22.9μm 0.35. These results can be compared with untreated cultures in which tongue length was 3.25μm 0.35, day 3 was 9.65μm 0.25 and day 7 was 13.5μm 0.15 post-wounding. In ex-vivo proliferation and migration cells were measured by determining the expression of nuclear proliferation marker Ki-67 and the expression of Phosphorylated cortactin respectively demonstrated that L. rhamnosus GG significantly increased NHEK proliferation and migration rates relative to controls. However, the dominant mechanism was migration because in ex-vivo skin treated with the L. rhamnosus GG up-regulated the gene expression of the chemokine receptor and ligands CXCR2 and CXCL2 comparing with controls (P=0.02, P=0.03 respectively, n=3). High levels of CXCL2/CXCL2 have already been implicated in multiple aspects of stimulation of wound healing through activation of keratinocyte migration. These data demonstrate that lysates from Lactobacillus rhamnosus GG increase re-epithelialization by stimulation of keratinocyte migration. The current study identifies the partial mechanism that contribute to stimulating the wound-healing process ex vivo in response to L. rhamnosus GG lysate is an increase in the production of CXCL2/ CXCR2 in ex vivo models. The use of probiotic lysates potentially offers new options to develop treatments that could improve wound healing.

Keywords: Lactobacillus rhamnosus GG, wounds, migration, lysate

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Authors: Sumera, Sanila Amber, Fatima Javed Mirza, Amjad Ali, Saadia Zahid

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Glioblastoma multiforme (GBM) is a widely spread and fatal primary brain tumor with an increased risk of relapse in spite of aggressive treatment. The current procedures for GBM diagnosis include invasive procedures i.e. resection or biopsy, to acquire tumor mass. Implementation of negligibly invasive tests as a potential diagnostic technique and biofluid-based monitoring of GBM stresses on discovering biomarkers in CSF and blood. Therefore, we performed a comprehensive in silico analysis to identify potential circulating biomarkers for GBM. Initially, six gene and protein databases were utilized to mine brain-specific proteins. The resulting proteins were filtered using a channel of five tools to predict the secretory proteins. Subsequently, the expression profile of the secreted proteins was verified in the brain and blood using two databases. Additional verification of the resulting proteins was done using Plasma Proteome Database (PPD) to confirm their presence in blood. The final set of proteins was searched in literature for their relationship with GBM, keeping a special emphasis on secretome proteome. 2145 proteins were firstly mined as brain-specific, out of which 69 proteins were identified as secretory in nature. Verification of expression profile in brain and blood eliminated 58 proteins from the 69 proteins, providing a final list of 11 proteins. Further verification of these 11 proteins further eliminated 2 proteins, giving a final set of nine secretory proteins i.e. OPCML, NPTX1, LGI1, CNTN2, LY6H, SLIT1, CREG2, GDF1 and SERPINI1. Out of these 9 proteins, 7 were found to be linked to GBM, whereas 2 proteins are not investigated in GBM so far. We propose that these secretory proteins can serve as potential circulating biomarker signatures of GBM and will facilitate the development of minimally invasive diagnostic methods and novel therapeutic interventions for GBM.

Keywords: glioblastoma multiforme, secretory proteins, brain secretome, biomarkers

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Authors: Himanshu Rohela

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BACKGROUND: Ewing sarcoma can arise in either bone or soft tissue. Extraskeletal Ewing sarcoma (EES) is an uncommon primary tumor of the soft tissues, accounting for 20 30% of all reported cases of ES. AIM: Was to investigate demographic distribution, survival analysis and factors affecting the survival and recurrence in patients of EES. METHODS: Retrospective study of 19 biopsy-proven EES was performed. Overall survival (OS) using log-rank test and factors affecting OS and local recurrence (LR) were evaluated for the entire cohort. RESULTS: Patients with EES had a mean age of 19.5 and it was more commonly seen in males (63%). Axial location (58%) and solitary presentation (84%) were more common. The average size was 11 cm, 3 of 19 were metastatic at presentation, with the lung beings the most common site for metastasis. 17 received NACT, 16 with VAC-IE regimen and 1 underwent a second line with GEM/DOCE regimen. Unplanned surgery was done in 2 of 19. 3 patients received definitive RT and 13 underwent surgical-wide local excision. 2 of 13 showed good response to NACT. 10 patients required readmission out of which 6 patients had chemotherapy-related complications, 2 had surgical site complications and one patient developed secondary AML post-completion of treatment. A total of 4 patients had a recurrence. One had local recurrence alone, one had distant recurrence alone and 2 patients had a distant and local recurrence both. Tumor size >10 cm, axial location, and previous unplanned surgery was associated with higher LR rate. The mean overall survival was 32 months (2.66 years), with higher rates seen in non-metastatic and non-recurrent settings. CONCLUSIONS: Early and accurate diagnosis is the key to the management of EES, with promising results seen via NACT and RO resection regimens. But further studies with larger study groups are needed to standardize the treatment protocol and evaluate its efficacy.

Keywords: Ewings, sarcoma, extraskeletal, chemotherapy

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