Search results for: pathological subtype

Authors: Yu-Wen Cheng, Jau-Der Ho, Liang-Huan Wu, Fan-Li Lin, Li-Huei Chen, Hung-Ming Chang, Yueh-Hsiung Kuo, George Hsiao

Abstract:

Retina glial activation and neuroinflammation have been confirmed to cause devastating responses in retinodegenerative diseases. The expression and activation of matrix metalloproteinase (MMP)-9 and inducible nitric oxide synthase (iNOS) could be exerted as the crucial pathological factors in glaucoma- and blue light-induced retinal injuries. The present study aimed to investigate the retinoprotective effects and mechanisms of fungal ingredient 3,4-dihydroxybenzalacetone (DBL) isolated from Phellinus linteus in the retinal glial activation and retinodegenerative animal models. According to the cellular studies, DBL significantly and concentration-dependently abrogated MMP-9 activation and expression in TNFα-stimulated retinal Müller (rMC-1) cells. We found the inhibitory activities of DBL were strongly through the STAT- and ERK-dependent pathways. Furthermore, DBL dramatically attenuated MMP-9 activation in the stimulated Müller cells exposed to conditioned media from LPS-stimulated microglia BV-2 cells. On the other hand, DBL strongly suppressed LPS-induced production of NO and ROS and expression of iNOS in microglia BV-2 cells. Consistently, the phosphorylation of STAT was substantially blocked by DBL in LPS-stimulated microglia BV-2 cells. In the evaluation of retinoprotective functions, the high IOP-induced scotopic electroretinographic (ERG) deficit and blue light-induced abnormal pupillary light response (PLR) were assessed. The deficit scotopic ERG responses markedly recovered by DBL in a rat model of glaucoma-like ischemia/reperfusion (I/R)-injury. DBL also reduced the aqueous gelatinolytic activity and retinal MMP-9 expression in high IOP-injured conditions. Additionally, DBL could restore the abnormal PLR and reduce retinal MMP-9 activation. In summary, DBL could ameliorate retinal neuroinflammation and MMP-9 activation by predominantly inhibiting STAT3 activation in the retinal Müller cells and microglia, which exhibits therapeutic potential for glaucoma and other retinal degenerative diseases.

Keywords: glaucoma, blue light, DBL, retinal Müller cell, MMP-9, STAT, Microglia, iNOS, ERG, PLR

Procedia PDF Downloads 111

Authors: Manas Kotepui, Kwuntida Uthaisar, Phiman Thirarattanasunthon, Bhukdee PhunPhuech, Nuoil Phiwklam

Abstract:

Introduction: Malaria due to Plasmodium vivax has placed huge burdens on the health, longevity, and general prosperity of large sections of the human population. This study aimed at prospectively collecting information on the clinical profile of Plasmodium vivax from subjects acutely infected with P. vivax residing in some of the highest malaria transmission regions in Thailand. Methods: A retrospective study of malaria cases, hospitalized between 2013 and 2015 was performed. Clinical characteristics, diagnosis, and parasitological results on admission, age, and gender were mined from medical records at Phop Phra Hospital located in endemic areas of Tak Province, Thailand. Venous blood samples were collected at the time of admission to the hospital to determine the present of parasite and also parasite count by thick and thin film examination, and also Complete blood count (CBC) parameters. Results: Results showed that patients infected with Plasmodium vivax (276 cases) had a high monocyte count (mean=390 cells/µL) during initial stage of infection and continuously lower during later stage (any stage with gametocyte, mean=230 cells/µL) of infection (P value=0.021) whereas, patients infected with Plasmodium vivax had a low basophil count (mean=20 cells/µL) during initial stage of infection and continuously higher during later stage of infection (mean at stage with gametocyte=70 cells/µL) (P value=0.033). In addition, patients with more than one stage infection tend to have lower lymphocyte count (mean=1180 cells/µL) than patients with only one stage infection (mean=1350 cells/µL)(P value=0.011) whereas, patients with more than one stage infection tend to have lower basophil count (mean=60 cells/µL) than patients with only one stage infection (mean=80 cells/µL) (P value=0.01). Conclusion: This study indicated that patients infected with Plasmodium vivax had high monocyte count and low basophil count during initial stage of infection which was continuously lower during later stage of infection. Patients with more than one stage infection tend to have lower lymphocyte count than patients with only one stage infection whereas, patients with more than one stage infection tend to have lower basophil count than patients with only one stage infection. This information contributes to better understanding of pathological characteristic of Plasmodium vivax infection.

Keywords: plasmodium vivax, Thailand, asexual erythrocytic stages, hematological parameters

Procedia PDF Downloads 180

Authors: Maryam Radan, Fereshteh Nejad Dehbashi, Vahid Bayati, Mahin Dianat, Seyyed Ali Mard, Zahra Mansouri

Abstract:

Pulmonary emphysema is a pathological respiratory condition identified by alveolar destruction which leads to limitation of airflow and diminished lung function. A substantial body of evidence suggests that mesenchymal stem cells (MSCs) have the ability to induce tissue repair primarily through a paracrine effect. In this study, we aimed to determine the efficacy of Intratracheal adipose-derived mesenchymal stem cells (ADSCs) therapy in comparison to this approach with that of Intravenous (Systemic) therapy. Fifty adult male Sprague–Dawley rats weighing between 180 and 200 g were used in this experiment. The animals were randomized to Control groups (Intratracheal or Intravenous vehicle), Elastase group (intratracheal administration of porcine pancreatic elastase; 25 U/kg on day 0 and day 10th), Elastase+Intratracheal ADSCs therapy (1x107 Cells, on day 28) and Elastase+Systemic ADSCs therapy (1x107 Cells, on day 28). The rats which not subjected to any treatment, considered as the control. All rats were sacrificed 3 weeks later. Morphometric findings in lung tissues (Mean linear intercept) confirmed the establishment of the emphysema model via alveolar disruption. Contrarily, ADSCs administration partially restored alveolar architecture. These results were associated with improving arterial oxygenation, reducing lung edema, and decreasing lung inflammation with higher significant effects in the Intratracheal therapy route. These results documented that the efficacy of intratracheal ADSCs was comparable with intravenous ADSCs therapy. Accordingly, the obtained data suggested that intratracheal delivery of ADSCs would enhance lung repair in pulmonary emphysema. Moreover, this method provides benefits over a systemic administration, such as the reduction of cell number and the low risk to engraft other organs.

Keywords: mesenchymal stem cell, emphysema, Intratracheal, systemic

Procedia PDF Downloads 183

Authors: Gi-Young Park, Dong Rak Kwon, Sung Cheol Cho

Abstract:

Objective: The synovium is known to be involved in many pathological characteristic processes. Also, synovitis is common in advanced osteoarthritis. We aimed to evaluate the clinical, radiographic, and ultrasound findings in patients with knee osteoarthritis and to compare the clinical and imaging findings between knee osteoarthritis with and without synovial hypertrophy confirmed by ultrasound. Methods: One hundred knees (54 left, 46 right) in 95 patients (64 women, 31 men; mean age, 65.9 years; range, 43-85 years) with knee osteoarthritis were recruited. The Visual Analogue Scale (VAS) was used to assess the intensity of knee pain. The severity of knee osteoarthritis was classified according to Kellgren and Lawrence's (K-L) grade on a radiograph. Ultrasound examination was performed by a physiatrist who had 24 years of experience in musculoskeletal ultrasound. Ultrasound findings, including the thickness of joint effusion in the suprapatellar pouch, synovial hypertrophy, infrapatellar tendinosis, meniscal tear or extrusion, and Baker cyst, were measured and detected. The thickness of knee joint effusion was measured at the maximal anterior-posterior diameter of fluid collection in the suprapatellar pouch. Synovial hypertrophy was identified as the soft tissue of variable echogenicity, which is poorly compressible and nondisplaceable by compression of an ultrasound transducer. The knees were divided into two groups according to the presence of synovial hypertrophy. The differences in clinical and imaging findings between the two groups were evaluated by independent t-test and chi-square test. Results: Synovial hypertrophy was detected in 48 knees of 100 knees on ultrasound. There were no significant differences in demographic parameters and VAS score except in sex between the two groups (P<0.05). Medial meniscal extrusion and tear were significantly more frequent in knees with synovial hypertrophy than those in knees without synovial hypertrophy. K-L grade and joint effusion thickness were greater in patients with synovial hypertrophy than those in patients without synovial hypertrophy (P<0.05). Conclusion: Synovial hypertrophy in knee osteoarthritis was associated with greater suprapatellar joint effusion and higher K-L grade and maybe a characteristic ultrasound feature of late knee osteoarthritis. These results suggest that synovial hypertrophy on ultrasound can be regarded as a predictor of rapid progression in patients with knee osteoarthritis.

Keywords: knee osteoarthritis, synovial hypertrophy, ultrasound, K-L grade

Procedia PDF Downloads 47

Authors: Laura Gleason, Sahithi Talasila, Lauren Banner, Ladan Afifi, Neda Nikbakht

Abstract:

Primary cutaneous anaplastic large cell lymphoma (pcALCL) accounts for 9% of all cutaneous T-cell lymphomas. pcALCL is classically characterized as a solitary papulonodule that often enlarges, ulcerates, and can be locally destructive, but overall exhibits an indolent course with overall 5-year survival estimated to be 90%. Distinguishing pcALCL from systemic ALCL (sALCL) is essential as sALCL confers a poorer prognosis with average 5-year survival being 40-50%. Although extremely rare, there have been several cases of ALK-positive ALCL diagnosed on skin biopsy without evidence of systemic involvement, which poses several challenges in the classification, prognostication, treatment, and follow-up of these patients. Objectives: We present a case of cutaneous ALK-positive ALCL without evidence of systemic involvement, and a narrative review of the literature to further characterize that ALK-positive ALCL limited to the skin is a distinct variant with a unique presentation, history, and prognosis. A 30-year-old woman presented for evaluation of an erythematous-violaceous papule present on her right chest for two months. With the development of multifocal disease and persistent lymphadenopathy, a bone marrow biopsy and lymph node excisional biopsy were performed to assess for systemic disease. Both biopsies were unrevealing. The patient was counseled on pursuing systemic therapy consisting of Brentuximab, Cyclophosphamide, Doxorubicin, and Prednisone given the concern for sALCL. Apropos of the patient we searched for clinically evident, cutaneous ALK-positive ALCL cases, with and without systemic involvement, in the English literature. Risk factors, such as tumor location, number, size, ALK localization, ALK translocations, and recurrence, were evaluated in cases of cutaneous ALK-positive ALCL. The majority of patients with cutaneous ALK-positive ALCL did not progress to systemic disease. The majority of cases that progressed to systemic disease in adults had recurring skin lesions and cytoplasmic localization of ALK. ALK translocations did not influence disease progression. Mean time to disease progression was 16.7 months, and significant mortality (50%) was observed in those cases that progressed to systemic disease. Pediatric cases did not exhibit a trend similar to adult cases. In both the adult and pediatric cases, a subset of cutaneous-limited ALK-positive ALCL were treated with chemotherapy. All cases treated with chemotherapy did not progress to systemic disease. Apropos of an ALK-positive ALCL patient with clinical cutaneous limited disease in the histologic presence of systemic markers, we discussed the literature data, highlighting the crucial issues related to developing a clinical strategy to approach this rare subtype of ALCL. Physicians need to be aware of the overall spectrum of ALCL, including cutaneous limited disease, systemic disease, disease with NPM-ALK translocation, disease with ALK and EMA positivity, and disease with skin recurrence.

Keywords: anaplastic large cell lymphoma, systemic, cutaneous, anaplastic lymphoma kinase, ALK, ALCL, sALCL, pcALCL, cALCL

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Authors: Esther Mafunda, Simbarashe Muparangi

Abstract:

The present paper tests the applicability of the Regression Hypothesis on the pathological language dissolution of a Shona male adult with Broca’s aphasia. It particularly assesses the prediction of the Regression Hypothesis, which states that the process according to which language is forgotten will be the reversal of the process according to which it will be acquired. The main aim of the paper is to find out whether mirror symmetries between L1 acquisition and L1 dissolution of tense in Shona and, if so, what might cause these regression patterns. The paper also sought to highlight the practical contributions that Linguistic theory can make to solving language-related problems. Data was collected from a 46-year-old male adult with Broca’s aphasia who was receiving speech therapy at St Giles Rehabilitation Centre in Harare, Zimbabwe. The primary data elicitation method was experimental, using the probe technique. The TART (Test for Assessing Reference Time) Shona version in the form of sequencing pictures was used to access tense by Broca’s aphasic and 3.5-year-old child. Using the SPSS (Statistical Package for Social Studies) and Excel analysis, it was established that the use of the future tense was impaired in Shona Broca’s aphasic whilst the present and past tense was intact. However, though the past tense was intact in the male adult with Broca’s aphasic, a reference to the remote past was made. The use of the future tense was also found to be difficult for the 3,5-year-old speaking child. No difficulties were encountered in using the present and past tenses. This means that mirror symmetries were found between L1 acquisition and L1 dissolution of tense in Shona. On the basis of the results of this research, it can be concluded that the use of tense in a Shona adult with Broca’s aphasia supports the Regression Hypothesis. The findings of this study are important in terms of speech therapy in the context of Zimbabwe. The study also contributes to Bantu linguistics in general and to Shona linguistics in particular. Further studies could also be done focusing on the rest of the Bantu language varieties in terms of aphasia.

Keywords: Broca’s Aphasia, regression hypothesis, Shona, language dissolution

Procedia PDF Downloads 61

Authors: Rajesh Kumar Suman, Ipseeta Ray Mohanty, Manjusha K. Borde, Ujjawala maheswari, Y. A. Deshmukh

Abstract:

Background: Metabolic syndrome encompasses cluster of risk factors for cardiovascular disease which includes abdominal obesity, dyslipidemia, hypertension, and hyperglycemia. The incidence of metabolic syndrome is on the rise globally. Objective: The present study was designed to develop a unique animal model that will mimic the pathological features seen in a large pool of individuals with diabetes and metabolic syndrome; suitable for pharmacological screening of drugs beneficial in this condition. Material and Methods: A combination of high fat diet (HFD) and low dose of streptozotocin (STZ) at 30, 35 and 40 mg/kg was used to induce metabolic syndrome co-existing with diabetes mellitus in Wistar rats. Results: The 40 mg/kg STZ produced sustained hyperglycemia and the dose was thus selected for our study to induce diabetes mellitus. Rat fed HFD (HF-DC) group showed significant (p < 0.001) increase in body weight on 4th and 7th week as compared with NC (Normal Control) group rats. However, the increase in body weight of HF-DC group rats was not sustained at the end of 10th weeks. Various components of metabolic syndrome such as dyslipidemia {(Increased Triglyceride, total Cholesterol, LDL Cholesterol and decreased HDL Cholesterol)}, diabetes mellitus (Blood Glucose, HbA1c, Serum Insulin, C-peptide), hypertension {Systolic Blood pressure (p < 0.001)} were mimicked in the developed model of metabolic syndrome co existing with diabetes mellitus. In addition significant cardiac injury as indicated by CPK-MB levels, artherogenic index, hs-CRP. The decline in hepatic function {(p < 0.01) increase in the level of SGPT (U/L)} and renal function {(increase in creatinine levels (p < 0.01)} when compared to NC group rats. The histopathological assessment confirmed presence of edema, necrosis and inflammation in Heart, Pancreas, Liver and Kidney of HFD-DC group as compared to NC. Conclusion: The present study has developed a unique rodent model of metabolic syndrome; with diabetes as an essential component.

Keywords: diabetes, metabolic syndrome, high fat diet, streptozotocin, rats

Procedia PDF Downloads 326

Authors: Fumihiro Ima, Shinichi Watanabe, Shingo Maeda, Haruna Imai, Hiroki Niimi

Abstract:

It is important to know growth rate of brain tumors before surgery because it influences treatment planning including not only surgical resection strategy but also adjuvant therapy after surgery. Amide proton transfer (APT) imaging is an emerging molecular magnetic resonance imaging (MRI) technique based on chemical exchange saturation transfer without administration of contrast medium. The underlying assumption in APT imaging of tumors is that there is a close relationship between the proliferative activity of the tumor and mobile protein synthesis. We aimed to evaluate the diagnostic performance of APT imaging of pre-and post-treatment brain tumors. Ten patients with brain tumor underwent conventional and APT-weighted sequences on a 3.0 Tesla MRI before clinical intervention. The maximum and the minimum APT-weighted signals (APTWmax and APTWmin) in each solid tumor region were obtained and compared before and after clinical intervention. All surgical specimens were examined for histopathological diagnosis. Eight of ten patients underwent adjuvant therapy after surgery. Histopathological diagnosis was glioma in 7 patients (WHO grade 2 in 2 patients, WHO grade 3 in 3 patients and WHO grade 4 in 2 patients), meningioma WHO grade1 in 2 patients and primary lymphoma of the brain in 1 patient. High-grade gliomas showed significantly higher APTW-signals than that in low-grade gliomas. APTWmax in one huge parasagittal meningioma infiltrating into the skull bone was higher than that in glioma WHO grade 4. On the other hand, APTWmax in another convexity meningioma was the same as that in glioma WHO grade 3. Diagnosis of primary lymphoma of the brain was possible with APT imaging before pathological confirmation. APTW-signals in residual tumors decreased dramatically within one year after adjuvant therapy in all patients. APT imaging demonstrated excellent diagnostic performance for the planning of surgery and adjuvant therapy of brain tumors.

Keywords: amides, magnetic resonance imaging, brain tumors, cell proliferation

Procedia PDF Downloads 115

Authors: Arjun Prakash, Samanvitha H.

Abstract:

BACKGROUND: Breast cancer is the commonest malignancy among women globally, with an estimated incidence of 2.3 million new cases as of 2020, representing 11.7% of all malignancies. As per Globocan data 2020, it accounted for 13.5% of all cancers and 10.6% of all cancer deaths in India. Early diagnosis and treatment can improve the overall morbidity and mortality, which necessitates the importance of differentiating benign from malignant breast masses. OBJECTIVE: The objective of the present study was to evaluate and compare the role of Digital Mammography (DM), B mode Ultrasound (USG), Shear Wave Elastography (SWE) and Strain Elastography (SE) in differentiating benign and malignant breast masses (ACR BI-RADS 3 - 5). Histo-Pathological Examination (HPE) was considered the Gold standard. MATERIALS & METHODS: We conducted a cross-sectional study on 53 patients with 64 breast masses over a period of 10 months. All patients underwent DM, USG, SWE and SE. These modalities were individually assessed to know their accuracy in differentiating benign and malignant masses. All Digital Mammograms were done using the Fujifilm AMULET Innovality Digital Mammography system and all Ultrasound examinations were performed on SAMSUNG RS 80 EVO Ultrasound system equipped with 2 to 9 MHz and 3 – 16 MHz linear transducers. All masses were subjected to HPE. Independent t-test and Chi-square or Fisher’s exact test were used to assess continuous and categorical variables, respectively. ROC analysis was done to assess the accuracy of diagnostic tests. RESULTS: Of 64 lesions, 51 (79.68%) were malignant and 13 (20.31%) (p < 0.0001) were benign. SE was the most specific (100%) (p < 0.0001) and USG (98%) (p < 0.0001) was the most sensitive of all the modalities. E max, E mean, E max ratio, E mean ratio and Strain Ratio of the malignant masses significantly differed from those of the benign masses. Maximum SWE value showed the highest sensitivity (88.2%) (p < 0.0001) among the elastography parameters. A combination of USG, SE and SWE had good sensitivity (86%) (p < 0.0001). CONCLUSION: A combination of USG, SE and SWE improves overall diagnostic yield in differentiating benign and malignant breast masses. Early diagnosis and treatment of breast carcinoma will reduce patient mortality and morbidity.

Keywords: digital mammography, breast cancer, ultrasound, elastography

Procedia PDF Downloads 77

Authors: S. El Ballal, H. El Sabbagh, M. Abd El Gaber, A. Eisa, A. Al Gamal

Abstract:

Cadmium is one of the most harmful heavy metals able to induce severe injury. In this study, sixty four male Sprague Dawley rats weighing (70-80 gm) were used. Rats were divided into 4 groups each group of 16 rats. Group A: served as control and received commercial ration and distilled water Group B: cadmium chloride was administered orally in water at dose of 300 ppm cadmium (560 mg/L as CdCl2). Group C: Animals received cadmium in drinking water in addition to administration of N-acetylcysteine (NAC) orally at a dose of 150 mg/kg body weight, equivalent to 1500 ppm in food. Group D: Animals received cadmium in drinking water in addition to administration of alpha lipoic acid (ALA) orally at a dose of 150 mg/kg body weight, equivalent to 1500 ppm in food. The experiment was continued for 2 months. Collection of blood and tissue samples was performed at 2, 4, 6, 8 weeks. Blood sample were collected for serum biochemical analysis including malondialdehyde (MDA), total antioxidants, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total protein, albumin, urea and uric acid. Tissue specimens were collected for histopathological examination including liver, kidney, brain and testis. Histopathological examination revealed that cadmium choloride induces pathological alterations which increased in severity with time. The use of NAC and ALA can ameliorate toxic effect of CdCl2. The results showed significant decrease MDA and significant increase total antioxidants in group C and D compared to group B, Liver enzymes include AST and ALT showed significant decrease. Regarding to results of total protein and albumin, they revealed significant increase. Urea and uric acid showed significant decrease. From our study we conclude that NAC and ALA have protective effect against cadmium toxicity.

Keywords: ALA, cadmium, histopathology, NAC

Procedia PDF Downloads 315

Authors: Sonia Mahajan Dinesh, Anant Dinesh, Madhavi Tripathi, Vinod Kumar Ramteke, Rajnish Sharma, Anupam Mondal

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Background: Neo-adjuvant chemotherapy plays an important role in treatment of breast cancer by decreasing the tumour load and it offers an opportunity to evaluate response of primary tumour to chemotherapy. Standard anatomical imaging modalities are unable to accurately reflect the response to chemotherapy until several cycles of drug treatment have been completed. Metabolic imaging using tracers like 18F-fluorodeoxyglucose (FDG) as a marker of glucose metabolism or amino acid tracers like L-methyl-11C methionine (MET) have potential role for the measurement of treatment response. In this study, our objective was to compare these two PET tracers for assessment of response to neoadjuvant chemotherapy, in locally advanced breast carcinoma. Methods: In our prospective study, 20 female patients with histology proven locally advanced breast carcinoma underwent PET-CT imaging using FDG and MET before and after three cycles of neoadjuvant chemotherapy (CAF regimen). Thereafter, all patients were taken for MRM and the resected specimen was sent for histo-pathological analysis. Tumour response to the neoadjuvant chemotherapy was evaluated by PET-CT imaging using PERCIST criteria and correlated with histological results. Responses calculated were compared for statistical significance using paired t- test. Results: Mean SUVmax for primary lesion in FDG PET and MET PET was 15.88±11.12 and 5.01±2.14 respectively (p<0.001) and for axillary lymph nodes was 7.61±7.31 and 2.75±2.27 respectively (p=0.001). Statistically significant response in primary tumour and axilla was noted on both FDG and MET PET after three cycles of NAC. Complete response in primary tumour was seen in only 1 patient in FDG and 7 patients in MET PET (p=0.001) whereas there was no histological complete resolution of tumor in any patient. Response to therapy in axillary nodes noted on both PET scans were similar (p=0.45) and correlated well with histological findings. Conclusions: For the primary breast tumour, FDG PET has a higher sensitivity and accuracy than MET PET and for axilla both have comparable sensitivity and specificity. FDG PET shows higher target to background ratios so response is better predicted for primary breast tumour and axilla. Also, FDG-PET is widely available and has the advantage of a whole body evaluation in one study.

Keywords: 11C-methionine, 18F-FDG, breast carcinoma, neoadjuvant chemotherapy

Procedia PDF Downloads 479

Authors: Fumihiro Imai, Shinichi Watanabe, Shingo Maeda, Haruna Imai, Hiroki Niimi

Abstract:

It is important to know the growth rate of brain tumors before surgery because it influences treatment planning, including not only surgical resection strategy but also adjuvant therapy after surgery. Amide proton transfer (APT) imaging is an emerging molecular magnetic resonance imaging (MRI) technique based on chemical exchange saturation transfer without the administration of a contrast medium. The underlying assumption in APT imaging of tumors is that there is a close relationship between the proliferative activity of the tumor and mobile protein synthesis. We aimed to evaluate the diagnostic performance of APT imaging of pre-and post-treatment brain tumors. Ten patients with brain tumor underwent conventional and APT-weighted sequences on a 3.0 Tesla MRI before clinical intervention. The maximum and the minimum APT-weighted signals (APTWmax and APTWmin) in each solid tumor region were obtained and compared before and after a clinical intervention. All surgical specimens were examined for histopathological diagnosis. Eight of ten patients underwent adjuvant therapy after surgery. Histopathological diagnosis was glioma in 7 patients (WHO grade 2 in 2 patients, WHO grade 3 in 3 patients, and WHO grade 4 in 2 patients), meningioma WHO grade 1 in 2 patients, and primary lymphoma of the brain in 1 patient. High-grade gliomas showed significantly higher APTW signals than that low-grade gliomas. APTWmax in one huge parasagittal meningioma infiltrating into the skull bone was higher than that in glioma WHO grade 4. On the other hand, APTWmax in another convexity meningioma was the same as that in glioma WHO grade 3. Diagnosis of primary lymphoma of the brain was possible with APT imaging before pathological confirmation. APTW signals in residual tumors decreased dramatically within one year after adjuvant therapy in all patients. APT imaging demonstrated excellent diagnostic performance for the planning of surgery and adjuvant therapy of brain tumors.

Keywords: amides, magnetic resonance imaging, brain tumors, cell proliferation

Procedia PDF Downloads 62

Authors: May Khei Hu, Kevin Leong, Fu Siong Ng, Nicholas Peter

Abstract:

Introduction: Sympathetic stimulation has been recognised as a potent stimulus of arrhythmogenesis in various cardiac pathologies, possibly by augmenting dispersion of repolarisation. The effects of sympathetic stimulation in healthy subjects however remain unclear. It is, therefore, crucial to first establish the effects of physiological stress on dispersion of repolarisation in healthy subjects before understanding these effects in pathological cardiac conditions. We hypothesised that activation-recovery interval (ARI; which is a surrogate of action potential duration) and dispersion of repolarisation decrease on sympathetic stimulation. Methods: Eight patients aged 18-55 years with structurally normal hearts underwent head-up tilt test (HUTT) and exercise tolerance test (ETT) while wearing the electrocardiographic imaging (ECGi) vest. Patients later underwent CT scan and the epicardial potentials are reconstructed using the ECGi software. Activation and recovery times were determined from the acquired electrograms. ARI was calculated and later corrected using Bazett’s formula. Global and regional dispersion of repolarisation were determined from standard deviation of the corrected ARI (ARIc). One-way analysis of variance (ANOVA) and Wilcoxon test were used to evaluate statistical significance. Results: Global ARIc increased significantly [p<0.01] when patients were tilted upwards but decreased significantly after five minutes [p<0.01]. A subsequent post- hoc analysis revealed that the decrease in R-R was more substantial compared to the change in ARI, resulting in the observed increase in ARIc. Global ARIc decreased on peak exercise [p<0.01] but increased on recovery [p<0.01]. Global dispersion increased significantly on peak exercise [p<0.05] although there were no significant changes in regional dispersion. There were no significant changes in both global and regional dispersion during tilt. Conclusion: ARIc decreases upon sympathetic stimulation in healthy subjects. Global dispersion of repolarisation increases upon exercise although there were no changes in global or regional dispersion during orthostatic stress.

Keywords: dispersion of repolarisation, sympathetic stimulation, Head-up tilt test (HUTT), Exercise tolerance test (ETT), Electrocardiographic imaging (ECGi)

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Authors: Binder Hans

Abstract:

Cancer is no longer seen as solely a genetic disease where genetic defects such as mutations and copy number variations affect gene regulation and eventually lead to aberrant cell functioning which can be monitored by transcriptome analysis. It has become obvious that epigenetic alterations represent a further important layer of (de-)regulation of gene activity. For example, aberrant DNA methylation is a hallmark of many cancer types, and methylation patterns were successfully used to subtype cancer heterogeneity. Hence, unraveling the interplay between different omics levels such as genome, transcriptome and epigenome is inevitable for a mechanistic understanding of molecular deregulation causing complex diseases such as cancer. This objective requires powerful downstream integrative bioinformatics methods as an essential prerequisite to discover the whole genome mutational, transcriptome and epigenome landscapes of cancer specimen and to discover cancer genesis, progression and heterogeneity. Basic challenges and tasks arise ‘beyond sequencing’ because of the big size of the data, their complexity, the need to search for hidden structures in the data, for knowledge mining to discover biological function and also systems biology conceptual models to deduce developmental interrelations between different cancer states. These tasks are tightly related to cancer biology as an (epi-)genetic disease giving rise to aberrant genomic regulation under micro-environmental control and clonal evolution which leads to heterogeneous cellular states. Machine learning algorithms such as self organizing maps (SOM) represent one interesting option to tackle these bioinformatics tasks. The SOMmethod enables recognizing complex patterns in large-scale data generated by highthroughput omics technologies. It portrays molecular phenotypes by generating individualized, easy to interpret images of the data landscape in combination with comprehensive analysis options. Our image-based, reductionist machine learning methods provide one interesting perspective how to deal with massive data in the discovery of complex diseases, gliomas, melanomas and colon cancer on molecular level. As an important new challenge, we address the combined portrayal of different omics data such as genome-wide genomic, transcriptomic and methylomic ones. The integrative-omics portrayal approach is based on the joint training of the data and it provides separate personalized data portraits for each patient and data type which can be analyzed by visual inspection as one option. The new method enables an integrative genome-wide view on the omics data types and the underlying regulatory modes. It is applied to high and low-grade gliomas and to melanomas where it disentangles transversal and longitudinal molecular heterogeneity in terms of distinct molecular subtypes and progression paths with prognostic impact.

Keywords: integrative bioinformatics, machine learning, molecular mechanisms of cancer, gliomas and melanomas

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Authors: Genziana Lay

Abstract:

A wide majority of older children and adolescents who enter the juvenile court system present with an array of problematic symptoms and behaviors including anxiety, depression, aggressive acting out, detachment, and substance abuse. Attachment theory offers a framework for understanding normative and pathological functioning, which during development is influenced by emotional, social and cognitive elements. There is clear evidence that children and adolescents with the highest risk of developing adaptation problems present an insecure attachment profile. Most offending minors have experienced dysfunctional family relationships as well as social and/or economic deprivation. Their maladaptive attachment develops not only through their relationship with caregivers but with the environment at large. Activation of their faulty attachment system leads them to feel emotionally overwhelmed and engage in destructive behaviors and decision-making. A psycho-social intervention with this population conceptualized as attachment therapy is a multi-faceted, practical approach that has shown excellent results in terms of increased psychological well-being and drastically reduced rates of re-offense/ destructive behavior. Through several; components including psychotherapy, monitoring, volunteering, meditation and socialization, the program focuses on seven dimensions: self-efficacy, responsibility, empathy/reparation, autonomy/security, containment/structure, insight building, and relational health. This paper presents the program and illustrates how the framework of attachment theory practically applied to psycho-social intervention has great therapeutic and social reparation potential. Preliminary evidence drawn from the Sassari Juvenile Court is very promising; this paper will illustrate these results and propose an even more comprehensive, applicable approach to psycho-social reparative intervention that leads to greater psychological health and reduced recidivism in the child and adolescent population.

Keywords: attachment, child, adolescent, crime, juvenile, psychosocial

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Authors: Getachew Belay Kassahun

Abstract:

Background: Aspartate aminotransferase to Platelet Ratio Index (APRI) currently becomes a biomarker for screening liver fibrosis since liver biopsy procedure is invasive and variation in pathological interpretation. Clinical Laboratory Standard Institute recommends establishing age, sex and environment specific reference interval for biomarkers in a homogenous population. The current study was aimed to derive community based reference interval of APRI aged between 12 and 60 years old in Mekelle city Tigrai, Northern Ethiopia. Method: Six hundred eighty eight study participants were collected from three districts in Mekelle city. The 3 districts were selected through random sampling technique and sample size to kebelles (small administration) were distributed proportional to household number in each district. Lottery method was used at household level if more than 2 study participants to each age partition were found. A community based cross sectional in a total of 534 study participants, 264 male and 270 females, were included in the final laboratory and data analysis but around 154 study participants were excluded through exclusion criteria. Aspartate aminotransferase was analyzed through Biosystem chemistry analyzer and Sysmix machine was used to analyze platelet. Man Whitney U test non parametric stastical tool was used to appreciate stastical difference among gender after excluding the outliers through Box and Whisker. Result: The study appreciated stastical difference among gender for APRI reference interval. The combined, male and female reference interval in the current study was 0.098-0.390, 0.133-0.428 and 0.090-0.319 respectively. The upper and lower reference interval of males was higher than females in all age partition and there was no stastical difference (p-value (<0.05)) between age partition. Conclusion: The current study showed using sex specific reference interval is significant to APRI biomarker in clinical practice for result interpretation.

Keywords: reference interval, aspartate aminotransferase to platelet ratio Index, Ethiopia, tigray

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Authors: Hanan Mohamed Abd Elmoneim, Rawan Saleh AlJawi, Razan Saleh AlJawi, Aseel Abdullah AlMasoudi , Zyad Adnan Turkistani, Anas Abdulkarim Alkhoutani , Ohood Musaed AlJuhani , Hanan Attiyah AlZahrani

Abstract:

Background Esophageal cancer is the eighth most common cancer worldwide. More than 90% of esophageal cancers are either squamous cell carcinoma or adenocarcinoma. Squamous dysplasia is a precancerous lesion for squamous cell carcinoma and Barrett's esophagus is the precancerous lesion for adenocarcinoma. Gastro-esophageal reflux disease (GERD) is the initiation factor for Barrett's esophagus. Cyclooxygenase-2 (COX-2) is a key enzyme in arachidonic metabolism. It appears to play an important role in gastrointestinal carcinogenesis. COX-2 activity may be a potential target for the prevention of cancer progression by selective COX-2 inhibitors, which decrease proliferation and increase apoptosis. Objectives To assess COX-2 expression in premalignant and malignant esophageal epitheliums changes and detect its roles in progression of these lesions. Materials and Methods We analyzed the expression of COX-2 immunohistochemically in 40 esophageal biopsies utilizing the streptavidin-biotin-peroxidase complex method on archival formalin fixed-paraffin embedded blocks. Histopathologically, 17 (42.5%) of cases were non-malignant cases which included GERD, Barrett's esophagus and squamous dysplasia. The malignant cases were 23 (57.5%) squamous cell carcinoma, adenocarcinoma and undifferentiated carcinoma. Results In non-malignant cases 7 (41.2%) out of 17 cases had high COX-2 expression. In squamous cell carcinoma 10 (83.3%) out of 12 cases had high COX-2 expression. The expression of COX-2 was high in all 9 (100%) cases of adenocarcinoma. COX-2 expression is significantly increased (P=0.005 and P=0.0001) in squamous cell carcinoma and adenocarcinoma respectively. There was a significant difference in COX-2 immunoreactivity between malignant and non-malignant lesions (P=0.0003). Conclusion COX-2 is responsible for the progression of esophageal diseases from benign to malignant. We recommend that COX-2 immunohistochemistry should be done routinely for premalignant and malignant esophageal lesions as selective COX-2 inhibitors will be helpful in the treatment. Further studies on molecular and genetic basis of COX-2 expression are needed to unmask its role and relation to progression of esophageal lesions.

Keywords: Cox-2, Esophageal adinocarcinoma, Esophageal squamous cell carcinoma, Immunohistochemistry.

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Authors: Kenichi Yamahara, Makiko Ohshima, Shunsuke Ohnishi, Hidetoshi Tsuda, Akihiko Taguchi, Toshihiro Soma, Hiroyasu Ogawa, Jun Yoshimatsu, Tomoaki Ikeda

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We have previously reported the therapeutic potential of rat fetal membrane(FM)-derived mesenchymal stem cells (MSCs) using various rat models including hindlimb ischemia, autoimmune myocarditis, glomerulonephritis, renal ischemia-reperfusion injury, and myocardial infarction. In this study, 1) we isolated and characterized MSCs from human amnion and chorion; 2) we examined their differences in the expression profile of growth factors and cytokines; and 3) we investigated the therapeutic potential and difference of these MSCs using murine hindlimb ischemia and acute graft-versus-host disease (GVHD) models. Isolated MSCs from both amnion and chorion layers of FM showed similar morphological appearance, multipotency, and cell-surface antigen expression. Conditioned media obtained from amnion- and chorion-derived MSCs inhibited cell death caused by serum starvation or hypoxia in endothelial cells and cardiomyocytes. Amnion and chorion MSCs secreted significant amounts of angiogenic factors including HGF, IGF-1, VEGF, and bFGF, although differences in the cellular expression profile of these soluble factors were observed. Transplantation of human amnion or chorion MSCs significantly increased blood flow and capillary density in a murine hindlimb ischemia model. In addition, compared to human chorion MSCs, human amnion MSCs markedly reduced T-lymphocyte proliferation with the enhanced secretion of PGE2, and improved the pathological situation of a mouse model of GVHD disease. Our results highlight that human amnionand chorion-derived MSCs, which showed differences in their soluble factor secretion and angiogenic/immuno-suppressive function, could be ideal cell sources for regenerative medicine.

Keywords: amnion, chorion, fetal membrane, mesenchymal stem cells

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Authors: Izabela P. Vatanabe, Rafaela Peron, Patricia Manzine, Marcia R. Cominetti

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Introduction: Considering the increase in life expectancy of world population, there is an emerging concern in health services to allocate better care and care to elderly, through promotion, prevention and treatment of health. It has been observed that frailty syndrome is prevalent in elderly people worldwide and this complex and heterogeneous clinical syndrome consist of the presence of physical frailty associated with cognitive dysfunction, though in absence of dementia. This can be characterized by exhaustion, unintentional weight loss, decreased walking speed, weakness and low level of physical activity, in addition, each of these symptoms may be a predictor of adverse outcomes such as hospitalization, falls, functional decline, institutionalization, and death. Cognitive frailty is a recent concept in literature, which is defined as the presence of physical frailty associated with mild cognitive impairment (MCI) however in absence of dementia. This new concept has been considered as a subtype of frailty, which along with aging process and its interaction with physical frailty, accelerates functional declines and can result in poor quality of life of the elderly. MCI represents a risk factor for Alzheimer's disease (AD) in view of high conversion rate for this disease. Comorbidities and physical frailty are frequently found in AD patients and are closely related to heterogeneity and clinical manifestations of the disease. The decreased platelets ADAM10 levels in AD patients, compared to cognitively healthy subjects, matched by sex, age and education. Objective: Based on these previous results, this study aims to evaluate whether ADAM10 platelet levels of could act as a biomarker of cognitive frailty. Methods: The study was approved by Ethics Committee of Federal University of São Carlos (UFSCar) and conducted in the municipality of São Carlos, headquarters of Federal University of São Carlos (UFSCar). Biological samples of subjects were collected, analyzed and then stored in a biorepository. ADAM10 platelet levels were analyzed by western blotting technique in subjects with MCI and compared to subjects without cognitive impairment, both with and without presence of frailty. Statistical tests of association, regression and diagnostic accuracy were performed. Results: The results have shown that ADAM10/β-actin ratio is decreased in elderly individuals with cognitive frailty compared to non-frail and cognitively healthy controls. Previous studies performed by this research group, already mentioned above, demonstrated that this reduction is still higher in AD patients. Therefore, the ADAM10/β-actin ratio appears to be a potential biomarker for cognitive frailty. The results bring important contributions to an accurate diagnosis of cognitive frailty from the perspective of ADAM10 as a biomarker for this condition, however, more experiments are being conducted, using a high number of subjects, and will help to understand the role of ADAM10 as biomarker of cognitive frailty and contribute to the implementation of tools that work in the diagnosis of cognitive frailty. Such tools can be used in public policies for the diagnosis of cognitive frailty in the elderly, resulting in a more adequate planning for health teams and better quality of life for the elderly.

Keywords: ADAM10, biomarkers, cognitive frailty, elderly

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Authors: Katarzyna Palus, Jarosław Całka

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Gastrointestinal disorders, especially acid-related diseases, including peptic and duodenal ulcers, gastroesophageal reflux disease, upper GI bleeding or stress-related mucosal disease, are currently serious health issues encountered very frequently in patients worldwide. However, to date, the response of sympathetic neurons to gastric mucosal injury and local inflammation following hyperacidity is unknown. Thus, the present study was designed to determine possible changes in expression of galanin (GAL) in the CSMG neurons supplying the prepyloric area of the porcine stomach in a physiological state and following experimentally-induced hyperacidity by using combined retrograde tracing and double-labelling immunohistochemistry. The choice of the domestic pig as an experimental model in the present study is not accidental and is justified by the high degree of physiological and anatomical similarity to human digestive system functions. In this experiment ten juvenile female pigs of the Large White Polish breed were used. The animals were divided into two groups: control and animals with hydrochloric acid infusion (HCl). The neuronal retrograde marker Fast Blue (FB) was injected into the anterior prepyloric wall of the stomach of all animals. After 23 days, animals of the HCl-group were reintroduced into a state of general anesthesia and intragastrically given 5 ml/kg of body weight of 0.25 M aqueous solution of hydrochloric acid. On the 28th day, all animals were euthanized. The CSMG complexes were then collected and the CSMG cryostat sections were stained immunocytochemically for GAL and TH (tyrosine hydroxylase). Immunohistochemistry revealed that in the control group 8.40 ± 0.53 % out of 200 FB-positive CSMG neurons contained GAL. In HCl group upregulation of the GAL-IR neurons to 22.52 ± 1.18 % were observed. All GAL-IR neurons in both groups showed the simultaneously TH immunoreactivity. Increase in the expression of GAL in FB-positive neurons of the HCL group may suggest its participation in the protective mechanisms of neurons in different pathological processes, such as gastric hyperacidity.

Keywords: coeliac-superior mesenteric ganglion complex, gastric innervation, hyperacidity, immunohistochemistry

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Authors: Panas Gerasimos, Kotidou Varvara, Halkiopoulos Constantinos, Gkintoni Evgenia

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As a result of growing technology and briefing by the internet, users resort to the internet and subsequently to the opinion of an expert. In many cases, they take control of their health in their hand and make a decision without the contribution of a doctor. According to that, this essay intends to analyze the confidence of searching health issues on the internet. For the fulfillment of this study, there has been a survey among doctors in order to find out the reasons a patient uses the internet about their health problems and the consequences that health information could lead by searching on the internet, as well. Specifically, the results regarding the research of the users demonstrate: a) the majority of users make use of the internet about health issues once or twice a month, b) individuals that possess chronic disease make health search on the internet more frequently, c) the most important topics that the majority of users usually search are pathological, dietary issues and the search of issues that are associated with doctors and hospitals. However, it observed that topic search varies depending on the users’ age, d) the most common sources of information concern the direct contact with doctors, as there is a huge preference from the majority of users over the use of the electronic form for their briefing and e) it has been observed that there is large lack of knowledge about e-health services. From the doctor's point of view, the following conclusions occur: a) almost all doctors use the internet as their main source of information, b) the internet has great influence over doctors’ relationship with the patients, c) in many cases a patient first makes a visit to the internet and then to the doctor, d) the internet significantly has a psychological impact on patients in order to for them to reach a decision, e) the most important reason users choose the internet instead of the health professional is economic, f) the negative consequence that emerges is inaccurate information, g) and the positive consequences are about the possibility of online contact with the doctor and contributes to the easy comprehension of the doctor, as well. Generally, it’s observed from both sides that the use of the internet in health issues is intense, which declares that the new means the doctors have at their disposal, produce the conditions for radical changes in the way of providing services and in the doctor-patient relationship.

Keywords: cognitive models, health marketing, e-health, psychological factors, digital marketing, e-health services

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Authors: Ilirian Laçi, Alketa Spahiu

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Big strums of thyroid glandule observed by a simple viewing can be witnessed in everyday life. Medical cabinets evidence patients withpalpablenodes of thyroid glandule, mainly nodes of the size of 10 millimeters. Further, more cases which have resulted in negative under palpation have resulted in positive at ultrasound examination. Therefore, the use of ultrasound for diagnosing has increased the number of patients with nodes of thyroid glandule in the last couple of decades in all countries, Albania included. Thus, there has been evidence of an increased number of patients affected by this pathology, where female patients dominate. Demographically, the capital shows high numbers due to the high population, but of interest is the high incidence of those areas distanced from the sea. While regarding related pathologies, no significant link was evidenced, an element of ancestry was evident in the nodes of the thyroid glandule. When we talk of nodes of the thyroid glandule, we should consider hyperplasia, neoplasia, and inflammatory diseases that cause nodes of the thyroid glandule. This increase parallels the world’s increase of the incidence of thyroid glandule, with malign cases, which are at about 5% and are not depended on size. Given the numbers, with most thyroid glandule nodes being benign, the main objective of the examination of the nodes was the determination of benign and malign cases to avoid undue surgery. Subject of this study were 212 patients that underwent fine-needle aspiration (FNA) under ultrasound guidance at the Medical University Center of Tirana. All the patients came to the Mother Teresa University Hospital from public and private hospitals and other polyclinics. These patients had an ultrasound examination before visiting the Center of Nuclear Medicine for a scintigraph of thyroid glandule in the period September 2016 and September 2017. To correlate, all patients had been examined via ultrasound of the thyroid glandule prior to the scintigraph. The ultrasound included evaluation of the number of nodes, their size, their solid, cystic, or solid-cystic structure, echogenicity according to the gray scale, the presence of calcification, the presence of lymph nodes, the presence of adenopathy, and the correlation of the cytology results from the Laboratory of Pathological Anatomy of Medical University Center of Tirana.

Keywords: thyroid nodes, fine needle aspiration, ultrasound, scintigraphy

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Authors: Shubhita Mathur, Ritika Kar Bahal, Priyanka Chauhan, Anil K. Tyagi

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Mycobacterium tuberculosis, the causative agent of human tuberculosis, is a major cause of mortality. Bacillus Calmette-Guérin (BCG), the only licensed vaccine available for protection against tuberculosis confers highly variable protection ranging from 0%-80%. Thus, novel vaccine strains need to be evaluated for their potential as a vaccine against tuberculosis. We had previously constructed a triple gene mutant of M. tuberculosis (MtbΔmms), having deletions in genes encoding for phosphatases mptpA, mptpB, and sapM that are involved in host-pathogen interaction. Though vaccination with Mtb∆mms strain induced protection in the lungs of guinea pigs, the mutant strain was not able to control the hematogenous spread of the challenge strain to the spleens. Additionally, inoculation with Mtb∆mms resulted in some pathological damage to the spleens in the early phase of infection. In order to overcome the pathology caused by MtbΔmms in the spleens of guinea pigs and also to control the dissemination of the challenge strain, MtbΔmms was genetically modified by disrupting bioA gene to generate MtbΔmmsb strain. Further, in vivo attenuation of MtbΔmmsb was evaluated, and its protective efficacy was assessed against virulent M. tuberculosis challenge in guinea pigs. Our study demonstrates that Mtb∆mmsb mutant was highly attenuated for growth and virulence in guinea pigs. Vaccination with Mtb∆mmsb mutant generated significant protection in comparison to sham-immunized animals at 4 and 12 weeks post-infection in lungs and spleens of the infected animals. Our findings provide evidence that deletion of genes involved in signal transduction and biotin biosynthesis severely attenuates the pathogen and the single immunization with the auxotroph was able to provide significant protection as compared to sham-immunized animals. The protection imparted by Mtb∆mmsb fell short in comparison to the protection observed in BCG-immunized animals. This study nevertheless indicates the importance of attenuated multiple gene deletion mutants of M. tuberculosis in generating protection against tuberculosis.

Keywords: Mycobacterium tuberculosis, BCG, MtbΔmmsb, bioA, guinea pigs

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Authors: A. V. Sokolov, S. V. Vorobyev, A. Yu. Efimtcev, V. Yu. Lobzin, I. A. Lupanov, O. A. Cherdakov, V. A. Fokin

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Alzheimer’s disease (AD) is the most common form of dementia. Different brain regions are involved to the pathological process of AD. The purpose of this study was to evaluate brain activation by visual memory task in patients with Alzheimer's disease and determine correlation between memory impairment and atrophy of memory specific brain regions of frontal and medial temporal lobes. To investigate the organization of memory and localize cortical areas activated by visual memory task we used functional magnetic resonance imaging and to evaluate brain atrophy of patients with Alzheimer's disease we used voxel-based morphometry. FMRI was performed on 1.5 T MR-scanner Siemens Magnetom Symphony with BOLD (Blood Oxygenation Level Dependent) technique, based on distinctions of magnetic properties of hemoglobin. For test stimuli we used series of 12 not related images for "Baseline" and 12 images with 6 presented before for "Active". Stimuli were presented 3 times with reduction of repeated images to 4 and 2. Patients with Alzheimer's disease showed less activation in hippocampal formation (HF) region and parahippocampal gyrus then healthy persons of control group (p<0.05). The study also showed reduced activation in posterior cingulate cortex (p<0.001). Voxel-based morphometry showed significant atrophy of grey matter in Alzheimer’s disease patients, especially of both temporal lobes (fusiform and parahippocampal gyri); frontal lobes (posterior cingulate and superior frontal gyri). The study showed correlation between memory impairment and atrophy of memory specific brain regions of frontal and medial temporal lobes. Thus, reduced activation in hippocampal formation and parahippocampal gyri, in posterior cingulate gyrus in patients with Alzheimer's disease correlates to significant atrophy of these regions, detected by voxel-based morphometry, and to deterioration of specific cognitive functions.

Keywords: Alzheimer’s disease, functional MRI, voxel-based morphometry

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Authors: F. Polito, M. Cucinotta, A. Conti, C. Lo Giudice, C. Tomasello, F. Angileri, D. La Torre, M. Aguennouz

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Glioblastoma multiforme (GBM) is the most aggressive form of brain tumors, with an extremely poor prognosis. Telomeres lenght is associated with tumor progression in several type of human cancers and telomere elongation is a common molecular feature of advanced malignancies. Among the telomeric shelterin proteins PTOP is required for telomeric protein complex assembly, telomerase recruitment and activity, and telomere length regulation through a PTOP-telomerase interaction. Previous studies suggest that PTOP upregulation is involved in radioresistance and telomere lengthening in colorectal cancer cells. Moreover, in human osteosarcoma cells PTOP deletion led to telomere shortening, increased apoptosis and radiation sensitivity enhancement. However, to date, little is known about the role of PTOP in progression of glioma cancers. In light of this background aim of the study is to investigate the expression of PTOP in different grades of human glioma and its correlation with the pathological grade of gliomas, grades of malignancy, proliferative activity and apoptosis. Fifteen Low Grade Astrocytomas (LGA), 18 Anaplastic Astrocytomas (AA) and 26 Glioblastoma Multiforme (GBM) samples were analyzed. Three samples of normal brain tissue (NBT) were used as controls. The expression levels of PTOP, h-TERT, BIRC1 and cyclin D1 were determined by real time PCR and/or western blot. Results obtained shows that PTOP expression in glioma tissues is tightly correlated with clinical grade ( p < 0.01 ). No correlation was found between PTOP expression and other clinicopathologic parameters. The expression of PTOP was positively correlated with the expression of hTERT and TERF1. Furthermore PTOP positively correlates with cyclin D1 and negatively correlates with the expression of BIRC1. Our findings indicate that PTOP might play key role in the progression of glioma regulating telomerase activity and likely through regulation of cell cycle and apoptosis. In conclusion results obtained prompted us to speculate that PTOP might represents a potential molecular bio marker and a therapeutic target for the treatment of glioblastoma tumors.

Keywords: glioblastoma, PTOP, telomere, brain tumors

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Authors: Ola Hall, Ibrahim Wahab, Thorsteinn Rognvaldsson, Mattias Ohlsson

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The subfield of poverty and welfare estimation that applies machine learning tools and methods on satellite imagery is a nascent but rapidly growing one. This is in part driven by the sustainable development goal, whose overarching principle is that no region is left behind. Among other things, this requires that welfare levels can be accurately and rapidly estimated at different spatial scales and resolutions. Conventional tools of household surveys and interviews do not suffice in this regard. While they are useful for gaining a longitudinal understanding of the welfare levels of populations, they do not offer adequate spatial coverage for the accuracy that is needed, nor are their implementation sufficiently swift to gain an accurate insight into people and places. It is this void that satellite imagery fills. Previously, this was near-impossible to implement due to the sheer volume of data that needed processing. Recent advances in machine learning, especially the deep learning subtype, such as deep neural networks, have made this a rapidly growing area of scholarship. Despite their unprecedented levels of performance, such models lack transparency and explainability and thus have seen limited downstream applications as humans generally are apprehensive of techniques that are not inherently interpretable and trustworthy. While several studies have demonstrated the superhuman performance of AI models, none has directly compared the performance of such models and human readers in the domain of poverty studies. In the present study, we directly compare the performance of human readers and a DL model using different resolutions of satellite imagery to estimate the welfare levels of demographic and health survey clusters in Tanzania, using the wealth quintile ratings from the same survey as the ground truth data. The cluster-level imagery covers all 608 cluster locations, of which 428 were classified as rural. The imagery for the human readers was sourced from the Google Maps Platform at an ultra-high resolution of 0.6m per pixel at zoom level 18, while that of the machine learning model was sourced from the comparatively lower resolution Sentinel-2 10m per pixel data for the same cluster locations. Rank correlation coefficients of between 0.31 and 0.32 achieved by the human readers were much lower when compared to those attained by the machine learning model – 0.69-0.79. This superhuman performance by the model is even more significant given that it was trained on the relatively lower 10-meter resolution satellite data while the human readers estimated welfare levels from the higher 0.6m spatial resolution data from which key markers of poverty and slums – roofing and road quality – are discernible. It is important to note, however, that the human readers did not receive any training before ratings, and had this been done, their performance might have improved. The stellar performance of the model also comes with the inevitable shortfall relating to limited transparency and explainability. The findings have significant implications for attaining the objective of the current frontier of deep learning models in this domain of scholarship – eXplainable Artificial Intelligence through a collaborative rather than a comparative framework.

Keywords: poverty prediction, satellite imagery, human readers, machine learning, Tanzania

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Authors: Shende Suraj Balu, A. B. Deoghare, K. M. Pandey

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The human middle ear (ME) is a delicate and vital organ. It has a complex structure that performs various functions such as receiving sound pressure and producing vibrations of eardrum and propagating it to inner ear. It consists of Tympanic Membrane (TM), three auditory ossicles, various ligament structures and muscles. Incidents such as traumata, infections, ossification of ossicular structures and other pathologies may damage the ME organs. The conditions can be surgically treated by employing prosthesis. However, the suitability of the prosthesis needs to be examined in advance prior to the surgery. Few decades ago, this issue was addressed and analyzed by developing an equivalent representation either in the form of spring mass system, electrical system using R-L-C circuit or developing an approximated CAD model. But, nowadays a three-dimensional ME model can be constructed using micro X-Ray Computed Tomography (μCT) scan data. Moreover, the concern about patient specific integrity pertaining to the disease can be examined well in advance. The current research work emphasizes to develop the ME model from the stacks of μCT images which are used as input file to MIMICS Research 19.0 (Materialise Interactive Medical Image Control System) software. A stack of CT images is converted into geometrical surface model to build accurate morphology of ME. The work is further extended to understand the dynamic behaviour of Harmonic response of the stapes footplate and umbo for different sound pressure levels applied at lateral side of eardrum using finite element approach. The pathological condition Cholesteatoma of ME is investigated to obtain peak to peak displacement of stapes footplate and umbo. Apart from this condition, other pathologies, mainly, changes in the stiffness of stapedial ligament, TM thickness and ossicular chain separation and fixation are also explored. The developed model of ME for pathologies is validated by comparing the results available in the literatures and also with the results of a normal ME to calculate the percentage loss in hearing capability.

Keywords: computed tomography (μCT), human middle ear (ME), harmonic response, pathologies, tympanic membrane (TM)

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Authors: Umamaheswari Shanmugam, Silvia Ronchi

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Software, artificial intelligence, and machine learning can improve healthcare through innovative and advanced technologies that can use the large amount and variety of data generated during healthcare services every day; one of the significant advantages of these new technologies is the ability to get experience and knowledge from real-world use and to improve their performance continuously. Healthcare systems and institutions can significantly benefit because the use of advanced technologies improves the efficiency and efficacy of healthcare. Software-defined as a medical device, is stand-alone software that is intended to be used for patients for one or more of these specific medical intended uses: - diagnosis, prevention, monitoring, prediction, prognosis, treatment or alleviation of a disease, any other health conditions, replacing or modifying any part of a physiological or pathological process–manage the received information from in vitro specimens derived from the human samples (body) and without principal main action of its principal intended use by pharmacological, immunological or metabolic definition. Software qualified as medical devices must comply with the general safety and performance requirements applicable to medical devices. These requirements are necessary to ensure high performance and quality and protect patients' safety. The evolution and the continuous improvement of software used in healthcare must consider the increase in regulatory requirements, which are becoming more complex in each market. The gap between these advanced technologies and the new regulations is the biggest challenge for medical device manufacturers. Regulatory requirements can be considered a market barrier, as they can delay or obstacle the device's approval. Still, they are necessary to ensure performance, quality, and safety. At the same time, they can be a business opportunity if the manufacturer can define the appropriate regulatory strategy in advance. The abstract will provide an overview of the current regulatory framework, the evolution of the international requirements, and the standards applicable to medical device software in the potential market all over the world.

Keywords: artificial intelligence, machine learning, SaMD, regulatory, clinical evaluation, classification, international requirements, MDR, 510k, PMA, IMDRF, cyber security, health care systems

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Authors: Uliana N. Tumanova, Viacheslav M. Lyapin, Vladimir G. Bychenko, Alexandr I. Shchegolev, Gennady T. Sukhikh

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It is well known that the gas formed as a result of postmortem decomposition of tissues can be detected already 24-48 hours after death. In addition, the conditions of keeping and storage of the corpse (temperature and humidity of the environment) significantly determine the rate of occurrence and development of posthumous changes. The presence of sepsis is accompanied by faster postmortem decomposition and decay of the organs and tissues of the body. The presence of gas in the vessels and cavities can be revealed fully at postmortem CT. Radiologists must certainly report on the detection of intraorganic or intravascular gas, wich was detected at postmortem CT, to forensic experts or pathologists before the autopsy. This gas can not be detected during autopsy, but it can be very important for establishing a diagnosis. To explore the possibility of postmortem CT for the evaluation of gas accumulations in the newborns' vessels, who died from congenital sepsis. Researched of 44 newborns bodies (25 male and 19 female sex, at the age from 6 hours to 27 days) after 6 - 12 hours of death. The bodies were stored in the refrigerator at a temperature of +4°C in the supine position. Grouped 12 bodies of newborns that died from congenital sepsis. The control group consisted of 32 bodies of newborns that died without signs of sepsis. Postmortem CT examination was performed at the GEMINI TF TOF16 device, before the autopsy. The localizations of gas accumulations in the vessels were determined on the CT tomograms. The sepsis diagnosis was on the basis of clinical and laboratory data and autopsy results. Gases in the vessels were detected in 33.3% of cases in the group with sepsis, and in the control group - in 34.4%. A group with sepsis most often the gas localized in the heart and liver vessels - 50% each, of observations number with the detected gas in the vessels. In the heart cavities, aorta and mesenteric vessels - 25% each. In control most often gas was detected in the liver (63.6%) and abdominal cavity (54.5%) vessels. In 45.5% the gas localized in the cavities, and in 36.4% in the vessels of the heart. In the cerebral vessels and in the aorta gas was detected in 27.3% and 9.1%, respectively. Postmortem CT has high diagnostic capabilities to detect free gas in vessels. Postmortem changes in newborns that died from sepsis do not affect intravascular gas production within 6-12 hours. Radiation methods should be used as a supplement to the autopsy, including as a kind of ‘guide’, with the indication to the forensic medical expert of certain changes identified during CT studies, for better definition of pathological processes during the autopsy. Postmortem CT can be recommend as a first stage of autopsy.

Keywords: congenital sepsis, gas, newborn, postmortem CT

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Authors: Kunal Garg, Louise Theusen Hermansan, Kanoktip Puttaraska, Oliver Hendricks, Heidi Pirttinen, Leona Gilbert

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The Germ Theory (one infectious determinant is equal to one disease) has unarguably evolved our capability to diagnose and treat infectious diseases over the years. Nevertheless, the advent of technology, climate change, and volatile human behavior has brought about drastic changes in our environment, leading us to question the relevance of the Germ Theory in our day, i.e. will vector-borne disease (VBD) sufferers produce multiple immune responses when tested for multiple microbes? Vector diseased patients producing multiple immune responses to different microbes would evidently suggest human polymicrobial infections (HPI). Ongoing diagnostic tools are exceedingly unequipped with the current research findings that would aid in diagnosing patients for polymicrobial infections. This shortcoming has caused misdiagnosis at very high rates, consequently diminishing the patient’s quality of life due to inadequate treatment. Equipped with the state-of-art scientific knowledge, PolyScan intends to address the pitfalls in current VBD diagnostics. PolyScan is a multiplex and multifunctional enzyme linked Immunosorbent assay (ELISA) platform that can test for numerous VBD microbes and allow simultaneous screening for multiple types of antibodies. To validate PolyScan, Lyme Borreliosis (LB) and spondyloarthritis (SpA) patient groups (n = 54 each) were tested for Borrelia burgdorferi, Borrelia burgdorferi Round Body (RB), Borrelia afzelii, Borrelia garinii, and Ehrlichia chaffeensis against IgM and IgG antibodies. LB serum samples were obtained from Germany and SpA serum samples were obtained from Denmark under relevant ethical approvals. The SpA group represented chronic LB stage because reactive arthritis (SpA subtype) in the form of Lyme arthritis links to LB. It was hypothesized that patients from both the groups will produce multiple immune responses that as a consequence would evidently suggest HPI. It was also hypothesized that the multiple immune response proportion in SpA patient group would be significantly larger when compared to the LB patient group across both antibodies. It was observed that 26% LB patients and 57% SpA patients produced multiple immune responses in contrast to 33% LB patients and 30% SpA patients that produced solitary immune responses when tested against IgM. Similarly, 52% LB patients and an astounding 73% SpA patients produced multiple immune responses in contrast to 30% LB patients and 8% SpA patients that produced solitary immune responses when tested against IgG. Interestingly, IgM immune dysfunction in both the patient groups was also recorded. Atypically, 6% of the unresponsive 18% LB with IgG antibody was recorded producing multiple immune responses with the IgM antibody. Similarly, 12% of the unresponsive 19% SpA with IgG antibody was recorded producing multiple immune responses with the IgM antibody. Thus, results not only supported hypothesis but also suggested that IgM may atypically prevail longer than IgG. The PolyScan concept will aid clinicians to detect patients for early, persistent, late, polymicrobial, & immune dysfunction conditions linked to different VBD. PolyScan provides a paradigm shift for the VBD diagnostic industry to follow that will drastically shorten patient’s time to receive adequate treatment.

Keywords: diagnostics, immune dysfunction, polymicrobial, TICK-TAG

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