Search results for: benign prostatic hypertrophy

Authors: Hussein Alahmer, Amr Ahmed

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Liver cancer is one of the common diseases that cause the death. Early detection is important to diagnose and reduce the incidence of death. Improvements in medical imaging and image processing techniques have significantly enhanced interpretation of medical images. Computer-Aided Diagnosis (CAD) systems based on these techniques play a vital role in the early detection of liver disease and hence reduce liver cancer death rate.  This paper presents an automated CAD system consists of three stages; firstly, automatic liver segmentation and lesion’s detection. Secondly, extracting features. Finally, classifying liver lesions into benign and malignant by using the novel contrasting feature-difference approach. Several types of intensity, texture features are extracted from both; the lesion area and its surrounding normal liver tissue. The difference between the features of both areas is then used as the new lesion descriptors. Machine learning classifiers are then trained on the new descriptors to automatically classify liver lesions into benign or malignant. The experimental results show promising improvements. Moreover, the proposed approach can overcome the problems of varying ranges of intensity and textures between patients, demographics, and imaging devices and settings.

Keywords: CAD system, difference of feature, fuzzy c means, lesion detection, liver segmentation

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Authors: Ng Ziyi Zoe, Yow Wei Quin

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Humor plays a pivotal role in our interaction with people. According to the age-related positivity effect, older adults (OA) demonstrate more positive emotions and are better able to modulate negative emotional states than younger adults (YA), suggesting an increase in humor appreciation with age. However, different types of humor might show different patterns of change in appreciation with age (e.g., incongruity-resolution humor, aggressive humor, self-vs.-other-deprecating humor). Thus, we aim to explore age-related effects in the perception of different types of humor in a single study, including the impact of local slang in humor appreciation. Twenty OA aged 60-and-above and 24 YA aged 13-20 were watched four short videos (i.e., benign, violent, satire+local slang, and others-deprecating humor) and rated how funny the videos were (from a scale of 1-not funny-at-all to 5-very funny). Participants were also asked to rank the videos in the order of most- to least-entertaining. Repeated measures of ANOVA found significant main effects of age, F(3,39)=12,88, p < .001, where OA gave higher ratings than YA (M=3.20 vs. 2.63), and humor type, F(3,123)=19.66, p < .001. Post-hoc analyses revealed a significant linear contrast where benign and violent humor had the lowest ratings while others-deprecating humor had the highest ratings. No significant interaction effect was found. The distribution of ranking ratings also differed between OA and YA (e.g., preferred satire+local slang and others-deprecating humor vs. overwhelmingly preferred other-deprecating humor, respectively). Overall, OA displayed a greater appreciation across various types of humor than YA. Humor perception will be discussed in the larger context of cognitive, societal, and cultural implications.

Keywords: humor, older adults, perception, age differences

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Authors: Shaira L. Kee, Michael Aaron G. Sy, Myles Joshua T. Tan, Hezerul Abdul Karim, Nouar AlDahoul

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Skin diseases are considered the fourth most common disease, with melanoma and non-melanoma skin cancer as the most common type of cancer in Caucasians. The alarming increase in Skin Cancer cases shows an urgent need for further research to improve diagnostic methods, as early diagnosis can significantly improve the 5-year survival rate. Machine Learning algorithms for image pattern analysis in diagnosing skin lesions can dramatically increase the accuracy rate of detection and decrease possible human errors. Several studies have shown the diagnostic performance of computer algorithms outperformed dermatologists. However, existing methods still need improvements to reduce diagnostic errors and generate efficient and accurate results. Our paper proposes an ensemble method to classify dermoscopic images into benign and malignant skin lesions. The experiments were conducted using the International Skin Imaging Collaboration (ISIC) image samples. The dataset contains 3,297 dermoscopic images with benign and malignant categories. The results show improvement in performance with an accuracy of 88% and an F1 score of 87%, outperforming other existing models such as support vector machine (SVM), Residual network (ResNet50), EfficientNetB0, EfficientNetB4, and VGG16.

Keywords: deep learning - VGG16 - efficientNet - CNN – ensemble – dermoscopic images - melanoma

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Authors: Chengcao Sun, Cuili Yang, Shujun Li, Ruilin Xue, Liang Wang, Yongyong Xi, Dejia Li

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Backgrounds: Sulforaphane, one of the most important isothiocyanates in the human diet, is known to have chemopreventive and antioxidant activities in different tissues via activation of NF-E2-related factor 2 (Nrf2)-mediated induction of antioxidant/phase II enzymes, such as heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1). However, its effects on muscular dystrophy remain unknown. This work was undertaken to evaluate the effects of Sulforaphane on Duchenne muscular dystrophy (DMD). Methods: 4-week-old mdx mice were treated with SFN by gavage (2 mg/kg body weight per day) for 8 weeks. Blood was collected from eye socket every week, and tibial anterior, extensor digitorum longus, gastrocnemius, soleus, triceps brachii muscles and heart samples were collected after 8-week gavage. Force measurements and mice exercise capacity assays were detected. GSH/GSSG ratio, TBARS, CK and LDH levels were analyzed by spectrophotometric methods. H&E staining was used to analyze histological and morphometric of skeletal muscles of mdx mice, and Evas blue dye staining was made to detect sarcolemmal integrity of mdx mice. Further, the role of Sulforaphane on Nrf2/ARE signaling pathway was analyzed by ELISA, western blot and qRT-PCR. Results: Our results demonstrated that SFN treatment increased the expression and activity of muscle phase II enzymes NQO1 and HO-1 with Nrf2 dependent manner. SFN significantly increased skeletal muscle mass, muscle force (~30%), running distance (~20%) and GSH/GSSG ratio (~3.2 folds) of mdx mice, and decreased the activities of plasma creatine phosphokinase (CK) (~45%) and lactate dehydrogenase (LDH) (~40%), gastrocnemius hypertrophy (~25%), myocardial hypertrophy (~20%) and MDA levels (~60%). Further, SFN treatment also reduced the central nucleation (~40%), fiber size variability, inflammation and improved the sarcolemmal integrity of mdx mice. Conclusions: Collectively, these results show that SFN can improve muscle function, pathology and protect dystrophic muscle from oxidative damage in mdx mice through Nrf2 signaling pathway, which indicate Nrf2 may have clinical implications for the treatment of patients with muscular dystrophy.

Keywords: sulforaphane, duchenne muscular dystrophy, Nrf2, oxidative stress

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Authors: Zahid Shafiq, Li Liu, Dong Wang, Yong-Jun Chen

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As synthetic organic methods are increasingly concerned with the growing importance of sustainable chemistry, iodine recently has emerged as an inexpensive, non-toxic, readily available and environmentally benign catalyst for various organic transformations to afford the corresponding products in high yields with high regio- and chemoselectivity. Iodine has found widespread applications in various organic synthesis such as Michael addition, coupling reaction and also in the multicomponent synthesis where it can efficiently activate C=C, C=O, C=N, and so forth. Iodine not only has been shown to be an efficient mild Lewis acid in various processes, but also due to its moderate nature, and water tolerance, reactions catalyzed by iodine can be effectively carried out in neutral media under very mild conditions. We have successfully described an efficient procedure for the nucleophilic substitution of the Baylis-Hillman (BH) adducts and their corresponding acetates with indoles to get α-substitution product using catalytic Silver Triflate (AgOTf) as Lewis acid. At this point, we were interested to develop an environmentally benign catalytic system to effect this substitution reaction and to avoid the use of metal Lewis acid as a catalyst. Since, we observed the formation of -product during the course of the reaction, we also became interested to explore the reaction conditions in order to control regioselectivity and to obtain both regioisomers. The developed methodology resulted in regioselective substitution products with controlled selectivity. Further, the substitution products were used to synthesize various Tri- and Tetracyclo Azepino indole derivatives via reductive amination.

Keywords: indole, regioselective, Baylis-Hillman, substitution

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Authors: Kieren Wilson, Gulnaz Majeed

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NHS constitution gives rights to the patient with suspected cancer to be seen by a cancer specialist within 2 weeks of referral. Guys and St Thomas Hospital (GSTT) is one of the largest cancer centres in London. NICE guidelines have provided guidance for health professionals to refer patients appropriately to RAC. In GSTT suspected gynae cancer referrals are mostly by NHS e-Referral Service with some fax, emails as well as paper referrals. The objective of this study was to evaluate compliance with 2-week referral pathway with emphasis on one stop diagnostic service with supporting efficient pathways. A prospective evaluation over 3 months (1 Jan 2017 to 31 Mar 2017) was undertaken. There were 26 clinics, 761 patients were booked in the clinics with a DNA rate of 13% (n=101) hence 606 patients were seen. Majority of referrals were for post menopausal bleeding (PMB) 25% (n=194) followed by cervical, vaginal, vulval reasons 23% (n=179) (abnormal cytology excluded as patients directly referred to colposcopy unit in GSTT), ovarian 7% (n=54) and endometrial 5% (n=41). Women with new or previous established diagnosis of cancer were 24, cervical (n=17), vulva (n=6) and vagina (n=1). Multifocal preinvasive disease vulva (VIN), vagina (VAIN) and cervix (CIN) was confirmed in twenty-six patients 4% (high prevalence in HIV patients). Majority of cervical referrals: PCB (n=14), cervical erosion (n=7), polyps (n=9) and cervical cyst were benign. However, two women with PMB had cervical cancer. Only 2 out of 13 referrals with vaginal concerns had VAIN. One case with non-cervical glandular cytology was confirmed to have endometrial cancer. One stop service based on the diagnostic support of ultrasound, colposcopy and hysteroscopy was achieved in 54% (n=359). Patients were discharged to GP, benign gynaecology, endometriosis, combined vulval/dermatology clinic or gynae oncology. 33% (n=202) required a second visit, 12% (n=70) third visit, 3% (n=19) fourth visit, 1% (n=4) fifth visit and 1% (n=6) sixth visit. Main reasons for follow ups were the unavailability of diagnostic slots, patient choice, need for interpreters, the discussion following gynae MDM review for triage to benign gynae, delay in availability of diagnostic results like histology/MRI/CT. Recommendations following this study are multi disciplinary review of pathways with the availability of additional diagnostic procedure slots to aim for one stop service. Furthermore, establishment of virtual and telephone consultations to reduce follow ups.

Keywords: multifocal disease, post menopausal bleeding, preinvasive disease, rapid access clinic

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Authors: Olaide O. Wahab, Lukman O. Olasunkanmi, Krishna K. Govender, Penny P. Govender

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The economic and environmental challenges associated with azo disperse dyes applications are due to poor aqueous solubility and low degradation tendency which stems from low chemical reactivity. Poor aqueous solubility property of this group of dyes necessitates the use of dispersing agents which increase operational costs and also release toxic chemical components into the environment, while their low degradation tendency is due to the high stability of the azo functional group (-N=N-) in their chemical structures. To address these problems, this study investigated theoretically the effects of some polar substituents on the aqueous solubility and reactivity properties of disperse yellow (DY) 119 dye with a view to theoretically develop new azo disperse dyes with improved solubility in water and higher degradation tendency in the environment using DMol³ computational code. All calculations were carried out using the Becke and Perdew version of Volsko-Wilk-Nusair (VWN-BP) level of density functional theory in conjunction with double numerical basis set containing polarization function (DNP). The aqueous solubility determination was achieved with conductor-like screening model for realistic solvation (COSMO-RS) in conjunction with known empirical solubility model, while the reactivity was predicted using frontier molecular orbital calculations. Most of the new derivatives studied showed evidence of higher aqueous solubility and degradation tendency compared to the parent dye. We conclude that these derivatives are promising alternative dyes for more economic and environmental benign dyeing practice and therefore recommend them for synthesis.

Keywords: aqueous solubility, azo disperse dye, degradation, disperse yellow 119, DMol³, reactivity

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Authors: Abubakar Dahiru Shuaibu, Atif Saeed Alzahrani, Md. Abdul Aziz

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Construction of eco-benign, cost effective, and high-performance supercapacitors with improved electrolytes and hierarchical porous electrodes is necessary for effective energy storage. In this study, a gel type organic redox electrolyte made of polyvinyl alcohol (PVA)-H2SO4 and an organic redox molecule, anthraquinone (PVA-H2SO4-AQ), was prepared by simple solution casting method and was used to construct a symmetric supercapacitor (SSC) with a high BET surface area (1612 m²/g) using activated carbon made from date stones (DSAC). The DSAC was synthesized by simple carbonization method followed by activation with potassium hydroxide. The SSC exhibit a high specific capacitance of 126.5 F/g at 0.5 A/g, as well as a high energy density of 17.5 Wh/kg at a power density of 250 W/kg with high capacitance retention (87%) after 1000 GCD cycles. The present research suggests that adding anthraquinone to a PVA-H2SO4 gel electrolyte improves the performance of the fabricated device significantly as compared to using pristine PVA-H₂SO₄ or 1M H₂SO₄ electrolytes. The research also presents a promising approach for the development of sustainable and eco-benign materials for energy storage applications. The use of date stone waste as a precursor material for activated carbon electrodes presents an opportunity for cost-effective and sustainable energy storage. Overall, the findings of this research have important implications for the future design and fabrication of high-performance and cost-effective supercapacitors

Keywords: date stone, activated carbon, anthraquinone, redox gel-electrolyte, supercapacitor

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Authors: C. M. Williams, R. English, P. King, I. M. Brown

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Introduction: Pseudoangiomatous Stromal Hyperplasia (PASH) is a benign fibrous proliferation of breast stroma affecting predominantly premenopausal women with no significant increased risk of breast cancer. Informal recommendations for management have continued to evolve over recent years from surgical excision to observation, although there are no specific national guidelines. This study assesses the safety of a non-surgical approach to PASH management by review of cases at a single centre. Methods: Retrospective case series review (January 2011 – August 2016) was conducted on consecutive PASH cases. Diagnostic classification (clinical, radiological and histological), management outcomes, and breast cancer incidence were recorded. Results: 43 patients were followed up for median of 25 months (3-64) with 75% symptomatic at presentation. 12% of cases (n=5) had a radiological score (BIRADS MMG or US) ≥ 4 of which 3 were confirmed malignant. One further malignancy was detected and proven radiologically occult and contralateral. No patients were diagnosed with a malignancy during follow-up. Treatment evolved from 67% surgical in 2011 to 33% in 2016. Conclusions: The management of PASH has transitioned in line with other published experience. The preliminary findings suggest this appears safe with no evidence of missed malignancies; however, longer follow up is required to confirm long-term safety. Recommendations: PASH with suspicious radiological findings ( ≥ U4/R4) warrants multidisciplinary discussion for excision. In the absence of histological or radiological suspicion of malignancy, PASH can be safely managed without surgery.

Keywords: benign breast disease, conservative management, malignancy, pseudoangiomatous stromal hyperplasia, surgical excision

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Authors: Abdoulie K. Ceesay

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Within the sequence of the whole genome, it is known that 99.9% of the human genome is similar, whilst our difference lies in just 0.1%. Among these minor dissimilarities, the most common type of genetic variations that occurs in a population is SNP, which arises due to nucleotide substitution in a protein sequence that leads to protein destabilization, alteration in dynamics, and other physio-chemical properties’ distortions. While causing variations, they are equally responsible for our difference in the way we respond to a treatment or a disease, including various cancer types. There are two types of SNPs; synonymous single nucleotide polymorphism (sSNP) and non-synonymous single nucleotide polymorphism (nsSNP). sSNP occur in the gene coding region without causing a change in the encoded amino acid, while nsSNP is deleterious due to its replacement of a nucleotide residue in the gene sequence that results in a change in the encoded amino acid. Predicting the effects of cancer related nsSNPs on protein stability, function, and dynamics is important due to the significance of phenotype-genotype association of cancer. In this thesis, Data of 5 oncogenes (ONGs) (AKT1, ALK, ERBB2, KRAS, BRAF) and 5 tumor suppressor genes (TSGs) (ESR1, CASP8, TET2, PALB2, PTEN) were retrieved from ClinVar. Five common in silico tools; Polyphen, Provean, Mutation Assessor, Suspect, and FATHMM, were used to predict and categorize nsSNPs as deleterious, benign, or neutral. To understand the impact of each variation on the phenotype, Maestro, PremPS, Cupsat, and mCSM-NA in silico structural prediction tools were used. This study comprises of in-depth analysis of 10 cancer gene variants downloaded from Clinvar. Various analysis of the genes was conducted to derive a meaningful conclusion from the data. Research done indicated that pathogenic variants are more common among ONGs. Our research also shows that pathogenic and destabilizing variants are more common among ONGs than TSGs. Moreover, our data indicated that ALK(409) and BRAF(86) has higher benign count among ONGs; whilst among TSGs, PALB2(1308) and PTEN(318) genes have higher benign counts. Looking at the individual cancer genes predisposition or frequencies of causing cancer according to our research data, KRAS(76%), BRAF(55%), and ERBB2(36%) among ONGs; and PTEN(29%) and ESR1(17%) among TSGs have higher tendencies of causing cancer. Obtained results can shed light to the future research in order to pave new frontiers in cancer therapies.

Keywords: tumor suppressor genes (TSGs), oncogenes (ONGs), non synonymous single nucleotide polymorphism (nsSNP), single nucleotide polymorphism (SNP)

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Authors: Hossein Anaraki-Ardakani, Tayebe Heidari-Rakati

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An environmentally benign protocol for the one-pot, three-component synthesis of Triazolo[1,2-a]indazole-1,3,8-trione derivatives by condensation of dimedone, urazole and aromatic aldehydes catalyzed by HClO4/SiO2 NPS as an ecofriendly catalyst with high catalytic activity and reusability at 100 ºC under solvent-free conditions is reported. The reaction proceeds to completion within 20-30 min in 77-86 % yield.

Keywords: one-pot reaction, dimedone, triazoloindazole, urazole

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Authors: Amira M. Hassanein, Nehal A. Salahuddin, Atsunori Matsuda, Toshiaki Hattori, Mona N. Elfiky

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New insights into the design of highly sensitive, carbon-based electrochemical sensors are presented in this work. This was achieved by exploring the interesting properties of conductive (Mg/Al) layered double hydroxide- Dodecyl Sulphate/Polypyrrole nanocomposites which were synthesized by in-situ polymerization of pyrrole during the assembly of (Mg/Al) layered double hydroxide, and by employing the anionic surfactant Dodecyl sulphate as a modifier. The morphology and surface area of the nanocomposites changed with the percentage of Pyrrole. Under optimal conditions, the modified carbon paste electrode successfully achieved detection limits of 0.057 and 0.134 nmol.L-1 of Terazosin hydrochloride in pharmaceutical formulation and spiked human serum fluid, respectively. Moreover, the sensors are highly stable, reusable, and free from interference by other commonly present excipients in drug formulations.

Keywords: layered double hydroxide, polypyrrole, terazosin hydrochloride, square-wave adsorptive anodic stripping voltammetry

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Authors: Shweta Dhindhwal

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Dopamine is an essential neurotransmitter in the central nervous system of all vertebrates and plays an important role in many processes such as motor function, learning and behavior, and sensory activity. One of the important functions of dopamine is release of pituitary hormones. It is synthesized from the amino acid tyrosine. Two types of dopamine receptors, D1-like and D2-like, have been reported in fish. The dopamine containing neurons are located in the olfactory bulbs, the ventral regions of the pre-optic area and tuberal hypothalamus. Distribution of the dopaminergic system has not been studied in the murrel, Channa punctatus. The present study deals with identification of D2 receptors in the brain of murrel. A phylogenetic tree has been constructed using partial sequence of D2 receptor. Distribution of putative dopaminergic neurons in the brain has been investigated. Also, formalin induced hypertrophy of neurosecretory cells in murrel has been studied.

Keywords: dopamine, fish, pre-optic area, murrel

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Authors: Massimo Miccoli, Luca Marangoni, Alberto Aniello Scaringi, Alessandro Marceddu, Alessandro Amicone

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The susceptibility of deep neural networks (DNNs) to adversarial manipulations is a recognized challenge within the computer vision domain. Adversarial examples, crafted by adding subtle yet malicious alterations to benign images, exploit this vulnerability. Various defense strategies have been proposed to safeguard DNNs against such attacks, stemming from diverse research hypotheses. Building upon prior work, our approach involves the utilization of autoencoder models. Autoencoders, a type of neural network, are trained to learn representations of training data and reconstruct inputs from these representations, typically minimizing reconstruction errors like mean squared error (MSE). Our autoencoder was trained on a dataset of benign examples; learning features specific to them. Consequently, when presented with significantly perturbed adversarial examples, the autoencoder exhibited high reconstruction errors. The architecture of the autoencoder was tailored to the dimensions of the images under evaluation. We considered various image sizes, constructing models differently for 256x256 and 512x512 images. Moreover, the choice of the computer vision model is crucial, as most adversarial attacks are designed with specific AI structures in mind. To mitigate this, we proposed a method to replace image-specific dimensions with a structure independent of both dimensions and neural network models, thereby enhancing robustness. Our multi-modal autoencoder reconstructs the spectral representation of images across the red-green-blue (RGB) color channels. To validate our approach, we conducted experiments using diverse datasets and subjected them to adversarial attacks using models such as ResNet50 and ViT_L_16 from the torch vision library. The autoencoder extracted features used in a classification model, resulting in an MSE (RGB) of 0.014, a classification accuracy of 97.33%, and a precision of 99%.

Keywords: adversarial attacks, malicious images detector, binary classifier, multimodal transformer autoencoder

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Authors: Menan M. Elsayed, Hussein A. Heshmat

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The aim of the study is to assess the effect of resistance training on muscle strength and physical performance of volleyball players of Physical Education College, Helwan University. The researcher used the experimental method of pre-post measurements of one group of 10 volleyball players. The execution of the program was through the period of 12/8/2018 to 12/10/2018; included 24 training units, 3 training units weekly for 8 weeks. The training program revealed an improvement in post measurement of muscle strength, IGF₁ (insulin-like growth factor 1), and physical performance of players. It may be concluded that the resistance training may include changes in hormones and muscle fibers leading to hypertrophy of the muscle and physical performance. It is recommended to use the results of the study in rationing the loads and training programs.

Keywords: IGF₁, muscle strength, physical performance, resistance training, volleyball players

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Authors: Adeleh Moshtaghi Zonouz, Issa Eskandari

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A simple, efficient, and green one-pot, four-component synthesis of highly substituted polyhydronaphthalenes in aqueous media is described. The method has such advantages as short reaction times, high yields, mild reaction conditions, operational simplicity and environmentally benign.

Keywords: polyhydronaphthalene, 2, 6-dicyanoanilines, multi-component reaction, aqueous media

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Authors: Yousef Reda

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Pancreatic cancer has an overall dismal prognosis. CT, MRI and Endoscopic Ultrasound are most often used to establish the diagnosis. We present a case of a patient found on abdominal CT and MRI to have an 8 mm cystic lesion within the head of the pancreas which was thought to be a benign intraductal papillary mucinous neoplasm (IPMN). Further evaluation by EUS demonstrated a 1 cm predominantly solid mass that was proven to be an adenocarcinoma by EUS-guided FNA. The patient underwent a Whipple procedure. The final pathology confirmed a 1 cm pT1 N0 pancreatic ductal adenocarcinoma. Case: A 63-year-old male presented with left upper quadrant pain and an abdominal CT demonstrated an 8 mm lesion within the head of the pancreas that was thought to represent a side branch IPMN. An MRI also showed similar findings. Four months later due to ongoing symptoms an EUS was performed to re-evaluate the pancreatic lesion. EUS revealed a predominantly solid hypoechoic, homogeneous mass measuring 12 mm x 9 mm. EUS-guided FNA was performed and was positive for adenocarcinoma. The patient underwent a Whipple procedure that confirmed it to be a ductal adenocarcinoma, pT1N0. The solid mass was noted to be adjacent to a cystic dilation with no papillary architecture and scant epithelium. The differential diagnosis resided between cystic degeneration of a primary pancreatic adenocarcinoma versus malignant degeneration within a side-branch IPMN. Discussion: The reported sensitivity of CT for pancreatic cancer is approximately 90%. For pancreatic tumors, less than 3 cm the sensitivity of CT is reduced ranging from 67-77%. MRI does not significantly improve overall detection rates compared to CT. EUS, however is superior to CT in the detection of pancreatic cancer, in particular among lesions smaller than 3 cm. EUS also outperforms CT and MRI in distinguishing neoplastic from non-neoplastic cysts. In this case, both MRI and CT failed to detect a small pancreatic adenocarcinoma. The addition of EUS and FNA to abdominal imaging can increase overall accuracy for the diagnosis of neoplastic pancreatic lesions. It may be prudent that when small lesions although appearing as a benign IPMN should further be evaluated by EUS as this would lead to potentially identifying earlier stage pancreatic cancers and improve survival in a disease which has a dismal prognosis.

Keywords: IPMN, MRI, EUS, CT

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Authors: Gloria M. Ntuba-Jua, Afui M. Mih, Eneke E. T. Bechem

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Prunus africana (Hook. F.) Kalkman, commonly known as Pygeum or African cherry belongs to the Rosaceae family. It is a medium to large, evergreen tree with a spreading crown of 10 to 20 m. It is used by the traditional medical practitioners for the treatment of over 45ailments in Cameroon and sub-Sahara Africa. In modern medicine, it is used in the treatment of benign prostrate hyperplasia (BPH), prostate gland hypertrophy (enlarged prostate glands). This is possible because of its ability to produce some secondary metabolites which are believed to have bioactivity against these ailments. The ready international market for the sale of Prunus bark, uncontrolled exploitation, illegal harvesting using inappropriate techniques and poor timing of harvesting have contributed enormously to making the plant endangered. It is known to harbor a large number of endophytic fungi with the potential to produce similar secondary metabolites as the parent plant. Alternative sourcing of medicinal principles through endophytic fungi requires succinct knowledge of the endophytic fungi. This will serve as a conservation measure for Prunus africana by reducing dependence on Prunus bark for such metabolites. This work thus sought to compare the production of some major secondary metabolites produced by P. africana and some of its associated endophytic fungi. The leaves and stem bark of the plant from different provenances were soaked in methanol for 72 hrs to yield the methanolic crude extract. The phytochemical screening of the methanolic crude extracts using different standard procedures revealed the presence of tannins, flavonoids, terpenoids, saponins, phenolics and steroids. Pure cultures of some predominantly isolated endophyte species from the difference Prunus provenances such as Curvularia sp, and Morphospecies P001 were also grown in Potato Dextrose Broth (PDB) for 21 days and later extracted with Methylene dichloride (MDC) solvent after 24hrs to produce crude culture extracts. Qualitative assessment of crude culture extracts showed the presence of tannins, terpenoids, phenolics and steroids particularly β-Sitosterol, (a major bioactive metabolite) as did the plant tissues. Qualitative analysis by thin layer chromatography (TLC) was done to confirm and compare the production of β-Sitosterol (as marker compounds) in the crude extracts of the plant and endophyte. Samples were loaded on TLC silica gel aluminium barked plate (Kieselgel 60 F254, 0.2 mm, Merck) using acetone/hexane, (3.0:7.0) solvent system. They were visualized under an ultra violet lamp (UV254 and UV360). TLC revealed that leaves had a higher concentration of β-sitosterol in terms of band intensity than stem barks from the different provenances. The intensity of β-sitosterol bands in the culture extracts of endophytes was comparable to the plant extracts except for Curvularia sp (very minute) whose band was very faint. The ability of these fungi to make β-sitosterol was confirmed by TLC analysis with the compound having chromatographic properties (retention factor) similar to those of β-sitosterol standard. The ability of these major endophytes to produce secondary metabolites similar to the host has therefore been demonstrated. There is, therefore, the potential of developing the in vitro production system of Prunus secondary metabolites thereby enhancing its conservation.

Keywords: Caneroon, endophytic fungi, Prunus africana, secondary metabolite

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Authors: Amirul Adlan, Motaz AlAqeel, Scott Evans, Vaiyapuri sumathi, Mark Davies, Rajesh Botchu

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Background & Objectives: Osteoid osteoma (OO) is a benign tumor of the bone commonly found in childhood and adolescence, causing bone pain, especially during the night. CT-guided radiofrequency ablation (RFA) is currently the mainstay treatment for OO. There is currently no literature reporting the outcomes of OO following RFA based on the histological presence of a nidus seen on a biopsy taken at the time of RFA. The primary aim of this study was to compare the clinical outcomes of OO between the group of patients with the presence of nidus on biopsy samples from RFA with those without nidus. Secondly, we aimed to examine other factors that may affect the outcomes of OO, reflecting our experience as a tertiary orthopedic oncology center. Methods: We retrospectively reviewed 88 consecutive patients diagnosed with osteoid osteoma treated with RFA between November 2005 and March 2015, consisting of 63 males (72%) and 25 females (28%). Sixty-six patients (75%) had nidus present in their biopsy samples. Patients’ mean age was 17.6 years (4-53). The median duration of follow-up was 12.5 months (6-20.8). Lesions were located in the appendicular skeleton in seventy-nine patients (90%), while nine patients (10%) had an OO in the axial skeleton. Outcomes assessed were based on patients’ pain alleviation (partial, complete, or no pain improvement) and the need for further interventions. Results: Pain improvement in the patient group with nidus in the histology sample was significantly better than in the group without nidus (OR 7.4, CI 1.35-41.4, p=0.021). The patient group with nidus on biopsy demonstrated less likelihood of having a repeat procedure compared to the group without nidus(OR 0.092, CI 0.016-0.542, p=0.008). Our study showed significantly better outcomes in pain improvement in appendicular lesions compared to the axially located lesions (p = 0.005). Patients with spinal lesions tend to have relatively poor pain relief than those with appendicular or pelvic lesions (p=0.007). Conclusions: Patients with nidus on histology had better pain alleviation compared to patients without nidus. The histological presence of nidus significantly reduces the chance of repeat interventions. The pain alleviation of osteoid osteoma following RFA is better in patients with appendicular lesions than spinal or axially located lesions.

Keywords: osteoid osteoma, benign tumour, radiofrequency ablation, oncology

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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: Diwei Lin, Amanda Tan, Rajinder Singh-Rai

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We present the first reported case of a concomitant Leydig cell tumor (LCT) and paratesticular leiomyoma in an adult male with a known history of bilateral cryptorchidism. An 80-year-old male presented with a 2-month history of a left testicular lump associated with mild discomfort and a gradual increase in size on a background of bilateral cryptorchidism requiring multiple orchidopexy procedures as a child. Ultrasound confirmed a lesion suspicious for malignancy and he proceeded to a left radical orchidectomy. Histopathological assessment of the left testis revealed a concomitant testicular LCT with malignant features and paratesticular leiomyoma. Leydig cell tumors (LCTs) are the most common pure testicular sex cord-stromal tumors, accounting for up to 3% of all testicular tumors. They can occur at almost any age, but are noted to have a bi-modal distribution, with a peak incidence at 6 to 10 and at 20 to 50 years of age. LCT’s are often hormonally active and can lead to feminizing or virilizing syndromes. LCT’s are usually regarded as benign but can rarely exhibit malignant traits. Paratesticular tumours are uncommon and their reported prevalence varies between 3% and 16%. They occur in a complex anatomical area which includes the contents of the spermatic cord, testicular tunics, epididymis and vestigial remnants. Up to 90% of paratesticular tumours are believed to originate from the spermatic cord, though it is often difficult to definitively ascertain the exact site of origin. Although any type of soft-tissue neoplasm can be found in the paratesticular region, the most common benign tumors reported are lipomas of the spermatic cord, adenomatoid tumours of the epididymis and leiomyomas of the testis. Genetic studies have identified potential mutations that could potentially cause LCTs, but there are no known associations between concomitant LCTs and paratesticular tumors. The presence of cryptorchidism in adults with both LCTs and paratesticular neoplasms individually has been previously reported and it appears intuitive that cryptorchidism is likely to be associated with the concomitant presentation in this case report. This report represents the first documented case in the literature of a unilateral concomitant LCT and paratesticular leiomyoma on a background of bilateral cryptorchidism.

Keywords: testicular cancer, leydig cell tumour, leiomyoma, paratesticular neoplasms

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Authors: Magdalena Chrabąszcz, Teresa Wolniewicz, Cezary Maciejewski, Joanna Czuwara

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BACKGROUND: Dermoscopy is a clinical tool known to improve the early detection of melanoma and other malignancies of the skin. Over the past few years melanoma has grown into a disease of socio-economic importance due to the increasing incidence and persistently high mortality rates. Early diagnosis remains the best method to reduce melanoma and non-melanoma skin cancer– related mortality and morbidity. Dermoscopy is a noninvasive technique that consists of viewing pigmented skin lesions through a hand-held lens. This simple procedure increases melanoma diagnostic accuracy by up to 35%. Dermoscopy is currently the standard for clinical differential diagnosis of cutaneous melanoma and for qualifying lesion for the excision biopsy. Like any clinical tool, training is required for effective use. The introduction of small and handy dermoscopes contributed significantly to the switch of dermatoscopy toward a first-level useful tool. Non-dermatologist physicians are well positioned for opportunistic melanoma detection; however, education in the skin cancer examination is limited during medical school and traditionally lecture-based. AIM: The aim of this randomized study was to determine whether the adjunct of dermoscopy to the standard fourth year medical curriculum improves the ability of medical students to distinguish between benign and malignant lesions and assess acceptability and satisfaction with the intervention. METHODS: We performed a prospective study in 2 cohorts of fourth-year medical students at Medical University of Warsaw. Groups having dermatology course, were randomly assigned to:  cohort A: with limited access to dermatoscopy from their teacher only – 1 dermatoscope for 15 people  Cohort B: with a full access to use dermatoscopy during their clinical classes:1 dermatoscope for 4 people available constantly plus 15-minute dermoscopy tutorial. Students in both study arms got an image-based test of 10 lesions to assess ability to differentiate benign from malignant lesions and postintervention survey collecting minimal background information, attitudes about the skin cancer examination and course satisfaction. RESULTS: The cohort B had higher scores than the cohort A in recognition of nonmelanocytic (P < 0.05) and melanocytic (P <0.05) lesions. Medical students who have a possibility to use dermatoscope by themselves have also a higher satisfaction rates after the dermatology course than the group with limited access to this diagnostic tool. Moreover according to our results they were more motivated to learn dermatoscopy and use it in their future everyday clinical practice. LIMITATIONS: There were limited participants. Further study of the application on clinical practice is still needed. CONCLUSION: Although the use of dermatoscope in dermatology as a specialty is widely accepted, sufficiently validated clinical tools for the examination of potentially malignant skin lesions are lacking in general practice. Introducing medical students to dermoscopy in their fourth year curricula of medical school may improve their ability to differentiate benign from malignant lesions. It can can also encourage students to use dermatoscopy in their future practice which can significantly improve early recognition of malignant lesions and thus decrease melanoma mortality.

Keywords: dermatoscopy, early detection of melanoma, medical education, skin cancer

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Authors: Margarita Ivanova, Julia Dao, Andrew Friedman, Neil Kasaci, Rekha Gopal, Ozlem Goker-Alpan

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In Fabry disease (FD), α-galactosidase A (α-Gal A) deficiency leads to the accumulation of globotriaosylceramide (Lyso-Gb3 and Gb3), triggering a pathologic cascade that causes the severity of organs damage. The heart is one of the several organs with high sensitivity to the α-Gal A deficiency. A subgroup of patients with significant residual of α-Gal A activity with primary cardiac involvement is occasionally referred to as “cardiac variant.” The cardiovascular complications are most frequently encountered, contributing substantially to morbidity, and are the leading cause of premature death in male and female patients with FD. The deposition of Lyso-Gb-3 and Gb-3 within the myocardium affects cardiac function with resultant progressive cardiovascular pathology. Gb-3 and Lyso-Gb-3 accumulation at the cellular level trigger a cascade of events leading to end-stage fibrosis. In the cardiac tissue, Lyso-Gb-3 deposition is associated with the increased release of inflammatory factors and transforming growth factors. Infiltration of lymphocytes and macrophages into endomyocardial tissue indicates that inflammation plays a significant role in cardiac damage. Moreover, accumulated data suggest that chronic inflammation leads to multisystemic FD pathology even under enzyme replacement therapy (ERT). NF-κB activation plays a subsequent role in the inflammatory response to cardiac dysfunction and advanced heart failure in the general population. TNFalpha/NF-κB signaling protects the myocardial evoking by ischemic preconditioning; however, this protective effect depends on the concentration of TNF-α. Thus, we hypothesize that TNF-α is a critical factor in determining the grade of cardio-pathology. Cardiac hypertrophy corresponds to the expansion of the coronary vasculature to maintain a sufficient supply of nutrients and oxygen. Coronary activation of angiogenesis and fibrosis plays a vital role in cardiac vascularization, hypertrophy, and tissue remodeling. We suggest that the interaction between the inflammatory pathways and cardiac vascularization is a bi-directional process controlled by secreted cytokines and growth factors. The co-coordination of these two processes has never been explored in FD. In a cohort of 40 patients with FD, biomarkers associated with inflammation and cardio hypertrophic remodeling were studied. FD patients were categorized into three groups based on LVmass/DSA, LVEF, and ECG abnormalities: FD with no cardio complication, FD with moderate cardio complication, and severe cardio complication. Serum levels of NF-kB, TNFalpha, Il-6, Il-2, MCP1, ING-gamma, VEGF, IGF-1, TGFβ, and FGF2 were quantified by enzyme-linked immunosorbent assays (ELISA). Among the biomarkers, MCP-1, INF-gamma, VEGF, TNF-alpha, and TGF-beta were elevated in FD patients. Some of these biomarkers also have the potential to correlate with cardio pathology in FD. Conclusion: The study provides information about the role of inflammatory pathways and biomarkers of cardio hypertrophic remodeling in FD patients. This study will also reveal the mechanisms that link intracellular accumulation of Lyso-GB-3 and Gb3 to the development of cardiomyopathy with myocardial thickening and resultant fibrosis.

Keywords: biomarkers, Fabry disease, inflammation, growth factors

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Authors: Leander Van Neste, Kirk Wojno

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The innate immune system reacts to foreign insult in several unique ways, one of which is phagocytosis of perceived threats such as cancer, bacteria, and viruses. The goal of this study was to look for evidence of phagocytosed RNA from tumor cells in circulating monocytes. While all monocytes possess phagocytic capabilities, the non-classical CD14+/FCGR3A+ monocytes and the intermediate CD14++/FCGR3A+ monocytes most actively remove threatening ‘external’ cellular materials. Purified CD14-positive monocyte samples from fourteen patients recently diagnosed with clinically localized prostate cancer (PCa) were investigated by single-cell RNA sequencing using the 10X Genomics protocol followed by paired-end sequencing on Illumina’s NovaSeq. Similarly, samples were processed and used as controls, i.e., one patient underwent biopsy but was found not to harbor prostate cancer (benign), three young, healthy men, and three men previously diagnosed with prostate cancer that recently underwent (curative) radical prostatectomy (post-RP). Sequencing data were mapped using 10X Genomics’ CellRanger software and viable cells were subsequently identified using CellBender, removing technical artifacts such as doublets and non-cellular RNA. Next, data analysis was performed in R, using the Seurat package. Because the main goal was to identify differences between PCa patients and ‘control’ patients, rather than exploring differences between individual subjects, the individual Seurat objects of all 21 patients were merged into one Seurat object per Seurat’s recommendation. Finally, the single-cell dataset was normalized as a whole prior to further analysis. Cell identity was assessed using the SingleR and cell dex packages. The Monaco Immune Data was selected as the reference dataset, consisting of bulk RNA-seq data of sorted human immune cells. The Monaco classification was supplemented with normalized PCa data obtained from The Cancer Genome Atlas (TCGA), which consists of bulk RNA sequencing data from 499 prostate tumor tissues (including 1 metastatic) and 52 (adjacent) normal prostate tissues. SingleR was subsequently run on the combined immune cell and PCa datasets. As expected, the vast majority of cells were labeled as having a monocytic origin (~90%), with the most noticeable difference being the larger number of intermediate monocytes in the PCa patients (13.6% versus 7.1%; p<.001). In men harboring PCa, 0.60% of all purified monocytes were classified as harboring PCa signals when the TCGA data were included. This was 3-fold, 7.5-fold, and 4-fold higher compared to post-RP, benign, and young men, respectively (all p<.001). In addition, with 7.91%, the number of unclassified cells, i.e., cells with pruned labels due to high uncertainty of the assigned label, was also highest in men with PCa, compared to 3.51%, 2.67%, and 5.51% of cells in post-RP, benign, and young men, respectively (all p<.001). It can be postulated that actively phagocytosing cells are hardest to classify due to their dual immune cell and foreign cell nature. Hence, the higher number of unclassified cells and intermediate monocytes in PCa patients might reflect higher phagocytic activity due to tumor burden. This also illustrates that small numbers (~1%) of circulating peripheral blood monocytes that have interacted with tumor cells might still possess detectable phagocytosed tumor RNA.

Keywords: circulating monocytes, phagocytic cells, prostate cancer, tumor immune response

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Authors: Mohammadjavad Sotoudeheian

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Heart failure (HF) prevalence, as a global cardiovascular problem, is increasing gradually. A variety of molecular mechanisms contribute to HF. Proteins involved in cardiac contractility regulation, such as ion channels and calcium handling proteins, are altered. Additionally, epigenetic modifications and gene expression can lead to altered cardiac function. Moreover, inflammation and oxidative stress contribute to HF. The progression of HF can be attributed to mitochondrial dysfunction that impairs energy production and increases apoptosis. Molecular mechanisms such as these contribute to the development of cardiomyocyte defects and HF and can be therapeutically targeted. The heart's contractile function is controlled by cardiomyocytes. Calpain, and its related molecules, including Bax, VEGF, and AMPK, are among the proteins involved in regulating cardiomyocyte function. Apoptosis is facilitated by Bax. Cardiomyocyte apoptosis is regulated by this protein. Furthermore, cardiomyocyte survival, contractility, wound healing, and proliferation are all regulated by VEGF, which is produced by cardiomyocytes during inflammation and cytokine stress. Cardiomyocyte proliferation and survival are also influenced by AMPK, an enzyme that plays an active role in energy metabolism. They all play key roles in apoptosis, angiogenesis, hypertrophy, and metabolism during myocardial inflammation. The role of calpains has been linked to several molecular pathways. The calpain pathway plays an important role in signal transduction and apoptosis, as well as autophagy, endocytosis, and exocytosis. Cell death and survival are regulated by these calcium-dependent cysteine proteases that cleave proteins. As a result, protein fragments can be used for various cellular functions. By cleaving adhesion and motility proteins, calcium proteins also contribute to cell migration. HF may be brought about by calpain-mediated pathways. Many physiological processes are mediated by the calpain molecular pathways. Signal transduction, cell death, and cell migration are all regulated by these molecular pathways. Calpain is activated by calcium binding to calmodulin. In the presence of calcium, calmodulin activates calpain. Calpains are stimulated by calcium, which increases matrix metalloproteinases (MMPs). In order to develop novel treatments for these diseases, we must understand how this pathway works. A variety of myocardial remodeling processes involve calpains, including remodeling of the extracellular matrix and hypertrophy of cardiomyocytes. Calpains also play a role in maintaining cardiac homeostasis through apoptosis and autophagy. The development of HF may be in part due to calpain-mediated pathways promoting cardiomyocyte death. Numerous studies have suggested the importance of the Ca2+ -dependent protease calpain in cardiac physiology and pathology. Therefore, it is important to consider this pathway to develop and test therapeutic options in humans that targets calpain in HF. Apoptosis, autophagy, endocytosis, exocytosis, signal transduction, and disease progression all involve calpain molecular pathways. Therefore, it is conceivable that calpain inhibitors might have therapeutic potential as they have been investigated in preclinical models of several conditions in which the enzyme has been implicated that might be treated with them. Ca 2+ - dependent proteases and calpains contribute to adverse ventricular remodeling and HF in multiple experimental models. In this manuscript, we will discuss the calpain molecular pathway's important roles in HF development.

Keywords: calpain, heart failure, autophagy, apoptosis, cardiomyocyte

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Authors: kamran Bhatti

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Objective: To evaluate spectrum and resistance rates to antibacterial agents in causative pathogens of bacterial prostatitis in patients from Southern Europe, the Middle East, and Africa. Materials: 1027 isolates from cultures of urine or expressed prostatic secretion, post-massage urine or seminal fluid, or urethral samples were considered. Results: Escherichia coli (32%) and Enterococcus spp. (21%) were the most common isolates. Other Gram-negative, Gram-positive, and atypical pathogens accounted for 22%, 20%, and 5%, respectively. Resistance was <15% for piperacillin/tazobactam and carbapenems (both Gram-negative and -positive pathogens); <5% for glycopeptides against Gram-positive; 7%, 14%, and 20% for aminoglycosides, fosfomycin, and macrolides against Gram-negative pathogens, respectively; 10% for amoxicillin/clavulanate against Gram-positive pathogens; <20% for cephalosporins and fluoroquinolones against to Gram-negative pathogens (higher against Gram-positive pathogens); none for macrolides against atypical pathogens, but 20% and 27% for fluoroquinolones and tetracyclines. In West Africa, the resistance rates were generally higher, although the highest rates for ampicillin, cephalosporins, and fluoroquinolones were observed in the Gulf area. Lower rates were observed in Southeastern Europe. Conclusions: Resistance to antibiotics is a health problem requiring local health authorities to combat this phenomenon. Knowledge of the spectrum of pathogens and antibiotic resistance rates is crucial to assess local guidelines for the treatment of prostatitis.

Keywords: enterobacteriacae; escherichia coli, gram-positive pathogens, antibiotic, bacterial prostatitis, resistance

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Authors: Maryam Sabbaghan, Pegah Sofalgar

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Over the past few decades, a significant amount of research activities in the chemical community has been directed towards green synthesis. This area of chemistry has received extensive attention because of environmentally benign processes as well as economically viable. In this article, the MgO nanoparticles were prepared by different methods in the present of ionic liquids. A wide range of Magnesium oxide particle sizes within the nanometer scale is obtained by these methods. The structure of these MgO particles was studied by using X-ray diffraction (XRD), Infrared spectroscopy (IR), and scanning electron microscopy (SEM). It was found that the formation of nanoparticle could involve the role of performed 'nucleus' and used template to control the growth rate of nucleuses. The crystallite size of the MgO products was in a range from 31 to 77 nm.

Keywords: MgO, ionic liquid, nanoparticles, green chemistry

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Authors: Parthasarathi Pramanik

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Body packing is a way of transfer drugs across the international border or any drug prohibited area. The drugs are usually hidden in body packets inside the anatomical body cavities like mouth, intestines, rectum, ear, vagina etc. Cocaine is a very common drug for body packing across the world. A 48 year old male was reported dead in his hotel after complaining of chest pain and vomiting. At autopsy, there were eighty-two white cylindrical body packs in the stomach, small and large intestines. Seals of few of the packets were opened. Toxicological examination revealed presence of cocaine in the stomach, liver, kidney and hair samples. Microscopically, presence of myocardial necrosis with interstitial oedema along with hypertrophy and fibrosis of the myocardial fibre suggested heart failure due to cocaine cardio toxicity. However, focal lymphocyte infiltration and perivascular fibrosis in the myocardium also indicated chronic cocaine toxicity of the deceased. After careful autopsy examination it was considered the victim was died due congestive heart failure secondary to acute and chronic cocaine poisoning.

Keywords: cardiac failure, cocaine, body packer, sudden death

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Authors: N. D'Amico, E. Grossi, B. Colombo, F. Rigiroli, M. Buscema, D. Fazzini, G. Cornalba, S. Papa

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Purpose: To characterize, through a radiomic approach, the nature of nodules considered non-specific by expert radiologists, recognized in magnetic resonance mammography (MRm) with T1-weighted (T1w) sequences with paramagnetic contrast. Material and Methods: 47 cases out of 1200 undergoing MRm, in which the MRm assessment gave uncertain classification (non-specific nodules), were admitted to the study. The clinical outcome of the non-specific nodules was later found through follow-up or further exams (biopsy), finding 35 benign and 12 malignant. All MR Images were acquired at 1.5T, a first basal T1w sequence and then four T1w acquisitions after the paramagnetic contrast injection. After a manual segmentation of the lesions, done by a radiologist, and the extraction of 150 radiomic features (30 features per 5 subsequent times) a machine learning (ML) approach was used. An evolutionary algorithm (TWIST system based on KNN algorithm) was used to subdivide the dataset into training and validation test and to select features yielding the maximal amount of information. After this pre-processing, different machine learning systems were applied to develop a predictive model based on a training-testing crossover procedure. 10 cases with a benign nodule (follow-up older than 5 years) and 18 with an evident malignant tumor (clear malignant histological exam) were added to the dataset in order to allow the ML system to better learn from data. Results: NaiveBayes algorithm working on 79 features selected by a TWIST system, resulted to be the best performing ML system with a sensitivity of 96% and a specificity of 78% and a global accuracy of 87% (average values of two training-testing procedures ab-ba). The results showed that in the subset of 47 non-specific nodules, the algorithm predicted the outcome of 45 nodules which an expert radiologist could not identify. Conclusion: In this pilot study we identified a radiomic approach allowing ML systems to perform well in the diagnosis of a non-specific nodule at MR mammography. This algorithm could be a great support for the early diagnosis of malignant breast tumor, in the event the radiologist is not able to identify the kind of lesion and reduces the necessity for long follow-up. Clinical Relevance: This machine learning algorithm could be essential to support the radiologist in early diagnosis of non-specific nodules, in order to avoid strenuous follow-up and painful biopsy for the patient.

Keywords: breast, machine learning, MRI, radiomics

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Authors: Yanuarti Retnaningrum, Cendrawasih A. Farmasyanti, Kuswahyuning

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Orthodontists find challenges in treating patients who have cases of macroglossia and multiple tooth agenesis because difficulties in determining the causes, formulating a diagnosis and the potential for relapse after treatment. Definition of macroglossia is a tongue enlargement due to muscle hypertrophy, tumor or an endocrine disturbance. Macroglossia may cause many problems such as anterior proclination of upper and lower incisors, development of general diastema and anterior and/ or posterior open bite. Treatment for such patients with multiple tooth agenesis and macroglossia can be complex and must consider orthodontic and/or surgical interventions. This article discusses an orthodontic non surgical approach to a patient with a general diastema in both maxilla and mandible associated with multiple tooth agenesis and macroglossia. Fixed orthodontic therapy with straightwire appliance was used for space closure in anterior region of maxilla and mandible, also to create a space suitable for future prosthetic restoration. After 12 months treatment, stable and functional occlusal relationships was achieved, although still have edentulous area in both maxilla and mandible. At the end of the orthodontic treatment was obtained with correct overbite and overjet values. After removal of the brackets, a maxillary and mandibular removable retainer combine with artificial tooth were placed for retention.

Keywords: general diastema, macroglossia, space closure, tooth agenesis

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