Search results for: epidemiology of cutaneous malignant melanoma

Authors: Anupama Sahoo, Bongyong Lee, Katia Boniface, Julien Seneschal, Sanjaya K. Sahoo, Tatsuya Seki, Chunyan Wang, Soumen Das, Xianlin Han, Michael Steppie, Sudipta Seal, Alain Taieb, Ranjan J. Perera

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Vitiligo is a common, chronic skin disorder characterized by loss of epidermal melanocytes and progressive depigmentation. Vitiligo has a complex immune, genetic, environmental, and biochemical etiology, but the exact molecular mechanisms of vitiligo development and progression, particularly those related to metabolic control, are poorly understood. Here we characterized the human vitiligo cell line PIG3V and the normal human melanocytes, HEM-l by RNA-sequencing, targeted metabolomics, and shotgun lipidomics. Melanocyte-enriched miR-211, a known metabolic switch in non-pigmented melanoma cells, was severely downregulated in vitiligo cell line PIG3V and skin biopsies from vitiligo patients, while its novel predicted targets transcriptional co-activator PGC1-α (PPARGC1A), ribonucleotide reductase regulatory subunit M2 (RRM2), and serine-threonine protein kinase TAO1 (TAOK1) were reciprocally upregulated. miR-211 binds to PGC1-α 3’UTR locus and represses it. Although mitochondrial numbers were constant, mitochondrial complexes I, II, and IV and respiratory responses were defective in vitiligo cells. Nanoparticle-coated miR-211 partially augmented the oxygen consumption rate in PIG3V cells. The lower oxygen consumption rate, changes in lipid and metabolite profiles, and increased reactive oxygen species production observed in vitiligo cells appear to be partly due to abnormal regulation of miR-211 and its target genes. These genes represent potential biomarkers and therapeutic targets in human vitiligo.

Keywords: metabolism, microRNA, mitochondria, vitiligo

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Authors: Yung-Chih Kuo, I-Hsuan Lee

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Solid lipid nanoparticles (SLNs) conjugated with aprotinin (Apr) and melanotransferrin antibody (Anti-MTf) were used to carry doxorubicin (Dox) across the blood–brain barrier (BBB) for glioblastoma multiforme (GBM) chemotherapy. Dox-entrapped SLNs with grafted Apr and Anti-MTf (Apr-Anti-MTf-Dox-SLNs) were applied to a cultured monolayer comprising human brain-microvascular endothelial cells (HBMECs) with regulation of human astrocyte (HAs) and to a proliferated colony of U87MG cells. Based on the average particle diameter, zeta potential, entrapping efficiency of Dox, and grafting efficiency of Apr and Anti-MTf, we found that 40% (w/w) 1,2-dipalmitoyl-sn-glycero-3-phosphocholine in lipids were appropriate for fabricating Apr-Anti-MTf-Dox-SLNs. In addition, Apr-Anti-MTf-Dox-SLNs could prevent Dox from fast dissolution and did not induce a serious cytotoxicity to HBMECs and HAs when compared with free Dox. Moreover, the treatments with Apr-Anti-MTf-Dox-SLNs enhanced the ability of Dox to infuse the BBB and to inhibit the growth of GBM. The current Apr-Anti-MTf-Dox-SLNs can be a promising pharmacotherapeutic preparation to penetrate the BBB for malignant brain tumor treatment.

Keywords: solid lipid nanoparticle, glioblastoma multiforme, blood–brain barrier, doxorubicin

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Authors: Thibaud Berthomier, Ali Mansour, Luc Bressollette, Frédéric Le Roy, Dominique Mottier, Léo Fréchier, Barthélémy Hermenault

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Deep Venous Thrombosis (DVT) occurs when a thrombus is formed within a deep vein (most often in the legs). This disease can be deadly if a part or the whole thrombus reaches the lung and causes a Pulmonary Embolism (PE). This disorder, often asymptomatic, has multifactorial causes: immobilization, surgery, pregnancy, age, cancers, and genetic variations. Our project aims to relate the thrombus epidemiology (origins, patient predispositions, PE) to its structure using ultrasound images. Ultrasonography and elastography were collected using Toshiba Aplio 500 at Brest Hospital. This manuscript compares two classification approaches: spectral clustering and scattering operator. The former is based on the graph and matrix theories while the latter cascades wavelet convolutions with nonlinear modulus and averaging operators.

Keywords: deep venous thrombosis, ultrasonography, elastography, scattering operator, wavelet, spectral clustering

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Authors: Katie-Beth Webster

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Mucormycosis is a rare opportunistic fungal infection that, if left untreated, can cause large scale tissue necrosis and death. There are a number of cases of this in the literature, most commonly in the head and neck region arising from sinuses. It is also usually found in immunocompromised patient subgroups. This study reviewed a number of cases of mucormycosis in previously fit and healthy young trauma patients to assess predisposing factors for infection and adequacy of current treatment paradigms. These trauma patients likely contracted the fungal infection from the soil at the site of the incident. Despite early washout and debridement of the wounds at the scene of the injury and on arrival in hospital, both these patients contracted mucormycosis. It was suspected that inadequate early debridement of soil contaminated limbs was one of the major factors that can lead to catastrophic tissue necrosis. In both cases, this resulted in the patients having a higher level of amputation than would have initially been required based on the level of their injury. This was secondary to cutaneous and soft tissue necrosis secondary to the fungal infiltration leading to osteomyelitis and systemic sepsis. In the literature, it appears diagnosis is often protracted in this condition secondary to inadequate early treatment and long processing times for fungal cultures. If fungal cultures were sent at the time of first assessment and adequate debridements are performed aggressively early, it could lead to these critically unwell trauma patients receiving appropriate antifungal and surgical treatment earlier in their episode of care. This is likely to improve long term outcomes for these patients.

Keywords: mucormycosis, plastic surgery, osteomyelitis, trauma

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Authors: Vishal Bhatnagar

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The objective of this study is to compare the efficacy of epidural analgesia of two amide local anesthetics, ropivacaine and levobupivacaine, with fentanyl for postoperative analgesia in major abdominal surgery CRS+HIPEC. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS+HIPEC) are done for primary peritoneal malignancies or peritoneal spread of malignant neoplasm. CRS and HIPEC are considered one of the most painful surgery among all major abdominal surgeries. Poorly managed postoperative pain elevates stress, increases anxiety, causes prolonged Hospital stay, increases opioid requirement and side effects, increases the cost of treatment and psychological effects on patient and family. It affects the quality of life of patients. The epidural technique provides better postoperative analgesia, earlier recovery of bowel function, fewer side effects, higher patient satisfaction, and an improvement in life quality in the postoperative days after abdominal surgery than other analgesic techniques.

Keywords: HIPEC, postoperative analgesia, cytoreductive surgery, VAS score, rescue analgesia

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Authors: Harish Rajak, Kamlesh Raghuwanshi

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Histone deacetylase (HDAC) are promising target for cancer treatment. The panobinostat (Farydak; Novartis; approved by USFDA in 2015) and chidamide (Epidaza; Chipscreen Biosciences; approved by China FDA in 2014) are the novel HDAC inhibitors ratified for the treatment of patients with multiple myeloma and peripheral T cell lymphoma, respectively. On the other hand, two other HDAC inhibitors, Vorinostat (SAHA; approved by USFDA in 2006) and Romidepsin (FK228; approved by USFDA in 2009) are already in market for the treatment of cutaneous T-cell lymphoma. Several hydroxamic acid based HDAC inhibitors i.e., belinostat, givinostat, PCI24781 and JNJ26481585 are in clinical trials. HDAC inhibitors consist of three pharmacophoric features - an aromatic cap group, zinc binding group (ZBG) and a linker chain connecting cap group to ZBG. Herein, we report synthesis, characterization and biological evaluation of HDAC inhibitors possessing substituted isatin moiety as cap group which recognize the surface of active enzyme pocket and thiosemicarbazide moiety incorporated as linker group responsible for connecting cap group to ZBG (hydroxamic acid). Several analogues were found to inhibit HDAC and cellular proliferation of Hela cervical cancer cells with GI50 values in the micro molar range. Some of the compounds exhibited promising results in vitro antiproliferative studies. Attempts were also made to establish the structure activity relationship among synthesized HDAC inhibitors.

Keywords: HDAC inhibitors, hydroxamic acid derivatives, isatin derivatives, antiproliferative activity, docking

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Authors: Tessalyn Morrison, Alexis Dinno, Taurica Salmon

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Sex and gender conflation continue to perpetuate the invisibility of gender minorities and obscure information about the ways that biological sex and gender affect health. The misuse of sex and gender terms, and their respective binaries, can yield inaccurate results. But more importantly, it contributes to the erasure of sex and gender minority health experiences. This paper discusses ways in which public health researchers can use sex and gender terms correctly and center the health experiences of intersex, transgender, non binary, and a-gender individuals. It includes promoting sensitivity in approaching minority communities, improving survey questions, and collaborating with sex and gender minority communities to improve research quality and participant experiences. Improving our standards for the quality of sex and gender term usage and centering sex and gender minorities in public health research are imperative to address the health inequalities faced by sex and gender minorities.

Keywords: epidemiology, gender, intersex, research methods, sex, transgender

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Authors: Lydia Tan, Philippe Lemey, Lieselot Houspie, Marco Viveen, Darren Martin, Frank Coenjaerts

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Introduction: Human respiratory syncytial virus (hRSV) is the leading cause of severe respiratory tract infections in infants under the age of two. Genomic substitutions and related evolutionary dynamics of hRSV are of great influence on virus transmission behavior. The evolutionary patterns formed are due to a precarious interplay between the host immune response and RSV, thereby selecting the most viable and less immunogenic strains. Studying genomic profiles can teach us which genes and consequent proteins play an important role in RSV survival and transmission dynamics. Study design: In this study, genetic diversity and evolutionary rate analysis were conducted on 36 RSV subgroup B whole genome sequences and 37 subgroup A genome sequences. Clinical RSV isolates were obtained from nasopharyngeal aspirates and swabs of children between 2 weeks and 5 years old of age. These strains, collected during epidemic seasons from 2001 to 2011 in the Netherlands and Belgium by either conventional or 454-sequencing. Sequences were analyzed for genetic diversity, recombination events, synonymous/non-synonymous substitution ratios, epistasis, and translational consequences of mutations were mapped to known 3D protein structures. We used Bayesian statistical inference to estimate the rate of RSV genome evolution and the rate of variability across the genome. Results: The A and B profiles were described in detail and compared to each other. Overall, the majority of the whole RSV genome is highly conserved among all strains. The attachment protein G was the most variable protein and its gene had, similar to the non-coding regions in RSV, more elevated (two-fold) substitution rates than other genes. In addition, the G gene has been identified as the major target for diversifying selection. Overall, less gene and protein variability was found within RSV-B compared to RSV-A and most protein variation between the subgroups was found in the F, G, SH and M2-2 proteins. For the F protein mutations and correlated amino acid changes are largely located in the F2 ligand-binding domain. The small hydrophobic phosphoprotein and nucleoprotein are the most conserved proteins. The evolutionary rates were similar in both subgroups (A: 6.47E-04, B: 7.76E-04 substitution/site/yr), but estimates of the time to the most recent common ancestor were much lower for RSV-B (B: 19, A: 46.8 yrs), indicating that there is more turnover in this subgroup. Conclusion: This study provides a detailed description of whole RSV genome mutations, the effect on translation products and the first estimate of the RSV genome evolution tempo. The immunogenic G protein seems to require high substitution rates in order to select less immunogenic strains and other conserved proteins are most likely essential to preserve RSV viability. The resulting G gene variability makes its protein a less interesting target for RSV intervention methods. The more conserved RSV F protein with less antigenic epitope shedding is, therefore, more suitable for developing therapeutic strategies or vaccines.

Keywords: drug target selection, epidemiology, respiratory syncytial virus, RSV

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Authors: Ibrahim Alshunaibir

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Infection with Helicobacter pylori is common worldwide but few studies focus on the prevalence and spread of the infection in Saudi Arabia. This study was undertaken to observe the epidemiology of Helicobacter pylori infection in patients suffering from gastrointestinal sign and symptoms in one of the largest hospitals in the capital of Saudi Arabia, Riyadh. Methods: Enzyme-linked immunosorbent assay (ELISA) was undertaken for this study with nearly 6000 samples collected and examined for patients suffering from (dyspeptic) symptoms ranging in their age from 5 to 75 years. Results: The prevalence of helicobacter infection was 67% increasing with age. Female shows higher percentage of H. pylori infection than male. Conclusions: The percentage rate was higher in female than male. This study shows a high percentage of helicobacter infection in Saudi Arabia.

Keywords: Helicobacter pylori, percentage, dyspeptic, Saudi Arabia

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Authors: Neda Menbari, Ramin Mehdiabadi

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Background: breast cancer remains a critical global health issue, constituting a leading cause of cancer-related mortality in women. MicroRNAs (miRs) are natural RNA molecules that play an important role in cellular processes and regulate post-transcriptional gene expression. MiR-216b-5p is a miR that acts as a tumor suppressor. The expression levels of FoxM1 and miR-216b-5p in malignant and control cells have been evaluated by quantitative polymerase chain reaction (qPCR) technique and flow cytometry. Results: the results of this study revealed a significant downregulation of miR-216b-5p in cancerous cells compared to the control MCF-10A cells (P=0.0004). Interestingly, the expression of miR-216b-5p exhibited an inverse relationship with key clinical indicators such as tumor size, grade, and lymph node invasion. Conclusion: The study's findings showed the prognostic value of miR-216b-5p levels in breast cancer, and its reduced expression correlates with unfavorable tumor characteristics. This research recommends performing more studies on the role of FoxM1 and miR-216b-5p in breast cancer pathology which potentially paving the way for targeted therapeutic interventions.

Keywords: breast cancer, gene expression, FOXM1, microRNA

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Authors: Salama A. Ouf, Amera A. El-Adly, Abdelaleam H. Mohamed

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Dermatophytosis is the infection of keratinized tissues such as hair, nail and the stratum corneum of the skin by dermatophytic fungi. Infection is generally cutaneous and restricted to the non-living cornified layers because of the inability of the fungi to penetrate the deeper tissues or organs of immunocompetent hosts. In Saudi Arabia, Onychomycosis is the most frequent infection (40.3%), followed by tinea capitis (21.9%), tinea pedis (16%), tinea cruris (15.1%), and tinea corporis (6.7%). Several azole compounds have been tried to control dermatophytic infection, however, the azole-containing medicines may interfere with the activity of hepatic microsomal enzymes, sex and thyroid hormones, and testosterone biosynthesis. In this research, antibody-conjugated nanoparticles stimulated by cold plasma and laser were evaluated in vitro against some dermatophytes isolated from the common types of tinea. Different types of nanomaterials were tested but silver nanoparticles (AgNPs) were proved to be most effective against the dermatophytes under test. The use of cold plasma coupled with antibody-conjugated nano-particles has severe impact on dermatophytes where the inhibition of growth, spore germination keratinase activity was more than 88% in the case of Trichophyton rubrum, T. violaceum, Microsprum canis and M. gypseum. Complete inhibition of growth for all dermatophytes was brought about by the interaction of conjugated nanoparticles, with cold plasma and laser treatment. The in vivo test with inoculated guinea pigs achieved promising results where the recovery from the infection reached 95% in the case of M. canis –inoculated pigs treated with AgNPs pretreated with cold plasma and laser.

Keywords: cold plasma, dermatophytes, laser, silver nanoparticles

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Authors: Sana Abbasa, Shahzad Bhattiab, Nadir Khan

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Sargassum siliquastrum is brown seaweed with traditional claims for some medicinal properties. This research was done to investigate the methanol extract of S. siliquastrum for antiproliferative activity against human cervical cancer cell line, HeLa and its mode of cell death. From methylene blue assay, S. siliquastrum exhibited antiproliferative activity on HeLa cells with IC50 of 3.87 µg/ml without affecting non-malignant cells. Phase contrast microscopy indicated the confluency reduction in HeLa cells and changes on the cell shape. Nuclear staining with Hoechst 33258 displayed the formation of apoptotic bodies and fragmented nuclei. S. siliquastrum also induced early apoptosis event in HeLa cells as confirmed by FITC-Annexin V/propidium iodide staining by flow cytometry analysis. Cell cycle analysis indicated growth arrest of HeLa cells at G1/S phase. Protein study by flow cytometry indicated the increment of p53, slight increase of Bax and unchanged level of Bcl-2. In conclusion, S. siliquastrum demonstrated an antiproliferative activity in HeLa cell by inducing G1/S cell cycle arrest via p53-mediated pathway.

Keywords: sargassum siliquastrum, cervical cancer, P53, antiproleferation

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Authors: Harim Mohsin, Afshan Channa, Beena Saad

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The Kocher Debre Semelaigne Syndrome (KDSS) is known as cretinism muscular hypertrophy. It is an unusual presentation in intellectually deficit children, commonly associated with congenital or iatrogenic hypothyroidism. The creatinine phosphokinase (CPK) is usually elevated and it’s commonly found in males, consanguineous marriage and ages 18 months to 10 years. It might be misdiagnosed without the classical features of hypothyroidism at first presentation. We present a case of 15 year old intellectually deficit female with epilepsy managed on phenytoin. She had rigidity, myxedema, calf muscle hypertrophy and agitation. The patient was managed as Neuroleptic Malignant Syndrome due to raised CPK of 40,680 IU/L and mixed presentation. Nevertheless, no improvement was noticed and thyroid profile was done to exclude alternative resources. Thyroid stimulating hormone (TSH) was 74.5 IU, Free T3 1.22 ng/dl, and Free T4 0.43 ng/dl. Thyroxine was started along with change in antiepileptic leading to recovery. This case report highlights the inconsistent finding of KDSS. The female gender, non-consanguineous marriage, delayed onset with primarily neuromuscular symptoms, and raised CPK is a rare demonstration in KDSS. Additionally, thyroid profile is not routinely done, which can lead to misdiagnosis and mismanagement.

Keywords: cretinism, hypothyroidism, intellectual deficit, KDSS

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Authors: Joel Mintz, Kyle Huntley, Waseem Wahood, Samuel Raine, Farzanna Haffizulla

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The effect of different state government interventions on COVID-19 health outcomes is currently unknown. Stay at home (SAH) orders, all non-essential business closures and school closures in the Northeastern US were examined. A linear correlation between the peak number of new daily COVID-19 positive tests, hospitalizations and deaths per capita and the elapsed time between government issued guidance and a fixed number of COVID-19 deaths in each state was performed. Earlier government interventions were correlated with lower peak healthcare burden. Statewide closures of schools and non-essential businesses showed significantly greater (p<.001) correlation to peak COVID-19 disease burden as compared to a statewide SAH. The implications of these findings require further study to determine the effectiveness of these interventions.

Keywords: Coronavirus, epidemiology, government intervention, public health, social distancing

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Authors: Sehreen Moorat, Mussarat Lakho

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A method of artificial intelligence using digital mammograms data has been proposed in this paper for detection of breast cancer. Many researchers have developed techniques for the early detection of breast cancer; the early diagnosis helps to save many lives. The detection of breast cancer through mammography is effective method which detects the cancer before it is felt and increases the survival rate. In this paper, we have purposed image processing technique for enhancing the image to detect the graphical table data and markings. Texture features based on Gray-Level Co-Occurrence Matrix and intensity based features are extracted from the selected region. For classification purpose, neural network based supervised classifier system has been used which can discriminate between benign and malignant. Hence, 68 digital mammograms have been used to train the classifier. The obtained result proved that automated detection of breast cancer is beneficial for early diagnosis and increases the survival rates of breast cancer patients. The proposed system will help radiologist in the better interpretation of breast cancer.

Keywords: medical imaging, cancer, processing, neural network

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Authors: Ilham Akbar Rahman, Aflah Dhea Bariz Yasta, Iin Fadhilah Utami Tamasse, Devina Juanita

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Meningioma is adult brain tumors originating from the meninges covering the brain and spinal cord. The females have approximately twice higher 2:1 than male in the incidence of meningioma. This study aimed to analyze the histopathological grading and clinical aspect in predicting the prognosis of meningioma patients. An observational study with cross sectional design was used on 53 meningioma patients treated at Dr. Wahidin Sudirohusodo hospital in 2016. The data then were analyzed using SPSS 20.0. Of 53 patients, mostly 41 (77,4%) were female and 12 (22,6%) were male. The distribution of histopathology patients showed the meningothelial meningioma of 18 (43,9%) as the most type found. Fibroplastic meningioma were 8 (19,5%), while atypical meningioma and psammomatous meningioma were 6 (14,6%) each. The rest were malignant meningioma and angiomatous meningioma which found in respectively 2 (4,9%) and 1 (2,4%). Our result found significant finding that mostly male were fibroblastic meningioma (50%), however meningothelial meningioma were found in the majority of female (54,8%) and also seizure comprised only in higher grade meningioma. On the outcome of meningioma patient treated operatively, histopathological grade remained insignificant (p > 0,05). This study can be used as prognostic value of meningioma patients based on gender, histopathological grade, and clinical manifestation. Overall, the outcome of the meningioma’s patients is good and promising as long as it is well managed.

Keywords: meningioma, prognostic value, histopathological grading, clinical manifestation

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Authors: Parag Katira, Frederika Rentzeperis, Zuzanna Nowicka, Giada Fiandaca, Thomas Veith, Jack Farinhas, Noemi Andor

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Resource limitations shape the outcome of competitions between genetically heterogeneous pre-malignant cells. One example of such heterogeneity is in the ploidy (DNA content) of pre-malignant cells. A whole-genome duplication (WGD) transforms a diploid cell into a tetraploid one and has been detected in 28-56% of human cancers. If a tetraploid subclone expands, it consistently does so early in tumor evolution, when cell density is still low, and competition for nutrients is comparatively weak – an observation confirmed for several tumor types. WGD+ cells need more resources to synthesize increasing amounts of DNA, RNA, and proteins. To quantify resource limitations and how they relate to ploidy, we performed a PAN cancer analysis of WGD, PET/CT, and MRI scans. Segmentation of >20 different organs from >900 PET/CT scans were performed with MOOSE. We observed a strong correlation between organ-wide population-average estimates of Oxygen and the average ploidy of cancers growing in the respective organ (Pearson R = 0.66; P= 0.001). In-vitro experiments using near-diploid and near-tetraploid lineages derived from a breast cancer cell line supported the hypothesis that DNA content influences Glucose- and Oxygen-dependent proliferation-, death- and migration rates. To model how subpopulations with variable DNA content compete in the resource-limited environment of the human brain, we developed a stochastic state-space model of the brain (S3MB). The model discretizes the brain into voxels, whereby the state of each voxel is defined by 8+ variables that are updated over time: stiffness, Oxygen, phosphate, glucose, vasculature, dead cells, migrating cells and proliferating cells of various DNA content, and treat conditions such as radiotherapy and chemotherapy. Well-established Fokker-Planck partial differential equations govern the distribution of resources and cells across voxels. We applied S3MB on sequencing and imaging data obtained from a primary GBM patient. We performed whole genome sequencing (WGS) of four surgical specimens collected during the 1ˢᵗ and 2ⁿᵈ surgeries of the GBM and used HATCHET to quantify its clonal composition and how it changes between the two surgeries. HATCHET identified two aneuploid subpopulations of ploidy 1.98 and 2.29, respectively. The low-ploidy clone was dominant at the time of the first surgery and became even more dominant upon recurrence. MRI images were available before and after each surgery and registered to MNI space. The S3MB domain was initiated from 4mm³ voxels of the MNI space. T1 post and T2 flair scan acquired after the 1ˢᵗ surgery informed tumor cell densities per voxel. Magnetic Resonance Elastography scans and PET/CT scans informed stiffness and Glucose access per voxel. We performed a parameter search to recapitulate the GBM’s tumor cell density and ploidy composition before the 2ⁿᵈ surgery. Results suggest that the high-ploidy subpopulation had a higher Glucose-dependent proliferation rate (0.70 vs. 0.49), but a lower Glucose-dependent death rate (0.47 vs. 1.42). These differences resulted in spatial differences in the distribution of the two subpopulations. Our results contribute to a better understanding of how genomics and microenvironments interact to shape cell fate decisions and could help pave the way to therapeutic strategies that mimic prognostically favorable environments.

Keywords: tumor evolution, intra-tumor heterogeneity, whole-genome doubling, mathematical modeling

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Authors: Hatem A. El-Mezayen, Ahmed Abdelmajeed, Fatehya Metwally, Usama Elsaly, Salwa Atef

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Tumor metastasis involves the dissemination of malignant cells into the basement membrane and vascular system contributes to the circulating pool of these markers. In this context our aim has been focused on development of a non-invasive. Circulating tumor cells (CTCs) represent a unique liquid biopsy carrying comprehensive biological information of the primary tumor. Herein, we sought to develop a novel score based on the combination of the most significant CTCs biomarkers with and routine laboratory tests for accurate detection of metastatic breast cancer. Methods: Cytokeratin 18 (CK18), Cytokeratin 19 (CK19), and CA15.3 were assayed in metastatic breast cancer (MBC) patients (75), non-MBC patients (50) and healthy control (20). Results: Areas under receiving operating curve (AUCs) were calculated and used for construction on novel score. A novel score named MBC-CTCs = CA15.3 (U/L) × 0.08 + CK 18 % × 2.9 + CK19 × 3.1– 510. That function correctly classified 87% of metastatic breast cancer at cut-off value = 0.55. (i.e great than 0.55 indicates patients with metastatic breast cancer and less than 0.55 indicates patients with non-metastatic breast cancer). Conclusion: MBC-CTCs is a novel, non-invasive and simple can applied to discriminate patients with metastatic breast cancer.

Keywords: metastatic breast cancer, circulating tumor cells, cytokeratin, EpiCam

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Authors: Loredana G. Marcu, David Marcu, Sanda M. Filip

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Advanced head and neck cancers are aggressive tumours, which require aggressive treatment. Treatment efficiency is often hindered by cancer cell repopulation during radiotherapy, which is due to various mechanisms triggered by the loss of tumour cells and involves both stem and differentiated cells. The aim of the current paper is to present in silico simulations of radiotherapy schedules on a virtual head and neck tumour grown with biologically realistic kinetic parameters. Using the linear quadratic formalism of cell survival after radiotherapy, altered fractionation schedules employing various treatment breaks for normal tissue recovery are simulated and repopulation mechanism implemented in order to evaluate the impact of various cancer cell contribution on tumour behaviour during irradiation. The model has shown that the timing of treatment breaks is an important factor influencing tumour control in rapidly proliferating tissues such as squamous cell carcinomas of the head and neck. Furthermore, not only stem cells but also differentiated cells, via the mechanism of abortive division, can contribute to malignant cell repopulation during treatment.

Keywords: radiation, tumour repopulation, squamous cell carcinoma, stem cell

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Authors: M. Shahana

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Introduction: Leprosy (Hansens) is one of the major health problems in the developing countries. Sixty percent of the world leprosy cases are in India. According to the 2006 census India has about 54% of the total new cases detected globally. The National Leprosy Elimination Programme in 2012 has reported 9.7% of childhood leprosy. There are only few studies related to paediatric leprosy. Aim: To study the epidemiology and various clinical presentations of leprosy in the paediatric age group. Material and Methods: A 4-year prospective study was done in the out-patient department of dermatology in a tertiary care hospital. All the patients were screened for leprosy and children with a confirmed diagnosis of leprosy were taken up for the study. Results: Total of 321 cases of Hansens were recorded during this period out of which 41 were children. The male to female ratio was 2.72:1. A positive family history was found in 18%. Most of them presented with single hypopigmented hypoanesthetic patch. Conclusions: Children presented with more of Borderline tuberculoid type and reactions or deformities were less common.

Keywords: Hansens, hypoaneasthetic patch, leprosy, reactions

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Authors: Hyeon Su Kim, Sungjin Park, Hae Ryung Chang, Hae Rim Jung, Young Zoo Ahn, Yon Hui Kim, Seungyoon Nam

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Ependymoma, one of the most common parenchymal spinal cord tumor, represents 3-6% of all CNS tumor. Especially intracranial ependymomas, which are more frequent in childhood, have a more poor prognosis and more malignant than spinal ependymomas. Although there are growing needs to understand pathogenesis, detailed molecular understanding of pathogenesis remains to be explored. A cancer cell is composed of complex signaling pathway networks, and identifying interaction between genes and/or proteins are crucial for understanding these pathways. Therefore, we explored each ependymoma in terms of differential expressed genes and signaling networks. We used Microsoft Excel™ to manipulate microarray data gathered from NCBI’s GEO Database. To analyze and visualize signaling network, we used web-based PATHOME algorithm and Cytoscape. We show HOX family and NEFL are down-regulated but SCL family is up-regulated in cerebrum and posterior fossa cancers over a spinal cancer, and JAK/STAT signaling pathway and Chemokine signaling pathway are significantly different in the both intracranial ependymoma comparing to spinal ependymoma. We are considering there may be an age-dependent mechanism under different histological pathogenesis. We annotated mutation data of each gene subsequently in order to find potential target genes.

Keywords: systems biology, ependymoma, deg, network analysis

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Authors: Paras Ram, Vikas Kumar

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The transmission of Malaria with seasonal were studied through the use of mathematical models. The data from the annual number of Malaria cases reported to the Division of Epidemiology, Ministry of Public Health, Thailand during the period 1997-2011 were analyzed. The transmission of Malaria with seasonal was studied by formulating a mathematical model which had been modified to describe different situations encountered in the transmission of Malaria. In our model, the population was separated into two groups: the human and vector groups, and then constructed a system of nonlinear differential equations. Each human group was divided into susceptible, infectious in hot season, infectious in rainy season, infectious in cool season and recovered classes. The vector population was separated into two classes only: susceptible and infectious vectors. The analysis of the models was given by the standard dynamical modeling.

Keywords: ferrofluid, magnetic field, porous medium, rotating disk, Neuringer-Rosensweig Model

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Authors: Samir El-Gendy, Doaa Zaghloul

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The current study dealt with the gross and microscopic anatomy of the integument of male ostrich in addition to the histological features of different areas of skin by light and SEM. The ostrich skin is characterized by prominent feather follicles and bristles. The number of feather follicles was determined per cm2 in different regions. The integument of ostrich had many modifications which appeared as callosities and scales, nail and toe pads. They were sternal, pubic and Achilles tendon callosities. The vacuolated epidermal cells were seen mainly in the skin of legs and to a lesser extent in the skin of back and Achilles areas. Higher lipogenic potential was expressed by epidermis from glabrous areas of ostrich skin. The dermal papillae were found in the skin of feathered area of neck and back and this was not a common finding in bird's skin which may give resistance against shearing forces in these regions of ostrich skin. The thickness of the keratin layer of ostrich varied, being thick and characteristically loose in the skin at legs, very thin and wavy at neck, while at Achilles skin area, scale and toe pad were thick and more compact, with the thickest very dense and wavy keratin layer at the nail. The dermis consisted of superficial layer of dense irregular connective tissue characterized by presence of many vacuoles of different sizes just under the basal lamina of the epithelium of epidermis and deep layer of dense regular connective tissue. This result suggested presence of fat droplets in this layer which may be to overcome the lack of good barrier of cutaneous water loss in epidermis.

Keywords: ostrich, light microscopy, scanning electron microscopy, integument, skin modifications

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Authors: Ghoul Rachid Brahim, Trad Khodja Rafik

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Vertebral localization of the hydatid cyst is a severe form of bone hydatidosis, is a parasitic infection caused by the larval forms of the tapeworms Echinococcus granulosus, The disease is slowly remaining silent (a long incubation period) which may explain why this pathology is often discovered at the stage of neurological complications. The objective of this study is to recall the clinical and radiological aspects of this condition and the importance of early diagnosis and appropriate management. We report a study of 5 patients with vertebral hydatidosis, four men and one woman, four (04) patients operated in the emergency setting for spinal cord compression (decompression by wide laminectomy with evacuation of intra and extra canal vesicles).Albendazole-based medical treatment is instituted in all patients. Results: The evolution was favorable for three patients, the other two patients reoperated for a local recurrence. Conclusion: Vertebral hydatidosis is a rare condition with a poor prognosis due to the risk of neurological damage, the infiltrating nature of bone lesions, the frequency of relapses and therapeutic difficulties. The only curative method remains surgery, which must aim for complete and large excision of the lesions as if it were a “malignant tumour”.

Keywords: hydatidosis, Echinococcosis granulosus, hydatid cyst, spinal cord compression, laminectomy

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Authors: Eddy K. Mukadi

Abstract:

This work is a documentary and descriptive study devoted to the epidemiological, clinical, histopathological and therapeutic profile of breast cancer deals with the department of gynecology and obstetrics of the university clinics of Kinshasa during the period from 1 January 2014 to 31 December 2014. We have identified 56 cases of breast cancer. These cancers accounted for 45.2% of gynecological mammary cancers. The youngest in our series was 18 years old while the oldest was 74 years old; And the mean age of these patients was 43.4 years and mostly multiparous (35.7%). Brides (60.7%) and bachelors (26.8%) were the most affected by breast cancer. The reasons for consultation were dominated by nodules in the breast (48.2%) followed by pain (35.7%) and nipple discharge (14.3%). In 89.2% of the cases, it was the advanced clinical stage (stage 3 and 4) and the infiltrating ductal carcinoma was the most frequent histological type (75%) The malignant tumor was mainly in the left breast (55.3%), and chemotherapy with hormone therapy and patey was the most convenient treatment (42.8%), while patey mastectomy was performed in 12.5% of patients. Because of the high incidence of breast cancer identified in our study, some preventive measures must be taken into account to address this public health problem, including breast autopalpation once a month, Early detection system development of a national breast cancer policy and the implementation of a national breast cancer control program.

Keywords: breast cancer, histopathological profile, epidemiological profile, Kinshasa

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Authors: Mohammed Jarrar, Shalini Behl, Nadia Shaheen, Abeer Fatima, Reem Nasab

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Skin aging is a slow multifactorial process influenced by both internal as well as external factors. Ultra-violet radiations (UV), diet, smoking and personal habits are the most common environmental factors that affect skin aging. Fat contents and fibrous proteins as collagen and elastin are core internal structural components. The direct influence of UV on elastin integrity and health is crucial on aging of skin by time. The deposition of abnormal elastic material is a major marker in a photo-aged skin. Searching for compounds that may protect against cutaneous photo-damage is highly valued. Retinoids and Alpha Hydroxy Acids protective and or repairing effects of UV have been endorsed by some researchers. For consolidating a better understanding of anti and protective effects of such anti-aging agents, we evaluated the combinatory effects of various dosages of lactic acid and retinol on the dermal fibroblasts elastin levels exposed to UV. The UV exposed cells showed significant reduction in the elastin levels. A combination of drugs with a higher concentration of lactic acid (30-35 mM) and a lower concentration of retinol (10-15mg/mL) showed to work better in enhancing elastin concentration in UV exposed cells. We assume this enhancement could be the result of increased tropo-elastin gene expression stimulated by retinol and lactic acid probably repaired the UV irradiated damage by enhancing the amount and integrity of the elastin fibers.

Keywords: alpha hydroxy acid, elastin, retinol, ultraviolet radiations

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Authors: Vandana Singh, Subash Singh

Abstract:

Introduction: Oral squamous cell carcinoma is the most common malignant tumor of the oral cavity. Normally the death of cell and the growth are active processes and depend not only on external factors but also on the expression of genes like Bcl-2, which activate and inhibit apoptosis. The term Bcl-2 is an acronym for B-cell lymphoma/ leukemia -2 genes. Objectives: An attempt was made to evaluate Bcl-2 oncoprotein expression in patients with oral precancer and cancer and to assess possible correlation between Bcl-2 oncoprotein expression and clinicopathological features of oral precancer and cancer. Material and Methods: This is a selective prospective clinical and immunohistochemical study. Clinicopathological examination is correlated with immunohistochemical findings. The immunolocalization of Bcl-2 protein is performed using the labeled streptavidin biotin (LSAB) method. To visualize the reaction, 3, 3-diaminobenzidine (DAB) is used. Results: Bcl-2 expression was positive in 11 [36.66 %, low Bcl-2 expression 3 (10.00 %), moderate Bcl-2 expression 7 (23.33 %), and high Bcl-2 expression 1 (3.33 %)] oral cancer cases and in 14 [87.50 %, low expression 8 (50 %), moderate expression 6 (37.50 %)] precancer cases. Conclusion: On the basis of the results of our study we conclude that positive Bcl-2 expression may be an indicator of poor prognosis in oral cancer and precancer. Relevance: It has been reported that there is deregulation of Bcl-2 expression during progression from oral epithelial dysplasia to squamous cell carcinoma. It can be used for revealing progression of epithelial dysplasia to malignancy and as a prognostic marker in oral precancer and cancer.

Keywords: BcL-2, immunohistochemistry, oral cancer, oral precancer

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Authors: Ceyda Okudu, Secil Eroglu, Khandakar A. S. M. Saadat, Sibel O. Balci

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Ring Finger Protein 2 (RNF2) is a member of polycomb repressive complex 1 (PRC1), which is one of the epigenetic regulators in the genome. When RNF2 combines with other PRC1 members, it mediates the mono-ubiquitination of Histon2A (H2A). In breast cancer, RNF2 is commonly overexpressed, and also it promotes metastasis and invasion in other aggressive tumors like melanoma, prostate, and hepatocarcinoma. The role of RNF2 in the metastasis and invasion of breast cancer has not yet been elucidated. Our aim is to observe the role of RNF2 in metastasis and invasion in this study by miRNA mediated RNF2 gene silencing in breast cancer cell lines. We selected miRNAs, targeting to RNF2 by searching online databases. miR-17-5p, miR20a-5p, and miR-106b-5p were transfected to breast cancer cell lines (MCF-7, MDA-MB-231, SK-BR-3, and ZR-75-1), and also we used normal breast epithelial cell line (hTERT-HME1) to compare RNF2 gene expression level. After 48-72 hours post-transfection, mRNAs were isolated from the cells, and gene expressions were measured by RT-qPCR after from cDNA syntheses. We observed that RNF2 was highly expressed in SK-BR-3 and MDA-MB-231 cell lines opposite to MCF-7 and ZR-75-1 cell lines. RNF2 was downregulated 5, 5 and 7 fold by miR17-5p, miR20a-5p and miR106b-5p respectively in MCF-7. However, in SK-BR-3 and ZR-75-1 cell lines, miRNAs did not affect significantly RNF2 gene expression level. miR20a-5p decreased RNF2 3 fold and miR17-5p and miR106b-5p did not affect MDA-MB-231. After gene expression analysis, we performed metastasis and invasion assay in MCF-7 cells. For metastasis, we used both wound healing assay and Transwell Cell Migration Assay, and we used Transwell Cell Invasion Assay for invasion. The data of this assay showed that miR17-5p and miR20a-5p decreased both invasion and metastasis level, but miR106b-5p has no effect. We would like to conclude that RNF2 can be targeted by miR17-5p, miR20a-5p and miR106b-5p in MCF-7 cells and also RNF2, which is one of the upregulated genes in aggressive tumor, can be decreased by using these miRNAs. In future, we would like to confirm these results at the protein level and also whether these miRNAs are direct target of RNF2 or not.

Keywords: breast cancer, epigenetic, microRNAs, RNF2

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Authors: Nermin Isik

Abstract:

Cryptosporidiosis is one of the most common parasitic infection in domesticated, caged, wild birds. Cryptosporidium sp. has been reported in over 30 avian species worldwide. Cryptosporidium meleagridis, Cryptosporidium baileyi and Cryptosporidium galli are recognised avian species of Cryptosporidium. This study was carried out to determine the prevalance of Cryptosporidium sp. in wild birds in Konya province, Turkey. Faecal samples were collected from 65 wild birds including 52 Podicipedidae (Podiceps cristatus), 11 Rallidae (Fulicia Atra), 2 Anitadia (Aytha ferina). Faecal samples were stained with Modified Ziehl-Neelsen staining technigue, they were examined under light microscope for the presence of Cryptosporidium sp. oocyts. Among the 65 faecal samples, 11 (16.9%) were found to be infected with Cryptosporidium sp. oocysts. The results of this study indicate that wild birds may play an important role in the epidemiology of Cryptosporidium. In conclusion, Cryptosporidiosis has suggested zoonotic potential and thus warrant further attention. In addition, biological and genetic studies are required to provide more information on Cryptosporidiosis.

Keywords: Cryptosporidium sp, wild birds, Konya, Turkey

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Authors: Krisada Lekdee, Sunee Sammatat, Nittaya Boonsit

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This paper proposes a GLMM with spatial and temporal effects for malaria data in Thailand. A Bayesian method is used for parameter estimation via Gibbs sampling MCMC. A conditional autoregressive (CAR) model is assumed to present the spatial effects. The temporal correlation is presented through the covariance matrix of the random effects. The malaria quarterly data have been extracted from the Bureau of Epidemiology, Ministry of Public Health of Thailand. The factors considered are rainfall and temperature. The result shows that rainfall and temperature are positively related to the malaria morbidity rate. The posterior means of the estimated morbidity rates are used to construct the malaria maps. The top 5 highest morbidity rates (per 100,000 population) are in Trat (Q3, 111.70), Chiang Mai (Q3, 104.70), Narathiwat (Q4, 97.69), Chiang Mai (Q2, 88.51), and Chanthaburi (Q3, 86.82). According to the DIC criterion, the proposed model has a better performance than the GLMM with spatial effects but without temporal terms.

Keywords: Bayesian method, generalized linear mixed model (GLMM), malaria, spatial effects, temporal correlation

Procedia PDF Downloads 417