Search results for: hereditary breast-ovarian cancer syndrome

Authors: Taurino S. R. Neto, Epitácio D. S. Neto, Flávio Signorelli, Gustavo G. M. Balbi, Alex H. Higashi, Mário Luiz R. Monteiro, Eloisa Bonfá, Danieli C. O. Andrade, Leandro C. Zacharias

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Purpose: To perform a multimodal evaluation, including the use of Optical Coherence Angiotomography (OCTA), in patients with primary antiphospholipid syndrome (PAPS) without ocular complaints and to compare them with healthy individuals. Methods: A complete structural and functional ophthalmological evaluation using OCTA and microperimetry (MP) exam in patients with PAPS, followed at a tertiary rheumatology outpatient clinic, was performed. All ophthalmologic manifestations were recorded and then statistical analysis was performed for comparative purposes; p <0.05 was considered statistically significant. Results: 104 eyes of 52 subjects (26 patients with PAPS without ocular complaints and 26 healthy individuals) were included. Among PAPS patients, 21 were female (80.8%) and 21 (80.8%) were Caucasians. Thrombotic PAPS was the main clinical criteria manifestation (100%); 65.4% had venous and 34.6% had arterial thrombosis. Obstetrical criteria were present in 34.6% of all thrombotic PAPS patients. Lupus anticoagulant was present in all patients. 19.2% of PAPS patients presented ophthalmologic findings against none of the healthy individuals. The most common retinal change was paracentral acute middle maculopathy (PAMM) (3 patients, 5 eyes), followed by drusen-like deposits (1 patient, 2 eyes) and pachychoroid pigment epitheliopathy (1 patient, 1 eye). Systemic hypertension and hyperlipidaemia were present in 100% of the PAPS patients with PAMM, while only six patients (26.1%) with PAPS without PAMM presented these two risk factors together. In the quantitative OCTA evaluation, we found significant differences between PAPS patients and controls in both the superficial vascular complex (SVC) and deep vascular complex (DVC) in the high-speed protocol, as well as in the SVC in the high-resolution protocol. In the analysis of the foveal avascular zone (FAZ) parameters, the PAPS group had a larger area of FAZ in the DVC using the high-speed method compared to the control group (p=0.047). In the quantitative analysis of the MP, the PAPS group had lower central (p=0.041) and global (p<0.001) retinal sensitivity compared to the control group, as well as in the sector analysis, with the exception of the inferior sector. In the quantitative evaluation of fixation stability, there was a trend towards worse stability in the PAPS subgroup with PAMM in both studied methods. Conclusions: PAMM was observed in 11.5% of PAPS patients with no previous ocular complaints. Systemic hypertension concomitant with hyperlipidemia was the most commonly associated risk factor for PAMM in patients with PAPS. PAPS patients present lower vascular density and retinal sensitivity compared to the control group, even in patients without PAMM.

Keywords: antiphospholipid syndrome, optical coherence angio tomography, optical coherence tomography, retina

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Authors: Jorge Iván Bañol-Betancur, Lina María Martínez-Sánchez, María de los Ángeles Rodríguez-Gázquez, Estefanía Bahamonde-Olaya, Ana María Gutiérrez-Tamayo, Laura Isabel Jaramillo-Jaramillo, Camilo Ruiz-Mejía, Natalia Morales-Quintero

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Acute chest pain is a distressing sensation between the diaphragm and the base of the neck and it represents a diagnostic challenge for any physician in the emergency department. Objective: To establish the main clinical and epidemiological characteristics of patients who present with chest pain to the emergency department in a private clinic from the city of Medellin, during 2014-2015. Methods: Cross-sectional retrospective observational study. Population and sample were patients who consulted for chest pain in the emergency department who met the eligibility criteria. The information was analyzed in SPSS program vr.21; qualitative variables were described through relative frequencies, and the quantitative through mean and standard deviation ‬or medians according to their distribution in the study population. Results: A total of 231 patients were evaluated, the mean age was 49.5 ± 19.9 years, 56.7% were females. The most frequent pathological antecedents were hypertension 35.5%, diabetes 10,8%, dyslipidemia 10.4% and coronary disease 5.2%. Regarding pain features, in 40.3% of the patients the pain began abruptly, in 38.2% it had a precordial location, for 20% of the cases physical activity acted as a trigger, and 60.6% was oppressive. Costochondritis was the most common cause of chest pain among patients with an established etiologic diagnosis, representing the 18.2%. Conclusions: Although the clinical features of pain reported coincide with the clinical presentation of an acute coronary syndrome, the most common cause of chest pain in study population was costochondritis instead, indicating that it is a differential diagnostic in the approach of patients with pain acute chest.

Keywords: acute coronary syndrome, chest pain, epidemiology, osteochondritis

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Authors: Mohanad Moustafa, Julia Sieberer, Rhys Davies

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Background: Orbital compartment syndrome (OCS) is a sight-threatening Ophthalmologic emergency caused by rapidly increasing intraorbital pressure. It is usually caused by a retrobulbar hemorrhage as a result of trauma. If not treated in a timely manner, permanent vision loss can occur. Lateral canthotomy and cantholysis are minor procedures that can be performed bedside with equipment available in the emergency department. The aim of the procedure is to release the attachments between the suspensory ligaments of the eye and the bony orbital wall, leading to a decrease in intraorbital pressure and preventing irreversible loss of vision. As most Ophthalmologists across the UK provide non-resident on-call service, this may lead to a delay in the treatment of OCS and stresses the need for Emergency medical staff to be able to provide this sight-saving procedure independently. Aim: To survey current training, experience, and confidence levels among Emergency Medicine doctors in performing emergency lateral canthotomy and to establish whether these variables change the following teaching from experienced ophthalmologists. RESULTS: Most EM registrars had little to no experience in performing lateral canthotomy and cantholysis. The majority of them showed a significant increase in their confidence to perform the procedure following ophthalmic-led teaching. The survey also showed that the registrars felt such training should be added to/part of the EM curriculum. Conclusion: The involvement of Ophthalmologists in the teaching of EM doctors to recognise and treat OCS independently may prevent delays in treatment and reduce the risk of permanent sight loss. This project showed potential in improving patient care and will lead to a National Survey of EM doctors across the UK.

Keywords: lateral canthotomy, retrobulbar hemorrhage, Ophthalmology, orbital compartment syndrome, sight loss, blindness

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Authors: Maryam Mohammad Hadi, Heather Nesbitt, Hamzah Masood, Hashim Ahmed, Mark Emberton, John Callan, Alexander MacRobert, Anthony McHale, Nikolitsa Nomikou

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Sonodynamic therapy (SDT) utilises ultrasound in combination with sensitizers, such as porphyrins, for the production of cytotoxic reactive oxygen species (ROS) and the confined ablation of tumours. Ultrasound can be applied locally, and the acoustic waves, at frequencies between 0.5-2 MHz, are transmitted efficiently through tissue. SDT does not require highly toxic agents, and the cytotoxic effect only occurs upon ultrasound exposure at the site of the lesion. Therefore, this approach is not associated with adverse side effects. Further highlighting the benefits of SDT, no cancer cell population has shown resistance to therapy-triggered ROS production or their cytotoxic effects. This is particularly important, given the as yet unresolved issues of radiation and chemo-resistance, to the authors’ best knowledge. Another potential future benefit of this approach – considering its non-thermal mechanism of action – is its possible role as an adjuvant to immunotherapy. Substantial pre-clinical studies have demonstrated the efficacy and targeting capability of this therapeutic approach. However, SDT has yet to be fully characterised and appropriately exploited for the treatment of cancer. In this study, a formulation based on multistimulus-responsive sensitizer-containing nanoparticles that can accumulate in advanced prostate tumours and increase the therapeutic efficacy of SDT has been developed. The formulation is based on a polyglutamate-tyrosine (PGATyr) co-polymer carrying hematoporphyrin. The efficacy of SDT in this study was demonstrated using prostate cancer as the translational exemplar. The formulation was designed to respond to the microenvironment of advanced prostate tumours, such as the overexpression of the proteolytic enzymes, cathepsin-B and prostate-specific membrane antigen (PSMA), that can degrade the nanoparticles, reduce their size, improving both diffusions throughout the tumour mass and cellular uptake. The therapeutic modality was initially tested in vitro using LNCaP and PC3 cells as target cell lines. The SDT efficacy was also examined in vivo, using male SCID mice bearing LNCaP subcutaneous tumours. We have demonstrated that the PGATyr co-polymer is digested by cathepsin B and that digestion of the formulation by cathepsin-B, at tumour-mimicking conditions (acidic pH), leads to decreased nanoparticle size and subsequent increased cellular uptake. Sonodynamic treatment, at both normoxic and hypoxic conditions, demonstrated ultrasound-induced cytotoxic effects only for the nanoparticle-treated prostate cancer cells, while the toxicity of the formulation in the absence of ultrasound was minimal. Our in vivo studies in immunodeficient mice, using the hematoporphyrin-containing PGATyr nanoparticles for SDT, showed a 50% decrease in LNCaP tumour volumes within 24h, following IV administration of a single dose. No adverse effects were recorded, and body weight was stable. The results described in this study clearly demonstrate the promise of SDT to revolutionize cancer treatment. It emphasizes the potential of this therapeutic modality as a fist line treatment or in combination treatment for the elimination or downstaging of difficult to treat cancers, such as prostate, pancreatic, and advanced colorectal cancer.

Keywords: sonodynamic therapy, nanoparticles, tumour ablation, ultrasound

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Authors: Bandhan Dey, Muhsina Bintoon Yiasha, Gulam Sulaman Choudhury

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Chest disease is one of the most problematic ailments in our regular life. There are many known chest diseases out there. Diagnosing them correctly plays a vital role in the process of treatment. There are many methods available explicitly developed for different chest diseases. But the most common approach for diagnosing these diseases is through X-ray. In this paper, we proposed a multi-classification deep learning model for diagnosing COVID-19, lung cancer, pneumonia, tuberculosis, and atelectasis from chest X-rays. In the present work, we used the transfer learning method for better accuracy and fast training phase. The performance of three architectures is considered: InceptionV3, VGG-16, and VGG-19. We evaluated these deep learning architectures using public digital chest x-ray datasets with six classes (i.e., COVID-19, lung cancer, pneumonia, tuberculosis, atelectasis, and normal). The experiments are conducted on six-classification, and we found that VGG16 outperforms other proposed models with an accuracy of 95%.

Keywords: deep learning, image classification, X-ray images, Tensorflow, Keras, chest diseases, convolutional neural networks, multi-classification

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Authors: Animesh Pan, Geoffrey D. Bothun

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With the development of nanotechnology, research in multifunctional delivery systems has a new pace and dimension. An incipient challenge is to design an all-in-one delivery system that can be used for multiple purposes, including tumor targeting therapy, radio-frequency (RF-), near-infrared (NIR-), light-, or pH-induced controlled release, photothermal therapy (PTT), photodynamic therapy (PDT), and medical diagnosis. In this regard, various inorganic nanoparticles (NPs) are known to show great potential as the 'functional components' because of their fascinating and tunable physicochemical properties and the possibility of multiple theranostic modalities from individual NPs. Magnetic, luminescent, and plasmonic properties are the three most extensively studied and, more importantly biomedically exploitable properties of inorganic NPs. Although successful attempts of combining any two of them above mentioned functionalities have been made, integrating them in one system has remained challenge. Keeping those in mind, controlled designs of complex colloidal nanoparticle system are one of the most significant challenges in nanoscience and nanotechnology. Therefore, systematic and planned studies providing better revelation are demanded. We report a multifunctional delivery platform-based liposome loaded with drug, iron-oxide magnetic nanoparticles (MNPs), and a gold shell on the surface of liposomes, were synthesized using a lipid with polyelectrolyte (layersomes) templating technique. MNPs and the anti-cancer drug doxorubicin (DOX) were co-encapsulated inside liposomes composed by zwitterionic phophatidylcholine and anionic phosphatidylglycerol using reverse phase evaporation (REV) method. The liposomes were coated with positively charge polyelectrolyte (poly-L-lysine) to enrich the interface with gold anion, exposed to a reducing agent to form a gold nanoshell, and then capped with thio-terminated polyethylene glycol (SH-PEG2000). The core-shell nanostructures were characterized by different techniques like; UV-Vis/NIR scanning spectrophotometer, dynamic light scattering (DLS), transmission electron microscope (TEM). This multifunctional system achieves a variety of functions, such as radiofrequency (RF)-triggered release, chemo-hyperthermia, and NIR laser-triggered for photothermal therapy. Herein, we highlight some of the remaining major design challenges in combination with preliminary studies assessing therapeutic objectives. We demonstrate an efficient loading and delivery system to significant cell death of human cancer cells (A549) with therapeutic capabilities. Coupled with RF and NIR excitation to the doxorubicin-loaded core-shell nanostructure helped in securing targeted and controlled drug release to the cancer cells. The present core-shell multifunctional system with their multimodal imaging and therapeutic capabilities would be eminent candidates for cancer theranostics.

Keywords: cancer thernostics, multifunctional nanostructure, photothermal therapy, radiofrequency targeting

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Authors: Shannon Rappe, Elizabeth Morse, David Phillippi

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Postpartum women with an opioid use disorder (OUD) are at high risk for treatment disengagement, leaving them vulnerable to overdose and death between seven and twelve months postpartum. Intensive case management programs have been proposed as an effective strategy to reduce barriers and increase treatment engagement among postpartum women. The purpose of this project is to determine the effects of early engagement in an intensive case management program on postpartum engagement and infant health outcomes among postpartum women with opioid use. This retrospective review of secondary data was collected on 225 infants, and 221 postpartum women enrolled in an intensive case management program in Tennessee between May 1, 2019, and May 5, 2020. Chi-squares were computed to examine the timing of engagement during pregnancy, maternal treatment outcomes, and infant health outcomes, including neonatal abstinence syndrome (NAS), birth weight, gestational age, and length of stay. The mean prenatal program engagement was 109 days (SD = 67.6); 16.7% (n = 37) enrolled during the first trimester, 37.6% (n = 83) in the second trimester, and 45.7% (n = 101) in the third trimester. Of the 221 women engaged, 45.2% (n = 100) remained engaged in the case of management at the time of data collection, and 40% (n = 89) remained engaged in MAT at the time of data collection. Twenty- five percent (n = 25) of mothers who graduated sustained engagement in MAT. Of 225 infants 28.9% (n = 65) had a positive NAS status, mean birth weight was 6.5 lbs. (SD = 19.3); mean gestational age was 38.3 weeks (SD = 19.3) and mean length of stay was 8.19 days (SD = 9.8). This study's findings identified that engaging mothers during pregnancy in a program designed to meet their unique challenges positively impacts both the mother and infant outcomes, regardless of their timing.

Keywords: intensive case management, neonatal abstinence syndrome, opioid addiction, opioid crisis, opioid use in pregnant women, postpartum addiction

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Authors: Lauren Zammerilla Westcott, Ronald C. Jones, James W. Fleshman

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The surgical treatment of breast cancer has rapidly evolved over the past 50 years, progressing from Halsted’s radical mastectomy to a public campaign of surgical options, aesthetic reconstruction, and patient empowerment. This article examines the happenings that led to the transition of breast surgery as a subset of general surgery to its own specialized field. Sparked by the research of Dr. Bernard Fisher and the first National Surgical Adjuvant Breast and Bowel Project trial in 1971, the field of breast surgery underwent significant growth over the next several decades, enabling general surgeons to limit their practices to the breast. High surgical volumes eventually led to the development of the first formal breast surgical oncology fellowship in a large community-based hospital at Baylor University Medical Center in 1982. The establishment of the American Society of Breast Surgeons, as well several landmark clinical trials and public campaign efforts, further contributed to the advancement of breast surgery, making it the specialized field of the current era.

Keywords: breast cancer, breast fellowship, breast surgery, surgical history

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Authors: Monika Kallubai, Shreya Dubey, Rajagopal Subramanyam

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Our study is all about the biological interactions of synthesized 5β-dihydrocortisol (Dhc) and 5β-dihydrocortisol acetate (DhcA) molecules with carrier protein Human Serum Albumin (HSA). The cytotoxic study was performed on breast cancer cell line (MCF-7) normal human embryonic kidney cell line (HEK293), the IC50 values for MCF-7 cells were 28 and 25 µM, respectively, whereas no toxicity in terms of cell viability was observed with HEK293 cell line. The further experiment proved that Dhc and DhcA induced 35.6% and 37.7% early apoptotic cells and 2.5%, 2.9% late apoptotic cells respectively. Morphological observation of cell death through TUNEL assay revealed that Dhc and DhcA induced apoptosis in MCF-7 cells. The complexes of HSA–Dhc and HSA–DhcA were observed as static quenching, and the binding constants (K) was 4.7±0.03×104 M-1 and 3.9±0.05×104 M-1, and their binding free energies were found to be -6.4 and -6.16 kcal/mol, respectively. The displacement studies confirmed that lidocaine 1.4±0.05×104 M-1 replaced Dhc, and phenylbutazone 1.5±0.05×104 M-1 replaced by DhcA, which explains domain I and domain II are the binding sites for Dhc and DhcA. Further, CD results revealed that the secondary structure of HSA was altered in the presence of Dhc and DhcA. Furthermore, the atomic force microscopy and transmission electron microscopy showed that the dimensions like height and molecular sizes of the HSA–Dhc and HSA–DhcA complex were larger compared to HSA alone. Detailed analysis through molecular dynamics simulations also supported the greater stability of HSA–Dhc and HSA–DhcA complexes, and root-mean-square-fluctuation interpreted the binding site of Dhc as domain IB and domain IIA for DhcA. This information is valuable for the further development of steroid derivatives with improved pharmacological significance as novel anti-cancer drugs.

Keywords: apoptosis, dihydrocortisol, fluorescence quenching, protein conformations

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Authors: Samy S. Eleawa, Mahmoud A. Alkhateeb, Fahaid H. Alhashem, Ismaeel bin-Jaliah, Hussein F. Sakr, Hesham M. Elrefaey, Abbas O. Elkarib, Mohammad A. Haidara, Abdullah S. Shatoor, Mohammad A. Khalil

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This effect of Resveratrol (RES) against CdCl2- induced toxicity in the rat testes was investigated. Seven experimental groups of adult male rats were formulated as follows: A) Controls + NS, B) Control+ vehicle (saline solution of hydroxypropyl cyclodextrin), C) RES treated, D) CdCl2 +NS, E) CdCl2+ vehicle, F) RES followed by CdCl2 and M) CdCl2 followed by RES. At the end of the protocol, serum levels of FSH, LH, and testosterone were measured in all groups. Testicular levels of TBARS and Super Oxide Dismutase (SOD) activity were also measured. Epidydidimal semen analysis was performed and testicular expression of Bcl-2, p53 and Bax were assessed by RT-PCR. Also, histopathological changes of testes were examined microscopically and described. Pre and Post administration of RES in cadmium chloride-intoxicated rats improved semen parameters including count, motility, daily sperm production and morphology, increased serum concentrations of gonadotropins and testosterone, decreased testicular lipid peroxidation and increased SOD activity. Not only RES attenuated cadmium chloride induced testicular histopathology but was also able to protect against the onset of cadmium chloride testicular toxicity. Cadmium chloride downregulated the anti-apoptotic gene Bcl2 and upregulated the expression of both pro-apoptotic genes p53 and Bax. Resveratrol protected from and partially reversed cadmium chloride testicular via upregulation of Bcl2 and down regulation of p53 and Bax gene expression. Antioxidant activity of RES protects against cadmium chloride testicular toxicity and partially reverses its effect via upregulation of BCl2 and downregulation of p53 and Bax expression. These findings have far reaching implications on subfertility and impotency frequently seen in hypertensive as well as metabolic syndrome patients.

Keywords: resveratrol, cadmium, infertility, sperm, testis, metabolic syndrome

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Authors: Yelin Zhao, Xinxiu Li, Martin Smelik, Oleg Sysoev, Firoj Mahmud, Dina Mansour Aly, Mikael Benson

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Background: Early diagnosis of pancreatic cancer is clinically challenging due to vague, or no symptoms, and lack of biomarkers. Polygenic risk score (PRS) scores may provide a valuable tool to assess increased or decreased risk of PC. This study aimed to develop such PRS by filtering genetic variants identified by GWAS using transcriptional programs identified by single-cell RNA sequencing (scRNA-seq). Methods: ScRNA-seq data from 24 pancreatic ductal adenocarcinoma (PDAC) tumor samples and 11 normal pancreases were analyzed to identify differentially expressed genes (DEGs) in in tumor and microenvironment cell types compared to healthy tissues. Pathway analysis showed that the DEGs were enriched for hundreds of significant pathways. These were clustered into 40 “programs” based on gene similarity, using the Jaccard index. Published genetic variants associated with PDAC were mapped to each program to generate program PRSs (pPRSs). These pPRSs, along with five previously published PRSs (PGS000083, PGS000725, PGS000663, PGS000159, and PGS002264), were evaluated in a European-origin population from the UK Biobank, consisting of 1,310 PDAC participants and 407,473 non-pancreatic cancer participants. Stepwise Cox regression analysis was performed to determine associations between pPRSs with the development of PC, with adjustments of sex and principal components of genetic ancestry. Results: The PDAC genetic variants were mapped to 23 programs and were used to generate pPRSs for these programs. Four distinct pPRSs (P1, P6, P11, and P16) and two published PRSs (PGS000663 and PGS002264) were significantly associated with an increased risk of developing PC. Among these, P6 exhibited the greatest hazard ratio (adjusted HR[95% CI] = 1.67[1.14-2.45], p = 0.008). In contrast, P10 and P4 were associated with lower risk of developing PC (adjusted HR[95% CI] = 0.58[0.42-0.81], p = 0.001, and adjusted HR[95% CI] = 0.75[0.59-0.96], p = 0.019). By comparison, two of the five published PRS exhibited an association with PDAC onset with HR (PGS000663: adjusted HR[95% CI] = 1.24[1.14-1.35], p < 0.001 and PGS002264: adjusted HR[95% CI] = 1.14[1.07-1.22], p < 0.001). Conclusion: Compared to published PRSs, scRNA-seq-based pPRSs may be used not only to assess increased but also decreased risk of PDAC.

Keywords: cox regression, pancreatic cancer, polygenic risk score, scRNA-seq, UK biobank

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Authors: Jose R. Garcia, Lexi Frankel, Amalia Ardeljan, Sergio Medina, Ali Yasback, Omar Rashid

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Background: Helicobacter pylori (H. pylori) is a gram-negative, spiral-shaped bacterium that affects nearly half of the population worldwide and humans serve as the principal reservoir. Infection rates usually follow an inverse relationship with hygiene practices and are higher in developing countries than developed countries. Incidence varies significantly by geographic area, race, ethnicity, age, and socioeconomic status. H. pylori is primarily associated with conditions of the gastrointestinal tract such as atrophic gastritis and duodenal peptic ulcers. Infection is also associated with an increased risk of carcinogenesis as there is evidence to show that H. pylori infection may lead to gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma. It is suggested that H. pylori infection may be considered as a systemic condition, leading to various novel associations with several different neoplasms such as colorectal cancer, pancreatic cancer, and lung cancer, although further research is needed. Emerging evidence suggests that H. pylori infection may offer protective effects against Mycobacterium tuberculosis as a result of non-specific induction of interferon- γ (IFN- γ). Similar methods of enhanced immunity may affect the development of bronchogenic carcinoma due to the antiproliferative, pro-apoptotic and cytostatic functions of IFN- γ. The purpose of this study was to evaluate the correlation between Helicobacter pylori infection and the incidence of bronchogenic carcinoma. Methods: The data was provided by a Health Insurance Portability and Accountability Act (HIPAA) compliant national database to evaluate the patients infected versus patients not infected with H. pylori using ICD-10 and ICD-9 codes. Access to the database was granted by the Holy Cross Health, Fort Lauderdale for the purpose of academic research. Standard statistical methods were used. Results:-Between January 2010 and December 2019, the query was analyzed and resulted in 163,224 in both the infected and control group, respectively. The two groups were matched by age range and CCI score. The incidence of bronchogenic carcinoma was 1.853% with 3,024 patients in the H. pylori group compared to 4.785% with 7,810 patients in the control group. The difference was statistically significant (p < 2.22x10-16) with an odds ratio of 0.367 (0.353 - 0.383) with a confidence interval of 95%. The two groups were matched by treatment and incidence of cancer, which resulted in a total of 101,739 patients analyzed after this match. The incidence of bronchogenic carcinoma was 1.929% with 1,962 patients in the H. pylori and treatment group compared to 4.618% with 4,698 patients in the control group with treatment. The difference was statistically significant (p < 2.22x10-16) with an odds ratio of 0.403 (0.383 - 0.425) with a confidence interval of 95%.

Keywords: bronchogenic carcinoma, helicobacter pylori, lung cancer, pathogen-associated molecular patterns

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Authors: Kebret Kebede, Anthony Scinta

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Obesity is the most prevalent global problem that continues to rise at alarming rates both in the industrialized and developing countries. Adipose tissue is an endocrine tissue that secretes numerous chemical signals, hormones, lipids, cytokines and coagulation factors as well as prompting insulin resistance which is a primary contributor to Type II Diabetes- one of its most common adverse effects on health. Other hormones whose levels are linked to obesity and nutritional state are leptin, IGF-1, and adiponectin. Several studies indicate that obesity is the leading cause of high levels of cholesterol that leads to fatty liver disease, gallstones, hypertension, increased risk for cancer and degenerative joint disease that primarily affects the weight bearing joints of the lower extremities. The activation of inflammatory pathways promotes synovial pathology that results in accelerated degeneration of the joints. The study examines the prevalence of obesity in the US female population in comparison to that of the developing world and its emergence as a significant and potentially modifiable risk factor in degenerative disease of the hip and knee joints that has resulted in staggering healthcare cost. Studies have shown that as the prevalence of obesity rises, we continue to see a rise in degenerative joint disease. The percentage of arthritis cases linked directly to obesity has risen from 3 percent in 1971 to 18 percent in 2002. A person with obesity is around 60 percent more likely to develop arthritis than someone of normal body weight. In women, obesity is associated with increased mortality from breast, cervical, endometrial and ovarian cancer that may accompany debilitating joint diseases and restricted mobility.

Keywords: obesity, endocrine, degenerative, mortality, joint diseases, cancer, debilitating, mobility

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Authors: S. N. Harun, H. Ahmad

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A series of ruthenium(II) complexes, including two novel compounds [Ru(dppz)2(L)]2+ where dppz = dipyrido-[3,2-a:2’,3’-c]phenazine, and L = 2-phenylimidazo[4,5-f][1,10]phenanthroline (PIP) or 2-(4-hydroxyphenyl)imidazo[4,5-f][1,10]phenanthroline (p-HPIP) have been synthesized and characterized. The previously reported complexes [Ru(bpy)2L]2+ and [Ru(phen)2L]2+ were also prepared. All complexes were characterized by elemental analysis, 1H-NMR spectroscopy, ESI-Mass spectroscopy and FT-IR spectroscopy. The photophysical properties were analyzed by UV-Visible spectroscopy and fluorescence spectroscopy. [Ru(dppz)2(PIP)]2+ and [Ru(dppz)2(p-HPIP)]2+ displayed ‘molecular light-switch’ effect as they have high emission in acetonitrile but no emission in water. The cytotoxicity of all complexes against cancer cell lines Hela and MCF-7 were investigated through standard MTT assay. [Ru(dppz)2(PIP)]2+ showed moderate toxicity on both MCF-7 and Hela with IC50 of 37.64 µM and 28.02 µM, respectively. Interestingly, [Ru(dppz)2(p-HPIP)]2+ exhibited remarkable cytotoxicity results with IC50 of 13.52 µM on Hela and 11.63 µM on MCF-7 cell lines which are comparable to the infamous anti-cancer drug, cisplatin. The cytotoxicity of this complex series increased as the ligands size extended in order of [Ru(bpy)2(L)]2+ < [Ru(phen)2(L)]2+ < [Ru(dppz)2(L)]2+.

Keywords: ruthenium, cytotoxicity, molecular light-switch, anticancer

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Authors: Sneha Noble, Rahul Krishnan, Uma G., D. K. Vijaykumar

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Breast-Cancer related Lymphedema is a major problem that affects many women. Lymphedema is the swelling that generally occurs in the arms or legs caused by the removal of or damage to lymph nodes as a part of cancer treatment. Treating it at the earliest possible stage is the best way to manage the condition and prevent it from leading to pain, recurrent infection, reduced mobility, and impaired function. So, this project aims to focus on the multi-modal approaches to identify the risks of Lymphedema in post-surgical oncology patients and prevent it at the earliest. The Kinect IR Sensor is utilized to capture the images of the body and after image processing techniques, the region of interest is obtained. Then, performing the voxelization method will provide volume measurements in pre-operative and post-operative periods in patients. The formation of a mathematical model will help in the comparison of values. Clinical pathological data of patients will be investigated to assess the factors responsible for the development of lymphedema and its risks.

Keywords: Kinect IR sensor, Lymphedema, voxelization, lymph nodes

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Authors: Christine P. Gibson, Ramona Alex, Michael Farney, Johana Vallejo-Elias, Mitra Esfandiarei

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Aortic aneurysm is the leading cause of death in Marfan syndrome (MFS), a connective tissue disorder caused by mutations in fibrillin-1 gene (FBN1). MFS aneurysm is characterized by weakening of the aortic wall due to elastin fibers fragmentation and disorganization. The above-average height and distinct physical features make young adults with MFS desirable candidates for competitive sports; but little is known about the exercise limit at which they will be at risk for aortic rupture. On the other hand, aerobic cardiovascular exercise has been shown to have protective effects on the heart and aorta. We have previously reported that mild aerobic exercise can delay the formation of aortic aneurysm in a mouse model of MFS. In this study, we aimed to investigate the effects of various levels of exercise intensity on the progression of aortic aneurysm in the mouse model. Starting at 4 weeks of age, we subjected control and MFS mice to different levels of exercise intensity (8m/min, 10m/min, 15m/min, and 20m/min, corresponding to 55%, 65%, 75%, and 85% of VO2 max, respectively) on a treadmill for 30 minutes per day, five days a week for the duration of the study. At 24 weeks of age, aortic tissue were isolated and subjected to structural and functional studies using histology and wire myography in order to evaluate the effects of different exercise routines on elastin fragmentation and organization and aortic wall elasticity/stiffness. Our data shows that exercise training at the intensity levels between 55%-75% significantly reduces elastin fragmentation and disorganization, with less recovery observed in 85% MFS group. The reversibility of elasticity was also significantly restored in MFS mice subjected to 55%-75% intensity; however, the recovery was less pronounced in MFS mice subjected to 85% intensity. Furthermore, our data shows that smooth muscle cells (SMCs) contractilion in response to vasoconstrictor agent phenylephrine (100nM) is significantly reduced in MFS aorta (54.84 ± 1.63 mN/mm2) as compared to control (95.85 ± 3.04 mN/mm2). At 55% of intensity, exercise did not rescue SMCs contraction (63.45 ± 1.70 mN/mm2), while at higher intensity levels, SMCs contraction in response to phenylephrine was restored to levels similar to control aorta [65% (81.88 ± 4.57 mN/mm2), 75% (86.22 ± 3.84 mN/mm2), and 85% (83.91 ± 5.42 mN/mm2)]. This study provides the first time evidence that high intensity exercise (e.g. 85%) may not provide the most beneficial effects on aortic function (vasoconstriction) and structure (elastin fragmentation, aortic wall elasticity) during the progression of aortic aneurysm in MFS mice. On the other hand, based on our observations, medium intensity exercise (e.g. 65%) seems to provide the utmost protective effects on aortic structure and function in MFS mice. These findings provide new insights into the potential capacity, in which MFS patients could participate in various aerobic exercise routines, especially in young adults affected by cardiovascular complications particularly aortic aneurysm. This work was funded by Midwestern University Research Fund.

Keywords: aerobic exercise, aortic aneurysm, aortic wall elasticity, elastin fragmentation, Marfan syndrome

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Authors: Shouta Sora, Shizuki Kuriu, Radhika Mishra, Ariunbuyan Sukhbaatar, Maya Sakamoto, Shiro Mori, Tetsuya Kodama

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Lymph node (LN) metastasis accounts for 20 - 30 % of all deaths in patients with head and neck cancer. Therefore, the control of metastatic lymph nodes (MLNs) is necessary to improve the life prognosis of patients with cancer. In a classical metastatic theory, tumor cells are thought to metastasize hematogenously through a bead-like network of lymph nodes. Recently, a lymph node-mediated hematogenous metastasis theory has been proposed, in which sentinel LNs are regarded as a source of distant metastasis. Therefore, the treatment of MLNs at the early stage is essential to prevent distant metastasis. Radiation therapy is one of the primary therapeutic modalities in cancer treatment. In addition, total body irradiation (TBI) has been reported to act as activation of natural killer cells and increase of infiltration of CD4+ T-cells to tumor tissues. However, the treatment effect of TBI for MLNs remains unclear. This study evaluated the possibilities of low-dose total body irradiation (L-TBI) and middle-dose total body irradiation (M-TBI) for the treatment of MLNs. Mouse breast cancer FM3A-Luc cells were injected into subiliac lymph node (SiLN) of MXH10/Mo/LPR mice to induce the metastasis to the proper axillary lymph node (PALN) and lung. Mice were irradiated for the whole body on 4 days after tumor injection. The L-TBI and M-TBI were defined as irradiations to the whole body at 0.2 Gy and 1.0 Gy, respectively. Tumor growth was evaluated by in vivo bioluminescence imaging system. In the non-irradiated group, tumor activities on SiLN and PALN significantly increased over time, and the metastasis to the lung from LNs was confirmed 28 days after tumor injection. The L-TBI led to a tumor growth delay in PALN but did not control tumor growth in SiLN and metastasis to the lung. In contrast, it was found that the M-TBI significantly delayed the tumor growth of both SiLN and PALN and controlled the distant metastasis to the lung compared with non-irradiated and L-TBI groups. These results suggest that the M-TBI is an effective treatment method for MLNs in the early stage and distant metastasis from lymph nodes via blood vessels connected with LNs.

Keywords: metastatic lymph node, lung metastasis, radiation therapy, total body irradiation, lymphatic system

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Authors: Jer-Yuh Liu, Je-Chiuan Ye, Jin-Ming Hwang

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Protein kinase C alpha (PKCα) is a key signaling molecule in human cancer development. As a therapeutic strategy, targeting PKCα is difficult because the molecule is ubiquitously expressed in non-malignant cells. PKCα is regulated by the cooperative interaction of the transcription factors myeloid zinc finger 1 (MZF-1) and Ets-like protein-1 (Elk-1) in human cancer cells. By conducting tissue array analysis, herein, we determined the protein expression of MZF-1/Elk-1/PKCα in various cancers. The data show that the expression of MZF-1/Elk-1 is correlated with that of PKCα in hepatocellular carcinoma (HCC), but not in bladder and lung cancers. In addition, the PKCα down-regulation by shRNA Elk-1 was only observed in the HCC SK-Hep-1 cells. Blocking the interaction between MZF-1 and Elk-1 through the transfection of their binding domain MZF-160–72 decreased PKCα expression. This step ultimately depressed the epithelial-mesenchymal transition potential of the HCC cells. These findings could be used to develop an alternative therapeutic strategy for patients with the PKCα-derived HCC.

Keywords: protein kinase C alpha, myeloid zinc finger 1, ets-like protein-1, hepatocellular carcinoma

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Authors: Krima M. Rohela, Raja Sabarinath Sundaralingam

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Humans have been launching rockets since the beginning of the space age in the late 1950s. We have come a long way since then, and the success rate for the launch of rockets has increased considerably. With every successful launch, there is a large amount of junk or debris which is released into the upper layers of the atmosphere. Space debris has been a huge concern for a very long time now. This includes the rocket shells released from the launch and the parts of defunct satellites. Some of this junk will come to fall towards the Earth and burn in the atmosphere. But most of the junk goes into orbit around the Earth, and they remain in orbits for at least 100 years. This can cause a lot of problems to other functioning satellites and may affect the future manned missions to space. The main concern of the space-debris is the increase in space activities, which leads to risks of collisions if not taken care of soon. These collisions may result in what is known as Kessler Syndrome. This debris can be removed by a space-based laser targeting system. Hence, the matter is investigated and discussed. The first step in this involves launching a satellite with a high-power laser device into space, above the debris belt. Then the target material is ablated with a focussed laser beam. This step of the process is highly dependent on the attitude and orientation of the debris with respect to the Earth and the device. The laser beam will cause a jet of vapour and plasma to be expelled from the material. Hence, the force is applied in the opposite direction, and in accordance with Newton’s third law of motion, this will cause the material to move towards the Earth and get pulled down due to gravity, where it will get disintegrated in the upper layers of the atmosphere. The larger pieces of the debris can be directed towards the oceans. This method of removal of the orbital debris will enable safer passage for future human-crewed missions into space.

Keywords: altitude, Kessler syndrome, laser ablation, Newton’s third law of motion, satellites, Space debris

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Authors: Sophie Mills, Leila L. Touil, Richard Sisson

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Introduction: The TNM classification is the global standard for the staging of head and neck cancers. Accurate clinical-radiological staging of tumours (cTNM) is essential to predict prognosis, facilitate surgical planning and determine the need for other therapeutic modalities. This study aims to determine the accuracy of pre-operative cTNM staging using pathological TNM (pTNM) and consider possible causes of TNM stage migration, noting any variation throughout the COVID-19 pandemic. Materials and Methods: A retrospective cohort study examined records of patients with surgical management of head and neck cancer at a tertiary head and neck centre from November 2019 to November 2020. Data was extracted from Somerset Cancer Registry and histopathology reports. cTNM and pTNM were compared before and during the first wave of COVID-19, as well as with other potential prognostic factors such as tumour site and tumour stage. Results: 119 cases were identified, of which 52.1% (n=62) were male, and 47.9% (n=57) were female with a mean age of 67 years. Clinical and pathological staging differed in 54.6% (n=65) of cases. Of the patients with stage migration, 40.4% (n=23) were up-staged and 59.6% (n=34) were down-staged compared with pTNM. There was no significant difference in the accuracy of cTNM staging compared with age, sex, or tumour site. There was a statistically highly significant (p < 0.001) correlation between cTNM accuracy and tumour stage, with the accuracy of cTNM staging decreasing with the advancement of pTNM staging. No statistically significant variation was noted between patients staged prior to and during COVID-19. Conclusions: Discrepancies in staging can impact management and outcomes for patients. This study found that the higher the pTNM, the more likely stage migration will occur. These findings are concordant with the oncology literature, which highlights the need to improve the accuracy of cTNM staging for more advanced tumours.

Keywords: COVID-19, head and neck cancer, stage migration, TNM staging

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Authors: Li-Kai Kuo, Shyh-Hau Wang

Abstract:

The kinetic trajectory of the median nerve (MN) in the wrist has shown to be capable of being applied to assess the carpal tunnel syndrome (CTS), and was found able to be detected by high-frequency ultrasound image via motion tracking technique. Yet, previous study may not quickly perform the measurement due to the use of a single element transducer for ultrasound image scanning. Therefore, previous system is not appropriate for being applied to clinical application. In the present study, B-mode ultrasound images of the wrist corresponding to movements of fingers from flexion to extension were acquired by clinical applicable real-time scanner. The kinetic trajectories of MN were off-line estimated utilizing two dimensional Baysian speckle tracking (TDBST) technique. The experiments were carried out from ten volunteers by ultrasound scanner at 12 MHz frequency. Results verified from phantom experiments have demonstrated that TDBST technique is able to detect the movement of MN based on signals of the past and present information and then to reduce the computational complications associated with the effect of such image quality as the resolution and contrast variations. Moreover, TDBST technique tended to be more accurate than that of the normalized cross correlation tracking (NCCT) technique used in previous study to detect movements of the MN in the wrist. In response to fingers’ flexion movement, the kinetic trajectory of the MN moved toward the ulnar-palmar direction, and then toward the radial-dorsal direction corresponding to the extensional movement. TDBST technique and the employed ultrasound image scanner have verified to be feasible to sensitively detect the kinetic trajectory and displacement of the MN. It thus could be further applied to diagnose CTS clinically and to improve the measurements to assess 3D trajectory of the MN.

Keywords: baysian speckle tracking, carpal tunnel syndrome, median nerve, motion tracking

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Authors: Farid Risheq, M. Zaid Alrisheq, Shuaa Al-Sadoon, Karim Al-Faqih, Mays Abdulazeez

Abstract:

Breast cancer is the most frequently diagnosed cancer worldwide, and a common cause of death among women. Various conventional anatomical imaging tools are utilized for diagnosis, histological assessment and TNM (Tumor, Node, Metastases) staging of breast cancer. Biopsy of sentinel lymph node is becoming an alternative to the axillary lymph node dissection. Advances in 18-Fluoro-Deoxi-Glucose Positron Emission Tomography/Computed Tomography (18FDG-PET/CT) imaging have facilitated breast cancer diagnosis utilizing biological trapping of 18FDG inside lesion cells, expressed as Standardized Uptake Value (SUVmax). Objective: To present the utility of 18FDG uptake PET/CT scans in detecting active extra lymph nodes and distant occult metastases for breast cancer staging. Subjects and Methods: Four female patients were presented with initially classified TNM stages of breast cancer based on conventional anatomical diagnostic techniques. 18FDG-PET/CT scans were performed one hour post 18FDG intra-venous injection of (300-370) MBq, and (7-8) bed/130sec. Transverse, sagittal, and coronal views; fused PET/CT and MIP modality were reconstructed for each patient. Results: A total of twenty four lesions in breast, extended lesions to lung, liver, bone and active extra lymph nodes were detected among patients. The initial TNM stage was significantly changed post 18FDG-PET/CT scan for each patient, as follows: Patient-1: Initial TNM-stage: T1N1M0-(stage I). Finding: Two lesions in right breast (3.2cm2, SUVmax=10.2), (1.8cm2, SUVmax=6.7), associated with metastases to two right axillary lymph nodes. Final TNM-stage: T1N2M0-(stage II). Patient-2: Initial TNM-stage: T2N2M0-(stage III). Finding: Right breast lesion (6.1cm2, SUVmax=15.2), associated with metastases to right internal mammary lymph node, two right axillary lymph nodes, and sclerotic lesions in right scapula. Final TNM-stage: T2N3M1-(stage IV). Patient-3: Initial TNM-stage: T2N0M1-(stage III). Finding: Left breast lesion (11.1cm2, SUVmax=18.8), associated with metastases to two lymph nodes in left hilum, and three lesions in both lungs. Final TNM-stage: T2N2M1-(stage IV). Patient-4: Initial TNM-stage: T4N1M1-(stage III). Finding: Four lesions in upper outer quadrant area of right breast (largest: 12.7cm2, SUVmax=18.6), in addition to one lesion in left breast (4.8cm2, SUVmax=7.1), associated with metastases to multiple lesions in liver (largest: 11.4cm2, SUV=8.0), and two bony-lytic lesions in left scapula and cervicle-1. No evidence of regional or distant lymph node involvement. Final TNM-stage: T4N0M2-(stage IV). Conclusions: Our results demonstrated that 18FDG-PET/CT scans had significantly changed the TNM stages of breast cancer patients. While the T factor was unchanged, N and M factors showed significant variations. A single session of PET/CT scan was effective in detecting active extra lymph nodes and distant occult metastases, which were not identified by conventional diagnostic techniques, and might advantageously replace bone scan, and contrast enhanced CT of chest, abdomen and pelvis. Applying 18FDG-PET/CT scan early in the investigation, might shorten diagnosis time, helps deciding adequate treatment protocol, and could improve patients’ quality of life and survival. Trapping of 18FDG in malignant lesion cells, after a PET/CT scan, increases the retention index (RI%) for a considerable time, which might help localize sentinel lymph node for biopsy using a hand held gamma probe detector. Future work is required to demonstrate its utility.

Keywords: axillary lymph nodes, breast cancer staging, fluorodeoxyglucose positron emission tomography/computed tomography, lymph nodes

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Authors: Gonzalo Ortiz de Elguea-Culebras, Raúl Sánchez-Vioquea, Adela Mena-Morales, Manuel Alaiz, Enrique Melero-Bravo, Esteban García-Romero, Javier Vioque, Lourdes Marchante-Cuevas, Julio Girón-Calle

Abstract:

Saffron (Crocus sativus L.) is a highly valued crop for the manufacture of spice that consists of the dried stigma of the flowers. This is in contrast to other underutilized parts of the saffron plant as leaves, which represent abundant biomass whose use might help to enhance the sustainability of the saffron crop. Saffron leaves contain significant amounts of phenolic compounds, 7.8 equivalent grams of gallic acid per 100g of extract, and are very promising compounds in terms of exploring novel uses of saffron leaves. Given that phenolic compounds have numerous effects on cancer-related biological pathways, we have investigated the in vitro antiproliferative effect of saffron leaf polyphenols against human colon adenocarcinoma cells (Caco-2). Polyphenols were extracted from leaves with 70% ethanol, defatted with hexane, and purified by solid phase extraction using C18 silica gel and then silica gel 60. Analysis of polyphenols was performed by HPLC-ESI-MS. Di-, tri-, and tetrahexosides of quercetin, kaempferol, and isorhamnetin, as well as C-hexosides like isoorientin and vitexin, were tentatively identified. Polyphenols strongly inhibited the proliferation of Caco-2 cells, which is consistent with model studies in which several of the polyphenols identified in saffron leaves have demonstrated their potential as chemopreventive agents in cancer. Due to the low profitability that saffron leaf currently represents, we consider these results very encouraging and that this by-product deserves further investigation as a potential source of active molecules against colorectal cancer.

Keywords: saffron leaves, agricultural by-products, polyphenols, antiproliferative effect, human colon adenocarcinoma cells

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Authors: Aihong Zhao, Priya Sastry, Mark L Field, Mohamad Bashir, Arvind Singh, David Richens

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Objectives: Intramural haematoma (IMH) is one of the pathologies, along with acute aortic dissection, that present as Acute Aortic Syndrome (AAS). Evidence suggests that unlike aortic dissection, some intramural haematomas may regress with medical management. However, intramural haematomas have been traditionally managed like acute aortic dissections. Given that some of these pathologies may regress with conservative management, it would be useful to be able to identify which of these may not need high risk emergency intervention. A computational aortic model was used in this study to try and identify intramural haematomas with risk of progression to aortic dissection. Methods: We created a computational model of the aorta with luminal blood flow. Reports in the literature have identified 11 mm as the radial clot thickness that is associated with heightened risk of progression of intramural haematoma. Accordingly, haematomas of varying sizes were implanted in the modeled aortic wall to test this hypothesis. The model was exposed to physiological blood flows and the stresses and strains in each layer of the aortic wall were recorded. Results: Size and shape of clot were seen to affect the magnitude of aortic stresses. The greatest stresses and strains were recorded in the intima of the model. When the haematoma exceeded 10 mm in all dimensions, the stress on the intima reached breaking point. Conclusion: Intramural clot size appears to be a contributory factor affecting aortic wall stress. Our computer simulation corroborates clinical evidence in the literature proposing that IMH diameter greater than 11 mm may be predictive of progression. This preliminary report suggests finite element modelling of the aortic wall may be a useful process by which to examine putative variables important in predicting progression or regression of intramural haematoma.

Keywords: intramural haematoma, acute aortic syndrome, finite element analysis,

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Authors: Ning Li, Jiacheng Zhang, Zheng Yang, Sylvia Kang

Abstract:

Introduction: Polycystic ovary syndrome (PCOS) is a common physiological symptom in women of reproductive age. Women with PCOS may have infrequent or prolonged menstrual periods and excess male hormone (androgen) levels. Mira analyzes the cycle profiles and the luteinizing hormone (LH) changes in urine, closely related to the fertility level of healthy women and PCOS women. From the difference between the two groups, Mira helps to understand the physiological state of PCOS women and their hormonal changes in the menstrual cycle. Methods: In this study, data from 1496 cycles and information from 342 women belonging to two groups (181 PCOS and 161 Healthy) were collected and analyzed. Women test their luteinizing hormone (LH) in urine daily with Mira fertility test wand and Mira analyzer, from the day after the menstruation to the starting day of the next menstruation. All the collected data meets Mira’s user agreement and users’ identification was removed. The cycle length, LH peak, and other cycle information of the PCOS group were compared with the Healthy group. Results: The average cycle length of PCOS women is 41 days and of the Healthy women is 33 days. 91.4% of cycle length is within 40 days for the Healthy group, while it decreases to 71.9% for the PCOS group. This means PCOS women have a longer menstrual cycle and more variation during the cycle. With more variation, the ovulation prediction becomes more difficult for the PCOS group. The deviation between the LH surge day and the predicted ovulation day, calculated by the starting day of the next menstruation minus 14 days, is greater in the PCOS group compared with the Healthy group. Also, 46.96% of PCOS women have an irregular cycle, and only 19.25% of healthy women show an irregular cycle. Conclusion: PCOS women have longer menstrual cycles and more variation during the menstrual cycles. The traditional ovulation prediction is not suitable for PCOS women.

Keywords: menstrual cycle, PCOS, urinary luteinizing hormone, Mira

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Authors: Katarzyna Lubecka, Kirsty Flower, Megan Beetch, Lucinda Kurzava, Hannah Buvala, Samer Gawrieh, Suthat Liangpunsakul, Tracy Gonzalez, George McCabe, Naga Chalasani, James M. Flanagan, Barbara Stefanska

Abstract:

Hepatocellular carcinoma (HCC), the most prevalent type of primary liver cancer, is the second leading cause of cancer death worldwide. Late onset of clinical symptoms in HCC results in late diagnosis and poor disease outcome. Approximately 85% of individuals with HCC have underlying liver cirrhosis. However, not all cirrhotic patients develop cancer. Reliable early detection biomarkers that can distinguish cirrhotic patients who will develop cancer from those who will not are urgently needed and could increase the cure rate from 5% to 80%. We used Illumina-450K microarray to test whether blood DNA, an easily accessible source of DNA, bear site-specific changes in DNA methylation in response to HCC before diagnosis with conventional tools (pre-diagnostic). Top 11 differentially methylated sites were selected for validation by pyrosequencing. The diagnostic potential of the 11 pyrosequenced probes was tested in blood samples from a prospective cohort of cirrhotic patients. We identified 971 differentially methylated CpG sites in pre-diagnostic HCC cases as compared with healthy controls (P < 0.05, paired Wilcoxon test, ICC ≥ 0.5). Nearly 76% of differentially methylated CpG sites showed lower levels of methylation in cases vs. controls (P = 2.973E-11, Wilcoxon test). Classification of the CpG sites according to their location relative to CpG islands and transcription start site revealed that those hypomethylated loci are located in regulatory regions important for gene transcription such as CpG island shores, promoters, and 5’UTR at higher frequency than hypermethylated sites. Among 735 CpG sites hypomethylated in cases vs. controls, 482 sites were assigned to gene coding regions whereas 236 hypermethylated sites corresponded to 160 genes. Bioinformatics analysis using GO, KEGG and DAVID knowledgebase indicate that differentially methylated CpG sites are located in genes associated with functions that are essential for gene transcription, cell adhesion, cell migration, and regulation of signal transduction pathways. Taking into account the magnitude of the difference, statistical significance, location, and consistency across the majority of matched pairs case-control, we selected 11 CpG loci corresponding to 10 genes for further validation by pyrosequencing. We established that methylation of CpG sites within 5 out of those 10 genes distinguish cirrhotic patients who subsequently developed HCC from those who stayed cancer free (cirrhotic controls), demonstrating potential as biomarkers of early detection in populations at risk. The best predictive value was detected for CpGs located within BARD1 (AUC=0.70, asymptotic significance ˂0.01). Using an additive logistic regression model, we further showed that 9 CpG loci within those 5 genes, that were covered in pyrosequenced probes, constitute a panel with high diagnostic accuracy (AUC=0.887; 95% CI:0.80-0.98). The panel was able to distinguish pre-diagnostic cases from cirrhotic controls free of cancer with 88% sensitivity at 70% specificity. Using blood as a minimally invasive material and pyrosequencing as a straightforward quantitative method, the established biomarker panel has high potential to be developed into a routine clinical test after validation in larger cohorts. This study was supported by Showalter Trust, American Cancer Society (IRG#14-190-56), and Purdue Center for Cancer Research (P30 CA023168) granted to BS.

Keywords: biomarker, DNA methylation, early detection, hepatocellular carcinoma

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Authors: Aleksandra Chałupnik, Zuzanna Chilimoniuk, Joanna Borowik, Aleksandra Borkowska, Anna Torres

Abstract:

Background: Precocious puberty is the occurrence of secondary sexual characteristics in girls before the age of 8. The diverse etiology of premature puberty is crucial to determine whether it is true precocious puberty, depending on the activation of the hypothalamic-pituitary-gonadal axis, or pseudo-precocious, which is independent of the activation of this axis. Whatever the cause, premature action of the sex hormones leads to the common symptoms of various forms of puberty. These include the development of sexual characteristics, acne, acceleration of growth rate and acceleration of skeletal maturation. Due to the possible genetic basis of the disorders, an interdisciplinary search for the cause is needed. Case report: The case report concerns a patient of a pediatric gynecology clinic who, at the age of two years, developed advanced thelarhe (M3) and started recurrent vaginal bleeding. In August 2019, gonadotropin suppression initially and after LHRH stimulation and high estradiol levels were reported at the Endocrinology Department. Imaging examinations showed a cyst in the right ovary projection. The bone age was six years. The entire clinical picture indicated pseudo- (peripheral) precocious in the course of ovarian autonomic cyst. In the follow-up ultrasound performed in September, the image of the cyst was stationary and normalization of estradiol levels and clinical symptoms was noted. In December 2019, cyst regression and normal gonadotropin and estradiol concentrations were found. In June 2020, white mucus tinged with blood on the underwear, without any other disturbing symptoms, was observed for several days. Two consecutive USG examinations carried out in the same month confirmed the change in the right ovary, the diameter of which was 25 mm with a very high level of estradiol. Germinal tumor markers were normal. On the Tanner scale, the patient scored M2P1. The labia and hymen had puberty features. The correct vaginal entrance was visible. Another active vaginal bleeding occurred in the first week of July 2020. The considered laparoscopic treatment was abandoned due to the lack of oncological indications. Treatment with Tamoxifen was recommended in July 2020. In the initiating period of treatment, no maturation progression, and even reduction of symptoms, no acceleration of growth and a marked reduction in the size of the cysts were noted. There was no bleeding. After the size of the cyst and hormonal activity increased again, the treatment was changed to Anastrozole, the effect of which led to a reduction in the size of the cyst. Conclusions: The entire clinical picture indicates alleged (peripheral) puberty. Premature puberty in girls, which is manifested as enlarged mammary glands with high levels of estrogens secreted by autonomic ovarian cysts and prepubertal levels of gonadotropins, may indicate McCune-Albright syndrome. Vaginal bleeding may also occur in this syndrome. Cancellation of surgical treatment of the cyst made it impossible to perform a molecular test that would allow to confirm the diagnosis. Taking into account the fact that cysts are often one of the first symptoms of McCune-Albrigt syndrome, it is important to remember about multidisciplinary care for the patient and careful search for skin and bone changes or other hormonal disorders.

Keywords: McCune Albrigth's syndrome, ovarian cyst, pediatric gynaecology, precocious puberty

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Authors: Mohammad Alkhatatbeh, Nehad Ayoub, Nizar Mhaidat, Nesreen Saadeh, Lisa Lincz

Abstract:

CD36 is involved in the development of atherosclerosis by enhancing macrophage endocytosis of oxidized-low density lipoproteins and foam cell formation. Soluble CD36 (sCD36) was found to be elevated in type 2 diabetic patients and was supposed to act as a marker of insulin resistance and atherosclerosis. In young subjects, sCD36 was associated with cardiovascular risk factors including obesity and hypertriglyceridemia. This study was conducted to further investigate the relationship between plasma sCD36 and cardiovascular risk factors among middle-aged patients with metabolic syndrome (MetS) and healthy controls. SCD36 concentrations were determined by enzyme-linked immunosorbent assays (ELISA) for 41 patients with MetS and 36 healthy controls. Data for other variables were obtained from patients' medical records. SCD36 concentrations were relatively low compared to most other studies and were not significantly different between the MetS group and controls (P-value=0.17). SCD36 was also not correlated with age, body mass index, glucose, lipid profile, serum electrolytes and blood counts. SCD36 was not significantly different between subjects with obesity, hyperglycemia, dyslipidemia, hypertension or cardiovascular disease and those without these abnormalities (P-value > 0.05). The inconsistency between results reported in this study and other studies may be unique to the study population or be a result of the lack of a reliable standardized method for determining absolute sCD36 concentrations. However, further investigations are required to assess CD36 tissue expression in the study population and to assess the accuracy of various commercially available sCD36 ELISA kits. Thus, the availability of a standardized simple sCD36 ELISA that could be performed in any basic laboratory would be more favorable to the specialized flow cytometry methods that detect CD36+ microparticles if it was to be used as a biomarker.

Keywords: metabolic syndrome, CD36, cardiovascular risk, obesity, type 2 diabetes mellitus

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Authors: Gurbanova J., Majidova N., Ali-Zade S., Hasanova A., Mikailzade P.

Abstract:

Currently, the problem of oncogynecological diseases is widespread and remains relevant in terms of quantitative growth. It is known that due to the increase in the number of benign diseases of the cervix, the development of precancerous conditions occurs. Benign diseases of the cervix represent the most common gynecological problem, which are often precursors of malignant neoplasms, especially cervical cancer. According to statistics, benign diseases of the cervix cover 25-45% of all gynecological diseases. Among women's oncogynecological diseases, cervical cancer ranks second in the world after breast cancer and ranks first in the mortality rate among oncological diseases in economically underdeveloped countries. We performed a comprehensive clinical and laboratory examination of 130 women aged 18 to 73 with benign cervical diseases. 59 (38.5%) women of reproductive age, as well as 39 (30%) premenopausal and 41 (31.5%) menopausal patients, participated in the study. Detailed anamnesis was collected from all patients, objective and gynecological examination was performed, laboratory and instrumental examinations (USM, IPV DNA, smear microscopy, and PCR bacteriological examination of sexually transmitted infections), simple and extended colposcopy, liquid-based РАР-smear smear and РАР-classic smear examinations were conducted. As a result of the research, the following nosological forms were found in women with benign diseases of the cervix: non-specific vaginitis in 10 (7.7%) cases; ectopia, endocervicitis - 60(46.2%); cervical ectropion - 7(5.4%); cervical polyp - 9(6.9%); cervical leukoplakia - 15(11.5%); atrophic vaginitis - 7(5.4%); condyloma - 12(9.2%); cervical stenosis - 2(1.5%); endometriosis of the cervix - was noted in 8 (6.2%) cases (p<0.001), respectively. Characteristics of the menstrual cycle among the examined women: normal cycle in 97 (74.6%) cases; oligomenorrhea – 23 (17.7%); polymenorrhea – 4(3.1%); algomenorrhea – noted in 6 (4.6%) cases (p<0.001). Cytological examination showed that: the specificity of liquid-based cytology was 76.2%, and the traditional PAP test was set at 70.6%. The overall diagnostic value was calculated to be 86% in liquid-based cytology and 78.5% in conventional PAP tests. Treatment of women with benign diseases of the cervix was carried out by diathermocoagulation method and "FOTEK EA 141M" device. It should be noted that 6 months after the treatment, after treatment with the "FOTEK EA 141M" device, there was no relapse in any patient. Recurrence was found in 23.7% of patients after diathermoelectrocoagulation. Thus, it is clear from the above that the study of cervical pathologies, the determination of optimal examinations, and effective treatment methods is one of the urgent problems facing obstetrics and gynecology.

Keywords: cervical cancer, cytological examination, PAP-smear, non-specific vaginitis

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Authors: Hanan Alsaeid Alshenawy

Abstract:

Background: Cervical dysplasia, which is potentially precancerous, has increased in young women. Detection of cervical is important for reducing morbidity and mortality in cervical cancer. This study analyzes the immunohistochemical expression of p16, HPV L1 capsid protein and Ki67 in cervical intraepithelial lesions and correlates them with lesion grade to develop a set of markers for diagnosis and detect the prognosis of cervical cancer precursors. Methods: 75 specimens were analyzed including 15 cases CIN 1, 28 CIN 2, 20 CIN 3, and 12 cervical squamous carcinoma, besides 10 normal cervical tissues. They were stained for p16, HPV L1 and Ki-67. Sensitivity, specificity, predictive values and accuracy were evaluated for each marker. Results: p16 expression increased during the progression from CIN 1 to carcinoma. HPV L1 positivity was detected in CIN 2 and decreased gradually as the CIN grade increased but disappear in carcinoma. Strong Ki-67 expression was observed with high grades CIN and carcinoma. p16, HPV L1 and Ki67 were sensitive but with variable specificity in detecting CIN lesions. Conclusions: p16, HPV L1 and Ki67 are useful set of markers in establishing the risk of high-grade CIN. They complete each other to reach accurate diagnosis and prognosis.

Keywords: p16, HPV L1, Ki67, CIN, cervical carcinoma

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