Search results for: gastric cancer surgery

Authors: Daniel Thompson, Muhammad Peerbux, Sophie Cerutti, Hansraj Bookun

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Introduction: Dialysis access is a key component of the care of patients with end stage renal failure. In our institution, a combined service of vascular surgeons and nephrologists are responsible for the creation and maintenance of arteriovenous fisultas (AVF), tenckhoff cathethers and Hickman/permcath lines. This poster investigates the last 10 years of dialysis access surgery conducted at St. Vincent’s Hospital Melbourne. Method: A cross-sectional retrospective analysis was conducted of patients of St. Vincent’s Hospital Melbourne (Victoria, Australia) utilising data collection from the Australasian Vascular Audit (Australian and New Zealand Society for Vascular Surgery). Descriptive demographic analysis was carried out as well as operation type, length of hospital stays, postoperative deaths and need for reoperation. Results: 2085 patients with renal failure were operated on between the years of 2011 and 2020. 1315 were male (63.1%) and 770 were female (36.9%). The mean age was 58 (SD 13.8). 92% of patients scored three or greater on the American Society of Anesthiologiests classification system. Almost half had a history of ischaemic heart disease (48.4%), more than half had a history of diabetes (64%), and a majority had hypertension (88.4%). 1784 patients had a creatinine over 150mmol/L (85.6%), the rest were on dialysis (14.4%). The most common access procedure was AVF creation, with 474 autologous AVFs and 64 prosthetic AVFs. There were 263 Tenckhoff insertions. We performed 160 cadeveric renal transplants. The most common location for AVF formation was brachiocephalic (43.88%) followed by radiocephalic (36.7%) and brachiobasilic (16.67%). Fistulas that required re-intervention were most commonly angioplastied (n=163), followed by thrombectomy (n=136). There were 107 local fistula repairs. Average length of stay was 7.6 days, (SD 12). There were 106 unplanned returns to theatre, most commonly for fistula creation, insertion of tenckhoff or permacath removal (71.7%). There were 8 deaths in the immediately postoperative period. Discussion: Access to dialysis is vital for patients with end stage kidney disease, and requires a multidisciplinary approach from both nephrologists, vascular surgeons, and allied health practitioners. Our service provides a variety of dialysis access methods, predominately fistula creation and tenckhoff insertion. Patients with renal failure are heavily comorbid, and prolonged hospital admission following surgery is a source of significant healthcare expenditure. AVFs require careful monitoring and maintenance for ongoing utility, and our data reflects a multitude of operations required to maintain usable access. The requirement for dialysis is growing worldwide and our data demonstrates a local experience in access, with preferred methods, common complications and the associated surgical interventions.

Keywords: dialysis, fistula, nephrology, vascular surgery

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Authors: Daniel Thompson, Muhammad Peerbux, Sophie Cerutti, Hansraj Riteesh Bookun

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Patients with carotid stenosis, which may be asymptomatic or symptomatic in the form of transient ischaemic attack (TIA), amaurosis fugax, or stroke, often require an endarterectomy to reduce stroke risk. Risks of this procedure include stroke, death, myocardial infarction, and cranial nerve damage. Carotid endarterectomy is most commonly performed under general anaesthetic, however, it can also be undertaken with a regional anaesthetic approach. Our tertiary centre generally performs carotid endarterectomy under regional anaesthetic. Our major tertiary hospital mostly utilises regional anaesthesia for carotid endarterectomy. We completed a cross-sectional analysis of all cases of carotid endarterectomy performed under regional anaesthesia across a 10-year period between January 2010 to March 2020 at our institution. 350 patients were included in this descriptive analysis, and demographic details for patients, indications for surgery, procedural details, length of surgery, and complications were collected. Data was cross tabulated and presented in frequency tables to describe these categorical variables. 263 of the 350 patients in the analysis were male, with a mean age of 71 ± 9. 172 patients had a history of ischaemic heart disease, 104 had diabetes mellitus, 318 had hypertension, and 17 patients had chronic kidney disease greater than Stage 3. 13.1% (46 patients) were current smokers, and the majority (63%) were ex-smokers. Most commonly, carotid endarterectomy was performed conventionally with patch arterioplasty 96% of the time (337 patients). The most common indication was TIA and stroke in 64% of patients, 18.9% were classified as asymptomatic, and 13.7% had amaurosis fugax. There were few general complications, with 9 wound complications/infections, 7 postoperative haematomas requiring return to theatre, 3 myocardial infarctions, 3 arrhythmias, 1 exacerbation of congestive heart failure, 1 chest infection, and 1 urinary tract infection. Specific complications to carotid endarterectomy included 3 strokes, 1 postoperative TIA, and 1 cerebral bleed. There were no deaths in our cohort. This analysis of a large cohort of patients from a major tertiary centre who underwent carotid endarterectomy under regional anaesthesia indicates the safety of such an approach for these patients. Regional anaesthesia holds the promise of less general respiratory and cardiac events compared to general anaesthesia, and in this vulnerable patient group, calls for comparative research between local and general anaesthesia in carotid surgery.

Keywords: anaesthesia, carotid endarterectomy, stroke, carotid stenosis

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Authors: Esra Yuksel, Dilek Duman, Levent Yeniay, Sezgin Ulukaya

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Sentinel lymph node biopsy (SLNB) is a minimal invasive technique with lower morbidity in axillary staging of breast cancer. Isosulfan blue stain is frequently used in SLNB and regarded as safe. The present case report aimed to report severe decrement in SpO2 following isosulfan blue administration, as well as skin and urine signs and inconsistency with clinical picture in a 67-year-old ,77 kg, ASA II female case that underwent SLNB under general anesthesia. Ten minutes after subcutaneous administration of 10 ml 1% isosulfan blue by the surgeons into the patient, who were hemodynamically stable, SpO2 first reduced to 87% from 99%, and then to 75% in minutes despite 100% oxygen support. Meanwhile, blood pressure and EtCO2 monitoring was unremarkable. After specifying that anesthesia device worked normally, airway pressure did not increase and the endotracheal tube has been placed accurately, the blood sample was taken from the patient for arterial gas analysis. A severe increase was thought in MetHb concentration since SpO2 persisted to be 75% although the concentration of inspired oxygen was 100%, and solution of 2500 mg ascorbic acid in 500 ml 5% Dextrose was given to the patient via intravenous route until the results of arterial blood gas were obtained. However, arterial blood gas results were as follows: pH: 7.54, PaCO2: 23.3 mmHg, PaO2: 281 mmHg, SaO2: %99, and MetHb: %2.7. Biochemical analysis revealed a blood MetHb concentration of 2%.However, since arterial blood gas parameters were good, hemodynamics of the patient was stable and methemoglobin concentration was not so high, the patient was extubated after surgery when she was relaxed, cooperated and had adequate respiration. Despite the absence of respiratory or neurological distress, SpO2 value was increased only up to 85% within 2 hours with 5 L/min oxygen support via face mask in the surgery room as the patient was extubated. At that time, the skin of particularly the upper part of her body has turned into blue, more remarkable on the face. The color of plasma of the blood taken from the patient for biochemical analysis was blue. The color of urine coming throughout the urinary catheter placed in intensive care unit was also blue. Twelve hours after 5 L/min. oxygen inhalation via a mask, the SpO2 reached to 90%. During monitoring in intensive care unit on the postoperative 1st day, facial color and urine color of the patient was still blue, SpO2 was 92%, and arterial blood gas levels were as follows: pH: 7.44, PaO2: 76.1 mmHg, PaCO2: 38.2 mmHg, SaO2: 99%, and MetHb 1%. During monitoring in clinic on the postoperative 2nd day, SpO2 was 95% without oxygen support and her facial and urine color turned into normal. The patient was discharged on the 3rd day without any problem.In conclusion, SLNB is a less invasive alternative to axillary dissection. However, false pulse oximeter reading due to pigment interference is a rare complication of this procedure. Arterial blood gas analysis should be used to confirm any fall in SpO2 reading during monitoring.

Keywords: isosulfan blue, pulse oximetry, SLNB, methemoglobinemia

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Authors: L. Hoade, O. O. Onafowokan, K. Anderson, G. E. Bartlett, E. D. Fern, M. R. Norton, R. G. Middleton

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Aims: Femoroacetabular impingement (FAI) was first recognised as a potential driver for hip pain at the turn of the last millennium. While there is an increasing trend towards surgical management of FAI by arthroscopic means, open surgical hip dislocation and debridement (SHD) remains the Gold Standard of care in terms of reported outcome measures. (1) Long-term functional and survivorship outcomes of SHD as a treatment for FAI are yet to be sufficiently reported in the literature. This study sets out to help address this imbalance. Methods: We undertook a retrospective review of our institutional database for all patients who underwent SHD for FAI between January 2003 and December 2008. A total of 223 patients (241 hips) were identified and underwent a ten year review with a standardised radiograph and patient-reported outcome measures questionnaire. The primary outcome measure of interest was survivorship, defined as progression to total hip arthroplasty (THA). Negative predictive factors were analysed. Secondary outcome measures of interest were survivorship to further (non-arthroplasty) surgery, functional outcomes as reflected by patient reported outcome measure scores (PROMS) scores, and whether a learning curve could be identified. Results: The final cohort consisted of 131 females and 110 males, with a mean age of 34 years. There was an overall native hip joint survival rate of 85.4% at ten years. Those who underwent a THA were significantly older at initial surgery, had radiographic evidence of preoperative osteoarthritis and pre- and post-operative acetabular undercoverage. In those whom had not progressed to THA, the average Non-arthritic Hip Score and Oxford Hip Score at ten year follow-up were 72.3% and 36/48, respectively, and 84% still deemed their surgery worthwhile. A learning curve was found to exist that was predicated on case selection rather than surgical technique. Conclusion: This is only the second study to evaluate the long-term outcomes (beyond ten years) of SHD for FAI and the first outside the originating centre. Our results suggest that, with correct patient selection, this remains an operation with worthwhile outcomes at ten years. How the results of open surgery compared to those of arthroscopy remains to be answered. While these results precede the advent of collison software modelling tools, this data helps set a benchmark for future comparison of other techniques effectiveness at the ten year mark.

Keywords: femoroacetabular impingement, hip pain, surgical hip dislocation, hip debridement

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Authors: Kirti Hira, A. Sajeli Begum, S. Mahibalan, Poorna Chandra Rao

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Introduction: Cancer is one of the leading causes of death worldwide. Although existing therapy effectively kills cancer cells, they do affect normal growing cells leading to many undesirable side effects. Hence there is need to develop effective as well as safe drug molecules to combat cancer, which is possible through phyto-research. The currently available plant-derived blockbuster drugs are the example for this. In view of this, an investigation was done to identify cytotoxic lead molecules from Hedyotis umbellata (Family Rubiaceae), a widely distributed weed in India. Materials and Methods: The methanolic extract of the whole plant of H. umbellata (MHU), prepared through Soxhlet extraction method was further fractionated with diethyl ether and n-butanol, successively. MHU, ether fraction (EMHU) and butanol fraction (BMHU) were lyophilized and were tested for the cytotoxic effect using 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay against non-small cell lung cancer (NSCLC) A549 cell lines. The potentially active EMHU was subjected to chromatographic purification using normal-phase silica columns, in order to isolate the responsible bioactive compounds. The isolated pure compounds were tested for their cytotoxic effect by MTT assay against A549 cells. Compound-3, which was found to be most active, was characterized using IR, 1H- and 13C-NMR and MS analysis. The study was further extended to decipher the mechanism of action of cytotoxicity of compound-3 against A549 cells through various in vitro cellular models. Cell cycle analysis was done using flow cytometry following PI (Propidium Iodide) staining. Protein analysis was done using Western blot technique. Results: Among MHU, EMHU, and BMHU, the non-polar fraction EMHU demonstrated a significant dose-dependent cytotoxic effect with IC50 of 67.7μg/ml. Chromatography of EMHU yielded seven compounds. MTT assay of isolated compounds explored compound-3 as potentially active one, which inhibited the growth of A549 cells with IC50value of 14.2μM. Further, compound-3 was identified as cedrelopsin, a coumarin derivative having molecular weight of 260. Results of in vitro mechanistic studies explained that cedrelopsin induced cell cycle arrest at G2/M phase and down-regulated the expression of G2/M regulatory proteins such as cyclin B1, cdc2, and cdc25C, dose dependently. This is the first report that explores the cytotoxic mechanism of cedrelopsin. Conclusion: Thus a potential small lead molecule, cedrelopsin isolated from H. umbellata, showing antiproliferative effect mediated by G2/M arrest in A549 cells was discovered. The effect of cedrelopsin against other cancer cell lines followed by in vivo studies can be performed in future to develop a new drug candidate.

Keywords: A549, cedrelopsin, G2/M phase, Hedyotis umbellata

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Authors: Hamza Assiry, Gamal A. Mohamed, Sabrin R. M. Ibrahim, Hossam M. Abdallah

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Chemical investigation of the aerial parts of Barleria trispinosa(Forssk.) Vahl. resulted in isolation of four major iridoids that were identified as 6,8-O,O-diacetylshanhiside methyl ester (acetyl barlerin) (1), 8-O-acetylshanzhiside methyl ester (barlerin) (2), shanzhiside methyl ester (3), and 6- ⍺ -L-rhamnopyranosyl-8-O-acetylshanzihiside methyl ester (4). The isolated compounds were confirmed by detailed one and two-dimensional NMR. Isolated compounds were tested for their cytotoxic activity on breast cancer (MCF-7, MDA-MB-231) and colon cancer (LS174T) cell linesusing sulphorhodamine B (SRB) assay. It is noteworthy that compound 1 demonstrated a significant cytotoxic potential towards MDA-MB-231 cell line with IC5016.7 ± 2.7µg / mL compared to doxorubicin whereas compounds 2, showed moderate cytotoxic potential with IC5021.2 ± 1.9µg / mL on MCF-7. The other compounds showed moderate activity on the tested cell lines.

Keywords: acanthaceae, cytotoxicity, metabolites, barleria trispinosa

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Authors: Amir Saber Gharamaleki, Beitollah Alipour, Zeinab Faghfoori, Ahmad YariKhosroushahi

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Colorectal cancer (CRC) is one of the most prevalent cancers and intestinal microbial community plays an important role in colorectal tumorigenesis. Probiotics have recently been assessed as effective anti-proliferative agents and thus this study was performed to examine whether CRC undergo apoptosis by treating with isolated Iranian native dairy yeast, Kluyveromyces marxianus YAS, secretion metabolites. The cytotoxicity assessments on cells (HT-29, Caco-2) were accomplished through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay as well as qualitative DAPI (4',6-diamidino-2-phenylindole staining) and quantitative (flow cytometry assessments) evaluations of apoptosis. To evaluate the main mechanism of apoptosis, Real time PCR method was applied. Kluyveromyces marxianus YAS secretions (IC50) showed significant cytotoxicity against HT-29 and Caco-2 cancer cell lines (66.57 % and 66.34 % apoptosis) similar to 5-Fluorouracil (5-FU) while apoptosis only was developed in 27.57 % of KDR normal cells. The prophylactic effects of Kluyveromyces marxianus (PTCC 5195), as a reference yeast, was not similar to Kluyveromyces marxianus YAS indicating strain dependency of bioactivities on CRC disease prevention. Based on real time PCR results, the main cytotoxicity is related to apoptosis phenomenon and the core related mechanism is depended on the overexpression of BAX, CASP 9, CASP 8 and CASP 3 inducing apoptosis genes. However, several investigations should be conducted to precisely determine the effective compounds to be used as anticancer therapeutics in the future.

Keywords: anticancer, anti-proliferative, apoptosis, cytotoxicity, yeast

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Authors: Shangerganesh Lingeshwaran

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In this presentation, we have performed numerical simulations for a reaction-diffusion equation with various nonlinear density-dependent diffusion operators and proliferation functions. The mathematical model represented by parabolic partial differential equation is considered to study the invasion of gliomas (the most common type of brain tumors) and to describe the growth of cancer cells and response to their treatment. The unknown quantity of the given reaction-diffusion equation is the density of cancer cells and the mathematical model based on the proliferation and migration of glioma cells. A standard Galerkin finite element method is used to perform the numerical simulations of the given model. Finally, important observations on the each of nonlinear diffusion functions and proliferation functions are presented with the help of computational results.

Keywords: glioma invasion, nonlinear diffusion, reaction-diffusion, finite eleament method

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Authors: Rose Virginy S. Bautista, Ida Marie Tabangay-Lim, Helen Bongalon-Amo, Jose Modesto B. Abellera

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Chordomas, particularly those of the spine and the head and neck region, represent a rare and locally aggressive group of malignancies. The complexity of these tumors -given the rarity, location, and involvement of neurovascular structures- imposes a challenge in the diagnosis and management. We herein report a case of spinal cord compression due to a prevertebral cervical chordoma. The patient presented with a gradually enlarging lateral neck mass, with progressive bilateral extremity weakness and urinary incontinence; preoperative biopsy showed chordoma. A multidisciplinary approach for the management of this case was made, involving neurosurgery, head and neck surgery, and radiation oncology services. Surgical collaboration between the two cutting services was done to have a radical excision of the tumor and spinal cord decompression. The patient was then referred for adjuvant radiation therapy. With this collaborative treatment strategy, more comprehensive and quality care could be provided to our patients.

Keywords: chordoma, surgical collaboration, spinal cord compression, neurosurgery, head and neck surgery

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Authors: Estefania Ponce-Amaya, Ana Lidia Arellano-Ortiz, Cecilia Diaz-Hernandez, Jose Alberto Lopez-Diaz, Antonio De La Mora-Covarrubias, Claudia Lucia Vargas-Requena, Mauricio Salcedo-Vargas, Florinda Jimenez-Vega

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Cervical Cancer (CC) is the second leading cause of death among women worldwide and it had been associated with a persistent infection of human papillomavirus (HPV). The goal of the current study was to identify the prevalence of HPV infection in women with abnormal Pap smear who were attended at Dysplasia Clinic of Ciudad Juarez, Mexico. Methods: Cervical samples from 146 patients, who attended the Colposcopy Clinic at Sanitary Jurisdiction II of Cd Juarez, were collected for histopathology and molecular study. DNA was isolated for the HPV detection by Polymerase Chain Reaction (PCR) using MY09/011 and GP5/6 primers. The associated risk factors were assessed by a questionnaire. The statistical analysis was performed by ANOVA, using EpiINFO V7 software. Results: HPV infection was present in 142 patients (97.3 %). The prevalence of HPV infection was distributed in a 96% of all evaluated groups, low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HISIL) and CC. We found a statistical significance (α = <0.05) between gestation and number of births as risk factors. The median values showed an ascending tend according with the lesion progression. However, CC showed a statistically significant difference with respect to the pre-carcinogenic stages. Conclusions: In these Mexican patients exists a high prevalence of HPV infection, and for that reason, we are studying the most prevalent HPV genotypes in this population.

Keywords: cervical cancer, HPV, prevalence hpv, squamous intraepithelial lesion

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Authors: Mina Rabipour, Elena Pallaske, Floyd Hassenrück, Rocio Rebollido-Rios

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Protein tyrosine kinases, including Lyn kinase of the Src family kinases (SFK), regulate cell proliferation, survival, and differentiation. Lyn kinase has been implicated in various cancers, positioning it as a promising therapeutic target. However, the conserved ATP-binding pocket across SFKs makes developing selective inhibitors challenging. This study aims to address this limitation by exploring the potential for allosteric modulation of Lyn kinase, focusing on how its structural dynamics and specific oncogenic mutations impact its conformation and function. To achieve this, we combined homology modeling, molecular dynamics simulations, and data science techniques to conduct microsecond-length simulations. Our approach allowed a detailed investigation into the interplay between Lyn’s catalytic and regulatory domains, identifying key conformational states involved in allosteric regulation. Additionally, we evaluated the structural effects of Dasatinib, a competitive inhibitor, and ATP binding on Lyn active conformation. Notably, our simulations show that cancer-related mutations, specifically I364L/N and E290D/K, shift Lyn toward an inactive conformation, contrasting with the active state of the wild-type protein. This may suggest how these mutations contribute to aberrant signaling in cancer cells. We conducted a dynamical network analysis to assess residue-residue interactions and the impact of mutations on the Lyn intramolecular network. This revealed significant disruptions due to mutations, especially in regions distant from the ATP-binding site. These disruptions suggest potential allosteric sites as therapeutic targets, offering an alternative strategy for Lyn inhibition with higher specificity and fewer off-target effects compared to ATP-competitive inhibitors. Our findings provide insights into Lyn kinase regulation and highlight allosteric sites as avenues for selective drug development. Targeting these sites may modulate Lyn activity in cancer cells, reducing toxicity and improving outcomes. Furthermore, our computational strategy offers a scalable approach for analyzing other SFK members or kinases with similar properties, facilitating the discovery of selective allosteric modulators and contributing to precise cancer therapies.

Keywords: lyn tyrosine kinase, mutation analysis, conformational changes, dynamic network analysis, allosteric modulation, targeted inhibition

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Authors: Ayeshmanthe Rathnayake, Siew Goh, Carmel Fenton, Ashutosh Hardikar

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Post-Operative Atrial Fibrillation (POAF) is the most frequent complication of cardiac surgery and is associated with reduced survival, increased rates of cognitive changes and cerebrovascular accident, heart failure, renal dysfunction, infection and length of stay, and hospital costs. Cardiac tamponade, although less common, carries high morbidity and mortality. Shed mediastinal blood in the pericardial space is a major source of intrapericardial oxidative stress and inflammation that triggers POAF. The utilisation of a left posterior pericardiotomy aims to shunt blood from the pericardium into the pleural space and have a role in the prevention of POAF as well as cardiac tamponade. 2118 patients had undergone isolated Coronary Artery Bypass Graft (CABG) at Royal Hobart Hospital from 2008-2021. They were divided into pericardiotomy vs control group. Patient baseline demographics, intraoperative data, and post-operative outcomes were reviewed retrospectively. Total incidence of new POAF and cardiac tamponade was 26.1% and 0.75%, respectively. Primary outcome of both the incidence of POAF(22.9% vs27.8%OR 0.77 p<0.05) and Cardiac Tamponade (0% vs 1.1% OR 0.85 p<0.05) were less in the pericardiotomy group.Increasing age, BMI, poor left ventricular function (EF <30%), and return to theatre were independent predictors of developing POAF. There were similar rates of return to theatre for bleeding however, no cases of tamponade in the pericardiotomy group. There were no complications attributable to left posterior pericardiotomy and the time added to the duration of surgery was minimal. Left posterior pericardiotomy is associated with a significant reduction in the incidence of POAFand cardiac tamponade and issafe and efficient.

Keywords: cardiac surgery, pericardiotomy, post-operative atrial fibrillation, cardiac tamponade

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Authors: Adam Haliński, Andrzej Haliński

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Introduction: Flexible ureterorenoscopy is a surgery technique used for the treatment of the upper urinary tract. It is very often used in adult patients; however, due to the advancing miniaturization of the equipment as well as its precision, this technique has also become possible in the treatment process in children. Material and method: We would like to present 26 cases of flexible ureterorenoscopy carried out in children with nephrolithiasis of the upper urinary tract aged 6 to 17 years. The average age was 9.5 years and the children were treated in our department from June 2013 to January 2015. The first surgery in Poland took place in our Department on 06.06.2013. Because of nephrolithiasis all the children had been subjected earlier to ESWL treatment, which was unsuccessful. Results: 14 children had deposits in the lower calyx, 9 children had deposits in the middle and lower calyx and in 3 children a stone was located in the initial ureter. An efficiency of 88 % was achieved. Conclusions: Flexible ureterorenoscopy is effective and minimally invasive tool both for the diagnosis and treatment of upper urinary tract. We believe that the advancing miniaturization of the equipment and gaining experience will enable carrying out of this procedure in smaller children with high efficiency.

Keywords: flexible ureterorenoscopy, urolithisis, endourology, nephrolithiasis

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Authors: S. Daneshi, G. Shahcheraghi, F. Ghaffarinejad

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Back ground: Osteoarthritis (OA) is the most common form of arthritis, affecting millions of people around the world during the aging process. Knee joint proprioception sense decrease with OA and Total Knee Arthroplasty (TKA) surgery may affect them. We investigated two parameters of proprioception sense (the joint position sense and kinesthesia) and standing balance in affected limbs before and after TKA, in patient with Knee OA. Methods and Materials: In this Analytic study, 10 patients who were candidate for TKA during two months in Dena Hospital of Shiraz, selected for further analysis. All of cases were female in range of 55-70 years old. Participants assessed before and two weeks after TKA using three instruments: electrogoniometer and continuous passive motion (CPM) to assess Knee joint position sense and kinesthesia in 20 and 45 degrees; and chronometer to assess duration of standing balance on affected leg with open and closed eyes. Results: To examine differences between before and after of TKA scorings Willcoxon Signed Rank and Mann-Whitney was performed which indicated no significant differences between knee joint position sense and kinesthesia in 20 and 45 degrees (P>0.05) and no significant differences between Standing Balance in a patient with knee OA before and after TKA (P>0.05). Conclusion: The study indicates that, OA can affect proprioception sense and standing balance but TKA doesn’t have any effect on these parameters. Intra articular structures such as cruciate ligaments and mines are responsible for proprioception sense in normal knee joint. Since in severe knee OA the number of mechanoreceptors in these intra articular structures decrease and their function reduce more than normal knee joint, so the anterior cruciate ligaments (ACL) become defected, thus after TKA surgery which this ligament is removed no significant change was found in proprioception sense. As a result of involving proprioception sense, muscles strength and the function of vestibular system in balance, standing balance did not show significant difference before and after TKA.

Keywords: knee joint, proprioception sense, standing balance, rehabilitation sciences

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Authors: Karol Rodriguez-Peña, Martha L. Macias-Rubalcava, Leticia Rocha-Zavaleta, Sergio Sanchez

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A bioassay-guided study for anti-cancer compounds from endophytes of the Mexican medicinal plant Amphipteryygium adstringens resulted in the isolation of a streptomycete capable of producing a group of compounds with high cytotoxic activity. Microorganisms from surface sterilized samples of various sections of the plant were isolated and all the actinomycetes found were evaluated for their potential to produce compounds with cytotoxic activity against cancer cell lines MCF7 (breast cancer) and HeLa (cervical cancer) as well as the non-tumoural cell line HaCaT (keratinocyte). The most active microorganism was picked for further evaluation. The identification of the microorganism was carried out by 16S rDNA gene sequencing, finding the closest proximity to Streptomyces scabrisporus, but with the additional characteristic that the strain isolated in this study was capable of producing colorful compounds never described for this species. Crude extracts of dichloromethane and ethyl acetate showed IC50 values of 0.29 and 0.96 μg/mL for MCF7, 0.51 and 1.98 μg/mL for HeLa and 0.96 and 2.7 μg/mL for HaCaT. Scaling the fermentation to 10 L in a bioreactor generated 1 g of total crude extract, which was fractionated by silica gel open column to yield 14 fractions. Nine of the fractions showed cytotoxic activity. Fraction 4 was chosen for subsequent purification because of its high activity against cancerous cell lines, lower activity against keratinocytes. HPLC-UV-MS/ESI was used for the evaluation of this fraction, finding at least 10 different compounds with high values of m/z (≈588). Purification of the compounds was carried out by preparative thin-layer chromatography. The prevalent compound was Steffimycin B, a molecule known for its antibiotic and cytotoxic activities and also for its low solubility in aqueous solutions. Along with steffimycin B, another five compounds belonging to the steffimycin family were isolated and at this moment their structures are being elucidated, some of which display better solubility in water: an attractive property for the pharmaceutical industry. As a conclusion to this study, the isolation of endophytes resulted in the discovery of a strain capable of producing compounds with high cytotoxic activity that need to be studied for their possible utilization.

Keywords: amphipterygium adstringens, cytotoxicity, streptomyces scabrisporus, steffimycin

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Authors: Akash Soogumbur

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Tourniquets are commonly used in orthopaedic surgery to provide hemostasis during procedures on the upper and lower limbs. However, there is a risk of complications associated with tourniquet use, such as nerve damage, skin necrosis, and compartment syndrome. The British Orthopaedic Association (BOAST) guidelines recommend the use of tourniquets at a pressure of 300 mmHg or less for a maximum of 2 hours. Research Aim: The aim of this study was to evaluate the effectiveness of a tourniquet checklist in improving compliance with the BOAST guidelines. Methodology: This was a retrospective study of all orthopaedic procedures performed at a single institution over a 12-month period. The study population included patients who had a tourniquet applied during surgery. Data were collected from the patients' medical records, including the duration of tourniquet use, the pressure used, and the method of exsanguination. Findings: The results showed that the use of the tourniquet checklist significantly improved compliance with the BOAST guidelines. Prior to the introduction of the checklist, compliance with the guidelines was 83% for the duration of tourniquet use and 73% for pressure used. After the introduction of the checklist, compliance increased to 100% for both duration of tourniquet use and pressure used. Theoretical Importance: The findings of this study suggest that the use of a tourniquet checklist can be an effective way to improve compliance with the BOAST guidelines. This is important because it can help to reduce the risk of complications associated with tourniquet use. Data Collection: Data were collected from the patients' medical records. The data included the following information: Patient demographics, procedure performed, duration of tourniquet use, pressure used, method of exsanguination. Analysis Procedures: The data were analyzed using descriptive statistics. The compliance with the BOAST guidelines was calculated as the percentage of patients who met the guidelines for the duration of tourniquet use and pressure used. Question Addressed: The question addressed by this study was whether the use of a tourniquet checklist could improve compliance with the BOAST guidelines. Conclusion: The results of this study suggest that the use of a tourniquet checklist can be an effective way to improve compliance with the BOAST guidelines. This is important because it can help to reduce the risk of complications associated with tourniquet use.

Keywords: tourniquet, pressure, duration, complications, surgery

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Authors: D. O. Miranda, L. R. Azevedo, J. F. C. Cordeiro, A. H. Dos Santos, S. F. Lisboa, F. S. Guimarães, G. S. Bisson

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Background: The Colorectal cancer (CRC) is one of the most common cancers and the fourth leading cause of cancer death in the world. The prevalence of psychiatric-disorders among CRC patients, mainly depression, is high, resulting in impaired quality of life and side effects of primary treatment. High levels of proinflammatory cytokines at tumor microenvironment is a feature of CRC and the literature suggests that those mediators could contribute to the development of psychiatric disorders. Nevertheless, the ability of tumor-associated biological processes to affect the central nervous system (CNS) has only recently been explored in the context of symptoms of depression and is still not well understood. Therefore, the aim of the present study was to test the hypothesis that depressive-like behavior in an experimental model of CCR induced by N-methyl-N-nitro-N-nitrosoguanidine (MNNG) was correlated to proinflammatory profile in the periphery and in the brain. Methods: Colorectal carcinogenesis was induced in adult C57BL/6 mice (n=12) by administration of MNNG (5mg/kg, 0.1ml/intrarectal instillation) 2 times a week, for 2 week. Control group (n=12) received saline (0.1ml/intrarectal instillation). Eight weeks after beginning of MNNG administration animals were submitted to the forced swim test (FST) and the sucrose preference test for evaluation, respectively, of depressive- and anhedonia-like behaviors. After behavioral evaluation, the colon was collected and brain regions dissected (cortex-C, striatum-ST and hippocampus-HIP) for posterior evaluation of cytokine levels (IL-1β, IL-10, IL-17, and CX3CL1) by ELISA. Results: MNNG induced depressive-like behavior, represented by increased immobility time in the FST (Student t test, p < 0.05) and lower sucrose preference (Student t test, p < 0.05). Moreover, there were increased levels of IL-1β, IL-17 and CX3CL1 in the colonic tissue (Student t test, p < 0.05) and in the brain (IL-1 β in the ST and HIP, Student t test, p < 0.05; IL-17 and CX3CL1 in the C and HIP, p < 0.05). IL-10 levels, in contrast, were decreased in both the colon (p < 0.05) and the brain (C and HIP, p < 0.05). Conclusions: The results obtained in the present work support the notion that tumor growth induces neuroinflammation in stress-related brain regions and depressive-like behavior, which could be related to the high incidence of depression in colorectal carcinogenesis. This work have important clinical and research implications, taken into account that cytokine levels may be a marker promissory for the developing depression in CRC patients. New therapeutic strategies to assist in alleviating mental suffering in cancer patients might result from a better understanding of the role of cytokines in the pathophysiology of depression in these subjects.

Keywords: cytokines, brain, depression, colorectal cancer

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Authors: Ankita Shukla, Tiratha Raj Singh

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Colorectal cancer (CRC) imposes serious mortality burden worldwide and it has been increasing for past consecutive years. Continuous efforts have been made so far to diagnose the disease condition and to identify the root cause for it. In this study, we performed the pathway level as well as the differential gene expression studies for CRC. We analyzed the gene expression profile GSE24514 from Gene Expression Omnibus (GEO) along with the gene pathways involved in the CRC. This analysis helps us to understand the behavior of the genes that have shown differential expression through their targeted pathways. Pathway analysis for the targeted genes covers the wider area which therefore decreases the possibility to miss the significant ones. This will prove to be beneficial to expose the ones that have not been given attention so far. Through this analysis, we attempt to understand the various neighboring genes that have close relationship to the targeted one and thus proved to be significantly controlling the CRC. It is anticipated that the identified hub and neighboring genes will provide new directions to look at the pathway level differently and will be crucial for the regulatory processes of the disease.

Keywords: mismatch repair, microsatellite instability, carcinogenesis, morbidity

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Authors: Fereydoon Bondarian, Samira Shaygan

Abstract:

Today, many nutritionists recommend the consumption of plants, fruits, and vegetables to provide the antioxidants needed by the body because the use of plant antioxidants usually causes fewer side effects and better treatment. Natural antioxidants increase the power of plasma antioxidants and reduce the incidence of some diseases, such as cancer. Bad lifestyles and environmental factors play an important role in increasing the incidence of cancer. In this study, different extracts of white teas taken from two types of tea available in Iran (clone 100 and Chinese hybrid) due to the presence of a hydroxyl functional group in their structure to inhibit free radicals and anticancer properties, using 3 aqueous, methanolic and aqueous-methanolic methods were used. The total polyphenolic content was calculated using the Folin-Ciocalcu method, and the percentage of inhibition and trapping of free radicals in each of the extracts was calculated using the DPPH method. With the help of high-performance liquid chromatography, a small amount of each catechin in the tea samples was obtained. Clone 100 white tea was found to be the best sample of tea in terms of all the examined attributes (total polyphenol content, antioxidant properties, and individual amount of each catechin). The results showed that aqueous and aqueous-methanolic extracts of Clone 100 white tea have the highest total polyphenol content with 27.59±0.08 and 36.67±0.54 (equivalent gallic acid per gram dry weight of leaves), respectively. Due to having the highest level of different groups of catechin compounds, these extracts have the highest property of inhibiting and trapping free radicals with 66.61±0.27 and 71.74±0.27% (mg/l) of the extracted sample against ascorbic acid). Using the MTT test, the inhibitory effect of clone 100 white tea extract in inhibiting the growth of HCT-116 colon cancer cells was investigated and the best time and concentration treatments were 500, 150 and 1000 micrograms in 8, 16 and 24 hours, respectively. To investigate gene expression changes, selected genes, including tumorigenic genes, proto-oncogenes, tumor suppressors, and genes involved in apoptosis, were selected and analyzed using the real-time PCR method and in the presence of concentrations obtained for white tea. White tea extract at a concentration of 1000 μg/ml 3 times 16, 8, and 24 hours showed the highest growth inhibition in cancer cells with 53.27, 55.8, and 86.06%. The concentration of 1000 μg/ml aqueous extract of white tea under 24-hour treatment increased the expression of tumor suppressor genes compared to the normal sample.

Keywords: catechin, gene expression, suppressor genes, colon cell line

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Authors: Khusboo Agrawal, S. Saraf

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Quercetin, a flavonol provides a cellular protection against UV induced oxidative damages due to its excellent free radical scavenging activity and direct pro-apoptopic effect on tumor cells. However, its topical use is limited due to its unfavorable physicochemical properties. The present study was aimed to evaluate the potential of mesoporous silica nanoparticles as topical carrier system for quercetin delivery. Complexes of quercetin with mesoporous silica was prepared with different weight ratios and characterized by thermo gravimetric analysis, X-ray diffraction, high resolution TEM, FT-IR spectroscopy, zeta potential measurements and differential scanning calorimetry The protective effect of this vehicle on UV-induced degradation of the quercetin was investigated revealing a certain positive influence of the inclusion on the photostability over time. Epidermal accumulation and transdermal permeation of this molecule were ex vivo evaluated by using Franz diffusion cells. The immobilization of Quercetin in mesoporous silica nanoparticles (MSNs) increased the stability without undermining the antioxidant efficacy.

Keywords: cancer, MSNs, quercetin, topical delivery

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Authors: Asif Bilal, Fouzia Tanvir, Sibtain Ahmad

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Estrogen receptor alpha, also known as estrogen receptor-1, is highly involved in risk of mammary carcinoma. The objectives of this study were to identify non-synonymous SNPs of estrogen receptor and their association with breast cancer and to identify the chemotherapeutic responses of phytochemicals against it via in-silico study design. For this purpose, different online tools. to identify pathogenic SNPs the tools were SIFT, Polyphen, Polyphen-2, fuNTRp, SNAP2, for finding disease associated SNPs the tools SNP&GO, PhD-SNP, PredictSNP, MAPP, SNAP, MetaSNP, PANTHER, and to check protein stability Mu-Pro, I-Mutant, and CONSURF were used. Post-translational modifications (PTMs) were detected by Musitedeep, Protein secondary structure by SOPMA, protein to protein interaction by STRING, molecular docking by PyRx. Seven SNPs having rsIDs (rs760766066, rs779180038, rs956399300, rs773683317, rs397509428, rs755020320, and rs1131692059) showing mutations on I229T, R243C, Y246H, P336R, Q375H, R394S, and R394H, respectively found to be completely deleterious. The PTMs found were 96 times Glycosylation; 30 times Ubiquitination, a single time Acetylation; and no Hydroxylation and Phosphorylation were found. The protein secondary structure consisted of Alpha helix (Hh) is (28%), Extended strand (Ee) is (21%), Beta turn (Tt) is 7.89% and Random coil (Cc) is (44.11%). Protein-protein interaction analysis revealed that it has strong interaction with Myeloperoxidase, Xanthine dehydrogenase, carboxylesterase 1, Glutathione S-transferase Mu 1, and with estrogen receptors. For molecular docking we used Asiaticoside, Ilekudinuside, Robustoflavone, Irinoticane, Withanolides, and 9-amin0-5 as ligands that extract from phytochemicals and docked with this protein. We found that there was great interaction (from -8.6 to -9.7) of these ligands of phytochemicals at ESR1 wild and two mutants (I229T and R394S). It is concluded that these SNPs found in ESR1 are involved in breast cancer and given phytochemicals are highly helpful against breast cancer as chemotherapeutic agents. Further in vitro and in vivo analysis should be performed to conduct these interactions.

Keywords: breast cancer, ESR1, phytochemicals, molecular docking

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Authors: Mukesh K., Siddiqui A. K., Abbas H., Gupta R.

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Background: General Anesthesia is a standard for breast onco-surgery. The issue of postoperative pain and the occurrence of nausea and vomiting has prompted the quest for a superior methodology with fewer complications. Over the recent couple of years, paravertebral block (PVB) has acquired huge fame either in combination with GA or alone for anesthetic management. In this study, we aim to evaluate the efficacy of morphine and clonidine as an adjunct to ropivacaine in a paravertebral block in breast cancer patients undergoing modified radical mastectomy. Methods: In this study, total 90 patients were divided into three groups (30 each) on the basis of computer-generated randomization. Group C (Control): Paravertebral block with 0.25% ropivacaine (19ml) and 1 ml saline; Group M- Paravertebral block with 0.25% ropivacaine(19ml) + 20 microgram/kg body weight morphine; Group N: Paravertebral block with 0.25% ropivacaine(19ml) +1.0 microgram/kg body weight clonidine. The postoperative pain intensity was recorded using the visual analog scale (VAS) and Sedation was observed by the Ramsay Sedation score (RSS). Results: The VAS was similar at 0hr, 2hr and 4 hr in the postoperative period among all the groups. There was a significant (p=0.003) difference in VAS from 6 hr to 20 hr in the postoperative period among the groups. A significant (p<0.05) difference was observed among the groups at 8 hr to 20 hr). The first requirement of analgesia was significantly (p=0.001) higher in Group N (7.70±1.74) than in Group C (4.43±1.43) and Group M (7.33±2.21). Conclusion: The morphine in the paravertebral block provides better postoperative analgesia. The consumption of rescue analgesia was significantly reduced in the morphine group as compared to the clonidine group. The procedure also proved to be safe as no complication was encountered in the paravertebral block in our study.

Keywords: ropivacaine, morphine, clonidine, paravertebral block

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Authors: Ying Li, Rui Hu, Shizhen Chen, Xin Zhou, Yunhuang Yang

Abstract:

Prostate cancer is one of the leading causes of cancer-related death among men. Prostate-specific antigen (PSA), a specific product of prostatic epithelial cells, is an important indicator of prostate cancer. Though PSA is not a specific serum biomarker for the screening of prostate cancer, it is recognized as an indicator for prostate cancer recurrence and response to therapy for patient’s post-prostatectomy. Since radical prostatectomy eliminates the source of PSA production, serum PSA levels fall below 50 pg/mL, and may be below the detection limit of clinical immunoassays (current clinical immunoassay lower limit of detection is around 10 pg/mL). Many clinical studies have shown that intervention at low PSA levels was able to improve patient outcomes significantly. Therefore, ultra-sensitive and precise assays that can accurately quantify extremely low levels of PSA (below 1-10 pg/mL) will facilitate the assessment of patients for the possibility of early adjuvant or salvage treatment. Currently, the commercially available ultra-sensitive ELISA kit (not used clinically) can only reach a detection limit of 3-10 pg/mL. Other platforms developed by different research groups could achieve a detection limit as low as 0.33 pg/mL, but they relied on sophisticated instruments to get the final readout. Herein we report a microfluidic platform for point-of-care (POC) detection of PSA with a detection limit of 0.5 pg/mL and without the assistance of any equipment. This platform is based on a previously reported volumetric-bar-chart chip (V-Chip), which applies platinum nanoparticles (PtNPs) as the ELISA probe to convert the biomarker concentration to the volume of oxygen gas that further pushes the red ink to form a visualized bar-chart. The length of each bar is used to quantify the biomarker concentration of each sample. We devised a long reading channel V-Chip (LV-Chip) in this work to achieve a wide detection window. In addition, LV-Chip employed a unique enzyme-free ELISA probe that enriched PtNPs significantly and owned 500-fold enhanced catalytic ability over that of previous V-Chip, resulting in a significantly improved detection limit. LV-Chip is able to complete a PSA assay for five samples in 20 min. The device was applied to detect PSA in 50 patient serum samples, and the on-chip results demonstrated good correlation with conventional immunoassay. In addition, the PSA levels in finger-prick whole blood samples from healthy volunteers were successfully measured on the device. This completely stand-alone LV-Chip platform enables convenient POC testing for patient follow-up in the physician’s office and is also useful in resource-constrained settings.

Keywords: point-of-care detection, microfluidics, PSA, ultra-sensitive

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Authors: Joana PaScoa Pinheiro, David Goncalves Ferreira, Filipe Ramos, Joaquim Soares Do Brito, Samuel Martins, Marco Sarmento

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Introduction: The SARS-CoV-2 (COVID-19) pandemic was identified in January 2020 in China, in the city of Wuhan. The increase in the number of cases over the following months was responsible for the restructuring of hospitals and departments in order to accommodate admissions related to COVID-19. Essential services, such as trauma, had to readapt to maintain their functionality and thus guarantee quick and safe access in case of an emergency. Objectives: This study describes the impact of COVID-19 on a Level III Trauma Center and particularly on the clinical management of hospitalized patients with spine injuries. Study Design & Methods: This is a retrospective cohort study whose results were obtained through the medical records of patients with spine injuries who underwent surgical intervention in the years 2019 and 2020 (period from March 1st to December 31st). A comparison between the two groups was made. In the study patients with injuries in the context of trauma were included who underwent surgery in the periods previously described. Patients hospitalized with a spine injury in a non-traumatic context and/or were not surgically treated were excluded. Results: In total, 137 patients underwent trauma spine surgery of which 71 in 2019 (51.8%) were without significant differences in intergroup comparisons. The most frequent injury mechanism in 2019 was motor vehicle crash (47.9%) compared to 2020 which was of a person falling from a height between 2-4 meters (37.9%). Cervical trauma was reported to be the most frequent spine injury in both years. There was a significant decrease in the need for intensive care in 2020, 51.4% vs 30.3%, p = .015 and the number of complications was also lower in 2020 (1.35% vs 0.98%), including the number of deaths, being the difference marginally significant. There were no significant differences regarding time for presentation to surgery or in the total days of hospitalization. Conclusions: The restructuring made in the trauma unit at a Level III Trauma Center in the context of the current COVID-19 pandemic was effective, with no significant differences between the years of 2019 vs 2020 when compared with the time for presentation to surgery or the number of days of hospitalization. It was also found that lockdown rules in 2020 were probably responsible for the decrease in the number of road traffic accidents, which justifies a significant decrease in the need for intensive care as well as in the number of complications in patients hospitalized in the context of spine trauma.

Keywords: trauma, spine, impact, covid-19

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Authors: Chih-Rong Shyr, Chi-Ping Huang

Abstract:

Intravesical BCG is the gold-standard therapy for high risk non-muscle invasive bladder cancer (NMIBC) after TURBT, but if not responsive to BCG, these BCG unresponsive patients face cystectomy that causes morbidity and comes with a morality risk. To provide the bladder sparing options for patients with BCG-unresponsive NMIBC, several new treatments have been developed to salvage the bladders and prevent progression to muscle invasive or metastatic, but however, most approved or developed treatments still fail in a significant proportion of patients without long term success. Thus more treatment options and the combination of different therapeutic modalities are urgently needed to change the outcomes. Xenogeneic rejection has been proposed to a mechanism of action to induce anti-tumor immunity for the treatment of cancers due to the similarities between rejection mechanism to xenoantigens (proteins, glycans and lipids) and anti-tumor immunities to tumor specific antigens (neoantigens, tumor associated carbohydrates and lipids). Xenogeneic urothelial cells (XUC) of porcine origin have been shown to induce anti-tumor immune responses to inhibit bladder tumor progression in mouse bladder cancer models. To further demonstrate the efficacy of the distinct intravesical XUC treatment in NMIBC, and the combined effects with chemotherapy and immune checkpoint inhibitors (ICIs) as a alternate therapeutic option, this study investigated the therapeutic effects and mechanisms of intravesical XUC immunotherapy in an orthotopic mouse immune competent model of NMIBC, generated from a mouse bladder cancer cell line. We found that the tumor progression was inhibited by intravescial XUC treatment and there was a synergy between intravesical XUC with intravesical chemotherapeutic agent, gemcitabine or systemic ICI, anti-PD1 antibody treatment. The cancer cell proliferation was decreased but the cell death was increased by the intravecisal XUC treatment. Most importantly, the mechanisms of action of intravesical XUC immunotherapy were found to be linked to enhanced infiltration of CD4+ and CD8+ T-cell as well as NK cells, but decreased presence of myeloid immunosuppressive cells in XUC treated tumors. The increased stimulation of immune cells of XUC treated mice to xenogeneic urothelial cells and mouse bladder cancer cells in immune cell proliferation and cytokine secretion were observed both as a monotherapy and in combination with intravesical gemcitabine or systemic anti PD-L1 treatment. In sum, we identified the effects of intravesical XUC treatment in monotherapy and combined therapy on tumor progression and its cellular and molecular events related to immune activation to understand the anti-tumoral mechanisms behind intravesical XUC immunotherapy for NMIBC. These results contribute to the understanding of the mechanisms behind successful xenogeneic cell immunotherapy against NMIBC and characterize a novel therapeutic approach with a new xenogeneic cell modality for BCG-unresponsive NMIBC.

Keywords: xenoantigen, neoantigen, rejection, immunity

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Authors: Caroline Mendes, Mary McNamara, Orla Howe

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For chemotherapy, a drug delivery system should be able to specifically target cancer cells and deliver the therapeutic dose without affecting normal cells. Folate receptors (FR) can be considered key targets since they are commonly over-expressed in cancer cells and they are the molecular marker used in this study. Here, cyclodextrin (CD) has being studied as a vehicle for delivering the chemotherapeutic drug, methotrexate (MTX). CDs have the ability to form inclusion complexes, in which molecules of suitable dimensions are included within the CD cavity. In this study, β-CD has been modified using folic acid so as to specifically target the FR molecular marker. Thus, the system studied here for drug delivery consists of β-CD, folic acid and MTX (CDEnFA:MTX). Cellular uptake of folic acid is mediated with high affinity by folate receptors while the cellular uptake of antifolates, such as MTX, is mediated with high affinity by the reduced folate carriers (RFCs). This study addresses the gene (mRNA) and protein expression levels of FRs and RFCs in the cancer cell lines CaCo-2, SKOV-3, HeLa, MCF-7, A549 and the normal cell line BEAS-2B, quantified by real-time polymerase chain reaction (real-time PCR) and flow cytometry, respectively. From that, four cell lines with different levels of FRs, were chosen for cytotoxicity assays of MTX and CDEnFA:MTX using the MTT assay. Real-time PCR and flow cytometry data demonstrated that all cell lines ubiquitously express moderate levels of RFC. These experiments have also shown that levels of FR protein in CaCo-2 cells are high, while levels in SKOV-3, HeLa and MCF-7 cells are moderate. A549 and BEAS-2B cells express low levels of FR protein. FRs are highly expressed in all the cancer cell lines analysed when compared to the normal cell line BEAS-2B. The cell lines CaCo-2, MCF-7, A549 and BEAS-2B were used in the cell viability assays. 48 hours treatment with the free drug and the complex resulted in IC50 values of 93.9 µM ± 9.2 and 56.0 µM ± 4.0 for CaCo-2 for free MTX and CDEnFA:MTX respectively, 118.2 µM ± 10.8 and 97.8 µM ± 12.3 for MCF-7, 36.4 µM ± 6.9 and 75.0 µM ± 8.5 for A549 and 132.6 µM ± 12.1 and 288.1 µM ± 16.3 for BEAS-2B. These results demonstrate that MTX is more toxic towards cell lines expressing low levels of FR, such as the BEAS-2B. More importantly, these results demonstrate that the inclusion complex CDEnFA:MTX showed greater cytotoxicity than the free drug towards the high FR expressing CaCo-2 cells, indicating that it has potential to target this receptor, enhancing the specificity and the efficiency of the drug.

Keywords: cyclodextrins, cancer treatment, drug delivery, folate receptors, reduced folate carriers

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Authors: Marwan Jarrah, Nadia Nugrush, Sukainah Ali, Areej Allawzi

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This research article investigates how illnesses (different types and severity) are expressed in Arabic discourse with a particular focus on input coming from Colloquial Jordanian Arabic (CJA). Drawing on a corpus of naturally occurring conversations, this article offers evidence that illnesses are predominantly expressed through two different sets of expressive strategies, namely direct expressive strategies (DES) and indirect expressive strategies (IES). The latter are exclusively used when cancer and mental health disorders are targeted. IES include the substitution of the name of the illness with some religious expressions (e.g., ʔallah ʔijdʒi:rna ‘May Allah keeps us safe’) or certain terms especially when cancer is meant (e.g., haðˤa:k ʔil-maraðˤ ‘that disease’). On the other hand, DES are used in conjunction with other illnesses (e.g., heart, kidneys, diabetes, etc.), regardless of their severity. DES include specific formulas that remarkably mention the name of the inflicted organ (e.g., [with-SOMEONE the ORGAN] as in ʕinduh ʔil-qalb ‘lit. with-him the heart’ meaning ‘He has a heart disease). We discuss the effects of religious beliefs and local norms and values in determining the use of these strategies.

Keywords: Illnesses, pragmatics, expressive strategies, religion

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Authors: Kapoor Anurag, Sharma Pradeep, Mittal K Kailash, Kumar Ajai, Jawad Kalbe, Amit Kumar Singh

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Background: Oral squamous cell carcinoma (OSCC) is the most prevalent malignant tumour on a global scale. Limited research has been conducted on tumour markers in oral cancer, and additional evaluation is required for several tumour producers that show clinical promise. The present study aimed to find out the co-relation of β-2 Microglobulin and Lipid Bound Sialic Acid in oral carcinoma patients. Methodology: The present case-control study was carried out on 35 patients with histopathologically confirmed OSCC and 35 age-matched controls. Serum concentrations of 2-Microglobulin and Total Sialic Acid (TSA) in the participants were determined via ELISA and spectrophotometric technique, respectively. Results: The OSCC group consisted of 20 males and 15 females, with an average age of 58 years, while the control group comprised 18 males and 17 females, with an average age of 55 years. Elevated levels of β2-microglobulin (3.87±0.12) and LSA (73.57±2.42) were observed in OSCC patients compared to controls (2.25±0.18; 65.21±2.06, respectively). Further examination based on smoking status revealed a significant increase in both β2-microglobulin and LSA levels among smokers compared to non-smokers (p < 0.05). Conclusion: The study suggests a notable association between higher levels of β2-microglobulin and LSA in oral squamous cell carcinoma (OSCC) patients who smoke compared to non-smokers. This observation leads to a hypothesis that this disparity could potentially serve as a significant contributing factor to the advancement of oral cancer.

Keywords: biochemistry human cancer, human, oral carcinoma, marker

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Authors: Ian Omung'a

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Breast cancer remains to be one of the deadliest cancers for women worldwide, with the risk of developing tumors being as high as 50 percent in Sub-Saharan African countries like Kenya. With as many as 42 percent of these cases set to be diagnosed late when cancer has metastasized and or the prognosis has become terminal, Full Field Digital [FFD] Mammography remains an effective screening technique that leads to early detection where in most cases, successful interventions can be made to control or eliminate the tumors altogether. FFD Mammograms have been proven to multiply more effective when used together with Computer-Aided Detection and Diagnosis [CADe] systems, relying on algorithmic implementations of Deep Learning techniques in Computer Vision to carry out deep pattern recognition that is comparable to the level of a human radiologist and decipher whether specific areas of interest in the mammogram scan image portray abnormalities if any and whether these abnormalities are indicative of a benign or malignant tumor. Within this paper, we review emergent Deep Learning techniques that will prove relevant to the development of State-of-The-Art FFD Mammogram CADe systems. These techniques will span self-supervised learning for context-encoded occlusion, self-supervised learning for pre-processing and labeling automation, as well as the creation of a standardized large-scale mammography dataset as a benchmark for CADe systems' evaluation. Finally, comparisons are drawn between existing practices that pre-date these techniques and how the development of CADe systems that incorporate them will be different.

Keywords: breast cancer diagnosis, computer aided detection and diagnosis, deep learning, whole mammogram classfication, ultrasound classification, computer vision

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Authors: Flavia Oliveira de A. M. Cruz, Edison Tostes Faria, Paula Elaine D. Reis

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When the breast is submitted to radiation therapy (RT), the most common effects are pain, skin changes, mobility restrictions, local sensory alteration, and fatigue. These effects, if not managed properly, may reduce the quality of life of cancer patients and may lead to the treatment discontinuation. Therefore, promoting knowledge and guidelines for symptom management remain a high priority for patients and a challenge for health professionals, due to the need to handle side effects in a population with a life-threatening disease. Printed materials are important strategies for supporting educative activities since they help the individual to assimilate and understand the amount of information transmitted. Nurses' behavior can be systematized through the use of an educative manual, which may be effective in promoting information regarding the treatment, self-care and how to control the effects of RT at home. In view of the importance of guaranteeing the validity of the material before its use, the objective of this research was to validate the content and appearance of an educative manual for breast cancer patients undergoing RT. The Theory of Psychometrics was used for the validation process in this descriptive methodological research. A minimum agreement rate (AR) of 80% was considered to guarantee the validity of the material. The data were collected from October to December 2017, by means of two assessments tools, constructed in the form of a Likert scale, with five levels of understanding. These instruments addressed different aspects of the evaluation, in view of two different groups of participants; 17 experts in the theme area of the educative manual, and 12 women that received RT previously to treat breast cancer. The manual was titled 'Orientation Manual: radiation therapy in breast', and was focused on breast cancer patients attended at the Department of Oncology of the Brasília University Hospital (UNACON/HUB). The research project was submitted to the Research Ethics Committee at the School of Health Sciences of the University of Brasília (CAAE: 24592213.1.0000.0030). Only two items of the assessment tool for the experts, one related to the manual's ability to promote behavioral and attitude changes and the other related to the extent of its use for other health services, obtained AR < 80% and were reformulated based on the participants' suggestions and in the literature. All other items were considered appropriate and/or complete appropriate in the three blocks proposed for the experts: objectives - 89%, structure and form - 93%, and relevance - 93%; and good and/or very good in the five blocks of analysis proposed for patients: objectives - 100%, organization - 100%, writing style - 100%, appearance - 100%, and motivation. The appearance and content validation of the educative manual proposed were attended to. The educative manual was considered relevant and pertinent and may contribute to the understanding of the therapeutic process by breast cancer patients during RT, as well as support clinical practice through the nursing consultation.

Keywords: oncology nursing, nursing care, validation studies, educational technology

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