Search results for: lung tumor

Authors: Suraj Sam Issaka, Anita Asamoah, Abass Gibrilla, Joseph Richmond Fianko

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Polycyclic aromatic hydrocarbons (PAHs) are a group of organic compounds that can form in edible oils during repeated frying and accumulate in fried foods. This study assesses the chances of health risks (carcinogenic and non-carcinogenic) due to PAHs levels in popular finger foods (bean cakes, plantain chips, doughnuts) fried in edible oils (mixed vegetable, sunflower, soybean) from the Ghanaian market. Employing probabilistic health risk assessment that considers variability and uncertainty in exposure and risk estimates provides a more realistic representation of potential health risks. Monte Carlo simulations with 10,000 iterations were used to estimate carcinogenic, mutagenic, and non-carcinogenic risks for different age groups (A: 6-10 years, B: 11-20 years, C: 20-70 years), food types (bean cake, plantain chips, doughnut), oil types (soybean, mixed vegetable, sunflower), and re-usage frying oil frequencies (once, twice, thrice). Our results suggest that, for age Group A, doughnuts posed the highest probability of carcinogenic risk (91.55%) exceeding the acceptable threshold, followed by bean cakes (43.87%) and plantain chips (7.72%), as well as the highest probability of unacceptable mutagenic risk (89.2%), followed by bean cakes (40.32%). Among age Group B, doughnuts again had the highest probability of exceeding carcinogenic risk limits (51.16%) and mutagenic risk limits (44.27%). At the same time, plantain chips exhibited the highest maximum carcinogenic risk. For adults age Group C, bean cakes had the highest probability of unacceptable carcinogenic (50.88%) and mutagenic risks (46.44%), though plantain chips showed the highest maximum values for both carcinogenic and mutagenic risks in this age group. Also, on non-carcinogenic risks across different age groups, it was found that age Group A) who consumed doughnuts had a 68.16% probability of a hazard quotient (HQ) greater than 1, suggesting potential cognitive impairment and lower IQ scores due to early PAH exposure. This group also faced risks from consuming plantain chips and bean cake. For age Group B, the consumption of plantain chips was associated with a 36.98% probability of HQ greater than 1, indicating a potential risk of reduced lung function. In age Group C, the consumption of plantain chips was linked to a 35.70% probability of HQ greater than 1, suggesting a potential risk of cardiovascular diseases.

Keywords: PAHs, fried foods, carcinogenic risk, non-carcinogenic risk, Monte Carlo simulations

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Authors: Eva de Mingo-Fernández, Lourdes Rubio Rico, Carmen Ortega-Segura, Montserrat Querol-García, Raúl González-Jauregui

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Today, one of the great challenges that the university faces is to get closer to society and transfer knowledge. The competency-based training approach favours a continuous interaction between practice and theory, which is why it is essential to establish real experiences with reflection and debate and to contrast them with personal and professional knowledge. Service-learning (SL) consists of an integration of academic learning with service in the community, which enables teachers to transfer knowledge with social value and students to be trained on the basis of experience of real needs and problems with the aim of solving them. SLE combines research, teaching, and social value knowledge transfer with the real social needs and problems of a community. Goal: The objective of this study was to design, implement, and evaluate a service-learning program in the subject of adult nursing for second-year nursing students. Methodology: After establishing collaboration with eight associations of people with different pathologies, the students were divided into eight groups, and each group was assigned an association. The groups were made up of 10-12 students. The associations willing to participate were for the following conditions: diabetes, multiple sclerosis, cancer, inflammatory bowel disease, fibromyalgia, heart, lung, and kidney diseases. The methodological design consisting of 5 activities was then applied. Three activities address personal and individual reflections, where the student initially describes what they think it is like to live with a certain disease. They then express their reflections resulting from an interview conducted by peers, in person or online, with a person living with this particular condition, and after sharing the results of their reflections with the rest of the group, they make an oral presentation in which they present their findings to the other students. This is followed by a service task in which the students collaborate in different activities of the association, and finally, a third individual reflection is carried out in which the students express their experience of collaboration. The evaluation of this activity is carried out by means of a rubric for both the reflections and the presentation. It should be noted that the oral presentation is evaluated both by the rest of the classmates and by the teachers. Results: The evaluation of the activity, given by the students, is 7.80/10, commenting that the experience is positive and brings them closer to the reality of the people and the area.

Keywords: academic learning integration, knowledge transfer, service-learning, teaching methodology

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Authors: AliAkbar Hafezi, Jalal Taherian, Jamshid Abedi, Mahsa Elahi, Behnam Kadkhodaei

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Background: Soft tissue sarcomas (STS) are generally treated with a combination of limb preservation surgery and radiation therapy. Today, preoperative radiation therapy is considered for accurate treatment volume and smaller field size. Therefore, this study was performed to compare preoperative with postoperative radiation therapy in patients with extremity STS. Methods: In this non-randomized clinical trial, patients with localized extremity STS referred to the orthopedic clinics in Iran from 2021 to 2023 were studied. Patients were randomly divided into two groups: preoperative and postoperative radiation therapy. The two groups of patients were compared in terms of acute (wound dehiscence and infection) and late (limb edema, subcutaneous fibrosis, and joint stiffness) complications and their severity, as well as local recurrence and other one-year outcomes. Results: A total of 80 patients with localized extremity STS were evaluated in two treatment groups. The groups were matched in terms of age, sex, history of diabetes mellitus, hypertension, smoking, involved side, involved extremity, lesion location, and tumor histopathology. The acute complications of treatment in the two groups of patients did not differ significantly (P > 0.05). Of the late complications, only joint stiffness between the two groups had significant statistical differences (P < 0.001). The severity of all three late complications in the postoperative radiation therapy group was significantly higher (P < 0.05). There was no significant difference between the two groups in terms of the rate of local recurrence of other one-year outcomes (P > 0.05). Conclusion: This study showed that in patients with localized extremity STS, the two therapeutic approaches of adjuvant and neoadjuvant radiation therapy did not differ significantly in terms of local recurrence and distant metastasis during the one-year follow-up period and due to fewer late complications in preoperative radiotherapy group, this treatment approach can be a better choice than postoperative radiation therapy.

Keywords: soft tissue sarcoma, extremity, preoperative radiation therapy, postoperative radiation therapy

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Authors: S. A. El-Marasy, S. A. El Awdan, R. M. Abd-Elsalam

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This study aimed to investigate the possible neuroprotective effect of chrysin on thioacetamide (TAA)-induced hepatic encephalopathy in rats. Also, the effect of chrysin on motor impairment, cognitive deficits, oxidative stress, neuroinflammation, apoptosis and histopathological damage was assessed. Male Wistar rats were randomly allocated into five groups. The first group received the vehicle (distilled water) for 21 days and is considered as normal group. While the second one received intraperitoneal dose of TAA (200 mg/kg) at three alternative days during the third week of the experiment to induce HE and is considered as control group. The other three groups were orally administered chrysin for 21 days (25, 50, 100 mg/kg) and starting from day 17; rats received intraperitoneal dose of TAA (200 mg/kg) at three alternative days. Then behavioral, biochemical, histopathological and immunohistochemical analyses were assessed. Then behavioral, biochemical, histopathological and immunohistochemical analyses were assessed. Chrysin reversed TAA-induced motor coordination in rotarod test, cognitive deficits in object recognition test (ORT) and attenuated serum ammonia, hepatic liver enzymes, reduced malondialdehyde (MDA), elevated reduced glutathione (GSH), reduced nuclear factor kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α) and Interleukin-6 (IL-6) brain contents. Chrysin administration also reduced Toll-4 receptor (TLR-4) gene expression, caspase-3 protein expression, hepatic necrosis and astrocyte swelling. This study depicts that chrysin exerted neuroprotective effect in TAA-induced HE rats, evidenced by improvement of cognitive deficits, motor incoordination and histopathological changes such as astrocyte swelling and vacuolization; hallmarks in HE, via reducing hyperammonemia, ameliorating hepatic function, in addition to its anti-oxidant, inactivation of TLR-4/NF-κB inflammatory pathway, and anti-apoptotic effects.

Keywords: chrysin, hepatic encephalopathy, oxidative stress, rats, thioacetamide, TLR4/NF-κB pathway

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Authors: Hajar Zarei, AliAkbar Zarenejadatashgah, Vuk Uskoković, Hiroshi Watabe

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The reactive oxygen species (ROS) generated by radiation in nuclear diagnostic imaging and radiotherapy could damage the structure of the proteins in noncancerous cells surrounding the tumor. The critical factor in many age-related diseases, such as Alzheimer, Parkinson, or Huntington diseases, is the oxidation of proteins by the ROS as molecular triggers of the given pathologies. Our studies by spectroscopic experiments showed doses close to therapeutic ones (1 to 5 Gy) could lead to changes of secondary and tertiary structures in BSA protein macromolecule as a protein model as well as the aggregation of polypeptide chain but without the fragmentation. For this reason, we investigated the radioprotective effects of natural (vitamin C and E) and synthetic materials (CNPs and FIOMPs) on the structural changes in BSA protein induced by gamma irradiation at a therapeutic dose (3Gy). In the presence of both vitamins and synthetic materials, the spectroscopic studies revealed that irradiated BSA was protected from the structural changes caused by ROS, according to in vitro research. The radioprotective property of CNPs and FIOMPs arises from enzyme mimetic activities (catalase, superoxide dismutase, and peroxidase) and their antioxidant capability against hydroxyl radicals. In the case of FIOMPs, a porous structure also leads to increased ROS recombination with each other in the same radiolytic track and subsequently decreased encounters with BSA. The hydrophilicity of vitamin C resulted in the major scavenging of ROS in the solvent, whereas hydrophobic vitamin E localized on the nonpolar patches of the BSA surface, where it did not only neutralize them thanks to the moderate BSA binding constant but also formed a barrier for diffusing ROS. To the best of our knowledge, there has been a persistent lack of studies investigating the radioactive effect of mentioned materials on proteins. Therefore, the results of our studies can open a new widow for application of these common dietary ingredients and new synthetic NPs in improving the safety of radiotherapy.

Keywords: reactive oxygen species, spectroscopy, bovine serum albumin, gamma radiation, radioprotection

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Authors: Tania Vasquez Mata, Luis A. Herrera, Cristian Arriaga Canon

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Background: Locally advanced breast cancer of the luminal B phenotype, poses challenges due to its variable response to neoadjuvant chemotherapy. A predictive biomarker is needed to identify patients who will not respond to treatment, allowing for alternative therapies. This study aims to validate the use of the lncRNA GATA3-AS1, as a predictive biomarker using RNA in situ hybridization. Research aim: The aim of this study is to determine if GATA3-AS1 can serve as a biomarker for resistance to neoadjuvant chemotherapy in patients with locally advanced luminal B breast cancer. Methodology: The study utilizes RNA in situ hybridization with predesigned probes for GATA3-AS1 on Formalin-Fixed Paraffin-Embedded tissue sections. The samples underwent pretreatment and protease treatment to enable probe penetration. Chromogenic detection and signal evaluation were performed using specific criteria. Findings: Patients who did not respond to neoadjuvant chemotherapy showed a 3+ score for GATA3-AS1, while those who had a complete response had a 1+ score. Theoretical importance: This study demonstrates the potential clinical utility of GATA3-AS1 as a biomarker for resistance to neoadjuvant chemotherapy. Identifying non-responders early on can help avoid unnecessary treatment and explore alternative therapy options. Data collection and analysis procedures: Tissue samples from patients with locally advanced luminal B breast cancer were collected and processed using RNA in situ hybridization. Signal evaluation was conducted under a microscope, and scoring was based on specific criteria. Questions addressed: Can GATA3-AS1 serve as a predictive biomarker for neoadjuvant chemotherapy response in locally advanced luminal B breast cancer? Conclusion: The lncRNA GATA3-AS1 can be used as a biomarker for resistance to neoadjuvant chemotherapy in patients with locally advanced luminal B breast cancer. Its identification through RNA in situ hybridization of tissue obtained from the initial biopsy can aid in treatment decision-making.

Keywords: biomarkers, breast neoplasms, genetics, neoadjuvant therapy, tumor

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Authors: Yori Gidron, Laura Caton, Irit Ben-Aharon

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Background: Many patients and even certain clinicians attribute cancer development to psychosocial factors. Yet, empirical data supports more the prognostic role, rather than the etiological role, of psychosocial factors in cancer. Part of the inconsistency may result from not considering possible moderating factors in the etiological role of psychosocial factors. One important candidate moderating factor is the vagal nerve, whose activity is indexed by heart-rate variability (HRV). The vagal nerve may prevent cancer since it reduces inflammation on the one hand, and since it increases anti-tumor immunity on the other hand. This study examined the moderating role of the vagus in the relation between life threatening events (LTE) and cancer development. Method: We re-analyzed data from the Lifelines Dutch longitudinal cohort study of over 150,000 people. The present study included 82,751 adults, who initially were cancer-free. We extracted information on background factors (e.g., age, gender, fat consumption), whether they ever experienced LTE, HRV and cancer diagnosis as reported by patients in annual clinic visits. HRV was derived from brief ECGs. Results: Of the full sample, 1011 people developed cancer during a follow-up. In the full sample, LTE significantly predicted cancer development (R.R = 1.063 p < .01) and HRV significantly predicted a reduced risk of cancer development (R.R = .506 p <.001). Importantly, LTE significantly predicted cancer only when HRV was low (R.R = 1.056, 95% CI: 1.007 - 1.108, p < .05) but not when HRV was high (R.R = 1.014; 95% CI: 0.916 - 1.122, p > 0.05), independent of confounders. Conclusions: To the best of our knowledge, this is the first study showing in a large sample that LTE predict cancer development, and that this occurs only when vagal nerve activity (HRV) is relatively low. These results could result from lack of vagal modulation of inflammation and also from lack of vagal modulation of stress responses. Results are in line with the cancer-protective role of the vagus. HRV needs to be routinely monitored in the population and future intervention trials need to examine whether vagal nerve activation can prevent cancer in people with LTE and with other cancer risk factors.

Keywords: cancer development, life-events, moderation, vagal nerve

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Authors: Fatimah A. Alhomaid

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The present study was planned to investigate the role of molecular changes and immunohistochemical in early detection of liver cancer in Saudi patients. our results were carried out on 54 patients liver cancer. We obtained our data from laboratory in King Khalid University Hospital. The specimens were taken (54) patients with liver cancer 34 male and 14 female and 2 control. The average age of varied from 37-85 years. The tumor was diagnosed as grade I in tow patients (male and female) and grade 2 in 45 patients (28 male and 17 female) while the grade 3 in 4 patients (all males). The specimens were processed for haematoxylin and eosin staining, immunohistochemical technique and flow cytometry analysis. Our study noted that most patients had adenocarcinoma which characterized by presence of signet-ring cells were very clear in advanced patients with adenocarcinoma. Our sections in adenocarcinoma in grade 2 and stage 3 had an increase in signet ring cells,an increase in the acini of glands and an increase in number of lymphocytes which spread to the muscular layer. With advancing the disease, there were haemorrhage in blood and increase in lymphocytes and increase in the number of nuclei in the tubular glands. Our study was carried on 48 patients, immunohistochemical diagnosis (CK20, PCNA, P53) and the analysis of DNA content by flow cytometry technique. Our study indicated that the presence of correlation between the immunohistochemical analysis for P53 and the grades. The reaction of P53 appeared as strong in nucleus in grades &stage 3 and appeared in other sections as dark brown pigment. Our study indicated that the absence of correlation between the immunohistochemical analysis for PCAN and the grades. In our sections there were strong reaction in the more 80% of nuclei in grade 1& stage 2. Our study indicated that the presence of correlation between the immunohistochemical analysis for CK20 and the grades. Our results indicated the presence of positive reaction in cytoplasm varied from weak to moderate in grade 3 & stage 4. Concerning the Flow cytometry technique our results indicated that the presence of correlation between the DNA and different stages of liver cancer.

Keywords: cancer, CK20, DNA, cytometry analysis, liver, immunohistochemical, molecular changes, PCNA, p53

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Authors: Aliya Sekenova, Vyacheslav Ogay

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The derivation of human induced pluripotent stem cells (iPSCs) from somatic cells by direct reprogramming opens wide perspectives in the regenerative medicine. It means the possibility to develop the personal and, consequently, any immunologically compatible cells for applications in cell-based therapy. The purpose of our study was to develop the technology for the production of NK cells from T cell-derived induced pluripotent stem cells (TiPSCs) for subsequent application in adoptive cancer immunotherapy. Methods: In this study iPSCs were derived from peripheral blood T cells using Sendai virus vectors expressing Oct4, Sox2, Klf4 and c-Myc. Pluripotent characteristics of TiPSCs were examined and confirmed with alkaline phosphatase staining, immunocytochemistry and RT-PCR analysis. For NK cell differentiation, embryoid bodies (EB) formed from (TiPSCs) were cultured in xenogeneic serum-free medium containing human serum, IL-3, IL-7, IL-15, SCF, FLT3L without using M210-B4 and AFT-024 stromal feeder cells. After differentiation, NK cells were characterized with immunofluorescence analysis, flow cytometry and cytotoxicity assay. Results: Here, we for the first time demonstrate that TiPSCs can effectively differentiate into functionally active NK cells without M210-B4 and AFT-024 xenogeneic stroma cells. Immunofluorescence and flow cytometry analysis showed that EB-derived cells can differentiate into a homogeneous population of NK cell expressing high levels of CD56, CD45 and CD16 specific markers. Moreover, these cells significantly express killing activation receptors such as NKp44 and NKp46. In the comparative analysis, we observed that NK cells derived using feeder-free culture system have more high killing activity against K-562 tumor cells, than NK cells derived by feeder-dependent method. Thus, we think that our obtained data will be useful for the development of large-scale production of NK cells for translation into cancer immunotherapy.

Keywords: induced pluripotent stem cells, NK cells, T cells, cell diffentiation, feeder cell-free culture system

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Authors: Anna Pick Kiong Ling, Jia May Chin, Rhun Yian Koh, Ying Pei Wong

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Background: Uncontrolled inflammation may cause serious inflammatory diseases if left untreated. Non-steroidal anti-inflammatory drug (NSAIDs) is commonly used to inhibit pro-inflammatory enzymes, thus, reduce inflammation. However, long term administration of NSAIDs leads to various complications. Medicinal plants are getting more attention as it is believed to be more compatible with human body. One of them is a flavonoid-containing medicinal plants, Strobilanthes crispus which has been traditionally claimed to possess anti-inflammatory and antioxidant activities. Nevertheless, its anti-inflammatory activities are yet to be scientifically documented. Objectives: This study aimed to examine the anti-inflammatory activity of S. crispus by investigating its effects on intracellular oxidative stress and prostaglandin E₂ (PGE₂) levels. Materials and Methods: In this study, the Maximum Non-toxic Dose (MNTD) of methanol extract of both leaves and stems of S. crispus was first determined using 3-(4,5-dimethylthiazolyl-2)-2,5-diphenytetrazolium Bromide (MTT) assay. The effects of S. crispus extracts at MNTD and half MNTD (½MNTD) on intracellular ROS as well as PGE₂ levels in 1.0 µg/mL LPS-stimulated RAW 264.7 macrophages were then be measured using DCFH-DA and a competitive enzyme immunoassay kit, respectively. Results: The MNTD of leaf extract was determined as 700µg/mL while for stem was as low as 1.4µg/mL. When LPS-stimulated RAW 264.7 macrophages were subjected to the MNTD of S. crispus leaf extract, both intracellular ROS and PGE₂ levels were significantly reduced. In contrast, stem extract at both MNTD and ½MNTD did not significantly reduce the PGE₂ level, but significantly increased the intracellular ROS level. Conclusion: The methanol leaf extract of S. crispus may possess anti-inflammatory properties as it is able to significantly reduce the intracellular ROS and PGE₂ levels of LPS-stimulated cells. Nevertheless, further studies such as investigating the interleukin, nitric oxide and cytokine tumor necrosis factor-α (TNFα) levels has to be conducted to further confirm the anti-inflammatory properties of S. crispus.

Keywords: anti-inflammatory, natural products, prostaglandin E2, reactive oxygen species

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Authors: Seham Samir Soliman, Ahmed A.Suliman, Khaled Fathy, Ahmed A. Sedik

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Cyclophosphamide (CP), an antineoplastic drug, has been found to induce reproductive damage. It is essential to develop approaches aimed at safeguarding ovarian tissue integrity in women experiencing reproductive toxicity as a result of chemotherapy. The current study was conducted to assess the impact of an extract derived from Moringa oleifera (M. oleifera) leaves on ovarian damage produced by CP. A total of 32 female Wistar Albino rats, which were in a healthy cycling state, were randomly separated into 4 groups, with every group contains 8 rats. The first group was administered intraperitoneal (i.p.) saline. The second group was administered a solitary intraperitoneal dosage of cyclophosphamide (200 mg/kg). The third one received M. oleifera extract (150 mg/kg orally) for 20 days, followed by i.p. of CP on the last day of the experiment. The fourth group received M. oleifera extract (250 mg/kg orally) for 20 days, followed by i.p. of CP on the last day of the experiment. Hormonal assessments, including luteinizing hormone (LH), estrogen (ES), and follicle-stimulating hormone (FSH), were performed 24 hours after CP administration. In addition, evaluating the antioxidant status and inflammatory response against CP. Moreover, conducting detailed histopathological and ultra-structural pictures of the ovary. Our findings reported that rats intoxicated with CP exhibited elevated levels of FSH, LH, malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), and a decrease in E₂, and glutathione (GSH) levels. Pre-treatment with M. oleifera extract (250 mg/kg orally) ameliorated the disturbance in hormonal changes, oxidative stress indices, and the levels of pro-inflammatory mediators. Also, the histopathological and ultra-structural pictures of the ovaries were improved significantly in rats. In conclusion, M. oleifera extract possesses a significant protective role against CP-induced acute reproductive toxicity via modulating the values of FSH, LH, E₂ and quenching the release of reactive oxygen species and inflammatory mediators in female rats.

Keywords: cyclophosphamide, Moringa oleifera, ovarian function, oxidative stress, pro-inflammatory mediators

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Authors: Parvin Samadi Pakchin, Reza Saber, Hossein Ghanbari, Yadollah Omidi

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Ovarian cancer is one of the leading cause of mortality among the gynecological malignancies, and it remains the one of the most prevalent cancer in females worldwide. Tumor markers are biochemical molecules in blood or tissues which can indicates cancers occurrence in the human body. So, the sensitive and specific detection of cancer markers typically recruited for diagnosing and evaluating cancers. Recently extensive research efforts are underway to achieve a simple, inexpensive and accurate device for detection of cancer biomarkers. Compared with conventional immunoassay techniques, electrochemical immunosensors are of great interest, because they are specific, simple, inexpensive, easy to handling and miniaturization. Moreover, in the past decade nanotechnology has played a crucial role in the development of biosensors. In this study, a signal-off electrochemical immunosensor for the detection of CA125 antigen has been developed using chitosan-gold nanoparticles (CS-AuNP) and multi-wall carbon nanotubes (MWCNT) composites. Toluidine blue (TB) is used as redox probe which is immobilized on the electrode surface. CS-AuNP is synthesized by a simple one step method that HAuCl4 is reduced by NH2 groups of chitosan. The CS-AuNP-MWCNT modified electrode has shown excellent electrochemical performance compared with bare Au electrode. MWCNTs and AuNPs increased electrochemical conductivity and accelerate electrons transfer between solution and electrode surface while excessive amine groups on chitosan lead to the effective loading of the biological material (CA125 antibody) and TB on the electrode surface. The electrochemical, immobilization and sensing properties CS-AuNP-MWCNT-TB modified electrodes are characterized by cyclic voltammetry, electrochemical impedance spectroscopy, differential pulse voltammetry and square wave voltammetry with Fe(CN)63−/4−as an electrochemical redox indicator.

Keywords: signal-off electrochemical biosensor, CA125, ovarian cancer, chitosan-gold nanoparticles

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

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

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

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Authors: Asma Zaib, Saeed Khan, Ayaz Ahmed Noonari, Sehrish Bint-e-Mohsin

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Breast cancer is the most common cancer among females worldwide and is estimated that more than 450,000 deaths are reported each year. It accounts for about 14% of all female cancer deaths. Angiogenesis plays an essential role in Breast cancer development, invasion, and metastasis. Breast cancer predominantly begins in luminal epithelial cells lining the normal breast ducts. Breast carcinoma likely requires coordinated efforts of both increased proliferation and increased motility to progress to metastatic stages.Resveratrol: a natural stilbenoid, has anti-inflammatory and anticancer effects that inhibits proliferation of variety of human cancer cell lines, including breast, prostate, stomach, colon, pancreatic, and thyroid cancers.The objective of this study is:To investigate anti-neoangiogenesis effects of Resveratrol in breast cancer and to analyze inhibitory effects of resveratrol on aromatase, Erα, HER2/neu, and VEGFR.Docking is the computational determination of binding affinity between molecule (protein structure and ligand).We performed molecular docking using Swiss-Dock and to determine docking effects of (1) Resveratrol with Aromatase, (2) Resveratrol with ERα (3) Resveratrol with HER2/neu and (4) Resveratrol with VEGFR2.Docking results of resveratrol determined inhibitory effects on aromatase with binding energy of -7.28 kcal/mol which shows anticancerous effects on estrogen dependent breast tumors. Resveratrol also show inhibitory effects on ERα and HER2/new with binging energy -8.02, and -6.74 respectively; which revealed anti-cytoproliferative effects upon breast cancer. On the other hand resveratrol v/s VEGFR showed potential inhibitory effects on neo-angiogenesis with binding energy -7.68 kcal/mol, angiogenesis is the important phenomenon that promote tumor development and metastasis. Resveratrol is an anti-breast cancer agent conformed by in silico studies, it has been identified that resveratrol can inhibit breast cancer cells proliferation by acting as competitive inhibitor of aromatase, ERα and HER2 neo, while neo-angiogemesis is restricted by binding to VEGFR which authenticates the anti-carcinogenic effects of resveratrol against breast cancer.

Keywords: angiogenesis, anti-cytoproliferative, molecular docking, resveratrol

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Authors: Mostafa Elbaba

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Because childhood renal diseases are grossly different compared to adult diseases, pediatric nephrology was founded as a specialty in 1965. Renal pathology specialty was introduced at the London Ciba Symposium in 1961. The history of renal pathology can be divided into two eras: one starting in the 1650s with the invention of the microscope, the second in the 1950s with the implementation of renal biopsy, and the presence of electron microscopy and immunofluorescence study. Prior to the 1950s, the study of diseased human kidneys was restricted to postmortem examination by gross pathology. In 1827, Richard Bright first described his triad of kidney disease, which was confirmed by morbid kidney changes at autopsy. In 1905 Friedrich Mueller coined the term “nephrosis” describing the inflammatory form of “degenerative” diseases, and later F. Munk added the term “lipoid nephrosis”. The most profound influence on renal diseases’ classification came from the publication of Volhard and Fahr in 1914. In 1899, Carl Max Wilhelm Wilms described Wilms' tumor of the kidneys in children. Chronic pyelonephritis was a popular renal diagnosis and the most common cause of uremia until the 1960s. Although kidney biopsy had been used early in the 1930s for renal tumors, the earliest reports of its use in the diagnosis of medical kidney disease were by Iversen and Brun in 1951, followed by Alwall in 1952, then by Pardo in 1953. The earliest intentional renal biopsies were done in 1944 by Nils Alwall, while the procedure was abandoned after the death of one of his 13 patients who biopsied. In 1950, Antonino Perez-Ara attempted renal biopsies, but his results were missed because of an unpopular journal publication. In the year 1951, Claus Brun and Poul Iverson developed the biopsy procedure using an aspiration technique. Popularizing renal biopsy practice is accredited to Robert Kark, who published his distinct work in 1954. He perfected the technique of renal biopsy in the prone position using the Vim-Silverman needle and used intravenous pyelography to improve the localization of the kidney.

Keywords: history, medicine, nephrology, pediatrics, pathology

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Authors: Paresh Patel, Priya Patel, Vaidehi Sorathiya, Navin Sheth

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The aim of present work was to fabricate Salmeterol Xinafoate (SX) metered dose inhaler (MDI) for asthma and to evaluate the SX loaded solid lipid nanoparticles (SLNs) for pulmonary delivery. Solid lipid nanoparticles can be used to deliver particles to the lungs via MDI. A modified solvent emulsification diffusion technique was used to prepare Salmeterol Xinafoate loaded solid lipid nanoparticles by using compritol 888 ATO as lipid, tween 80 as surfactant, D-mannitol as cryoprotecting agent and L-leucine was used to improve aerosolization behaviour. Box-Behnken design was applied with 17 runs. 3-D surface response plots and contour plots were drawn and optimized formulation was selected based on minimum particle size and maximum % EE. % yield, in vitro diffusion study, scanning electron microscopy, X-ray diffraction, DSC, FTIR also characterized. Particle size, zeta potential analyzed by Zetatrac particle size analyzer and aerodynamic properties was carried out by cascade impactor. Pre convulsion time was examined for control group, treatment group and compare with marketed group. MDI was evaluated for leakage test, flammability test, spray test and content per puff. By experimental design, particle size and % EE found to be in range between 119-337 nm and 62.04-76.77% by solvent emulsification diffusion technique. Morphologically, particles have spherical shape and uniform distribution. DSC & FTIR study showed that no interaction between drug and excipients. Zeta potential shows good stability of SLNs. % respirable fraction found to be 52.78% indicating reach to the deep part of lung such as alveoli. Animal study showed that fabricated MDI protect the lungs against histamine induced bronchospasm in guinea pigs. MDI showed sphericity of particle in spray pattern, 96.34% content per puff and non-flammable. SLNs prepared by Solvent emulsification diffusion technique provide desirable size for deposition into the alveoli. This delivery platform opens up a wide range of treatment application of pulmonary disease like asthma via solid lipid nanoparticles.

Keywords: salmeterol xinafoate, solid lipid nanoparticles, box-behnken design, solvent emulsification diffusion technique, pulmonary delivery

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Authors: Lucja Rodzik, Joanna Lewandowska-Lancucka, Michal Szuwarzynski, Krzysztof Szczubialka, Maria Nowakowska

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The analysis of nucleobases is of great importance for bioscience since their abnormal concentration in body fluids suggests the deficiency and mutation of the immune system, and it is considered to be an important parameter for diagnosis of various diseases. The presented conjugate meets the need for development of the effective, selective and highly sensitive sensor for nucleobase/nucleoside detection. The novel, highly fluorescent cadmium telluride quantum dots (CdTe QDs) functionalized with thymine and stabilized with thioglycolic acid (TGA) conjugates has been developed and thoroughly characterized. Successful formation of the material was confirmed by elemental analysis, and UV–Vis fluorescence and FTIR spectroscopies. The crystalline structure of the obtained product was characterized with X-ray diffraction (XRD) method. The composition of CdTe QDs and their thymine conjugate was also examined using X-ray photoelectron spectroscopy (XPS). The size of the CdTe-thymine was 3-6 nm as demonstrated using atomic force microscopy (AFM) and high resolution transmission electron microscopy (HRTEM) imaging. The plasmon resonance fluorescence band at 540 nm on excitation at 351 nm was observed for these nanoparticles. The intensity of this band increased with the increase in the amount of conjugated thymine with no shift in its position. Based on the fluorescence measurements, it was found that the CdTe-thymine conjugate interacted efficiently and selectively not only with adenine, a nucleobase complementary to thymine, but also with nucleosides and adenine-containing modified nucleosides, i.e., 5′-deoxy-5′-(methylthio)adenosine (MTA) and 2’-O-methyladenosine, the urinary tumor markers which allow monitoring of the disease progression. The applicability of the CdTe-thymine sensor for the real sample analysis was also investigated in simulated urine conditions. High sensitivity and selectivity of CdTe-thymine fluorescence towards adenine, adenosine and modified adenosine suggest that obtained conjugate can be potentially useful for development of the biosensor for complementary nucleobase/nucleoside detection.

Keywords: CdTe quantum dots, conjugate, sensor, thymine

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Authors: Eitan Yefenof

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Glucocorticoid (GC) hormones, e.g. Dexamethasone and Prednisone, are widely used in the therapy of leukemia and lymphoma owing to their apoptogenic effect on lymphoid cells. However, the emergence of GC resistant cells during therapy is a major cause for treatment failure, urging the need for novel strategies that maintain leukemia sensitivity to the pro-apoptotic activity of GCs. GCs act by binding to the GC receptor (GR), which, in its inactive state, is sequestered in the cytosol by a multi-subunit complex of heat shock proteins. Upon ligand binding, the complex dissociates, allowing GR activation and translocation to the nucleus, where it regulates transcription of multiple genes. We demonstrated that in addition to gene expression, GR also regulates microRNA (miR) expression. Deep-sequencing analysis revealed 14 miRs that are regulated in GC-sensitive but resistant leukemias upon treatment with GC. GC up-regulates miR-103, miR-15~16 and miR-30e/d, while down-regulates miR-17, mir-18a, miR-19a, miR-19b, miR-20a and miR-92a (members of the miR-17∼92a multi-cistron). Upon transfection, miR-103 confers GC apoptotic sensitivity to otherwise GC-resistant cell. Furthermore, knocking down miR-103 expression reduces the GC apoptotic response of sensitive cells. miR-103 abrogates c-Myc expression, an oncogenic transcription factor which is deregulated in many cancers. In addition, miR-103 up-regulates Bim, a pro-apoptotic protein crucial for GC-induced death. Activated glycogen synthase kinase 3 (GSK3) is also crucial for GC-induced apoptosis. GSK3 is active in GC-sensitive but not in GC-resistant cells. We found that GSK3 associates with the GR multi-subunit complex. Upon GC exposure, it dissociates from the GR and interacts with Bim to enable activation of the mitochondrial apoptosis pathway. miR-103 mediated c-Myc ablation is followed by down-regulation of the multi-cistron miR-17~92a, in particular miR-18a and miR-20a. miR-18a targets GR for degradation whereas miR-20a targets Bim degradation. Hence, miR-103 acts, in concert with Bim and GR, as a "tumor suppressor" that leads to reduced proliferation, cell-cycle arrest and cell death. We suggest that miR-103 can provide a diagnostic tool that predicts the sensitivity of leukemia to GC based therapy. Furthermore, exosomal delivery of miR-103 or up-regulation of the endogenous miR-103 could confer apoptotic sensitivity to resistant cells at the outset, thus becoming a useful therapeutic tool combined with GCs.

Keywords: apoptosis, leukemia, micro-RNA, steroids

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Authors: Marjan Moradi Fard, Hossein Rassi, Masoud Houshmand

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Aim: Breast cancer is one of the most common cancers affecting the morbidity and mortality of Iranian women. This disease is a result of collective alterations of oncogenes and tumor suppressor genes. Studies have produced conflicting results concerning the role of p53 codon 72 polymorphism (G>C) and miR-146a rs2910164 polymorphism (G>C) on the risk of several cancers; therefore, a research was performed to estimate the association between the p53 codon 72 polymorphism and miR-146a rs2910164 polymorphism in breast cancer. Methods and Materials: A total of 45 archival breast cancer samples from khatam hospital and 40 healthy samples were collected. Verification of each cancer reported in a relative was sought through the pathology reports of the hospital records. Then, DNA extracted from all samples by standard methods and p53 codon 72 polymorphism genotypes and miR-146a rs2910164 polymorphism genotypes were analyzed using multiplex PCR. The tubules, mitotic activity, necrosis, polymorphism and grade of breast cancer were staged by Nottingham histological grading and immunohistochemical staining of the sections from the paraffin wax embedded tissues for the expression of ER, PR and p53 was carried out using a standard method. Finally, data analysis was performed using the 7 version of the Epi Info(TM) 2012 software and test chi-square(x2) for trend. Results: Successful DNA extraction was assessed by PCR amplification of b-actin gene (99 bp). According to the results, p53 GG genotype and miR-146a rs2910164 CC genotype was significantly associated with increased risk of breast cancer in the study population. In this study, we established that tumors of p53 GG genotype and miR-146a rs2910164 CC genotype exhibited higher mitotic activity, higher polymorphism, lower necrosis, lower tubules, higher ER- and PR-negatives and lower TP53-positives than the other genotypes. Conclusion: The present study provided preliminary evidence that a p53 GG genotype may effect breast cancer risk in the study population, interacting synergistically with miR-146a rs2910164 CC genotype. Our results demonstrate that the testing of p53 codon 72 polymorphism genotypes and miR-146a rs2910164 polymorphism genotypes in combination with clinical parameters can serve as major risk factors in the early identification of breast cancers.

Keywords: breast cancer, p53 codon 72 polymorphism, miR-146a rs2910164 polymorphism, genotypes

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

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

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

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Authors: Hani M. Alothaid, Louise Robson, Richmond Muimo

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Cystic fibrosis (CF) is a disease that affects respiratory function and in EU it affects about 1 in 2,500 live births with an average 40-year life expectancy. This disease caused by mutations within the gene encoding the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) chloride channel leading to dysregulation of epithelial fluid transport and chronic lung inflammation, suggesting functional alterations of immune cells. In airways, CFTR been found to form a functional complex with S100A10 and AnxA2 in a cAMP/PKA dependent manner. The multiprotein complex of AnxA2-S100A10 and CFTR is also regulated by calcineurin. The aim of this study was i) to investigate whether chloride ion (Cl−) channels are activated by Pseudomonas aeruginosa lipopolysaccharide (LPS from PA), ii) if this activation is regulated by cAMP/PKA/calcineurin pathway and iii) to investigate the role of LPS-activated Cl− channels in the release of pro-inflammatory cytokines by immune cells. Human peripheral blood monocytes were used in the study. Whole-cell patch records showed that LPS from PA can activate Cl− channels, including CFTR and outwardly-rectifying Cl− channel (ORCC). This activation appears to require an intact PKA/calcineurin signalling pathway. The Gout in the presence of LPS was significantly inhibited by diisothiocyanatostilbene-disulfonic acid (DIDS), an ORCC blocker (p<0.001). The Gout was further suppressed by CFTR(inh)-172, a specific inhibitor for CFTR channels (p<0.001). Monocytes pre-incubated with PKA inhibitor or calcineurin inhibitor before stimulated with LPS from PA that were resulted in DIDS and CFTR(inh)-172 insensitive currents. Activation of both ORCC and CFTR was however, observed in response to monocytes exposure to LPS. Additionally, ELISA showed that the CFTR and ORCC play a role in mediating the release of pro-inflammatory cytokines such as IL-1β upon exposure of monocytes to LPS. However, this secretion was significantly inhibited due to CFTR and ORCC inhibition. However, Cl− may play a role in IL-1β release independent of cAMP/PKA/calcineurin signalling due to the enhancement of IL-1β secretion even when cAMP/PKA/calcineurin pathway was inhibited. In conclusion, our data confirmed that LPS from PA activates Cl− channels in human peripheral blood monocytes. Our data also confirmed that Cl− channels were involved in IL-1β release in monocytes upon exposure to LPS. However, it has been found that PKA and calcineurin does not seem to influence the Cl− dependent cytokine release.

Keywords: cystic fibrosis, CFTR, Annexin A2, S100A10, PP2B, PKA, outwardly-rectifying Cl− channel, Pseudomonas aeruginosa

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Authors: Shaikah Alsubayae, Gianluigi Casse, Carlos Chavez, Jon Taylor, Alan Taylor, Mohammad Alsulimane

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Achieving precise radiotherapy through carbon therapy necessitates the accurate monitoring of radiation dose distribution within the patient's body. This process is pivotal for targeted tumor treatment, minimizing harm to healthy tissues, and enhancing overall treatment effectiveness while reducing the risk of side effects. In our investigation, we adopted a methodological approach to monitor secondary proton doses in carbon therapy using Monte Carlo (MC) simulations. Initially, Geant4 simulations were employed to extract the initial positions of secondary particles generated during interactions between carbon ions and water, including protons, gamma rays, alpha particles, neutrons, and tritons. Subsequently, we explored the relationship between the carbon ion beam and these secondary particles. Interaction vertex imaging (IVI) proves valuable for monitoring dose distribution during carbon therapy, providing information about secondary particle locations and abundances, particularly protons. The IVI method relies on charged particles produced during ion fragmentation to gather range information by reconstructing particle trajectories back to their point of origin, known as the vertex. In the context of carbon ion therapy, our simulation results indicated a strong correlation between some secondary particles and the range of carbon ions. However, challenges arose due to the unique elongated geometry of the target, hindering the straightforward transmission of forward-generated protons. Consequently, the limited protons that did emerge predominantly originated from points close to the target entrance. Fragment (protons) trajectories were approximated as straight lines, and a beam back-projection algorithm, utilizing interaction positions recorded in Si detectors, was developed to reconstruct vertices. The analysis revealed a correlation between the reconstructed and actual positions.

Keywords: radiotherapy, carbon therapy, monitor secondary proton doses, interaction vertex imaging

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Authors: Shadia Al-Bahlani, Ruqaya Al-Rashdi, Shadia Al-Sinawi, Maya Al-Bahri

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Background: Breast cancer is the most common cancer in women worldwide. Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer, which is defined by the absence of Estrogen (ER), Progesterone (PR) and Human epidermal growth factor (Her-2) receptors. The calpain system plays an important role in many cellular processes including apoptosis, necrosis, cell signaling and proliferation. The role of clapins in pathogenesis and tumor progression has been studied in certain cancer types; however, its definite role is not yet established in breast cancer especially in the TNBC subtype. Objectives: This study aims to measure calpain-1 expression and correlate this measurement with the proliferating/apoptotic index as well with the prognostic factors in TNBC patients’ tissue. Materials and Methods: Thirty nine paraffin blocks from patients diagnosed with TNBC were used to measure the expression of calpain-1 and Ki-67 (proliferating marker) proteins using immunohistochemistry. Apoptosis was assessed morphological and biochemically using conventional Haematoxylin and Eosin (H&E) staining method and terminal deoxynucleotidyl transferase-mediate dUTP nick and labeling (TUNEL) assay respectively. Data was statistically analyzed using Pearson X2 test of association. Results: Calpain-1 content was visualized in the nucleus of the TNBC cells and its expression varied from low to high among the patients tissue. Calpain expression showed no significant correlation with the proliferating/apoptotic index as well with the clinicopathological variables. Apoptotic counts quantified by H&E staining showed significant association with the apoptotic TUNEL assay, validating both approaches. Conclusion: Although calpain-1 expression showed no significant association with the clinical outcome, its variable level of expression might indicate a hidden role in breast cancer tissue. Larger number of samples and different mode of assessments are needed to fully investigate such role. Exploring the involvement of calpain-1 in cancer progression might help in considering it as a biomarker of breast cancer.

Keywords: breast cancer, calpain, apoptosis, prognosis

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Authors: Alexander Heckman, Rohan Goswami, Zachi Attia, Paul Friedman, Peter Noseworthy, Demilade Adedinsewo, Pablo Moreno-Franco, Rickey Carter, Tathagat Narula

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Background: Postoperative atrial fibrillation (POAF) is associated with adverse health consequences, higher costs, and longer hospital stays. Utilizing existing predictive models that rely on clinical variables and circulating biomarkers, multiple societies have published recommendations on the treatment and prevention of POAF. Although reasonably practical, there is room for improvement and automation to help individualize treatment strategies and reduce associated complications. Methods and Results: In this retrospective cohort study of solid organ transplant recipients, we evaluated the diagnostic utility of a previously developed AI-based ECG prediction for silent AF on the development of POAF within 30 days of transplant. A total of 2261 non-cardiac transplant patients without a preexisting diagnosis of AF were found to have a 5.8% (133/2261) incidence of POAF. While there were no apparent sex differences in POAF incidence (5.8% males vs. 6.0% females, p=.80), there were differences by race and ethnicity (p<0.001 and 0.035, respectively). The incidence in white transplanted patients was 7.2% (117/1628), whereas the incidence in black patients was 1.4% (6/430). Lung transplant recipients had the highest incidence of postoperative AF (17.4%, 37/213), followed by liver (5.6%, 56/1002) and kidney (3.6%, 32/895) recipients. The AUROC in the sample was 0.62 (95% CI: 0.58-0.67). The relatively low discrimination may result from undiagnosed AF in the sample. In particular, 1,177 patients had at least 1 AI-ECG screen for AF pre-transplant above .10, a value slightly higher than the published threshold of 0.08. The incidence of POAF in the 1104 patients without an elevated prediction pre-transplant was lower (3.7% vs. 8.0%; p<0.001). While this supported the hypothesis that potentially undiagnosed AF may have contributed to the diagnosis of POAF, the utility of the existing AI-ECG screening algorithm remained modest. When the prediction for POAF was made using the first postoperative ECG in the sample without an elevated screen pre-transplant (n=1084 on account of n=20 missing postoperative ECG), the AUROC was 0.66 (95% CI: 0.57-0.75). While this discrimination is relatively low, at a threshold of 0.08, the AI-ECG algorithm had a 98% (95% CI: 97 – 99%) negative predictive value at a sensitivity of 66% (95% CI: 49-80%). Conclusions: This study's principal finding is that the incidence of POAF is rare, and a considerable fraction of the POAF cases may be latent and undiagnosed. The high negative predictive value of AI-ECG screening suggests utility for prioritizing monitoring and evaluation on transplant patients with a positive AI-ECG screening. Further development and refinement of a post-transplant-specific algorithm may be warranted further to enhance the diagnostic yield of the ECG-based screening.

Keywords: artificial intelligence, atrial fibrillation, cardiology, transplant, medicine, ECG, machine learning

Procedia PDF Downloads 137

Authors: Yulistiani Yulistiani, Wenny Nilamsari, Laurin Winarso, Rizkiya Rizkiya, Zamrotul Izzah, Budi Suprapti, Arif Bachtiar

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Approximately, a million new cases of TB have been found out per year, making Indonesia as the second greatest country with TBC after India. Nevertheless, until now, there are still many patients failure to conventional therapy with oral anti tuberculosis. Thus, the discovery of supplement therapy is urgently needed. Many studies showed that probiotic had the positive impact in lung diseases, diarrhea, pneumonia and it was attributed to its capability to balance the level of cytokine pro-inflammatory and anti-inflammatory. It was demonstrated in active disease the production of IFN-γ is strongly depressed and IL-10 level increases. This study aimed to investigate the effect of probiotic (multi strains) and vitamin B complex supplementation on IFN-γ and IL-10 level in patients with TB infection during intensive phase therapy. A randomized controlled trial, open labeled was conducted in TB patients with the following criteria: 1) age 18-55 years old 2) receiving oral antituberculosis during intensive therapy 3) not using probiotic, vitamin B1, B6, B12 2 weeks before enrollment 4) willing to participate in this study and signed an informed consent. While, patients with HIV, pregnant, had the history of diabetes mellitus, using corticosteroid or other immunosuppressants were excluded. IFN-γ and IL-10 levels were drawn before observation and after a month observation. The assay was performed by ELISA. There were seven patients in treated group and five patients in controlled group obtained in this study. Between groups, there was no statistical difference in comorbid, age, and disease duration. The mean level of IFN-γ after a month observation increased in treated group and controlled group, which were 31.47 ± 105.46 pg/ml and 15.09 ± 24.23 pg/ml, respectively (p> 0.005). Although, there were not statistically different, treated group showed a greater increase of IFN-γ level than that of the controlled group. IFN-γ plays an important role in immune response to Mycobacterium Tuberculosis, by activating macrofag, monosit and furthermore killing Mycobacterium Tuberculosis. Thus the level was expected to increase after supplementation with probiotic and Vitamin B complex. While the mean level of IL-10 also increased after one month observation in the treated group and controlled group (4.28 ± 12.29 pg/ml and 5.77± 6.21 pg/ml, respectively) (p>0.005). To be compared, the increased level of IL-10 in the treated group were lower than the controlled group, although it was not statistically different. IL-10 is a cytokine anti-inflammatory, thus, the level after the observation was expected to decrease. In this study, a month therapy of probiotic and vitamin B complex was not able to demonstrate the decrease of the IL-10 level. It is suggested to prolong observation up to 2 months, because, in intensive phase, the level of cytokine anti-inflammatory is very high, so the longer therapy is needed. It is indicated that supplementation therapy with probiotic and vitamin B complex to Oral Anti-Tuberculosis may have a positive effect on increasing IFN-γ level and slowing the progression of IL-10.

Keywords: TB Infection, IFN-γ, IL-10, probiotic, vitamin B complex

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Authors: Shilu Deepa Thomas, P. Jayaprakash, Dorota Łazewska, Katarzyna Kieć-Kononowicz, B. Sadek

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A large body of evidence suggests the involvement of cognitive impairment, increased levels of inflammation and oxidative stress in the pathogenesis of autism spectrum disorder (ASD). ASD commonly coexists with psychiatric conditions like anxiety and cognitive challenges, and individuals with ASD exhibit significant levels of inflammation and immune system dysregulation. Previous Studies have identified elevated levels of pro-inflammatory markers such as IL-1β, IL-6, IL-2 and TNF-α, particularly in young children with ASD. The current therapeutic options for ASD show limited effectiveness, signifying the importance of exploring an efficient drugs to address the core symptoms. The role of histamine H3 receptors (H3Rs) in memory and the prospective role of H3R antagonists in pharmacological control of neurodegenerative disorders, e.g., ASD, is well-accepted. Hence, the effects of chronic systemic administration of H3R antagonist E159 on autistic-like repetitive behaviors, social deficits, memory and anxiety parameters, as well as neuroinflammation in Black and Tan BRachyury (BTBR) mice, were evaluated using Y maze, Barnes maze, self-grooming, open field and three chamber social test. E159 (2.5, 5 and 10 mg/kg, i.p.) dose-dependently ameliorated repetitive and compulsive behaviors by reducing the increased time spent in self-grooming and improved reduced spontaneous alternation in BTBR mice. Moreover, treatment with E159 attenuated disturbed anxiety levels and social deficits in tested male BTBR mice. Furthermore, E159 attenuated oxidative stress by significantly increasing GSH, CAT, and SOD and decreasing the increased levels of MDA in the cerebellum as well as the hippocampus. In addition, E159 decreased the elevated levels of proinflammatory cytokines (tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), and IL-6). The observed results show that H3R antagonists like E159 may represent a promising novel pharmacological strategy for the future treatment of ASD.

Keywords: histamine H3 receptors, antagonist E159, autism, behaviors, mice

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Authors: Kyung Jin Kim, Jiwon Kwak, Jae-Hoon Lee, Soo Suk Lee

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MicroRNAs (miRNA) are a class of endogenous, single-stranded, small, and non-protein coding RNA molecules typically 20-25 nucleotides long. They are thought to regulate the expression of other genes in a broad range by binding to 3’- untranslated regions (3’-UTRs) of specific mRNAs. The detection of miRNAs is very important for understanding of the function of these molecules and in the diagnosis of variety of human diseases. However, detection of miRNAs is very challenging because of their short length and high sequence similarities within miRNA families. So, a simple-to-use, low-cost, and highly sensitive method for the detection of miRNAs is desirable. In this study, we demonstrate a novel bi-directional extension (BDE) assay. In the first step, a specific linear RT primer is hybridized to 6-10 base pairs from the 3’-end of a target miRNA molecule and then reverse transcribed to generate a cDNA strand. After reverse transcription, the cDNA was hybridized to the 3’-end which is BDE sequence; it played role as the PCR template. The PCR template was amplified in an SYBR green-based quantitative real-time PCR. To prove the concept, we used human brain total RNA. It could be detected quantitatively in the range of seven orders of magnitude with excellent linearity and reproducibility. To evaluate the performance of BDE assay, we contrasted sensitivity and specificity of the BDE assay against a commercially available poly (A) tailing method using miRNAs for let-7e extracted from A549 human epithelial lung cancer cells. The BDE assay displayed good performance compared with a poly (A) tailing method in terms of specificity and sensitivity; the CT values differed by 2.5 and the melting curve showed a sharper than poly (A) tailing methods. We have demonstrated an innovative, cost-effective BDE assay that allows improved sensitivity and specificity in detection of miRNAs. Dynamic range of the SYBR green-based RT-qPCR for miR-145 could be represented quantitatively over a range of 7 orders of magnitude from 0.1 pg to 1.0 μg of human brain total RNA. Finally, the BDE assay for detection of miRNA species such as let-7e shows good performance compared with a poly (A) tailing method in terms of specificity and sensitivity. Thus BDE proves a simple, low cost, and highly sensitive assay for various miRNAs and should provide significant contributions in research on miRNA biology and application of disease diagnostics with miRNAs as targets.

Keywords: bi-directional extension (BDE), microRNA (miRNA), poly (A) tailing assay, reverse transcription, RT-qPCR

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Authors: Maierhaba Mijiti

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Objective：The aim is to understand the relationship between the expression level of the long-non-coding RNA LINC AC008063 and the clinicopathological parameters of patients with head and neck squamous cell carcinoma (HNSCC), and to clarify the biological function of LINC AC008063 in HNSCC cells. Moreover, it provides a potential biomarker for the diagnosis, treatment, and prognosis evaluation of HNSCC. Methods: The expression level of LINC AC008063 in the HNSCC was analyzed using transcriptome sequencing data from the TCGA (The cancer genome atlas) database. The expression levels of LINC AC008063 in human embryonic lung diploid cells 2BS, human immortalized keratinocytes HACAT, HNSCC cell lines CAL-27, Detroit562, AMC-HN-8, FD-LSC-1, FaDu and WSU-HN30 were determined by real-time quantitative PCR (qPCR). RNAi (RNA interference) was introduced for LINC AC008063 knockdown in HNSCC cell lines, the localization and abundance analysis of LINC AC008063 was determined by RT-qPCR, and the biological functions were examined by CCK-8, clone formation, flow cytometry, transwell invasion and migration assays, Seahorse assay. Results: LINC AC008063 was upregulated in HNSCC tissue (P<0.001), and verified b CCK-8, clone formation, flow cytometry, transwell invasion and migration assays, Seahorse assayy qPCR in HNSCC cell lines. The survival analysis revealed that the overall survival rate (OS) of patients with high LINC AC008063 expression group was significantly lower than that in the LINC AC008063 expression group, the median survival times for the two groups were 33.10 months and 61.27 months, respectively (P=0.002). The clinical correlation analysis revealed that its expression was positively correlated with the age of patients with HNSCC (P<0.001) and positively correlated with pathological state (T3+T4＞T1+T2, P=0.03). The RT-qPCR results showed that LINC AC008063 was mainly enriched in cytoplasm (P=0.01). Knockdown of LINC AC008063 inhibited proliferation, colony formation, migration and invasion; the glycolytic capacity was significantly decreased in HNSCC cell lines (P＜0.05). Conclusion: High level of LINC AC008063 was associated with the malignant progression of HNSCC as well as promoting the important biological functions of proliferation, colony formation, migration and invasion; in particular, the glycolytic capacity was decreased in HNSCC cells. Therefore, LINC AC008063 may serve as a potential biomarker for HNSCC and a distinct molecular target to inhibit glycolysis.

Keywords: head and neck squamous cell carcinoma, oncogene, long non-coding RNA, LINC AC008063, invasion and metastasis

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Authors: Di Luo, Maria Buchberger, Anja Pickhard

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Objectives: The purpose of this study was to assess and compare the diagnostic accuracy of four common morphological approaches, including sonography, computed tomography (CT), positron emission tomography/computed tomography (PET/CT), and magnetic resonance imaging (MRI) for the evaluation of cervical lymph node metastases in head and neck squamous cell carcinoma (HNSCC) patients. Material and Methods: Included in this retrospective study were 26 patients diagnosed with HNSCC between 2010 and 2011 who all underwent sonography, CT, PET/CT, and MRI imaging before neck dissection. Morphological data were compared to the corresponding histopathological results. Statistical analysis was performed with SPSS statistic software (version 26.0), calculating sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for detection of cervical lymph node metastases. Results: The 5-year survival rate of the patient collective was 55.5%.Risk factors for survival included initial primary tumor stage, initial lymph node stage, initial metastasis status, and therapeutic approaches. Cox regression showed initial metastasis status(HR 8.671, 95%CI 1.316-57.123, p=0.025) and therapeutic approaches(HR 6.699, 95%CI 1.746-25.700, p=0.006)to be independent predictive risk factors for survival. Sensitivity was highest for MRI (96% compared to 85% for sonography and 89% for CT and PET/CT). Specificity was comparable with 95 % for CT and 98 % for sonography and PET/CT, but only 68% for MRI. While the MRI showed the least PPV (34%) compared to all other methods (85% for sonography,75% for CT, and 86% for PET/CT), the NPV was comparable in all methods(98-99%). The overall accuracy of cervical lymph node metastases detection was comparable for sonography, CT, and PET/CT with 96%,97%,94%, respectively, while MRI had only 72% accuracy. Conclusion: Since the initial status of metastasis is an independent predictive risk factor for patients’ survival, efficient detection is crucial to plan adequate therapeutic approaches. Sonography, CT, and PET/CT have better diagnostic accuracy than MRI for the evaluation of cervical lymph node metastases in HNSCC patients.

Keywords: cervical lymph node metastases, diagnostic accuracy, head and neck squamous carcinoma, risk factors, survival

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Authors: Diwei Lin, Amanda Tan, Rajinder Singh-Rai

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

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

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