Search results for: in vitro and in vivo cancer therapy

Authors: Emmanouel Koumoulas, Aikaterini Rokkou, Marios Moschakis

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Theagenio" in Thessaloniki exists and works for three centuries now as a hospital. Since 1975, it has been operating as an Integrated Special Cancer Hospital and since 1985 it has been integrated into the National Health System. "Theagenio" Cancer Hospital is located at the central web of Thessaloniki residential complex and consists of two buildings, the "Symeonidio Research Center", which was completed in 1962 and the Nursing Ward, a project that was later completed in 1975. This paper examines the design of the Hospital Unit according to the requirements of the energy design of buildings. Initially, the energy characteristics of the Hospital are recorded, followed by a detailed presentation of the electromechanical installations. After the existing situation has been captured and with the help of the software TEE-KENAK, different scenarios for the energy upgrading of the buildings have been studied. Proposals for upgrading concern both the shell, e.g. installation of external thermal insulation, replacement of frames, addition of shading systems, etc. as well as electromechanical installations, e.g. use of ceiling fans, improvements in heating and cooling systems, interventions in lighting, etc. The simulation calculates the future energy status of the buildings and presents the economic benefits of the proposed interventions with reference to the environmental profits that arise.

Keywords: energy consumption in hospitals, energy saving interventions, energy upgrading, hospital facilities

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Authors: Ankan Roy, Niharika, Samir Kumar Patra

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Anomalous nexus of complex topological assemblies and spatiotemporal epigenetic choreography at chromosomal territory may forms the most sophisticated regulatory layer of gene expression in cancer. Colon cancer is one of the leading malignant neoplasms of the lower gastrointestinal tract worldwide. There is still a paucity of information about the complex molecular mechanisms of colonic cancerogenesis. Bioinformatics prediction and analysis helps to identify essential genes and significant pathways for monitoring and conquering this deadly disease. The present study investigates and explores potential hub genes as biomarkers and effective therapeutic targets for colon cancer treatment. Colon cancer patient sample containing gene expression profile datasets, such as GSE44076, GSE20916, and GSE37364 were downloaded from Gene Expression Omnibus (GEO) database and thoroughly screened using the GEO2R tool and Funrich software to find out common 2 differentially expressed genes (DEGs). Other approaches, including Gene Ontology (GO) and KEGG pathway analysis, Protein-Protein Interaction (PPI) network construction and hub gene investigation, Overall Survival (OS) analysis, gene correlation analysis, methylation pattern analysis, and hub gene-Transcription factors regulatory network construction, were performed and validated using various bioinformatics tool. Initially, we identified 166 DEGs, including 68 up-regulated and 98 down-regulated genes. Up-regulated genes are mainly associated with the Cytokine-cytokine receptor interaction, IL17 signaling pathway, ECM-receptor interaction, Focal adhesion and PI3K-Akt pathway. Downregulated genes are enriched in metabolic pathways, retinol metabolism, Steroid hormone biosynthesis, and bile secretion. From the protein-protein interaction network, thirty hub genes with high connectivity are selected using the MCODE and cytoHubba plugin. Survival analysis, expression validation, correlation analysis, and methylation pattern analysis were further verified using TCGA data. Finally, we predicted COL1A1, COL1A2, COL4A1, SPP1, SPARC, and THBS2 as potential master regulators in colonic cancerogenesis. Moreover, our experimental data highlights that disruption of lipid raft and RAS/MAPK signaling cascade affects this gene hub at mRNA level. We identified COL1A1, COL1A2, COL4A1, SPP1, SPARC, and THBS2 as determinant hub genes in colon cancer progression. They can be considered as biomarkers for diagnosis and promising therapeutic targets in colon cancer treatment. Additionally, our experimental data advertise that signaling pathway act as connecting link between membrane hub and gene hub.

Keywords: hub genes, colon cancer, DNA methylation, epigenetic engineering, bioinformatic predictions

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Authors: Mei-Ling Chan, Jin-Ming Wu, Konstantin V. Kudryavtsev, Jih-Hwa Guh

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Prostate cancer is one of the most common malignant disease in men. KUD983 is an enantiomerically pure β-dipeptide derivative, which may have anti-cancer effects. In the present study, KUD983 exhibits powerful activity against hormone-refractory prostate cancer (HRPC) PC-3 and DU145 cells. The IC50 values of KUD983 in PC-3 and DU145 cells are 0.56±0.07M and 0.50±0.04 M respectively. KUD983 induced G1 arrest of the cell cycle and subsequent apoptosis associated with the down-regulation of several related proteins including cyclin D1, cyclin E and Cdk4, and the de-phosphorylation of RB. The protein expressions of nuclear and total c-Myc protein, which was able to regulate the expression of both cyclin D1 and cyclin E, were significantly suppressed by KUD983. Phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) is an important signaling pathway that influences the energy metabolism, cell cycle, proliferation, survival and apoptosis of cells, and is associated with numerous other signaling pathways. The Western Blot data revealed that KUD983 inhibited PI3K/Akt and mTOR/p70S6K/4E-BP1 pathways. The transient transfection of constitutively active myristylated Akt (myr-Akt) cDNA significantly reversed KUD983-induced caspase activation but did not abolish the suppression of mTOR/p70S6K/4E-BP1 signaling cascade indicating the presence of both Akt-dependent and -independent pathways. Moreover, KUD983-induced effect was collaborated with the down-regulation of anti-apoptotic Bcl-2 members (e.g., Bcl-2, and Mcl-1) and IAP family members (e.g., survivin). Furthermore, KUD983 induced autophagic cell death using confocal microscopic examination, investigating the level of conversion of LC3-I to LC3-II and flow cytometric detection of AVO-positive cells. Taken together, the data suggest that KUD983 is an anticancer β-dipeptide against HRPCs through the inhibition of cell proliferation and induction of apoptotic and autophagic cell death. The suppression of signaling pathways mediated by c-Myc, PI3K/Akt and mTOR/p70S6K/4E-BP1 and the collaboration with down-regulation of Mcl-1 and survivin may indicate the mechanism of KUD983 against HRPC.

Keywords: β-dipeptide, hormone-refractory prostate cancer, mTOR, PI3K/Akt

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Authors: Thabiso M. Sebolai, Victor Mlambo, Solomon Tefera, Othusitse R. Madibela

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In some tree species, sustained herbivory can induce changes in biosynthetic pathways resulting in overproduction of anti-nutritional secondary plant compounds. This inductive mechanism, which has not been demonstrated in semi-arid rangelands of South Africa, may result in browse leaves of lower nutritive value. In this study we investigate the interactive effect of browsing pressure and tree species on chemical composition, buffer nitrogen solubility index (NSI), in vitro ruminal dry matter degradability (IVDMD) and in vitro ruminal N degradability (IVND) of leaves. Leaves from Maytenus capitata, Olea africana, Coddia rudis, Carissa macrocarpa, Rhus refracta, Ziziphus mucronata, Boscia oliedes, Grewia robusta, Phyllanthus vessucosus and Ehretia rigida trees growing in a communal grazing area were harvested at two heights: browsable ( < 1.5 m) and non-browsable ( > 1.5 m), representing high and low browsing pressure, respectively. The type of animals utilizing the communal rangeland includes cattle at 1 livestock unit (450kg)/12 to 15 hectors and goats at 1 livestock unit/4 ha. Harvested leaves were dried, milled and analysed for proximate components, soluble phenolics, condensed tannins, minerals and in vitro ruminal fermentation. A significant plant species and harvesting height interaction effect (P < 0.05) was observed for total nitrogen (N) and soluble phenolics concentration. Tree species and harvesting height affected (P < 0.05) condensed tannin (CTs) content where samples harvested from the non-browsable height had higher (0.61 AU550 nm/200 mg) levels than those harvested at browsable height (0.55 AU550 nm/200 mg) while their interaction had no effects. Macro and micro-minerals were only influenced (P < 0.05) by browse species but not harvesting height. Species and harvesting height interacted (P < 0.05) to influence IVDMD and IVND of leaves at 12, 24 and 36 hours of incubation. The different browse leaves contained moderate to high protein, moderate level of phenolics and minerals, suggesting that they have the potential to provide supplementary nutrients for ruminants during the dry seasons.

Keywords: browse plants, chemical composition, harvesting heights, phenolics

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Authors: A. Watson, G. Telford, D. I. Pritchard

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Objective: We investigated the immunomodulatory ability of licorice (Glycyrrhiza glabra). Such activities could have value for the management of common immunological diseases in dogs, such as environmental allergy. This study investigated the potential of a Licorice root extract (LRE) to influence the relative expression of Th-1, Th-2, and Th-17 cytokines in canine peripheral blood mononuclear cells (PBMC). Methods: A LRE was prepared using an alcoholic-aqueous-based solvent method. The extract was tested in three in vitro assays using canine leukocytes to determine its toxicity and immunoregulatory profile. Extract toxicity was assessed using the human T-lymphocyte cell line, Jurkat E6.1. The impact of the extract on the proliferation of concanavalin-activated canine PBMC was also determined. Finally, the extract was assessed for its ability to influence cytokine release in activated PBMC, measuring culture medium concentrations of interleukin-17, interferon gamma, and interleukin-4. One-way ANOVA followed by Dunnett’s post-test was used for statistics using concanavalin positive control as reference (p ≤ 0.05). Results: There was evidence that the LRE had specific immunomodulatory properties, causing significant inhibition of IL4 expression over a non-toxic/non-cytostatic concentration range (p < 0.001). In the same cell incubations, there was no significant impact on IL17 nor IFNg over the same non-toxic/non-cytostatic concentration range. Conclusion: The study provides in vitro evidence that LRE preferentially reduces the expression of a Th-2-type cytokine, IL4. The dog population, as with humans, is prone to conditions associated with a Th-2 bias of the immune system, such as environmental allergy. Based on these results, licorice merits further evaluation as a useful immune modulator for such allergic diseases.

Keywords: cytokine, Glycyrrhiza glabra, peripheral blood mononuclear cells, T-cell activation

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Authors: Tunca Gul Altuntas, Aziz Baydar, Cemre Acar, Sezen Yılmaz, Tulay Coban

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Free radicals, which are generated in many bioorganic redox processes, play a role in the pathogenesis of several diseases including cancer, arthritis, hemorrhagic shock, inflammatory, cardiovascular, neurodegenerative diseases and age-related degenerative brain diseases. Exposures of normal cell to free radical damages several structures, oxidizes nucleic acids, proteins, lipids, or DNA. Compounds interfere with the action of reactive oxygen species might be useful in prevention and treatment of these pathologies. A series of indole compounds containing piperazine ring were synthesized. Coupling of indole-2-carboxylic acid with monosubstituted piperazines was accomplished with 1,1’-carbonyldiimidazole (CDI) in a good yield. The structures of prepared compounds were verified in good agreement with their 1H NMR (nuclear magnetic resonance), MS (mass spectrophotometry), and IR (infrared spectrophotometry) characteristics. In this work, all synthetized indole derivatives were screened in vitro for their antioxidative potential against vitamin E (α-tocopherol) using different antioxidant assays such as superoxide anion formation, lipid peroxidation levels in rat liver, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) stable radical scavenging activity. The synthesized compounds showed various levels of inhibition compared to vitamin E. This may give promising results for the development of new antioxidant agents.

Keywords: antioxidant, indoles, piperazines, reactive oxygen species

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Authors: Sutinon Yuchomsuk, Satchachon Changthom, Pruet Areesawangvong, Monsiri Jinapen

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Background: Esophageal squamous cell carcinoma can be presented with many symptoms, such as dysphagia or weight loss. However, in some circumstances, rare presentations can be found, e.g., dyspnea, which is more common in pulmonary malignancy. And dyspnea is also one of the most common presentations of COVID-19 infection. So, in this case, we can learn from many points in patient symptoms and findings leading to the diagnosis of esophageal squamous cell carcinoma. Method: This research is a case-report study including one patient from Mahasarakham Hospital, Thailand. Data were collected during December 2021. Result: A 55-year-old Thai male patient with an unknown past medical history presented with dyspnea and shortness of breath for the duration of three days prior to admission. His symptom also included cough, fever, and sore throat. Laboratory results indicated that the patient had COVID-19 pneumonia. Further investigation showed that he had cardiac tamponade and suspected pulmonary/esophageal cancer. Lung biopsy and pericardiocentesis were done, which were positive for carcinoma from pericardial effusion but negative for malignancy from the lung biopsy. Later esophagogastroduodenoscopy was done with endoscopic tissue biopsy; the result was positive for squamous cell carcinoma of the esophagus. Conclusion: Most commonly, esophageal cancer is presented with dysphagia or weight loss. However, in some rare cases, patients can also be presented with dyspnea due to cardiac tamponade. And in recent years, COVID-19 has become a pandemic all over the world, sometimes masking symptoms of other diseases. Such as in this case, the patient didn’t improve after the pneumonia was resolved, which led to the final diagnosis of metastatic esophageal cancer.

Keywords: esophageal cancer, cardiac tamponade, metastatic squamous cell carcinoma, COVID-19 infection

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Authors: Burcu Babadağ Savaş, Nihal Orlu, Güler Balcı Alparslan, Ertuğrul Çolak, Cengiz Korkmaz

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Introduction/objectives: We aimed to investigate the effect of humor on pain and state anxiety in patients with rheumatoid arthritis (RA) receiving biologic intravenous (IV) infusion therapy. Method: The study sample consisted of 36 patients who met the classification criteria for RA and inclusion criteria in a rheumatology outpatient clinic at a university hospital between September 2020 and November 2021. Two sample groups were formed: the intervention group (watching a comedy movie) (n=18) and the control group (n=18). The intervention group consisted of the patient watching a comedy movie of his/her choice from an archive created by the researchers during the biological IV infusion therapy (approximately 90-120 minutes). The data collection instruments used before and after the test were the descriptive identification form, the visual analog scale (VAS), and the state anxiety scale. Results: The mean VAS scores of patients in the intervention group were 5.05 ± 2.01 in the pre-test and 2.61 ± 1.91 in the post-test. The mean state anxiety scores of patients in the intervention group were 45.94 ± 9.97 in the pre-test and 34.22 ± 6.57 in the post-test. Thus, patients who watched comedy movies during biologic IV infusion therapy in the infusion center had a greater reduction in pain scores than the control group and the effect size was small. Although there was a decrease in state anxiety scores in both groups, there was no significant difference between groups and the effect size was not relevant. Conclusions: During IV infusion therapy, watching comedy movies is recommended as a nursing care intervention for reducing pain in patients with RA in cooperation with other health professionals.

Keywords: watching comedy movie, humor, pain, anxiety, nursing, care

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Authors: Naouel Boussoualim, Hayat Trabsa, Imane Krache, Seddik Khennouf, Noureddine Charef, Lekhmici Arrar, Abderrahmane Baghiani

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Purpose: To evaluate the in-vitro inhibition of xanthine oxidase (purified from bovine milk) by extracts of Lycium arabicum, as well as it is in vivo hypouricemic and renal protective effects. Methods: Four extracts of Lycium arabicum, methanol (CrE), chloroform (ChE), ethyl acetate (EaE) and aqueous (AqE) extracts, were screened for their total phenolics and potential inhibitory effects on purified bovine milk xanthine oxidase (XO) activity by measuring the formation of uric acid or superoxide radical. The mode of inhibition was investigated and compared with the standard drugs, allopurinol, quercitin, and catechin. To evaluate their hypouricemic effect, the extracts were administered to potassium oxonate-induced hyperuricemic mice at a dose of 50 mg/kg body weight. Results: The results showed that EaE had the highest content of phenolic compounds and was the most potent inhibitor of uric acid formation (IC50 = 0.017 ± 0.001 mg/mL) and formation of superoxide (IC50 = 0.035 ± 0.001 mg/ml). Lineweaver-Burk analysis showed that CrE and EaE inhibited XO competitively, whereas the inhibitory activities exerted by ChE and AqE were of a mixed type. Intraperetoneal injection of L. arabicum extracts (50 mg/kg) elicited hypouricemic actions in hyperuricemic mice. Hyperuricemic mice presented a serum uric acid concentration of 4.71 ± 0.29 mg/L but this was reduced to 1.78 ± 0.11 mg/L by EaE, which was the most potent hyporuricemic extract. Conclusion: L. arabicum fractions have a strong inhibitory effect on xanthine oxidase and and also have a significantly lowering effect on serum and liver creatinine and urea levels in hyperuricemic mice.

Keywords: lycium arabicum, uric acid, creatinine, superoxide, phenolic compounds, flavonoids, hyperuricemia

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Authors: Asiya Mahtab, Sushama Talegaonkar

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The research is aimed at developing targeted lipid-based nanocarrier systems of chondroitin sulfate (CS) to deliver an antirheumatic drug to the inflammatory site in arthritic paw. Lipid-based nanoparticle (TEF-lipo) was prepared by using a thin-film hydration method. The coating of prepared drug-loaded nanoparticles was done by the ionic interaction mechanism. TEF-lipo and CS-coated lipid nanoparticle (CS-lipo) were characterized for mean droplet size, zeta potential, and surface morphology. TEF-lipo and CS-lipo were further subjected to in vitro cell line studies on RAW 264.7 murine macrophage, U937, and MG 63 cell lines. The pharmacodynamic study was performed to establish the effectiveness of the prepared lipid-based conventional and targeted nanoparticles in comparison to pure drugs. Droplet size and zeta potential of TEF-lipo were found to be 128. 92 ± 5.42 nm and +12.6 ± 1.2 mV. It was observed that after the coating of TEF-lipo with CS, particle size increased to 155.6± 2.12 nm and zeta potential changed to -10.2± 1.4mV. Transmission electron microscopic analysis revealed that the nanovesicles were uniformly dispersed and detached from each other. Formulations followed sustained release pattern up to 24 h. Results of cell line studies ind icated that CS-lipo formulation showed the highest cytotoxic potential, thereby proving its enhanced ability to kill the RAW 264.7 murine macrophage and U937 cells when compared with other formulations. It is clear from our in vivo pharmacodynamic results that targeted nanocarriers had a higher inhibitory effect on arthritis progression than nontargeted nanocarriers or free drugs. Results demonstrate that this approach will provide effective treatment for rheumatoid arthritis, and CS served as a potential prophylactic against the advancement of cartilage degeneration.

Keywords: adjuvant induced arthritis, chondroitin sulfate, rheumatoid arthritis, teriflunomide

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Authors: Zahra Dehghani, Hoda Dehghani, Elham Zarenezhad

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1,2,3-Triazole derivatives are important compounds in medicinal chemistry owing to their wide applications in drug discovery. They can readily associate with biologically targets through the hydrogen bonding and dipole interactions. The 1,2,3-triazole core is a key structural motif in many bioactive compounds, exhibiting a broad spectrum of biological activities, such as antiviral, anticancer, anti-HIV, antibiotic, antibacterial, and antimicrobial. Additionally, they have found significant industrial applications as dyes, agrochemicals, corrosion inhibitors, photo stabilizers, and photographic materials. we disclose the synthesis and characterization of 1-azido-3-(aryl-2-yloxy)propan-2-ol drivatives. The chemistry works well with various ß-azido alcohols involving aryloxy, alkoxy and alkyl residues, and also tolerates a wide spectrum of electron-donating and electron-withdrawing functional groups in both alkyne and azide molecules. Most of ß-azidoalcohols used in these experiments were pre-synthesized by the regioselective ring opening reaction of corresponded epoxides with sodium azide, whereas the majority of terminal alkynes were prepared via SN2-type reaction of propargyl bromide and corresponded nucleophiles. To evaluate the bioactivity of title compounds, the in vitro antifungal activity of all compound was investigated against several pathogenic fungi including Candida albicans, Candida krusei, Aspergillus niger, and Trichophyton rubrum , clotrimazole and fluconazole was used as standard antifungal drugs, also To understand the antibacterial activity of synthesized compounds, they were in vitro screened against E. coli and S. aureus as Gram-negative and Gram-positive bacteria, respectively. The in vitro tests have shown the promising antifungal but marginal antibacterial activity against tested fungi and bacteria.

Keywords: biological activities, antibacterial, antifungal, 1, 2, 3-Triazole

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Authors: Djebbar Atmani, Dina Kilani, Tristan Richard

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Medicinal plants are an important source for the discovery of potential new substances for use in medicine and food. Pistacia lentiscus, Fraxinus angustifolia and Clematis flammula, plants growing in the Mediterranean basin, are widely used in traditional medicine. Therefore, the present study was designed to investigate their antioxidant, anti-inflammatory, antidiabetic, anti-mutagenic/genotoxic and neuroprotective potential and identification of active compounds using appropriate methodology. Plant extracts and fractions exhibited high scavenging capacity against known radicals, enhanced superoxide dismutase and catalase activitiesand restored blood glucose levels, in vivo, to normal values, in agreement with the in vitro enzymatic inhibition data, through inhibition of amylase and glucosidase activities. Administration of Pistacia lentiscus extracts significantly decreased carrageenan-induced mice paw oedema and reduced effectively IL-1β levels in cell culture, whereas Fraxinus angustifolia extracts showed good healing capacity against wounds when applied topically on rabbits. Pistacia lentiscus and Fraxinus angustifolia extracts showed good neuro-protection and restored cognitive functions in mice, while Clematis flammula extracts showed potent anti-ulcerogenic activity associated to a promising anti-mutagenic/genotoxic activity. HPLC-MS and NMR analyses allowed the identification and structural elucidation of several known and new anthocyanins, flavonols and flavanols. Therefore, Pistacia lentiscus, Fraxinus angustifolia and Clematis flammulacould be used in palliative treatments against inflammatory conditions and diabetes complications, as well as against deterioration of cognitive functions.

Keywords: pistacia lentiscus, clematis flammula, fraxinus angustifolia, phenolic compounds, biological activity

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Authors: Anne-Loes K. Warps, Rob A. E. M. Tollenaar, Pieter J. Tanis, Jan Willem T. Dekker

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Anastomotic leakage after colorectal cancer surgery remains a severe complication. Early diagnosis and treatment are essential to prevent further adverse outcomes. In the literature, it has been suggested that earlier reintervention is associated with better survival, but anastomotic leakage can occur with a highly variable time interval to index surgery. This study aims to evaluate the time-interval between rectal cancer resection with primary anastomosis creation and reoperation, in relation to short-term outcomes, stratified for the use of a defunctioning stoma. Methods: Data of all primary rectal cancer patients that underwent elective resection with primary anastomosis during 2013-2019 were extracted from the Dutch ColoRectal Audit. Analyses were stratified for defunctioning stoma. Anastomotic leakage was defined as a defect of the intestinal wall or abscess at the site of the colorectal anastomosis for which a reintervention was required within 30 days. Primary outcomes were new stoma construction, mortality, ICU admission, prolonged hospital stay and readmission. The association between time to reoperation and outcome was evaluated in three ways: Per 2 days, before versus on or after postoperative day 5 and during primary versus readmission. Results: In total 10,772 rectal cancer patients underwent resection with primary anastomosis. A defunctioning stoma was made in 46.6% of patients. These patients had a lower anastomotic leakage rate (8.2% vs. 11.6%, p < 0.001) and less often underwent a reoperation (45.3% vs. 88.7%, p < 0.001). Early reoperations (< 5 days) had the highest complication and mortality rate. Thereafter the distribution of adverse outcomes was more spread over the 30-day postoperative period for patients with a defunctioning stoma. Median time-interval from primary resection to reoperation for defunctioning stoma patients was 7 days (IQR 4-14) versus 5 days (IQR 3-13 days) for no-defunctioning stoma patients. The mortality rate after primary resection and reoperation were comparable (resp. for defunctioning vs. no-defunctioning stoma 1.0% vs. 0.7%, P=0.106 and 5.0% vs. 2.3%, P=0.107). Conclusion: This study demonstrated that early reinterventions after anastomotic leakage are associated with worse outcomes (i.e. mortality). Maybe the combination of a physiological dip in the cellular immune response and release of cytokines following surgery, as well as a release of endotoxins caused by the bacteremia originating from the leakage, leads to a more profound sepsis. Another explanation might be that early leaks are not contained to the pelvis, leading to a more profound sepsis requiring early reoperations. Leakage with or without defunctioning stoma resulted in a different type of reinterventions and time-interval between surgery and reoperation.

Keywords: rectal cancer surgery, defunctioning stoma, anastomotic leakage, time-interval to reoperation

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Authors: K. Shailaja

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The advanced glycation end products (AGEs) formed between the reducing sugar and protein as a result of Oxidative stress and non-enzymatic glycosylation play an important role in pathogenesis of diabetes and aging complication. Glycation results in the production of free radicals. The oxidation process is believed to play an important role in AGEs formation. Thus agents with antioxidative property and antiglycation activity may retard the process of AGEs formation. Selected medicinal plants for the present study include Catharanthus roseus, Bougainvillea spectabilis (pink flowers), Cinnamomum tamala, Cinnamomum zeylanica, Abutilon indicum, Asparagus racemosus, and Sapindus emarginatus. The crude ethanolic extracts of the selected medicinal plants at varying concentrations ranging from 1-100 mg/ml were evaluated for in vitro antioxidant and protein glycation activities by FRAP and glucose-BSA assay respectively. Among all the plants tested, Bougainvillea spectabilis, Catharanthus roseus and Abutilon indicum showed strong antioxidant activity The antioxidant activity was expressed as mg of Gallic acid/ gm sample which was found to be 4.3 mg, 1.3mg, and 1.3mg respectively for Bougainvillea spectabilis, Catharanthus roseus and Abutilon indicum. The results of inhibition of the initial glycation product i.e., fructosamine was found to be 35% for Asparagus racemosus, Cinnamomum tamala and Abutilon indicum followed by the other plant extracts. The results indicate that these plants are potential sources of natural antioxidants which have free radical scavenging activity and might be used not only for reducing oxidative stress in diabetes but also open a new research avenues in the field of Natural Products.

Keywords: in vitro antioxidant activity, anti-glycation activity, ethanol extracts, polyphenols, Catharanthus roseus, Cinnamomum tamala

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Authors: Chi-Jung Chung, Chao-Hsiang Chang, Chiu-Shong Liu, Sheng-Wei Li, Mu-Chi Chung, Ting-Jie Wen, Hui-Ling Lee

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Cigarette smoke contains volatile organic compounds (VOCs), such as acrylamide, 1,3-butadiene, and benzene. This study aimed to explore the associations between the urinary levels of cotinine and VOC metabolites and the risk of urothelial carcinoma (UC). A hospital-based case–control study involving two groups matched on the basis of age ( ± 3 years) and gender was designed. UC was clinically diagnosed through urological examinations and pathologically verified. Smoking-related information was collected through questionnaires and face-to-face interviews with all study participants. Urine samples were collected for the analysis of the urinary levels of VOC metabolites, cotinine, and 8-hydroxydeoxygua- nosine (8-OHdG), which was selected as a proxy of oxidative stress. Multiple logistic regressions were applied to estimate the risk of UC. The urinary cotinine and 8-OHdG levels of the UC group were higher than those of the control group. The urinary levels of VOC metabolites, including N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA), N- acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine, N-acetyl-S- (4- hydroxy-2-buten-1-yl)-Lcysteine-3, trans, trans-muconic acid (t,t- MA), and S-phenylmercapturic acid (SPMA) increased as the urinary levels of cotinine increased. Relevant dose-response relationships between the risk of UC risk and the urinary levels of AAMA , t,t-MA, SPMA, and 8-OHdG were found after adjusting for potential risk factors. The UC risk of participants with high urinary levels of cotinine, AAMA, t,t-MA, SPMA, and 8-OHdG were 3.5–6-fold higher than those of other participants. Increased urinary levels of VOC metabolites were associated with smoking-related UC risk. The development of UC should be explored in large-scale in vitro or in vivo studies with the repeated measurement of VOC metabolites.

Keywords: volatile organic compound, urothelial carcinoma, cotinine, 8-hydroxydeoxyguanosine

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Authors: Dipali Nagaonkar, Mahendra Rai

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Chitosan, a carbohydrate polymer at nanoscale level has gained considerable momentum in drug delivery applications due to its inherent biocompatibility and non-toxicity. However, conventional synthetic strategies for chitosan nanoparticles mainly rely upon physicochemical techniques, which often yield chitosan microparticles. Hence, there is an emergent need for development of controlled synthetic protocols for chitosan nanoparticles within the nanometer range. In this context, we report the green synthesis of size controlled chitosan nanoparticles by using Pongamia pinnata (L.) leaf extract. Nanoparticle tracking analysis confirmed formation of nanoparticles with mean particle size of 85 nm. The stability of chitosan nanoparticles was investigated by zetasizer analysis, which revealed positive surface charged nanoparticles with zeta potential 20.1 mV. The green synthesized chitosan nanoparticles were further explored for encapsulation and controlled release of antioxidant biomolecule, quercetin. The resulting drug loaded chitosan nanoparticles showed drug entrapment efficiency of 93.50% with drug-loading capacity of 42.44%. The cumulative in vitro drug release up to 15 hrs was achieved suggesting towards efficacy of green synthesized chitosan nanoparticles for drug delivery applications.

Keywords: Chitosan nanoparticles, green synthesis, Pongamia pinnata, quercetin

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Authors: M. R. Vijayakumar, K. Priyanka, Ramoji Kosuru, Lakshmi, Sanjay Singh

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Trans resveratrol (RES) is a non-flavonoid poly-phenolic compound proved for its therapeutic and preventive effect against various types of cancer. However, the practical application of RES in cancer treatment is limited because of its higher dose (up to 7.5 g/day in humans), low biological half life, rapid metabolism and faster elimination in mammals. PEGylated core-shell type lipid polymer hybrid nanoparticles are the novel drug delivery systems for long circulation and improved anti cancer effect of its therapeutic payloads. Therefore, the main objective of this study is to extend the biological half life (long circulation) and improve the therapeutic efficacy of RES through core shell type of nanoparticles. D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS), a novel surfactant is applied for the preparation of PEGylated lipid polymer hybrid nanoparticles. The prepared nanoparticles were evaluated by various state of the art techniques such as dynamic light scattering (DLS) technique for particle size and zeta potential, TEM for shape, differential scanning calorimetry (DSC) for interaction analysis and XRD for crystalline changes of drug. Entrapment efficiency and invitro drug release were determined by ultracentrifugation method and dialysis bag method, respectively. Cancer cell viability studies were performed by MTT assay, respectively. Pharmacokinetic studies after i.v administration were performed in sprague dawley rats. The prepared NPs were found to be spherical in shape with smooth surfaces. Particle size and zeta potential of prepared NPs were found to be in the range of 179.2±7.45 to 266.8±9.61 nm and -0.63 to -48.35 mV, respectively. DSC revealed absence of potential interaction. XRD study revealed presence of amorphous form in nanoparticles. Entrapment efficiency was found to be 83.7 % and drug release was found to be in controlled manner. MTT assay showed low MEC and pharmacokinetic studies showed higher AUC of nanoformulaition than its pristine drug. All these studies revealed that the RES loaded PEG modified core-shell type lipid polymer hybrid nanoparticles can be an alternative tool for chemopreventive and therapeutic application of RES in cancer.

Keywords: trans resveratrol, cancer nanotechnology, long circulating nanoparticles, bioavailability enhancement, core shell nanoparticles, lipid polymer hybrid nanoparticles

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Authors: Sally Shepherd, Richard De Boer, Craig Murphy

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Background: Invasive lobular carcinoma (ILC) can metastasize to atypical sites within the peritoneal cavity, gastrointestinal, or genitourinary tract. Management varies depending on the symptom presentation, extent of disease burden, particularly if the primary disease is occult, and patient wishes. Case Series: 6 patients presented with general surgical presentations of ILC, including incomplete large bowel obstruction, cholecystitis, persistent lower abdominal pain, and faecal incontinence. 3 were diagnosed with their primary and metastatic disease in the same presentation, whilst 3 patients developed metastasis from 5 to 8 years post primary diagnosis of ILC. Management included resection of the metastasis (laparoscopic cholecystectomy), excision of the primary (mastectomy and axillary clearance), followed by a combination of aromatase inhibitors, biologic therapy, and chemotherapy. Survival post diagnosis of metastasis ranged from 3 weeks to 7 years. Conclusion: Metastatic ILC must be considered with any gastrointestinal or genitourinary symptoms in patients with a current or past history of ILC. Management may not be straightforward to chemotherapy if the acute pathology is resulting in a surgically resectable disease.

Keywords: breast cancer, gastrointestinal metastasis, invasive lobular carcinoma, metastasis

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Authors: B. J. Mahen, N. E. Lloyd-Gale, S. Johnson, W. P. Rakowicz, M. J. Harris, A. D. Miller

Abstract:

Background: Migraine is a leading cause of disability in the world. Calcitonin gene-related peptide (CGRP) receptor antagonists offer an approach to migraine prophylaxis by inhibiting the inflammatory and vasodilatory effects of CGRP. In recent years, NICE licensed the use of three CGRP-receptor antagonists: Fremanezumab, Galcanezumab, and Erenumab. Here, we present the outcomes of CGRP-antagonist treatment in a cohort of patients who suffer from episodic or chronic migraine and have failed at least three oral prophylactic therapies. Methods: We offered CGRP antagonists to 86 patients who met the NICE criteria to start therapy. We recorded the number of headache days per month (HDPM) at 0 weeks, 3 months, and 12 months. Of those, 26 patients were switched to an alternative treatment due to poor response or side effects. Of the 112 total cases, 9 cases did not sufficiently maintain their headache diary, and 5 cases were not followed up at 3 months. We have therefore included 98 sets of data in our analysis. Results: Fremanezumab achieved a reduction in HDPM by 51.7% at 3 months (p<0.0001), with 63.7% of patients meeting NICE criteria to continue therapy. Patients trialed on Galcanezumab attained a reduction in HDPM by 47.0% (p=0.0019), with 51.6% of patients meeting NICE criteria to continue therapy. Erenumab, however, only achieved a reduction in HDPM by 17.0% (p=0.29), and this was not statistically significant. Furthermore, 34.4%, 9.7%, and 4.9% of patients taking Fremanezumab, Galcanezumab, and Erenumab, respectively, continued therapy beyond 12 months. Of those who attempted drug holidays following 12 months of treatment, migraine symptoms relapsed in 100% of cases. Conclusion: We observed a significant improvement in HDPM amongst episodic and chronic migraine patients following treatment with Fremanezumab or Galcanezumab.

Keywords: migraine, CGRP, fremanezumab, galcanezumab, erenumab

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Authors: Mariya Yeldhos, G. Hema, Sowmya Narayanan, L. Dhiviyalakshmi

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Insomnia is one of the most prevalent psychological disorders worldwide. Some of the deficiencies of the current treatments of insomnia are: side effects in the case of sleeping pills and high costs in the case of psychotherapeutic treatment. In this paper, we propose a device which provides a combination of audio visual entrainment and acupressure based compression therapy for insomnia. This device provides drug-free treatment of insomnia through a user friendly and portable device that enables relaxation of brain and muscles, with certain advantages such as low cost, and wide accessibility to a large number of people. Tools adapted towards the treatment of insomnia: -Audio -Continuous exposure to binaural beats of a particular frequency of audible range -Visual -Flash of LED light -Acupressure points -GB-20 -GV-16 -B-10

Keywords: insomnia, acupressure, entrainment, audio-visual entrainment

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Authors: Salim Cerig, Fatime Geyikoglu, Pınar Akpulat, Suat Colak, Hasan Turkez, Murat Bakir, Mirkhalil Hosseinigouzdagani, Kubra Koc

Abstract:

This study was designed to evaluate whether carvacrol (CAR) could provide protection against lung injury by acute pancreatitis development. The rats were randomized into groups to receive (I) no therapy; (II) 50 μg/kg cerulein at 1h intervals by four intraperitoneal injections (i.p.); (III) 50, 100 and 200 mg/kg CAR by one i.p.; and (IV) cerulein+CAR after 2h of cerulein injection. 12h later, serum samples were obtained to assess pancreatic function the lipase and amylase values. The animals were euthanized and lung samples were excised. The specimens were stained with hematoxylin-eosin (H&E), periodic acid–Schif (PAS), Mallory's trichrome and amyloid. Additionally, oxidative DNA damage was determined by measuring as increases in 8-hydroxy-deoxyguanosine (8-OH-dG) adducts. The results showed that the serum activity of lipase and amylase in AP rats were significantly reduced after the therapy (p<0.05). We also found that the 100 mg/kg dose of CAR significantly decreased 8-OH-dG levels. Moreover, the severe pathological findings in the lung such as necrosis, inflammation, congestion, fibrosis, and thickened alveolar septum were attenuated in the AP+CAR groups when compared with AP group. Finally, the magnitude of the protective effect on lung is certain, and CAR is an effective therapy for lung injury caused by AP.

Keywords: antioxidant activity, acute pancreatitis, carvacrol, experimental, lung injury, oxidative DNA damage

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Authors: Desta Gebretekle Shiferaw, Balakrishna Kalluraya

Abstract:

Triazoles are basic five-membered ring heterocycles with an unsaturated, six-delocalized electron ring system. Since the dawn of click chemistry, triazoles have represented a functional heterocyclic core that has been the foundation of medicinal chemistry. The compounds with 1,2,3-triazole rings can be used in several fields, including medicine, organic synthesis, polymer chemistry, fluorescent imaging, horticulture, and industries, to name a few. Besides that, they found it to have health applications in the prevention and reduction of the risk of diseases, such as anti-cancer, antimicrobial, antiviral, and anti-inflammatory properties. Here, we present the synthesis of twelve 1,2,3-triazolyl chalcone derivatives (4a–l), which were produced in high yields by coupling substituted aldehydes and triazolyl acetophenone (3a–d) in ethanol. The title products were characterized by physicochemical, infrared, nuclear magnetic resonance, and mass spectral methods. The in vitro tests were used to evaluate the antioxidant and antimicrobial activity of each of the prepared molecules. The preliminary assessment and 2,2-diphenyl-1-picrylhydrazyl activity of the title compounds showed significantly higher antibacterial activity and moderate-to-good antifungal and antioxidant activities compared to their standards. This work presents the synthesis of triazolyl chalcone derivatives and their biological activity. Based on the findings, these compounds could be used as lead compounds in antimicrobial and antioxidant research in the future.

Keywords: antibacterial activity, antifungal activity, antioxidant activity, chalcone, 1, 2, 3-triazole

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Authors: Honey Bryant, Elvina Chu

Abstract:

Stroke is the leading cause of disability in adults in Canada and directly related to depression, anxiety, and sleep disorders; with an estimated annual cost of $50 billion in health care. Strokes not only impact the individual but society as a whole. Current stroke rehabilitation does not include Music Therapy, although it has success in clinical research in the use of stroke rehabilitation. This study examines the use of neurologic music therapy (NMT) in conjunction with stroke rehabilitation to improve sleep quality, reduce stress levels, and promote neurogenesis. Existing research on NMT in stroke is limited, which means any conclusive information gathered during this study will be significant. My novel hypotheses are a.) stroke patients will become less depressed and less anxious with improved sleep following NMT. b.) NMT will reduce stress levels and promote neurogenesis in stroke patients admitted for rehabilitation. c.) Beneficial effects of NMT will be sustained at least short-term following treatment. Participants were recruited from the in-patient stroke rehabilitation program at Providence Care Hospital in Kingston, Ontario, Canada. All participants-maintained stroke rehabilitation treatment as normal. The study was spilt into two groups, the first being Passive Music Listening (PML) and the second Neurologic Music Therapy (NMT). Each group underwent 10 sessions of intensive music therapy lasting 45 minutes for 10 consecutive days, excluding weekends. Psychiatric Assessments, Epworth Sleepiness Scale (ESS), Hospital Anxiety & Depression Rating Scale (HADS), and Music Engagement Questionnaire (MusEQ), were completed, followed by a general feedback interview. Physiological markers of stress were measured through blood pressure measurements and heart rate variability. Serum collections reviewed neurogenesis via Brain-derived neurotrophic factor (BDNF) and stress markers of cortisol levels. As this study is still on-going, a formal analysis of data has not been fully completed, although trends are following our hypotheses. A decrease in sleepiness and anxiety is seen upon the first cohort of PML. Feedback interviews have indicated most participants subjectively felt more relaxed and thought PML was useful in their recovery. If the hypothesis is supported, larger external funding which will allow for greater investigation of the use of NMT in stroke rehabilitation. As we know, NMT is not covered under Ontario Health Insurance Plan (OHIP), so there is limited scientific data surrounding its uses as a clinical tool. This research will provide detailed findings of the treatment of neuropsychiatric aspects of stroke. Concurrently, a passive music listening study is being designed to further review the use of PML in rehabilitation as well.

Keywords: music therapy, psychotherapy, neurologic music therapy, passive music listening, neuropsychiatry, counselling, behavioural, stroke, stroke rehabilitation, rehabilitation, neuroscience

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Authors: Muhammad Maqsood, Yasir Nawab, Syed Talha Ali Hamdani

Abstract:

Stretchable fabrics have diverse applications ranging from casual apparel to performance sportswear and compression therapy. Compression therapy is the universally accepted treatment for the management of hypertrophic scarring after severe burns. Mostly stretchable knitted fabrics are used in compression therapy but in the recent past, some studies have also been found on bi-stretch woven fabrics being used as compression garments as they also have been found quite effective in the treatment of oedema. Therefore, the objective of the present study is to compare the compression properties of stretchable knitted and bi-stretch woven fabrics for compression garments. For this purpose four woven structures and four knitted structures were produced having the same areal density and their compression, comfort and mechanical properties were compared before and after 5, 10 and 15 washes. Four knitted structures used were single jersey, single locaste, plain pique and the honeycomb, whereas four woven structures produced were 1/1 plain, 2/1 twill, 3/1 twill and 4/1 twill. The compression properties of the produced samples were tested by using kikuhime pressure sensor and it was found that bi-stretch woven fabrics possessed better compression properties before and after washes and retain their durability after repeated use, whereas knitted stretchable fabrics lost their compression ability after repeated use and the required sub garment pressure of the knitted structures after 15 washes was almost half to that of woven bi-stretch fabrics.

Keywords: compression garments, knitted structures, medical textiles, woven bi-stretch

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Authors: Kyra Kannen, Sonja D. Roelen, Sebastian Schnieder, Jarek Krajewski, Steffen Holsteg, André Karger, Johanna Askeridis, Celina Slawik, Philip Mildner, Jens Piesk, Ruslan David, Holger Kürten, Benjamin Oster, Robert Malzan, Mike Ludemann

Abstract:

Virtual Reality (VR) is increasingly recognized for its potential in transforming mental disorder treatment, offering advantages such as cost-effectiveness, time efficiency, accessibility, reduced stigma, and scalability. While the application of VR in the context of anxiety disorders has been extensively evaluated and demonstrated to be effective, the utilization of VR as a therapeutic treatment for depression remains under-investigated. Our goal is to pioneer immersive VR therapy modules for treating major depression, alongside a web-based system for home use. We develop a modular digital therapy platform grounded in psychodynamic therapy interventions which addresses stress reduction, exploration of social situations and relationship support, social skill training, avoidance behavior analysis, and psychoeducation. In addition, an automated depression monitoring system, based on acoustic voice analysis, is implemented in the form of a speech-based diary to track the affective state of the user and depression severity. The use of immersive VR facilitates patient immersion into complex and realistic interpersonal interactions with high emotional engagement, which may contribute to positive treatment acceptance and satisfaction. In a proof-of-concept study, 45 depressed patients were assigned to VR or web-platform modules, evaluating user experience, usability and additional metrics including depression severity, mindfulness, interpersonal problems, and treatment satisfaction. The findings provide valuable insights into the effectiveness and user-friendliness of VR and web modules for depression therapy and contribute to the refinement of more tailored digital interventions to improve mental health.

Keywords: virtual reality therapy, digital health, depression, psychotherapy

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Authors: Rossana Taravella, Gilberto M. Cellura, Giuseppe Cirrincione, Salvatore Asciutto, Marco Caruso, Massimo Benedetto, Renato Ciofalo, Giuliana Pace, Salvatore Novo

Abstract:

Objectives: This retrospective analysis sought to evaluate 1-month outcomes and therapy effectiveness of a population of patients treated with MitraClip therapy. We describe in this article the preliminary results of primary effectiveness endpoint. Background: Percutaneous Mitral Repair is being developed to treat severe mitral regurgitation (MR), with increasing real-world cases of functional MR (FMR). In the EVEREST (Endovascular Valve Edge-to-Edge Repair Study)II trial, the percutaneous device showed superior safety but less reduction in MR at 1year. 4-year outcomes from EVEREST II trial showed no difference in the prevalence of moderate-severe and severe MR or mortality at 4years between surgical mitral repair and percutaneous approach. Methods: We analysed retrospectively collected data from one center experience in Italy enrolled from January 2011 to December 2016. The study included 62 patients [mean age 74±11years, 43 men (69%)] with MR of at least grade3+. Most of the patients had functional MR, were in New York Heart Association (NYHA) functional class III or IV, with a large portion (78%) of mild-to-moderate Tricuspid Regurgitation (TR). One or more clips were implanted in 67 procedures (62 patients). Results and Conclusions: Severity of MR was reduced in all successfully treated patients,54(90%) were discharged with MR≤2+ (primary effectiveness endpoint). Clinical 1-month follow-up data showed an improvement in NYHA functional class (42 patients (70%) in NYHA class I-II). 60 of 62 (97 %) successfully treated patients were free from death and mitral valve surgery at 1-month follow-up. MitraClip therapy reduces functional MR with acute MR reduction to <2+ in the great majority of patients, with a large freedom from death, surgery or recurrent MR in a great portion of patients.

Keywords: MitraClip, mitral regurgitation, heart valves, catheter-based therapy

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Authors: Amira ben Hassine, A. Valverde, V. Serafín, C. Muñoz-San Martín, M. Garranzo-Asensio, M. Gamella, R. Barderas, M. Pedrero, N. Raouafi, S. Campuzano, P. Yáñez-Sedeño, J. M. Pingarrón

Abstract:

This work describes the development of a dual electrochemical immunosensing platform for accurate determination of two target proteins, IL-13 Receptor α2 (IL-13Rα2) and E-cadherin (E-cad). The proposed methodology is based on the use of sandwich immunosensing approaches (involving horseradish peroxidase-labeled detector antibodies) implemented onto magnetic microbeads (MBs) and amperometric transduction at screen-printed dual carbon electrodes (SPdCEs). The magnetic bioconjugates were captured onto SPdCEs and the amperometric transduction was performed using the H2O2/hydroquinone (HQ) system. Under optimal experimental conditions, the developed bio platform demonstrates linear concentration ranges of 1.0–25 and 5.0-100 ng mL-1, detection limits of 0.28 and 1.04 ng mL-1 for E-cad and IL-13Rα2, respectively, and excellent selectivity against other non-target proteins. The developed immuno-platform also offers a good reproducibility among amperometric responses provided by nine different sensors constructed in the same manner (Relative Standard Deviation values of 3.1% for E-cad and 4.3% for IL-13Rα2). Moreover, obtained results confirm the practical applicability of this bio-platform for the accurate determination of the endogenous levels of both extracellular receptors in colon cancer cells (both intact and lysed) with different metastatic potential and serum and tissues from patients diagnosed with colorectal cancer at different grades. Interesting features in terms of, simplicity, speed, portability and sample amount required to provide quantitative results, make this immuno-platform more compatible than conventional methodologies with the clinical diagnosis and prognosis at the point of care.

Keywords: electrochemistry, mmunosensors, biosensors, E-cadherin, IL-13 receptor α2, cancer colorectal

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Authors: Ammar Asma, Bouafia Nabiha, Dhahri Meriem, Ben Cheikh Asma, Ezzi Olfa, Chafai Rim, Njah Mansour

Abstract:

Despite recent advances in treatment of the lung cancer patients, the prognosis remains poor. Information is limited regarding health related quality of life (QOL) status of advanced lung cancer patients. The purposes of this study were: to assess patient reported symptom burden, to measure their QOL, and to identify determinant factors associated with QOL. Materials/Methods: A cross sectional study of 60 patients was carried out from over the period of 03 months from February 1st to 30 April 2016. Patients were recruited in two department of health care: Pneumology department in a university hospital in Sousse and an oncology unit in a University Hospital in Kairouan. Patients with advanced stage (III and IV) of lung cancer who were hospitalized or admitted in the day hospital were recruited by convenience sampling. We used a questionnaire administrated and completed by a trained interviewer. This questionnaire is composed of three parts: demographic, clinical and therapeutic information’s, QOL measurements: based on the SF-36 questionnaire, Symptom’s burden measurement using the Lung Cancer Symptom Scale (LCSS). To assess Correlation between symptoms burden and QOL, we compared the scores of two scales two by two using the Pearson correlation. To identify factors influencing QOL in Lung cancer, a univariate statistical analysis then, a stepwise backward approach, wherein the variables with p< 0.2, were carried out to determine the association between SF-36 scores and different variables. Results: During the study period, 60 patients consented to complete symptom and quality of life questionnaires at a single point time (72% were recruited from day hospital). The majority of patients were male (88%), age ranged from 21 to 79 years with a mean of 60.5 years. Among patients, 48 (80%) were diagnosed as having non-small cell lung carcinoma (NSCLC). Approximately, 60 % (n=36) of patients were in stage IV, 25 % in stage IIIa and 15 % in stage IIIb. For symptom burden, the symptom burden index was 43.07 (Standard Deviation, 21.45). Loss of appetite and fatigue were rated as the most severe symptoms with mean scores (SD): 49.6 (25.7) and 58.2 (15.5). The average overall score of SF36 was 39.3 (SD, 15.4). The physical and emotional limitations had the lowest scores. Univariate analysis showed that factors which influence negatively QOL were: married status (p<0.03), smoking cessation after diagnosis (p<0.024), LCSS total score (p<0.001), LCSS symptom burden index (p<0.001), fatigue (p<0.001), loss of appetite (p<0.001), dyspnea (p<0.001), pain (p<0.002), and metastatic stage (p<0.01). In multivariate analysis, unemployment (p<0.014), smoking cessation after diagnosis (p<0.013), consumption of analgesic (p<0.002) and the indication of an analgesic radiotherapy (p<0.001) are revealed as independent determinants of QOL. The result of the correlation analyses between total LCSS scores and the total and individual domain SF36 scores was significant (p<0.001); the higher total LCSS score is, the poorer QOL is. Conclusion: A built in support of lung cancer patients would better control the symptoms and promote the QOL of these patients.

Keywords: quality of life, lung cancer, metastasis, symptoms burden

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Authors: Avigail Moor, Michal Otmazgin, Hagar Tsiddon, , Avivit Mahazri

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The goal of the present study was to refine sexual assault therapy through the examination of the level of agreement between survivor and therapist assessments of key recovery-promoting therapeutic interventions. This is the first study to explore the level of agreement between those who partake in the treatment process from either position. Semi structured interviews were conducted in this qualitative study with 10 survivors and 10 experienced therapists. The results document considerable concurrence between them regarding relational and trauma processing treatment components alike. Together, these reports outline key effective interventions, both common and specific in nature, concomitantly supported by both groups.

Keywords: sexual assault, rape treatment, therapist training, psychotherapy

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Authors: Prajna Paramita Naik, Sujit Kumar Bhutia

Abstract:

Background: Regardless of the development multimodal treatment strategies, oral squamous cell carcinoma (OSCC) is often associated with a high rate of recurrence, metastasis and chemo- and radio- resistance. The present study inspected the relevance of CD44, ABCB1 and ADAM17 expression as a putative stem cell compartment in oral squamous cell carcinoma (OSCC) and deciphered the role of autophagy in regulating the expression of aforementioned proteins, stemness and chemoresistance. Methods: A retrospective analysis of CD44, ABCB1 and ADAM17 expression with respect to the various clinicopathological factors of sixty OSCC patients were determined via immunohistochemistry. The correlation among CD44, ABCB1 and ADAM17 expression was established. Sphere formation assay, flow cytometry and fluorescence microscopy were conducted to elucidate the stemness and chemoresistance nature of established cisplatin-resistant oral cancer cells (FaDu). The pattern of expression of CD44, ABCB1 and ADAM17 in parental (FaDu-P) and resistant FaDu cells (FaDu-CDDP-R) were investigated through fluorescence microscopy. Western blot analysis of autophagy marker proteins was performed to compare the status of autophagy in parental and resistant FaDu cell. To investigate the role of autophagy in chemoresistance and stemness, sphere formation assay, immunofluorescence and Western blot analysis was performed post transfection with siATG14 and the level of expression of autophagic proteins, mitochondrial protein and stemness-associated proteins were analyzed. The statistical analysis was performed by GraphPad Prism 4.0 software. p-value was defined as follows: not significant (n.s.): p > 0.05;*: p ≤ 0.05; **: p ≤ 0.01; ***: p ≤ 0.001; ****: p ≤ 0.0001 were considered statistically significant. Results: In OSCC, high CD44, ABCB1 and ADAM17 expression were significantly correlated with higher tumor grades and poor differentiation. However, the expression of these proteins was not related to the age and sex of OSCC patients. Moreover, the expression of CD44, ABCB1 and ADAM17 were positively correlated with each other. In vitro and OSCC tissue double labeling experiment data showed that CD44+ cells were highly associated with ABCB1 and ADAM17 expression. Further, FaDu-CDDP-R cells showed higher sphere forming capacity along with increased fraction of the CD44+ population and β-catenin expression FaDu-CDDP-R cells also showed accelerated expression of CD44, ABCB1 and ADAM17. A comparatively higher autophagic flux was observed in FaDu-CDDP-R against FaDu-P cells. The expression of mitochondrial proteins was noticeably reduced in resistant cells as compared to parental cells indicating the occurrence of autophagy-mediated mitochondrial degradation in oral cancer. Moreover, inhibition of autophagy was coupled with the decreased formation of orospheres suggesting autophagy-mediated stemness in oral cancer. Blockade of autophagy was also found to induce the restoration of mitochondrial proteins in FaDu-CDDP-R cells indicating the involvement of mitophagy in chemoresistance. Furthermore, a reduced expression of CD44, ABCB1 and ADAM17 was also observed in ATG14 deficient cells FaDu-P and FaDu-CDDP-R cells. Conclusion: The CD44+ ⁄ABCB1+ ⁄ADAM17+ expression in OSCC might be associated with chemoresistance and a putative CSC compartment. Further, the present study highlights the contribution of mitophagy in chemoresistance and confirms the potential involvement of autophagic regulation in acquisition of stem-like characteristics in OSCC.

Keywords: ABCB1, ADAM17, autophagy, CD44, chemoresistance, mitophagy, OSCC, stemness

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