Search results for: survival

Authors: Padma Chutoo, Elena Kulinskaya, Ilyas Bakbergenuly, Nicholas Steel, Dmitri Pchejetski

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Transient ischaemic attacks (TIAs) are warning signs for future strokes. TIA patients are at increased risk of stroke and cardio-vascular events after a first episode. A majority of studies on TIA focused on the occurrence of these ancillary events after a TIA. Long-term mortality after TIA received only limited attention. We undertook this study to determine the long-term hazards of all-cause mortality following a first episode of a TIA using anonymised electronic health records (EHRs). We used a retrospective case-control study using electronic primary health care records from The Health Improvement Network (THIN) database. Patients born prior to or in year 1960, resident in England, with a first diagnosis of TIA between January 1986 and January 2017 were matched to three controls on age, sex and general medical practice. The primary outcome was all-cause mortality. The hazards of all-cause mortality were estimated using a time-varying Weibull-Cox survival model which included both scale and shape effects and a random frailty effect of GP practice. 20,633 cases and 58,634 controls were included. Cases aged 39 to 60 years at the first TIA event had the highest hazard ratio (HR) of mortality compared to matched controls (HR = 3.04, 95% CI (2.91 - 3.18)). The HRs for cases aged 61-70 years, 71-76 years and 77+ years were 1.98 (1.55 - 2.30), 1.79 (1.20 - 2.07) and 1.52 (1.15 - 1.97) compared to matched controls. Aspirin provided long-term survival benefits to cases. Cases aged 39-60 years on aspirin had HR of 0.93 (0.84 - 1.00), 0.90 (0.82 - 0.98) and 0.88 (0.80 - 0.96) at 5 years, 10 years and 15 years, respectively, compared to cases in the same age group who were not on antiplatelets. Similar beneficial effects of aspirin were observed in other age groups. There were no significant survival benefits with other antiplatelet options. No survival benefits of antiplatelet drugs were observed in controls. Our study highlights the excess long-term risk of death of TIA patients and cautions that TIA should not be treated as a benign condition. The study further recommends aspirin as the better option for secondary prevention for TIA patients compared to clopidogrel recommended by NICE guidelines. Management of risk factors and treatment strategies should be important challenges to reduce the burden of disease.

Keywords: dual antiplatelet therapy (DAPT), General Practice, Multiple Imputation, The Health Improvement Network(THIN), hazard ratio (HR), Weibull-Cox model

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Authors: Mohd. A. M. Rahim, Yahaya Hassan, Mathumalar L. Fahrni

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Second line antiretroviral therapy (ART) regimen is used when patients fail their first line regimen. There are many factors such as non-adherence, drug resistance as well as virological and immunological failure that lead to second line highly active antiretroviral therapy (HAART) regimen treatment failure. This study was aimed at determining predictor factors to treatment failure with second line HAART and analyzing median survival time. An observational, retrospective study was conducted in Sungai Buloh Hospital (HSB) to assess current status of HIV patients treated with second line HAART regimen. Convenience sampling was used and 104 patients were included based on the study’s inclusion and exclusion criteria. Data was collected for six months i.e. from July until December 2013. Data was then analysed using SPSS version 18. Kaplan-Meier and Cox regression analyses were used to measure median survival times and predictor factors for treatment failure. The study population consisted mainly of male subjects, aged 30-45 years, who were heterosexual, and had HIV infection for less than 6 years. The most common second line HAART regimen given was lopinavir/ritonavir (LPV/r)-based combination. Kaplan-Meier analysis showed that patients on LPV/r demonstrated longer median survival times than patients on indinavir/ritonavir (IDV/r) based combination (p<0.001). The commonest reason for a treatment to fail with second line HAART was non-adherence. Based on Cox regression analysis, other predictor factors for treatment failure with second line HAART regimen were age and mode of HIV transmission.

Keywords: adherence, antiretroviral therapy, second line, treatment failure

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Authors: Edmar Jose da Rocha

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This paper is a study on Brazilian irregular migrants living and working in two global cities in Europe, Milan and London. The aim of the journal is to show out why Brazilian choose irregular migration to Milan and London as a strategy. Few studies in Europe have focused on groups coming from the same place of origin and residing in different cities in comparative studies. It is this international comparison that makes this research original. Both in London and Milan there is an economic migration. The reasons showed to migrate to Milan were marriage, citizenship and work. The reasons indicated to migrate to London were work, studies and a better life. In London marriage is a channel for regularisation and citizenship. In both countries, fake documents is a channel for undocumented people to get a job and health care.

Keywords: border, immigration, integration, survival strategies, undocumented, regularisation

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Authors: Frank Alexis, Jenny Antonia Rodriguez Leon, Cristobal Leonardo Dominguez Borbor, Mery Rosario Ramirez Munoz

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The shrimp industry has increased in the last years to the point of becoming one of the most dynamic industries. However, the appearance of diseases that significantly affect the production of shrimps has been an obstacle for the shrimp industry. We hypothesized that natural fibers from biodiversity can stimulate the immune system to prevent shrimp diseases like vibriosis. In this project, we extracted the fibers from vegetal sources in Ecuador and characterized them using common techniques like XRD, SEM, and then we tested the effect of fibers as immunostimulants for shrimps in-vitro and in-vivo using small aquarium and large pools. Our results demonstrate that vegetal fibers can significantly increase the survival of shrimps. Moreover, the production of shrimps in a large pool was significantly increased. Lastly, the test of color and taste successfully surpass the control group of shrimps not treated with fiber food supplements.

Keywords: fibers, immunostimulant, shrimp, vibriosis

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Authors: Sidra Suleman, Maliha Suleman, Stephen Brindley

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Oral rehabilitation of head and neck cancer patients plays a crucial role in the quality of life for such individuals post-treatment. Placement of dental implants or implant-retained prostheses can help restore oral function and aesthetics, which is often compromised following surgery. Conventional prosthodontic techniques can be insufficient in rehabilitating such patients due to their altered anatomy and reduced oral competence. Hence, there is a strong clinical need for the placement of dental implants. With an increasing incidence of head and neck cancer patients, the demand for such treatment is rising. Aim: The aim of the study was to determine the survival rate of dental implants in head and neck cancer patients placed at the Restorative and Maxillofacial Department, Royal Stoke University Hospital (RSUH), United Kingdom. Methodology: All patients who received dental implants between January 1, 2013 to December 31, 2020 were identified. Patients were excluded based on three criteria: 1) non-head and neck cancer patients, 2) no outpatient follow-up post-implant placement 3) provision of non-dental implants. Scanned paper notes and electronic records were extracted and analyzed. Implant survival was defined as fixtures that had remained in-situ / not required removal. Sample: Overall, 61 individuals were recruited from the 143 patients identified. The mean age was 64.9 years, with a range of 35 – 89 years. The sample included 37 (60.7%) males and 24 (39.3%) females. In total, 211 implants were placed, of which 40 (19.0%) were in the maxilla, 152 (72.0%) in the mandible and 19 (9.0%) in autogenous bone graft sites. Histologically 57 (93.4%) patients had squamous cell carcinoma, with 43 (70.5%) patients having either stage IVA or IVB disease. As part of treatment, 42 (68.9%) patients received radiotherapy, which was carried out post-operatively for 29 (69.0%) cases. Whereas 21 (34.4%) patients underwent chemotherapy, 13 (61.9%) of which were post-operative. The Median follow-up period was 21.9 months with a range from 0.9 – 91.4 months. During the study, 23 (37.7%) patients died and their data was censored beyond the date of death. Results: In total, four patients who had received radiotherapy had one implant failure each. Two mandibular implants failed secondary to osteoradionecrosis, and two maxillary implants did not survive as a result of failure to osseointegrate. The overall implant survival rates were 99.1% at three years and 98.1% at both 5 and 7 years. Conclusions: Although this data shows that implant failure rates are low, it highlights the difficulty in predicting which patients will be affected. Future studies involving larger cohorts are warranted to further analyze factors affecting outcomes.

Keywords: oncology, dental implants, survival, restorative

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Authors: Jin Hun Choi, So Hyun Ahn, Seong Keun Wang, Ik-Seung Chee, Jung Lan Kim, Sun Woo Lee

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Objectives: The purpose of the study is to investigate the effects of day hospital care in hospitalized schizophrenic patients in terms of treatment adherence and treatment outcomes. Methods: Among schizophrenic patients hospitalized between 2011 and 2012, 23 day hospital care patient and 40 control subjects were included in the study. All candidates underwent Beck Cognitive Insight Scale, Drug Attitude Inventory, World Health Organization Quality of Life Assessment and Psychological Well-Being Scale when their symptoms were stabilized during hospitalization, and after being discharged, 23 patients received day hospital care for two months and then changed to out-patient care while 40 patients received out-patient care immediately after discharge. At the point of two months of out-patient care, the treatment adherence of the two groups was evaluated; tracking observation was performed until February, 2013, and survival rates were compared between the two groups. Results: Treatment adherence was higher in the day hospital care group than in the control group. Kaplan-Meier survival analysis showed a higher survival rate for the day hospital care group compared to the control group. Levels of cognitive insight and quality of life were higher after day hospital care than before day hospital care in the day hospital care group. Conclusions: Through the study, it was confirmed that when hospitalized schizophrenic patients received continuous day hospital care after being discharged, they received further out-patient care more faithfully. The study is considered to aid in the understanding regarding schizophrenic patients’ treatment adherence issues and improvement of treatment outcomes.

Keywords: schizophrenia, day hospital care, adherence, outcomes

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Authors: Junhong Li, Danni Cheng, Yaxin Luo, Xiaowei Yi, Ke Qiu, Wendu Pang, Minzi Mao, Yufang Rao, Yao Song, Jianjun Ren, Yu Zhao

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Background: The number of multiple cancer patients was increasing, and the impact of prior cancer history on salivary gland cancer patients remains unclear. Methods: Clinical, demographic and pathological information on salivary gland cancer patients were retrospectively collected from the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2017, and the characteristics and prognosis between patients with a prior cancer and those without prior caner were compared. Univariate and multivariate cox proportional regression models were used for the analysis of prognosis. A risk score model was established to exam the impact of treatment on patients with a prior cancer in different risk groups. Results: A total of 9098 salivary gland cancer patients were identified, and 1635 of them had a prior cancer history. Salivary gland cancer patients with prior cancer had worse survival compared with those without a prior cancer (p<0.001). Patients with a different type of first cancer had a distinct prognosis (p<0.001), and longer latent time was associated with better survival (p=0.006) in the univariate model, although both became nonsignificant in the multivariate model. Salivary gland cancer patients with a prior cancer were divided into low-risk (n= 321), intermediate-risk (n=223), and high-risk (n=62) groups and the results showed that patients at high risk could benefit from surgery, radiation therapy, and chemotherapy, and those at intermediate risk could benefit from surgery. Conclusion: Prior cancer history had an adverse impact on the survival of salivary gland cancer patients, and individualized treatment should be seriously considered for them.

Keywords: prior cancer history, prognosis, salivary gland cancer, SEER

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Authors: Zoe Goldberger, Priscilla S. Briquez, Jeffrey A. Hubbell

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Tumor cells have mutations resulting from genetic instability that the immune system can actively recognize. Immune checkpoint immunotherapy (ICI) is commonly used in the clinic to re-activate immune reactions against mutated proteins, called neoantigens, resulting in tumor remission in cancer patients. However, only around 20% of patients show durable response to ICI. While tumor mutational burden (TMB) has been approved by the Food and Drug Administration (FDA) as a criterion for ICI therapy, the relevance of the subcellular localizations of the mutated proteins within the tumor cell has not been investigated. Here, we hypothesized that localization of mutations impacts the effect of immune responsiveness to ICI. We analyzed publicly available tumor mutation sequencing data of ICI treated patients from 3 independent datasets. We extracted the subcellular localization from the UniProtKB/Swiss-Prot database and quantified the proportion of membrane, cytoplasmic, nuclear, or secreted mutations per patient. We analyzed this information in relation to response to ICI treatment and overall survival of patients showing with 1722 ICI-treated patients that high mutational burden localized at the membrane (mTMB), correlate with ICI responsiveness, and improved overall survival in multiple cancer types. We anticipate that our results will ameliorate predictability of cancer patient response to ICI with potential implications in clinical guidelines to tailor ICI treatment. This would not only increase patient survival for those receiving ICI, but also patients’ quality of life by reducing the number of patients enduring non-effective ICI treatments.

Keywords: cancer, immunotherapy, membrane neoantigens, efficacy prediction, biomarkers

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Authors: Banu Pradheepa Kamarajan, Muthusamy Ananthasubramanian

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Biofilm forming Pseudomonads occupy the top third position in causing hospital acquired infections. P. aeruginosa is notoriously known for its tendency to develop drug resistance. Major classes of drug such as β-lactams, aminoglycosides, quinolones, and polymyxins are found ineffective against multi-drug resistance Pseudomonas. To combat the infections, rather than administration of a single antibiotic, use of combinations (tobramycin and essential oils from plants and/or silver nanoparticles, chitosan, nitric oxide, cis-2-decenoic acid) in single formulation are suggested to control P. aeruginosa biofilms. Conventional techniques to prevent hospital-acquired implant infections such as coatings with antibiotics, controlled release of antibiotics from the implant material, contact-killing surfaces, coating the implants with functional DNase I and, coating with glycoside hydrolase are being followed. Coatings with bioactive components besides having limited shelf-life, require cold-chain and, are likely to fail when bacteria develop resistance. Recently identified nano-scale physical architectures on the insect wings are expected to have potential bactericidal property. Nanopillars are bactericidal to Staphylococcus aureus, Bacillus subtilis, K. pnuemoniae and few species of Pseudomonas. Our study aims to investigate the survival rate of biofilm forming Pseudomonas aeruginosa strain over non-biofilm forming strain on the nanopillar architecture of dragonfly (Pantala flavescens) wing. Dragonflies were collected near house-hold areas and, insect identification was carried out by the Department of Entomology, Tamilnadu Agricultural University, Coimbatore, India. Two strains of P. aeruginosa such as PAO1 (potent biofilm former) and MTCC 1688 (non-weak biofilm former) were tested against the glass coverslip (control) and wings of dragonfly (test) for 48 h. The wings/glass coverslips were incubated with bacterial suspension in 48-well plate. The plates were incubated at 37 °C under static condition. Bacterial attachment on the nanopillar architecture of the wing surface was visualized using FESEM. The survival rate of P. aeruginosa was tested using colony counting technique and flow cytometry at 0.5 h, 1 h, 2 h, 7 h, 24 h, and 48 h post-incubation. Cell death was analyzed using propidium iodide staining and DNA quantification. The results indicated that the survival rate of non-biofilm forming P. aeruginosa is 0.2 %, whilst that of biofilm former is 45 % on the dragonfly wings at the end of 48 h. The reduction in the survival rate of biofilm and non-biofilm forming P. aeruginosa was 20% and 40% respectively on the wings compared to the glass coverslip. In addition, Fourier Transformed Infrared Radiation was used to study the modification in the surface chemical composition of the wing during bacterial attachment and, post-sonication. This result indicated that the chemical moieties are not involved in the bactericidal property of nanopillars by the conserved characteristic peaks of chitin pre and post-sonication. The nanopillar architecture of the dragonfly wing efficiently deters the survival of non-biofilm forming P. aeruginosa, but not the biofilm forming strain. The study highlights the ability of biofilm formers to survive on wing architecture. Understanding this survival strategy will help in designing the architecture that combats the colonization of biofilm forming pathogens.

Keywords: biofilm, nanopillars, Pseudomonas aeruginosa, survival rate

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Authors: Muhammad Anjum Aqueel, Zaighum Abbas, Mubasshir Sohail, Muhammad Abubakar, Hafiz Khurram Shurjeel, Abu Bakar Muhammad Raza, Muhammad Afzal, Sami Ullah

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Keeping in view the increasing demand, queen of Apis mellifera L. (Hymenoptera: Apidae) was reared artificially in this experiment at varying diets including royal jelly. Larval duration, pupal duration, weight, and size of pupae were evaluated at different diets including royal jelly. Queen larvae were raised by Doo Little grafting method. Four different diets were mixed with royal jelly and applied to larvae. Fructose, sugar, yeast, and honey were provided to rearing queen larvae along with same amount of royal jelly. Larval and pupal duration were longest (6.15 and 7.5 days, respectively) at yeast and shortest on honey (5.05 and 7.02 days, respectively). Heavier and bigger pupae were recorded on yeast (168.14 mg and 1.76 cm, respectively) followed by diets having sugar and honey. Due to production of heavier and bigger pupae, yeast was considered as best artificial diet for the growing queen larvae. So, in the second part of experiment, different amounts of yeast were provided to growing larvae along with fixed amount (0.5 g) of royal jelly. Survival rates of the larvae and queen bee were 70% and 40% in the 4-g food, 86.7% and 53.3% in the 6-g food, and 76.7% and 50% in the 8-g food. Weight of adult queen bee (1.459±0.191 g) and the number of ovarioles (41.7±21.3) were highest at 8 g of food. Results of this study are helpful for bee-keepers in producing fitter queen bees.

Keywords: apis melifera l, dietary effect, survival and development, honey bee queen

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Authors: Alice Sanwald, Thomas Schober

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We analyze mortality and follow-up costs of heart attack patients using administrative data from Austria (2002-2011). As treatment intensity in a hospital largely depends on whether it has a catheterization laboratory, we focus on the effects of patients' initial admission to these specialized hospitals. To account for the nonrandom selection of patients into hospitals, we exploit individuals' place of residence as a source of exogenous variation in an instrumental variable framework. We find that the initial admission to specialized hospitals increases patients' survival chances substantially. The effect on 3-year mortality is -9.5 percentage points. A separation of the sample into subgroups shows the strongest effects in relative terms for patients below the age of 65. We do not find significant effects on longterm inpatient costs and find only marginal increases in outpatient costs.

Keywords: acute myocardial infarction, mortality, costs, instrumental variables, heart attack

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Authors: Rasime Kalkan, Emine Ikbal Atli, Ali Arslantaş, Muhsin Özdemir, Sevilhan Artan

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Glioblastoma (WHO grade IV), is the malignant form of brain tumor, the genetic background of the GBM is highly variable. The tumor mass of a GBM is multilayered and every tumor layer shows distinct characteristics with a different cell population. The treatment planning of GBM should be focused on the tumor genetic characteristics. We screened primary glioblastoma multiforme (GBM) in a population-based study for MGMT and RARβ methylation and IDH1 mutation correlated them with clinical data and treatment. There was no correlation between MGMT-promoter methylation and overall survival. The overall survival time of the patients with methylated RARβ was statically (OS;p<0,05) significance between the patients who were treated with chemotherapy and radiotherapy. Here we showed the status of IDH1 gene associatied with younger age. We demonstrated that the together with MGMT gene the RARβ gene should be used as a potantial treatment decision marker for GBMs.

Keywords: RARβ, primary glioblastoma multiforme, methylation, MGMT

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Authors: Yemane Hailu Fissuh, Zhongzhan Zhang

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An estimating equation technique is an alternative method of the widely used maximum likelihood methods, which enables us to ease some complexity due to the complex characteristics of time-varying covariates. In the situations, when both the time-varying covariates and left-truncation are considered in the model, the maximum likelihood estimation procedures become much more burdensome and complex. To ease the complexity, in this study, the modified estimating equations those have been given high attention and considerations in many researchers under semiparametric transformation model was proposed. The purpose of this article was to develop the modified estimating equation under flexible and general class of semiparametric transformation models for left-truncated and right censored survival data with time-varying covariates. Besides the commonly applied Cox proportional hazards model, such kind of problems can be also analyzed with a general class of semiparametric transformation models to estimate the effect of treatment given possibly time-varying covariates on the survival time. The consistency and asymptotic properties of the estimators were intuitively derived via the expectation-maximization (EM) algorithm. The characteristics of the estimators in the finite sample performance for the proposed model were illustrated via simulation studies and Stanford heart transplant real data examples. To sum up the study, the bias for covariates has been adjusted by estimating density function for the truncation time variable. Then the effect of possibly time-varying covariates was evaluated in some special semiparametric transformation models.

Keywords: EM algorithm, estimating equation, semiparametric transformation models, time-to-event outcomes, time varying covariate

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Authors: Omar Alhamd, Peter A. Thomas, Trevor J. Greenhough, Annette K. Shrive

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The Pseudomonas syringae species complex includes many plant pathogenic strains with highly specific interactions with varied host species and cultivars. The rapid spread of these bacteria over the last ten years has become a cause for concern. Nanoparticles have previously shown promise in microbiological action. We have therefore investigated in vitro and in vivo the effects of different types and sizes of nanoparticles in order to provide quantitative information about their effect on the bacteria. The effects of several different nanoparticles against several bacteria strains were investigated. The effect of NP on bacterial growth was studied by measuring the optical density, biochemical and nutritional tests, and transmission electron microscopy (TEM) to determine the shape and size of NP. Our results indicate that their effects varied, with either a negative or a positive impact on both bacterial and plant growth. Additionally, the methods of exposure to nanoparticles have a crucial role in accumulation, translocation, growth response and bacterial growth. The results of our studies on the behaviour and effects of nanoparticles in model plants showed. Cerium oxide (CeO₂) and silver (Ag) NP showed significant antibacterial activity against several pathogenic bacteria. It was found that titanium nanoparticles (TiO₂) can have either a negative or a positive impact, according to concentration and size. It is also thought that environmental conditions can have a major influence on bacterial growth. Studies were therefore also carried out under some environmental stress conditions to test bacterial survival and to assess bacterial virulence. All results will be presented including information about the effects of different nanoparticles on Pseudomonas syringae bacteria.

Keywords: plant microbiome, nanoparticles, 16S rRNA gene sequencing, bacterial survival

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Authors: Purva Nemavarkar, Badri Narain Pandey, Jitendra Kumar

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Introduction: The objective was to understand the effect of various radioprotectors on DNA damage repair enzyme and survival in gamma-irradiated wild and cdc mutants of S. pombe (fission yeast) cultured under permissive and restrictive conditions. DNA repair process, as influenced by radioprotectors, was measured by activity of DNA polymerase in the cells. The use of single cell gel electrophoresis assay (SCGE) or Comet Assay to follow gamma-irradiation induced DNA damage and effect of radioprotectors was employed. In addition, studying the effect of caffeine at different concentrations on S-phase of cell cycle was also delineated. Materials and Methods: S. pombe cells grown at permissive temperature (250C) and/or restrictive temperature (360C) were followed by gamma-radiation. Percentage survival and activity of DNA Polymerase (yPol II) were determined after post-irradiation incubation (5 h) with radioprotectors such as Caffeine, Curcumin, Disulphiram, and Ellagic acid (the dose depending on individual D 37 values). The gamma-irradiated yeast cells (with and without the radioprotectors) were spheroplasted by enzyme glusulase and subjected to electrophoresis. Radio-resistant cells were obtained by arresting cells in S-phase using transient treatment of hydroxyurea (HU) and studying the effect of caffeine at different concentrations on S-phase of cell cycle. Results: The mutants of S. pombe showed insignificant difference in survival when grown under permissive conditions. However, growth of these cells under restrictive temperature leads to arrest in specific phases of cell cycle in different cdc mutants (cdc10: G1 arrest, cdc22: early S arrest, cdc17: late S arrest, cdc25: G2 arrest). All the cdc mutants showed decrease in survival after gamma radiation when grown at permissive and restrictive temperatures. Inclusion of the radioprotectors at respective concentrations during post irradiation incubation showed increase in survival of cells. Activity of DNA polymerase enzyme (yPol II) was increased significantly in cdc mutant cells exposed to gamma-radiation. Following SCGE, a linear relationship was observed between doses of irradiation and the tail moments of comets. The radioprotection of the fission yeast by radioprotectors can be seen by the reduced tail moments of the yeast comets. Caffeine also exhibited its radio-protective ability in radio-resistant S-phase cells obtained after HU treatment. Conclusions: The radioprotectors offered notable radioprotection in cdc mutants when added during irradiation. The present study showed activation of DNA damage repair enzyme (yPol II) and an increase in survival after treatment of radioprotectors in gamma irradiated wild type and cdc mutants of S. pombe cells. Results presented here showed feasibility of applying SCGE in fission yeast to follow DNA damage and radioprotection at high doses, which are not feasible with other eukaryotes. Inclusion of caffeine at 1mM concentration to S phase cells offered protection and did not decrease the cell viability. It can be proved that at minimal concentration, caffeine offered marked radioprotection.

Keywords: radiation protection, cell cycle, fission yeast, comet assay, s-phase, DNA repair, radioprotectors, caffeine, curcumin, SCGE

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Authors: Ariyan S. Araghi, Guy C. Jackson, Stephen J. Bonsor

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Materials & Methods: A systematic literature search was undertaken using pre-determined inclusion and exclusion criteria. This review followed the Preferred Reporting Items for Systemic Reviews and Meta-Analysis (PRISMA) statement. Several databases were used to search for randomised control trials and longitudinal cohort studies, which were published less than thirty years ago. A total of 54 studies met the predefined inclusion criteria. Four studies reviewed the success, survival, and failure characteristics of zirconia framework resin retained bridges, whilst two reviewed non-precious metal resin retained bridges. Results: The analysis of the studies revealed an overall survival rate of 95.9% for zirconia-based restorations compared to 90.7% for non-precious metal frameworks. Non-precious metal resin retained bridges displayed a higher overall failure rate of 11.9% compared to 4.6% for zirconia-based restorations in the analysed papers. The most frequent complications were wing debonding for the non-precious metal wing group, whereas substructure fracture and veneering ceramic fracture were more prevalent for the zirconia arm of the study. Conclusion: Both types of resin retained bridges provide effective medium to long-term survival. Zirconia-based frameworks will provide marginally increased success and survival and greatly improved aesthetics. However, catastrophic failure is more likely with zirconia-based restorations. Non-precious metal is time tested but performs worse than its zirconia counterpart with regards to longevity; it does not exhibit the same framework fractures as zirconia. Cement choice and attention to the adhesive bonding systems used appear to be paramount to restoration longevity with both restoration subtypes. Furthermore, improved longevity can be seen when air particle abrasion is incorporated into the adhesive protocol. Within the limitations of this study, it has been determined that zirconia-based resin retained bridges can be effectively used in anterior cantilever bridges. Clinical Significance: Zirconia-based resin retained bridges have been demonstrating promising results in terms of improved success and survival characteristics, together with improved aesthetics when compared to non-precious metal winged resin retained bridges. Their popularity is increasing in the age of digital dentistry as many restorations are manufactured using such technology. It is essential that clinicians understand the limitations of each material type and principles of adhesion to ensure restoration longevity.

Keywords: resin retained bridge, fixed partial denture, zirconia bridge, adhesive bridge

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Authors: Bhawna Chandravanshi, Ramesh Bhonde

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In the present study, we focused on the improvisation of islet survival in hypoxia. The Islet-like cell aggregates (ICAs) derived from Wharton's jelly mesenchymal stem cells (WJ-MSC) were cultured with and without WJ-MSC for 48h in hypoxia and normoxia and tested for their direct trophic effect on β cell survival. The WJ MSCs themselves secreted insulin upon glucose challenge and expressed the pancreatic markers at both transcription and translational level (C-peptide, Insulin, Glucagon and Glut 2). Direct contact of MSCs with ICAs facilitate the highest viability under hypoxia as evidenced by fluorescein diacetate/propidium iodide and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cytokine analysis of the co-cultured ICAs revealed amplification of anti-inflammatory cytokine-like TGFβ and TNFα accompanied by depletion of pro-inflammatory cytokines. The increment in VEGF and PDGFa was also seen showing their ability to vascularize upon transplantation. This was further accompanied by reduction in total reactive oxygen species, nitric oxide, and super oxide ions and down-regulation of Caspase3, Caspase8, p53 and up regulation of Bcl2 confirming prevention of apoptosis in ICAs. There was a significant reduction in the expression of p38 protein in the presence of MSCs making the ICAs responsive to glucose. Taken together our data demonstrate for the first time that the WJ-MSC expressed pancreatic markers and their supplementation protected engineered islets against hypoxia, oxidative stress, and inflammatory cytokines by inhibiting p38 MAPK protein.

Keywords: hypoxia, islet-like cell aggregates, inflammatory cytokines, oxidative stress

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Authors: Shi-xia Xu, Zai-wen Zhang, Ru-xue Chen, Shan Zhou, Xiang-feng Tang

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Objective: The clinical influence of HLA-DPB1 mismatches on clinical outcome of HSCT is less clear. This is the first meta-analysis to study the HLA-DPB1 matching statues on clinical outcomes after unrelated donor HSCT. Methods: We searched the CIBMTR, Cochrane Central Register of Controlled Trials (CENTRAL) and related databases (1995.01–2017.06) for all relevant articles. Comparative studies were used to investigate the HLA-DPB1 loci mismatches on clinical outcomes after unrelated donor HSCT, such as the disease-free survival (DFS), overall survival, GVHD, relapse, and transplant-related mortality (TRM). We performed meta-analysis using Review Manager 5.2 software and funnel plot to assess the bias. Results: At first, 1246 articles were retrieved, and 18 studies totaling 26368 patients analyzed. Pooled comparisons of studies found that the HLA-DPB1 mismatched group had a lower rate of DFS than the DPB1-matched group, and lower OS in non-T cell depleted transplantation. The DPB1 mismatched group has a higher incidence of aGVHD and more severe ( ≥ III degree) aGvHD, lower rate of relapse and higher TRM. Moreover, compared with 1-antigen mismatch, 2-antigen mismatched led to a higher risk of TRM and lower relapse rate. Conclusions: This meta-analysis indicated HLA-DPB1 has important influence on survival and transplant-related complications during unrelated donor HSCT and HLA-DPB1 donor selection strategies have been proposed based on a personalized algorithm.

Keywords: human leukocyte antigen, DPB1, transplant, meta-analysis, outcome

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Authors: Suphat Rittirat, Sutha Klaocheed, Somporn Prasertsongskun, Kanchit Thammasiri

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Protocorms of Phalaenopsis cornu-cervi (Breda) Blume & Rchb. f. were successfully cryopreserved using a vitrification method. Two-month old protocorms at GI 4 stage were precultured in liquid MS medium supplemented with different concentrations of sucrose (0.3, 0.5, 0.7, 0.9 and 1.2 M) at 25±1°C for 2 days on an orbital shaker at 110 rpm. The protocorms were treated with loading solution (2 M glycerol plus 0.4 M sucrose) for 20 minutes at 25±1°C. Then, the protocorms were sufficiently dehydrated with vitrification solution (plant vitrification solution 2, PVS2) for various times (0, 30, 60, 90 and 120 minutes) at 25±1°C and stored in liquid nitrogen for 1 day. After rapid thawing in water bath at 40°C for 2 minutes, the explants were washed by MS liquid medium containing 0.5 ml of 1.2 M sucrose for 20 minutes. The results shown that the protocorms were precultured in liquid MS medium containing 0.5 M sucrose and dehydrated with vitrification solution for 60 minutes had the highest survival percentage of protocorm at 31±1.0 % as measured by Evan’s blue. No survival rate of protocorms was found without vitrification treatments.

Keywords: protocorms, cryopreservation, Phalaenopsis cornu-cervi, vitrification

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Authors: M. R. Aher, R. B. Laware, G. S. Asane, B. S. Kuchekar

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Objective: Studies have shown that a new combination therapy with Artemisinin derivatives and curcumin is unique, with potential advantages over known ACTs. In present study an attempt was made to prepare microparticulate drug delivery system of Curcumin-Zn complex and evaluate it in combination with artemether for antimalarial activity. Material and method: Curcumin Zn complex was prepared and encapsulated using sodium alginate. Microparticles thus obtained are further coated with various enteric polymers at different coating thickness to control the release. Microparticles are evaluated for encapsulation efficiency, drug loading and in vitro drug release. Roentgenographic Studies was conducted in rabbits with BaSO 4 tagged formulation. Optimized formulation was screened for antimalarial activity using P. berghei-infected mice survival test and % paracetemia inhibition, alone (three oral dose of 5mg/day) and in combination with arthemether (i.p. 500, 1000 and 1500µg). Curcumin-Zn(II) was estimated in serum after oral administration to rats by using spectroflurometry. Result: Microparticles coated with Cellulose acetate phthalate showed most satisfactory and controlled release with 479 min time for 60% drug release. X-ray images taken at different time intervals confirmed the retention of formulation in GI tract. Estimation of curcumin in serum by spectroflurometry showed that drug concentration is maintained in the blood for longer time with tmax of 6 hours. The survival time (40 days post treatment) of mice infected with P. berghei was compared to survival after treatment with either Curcumin-Zn(II) microparticles artemether combination, curcumin-Zn complex and artemether. Oral administration of Curcumin-Zn(II)-artemether prolonged the survival of P.berghei-infected mice. All the mice treated with Curcumin-Zn(II) microparticles (5mg/day) artemether (1000µg) survived for more than 40 days and recovered with no detectable parasitemia. Administration of Curcumin-Zn(II) artemether combination reduced the parasitemia in mice by more than 90% compared to that in control mice for the first 3 days after treatment. Conclusion: Antimalarial activity of the curcumin Zn-artemether combination was more pronounced than mono therapy. A single dose of 1000µg of artemether in curcumin-Zn combination gives complete protection in P. berghei-infected mice. This may reduce the chances of drug resistance in malaria management.

Keywords: formulation, microparticulate drug delivery, antimalarial, pharmaceutics

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Authors: A. Bere, H. G. Sithuba, K. Kyei, C. Sigauke

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We employ a discrete logit survival model to investigate the risk factors for early alcohol intake among students at two tertiary institutions in Thohoyandou, South Africa. Data were collected from a sample of 744 students using a self-administered questionnaire. Significant covariates were arrived at through a regularization algorithm implemented using the glmmLasso package. The tuning parameter was determined using a five-fold cross-validation algorithm. The baseline hazard was modelled as a smooth function of time through the use of spline functions. The results show that the hazard of initial alcohol intake peaks at the age of about 16 years and that at any given time, being of a male gender, prior use of other drugs, having drinking peers, having experienced negative life events and physical abuse are associated with a higher risk of alcohol intake debut.

Keywords: cross-validation, discrete hazard model, LASSO, smooth baseline hazard

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Authors: S. Sudhakar, Geetha Manjunath, Siva Teja Kakileti, Himanshu Madhu

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Diagnosis of breast cancer at early stages has seen better clinical and survival outcomes. Survival rates in developing countries like India are very low due to accessibility and affordability issues of screening tests such as Mammography. In addition, Mammography is not much effective in younger women with dense breasts. This leaves a gap in current screening methods. Thermalytix is a new technique for detecting breast abnormality in a non-contact, non-invasive way. It is an AI-enabled computer-aided diagnosis solution that automates interpretation of high resolution thermal images and identifies potential malignant lesions. The solution is low cost, easy to use, portable and is effective in all age groups. This paper presents the results of a retrospective comparative analysis of Thermalytix over Mammography and Clinical Breast Examination for breast cancer screening. Thermalytix was found to have better sensitivity than both the tests, with good specificity as well. In addition, Thermalytix identified all malignant patients without palpable lumps.

Keywords: breast cancer screening, radiology, thermalytix, artificial intelligence, thermography

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Authors: Shailendra Kumar, Kamal Kumar Gupta

Abstract:

Dysdercus koenigii is an economically important pest of cotton worldwide. The pest damages the crop by sucking sap, staining lint, reducing the oil content of the seeds and deteriorating the quality of cotton. Plant possesses a plethora of secondary metabolites which are used as defense mechanism against herbivores. One of the important categories of such chemicals is insect growth regulators and the intermediates in their biosynthesis. Farnesol belongs to sesquiterpenoid. It is an intermediate in Juvenile hormone biosynthetic pathway in insects has been widely reported in the variety of plants. This chemical can disrupt the normal metabolic function and therefore, affects various life processes of the insects. Present study tested the efficacy of farnesol against Dysdercus koenigii. 2μl of 5% (100µg) and 10% (200µg) of the farnesol was applied topically on the dorsum of thoracic region of the newly emerged fifth instar nymphs of Dysdercus. The treated insects were observed daily for their survival, weight gain, and developmental anomalies for a period of ten days. The results indicated that treatment with 200µg farnesol decreased survival of the insects to 70% after 24h of exposure. At lower doses, no significant decrease in the survival was observed. However, the surviving nymphs showed alteration in growth, development, and metamorphosis. The weight gain in the treated nymphs showed deviation from control. The treated nymphs showed an increase in mortality during subsequent days and increase in the nymphal duration. The number of nymphs undergoing metamorphosis decreased to 46% and 88% in the treatments with the dose of 200µg and 100µg respectively. Severe developmental anomalies were also observed in the treated nymphs. The treated nymphs moulted into supernumerary nymphs, adultoids, adults with exuviae attached and adults with wing deformities. On treatment with 200µg; 26% adultoid, 4% adults with exuviae attached and 12% adults with wing deformed were produced. Treatment with 100µg resulted in production of 34% adultoid, 26% adults with deformed wing and 4% adults with exuviae attached. Many of the treated nymphs did not metamorphose into adults, remained in nymphal stage and died. Our results indicated potential application plant-derived secondary metabolites like farnesol in the management of Dysdercus population.

Keywords: development, Dysdercus koenigii, farnesol, survival

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Authors: Sunil Kayesth, Kamal Kumar Gupta

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The development of resistance among insects and pests, environmental contamination and adverse effects on non-target organisms is contributed by the indiscriminate use of chemical based insecticides. To overcome these environmental and other ecological issues that are need to replace these harmful toxic compounds. The present study was designed to evaluate the effect of Catharanthus roseus, Ocimum sanctum and Lantana camara plants volatiles on survival and longevity of Dysdercus koenigii. The hexane extract and ethanol extracts of these three plants were used. The fifth instars were exposed to hexane extract with concentrations of 10%, 5%, 2.5% 1.25%, 0.1%, 0.5% 0.25%, 0.125% and 0.0625% while, adults were treated with10%, 5%, 2.5% and 1.25%. 1-ml of each of these concentrations was used to make a thin film in sterilized glass jars of 500 ml capacity. Fifteen- newly emerged fifth instar nymphs and adult bugs were treated separately with the extracts for 24- hour exposure to the plant volatiles. For ethanol extracts cottonseed were treated with ethanol extracts of 10%, 5%, 2.5% and 1.25% concentrations. The treated seeds were provided to the Dysdercus for a period of 24 hours and their feeding behaviour was observed. The effect of hexane and ethanol extract of these plants was observed and readings were recorded for 15 days. Survival and longevity of both fifth instars and adults were in correlation with the concentrations of the plant extracts. Among three plant extracts, Ocimum hexane extract was most toxic and Catharanthus was moderate while Lantana was least toxic. The ethanol extracts of Lantana was highly antifeedent while Ocimum was moderate and Catharanthus was least antifeedent. Both Catharanthus and Ocimum appeared to have potential molecules, which possessed insecticidal activity while Ocimum and Lantana showed antifeedent activities. These insecticidal and antifeedent properties may be used in IPM.

Keywords: Catharanthus roseus, Ocimum sanctum, Lantana camara, Dysdercus koenigii

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Authors: Rasha Ahmadi

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Glioblastoma is one of the most frequent brain malignancies, having a high mortality rate and limited survival in individuals with this malignancy. Despite different treatments and surgery, recurrence of glioblastoma cancer stem cells may arise as a subsequent tumor. For this reason, it is crucial to research the markers associated with glioblastoma stem cells and specifically their microenvironment. In this study, using bioinformatics analysis, we analyzed and nominated genes in the microenvironment pathways of glioblastoma stem cells. In this study, an appropriate database was selected for analysis by referring to the GEO database. This dataset comprised gene expression patterns in stem cells derived from glioblastoma patients. Gene clusters were divided as high and low expression. Enrichment databases such as Enrichr, STRING, and GEPIA were utilized to analyze the data appropriately. Finally, we extracted the potential genes 2700 high-expression and 1100 low-expression genes are implicated in the metabolic pathways of glioblastoma cancer progression. Cellular senescence, MAPK, TNF, hypoxia, zimosterol biosynthesis, and phosphatidylinositol metabolism pathways were substantially expressed and the metabolic pathways were downregulated. After assessing the association between protein networks, MSMP, SOX2, FGD4 ,and CNTNAP3 genes with high expression and DMKN and SBSN genes with low were selected. All of these genes were observed in the survival curve, with a survival of fewer than 10 percent over around 15 months. hsa-mir-192-5p, hsa-mir-129-5p, hsa-mir-215-5p, hsa-mir-335-5p, and hsa-mir-340-5p played key function in glioblastoma cancer stem cells microenviroments. We introduced critical genes through integrated and regular bioinformatics studies by assessing the amount of gene expression profile data that can play an important role in targeting genes involved in the energy and microenvironment of glioblastoma cancer stem cells. Have. This study indicated that hsa-mir-192-5p, and hsa-mir-129-5p are appropriate candidates for this.

Keywords: Glioblastoma, Cancer Stem Cells, Biomarker Discovery, Gene Expression Profiles, Bioinformatics Analysis, Tumor Microenvironment

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Authors: Adrita Banerjee, Ajeet Kumar Singh

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Antenatal care (ANC) from a skilled provider is important to monitor the pregnancy and reduce the risk of morbidity for mother and baby during pregnancy and delivery. The quality of antenatal care can be monitored through the content of services received and the kind of information mothers are given during their visit. Objective: The paper tries to examine the association between ANC check-ups and size/ birth weight. It also focuses on investigating the relationship between utilization of recommended prenatal care for mothers and its effect on infant survival in Nepal. Data and methods: This paper uses data from Nepal demographic Health Survey 2011. To understand the relationship bi-variate statistical analysis and logistic regressions has been done. Maternal health care utilization include ANC check-ups i.e. the type of ante-natal care providers, the number and timing of the visit. The various components of the check-ups include intake of iron tablets/syrups, intestinal parasitic drugs, etc. Results: The results show that women who had no antenatal care visits about 40% had small sized babies at the time of birth compared to women to had at least 3 ANC check up. Women who had at least 3 check-ups 17% of the babies have a small size. It has also been found that about 50 % of the women prefer ANC check-ups during pregnancies which have resulted in lowering the infant mortality by about 40% during 1996-2011. Conclusion: Ante natal care check is care and monitoring of the pregnant woman and her foetus throughout pregnancy. ANC checks have an effect on the infant health and child survival. A woman who had at least three check-ups the possibilities of adverse effect on infant health and infant survival was significantly lower. The findings argue for a more enhanced focus on ANC check-ups for improving the maternal and child health in Nepal.

Keywords: maternal, health, pregnancy, outcome

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Authors: Mulue Girmay Gebreslasie

Abstract:

Entomopathogenic fungi are naturally safe and eco-friendly biological agents. Their potential of host specificity and ease handling made them appealing options to substitute synthetic pesticides in pest control programs. However, they are highly delicate and unstable under field conditions. Therefore, the current experiment was held to search out persistent fungal strains by defining the relationship between invitro heat tolerance and field persistence. Current results on leaf and soil persistence assay revealed that strains of Metarhizium species, M. pingshaense (F2685), M. pingshaense (MS2) and M. brunneum (F709) exhibit maximum cumulative CFUs count, relative survival rate and least percent of CFUs reductions showed significant difference at 7 days and 28 days post inoculations (dpi) in hot seasons from sampled soils and leaves and in cold season from soil samples. Whereas relative survival of B. brongniartii (TNO6) found significantly higher in cold weather leaf treatment application as compared to hot season and found as persistent as other fungal strains, while higher deterioration of fungal conidia seen with M. pingshaense (MS2). In the current study, strains of Beauveria brongniartii (TNO6) and Cordyceps javanica (Czy-LP) were relatively vulnerable in field condition with utmost colony forming units (CFUs) reduction and least survival rates. Further, the relationship of the two parameters (heat tolerance and field persistence) was seen with strong linear positive correlations elucidated that heat test could be used in selection of field persistent fungal strains for hot season applications.

Keywords: integrated pest management, biopesticides, Insect pathology and microbial control, entomology

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Authors: Sudeshna Mukherjee, Leena Fageria, R. Venkataramana Dilip, Rajdeep Chowdhury, Jitendra Panwar

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Metal nanoparticles in recent years have gained importance in cancer therapy due to their enhanced permeability retention effect. Among various nanomaterials, silver nanoparticles (AgNPs) have received considerable attention due to their unique properties like conductivity, chemical stability, relative lower toxicity and outstanding therapeutic potential, such as anti-inflammatory, antimicrobial and anti-cancerous activities. In this study, we took a greener approach to synthesize silver nanoparticle from fungus and analyze its effects on both epithelial and mesenchymal derived cancer cells. Much research has been done on nanoparticle-induced apoptosis, but little is known about its role in autophagy. In our study, the silver nanoparticles were seen to induce autophagy which was analyzed by studying the expression of several autophagy markers like, LC3B-II and ATG genes. Monodansylcadaverine (MDC) assay also revealed the induction of autophagy upon treatment with AgNPs. Inhibition of autophagy by chloroquine resulted in increased cell death suggesting autophagy as a survival strategy adopted by the cells. In parallel to autophagy induction, silver nanoparticles induced ROS accumulation. Interestingly, autophagy inhibition by chloroquine increased ROS level, resulting in enhanced cell death. We further analyzed MAPK signaling upon AgNP treatment. It was observed that along with autophagy, activation of JNK signaling served as pro-survival while ERK signaling served as a pro-death signal. Our results provide valuable insights into the role of autophagy upon AgNP exposure and provide cues to probabilistic strategies to effectively sensitize cancer cells.

Keywords: autophagy, JNK signalling, reactive oxygen species, silver nanoparticles

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Authors: Saha Saradindu, Das Payel, Somdeb BoseDasgupta

Abstract:

Tuberculosis caused by Mycobacteria tuberculosis is a dreadful disease and more so with the advent of extreme and total drug-resistant species. Mycobacterial pathogenesis is an ever-changing paradigm from phagosome maturation block to phagosomal escape into macrophage cytosol and finally acid tolerance and survival inside the lysosome. Mycobacteria are adept at subverting the host immune response by highjacking host cell signaling and secreting virulence factors. One such virulence factor is a ser/thr kinase; Protein kinase G (PknG), which is known to prevent phagosome maturation. The host substrates of PknG, allowing successful pathogenesis still remain an enigma. Hence we carried out a comparative phosphoproteomic screen and identified a number of substrates phosphorylated by PknG. We characterized some of these substrates in vivo and in vitro and observed that PknG mediated phosphorylation of these substrates leads to reduced TNFa production as well as decreased response to TNFa induced macrophage necroptosis, thus enabling mycobacterial survival and proliferation.

Keywords: mycobacteria, Protein kinase G, phosphoproteomics, necroptosis

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Authors: Anna Rudzińska, Katarzyna Szklener, Pola Juchaniuk, Anna Rodzajweska, Katarzyna Machulska-Ciuraj, Monika Rychlik- Grabowska, Michał łOziński, Agnieszka Kolak-Bruks, SłAwomir Mańdziuk

Abstract:

Introduction: Immune checkpoint inhibition (ICI) belongs to the modern forms of anti-cancer treatment. Due to the constant development and continuous research in the field of ICI, many aspects of the treatment are yet to be discovered. One of the less researched aspects of ICI treatment is the influence of the adverse effects on the treatment success rate. It is suspected that adverse events in the course of the ICI treatment indicate a better response rate and correlate with longer progression-free- survival. Methodology: The research was conducted with the usage of the documentation of the Department of Clinical Oncology and Chemotherapy. Data of the patients with a lung cancer diagnosis who were treated between 2019-2022 and received ICI treatment were analyzed. Results: Out of over 133 patients whose data was analyzed, the vast majority were diagnosed with non-small cell lung cancer. The majority of the patients did not experience adverse effects. Most adverse effects reported were classified as grade 1 or grade 2 according to CTCAE classification. Most adverse effects involved skin, thyroid and liver toxicity. Statistical significance was found for the adverse effect incidence and overall survival (OS) and progression-free survival (PFS) (p=0,0263) and for the time of toxicity onset and OS and PFS (p<0,001). The number of toxicity sites was statistically significant for prolonged PFS (p=0.0315). The highest OS was noted in the group presenting grade 1 and grade 2 adverse effects. Conclusions: Obtained results confirm the existence of the prolonged OS and PFS in the adverse-effects-charged patients, mostly in the group presenting mild to intermediate (Grade 1 and Grade 2) adverse effects and late toxicity onset. Simultaneously our results suggest a correlation between treatment response rate and the toxicity grade of the adverse effects and the time of the toxicity onset. Similar results were obtained in several similar research conducted - with the proven tendency of better survival in mild and moderate toxicity; meanwhile, other studies in the area suggested an advantage in patients with any toxicity regardless of the grade. The contradictory results strongly suggest the need for further research on this topic, with a focus on additional factors influencing the course of the treatment.

Keywords: adverse effects, immunotherapy, lung cancer, PD-1/PD-L1 inhibitors

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