Search results for: Bernoulli trials

Authors: Maatouk Mohamed, Nouira Mariem, Hamdi Kbir Gh, Mahjoubi M. F., Ben Moussa M.

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Background and aim: Preoperative biliary drainage (PBD) has been introduced to lower bilirubin levels and to control the negative effects of obstructive jaundice in patients with malignant obstructive jaundice undergoing pancreaticoduodenectomy (PD). The optimal time interval between PBD and PD is still not clear. Delaying surgery by 4 to 6 weeks is the commonly accepted practice. However, delayed PD has been shown to decrease the rate of resection and adversely affect the tumor grading and prognosis. Thus, the purpose of our systematic review and meta-analysis was to evaluate the optimal period for PBD prior to PD: short or prolonged in terms of postoperative morbidity and survival outcomes. Methods: Trials were searched in PubMed, Science Direct, Google Scholar, and Cochrane Library until November 2022. Studies using PBD in patients with malignant obstructive jaundice that compared short duration group (SDG) (surgery performed within 3-4 weeks) with prolonged duration group (PDG) (at least 3-4 weeks after PBD) were included in this study. The risk of bias was assessed using the Rob v2 and Robins-I tools. The priori protocol was published in PROSPERO (ID: CRD42022381405). Results: Seven studies comprising 1625 patients (SDG 870, PDG 882) were included. All studies were non-randomized, and only one was prospective. No significant differences were observed between the SDG and PDG in mortality (OR= 0.59; 95% CI [0.30, 1.17], p=0.13), major morbidity (Chi² = 30.28, p <0.00001; I² = 87%), pancreatic fistula (Chi² = 6.61, p = 0.25); I² = 24%), post pancreatectomy haemorrhage (OR= 1.16; 95% CI [0.67, 2.01], p=0.59), positive drainage culture (OR= 0.36; 95% CI [0.10, 1.32], p=0.12), septic complications (OR= 0.78; 95% CI [0.23, 2.72], p=0.70), wound infection (OR= 0.08, p=0.07), operative time (MD= 0.21; p=0.21). Conclusion: Early surgery within 3 or 4 weeks after biliary drainage is both safe and effective. Thus, it is reasonable to suggest early surgery following PBD for patients having resectable periampullary cancers.

Keywords: preoperative biliary drainage, pancreatic cancer, pancreatic surgery, complication

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Authors: B. Yermekbayeva, A. Gulyayaev, T. Nurgozhin, C. Bektur

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Cytisine aminophosphonate under the name "Cytafat" was approved for clinical trials in Republic of Kazakhstan as a putative liver protecting drug for the treatment of acute toxic hepatitis. A method of conducting the clinical trial is a double blind study. Total number of patients -71, aged from 16 to 56 years. Research on healthy volunteers determined the maximal tolerable doze of "Cytafat" as 200 mg/kg. Side effects when administered at high dozes (100-200 mg/kg) are tachycardia and increase of arterial blood pressure. The drug is tested in the treatment of 28 patients with a syndrome of hepatocellular failure (a poisoning with substitutes of alcohol, rat poison, or medical products). "Cytafat" was intravenously administered at a dose of 10 mg/kg in 200 ml of 5 % glucose solution once daily. The number of administrations: 1-3. In the comparison group, 23 patients were treated intravenously once a day with “Essenciale H” at a dose of 10 ml. 20 patients received a placebo (10 ml of glucose intravenously). In all cases of toxic hepatopathology the significant positive clinical effect of the testing drug distinguishable from placebo and surpassing the alternative was observed. Within a day after administration a sharp reduction of cytolitic syndrome parameters (ALT, AST, alkaline phosphatase, thymol turbidity test, GGT) was registered, a reduction of the severity of cholestatic syndrome (bilirubin decreased) was recorded, significantly decreased indices of lipid peroxidation. The following day, in all cases the positive dynamics was determined with ultrasound study (reduction of diffuse changes and events of reactive pancreatitis), hepatomegaly disappeared. Normalization of all parameters occurred in 2-3 times faster, than when using the drug "Essenciale H" and placebo. Average term of elimination of toxic hepatopathy when using the drug "Cytafat" -2,8 days, "Essenciale H" -7,2 days, and placebo -10,6 days. The new drug "Cytafat" has expressed cytoprotective properties.

Keywords: cytisine, cytoprotection, hepatopathy, hepatoprotection

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Authors: Akshay Patil

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Objective: Mediation analysis identifies causal pathways by testing the relationships between the NCR, the OS, and an intermediate variable that mediates the relationship between the Nimotuzumab-cisplatin-radiation (NCR) and OS. Introduction: In randomized controlled trials, the primary interest is in the mechanisms by which an intervention exerts its effects on the outcomes. Clinicians are often interested in how the intervention works (or why it does not work) through hypothesized causal mechanisms. In this work, we highlight the value of understanding causal mechanisms in randomized trial by applying causal mediation analysis in a randomized trial in oncology. Methods: Data was obtained from a phase III randomized trial (Subgroup of HPVNOCP). NCR is reported to significantly improve the OS of patients locally advanced head and neck cancer patients undergoing definitive chemoradiation. Here, based on trial data, the mediating effect of NCR on patient overall survival was systematically quantified through progression-free survival(PFS), disease free survival (DFS), Loco-regional failure (LRF), and the disease control rate (DCR), Overall response rate (ORR). Effects of potential mediators on the HR for OS with NCR versus cisplatin-radiation (CR) were analyzed by Cox regression models. Statistical analyses were performed using R software Version 3.6.3 (The R Foundation for Statistical Computing) Results: Effects of potential mediator PFS was an association between NCR treatment and OS, with an indirect-effect (IE) 0.76(0.62 – 0.95), which mediated 60.69% of the treatment effect. Taking into account baseline confounders, the overall adjusted hazard ratio of death was 0.64 (95% CI: 0.43 – 0.96; P=0.03). The DFS was also a significant mediator and had an IE 0.77 (95% CI; 0.62-0.93), 58% mediated). Smaller mediation effects (maximum 27%) were observed for LRF with IE 0.88(0.74 – 1.06). Both DCR and ORR mediated 10% and 15%, respectively, of the effect of NCR vs. CR on the OS with IE 0.65 (95% CI; 0.81 – 1.08) and 0.94(95% CI; 0.79 – 1.04). Conclusion: Our findings suggest that PFS and DFS were the most important mediators of the OS with nimotuzumab to weekly cisplatin-radiation in HPVNOCP.

Keywords: mediation analysis, cancer data, survival, NCR, HPV negative oropharyngeal

Procedia PDF Downloads 119

Authors: Memoona Ramzan, Bushra Tabassum, Anwar Khan, Muhammad Tariq, Mudassar Fareed Awan, Idrees Ahmad Nasir, Zahida Qamar, Naila Shahid, Tayyab Husnain

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Biological control is a novel approach being used in crop protection nowadays. Bacteria like Bacillus and Pseudomonas are reported for this purpose and few of their products are commercially available too. Rhizosphere and phyllosphere of healthy cotton plants were used as a source to isolate bacteria capable of exhibiting properties worthy for selection as biocontrol agent. For this purpose all isolated strains were screened for the activities like phosphate solubilization, Indole acetic acid (IAA) production and biocontrol against fungi. Two strains S1HL3 and S1HL4 showed phosphate solubilization and IAA production simultaneously while two other JS2HR4 and JS3HR2 were good inhibitors of fungal pathogens. Through biochemical and molecular characterization these bacteria were identified as P. aeruginosa, Burkholderia and Bacillus respectively. In green house trials of these isolates against Cotton leaf curl virus (CLCuV), seven treatments including individual bacterial isolate and consortia were included. Treated plants were healthy as compared to control plants in which upto 74% CLCuV symptomatic plants exist. Maximum inhibition of CLCuV was observed in T7 treated plants where viral load was only 0.4% as compared to control where viral load was upto 74%. This treatment consortium included Bacillus and Pseudomonas isolates; S1HL3, S1HL4, JS2HR4 and JS3HR2. Principal Component Biplot depicted highly significant correlation between percentage viral load and the disease incidence.

Keywords: cotton leaf curl virus, biological control, bacillus, pseudomonas

Procedia PDF Downloads 353

Authors: Anika Chebrolu

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Mono-targeted drugs can be of limited efficacy against complex diseases. Recently, multi-target drug design has been approached as a promising tool to fight against these challenging diseases. However, the scope of current computational approaches for multi-target drug design is limited. DeepLig presents a de-novo drug discovery platform that uses reinforcement learning to generate and optimize novel, potent, and multitargeted drug candidates against protein targets. DeepLig’s model consists of two networks in interplay: a generative network and a predictive network. The generative network, a Stack- Augmented Recurrent Neural Network, utilizes a stack memory unit to remember and recognize molecular patterns when generating novel ligands from scratch. The generative network passes each newly created ligand to the predictive network, which then uses multiple Graph Attention Networks simultaneously to forecast the average binding affinity of the generated ligand towards multiple target proteins. With each iteration, given feedback from the predictive network, the generative network learns to optimize itself to create molecules with a higher average binding affinity towards multiple proteins. DeepLig was evaluated based on its ability to generate multi-target ligands against two distinct proteins, multi-target ligands against three distinct proteins, and multi-target ligands against two distinct binding pockets on the same protein. With each test case, DeepLig was able to create a library of valid, synthetically accessible, and novel molecules with optimal and equipotent binding energies. We propose that DeepLig provides an effective approach to design multi-targeted drug therapies that can potentially show higher success rates during in-vitro trials.

Keywords: drug design, multitargeticity, de-novo, reinforcement learning

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Authors: Abhishek Pandey

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Ibuprofen and Acetaminophen is widely used as prescription & non-prescription medicine. Ibuprofen mainly used in the treatment of mild to moderate pain related to headache, migraine, postoperative condition and in the management of spondylitis, osteoarthritis and rheumatoid arthritis. Acetaminophen is used as an analgesic and antipyretic drug. Ibuprofen having high tendency of sticking to punches of tablet punching machine while Acetaminophen is not ordinarily compressible to tablet formulation because Acetaminophen crystals are very hard and brittle in nature and fracture very easily when compressed producing capping and laminating tablet defects therefore wet granulation method is used to make them compressible. The aim of study was to prepare Ibuprofen and Acetaminophen tablets by direct compression and top spray granulation technique. In this Investigation tablets were prepared by using directly compressible grade excipients. Dibasic calcium phosphate, lactose anhydrous (DCL21), microcrystalline cellulose (Avicel PH 101). In order to obtain best or optimized formulation, nine different formulations were generated among them batch F7, F8, F9 shows good results and within the acceptable limit. Formulation (F7) selected as optimize product on the basis of dissolution study. Furtherly, directly compressible granules of both drugs were prepared by using top spray granulation technique in fluidized bed processor equipment and compressed .In order to obtain best product process optimization was carried out by performing four trials in which various parameters like inlet air temperature, spray rate, peristaltic pump rpm, % LOD, properties of granules, blending time and hardness were optimized. Batch T3 coined as optimized batch on the basis physical & chemical evaluation. Finally formulations prepared by both techniques were compared.

Keywords: direct compression, top spray granulation, process optimization, blending time

Procedia PDF Downloads 335

Authors: N. Seemuang, T. McLeay, T. Slatter

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Worn tools have a direct effect on the surface finish and part accuracy. Tool condition monitoring systems have been developed over a long period and used to avoid a loss of productivity resulting from using a worn tool. However, the majority of tool monitoring research has applied expensive sensing systems not suitable for production. In this work, the cutting sound in turning machine was studied using microphone. Machining trials using seven cutting conditions were conducted until the observable flank wear width (FWW) on the main cutting edge exceeded 0.4 mm. The cutting inserts were removed from the tool holder and the flank wear width was measured optically. A microphone with built-in preamplifier was used to record the machining sound of EN24 steel being face turned by a CNC lathe in a wet cutting condition using constant surface speed control. The sound was sampled at 50 kS/s and all sound signals recorded from microphone were transformed into the frequency domain by FFT in order to establish the frequency content in the audio signature that could be then used for tool condition monitoring. The extracted feature from audio signal was compared to the flank wear progression on the cutting inserts. The spectrogram reveals a promising feature, named as ‘spindle noise’, which emits from the main spindle motor of turning machine. The spindle noise frequency was detected at 5.86 kHz of regardless of cutting conditions used on this particular CNC lathe. Varying cutting speed and feed rate have an influence on the magnitude of power spectrum of spindle noise. The magnitude of spindle noise frequency alters in conjunction with the tool wear progression. The magnitude increases significantly in the transition state between steady-state wear and severe wear. This could be used as a warning signal to prepare for tool replacement or adapt cutting parameters to extend tool life.

Keywords: tool wear, flank wear, condition monitoring, spindle noise

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Authors: Hushyar Azari

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Aim and background: Deep brain stimulation (DBS) is regarded as an important therapeutic choice for Parkinson's disease (PD). The two most common targets for DBS are the subthalamic nucleus (STN) and globus pallidus (GPi). This review was conducted to compare the clinical effectiveness of these two targets. Methods: A systematic literature search in electronic databases: Embase, Cochrane Library and PubMed were restricted to English language publications 2010 to 2021. Specified MeSH terms were searched in all databases. Studies which evaluated the Unified Parkinson's Disease Rating Scale (UPDRS) III were selected by meeting the following criteria: (1) compared both GPi and STN DBS; (2) had at least three months follow-up period; (3)at least five participants in each group; (4)conducted after 2010. Study quality assessment was performed using the Modified Jadad Scale. Results: 3577 potentially relevant articles were identified, of these, 3569 were excluded based on title and abstract, duplicate and unsuitable article removal. Eight articles satisfied the inclusion criteria and were scrutinized (458 PD patients). According to Modified Jadad Scale, the majority of included studies had low evidence quality which was a limitation of this review. 5 studies reported no statistically significant between-group difference for improvements in UPDRS ш scores. At the same time, there were some results in terms of pain, action tremor, rigidity, and urinary symptoms, which indicated that STN DBS might be a better choice. Regarding the adverse effects, GPi was superior. Conclusion: It is clear that other larger randomized clinical trials with longer follow-up periods and control groups are needed to decide which target is more efficient for deep brain stimulation in Parkinson’s disease and imposes fewer adverse effects on the patients. Meanwhile, STN seems more reasonable according to the results of this systematic review.

Keywords: brain stimulation, globus pallidus, Parkinson's disease, subthalamic nucleus

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Authors: Muhammad Umer, Aishwariya Giri, Umaiyma Rakha

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Mimicked from the humpback whale flippers, the application of tubercle technology is seen to be particularly advantageous at high angles of attack. This particular advantage is of paramount importance when it comes to structures producing lift at high angles of attack. This characteristic of the technology makes it ideal for horizontal stabilizers and selecting the same as the subject of study to identify and exploit the advantage highlighted by researchers on airfoils, this project aims in establishing a foundation for the application of the bio-mimicked technology on an existing aircraft. Using a baseline and 2 tubercle configuration integrated models, the project targets to achieve the twin aim of highlighting the possibility and merits over the base model and also choosing the right configuration in providing the best characteristic suitable for high angles of attack. To facilitate this study, the required models are generated using Solidworks followed by trials in a virtual aerodynamic environment using Fluent in Ansys for resolving the project objectives. Following a structured plan, the aim is to initially identify the advantages mathematically and then selecting the optimal configuration, simulate the end configuration at angles mimicking the actual operation envelope for the particular structure. Upon simulating the baseline configuration at various angles of attack, the stall angle was determined to be 22 degrees. Thus, the tubercle configurations will be simulated and compared at 4 different angles of attacks: 0, 10, 20, and 24. Further, after providing the optimum configuration of horizontal stabilizers, this study aims at the integration of aircraft structure so that the results better imply the end deliverables of real life application. This draws the project scope closer at this point into longitudinal static stability considerations and improvements in the manoeuvrability characteristics. The objective of the study is to achieve a complete overview ready for real life application with marked benefits obtainable from bio morphing of the tubercle technology.

Keywords: flow simulation, horizontal stabilizer, stability enhancement, tubercle

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Authors: Kayode Fatokun, Nozipho N. Motsa

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Field experiments were carried out during the summer/autumn (first trial) and winter/spring (second trial) seasons of 2019 and 2021 inDlangubo, Ngwelezane, and Mtubatubaareas of KwaZulu-Natal Province of South Africa to study the drought amelioration effects and impact of 2 locally available organic wastes [filter cake (FC) and macadamia husk compost (MHC)] on the productivity, and physiological responses of 4 orange-fleshed sweet potato cultivars (Buregard cv., Impilo, W-119 and 199062.1). The effects of FC and MHC were compared with that of inorganic fertilizer (IF) [2:3:2 (30)], FC+IF, MHC+IF, and control. The soil amendments were applied in the first trials only. Climatic data such as humidity, temperature, and rainfall were taken via remote sensing. The results of the first trial indicated that filter cake and IF significantly performed better than MHC. While the strength of filter cake may be attributable to its rich array of mineral nutrients such as calcium, magnesium, potassium, sodium, zinc, copper, manganese, iron, and phosphorus. The little performance from MHC may be attributable to its water holding capacity. Also, a positive correction occurred between the yield of the test OFSP cultivars and climatic factors such as rainfall, NDVI, and NDWI values. Whereas the inorganic fertilizer did not have any significant effect on the growth and productivity of any of the tested sweet potato cultivars in the second trial; FC, and MHC largely maintained their significant performances. In conclusion, the use of FC is highly recommended in the production of the test orange-fleshed sweet potato cultivars. Also, the study indicated that both FC and MHC may not only supply the needed plant nutrients but has the capacity to reduce the impact of drought on the growth of the test cultivars. These findings are of great value to farmers, especially the resource-poorones.

Keywords: amendments, drought, filter cake, macadamia husk compost, sweet potato

Procedia PDF Downloads 67

Authors: Paula Lopez-Arce, Hector Altamirano, Dimitrios Rovas, James Berry, Bryan Hindle, Steven Hodgson

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Efficient mould remediation and accurate moisture diagnostics leading to condensation and mould growth in dwellings are largely untapped. Number of factors are contributing to the rising trend of excessive moisture in homes mainly linked with modern living, increased levels of occupation and rising fuel costs, as well as making homes more energy efficient. Environmental monitoring by means of data collection though loggers sensors and survey forms has been performed in a range of buildings from different UK regions. Air and surface temperature and relative humidity values of residential areas affected by condensation and/or mould issues were recorded. Additional measurements were taken through different trials changing type, location, and position of loggers. In some instances, IR thermal images and ventilation rates have also been acquired. Results have been interpreted together with environmental key parameters by processing and connecting data from loggers and survey questionnaires, both in buildings with and without moisture issues. Monitoring exercises carried out during Winter and Spring time show the importance of developing and following accurate protocols for guidance to obtain consistent, repeatable and comparable results and to improve the performance of environmental monitoring. A model and a protocol are being developed to build a diagnostic tool with the goal of performing a simple but precise residential atmospheric moisture diagnostics to distinguish the cause entailing condensation and mould generation, i.e., ventilation, insulation or heating systems issue. This research shows the relevance of monitoring and processing environmental data to assign moisture risk levels and determine the origin of condensation or mould when dealing with a building atmospheric moisture excess.

Keywords: environmental monitoring, atmospheric moisture, protocols, mould

Procedia PDF Downloads 116

Authors: Yu-Ju Tsai, Ching-Chun Wang, Wen-Tzu Tang, Huei-Ming Chai

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A pronated foot is frequently associated with a hypermobile first ray, then developing further severe foot problems. Low-Dye taping with athletic tape has been widely used to restrict excessive first ray motion and re-build height of the medial longitudinal arch in general population with pronated foot. It is not the case, however, for sprinters since they feel too much restriction of foot motions. Currently, the kinesio tape, more elastic than the athletic tape, has been widely used to re-adjust joint positions. It was interesting whether modified low-Dye taping using kinesio tape was beneficial for altering first ray mobility and still giving enough arch support. The purpose of this study was to investigate the effect of modified low-Dye taping on first ray mobility test and 60-m sprint time for sprinters with pronated foot. The significance of this study provides new insight into a treatment alternative of modified low-Dye taping for sprinter with pronated foot. Ten young male sprinters, aged 20.8±1.6 years, with pronated foot were recruited for this study. The pronated foot was defined as the foot that the navicular drop test was greater than 1.0 cm. Three optic shutters were placed at the start, 30-m, and 60-m sites to record sprint time. All participants were asked to complete 3 trials of the 60-m dash with both taping and non-taping conditions in a random order. The low-Dye taping was applied using the method postulated by Ralph Dye in 1939 except the kinesio tape was used instead. All outcome variables were recorded for taping and non-taping conditions. Paired t-tests were used to analyze all outcome variables between 2 conditions. Although there were no statistically significant differences in dorsal and plantar mobility between taping and non-taping conditions, a statistical significance was found in a total range of motion (dorsiflexion plus plantarflexion angle) of the first ray when a modified low-Dye taping was applied (p < 0.05). Time to complete 60-m sprint was significantly increased with low-Dye taping (p < 0.05) while no significance was found for time to 30-m. it indicated that modified low-Dye taping changed maximum sprint speed of 60-m dash. Conclusively, modified low-Dye taping was capable of increasing first ray mobility and further altered maximum sprint speed.

Keywords: first ray mobility, kinesio taping, pronated foot, sprint time

Procedia PDF Downloads 249

Authors: Denis Duagi, Ben Carter, Maria Farrelly, Stephen Lisk, June S. L. Brown

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Background: Adolescence represents a distinctive phase of development, and variables linked to this developmental period could affect the efficiency of prevention and treatment for depression and anxiety, as well as the long-term prognosis. The objectives of this study were to investigate the long-term effectiveness of psychosocial interventions for adolescents on depression and anxiety symptoms and to assess the influence of different intervention parameters on the long-term effects. Methods: Searches were carried out on the 11ᵗʰ of August 2022 using five databases (Cochrane Library, Embase, Medline, PsychInfo, Web of Science), as well as trial registers. Randomized controlled trials of psychosocial interventions targeting specifically adolescents were included if they assessed outcomes at 1-year post-intervention or more. The Cochrane risk of bias-2 quality assessment tool was used. The primary outcome was depression, and studies were pooled using a standardised mean difference, with an associated 95% confidence interval, p-value, and I². The study protocol was pre-registered (CRD42022348668). Findings: A total of 57 reports (n= 46,678 participants) were included in the review. Psychosocial interventions led to small reductions in depressive symptoms, with a standardised mean difference (SMD) at 1-year of -0.08 (95%CI -0.20, -0.03, p=0.002, I²=72%), 18-months SMD=-0.12, 95% CI -0.22, -0.01, p=0.03, I²=63%) and 2-years SMD=-0.12 (95% CI -0.20, -0.03, p=0.01, I²=68%). Sub-group analyses indicated that targeted interventions produced stronger effects, particularly when delivered by trained mental health professionals (K=18, SMD=-0.24, 95% CI -0.38, -0.10, p=0.001, I²=60%). No effects were detected for anxiety at any assessment. Conclusion: Psychosocial interventions specifically targeting adolescents were shown to have small but positive effects on depression symptoms but not anxiety symptoms, which were sustained for up to 2 years. These findings highlight the potential population-level preventive effects if such psychosocial interventions become widely implemented in accessible settings such as schools.

Keywords: psychosocial, adolescent, interventions, depression, anxiety, meta-analysis, randomized controlled trial

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Authors: Mohammed S. Mohammed, Asmaa M. S. Mohammed

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Background: To achieve the quality of cancer care, the oncologic academic programs should be continuously developed with establishing new ones. We highlighted three disciplines, Clinical nutrition, medical biophysics and radiobiology and Psycho-oncology programs; without a doubt, the Egyptian National Cancer Institute, in ‎the accreditation era, will be establishing them ‎ due to their importance in improving the skills of cancer practitioners. Methods: The first suggested program in Clinical Nutrition that is dealing with the assessment of the patient's well-being before, during and after treatment to avoid the defects in the metabolism resulting from the cancer disease and its treatment by giving the supplements in the patient's diet. The second program is Medical Biophysics and Radiobiology, which there's no denying that it ‎is ‎provided ‎in Cairo University as a good program in the faculty of science but lacks the clinical ‎practice. Hence, it is probably better to establish this program in our institute to ‎improve the ‎practitioner skills and introduce a tailored radiation therapy regimen for every patient according to ‎their characteristic profile.‎ While patients are receiving their treatment, the risk of post-traumatic stress disorder arises, so the importance of the third program, Psycho-Oncology, is clearly obtained. This program is concerned with the psychological, social, behavioral, and ethical aspects of cancer. The area of multi-disciplinary interest has boundaries with the major specialties in oncology: the clinical disciplines (surgery, medicine, pediatrics, and radiotherapy), epidemiology, immunology, endocrinology, biology, pathology, bioethics, palliative care, rehabilitation medicine, clinical trials research and decision making, as well as psychiatry and psychology. Results: It is a prospective academic plan which is compatible with the institutional vision and its strategic plan. Conclusion: In this context, evaluating and understanding the suggested academic programs has become a mandatory part of cancer care. And it is essential to be provided by the NCI.

Keywords: clinical nutrition, psycho-oncology, medical biophysics and radiobiology, medical education

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Authors: Abeer F. Almarzouki, Christopher A. Brown, Richard J. Brown, Anthony K. P. Jones

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Although relief is commonly assumed to be a direct reflection of pain reduction, it seems to be driven by complex emotional interactions in which pain reduction is only one component. For example, termination of a painful/aversive event may be relieving and rewarding. Accordingly, in this study, whether terminating an aversive negative prediction of pain would be reflected in a greater relief experience was investigated, with a view to separating apart the effects of the manipulation on pain and relief. We use aversive conditioning paradigm to investigate the perception of relief in an aversive (threat) vs. positive context. Participants received positive predictors of a non-painful outcome which were presented within either a congruent positive (non-painful) context or an incongruent threat (painful) context that had been previously conditioned; trials followed by identical laser stimuli on both conditions. Participants were asked to rate the perceived intensity of pain as well as their perception of relief in response to the cue predicting the outcome. Results demonstrated that participants reported more pain in the aversive context compared to the positive context. Conversely, participants reported more relief in the aversive context compares to the neutral context. The rating of relief in the threat context was not correlated with pain reports. The results suggest that relief is not dependant on pain intensity. Consistent with this, relief in the threat context was greater than that in the positive expectancy condition, while the opposite pattern was obtained for the pain ratings. The value of relief in this study is better appreciated in the context of an impending negative threat, which is apparent in the higher pain ratings in the prior negative expectancy compared to the positive expectancy condition. Moreover, the more threatening the context (as manifested by higher unpleasantness/higher state anxiety scores), the more the relief is appreciated. The importance of the study highlights the importance of exploring relief and pain intensity in monitoring separately or evaluating pain-related suffering. The results also illustrate that the perception of painful input may largely be shaped by the context and not necessarily stimulus-related.

Keywords: aversive context, pain, predictions, relief

Procedia PDF Downloads 109

Authors: Xinxiu Li, Chuqian Zheng, Yanyan Qian, Hong Fan

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Objectives: In hepatocellular carcinoma (HCC), oncogenes are continuously and robustly transcribed due to aberrant expression of essential components of the trans-acting super-enhancers (SE) complex. Preclinical and clinical trials are now being conducted on small-molecule inhibitors that target core-transcriptional components, including as transcriptional bromodomain protein 4 (BRD4) and cyclin-dependent kinase 7 (CDK7), in a number of malignant tumors. This study aims to explore whether co-overexpression of BRD4 and CDK7 is a potential marker of worse prognosis and a combined therapeutic target in HCC. Methods: The expression pattern of BRD4 and CDK7 and their correlation with prognosis in HCC were analyzed by RNA sequencing data and survival data of HCC patients from TCGA and GEO datasets. The protein levels of BRD4 and CDK7 were determined by immunohistochemistry (IHC), and survival data of patients were analyzed using the Kaplan-Meier method. The mRNA expression levels of genes in HCC cell lines were evaluated by quantitative PCR (q-PCR). CCK-8 and colony formation assays were conducted to assess cell proliferation of HCC upon treatment with BRD4 inhibitor JQ1 or/and CDK7 inhibitor THZ1. Results: It was shown that BRD4 and CDK7 were often overexpressed in HCCs and were associated with poor prognosis of HCC by analyzing the TCGA and GEO datasets. BRD4 or CDK7 overexpression was related to a lower survival rate. It's interesting to note that co-overexpression of CDK7 and BRD4 was a worse prognostic factor in HCC. Treatment with JQ1 or THZ1 alone had an inhibitory effect on cell proliferation; however, when JQ1 and THZ1 were combined, there was a more notable suppression of cell growth. At the same time, the combined use of JQ1 and THZ1 synergistically suppresses the expression of HCC driver genes. Conclusion: Our research revealed that BRD4 and CDK7 coupled can be a useful biomarker in HCC prognosis and the combination of JQ1 and THZ1 can be a promising therapeutic therapy against HCC.

Keywords: BRD4, CDK7, cell proliferation, combined inhibition

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Authors: M. Hirani, M. Devine, O. Obisesan, C. Bryant

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Introduction: The use of four or more implants to support a fixed prosthesis in the edentulous mandible is well documented, with high levels of clinical outcomes recorded. Despite this, the use of three implant-supported fixed prostheses offers the potential to deliver a more cost-effective method of oral rehabilitation in the lower arch, an important consideration given that edentulism is most prevalent in low-income subpopulations. The purpose of this study aimed to evaluate the implant and prosthetic survival rate, changes in marginal bone level, and patient satisfaction associated with a three-implant-supported fixed prosthesis for rehabilitation of the edentulous mandible over a follow-up period of at least one year. Methods: A comprehensive literature search was performed to evaluate studies that met the selection criteria. The information extracted included the study design and population, participant demographics, observation period, loading protocol, and the number of implants placed together with the required outcome measures. Mean values and standard deviations (SD) were calculated using SPSS® (IBM Corporation, New York, USA), and the level of statistical significance across all comparative studies described was set at P < 0.05. Results: The eligible studies included a total of 1968 implants that were placed in 652 patients. The subjects ranged in age from 33-89 years, with a mean of 63.2 years. The mean cumulative implant and prosthetic survival rates were 95.5% and 96.2%, respectively, over a mean follow-up period of 3.25 years. The mean marginal bone loss recorded was 1.04 mm, and high patient satisfaction rates were reported across the studies. Conclusion: Current evidence suggests that a three implant-supported fixed prosthesis for the edentulous mandible is a successful treatment strategy presenting high implant and prosthetic survival rates over the short-to-medium term. Further well-designed controlled clinical trials are required to evaluate longer-term outcomes, with supplemental data correlating implant dimensions and prosthetic design.

Keywords: implants, mandible, fixed, prosthesis

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Authors: R. K. Agrawal, Shiv Agrawal

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Fines and micro create fundamental problems of respiration. From mines to mills steel plants generate lot of pollutants. Legislation & Government laws are stricter day by day & each plant has to think of recycling, reuse &reintegration of pollutants generated during the process of steel making. This paper deals with experiments conducted in Bhilai Steel Plant and Real Ispat and Power Limited for reuse, recycle & reintegrate some of the steel making process fines. Iron ore fines with binders have been agglomerated to be used as a part of the charge for small furnaces. This will improve yield at nominal cost. Rolling mill fines have been recycled to increase the yield of sinter making. This will solve the problems of fine disposal. Huge saving on account of recycling will be achieved. Lime fines after briquetting is used along with prime lime. Lime fines have also been used as a binding material during production of fly ash bricks. These fines serve as low-cost binder. Experiments have been conducted along with coke breeze & gas cleaning plant sludge. As a result, the anti-sloping compound has been developed for converter vessels. Dolo char and Char during Sponge Iron production have been successfully used in power generation and brick making. Pellets have been made with ventilation dust & flue dust. These samples have been tried as a coolant in the converter. Pellets have been made with Sinter Plant electrostatic precipitator micro fines with liquid binder. Trials have been conducted to reuse these pellets in sinter making. Coke breeze from coke-ovens fines and mill scale along with binders were agglomerated. This was used in furnace after attaining required screening and reactivity index. These actions will definitely bring social, economic and environment-friendly universe.

Keywords: briquette, dolo char, electrostatic precipitator, pellet, sinter

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Authors: Adelson G. Guillarte, M. D., Noel J. Belonguel, Jarungchai Anton S. Vatanagul

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Patients with malignant middle cerebral infarction (MCA) (with massive brain swelling and herniation) were reported to have a mortality rate of 80% even with the appropriate conservative medical therapy. European Trials (DECIMAL, DESTINY I, and II, HAMLET) showed significant improvement in mortality and functional outcome with hemicraniectomy. No known published local studies in the region, thus a local study is vital. This is a single center, retrospective, descriptive, cross-sectional, chart review study which includes ≥18 year-old patients with malignant MCA infarction, who underwent hemicraniectomy, and those who were given conservative medical therapy alone, from January 2008 to December 2012 at Perpetual Succour Hospital. Excluded were patients whose charts are with insufficient data, prior MCA stroke, with concomitant intracerebral hemorrhage and with other serious medical conditions or terminal illnesses. Minimum of 32 populations were needed. Data were presented in mean, standard deviation, frequency and percentage distribution. Man n Whitney U test and Chi Square test were used. P-values lesser than 0.05 alpha were considered statistically significant. A total of 672 stroke patients were admitted. 34 patients pass the inclusion criteria. 9 underwent hemicraniectomy and 25 were treated by conservative medical therapy alone. Although not statistically significant (64% vs 33%, p=0.112) there were more patients noted improved in the conservative treatment group. Meanwhile, the Hemicraniectomy group have increased percentage of mortality (67%) (p=0.112). There was a decreasing trend in the average NIHSS score in both groups from admission to post-op 7 days (p=0.198, p=0.78). A bigger multicenter prospective study is recommended to control inherent biases and limitations of a retrospective and smaller study.

Keywords: cerebral infarct, hemicraniectomy, ischemic stroke, malignant middle cerebral artery (MCA) infarct

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Authors: Nuo Xu, Sijing Chen

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Background: Childbirth is considered a critical traumatic event throughout our lives, positively or negatively impacting the mother's physiology, psychology, and even the whole family. Adverse birth experiences, such as labor pain, anxiety, and fear can negatively impact the mother. Studies had shown that the immersive nature of VR can distract attention from pain and increase focus on interventions for pain relief. However, the existing studies that applied VR to maternal delivery were still in their infancy and showed disparate results, and the small sample size is not representative, so this review analyzed the effects of VR in labor, such as on maternal pain and anxiety, with a view to providing a basis for future applications. Search strategy: We searched Pubmed, Embase, Web of Science, the Cochrane Library, CINAHL, China National Knowledge Infrastructure, Wan-Fang database from the building to November 17, 2021. Selection Criteria: Randomized controlled trials (RCTs) that intervened the pregnant women aged 18-35 years with gestational >34 weeks and without complications with VR technology were contained within this review. Data Collection and Analysis: Two researchers completed the study selection, data extraction, and assessment of study quality. For quantitative data we used MD or SMD, and RR (risk ratio) for qualitative data. Random-effects model and 95% confidence interval (95% CI) were used. Main Results: 12 studies were included. Using VR could relieve pain during labor (MD=-1.81, 95% CI (-2.04, -1.57), P< 0.00001) and active period (SMD=-0.41, 95% CI (-0.68, -0.14), P= 0.003), reduce anxiety (SMD=-1.39, 95% CI (-1.99, -0.78), P< 0.00001) and improve satisfaction (RR = 1.32; 95% CI (1.10, 1.59); P = 0.003), but the effect on the duration of first (SMD=-1.12, 95% CI (-2.38, 0.13), P=0.08) and second (SMD=-0.22, 95% CI (-0.67, 0.24), P=0.35) stage of labor was not statistically significant. Conclusions: Compared with conventional care, VR technology can relieve labor pain and anxiety and improve satisfaction. However, extensive experimental validation is still needed.

Keywords: virtual reality, delivery, labor pain, anxiety, meta-analysis, systematic review

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Authors: Shasline Gedeon, Tiffany W. Ardley, Ying Wang, Nathan J. Gesmundo, Katarina A. Sarris, Ana L. Aguirre

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Drug discovery and delivery involve drug targeting, an approach that helps find a drug against a chosen target through high throughput screening and other methods by way of identifying the physical properties of the potential lead compound. Physical properties of potential drug candidates have been an imperative focus since the unveiling of Lipinski's Rule of 5 for oral drugs. Throughout a compound's journey from discovery, clinical phase trials, then becoming a classified drug on the market, the desirable properties are optimized while minimizing/eliminating toxicity and undesirable properties. In the pharmaceutical industry, the ability to generate molecules in parallel with maximum efficiency is a substantial factor achieved through sp²-sp² carbon coupling reactions, e.g., Suzuki Coupling reactions. These reaction types allow for the increase of aromatic fragments onto a compound. More recent literature has found benefits to decreasing aromaticity, calling for more sp³-sp² carbon coupling reactions instead. The objective of this project is to provide a comparison between various sp³-sp² carbon coupling methods and reaction conditions, collecting data on production of the desired product. There were four different coupling methods being tested amongst three cores and 4-5 installation groups per method; each method ran under three distinct reaction conditions. The tested methods include the Photoredox Decarboxylative Coupling, the Photoredox Potassium Alkyl Trifluoroborate (BF3K) Coupling, the Photoredox Cross-Electrophile (PCE) Coupling, and the Weix Cross-Electrophile (WCE) Coupling. The results concluded that the Decarboxylative method was very difficult in yielding product despite the several literature conditions chosen. The BF3K and PCE methods produced competitive results. Amongst the two Cross-Electrophile coupling methods, the Photoredox method surpassed the Weix method on numerous accounts. The results will be used to build future libraries.

Keywords: drug discovery, high throughput chemistry, photoredox chemistry, sp³-sp² carbon coupling methods

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Authors: Rajesh S. Mony, Vaidyaratnam Oushadhasala

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An attempt is made in this study to evolve a drug development modality based on classical Ayurvedic knowledge base as well as on modern scientific methodology. The present study involves (a) identification of a specific ailment condition, (b) the selection of a polyherbal formulation, (c) deciding suitable extraction procedure, (d) confirming the efficacy of the combination by in-vitro trials and (e) fixing up the recommended dose. The ailment segment selected is arthritic condition. The selected herbal combination is Kunturushka, Vibhitaki, Guggulu, Haridra, Maricha and Nirgundi. They were selected as per Classical Ayurvedic references, Authentified as per API (Ayurvedic Pharmacopeia of India), Extraction of each drug was done by different ratios of Hydroalcoholic menstrums, Invitro assessment of each extract after removing residual solvent for anti-Inflammatory, anti-arthritic activities (by UV-Vis. Spectrophotometer with positive control), Invitro assessment of each extract for COX enzyme inhibition (by UV-Vis. Spectrophotometer with positive control), Selection of the extracts was made having good in-vitro activity, Performed the QC testing of each selected extract including HPTLC, that is the in process QC specifications, h. Decision of the single dose with mixtures of selected extracts was made as per the level of in-vitro activity and available toxicology data, Quantification of major groups like Phenolics, Flavonoids, Alkaloids and Bitters was done with both standard Spectrophotometric and Gravimetric methods, Method for Marker assay was developed and validated by HPTLC and a good resolved HPTLC finger print was developed for the single dosage API (Active Pharmaceutical Ingredient mixture of extracts), Three batches was prepared to fix the in process and API (Active Pharmaceutical Ingredient) QC specifications.

Keywords: drug development, antiinflammatory, quality stardardisation, planar chromatography

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Authors: Hailemariam Solomon, Taye Tadesse, Daniel Nadew, Firezer Girma

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Sorghum is an important crop in semi-arid regions and has shown resilience to drought stress. However, recurrent drought is affecting its productivity. Therefore, it is necessary to explore genes that contribute to drought stress adaptation to increase sorghum productivity. The aim of this study is to evaluate and determine the effect of root system traits, specifically root angle, on drought stress adaptation and grain yield performance in sorghum genotypes. A total of 428 sorghum genotypes from the Ethiopian breeding program were evaluated in three drought-stress environments. Field trials were conducted using a row-column design with three replications. Root system traits were phenotyped using a high-throughput phenotyping platform and analyzed using a row-column design with two replications. Data analysis was performed using R software and regression analysis. The study found significant variations in root system architecture among the sorghum genotypes. Non-stay-green genotypes had a grain yield ranging from 1.63 to 3.1 tons/ha, while stay-green genotypes had a grain yield ranging from 2.4 to 2.9 tons/ha. The analysis of root angle showed that non-stay-green genotypes had an angle ranging from 8.0 to 30.5 degrees, while stay-green genotypes had an angle ranging from 12.0 to 29.0 degrees. Improved varieties exhibited angles between 14.04 and 19.50 degrees. Positive and significant correlations were observed between leaf areas and shoot dry weight, as well as between leaf width and shoot dry weight. Negative correlations were observed between root angle and leaf area, as well as between root angle and root length. This research highlights the importance of root system architecture, particularly root angle traits, in enhancing grain yield production in drought-stressed conditions. It also establishes an association between root angle and grain yield traits for maximizing sorghum productivity.

Keywords: roor sysytem architecture, root angle, narrow root angle, wider root angle, drought

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Authors: Magdalena Bury-Kaminska, Aneta Szudy-Szczyrek, Aleksandra Nowaczynska, Olga Jankowska-Lecka, Marek Hus, Klaudia Kot

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Introduction: The aim of the research was to determine the changes in cognitive functioning in patients with plasma cell myeloma by comparing patients’ state before the treatment and during chemotherapy as well as to determine the biological factors that can be used to predict patients’ cognitive state. Methods: The patients underwent the research procedure twice: before chemotherapy and after 4-6 treatment cycles. A psychological test and measurement of the following biological variables were carried out: TNF-α (tumor necrosis factor), IL-6 (interleukin 6), IL-10 (interleukin 10), BDNF (brain-derived neurotrophic factor). The following research methods were implemented: the Montreal Cognitive Assessment (MoCA), Battery of Tests for Assessing Cognitive Functions PU1, experimental and clinical trials based on the Choynowski’s Memory Scale, Stroop Color-Word Interference Test (SCWT), depression measurement questionnaire. Results: The analysis of the research showed better cognitive functions of patients during chemotherapy in comparison to the phase before it. Moreover, neurotrophin BDNF allows to predict the level of selected cognitive functions (semantic fluency and execution control) already at the diagnosis stage. After 4-6 cycles, it is also possible to draw conclusions concerning the extent of working memory based on the level of BDNF. Cytokine TNF-α allows us to predict the level of letter fluency during anti-cancer treatment. Conclusions: It is possible to presume that BDNF has a protective influence on patients’ cognitive functions and working memory and that cytokine TNF-α co-occurs with a diminished execution control and better material grouping in terms of phonological fluency. Acknowledgment: This work was funded by the National Science Center in Poland [grant no. 2017/27/N/HS6/02057.

Keywords: chemobrain, cognitive impairment, non−central nervous system cancers, hematologic diseases

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Authors: Snezana Rajkovic, Miroslava Markovic, Ljubinko Rakonjac, Aleksandar Lucic, Radoslav Rajkovic

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Woolly apple aphid, Eriosoma lanigerum (Hausmann) is a widely distributed pest of apple trees, especially where its parasites have been killed by insecticides. It can also be found on pear, hawthorn, mountain ash, and elm trees. Relatively small to medium-sized aphids, characterized by a reddish-brown body, a blood-red stain when crushed and a fluffy, flocculent wax covering. Specialized dermal glands produce the characteristic fluffy or powdery wax, which gives E. lanigerum its characteristic 'woolly' appearance. Also, woolly apple aphid is a problemm in nursery production of spure.The experiments were carried out in the nursery “Nevade” in Gornji Milanovac, "Srbijasume" on the spruce seedlings, aged 2 years. In this study, organic insecticide King Bo, aqueous solution (a. i. oxymatrine 0.2% + psoralen 0.4%), manufacturer Beijing Kingbo Biotech Co. Ltd., Beijing, China. extracted from plants and used as pesticides in nursery production were investigated. King Bo, bioinsecticide is manufactured from refined natural herbal extract several wild medicinal plants, such as Sophora flavescens Ait, Veratrum nigrum L, A. Carmichael, etc. Oxymatrine 2.4 SL is a stomach poison that has antifeeding and repellent action. This substance stimulates development and growth in a host plant and also controls the appearance of downy mildew.The trials were set according to instructions of methods-monitoring of changes in the number of larvae and adults compared to before treatment. The treatment plan was made according to fully randomized block design. The experiment was conducted in four repetitions. The basic plot had the area of 25 m2. Phytotoxicity was estimated by PP methods 1/135 (2), the intensity of infection according to Towsend-Heuberger, the efficiency by Abbott, the analysis of variance with Ducan test and PP/181 (2).

Keywords: bioinsecticide, efficacy, nurssery production, woolly apple aphid

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Authors: Anjali Sidhu, Anju Bala, Amit Kumar

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Metal nanoparticles have the potential to revolutionize the agriculture owing to sizzling interdisciplinary nano-technological application domain. Numerous patents and products incorporating engineered nanoparticles (NPs) entered into agro-applications with the collective goal to promote proficiency as well as sustainability with lower input and generating meager waste than conventional products and approaches. Loose smut of wheat caused by Ustilago segetum tritici is an internally seed-borne pathogen. It is dormant in the seed unless the seed germinates and its symptoms are expressed at the reproductive stage of the plant only. Various seed treatment agents are recommended for this disease but due to the inappropriate methods of seed treatments used by farmers, each and every seed may not get treated, and the infected seeds escape the fungicidal action. The antimicrobial potential and small size of nanoparticles made them the material of choice as they could enter each seed and restrict the pathogen inside the seed due to the availability of more number of nanoparticles per unit volume of the nanoformulations. Nanoparticles of diverse nature known for their in vitro antimicrobial activity viz. ZnO, MgO, CuS and AgNPs were synthesized, surface modified and characterized by traditional methods. They were applied on infected wheat seeds which were then grown in pot conditions, and their mycelium was tracked in the shoot and leaf region of the seedlings by microscopic staining techniques. Mixed responses of inhibition of this internal mycelium were observed. The time and method of application concluded to be critical for application, which was optimised in the present work. The results implicated that there should be field trails to get final fate of these pot trails up to commercial level. The success of their field trials could be interpreted as a revolution to replace high dose organic fungicides of high residue behaviour.

Keywords: metal nanoparticles, nanopriming, seed borne pathogen, Ustilago segetum tritici

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Authors: Ramanish Ravishankar, Azar Hussain, Mahmoud Loubani, Mubarak Chaudhry

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Background and Aims: Currently, there are no strict guidelines in cardiopulmonary bypass temperature management in cardiac surgery not involving the aortic arch. This study aims to compare patient outcomes undergoing mild hypothermia and normothermia. The aim of this study was to compare patient outcomes between mild hypothermia and normothermia undergoing on-pump cardiac surgery not involving the aortic arch. Methods: This was a retrospective cohort study from January 2015 until May 2023. Patients who underwent cardiac surgery with cardiopulmonary bypass temperatures ≥32oC were included and stratified into mild hypothermia (32oC – 35oC) and normothermia (>35oC) cohorts. Propensity matching was applied through the nearest neighbour method (1:1) using the risk factors detailed in the EuroScore using RStudio. The primary outcome was mortality. Secondary outcomes included post-op stay, intensive care unit readmission, re-admission, stroke, and renal complications. Patients who had major aortic surgery and off-pump operations were excluded. Results: Each cohort had 1675 patients. There was a significant increase in overall mortality with the mild hypothermia cohort (3.59% vs. 2.32%; p=0.04912). There was also a greater stroke incidence (2.09% vs. 1.13%; p=0.0396) and transient ischaemic attack (TIA) risk (3.1% vs. 1.49%; p=0.0027). There was no significant difference in renal complications (9.13% vs. 7.88%; p=0.2155). Conclusions: Patient’s who underwent mild hypothermia during cardiopulmonary bypass have a significantly greater mortality, stroke, and transient ischaemic attack incidence. Mild hypothermia does not appear to provide any benefit over normothermia and does not appear to provide any neuroprotective benefits. This shows different results to that of other major studies; further trials and studies need to be conducted to reach a consensus.

Keywords: cardiac surgery, therapeutic hypothermia, neuroprotection, cardiopulmonary bypass

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Authors: Florian Vincent Haase, Adrian Dierl, Anna Henke, Ralf Woll, Ennes Sarradj

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Structured sheet metals and structured sandwich sheet metals are three-dimensional, lightweight structures with increased stiffness which are used in the automotive industry. The impedance, a figure of resistance of a structure to vibrations, will be determined regarding plain sheets, structured sheets, and structured sandwich sheets. The aim of this paper is generating an experimental design in order to minimize costs and duration of experiments. The design of experiments will be used to reduce the large number of single tests required for the determination of correlation between the impedance and its influencing factors. Full and fractional factorials are applied in order to systematize and plan the experiments. Their major advantages are high quality results given the relatively small number of trials and their ability to determine the most important influencing factors including their specific interactions. The developed full factorial experimental design for the study of plain sheets includes three factor levels. In contrast to the study of plain sheets, the respective impedance analysis used on structured sheets and structured sandwich sheets should be split into three phases. The first phase consists of preliminary tests which identify relevant factor levels. These factor levels are subsequently employed in main tests, which have the objective of identifying complex relationships between the parameters and the reference variable. Possible post-tests can follow up in case additional study of factor levels or other factors are necessary. By using full and fractional factorial experimental designs, the required number of tests is reduced by half. In the context of this paper, the benefits from the application of design for experiments are presented. Furthermore, a multistage approach is shown to take into account unrealizable factor combinations and minimize experiments.

Keywords: structured sheet metals, structured sandwich sheet metals, impedance measurement, design of experiment

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Authors: Zahra R. Almansoor

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Background: Selective serotonin reuptake inhibitors (SSRI’s) and cognitive behavioural therapy (CBT) are the main treatment methods used for patients with obsessive compulsive disorder (OCD) under the National Institute of Health and Care Excellence (NICE) guidelines. Yet many patients are left with residual symptoms or remit, so several other therapeutic approaches have been explored. Objective: The objective was to systematically review the available literature regarding the treatment efficacy of current and potential approaches and diagnostic strategies. Method: First, studies were examined concerning diagnosis, prognosis, and influencing factors. Then, one reviewer conducted a systematic search of six databases using stringent search terms. Results of studies exploring the efficacy of treatment interventions were analysed and compared separately for adults and children. This review was limited to randomised controlled trials (RCT’s) conducted from 2016 onwards, and an improved Y-BOCS (Yale- Brown obsessive compulsive scale) score was the primary outcome measure. Results: Technology-based interventions including internet-based cognitive behavioural therapy (iCBT) were deemed as potentially effective. Discrepancy remains about the benefits of SSRI use past one year, but potential medication adjuncts include amantadine. Treatments such as association splitting and family and mindfulness strategies also have future potential. Conclusion: A range of potential therapies exist, either as treatment adjuncts to current interventions or as sole therapies. To further improve efficacy, it may be necessary to remodel the current NICE stepped-care model, especially regarding the potential use of lower intensity, cheaper treatments, including iCBT. Although many interventions show promise, further research is warranted to confirm this.

Keywords: family and group treatment, mindfulness strategies, novel treatment approaches, standard treatment, technology-based interventions

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Authors: Sutapa Som Chaudhury, Chitrangada Das Mukhopadhyay

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Alzheimer’s disease is a well-known form of dementia since its discovery in 1906. Current Food and Drug Administration approved medications e.g. cholinesterase inhibitors, memantine offer modest symptomatic relief but do not play any role in disease modification or recovery. In last three decades many small molecules, chaperons, synthetic peptides, partial β-secretase enzyme blocker have been tested for the development of a drug against Alzheimer though did not pass the 3rd clinical phase trials. Here in this study, we designed a PEGylated, aminogenic, tripeptidic polymer with two different molecular weights based on the aggregation prone amino acid sequence 17-20 in amyloid beta (Aβ) 1-42. Being conjugated with poly-ethylene glycol (PEG) which self-assembles into hydrophilic nanoparticles, these PEGylated tripeptides constitute a very good drug delivery system crossing the blood brain barrier while the peptide remains protected from proteolytic degradation and non-specific protein interactions. Moreover, being completely aminogenic they would not raise any side effects. These peptide inhibitors were evaluated for their effectiveness against Aβ42 fibrillation at an early stage of oligomer to fibril formation as well as preformed fibril clearance via Thioflavin T (ThT) assay, dynamic light scattering analyses, atomic force microscopy and scanning electron microscopy. The inhibitors were proved to be safe at a higher concentration of 20µM by the reduction assay of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) dye. Moreover, SHSY5Y neuroblastoma cells have shown a greater survivability when treated with the inhibitors following Aβ42 fibril and oligomer treatment as compared with the control Aβ42 fibril and/or oligomer treated neuroblastoma cells. These make the peptidic inhibitors a promising compound in the aspect of the discovery of alternative medication for Alzheimer’s disease.

Keywords: Alzheimer’s disease, alternative medication, amyloid beta, PEGylated peptide

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