Search results for: therapeutic response

Authors: Amandeep Thakur, Yi-Hsuan Chu, Chun-Hsu Pan, Kunal Nepali

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The transfer of ADP-ribose residues onto target substrates from nicotinamide adenine dinucleotide (NAD) (PARylation) is catalyzed by Poly (ADP-ribose) polymerases (PARPs). Amongst the PARP family members, the DNA damage response in cancer is majorly regulated by PARP1 and PARP2. The blockade of DNA repair by PARP inhibitors leads to the progression of DNA single-strand breaks (induced by some triggering factors) to double-strand breaks. Notably, PARP inhibitors are remarkably effective in cancers with defective homologous recombination repair (HRR). In particular, cancer cells with BRCA mutations are responsive to therapy with PARP inhibitors. The aforementioned requirement for PARP inhibitors to be effective confers a narrow activity spectrum to PARP inhibitors, which hinders their clinical applicability. Thus, the quest to expand the application horizons of PARP inhibitors beyond BRCA mutations is the need of the hour. Literature precedents reveal that HDAC inhibition induces BRCAness in cancer cells and can broaden the therapeutic scope of PARP inhibitors. Driven by such disclosures, dual inhibitors targeting both PARP and HDAC enzymes were designed by our research group to extend the efficacy of PARP inhibitors beyond BRCA-mutated cancers to cancers with induced BRCAness. The design strategy involved the installation of Veliparib, an investigational PARP inhibitor, as a surface recognition part in the HDAC inhibitor pharmacophore model. The chemical architecture of veliparib was deemed appropriate as a starting point for the generation of dual inhibitors by virtue of its size and structural flexibility. A validatory docking study was conducted at the outset to predict the binding mode of the designed dual modulatory chemical architectures. Subsequently, the designed chemical architectures were synthesized via a multistep synthetic route and evaluated for antitumor efficacy. Delightfully, one compound manifested impressive anti-leukemic effects (HL-60 cell lines) mediated via dual inhibition of PARP and class I HDACs. The outcome of the western blot analysis revealed that the compound could downregulate the expression levels of PARP1 and PARP2 and the HDAC isoforms (HDAC1, 2, and 3). Also, the dual PARP-HDAC inhibitor upregulated the protein expression of the acetyl histone H3, confirming its abrogation potential for class I HDACs. In addition, the dual modulator could arrest the cell cycle at the G0/G1 phase and induce autophagy. Further, polymer-based nanoformulation of the dual inhibitor was furnished to afford targeted delivery of the dual inhibitor at the cancer site. Transmission electron microscopy (TEM) results indicate that the nanoparticles were monodispersed and spherical. Moreover, the polymeric nanoformulation exhibited an appropriate particle size. Delightfully, pH-sensitive behavior was manifested by the polymeric nanoformulation that led to selective antitumor effects towards the HL-60 cell lines. In light of the magnificent anti-leukemic profile of the identified dual PARP-HDAC inhibitor, in-vivo studies (pharmacokinetics and pharmacodynamics) are currently being conducted. Notably, the optimistic findings of the aforementioned study have spurred our research group to initiate several medicinal chemistry campaigns to create bifunctional small molecule inhibitors addressing PARP as the primary target.

Keywords: PARP inhibitors, HDAC inhibitors, BRCA mutations, leukemia

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Authors: Esther N. Maina, Anna Skowronska, Sridhar Chaganti, Malcolm A. Taylor, Paul G. Murray, Tatjana Stankovic

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Epstein-Barr virus (EBV) has been implicated in the pathogenesis of human tumours of B-cell origin. The demonstration that a proportion of Hodgkin lymphomas and all Burkitt’s lymphomas harbour EBV suggests that the virus contributes to the development of these malignancies. However, the mechanisms of lymphomagenesis remain largely unknown. To determine whether EBV causes DNA damage and alters DNA damage response in cells of EBV-driven lymphoma origin, Germinal Centre (GC) B cells were infected with EBV and DNA damage responses to gamma ionising radiation (IR) assessed at early time points (12hr – 72hr) after infection and prior to establishment of lymphoblastoid (LCL) cell lines. In the presence of EBV, we observed induction of spontaneous DNA DSBs and downregulation of ATM-dependent phosphorylation in response to IR. This downregulation coincided with reduced ability of infected cells to repair IR-induced DNA double-strand breaks, as measured by the kinetics of gamma H2AX, a marker of double-strand breaks, and by the tail moment of the comet assay. Furthermore, we found that alteration of DNA damage responses coincided with the expression of LMP-1 protein. The presence of the EBV virus did not affect the localization of the ATM-dependent DNA repair proteins to sites of damage but instead lead to an increased expression of PP5, a phosphatase that regulates ATM function. The impact of the virus on DNA repair was most prominent 24h after infection, suggesting that this time point is crucial for the viral establishment in B cells. Our results suggest that during an early infection EBV virus dampens crucial cellular responses to DNA double-strand breaks which facilitate successful viral infection, but at the same time might provide the mechanism for tumor development.

Keywords: EBV, ATM, DNA damage, germinal center cells

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Authors: David Whitehouse

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Some of the strengths of online teaching include flexibility, creativity, and comprehensiveness. A challenge can be motivation. How can an instructor repeating the same lessons over and over, day in and day out, year after year, maintain motivation? Enthusiasm? Does motivating the student and creating enthusiasm in class build the same things inside the instructor? The answers lie in the adoption of what I label EUQ—The Empathy and Understanding Quotient. In the online environment, students who are adults have many demands on their time: civilian careers, families (spouse, children, older parents), and sometimes even military service. Empathetic responses on the part of the instructor will lead to open and honest communication on the part of the student, which will lead to understanding on the part of the instructor and a rise in motivation in both parties. Understanding the demands can inform an instructor’s relationship with the student throughout the temporal parameters of classwork. In practicing EUQ, instructors can build motivation in their students and find internal motivation in an enhanced classroom dynamic. The presentation will look at what motivates a student to accomplish more than the minimum required and how that can lead to excellent results for an instructor’s own motivation. Through direct experience of having students give high marks on post-class surveys and via direct messaging, the presentation will focus on how applying EUQ in granting extra time, searching for intent while grading, communicating with students via Quick Notes, responses in Forums, comments in Assignments, and comments in grading areas - - - how applying these things infuses enthusiasm and energy in the instructor which drive creativity in teaching. Three primary ways of communicating with students will be given as examples. The positive response and negative response each for a Forum, an Assignment, and a Message will be explored. If there is time, participants will be invited to craft their own EUQ responses in a role playing exercise involving two common classroom scenarios—late work and plagiarism.

Keywords: education, instruction, motivation, online, teaching

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Authors: Mohammad Hossain Validad

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Background and Aim: Epidemic keratoconjunctivitis is a type of conjunctivitis caused by adenoviruses that can spread rapidly through direct and indirect contact. The aim of this study was to evaluate the therapeutic effects of Povidone-Iodine 0.4% and 0.2% in improving the symptoms and signs of patients with epidemic keratoconjunctivitis. Materials and Methods: In this clinical trial study, 60 patients with a mean age of 27.8±8.4 years who were eligible for inclusion criteria were randomly divided into three groups. The first group received eye drops of Povidone-Iodine 0.4% and betamethasone 0.1%, the second group received PovidoneIodine 0.2% and betamethasone 0.1% and the third group received betamethasone 0.1%. Follow-ups were on the first, fourth, seventh and tenth days after starting treatment. Parameters examined at each examination were hyperaemia, mucopurulent discharge, eyelid edema, hemorrhage, and subepithelial infiltration. Results: The results showed that mucopurulent discharge on the fourth day of the examination (P = 0.005) and the seventh day of the examination (P = 0.001) were significantly different in the three treatment groups. Sub-epithelial infiltration on the tenth day after treatment did not show a significant difference in the 3 groups (P = 0.287). Conclusion: Based on the results of this study, Povidone-Iodine is more effective in relieving some of signs of EKC, such as reduced mucopurulent discharge than steroids alone.

Keywords: EKC, topical bethadine, adenovirus, sub epithelial opacity

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Authors: A. Sohouli, A. Suleman

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This study focuses on reliability analysis of variable stiffness composite laminate structures to investigate the potential structural improvement compared to conventional (straight fibers) composite laminate structures. A computational framework was developed which it consists of a deterministic design step and reliability analysis. The optimization part is Discrete Material Optimization (DMO) and the reliability of the structure is computed by Monte Carlo Simulation (MCS) after using Stochastic Response Surface Method (SRSM). The design driver in deterministic optimization is the maximum stiffness, while optimization method concerns certain manufacturing constraints to attain industrial relevance. These manufacturing constraints are the change of orientation between adjacent patches cannot be too large and the maximum number of successive plies of a particular fiber orientation should not be too high. Variable stiffness composites may be manufactured by Automated Fiber Machines (AFP) which provides consistent quality with good production rates. However, laps and gaps are the most important challenges to steer fibers that effect on the performance of the structures. In this study, the optimal curved fiber paths at each layer of composites are designed in the first step by DMO, and then the reliability analysis is applied to investigate the sensitivity of the structure with different standard deviations compared to the straight fiber angle composites. The random variables are material properties and loads on the structures. The results show that the variable stiffness composite laminate structures are much more reliable, even for high standard deviation of material properties, than the conventional composite laminate structures. The reason is that the variable stiffness composite laminates allow tailoring stiffness and provide the possibility of adjusting stress and strain distribution favorably in the structures.

Keywords: material optimization, Monte Carlo simulation, reliability analysis, response surface method, variable stiffness composite structures

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Authors: Navneet Kalia, Lalit Mohan Verma, Vinay Guleria

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Introduction: Design Flood studies are essential for effective planning and functioning of water resource projects. Design flood estimation for Sunni Dam Hydro Electric Project located in State of Himachal Pradesh, India, on the river Satluj, was a big challenge in view of the river flowing in the Himalayan region from Tibet to India, having a large catchment area of varying topography, climate, and vegetation. No Discharge data was available for the part of the river in Tibet, whereas, for India, it was available only at Khab, Rampur, and Luhri. The estimation of Design Flood using standard methods was not possible. This challenge was met using two different approaches for upper (snow-fed) and lower (rainfed) catchment using Flood Frequency Approach and Hydro-metrological approach. i) For catchment up to Khab Gauging site (Sub-Catchment, C1), Flood Frequency approach was used. Around 90% of the catchment area (46300 sqkm) up to Khab is snow-fed which lies above 4200m. In view of the predominant area being snow-fed area, 1 in 10000 years return period flood estimated using Flood Frequency analysis at Khab was considered as Probable Maximum Flood (PMF). The flood peaks were taken from daily observed discharges at Khab, which were increased by 10% to make them instantaneous. Design Flood of 4184 cumec thus obtained was considered as PMF at Khab. ii) For catchment between Khab and Sunni Dam (Sub-Catchment, C2), Hydro-metrological approach was used. This method is based upon the catchment response to the rainfall pattern observed (Probable Maximum Precipitation - PMP) in a particular catchment area. The design flood computation mainly involves the estimation of a design storm hyetograph and derivation of the catchment response function. A unit hydrograph is assumed to represent the response of the entire catchment area to a unit rainfall. The main advantage of the hydro-metrological approach is that it gives a complete flood hydrograph which allows us to make a realistic determination of its moderation effect while passing through a reservoir or a river reach. These studies were carried out to derive PMF for the catchment area between Khab and Sunni Dam site using a 1-day and 2-day PMP values of 232 and 416 cm respectively. The PMF so obtained was 12920.60 cumec. Final Result: As the Catchment area up to Sunni Dam has been divided into 2 sub-catchments, the Flood Hydrograph for the Catchment C1 has been routed through the connecting channel reach (River Satluj) using Muskingum method and accordingly, the Design Flood was computed after adding the routed flood ordinates with flood ordinates of catchment C2. The total Design Flood (i.e. 2-Day PMF) with a peak of 15473 cumec was obtained. Conclusion: Even though, several factors are relevant while deciding the method to be used for design flood estimation, data availability and the purpose of study are the most important factors. Since, generally, we cannot wait for the hydrological data of adequate quality and quantity to be available, flood estimation has to be done using whatever data is available. Depending upon the type of data available for a particular catchment, the method to be used is to be selected.

Keywords: design flood, design storm, flood frequency, PMF, PMP, unit hydrograph

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Authors: Feng Zhang, Li Chen, Desong Kong, Xiaoping Zhang, Xiaojing Zhu, Yin Lu, Shizhong Zheng

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Sinusoidal pathological angiogenesis is a novel therapeutic target for liver fibrosis. We demonstrated that curcumin ameliorated fibrotic injury and sinusoidal angiogenesis in rat liver with fibrosis caused by carbon tetrachloride. Curcumin reduced the expression of angiogenic markers in fibrotic liver. Experiments in vitro showed that the viability and vascularization of rat liver sinusoidal endothelial cells (LSECs) were not impaired by curcumin. Further investigations showed that curcumin inhibited VEGF expression in hepatic stellate cells (HSCs) by disrupting PDGF-βR/ERK and mTOR pathways. HSC motility and vascularization were also suppressed by curcumin via blocking PDGF-βR/FAK/RhoA cascade. Gain- or loss-of-function analyses revealed that activation of PPARγ was required for curcumin to inhibit angiogenic properties of HSCs. We concluded that curcumin attenuated sinusoidal angiogenesis in liver fibrosis possibly by targeting HSCs via a PPARγ activation-dependent mechanism. PPARγ could be a target molecule for reducing pathological angiogenesis during liver fibrosis.

Keywords: angiogenesis, hepatic stellate cell, curcumin, peroxisome proliferator-activated receptor-γ

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Authors: Virginia Maskill, Philippa Seaton, Marie Crowe, Maree Inder

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A diagnosis of a chronic condition, including Type 2 diabetes can significantly impact an individual’s self-identity which in turn can have considerable implications on how they adapt to, and self-manage their condition. This paper reports on the findings from a qualitative PhD study of forty participants diagnosed with Type 2 diabetes mellitus and comorbid conditions. The primary objective of the study explored the impact conditions had on self-identity and the relationship with self-management practices. Participants were recruited from a larger study which explored the effectiveness of a therapeutic intervention on glycemic control. Interviews were audio-recorded, transcribed verbatim and analysed utilising a narrative thematic analysis methodological approach including a transitional conceptual framework. The majority of participants experienced a loss of their normal self and struggled to integrate diabetes and comorbid conditions into their self-identity. Acceptance, knowledge and integration of conditions were often found to directly influence self-management practices with individuals commonly experiencing four transitional phases from the onset of diagnosis. Successful negotiation of these four phases was influenced by a range of variables which also impacted on an individual’s self-identity and in turn their self-management practices.

Keywords: comorbidity, type two diabetes, self-identity, self-management

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Authors: Odaleia de O. Farias, Suzelene C. Marinho, Ecleidson B. Fragoso, Daniel S. Lima, Francisco R. S. Lira, Lara S. Araújo, Gabriel dos S. D. Soares

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In populous cities, prehospital care services that use vehicles alternative to ambulances are needed in order to reduce costs and improve response time to occurrences in areas with large concentration of people, such as leisure and tourism spaces. In this context, it was implanted a program called BIKE VIDA, that is innovative quick access and assistance program. The aim of this study is to describe the implantation and initial profile of occurrences performed by an urgency/emergency pre-hospital care service through paramedics on bicycles. It is a cross-sectional, descriptive study carried out in the city of Fortaleza, Ceara, Brazil. The data included service records from July to August 2017. Ethical aspects were respected. The service covers a perimeter of 4.5 km, divided into three areas with perimeter of 1.5 km for each paramedic, attending from 5 am to 9 pm. Materials transported by bicycles include External Automated Defibrillator - DEA, portable oxygen, oximeter, cervical collar, stethoscope, sphygmomanometer, dressing and immobilization materials and personal protective equipment. Occurrences are requested directly by calling the emergency number 192 or through direct approach to the professional. In the first month of the program, there were 93 emergencies/urgencies, mainly in the daytime period (71,0%), in males (59,7%), in the age range of 26 to 45 years (46,2%). The main nature was traumatic incidents (53.3%). Most of the cases (88,2%) did not require ambulance transport to the hospital, and there were two deaths. Pre-hospital service through bicycles is an innovative strategy in Brazil and has shown to be promising in terms of reducing costs and improving the quality of the services offered.

Keywords: emergency, response time, prehospital care, urgency

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Authors: Atitallah Sofien, Bouyahia Olfa, Hadj Salah Ibrahim, Ben Saleh Foued, Missaoui Nada, Ben Rabeh Rania, Yahyaoui Salem, Mazigh Sonia, Boukthir Samir

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Introduction: Carbon monoxide (CO) poisoning is a common pathology responsible for high morbidity and mortality worldwide. Aim: The purpose of this study was to determine the epidemiological profile of CO poisoning as well as its clinical, paraclinical, therapeutic, and evolutionary aspects. Methods: Our study included observations of CO poisoning in children hospitalized in the pediatric department C of the Children's Hospital in Tunis over a period of 3 years. Results: We have collected 199 cases of CO poisoning in children. The average age was 5.43 years, with a sex ratio of 0.98. The source of CO was inside the home in 73.2% of cases, and it was the gas bath heater in 68.8% of cases. The intoxication was collective in 93.5% of the cases, and it occurred during the month of January in 35.8% of the cases. The clinical manifestations were headaches in 69.5% of cases. The rate of carboxyhemoglobin was pathological in 73.9% of cases. All patients received normobaric oxygen therapy, and only 3.6% of patients had a hyperbaric oxygen therapy session. We did not deplore any case of death in our study. Conclusion: CO poisoning remains a public health problem in Tunisia with high morbidity. The risk of secondary complications, particularly neuropsychiatric, requires clinical and possibly neuroradiological monitoring of these victims.

Keywords: poisoning, carbon monoxide, children, hyperbaric oxygenation

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Authors: Adaku Thelma Olatise

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Mental health disparities among women from diverse ethnic, cultural, and religious backgrounds remain a pressing concern, particularly as current psychotherapeutic models often fail to address the unique challenges these groups face. This is of particular concern since epidemiological studies across various countries and cultures consistently demonstrate higher prevalence rates of common mental disorders amongst these groups of women because of a lack of access to culturally oriented psychotherapeutic services. This literature review aims to examine how CCAs in psychotherapy can address the specific ethnic, cultural, and religious challenges women encounter in accessing mental health care. A search of relevant articles was conducted through PsycARTICLES and PubMed databases, using terms such as ‘mental health’, ‘women’, ‘culture’, and ‘ethnic minorities’. Supplementary searches on Google Scholar were also performed to capture literature not covered by traditional databases. While the importance of cross-cultural approaches in psychotherapy has become more apparent because people from diverse ethnic backgrounds inevitably perceive the world through different lenses, influencing their interpretations of human behavior and norms, there is a notable gap in the literature in understanding the influences of using of CCAs in psychotherapy amongst women of an ethnic minority. This gap not only reflects a poor understanding of the complex stressors faced by these women—such as familial, communal, and societal expectations—but also highlights the lack of support and culturally adapted interventions available to them. Even though scholars have posited that aligning treatment approaches with patients' cultural backgrounds is important to enhance therapeutic effectiveness, and the acknowledgment of culture is crucial in psychotherapy theory and practice. As well as the increasing global focus on psychotherapy applications that integrate non-Western practices, such as spiritual healing and community-based interventions, the adaptation of these approaches in mainstream mental health care has remained limited. This review found that the expectations and experiences of ethnic minority women were heavily influenced by family and community pressures. However, there were limited evidence-based, culturally oriented psychotherapeutic interventions tailored to ethnic minority women. This gap extends to inadequate representation of minority groups in clinical research, as well as a lack of culturally validated mental health outcome measures. Furthermore, studies have shown that psychotherapeutic models have largely been Western-oriented and Euro-centric because of socially constructed hierarchies. The origin of psychology from the Western world has predominantly reflected Western cultural traditions, shaped by historical, linguistic, and sociopolitical influences. These factors have led to a lack of recognition of therapeutic approaches from minority ethnic groups and the biases that emanate from hegemonic cultural beliefs and power dynamics influence the decisions about which psychotherapeutic modalities to integrate and practice. Therefore, this plethora of factors adds to the challenges women from ethnically and culturally diverse backgrounds face in accessing mental health services at the individual, familial, community, and societal levels. In conclusion, a cross-cultural approach is urgently needed within psychotherapy to address these challenges, ensuring that treatment frameworks are both culturally sensitive and gender responsive. Only by considering the lived experiences of minority women, particularly in relation to their cultural and religious contexts, can mental health services provide the appropriate care necessary to support their well-being.

Keywords: mental health, women, culture, ethnicity

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Authors: F. J. Puertas, M. Castro, A. Tebar, P. J. Fito, R. Gadea, J. M. Monzó, R. J. Colom

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There is a great diversity of diseases that affect the integrity of the walls of the esophagus, generally of a digestive nature. Among them, gastroesophageal reflux is a common disease in the general population, affecting the patient's quality of life; however, there are still unmet diagnostic and therapeutic issues. The consequences of untreated or asymptomatic acid reflux on the esophageal mucosa are not only pain, heartburn, and acid regurgitation but also an increased risk of esophageal cancer. Currently, the diagnostic methods to detect problems in the esophageal tract are invasive and annoying, as 24-hour impedance-pH monitoring forces the patient to be uncomfortable for hours to be able to make a correct diagnosis. In this work, the development of a sensor able to measure in depth is proposed, allowing the detection of liquids circulating in the esophageal tract. The multisensor detection system is based on radiofrequency photospectrometry. At an experimental level, consumers representative of the population in terms of sex and age have been used, placing the sensors between the trachea and the diaphragm analyzing the measurements in vacuum, water, orange juice and saline medium. The results obtained have allowed us to detect the appearance of different liquid media in the esophagus, segregating them based on their ionic content.

Keywords: bioimpedance, dielectric spectroscopy, gastroesophageal reflux, GERD

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Authors: Venkatgiri, Ranganath, L. Nagaraja, B. N. Sagar Pandav, S. M. Usturge, D. Dilipkumar, B. V. Shivprakash, B. Bhagwanthappa, D. Jahangir

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A comparative evaluation of Tramadol and Pentazocine as a pre-emptive analgesic in clinical cases of female dogs undergoing ovariohysterectomy was undertaken during this study. During the study, the following parameters were assessed viz., Rectal temperature (ᵒF), Respiratory rate (breaths/min) and Heart rate (beats/min). Hematological and biochemical parameters viz., total erythrocyte count (TEC) (millions/cmm), hemoglobin (g %), otal leucocytes count (TLC) (thousands/cmm), differential leucocytes count (DLC) (%), serum creatinine (mg/dl), plasma protein (mg/dl), blood glucose (mg/dl) was estimated before the surgery and after administration of general anaesthesia and immediate postoperative periods of 0, 12 and 24 hr respectively. Mean Total Pain Score (MTPS) includes measurement of parameters like posture, vocalization, activity level, response to palpation and agitation at different intervals was calculated before surgery and after administration of general anesthesia and post-operative periods of 1, 2, 4, 6, 12hrs and 24 hrs respectively. Mean Total Pain Score (MTPS) was given for each parameter (Posture, Vocalization, Activity Level, Response to Palpation and Agitation) like 0,1,2,3. (maximum score will be given was 4.). Results were revealed in all three groups including control group. There were significant minor alterations in physiological, hematological and biochemical parameters. MTPS (mean total pain score) were revealed and found a significant alteration when compared with control group. In conclusion, Tramadol found to be a better analgesic and had up to 8hrs of analgesic effect and Pentazocine is superior in post-operative pain management when compared to Tramadol because this group of dogs experienced less surgical stress, consumed less anesthetic dose, they recovered early, and they had less MTPS score.

Keywords: dog, pentazocine, tramadol, ovariohysterectomy

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Authors: Sandeep Pandey, Nimra Habib, Ranjana Singh, Abbas Ali Mahdi

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Leukemia is a malignancy of blood that mainly affects children and young adults; while advancement in the early diagnosis will have the potential to improve the outcome of diseases. A wide range of disease including leukemia shows inflammatory signals in their pathogenesis. In a pilot study conducted in our laboratory, 52 people were screened, of which 26 had leukemia and 26 were free from any kind of malignancy. We performed the estimation of the inflammatory cytokine Interleukin-8 and it was found significantly raised in all the leukemia patients concerning healthy volunteers who participated in the study. Flow cytometry had been performed for the confirmation of leukemia and further genomic, and proteomic, analyses of the sample revealed that IL-8 levels showed a positive correlation in patients with leukemia. The results had shown constitutive secretion of interleukin-8 by leukemia cells. So, our finding demonstrated that IL-8 is considered to have a role in the pathogenesis of leukemia, and quantification of IL-8 levels in leukemia conditions might be more useful and feasible in the clinical setting for the prediction of drug responses where it may represent a putative target for innovative diagnostic toward effective therapeutic approaches. However, further research explorations in this area are needed that include a greater number of patients with all different forms of leukemia, and estimating their IL-8 levels may hold the key for the additional predictive values on the recurrence of leukemia and its prognosis.

Keywords: T-ALL, IL-8, leukemia pathogenesis, cancer therapeutics

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Authors: R. Abdeldjebar, B. Labbaci, L. Missoum, B. Moudden, M. Djermane

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The basic components of a composite material made him very sensitive to damage, which requires techniques for detecting damage reliable and efficient. This work focuses on the detection of damage by vibration analysis, whose main objective is to exploit the dynamic response of a structure to detect understand the damage. The experimental results are compared with those predicted by numerical models to confirm the effectiveness of the approach.

Keywords: experimental, composite, vibration analysis, damage

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Authors: Adinew Gebremeskel Tizazu

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The effect of soil-structure interaction on the dynamic response of reinforced concrete buildings of regular and symmetrical geometry are considered in this study. The structures are presumed to be generally embedded in a homogenous soil formation underlain by very stiff material or bedrock. The structure-foundation–soil system is excited at the base by an earthquake ground motion. The superstructure is idealized as a system with lumped masses concentrated at the floor levels, and coupled with the substructure. The substructure system, which comprises of the foundation and soil, is represented, and replaced by springs and dashpots. Frequency-dependent impedances of the foundation system are incorporated in the discrete model in terms of the springs and dashpots coefficients. The excitation applied to the model is field ground motions of actual earthquake records. Modal superposition principle is employed to transform the equations of motion in geometrical coordinates to modal coordinates. However, the modal equations remain coupled with respect to damping terms due to the difference in damping mechanisms of the superstructure and the soil. Hence, proportional damping for the coupled structural system may not be assumed. An iterative approach is adopted and programmed to solve the system of coupled equations of motion in modal coordinates to obtain the displacement responses of the system. Parametric studies for responses of building structures with regular and symmetric plans of different structural properties and heights are made for fixed and flexible base conditions, for different soil conditions encountered in Addis Ababa. The displacement, base shear and base overturning moments are used in the comparison of different types of structures for various foundation embedment depths, site conditions and height of structures. These values are compared against those of fixed base structure. The study shows that the flexible base structures, generally exhibit different responses from those structures with fixed base. Basically, the natural circular frequencies, the base shears and the inter-story displacements for the flexible base are less than those of the fixed base structures. This trend is particularly evident when the flexible soil has large thickness. In contrast, the trend becomes less predictable, when the thickness of the flexible soil decreases. Moreover, in the latter case, the iteration undulates significantly making the prediction difficult. This is attributed to the highly jagged nature of the impedance functions of frequencies for such formations. In this case, it is difficult to conclude whether the conventional fixed-base approach yields conservative design forces, as is the case for soil formations of large thickness.

Keywords: effect of soil structure, dynamic response corroborated, the modal superposition principle, parametric studies

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Authors: Swati Srivastava, Mattia Lauriola, Yuval Gilad, Adi Kimchi, Yosef Yarden

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The glucocorticoid receptor (GR) has been proposed to play important, but incompletely understood roles in cancer. Glucocorticoids (GCs) are widely used as co-medication of various carcinomas, due to their ability to reduce the toxicity of chemotherapy. Furthermore, GR antagonism has proven to be a strategy to treat triple negative breast cancer and castration-resistant prostate cancer. These observations suggest differential GR involvement in cancer subtypes. The goal of our study has been to elaborate the current understanding of GR signaling in tumor progression and metastasis. Our study involves two cellular models, non-tumorigenic breast epithelial cells (MCF10A) and Ewing sarcoma cells (CHLA9). In our breast cell model, the results indicated that the GR agonist dexamethasone inhibits EGF-induced mammary cell migration, and this effect was blocked when cells were stimulated with a GR antagonist, namely RU486. Microarray analysis for gene expression revealed that the mechanism underlying inhibition involves dexamenthasone-mediated repression of well-known activators of EGFR signaling, alongside with enhancement of several EGFR’s negative feedback loops. Because GR mainly acts primarily through composite response elements (GREs), or via a tethering mechanism, our next aim has been to find the transcription factors (TFs) which can interact with GR in MCF10A cells.The TF-binding motif overrepresented at the promoter of dexamethasone-regulated genes was predicted by using bioinformatics. To validate the prediction, we performed high-throughput Protein Complementation Assays (PCA). For this, we utilized the Gaussia Luciferase PCA strategy, which enabled analysis of protein-protein interactions between GR and predicted TFs of mammary cells. A library comprising both nuclear receptors (estrogen receptor, mineralocorticoid receptor, GR) and TFs was fused to fragments of GLuc, namely GLuc(1)-X, X-GLuc(1), and X-GLuc(2), where GLuc(1) and GLuc(2) correspond to the N-terminal and C-terminal fragments of the luciferase gene.The resulting library was screened, in human embryonic kidney 293T (HEK293T) cells, for all possible interactions between nuclear receptors and TFs. By screening all of the combinations between TFs and nuclear receptors, we identified several positive interactions, which were strengthened in response to dexamethasone and abolished in response to RU486. Furthermore, the interactions between GR and the candidate TFs were validated by co-immunoprecipitation in MCF10A and in CHLA9 cells. Currently, the roles played by the uncovered interactions are being evaluated in various cellular processes, such as cellular proliferation, migration, and invasion. In conclusion, our assay provides an unbiased network analysis between nuclear receptors and other TFs, which can lead to important insights into transcriptional regulation by nuclear receptors in various diseases, in this case of cancer.

Keywords: epidermal growth factor, glucocorticoid receptor, protein complementation assay, transcription factor

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Authors: Shahid Noor, Kazim Najjad, Muhammad Nasir, Irshad Bhutto, Abdul Samad Memon, Khurram Anwar, Tehseen Riaz, Mian Muhammad Hanif, Nauman A. Mallik, Saeed Ahmed, Israr Ahmed, Ali Yasir

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Background: Musculoskeletal pain is the most common complaint presented to the health practitioner. It is well known that untreated or under-treated pain can have a significant negative impact on an individual’s quality of life (QoL). Objectives: This study was conducted across 10 sites in six (6) major cities of Pakistan to evaluate the tolerability, safety, and the clinical response of Nuberol Forte® (Paracetamol 650 mg + Orphenadrine 50 mg) to musculoskeletal pain in routine Pakistani practice and its impact on improving the patient’s QoL. Design & Methods: This NFORT-EFFECT observational, prospective multicenter study was conducted in compliance with Good Clinical Practice guidelines and local regulatory requirements. The study sponsor was "The Searle Company Limited, Pakistan. To maintain the GCP compliances, the sponsor assigned the CRO for the site and data management. Ethical approval was obtained from an independent ethics committee. The IEC reviewed the progress of the study. Written informed consent was obtained from the study participants, and their confidentiality was maintained throughout the study. A total of 399 patients with known prescreened musculoskeletal conditions and pain who attended the study sites were recruited, as per the inclusion/exclusion criteria (clinicaltrials.gov ID# NCT04765787). The recruited patients were then prescribed Paracetamol (650 mg) and Orphenadrine (50 mg) combination (Nuberol Forte®) for 7 to 14 days as per the investigator's discretion based on the pain intensity. After the initial screening (visit 1), a follow-up visit was conducted after 1-2 weeks of the treatment (visit 2). Study Endpoints: The primary objective was to assess the pain management response of Nuberol Forte treatment and the overall safety of the drug. The Visual Analogue Scale (VAS) scale was used to measure pain severity. Secondary to pain, the patients' health-related quality of life (HRQoL) was also assessed using the Muscle, Joint Measure (MJM) scale. The safety was monitored on the first dose by the patients. These assessments were done on each study visit. Results: Out of 399 enrolled patients, 49.4% were males, and 50.6% were females with a mean age of 47.24 ± 14.20 years. Most patients were presented with Knee Osteoarthritis (OA), i.e., 148(38%), followed by backache 70(18.2%). A significant reduction in the mean pain score was observed after the treatment with the combination of Paracetamol and Orphenadrine (p<0.05). Furthermore, an overall improvement in the patient’s QoL was also observed. During the study, only ten patients reported mild adverse events (AEs). Conclusion: The combination of Paracetamol and Orphenadrine (Nuberol Forte®) exhibited effective pain management among patients with musculoskeletal conditions and also improved their QoL.

Keywords: musculoskeletal pain, orphenadrine/paracetamol combination, pain management, quality of life, Pakistani population

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Authors: Srinivasan Chandrasekaran, Shihas A. Khader

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Motion response of floating structures is of great concern in marine engineering. Nonlinearity is an inherent property of any floating bodies subjected to irregular waves. These floating structures are continuously subjected to environmental loadings from wave, current, wind etc. This can result in undesirable motions of the vessel which may challenge the operability. For a floating body to remain in its position, it should be able to induce a restoring force when displaced. Mooring is provided to enable this restoring force. This paper discuss the hydrodynamic performance and motion characteristics of an 8 point spread mooring system applied to a pipe laying barge operating in the West African sea. The modelling of the barge is done using a computer aided-design (CAD) software RHINOCEROS. Irregular waves are generated using a suitable wave spectrum. Both frequency domain and time domain analysis is done. Numerical simulations based on potential theory are carried out to find the responses and hydrodynamic performance of the barge in both free floating as well as moored conditions. Initially, potential flow frequency domain analysis is done to obtain the Response Amplitude Operator (RAO) which gives an idea about the structural motion in free floating state. RAOs for different wave headings are analyzed. In the following step, a time domain analysis is carried out to obtain the responses of the structure in the moored condition. In this study, wave induced motions are only taken into consideration. Wind and current loads are ruled out and shall be included in future studies. For the current study, 5000 seconds simulation is taken. The results represent wave-induced motion responses, mooring line tensions and identifies critical mooring lines.

Keywords: irregular wave, moored barge, time domain analysis, numerical simulation

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Authors: Nursac Akyol, Merve S. Turan, Mustafa Ozcelik, Erdogan Kucukoner, Erkan Karacabey

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Traditional raisin production is a long time drying process under sunlight. During this procedure, grapes are open to some environmental effects besides the adverse effects of the long drying period. Thus, there is a need to develop an alternative method being applicable instead of traditional one. To this extent, a combination of a potential pretreatment (carbonic maceration, CM) with convectional oven drying was examined. CM application was used in raisin production (grape drying) as a pretreatment process before oven drying. Pressure, temperature and time were examined as application parameters of CM. In conventional oven drying, the temperature is a process variable. The aim is to find out how CM and convectional drying processes affect the drying characteristics of grapes as well as their physical and chemical properties. For this purpose, the response surface method was used to determine both the effects of the variables and the optimum pretreatment and drying conditions. The optimum conditions of CM for raisin production were 0.3 MPa of pressure value, 4°C of application temperature and 8 hours of application time. The optimized drying temperature was 77°C. The results showed that the application of CM before the drying process improved the drying characteristics. Drying took only 389 minutes for grapes pretreated by CM under optimum conditions and 495 minutes for the control group dried only by the conventional drying process. According to these results, a decrease of 21% was achieved in the time requirement for raisin production. Also, it was observed that the samples dried under optimum conditions had similar physical properties as those the control group had. It was seen that raisin, which was dried under optimum conditions were in better condition in terms of some of the bioactive contents compared to control groups. In light of all results, it is seen that CM has an important potential in the industrial drying of grape samples. The current study was financially supported by TUBITAK, Turkey (Project no: 116R038).

Keywords: drying time, pretreatment, response surface methodlogy, total phenolic

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Authors: Nosratollah Hedayatpour, Hamid Reza Taheri, Mehrdad Fathi

Abstract:

Introduction: Quadriceps femoris muscle is frequently involved in various movements e.g., jumping, landing) during sport and/or daily activities. During ballistic movement when individuals are faced with unexpected knee perturbation, fast twitch muscle fibers contribute to force production to stabilize knee joint. Fast twitch muscle fiber is more susceptible to fatigue and therefor may reduce the ability of the quadriceps muscle to stabilize knee joint during fast perturbation. Aim: The aim of this study was to investigate the effect of fatigue on postural response of the knee extensor muscles to fast and slow perturbations. Methods: Fatigue was induced to the quadriceps muscle using a KinCom Isokinetic Dynamometer (Chattanooga, TN). Bipolar surface electromyography (EMG) signals were simultaneously recorded from quadriceps components (vastus medialis, rectus femoris, and vastus lateralis) during pre- and post-fatigue postural perturbation performed at two different velocities of 120 ms and 250 mes. Results: One-way ANOVA showed that maximal voluntary knee extension force and time to task failure, and associated EMG activities were significantly reduced after fatiguing knee exercise (P< 0.05). Two-ways ANOVA also showed that ARV of EMG during backward direction was significantly larger than forward direction (P< 0.05), and during fast-perturbation it was significantly higher than slow-perturbation (P< 0.05). Moreover, ARV of EMG was significantly reduced during post fatigue perturbation, with the largest reduction identified for fast-perturbation compared with slow perturbation (P< 0.05). Conclusion: A larger reduction in muscle activity of the quadriceps muscle was observed during post fatigue fast-perturbation to stabilize knee joint, most likely due to preferential recruitment of fast twitch muscle fiber which are more susceptible to fatigue. This may partly explain that why knee injuries is common after fast ballistic movement.

Keywords: electromyography, fast-slow perturbations, fatigue, quadriceps femoris muscle

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Authors: Cristina Costescu, Carmen David, Adrian Roșan

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Executive functions (EF) and emotion regulation strategies are processes that allow individuals to function in an adaptative way and to be goal-oriented, which is essential for success in daily living activities, at school, or in social contexts. The Emotion Regulation and Executive Functioning Scale for Children and Adolescents (REMEX) represents an empirically based tool (based on the model of EF developed by Diamond) for evaluating significant dimensions of child and adolescent EFs and emotion regulation strategies, mainly in school contexts. The instrument measures the following dimensions: working memory, inhibition, cognitive flexibility, executive attention, planning, emotional control, and emotion regulation strategies. Building the instrument involved not only a top-down process, as we selected the content in accordance with prominent models of FE, but also a bottom-up one, as we were able to identify valid contexts in which FE and ER are put to use. For the construction of the instrument, we implemented three focus groups with teachers and other professionals since the aim was to develop an accurate, objective, and ecological instrument. We used the focus group method in order to address each dimension and to yield a bank of items to be further tested. Each dimension is addressed through a task that the examiner will apply and through several items derived from the main task. For the validation of the instrument, we plan to use item response theory (IRT), also known as the latent response theory, that attempts to explain the relationship between latent traits (unobservable cognitive processes) and their manifestations (i.e., observed outcomes, responses, or performance). REMEX represents an ecological scale that integrates a current scientific understanding of emotion regulation and EF and is directly applicable to school contexts, and it can be very useful for developing intervention protocols. We plan to test his convergent validity with the Childhood Executive Functioning Inventory (CHEXI) and Emotion Dysregulation Inventory (EDI) and divergent validity between a group of typically developing children and children with neurodevelopmental disorders, aged between 6 and 9 years old. In a previous pilot study, we enrolled a sample of 40 children with autism spectrum disorders and attention-deficit/hyperactivity disorder aged 6 to 12 years old, and we applied the above-mentioned scales (CHEXI and EDI). Our results showed that deficits in planning, bebavior regulation, inhibition, and working memory predict high levels of emotional reactivity, leading to emotional and behavioural problems. Considering previous results, we expect our findings to provide support for the validity and reliability of the REMEX version as an ecological instrument for assessing emotion regulation and EF in children and for key features of its uses in intervention protocols.

Keywords: executive functions, emotion regulation, children, item response theory, focus group

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Authors: Michelle Maurer, Antonia Last, Mark S. Gresnigt, Bernhard Hube, Alexander S. Mosig

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The intestinal epithelium forms an essential barrier to prevent translocation of microorganisms, toxins or other potentially harmful molecules into the bloodstream. In particular, dendritic cells of the intestinal epithelium orchestrate an adapted response of immune tolerance to commensals and immune defense against invading pathogens. Systemic inflammation is typically associated with a dysregulation of this adapted immune response and is accompanied by a disruption of the epithelial and endothelial gut barrier which enables dissemination of pathogens within the human body. To understand the pathophysiological mechanisms underlying the inflammation-associated gut barrier breakdown, it is crucial to elucidate the complex interplay of the host and the intestinal microbiome. A microfluidically perfused three-dimensional intestine-on-chip model was established to emulate these processes in the presence of immune cells, commensal bacteria, and facultative pathogens. Multi-organ tissue flow (MOTiF) biochips made from polystyrene were used for microfluidic perfusion of the intestinal tissue model. The biochips are composed of two chambers separated by a microporous membrane. Each chamber is connected to inlet and outlet channels allowing independent perfusion of the individual channels and application of microfluidic shear stress. Human umbilical vein endothelial cells (HUVECs), monocyte-derived macrophages and intestinal epithelial cells (Caco-2) were assembled on the biochip membrane. Following 7 – 14 days of growth in the presence of physiological flow conditions, the epithelium was colonized with the commensal bacterium Lactobacillus rhamnosus, while the endothelium was perfused with peripheral blood mononuclear cells (PBMCs). Additionally, L. rhamnosus was co-cultivated with the opportunistic fungal pathogen Candida albicans. Within one week of perfusion, the epithelial cells formed self-organized and well-polarized villus- and crypt-like structures that resemble essential morphological characteristics of the human intestine. Dendritic cells were differentiated in the epithelial tissue that specifically responds to bacterial lipopolysaccharide (LPS) challenge. LPS is well-tolerated at the luminal epithelial side of the intestinal model without signs of tissue damage or induction of an inflammatory response, even in the presence of circulating PBMC at the endothelial lining. In contrast, LPS stimulation at the endothelial side of the intestinal model triggered the release of pro-inflammatory cytokines such as TNF, IL-1β, IL-6, and IL-8 via activation of macrophages residing in the endothelium. Perfusion of the endothelium with PBMCs led to an enhanced cytokine release. L. rhamnosus colonization of the model was tolerated in the immune competent tissue model and was demonstrated to reduce damage induced by C. albicans infection. A microfluidic intestine-on-chip model was developed to mimic a systemic infection with a dysregulated immune response under physiological conditions. The model facilitates the colonization of commensal bacteria and co-cultivation with facultative pathogenic microorganisms. Both, commensal bacteria alone and facultative pathogens controlled by commensals, are tolerated by the host and contribute to cell signaling. The human intestine-on-chip model represents a promising tool to mimic microphysiological conditions of the human intestine and paves the way for more detailed in vitro studies of host-microbiota interactions under physiologically relevant conditions.

Keywords: host-microbiota interaction, immune tolerance, microfluidics, organ-on-chip

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Authors: Affan Ahmed

Abstract:

This research investigates the impact of the geomagnetic storm occurring from April 22 to April 26, 2023, on the Earth’s ionosphere, with a focus on analyzing specific ionospheric parameters to understand the storm's effects on ionospheric stability and GNSS signal propagation. Geomagnetic storms, caused by intensified solar wind-magnetosphere interactions, can significantly disturb ionospheric conditions, impacting electron density, Total Electron Content (TEC), and thermospheric composition. Such disturbances are particularly relevant to satellite-based navigation and communication systems, as fluctuations in ionospheric parameters can degrade signal integrity and reliability. In this study, data were obtained from multiple sources, including OMNIWeb for parameters like Dst, Kp, Bz, Electric Field, and solar wind pressure, GUVI for O/N₂ ratio maps, and TEC data from low-, mid-, and high-latitude stations available on the IONOLAB website. Additional Equatorial Electrojet (EEJ) and geomagnetic data were acquired from INTERMAGNET. The methodology involved comparing storm-affected data from April 22 to April 26 with quiet days in April 2023, using statistical and wavelet analysis to assess variations in parameters like TEC, O/N₂ ratio, and geomagnetic indices. The results show pronounced fluctuations in TEC and other ionospheric parameters during the main phase of the storm, with spatial variations observed across latitudes, highlighting the global response of the ionosphere to geomagnetic disturbances. The findings underline the storm’s significant impact on ionospheric composition, particularly in mid- and high-latitude regions, which correlates with increased GNSS signal interference in these areas. This study contributes to understanding the ionosphere’s response to geomagnetic activity, emphasizing the need for robust models to predict and mitigate space weather effects on GNSS-dependent technologies.

Keywords: geomagnetic storms, ionospheric disturbances, space weather effects, magnetosphere-ionosphere coupling

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Authors: Dalal Albudaiwi, Mike Allen, Talal Alhaji, Shahnaz Khadimehzadah

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As a pandemic, COVID-19 has impacted the whole world since November 2019. In other words, every organization, industry, and institution has been negatively affected by the Coronavirus. The uncertainty of how long the pandemic will last caused chaos at all levels. As with any other institution, public libraries were affected and transmitted into online services and resources. As internationally, have been witnessed that some public libraries were well-prepared for such disasters as the pandemic, and therefore, collections, users, services, technologies, staff, and budgets were all influenced. Public libraries’ policies did not mention any plan regarding such a pandemic. Instead, there are several rules in the guidelines about disasters in general, such as natural disasters. In this pandemic situation, libraries have been involved in different uneasy circumstances. However, it has always been apparent to public libraries the role they play in serving their communities in excellent and critical times. It dwells into the traditional role public libraries play in providing information services and sources to satisfy their information-based community needs. Remarkably increasing people’s awareness of the importance of informational enrichment and enhancing society’s skills in dealing with information and information sources. Under critical circumstances, libraries play a different role. It goes beyond the traditional part of information providers to the untraditional role of being a social institution that serves the community with whatever capabilities they have. This study takes two significant directions. The first focuses on investigating how libraries have responded to COVID-19 and how they manage disasters within their organization. The second direction focuses on how libraries help their communities to act during disasters and how to recover from the consequences. The current study examines how libraries prepare for disasters and the role of public libraries during disasters. We will also propose “measures” to be a model that libraries can use to evaluate the effectiveness of their response to disasters. We intend to focus on how libraries responded to this new disaster. Therefore, this study aims to develop a comprehensive policy that includes responding to a crisis such as Covid-19. An analytical lens inside the libraries as an organization and outside the organization walls will be documented based on analyzing disaster-related literature published in the LIS publication. The study employs content analysis (CA) methodology. CA is widely used in the library and information science. The critical contribution of this work is to propose solutions it provides to libraries and planers to prepare crisis management plans/ policies, specifically to face a new global disaster such as the COVID-19 pandemic. Moreover, the study will help library directors to evaluate their strategies and to improve them properly. The significance of this study lies in guiding libraries’ directors to enhance the goals of the libraries to guarantee crucial issues such as: saving time, avoiding loss, saving budget, acting quickly during a crisis, maintaining libraries’ role during pandemics, finding out the best response to disasters, and creating plan/policy as a sample for all libraries.

Keywords: Covid-19, policy, preparedness, public libraries

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Authors: Zineb Ouahdi

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Spirocyclic compound derivatives, with their unique heterocyclic motifs, serve as a continual source of inspiration in the pursuit of developing potential therapeutic agents. These compounds are diverse in their chemical structures; some have fully saturated skeletons, while others are partially unsaturated. Nevertheless, these compounds share a characteristic feature with natural products - the presence of at least one heteroatom in one of their rings. The inclusion of a C = O dipolarophile in pyridazinones imparts an exciting aspect for 1,3-dipolar cycloaddition reactions, the focal point of our study. Our research has involved a detailed theoretical investigation of the reaction between ethyl (Z)-2-bromo-2-(2-(p-tolyl)hydrazono)acetate and 6-methyl-4,5-dihydropyridazine-3(2H)-one. This has been accomplished using the DFT/B3LYP/6-31g(d,p) method, intending to illuminate the chemical pathway of this reaction. The chemical reactivity theories we used for this purpose included FMO, TS, and local and global indices derived from conceptual DFT. The theoretical framework outlined in this study allowed us to propose a reaction mechanism for cycloaddition reactions. It also enabled the identification of the potential activities of the analyzed compounds (P1, P2, P3, P4, P5, and P6) against the major protease of the coronavirus disease (COVID-19). This was achieved using various computational tools, including AutoDock Tools, Autodock Vina, Autodock 4, and PYRX.

Keywords: MEDT, pyridazin, cycloaddition, FMO, DFT, docking

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Authors: Eddy K. Mukadi

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This work is a documentary and descriptive study devoted to the epidemiological, clinical, histopathological and therapeutic profile of breast cancer deals with the department of gynecology and obstetrics of the university clinics of Kinshasa during the period from 1 January 2014 to 31 December 2014. We have identified 56 cases of breast cancer. These cancers accounted for 45.2% of gynecological mammary cancers. The youngest in our series was 18 years old while the oldest was 74 years old; And the mean age of these patients was 43.4 years and mostly multiparous (35.7%). Brides (60.7%) and bachelors (26.8%) were the most affected by breast cancer. The reasons for consultation were dominated by nodules in the breast (48.2%) followed by pain (35.7%) and nipple discharge (14.3%). In 89.2% of the cases, it was the advanced clinical stage (stage 3 and 4) and the infiltrating ductal carcinoma was the most frequent histological type (75%) The malignant tumor was mainly in the left breast (55.3%), and chemotherapy with hormone therapy and patey was the most convenient treatment (42.8%), while patey mastectomy was performed in 12.5% of patients. Because of the high incidence of breast cancer identified in our study, some preventive measures must be taken into account to address this public health problem, including breast autopalpation once a month, Early detection system development of a national breast cancer policy and the implementation of a national breast cancer control program.

Keywords: breast cancer, histopathological profile, epidemiological profile, Kinshasa

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Authors: Kathryn Strachan, Sameer Otoom, Amal AL-Gallaf, Ahmed Al Ansari

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Introduction: Introducing a reliable method to select graduates for an award in higher education can be challenging but is not impossible. Multisource feedback (MSF) is a popular assessment tool that relies on evaluations of different groups of people, including physicians and non-physicians. It is useful for assessing several domains, including professionalism, communication and collaboration and may be useful for selecting the best interns to receive a University award. Methods: 16 graduates responded to an invitation to participate in the student award, which was conducted by the Royal College of Surgeons of Ireland-Bahrain Medical University of Bahrain (RCSI Bahrain) using the MSF process. Five individuals from the following categories rated each participant: physicians, nurses, and fellow students. RCSI Bahrain graduates were assessed in the following domains; professionalism, communication, and collaboration. Mean and standard deviation were calculated and the award was given to the graduate who scored the highest among his/her colleagues. Cronbach’s coefficient was used to determine the questionnaire’s internal consistency and reliability. Factor analysis was conducted to examine for the construct validity. Results: 16 graduates participated in the RCSI-Bahrain interns’ award based on the MSF process, giving us a 16.5% response rate. The instrument was found to be suitable for factor analysis and showed 3 factor solutions representing 79.3% of the total variance. Reliability analysis using Cronbach’s α reliability of internal consistency indicated that the full scale of the instrument had high internal consistency (Cronbach’s α 0.98). Conclusion: This study found the MSF process to be reliable and valid for selecting the best graduates for the interns’ awards. However, the low response rates may suggest that the process is not feasible for allowing the majority of the students to participate in the selection process. Further research studies may be required to support the feasibility of the MSF process in selecting graduates for the university award.

Keywords: MSF, RCSI, validity, Bahrain

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Authors: M. Krishna

Abstract:

The study was intended to identify if scalp cooling therapy is effective on preventing chemotherapy-induced hair loss among cancer patients. Critical literature of non-randomized controlled trials was used to investigate whether scalp cooling therapy is effective on preventing chemotherapy-induced alopecia. The review identified that scalp cooling therapy is effective on preventing chemotherapy-induced alopecia. Most of the patients receiving chemotherapy experience alopecia. It is also perceived as the worst effect of chemotherapy. This may be severe and lead the patients to withdraw the chemo treatment. The image disturbance caused by alopecia will make the patient depressed and will lead to declined immunity. With the knowledge on effectiveness of scalp cooling therapy on preventing chemotherapy-induced alopecia, patient undergoing chemotherapy will not be hesitant to undergo the treatment. Patients are recommended to go through scalp cooling therapy every chemo cycle and the proper therapy duration is 30 minutes before, during chemo. The suggested duration of the scalp cooling therapy is 45-90 minutes for an effective and positive outcome. This finding is excluding other factors of alopecia such as menopause, therapeutic drugs, poor hair density, liver function problems, and drug regimes.

Keywords: alopecia, cancer, chemotherapy, scalp cooling therapy

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Authors: Akash Bera, Suraj Singh, Jacinta Dsouza, Ramakrishna V. Hosur, Pushpa Mishra

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Ultraviolet C (UVC) radiation induces apoptosis in mammalian cells and it is suggested that the mechanism by which this occurs is the mitochondrial pathway of apoptosis through the release of cytochrome c from the mitochondria into the cytosol. The Bcl-2 family of proteins pro-and anti-apoptotic is the regulators of the mitochondrial pathway of apoptosis. Upon UVC irradiation, the proliferation of apoptosis is enhanced through the downregulation of the anti-apoptotic protein Bcl-xl and up-regulation of Bax. Although the participation of the Bcl-2 family of proteins in apoptosis appears responsive to UVC radiation, to the author's best knowledge, it is unknown how the structure and, effectively, the function of these proteins are directly impacted by UVC exposure. In this background, we present here a structural rationale for the effect of UVC irradiation in restoring apoptosis using two of the relevant proteins, namely, Bid-FL and Bcl-xl ΔC, whose solution structures have been reported previously. Using a variety of biophysical tools such as circular dichroism, fluorescence and NMR spectroscopy, we show that following UVC irradiation, the structures of Bcl-xlΔC and Bid-FL are irreversibly altered. Bcl-xLΔC is found to be more sensitive to UV exposure than Bid-FL. From the NMR data, dramatic structural perturbations (α-helix to β-sheet) are seen to occur in the BH3 binding region, a crucial segment of Bcl-xlΔC which impacts the efficacy of its interactions with pro-apoptotic tBid. These results explain the regulation of apoptosis by UVC irradiation. Our results on irradiation dosage dependence of the structural changes have therapeutic potential for the treatment of cancer.

Keywords: Bid, Bcl-xl, UVC, apoptosis

Procedia PDF Downloads 127