Side Resistance Research Articles

PHYTOCHEMICALS ANALYSIS AND CYTOTOXIC ACTIVITY OF Lansium domesticum Corr EXTRACT-CISPLATIN COMBINATION AGAINST PANC-1 CELL LINE

The use of chemotherapy such as cisplatin in treating cancer alone can cause many problems, including side effects and resistance. Therefore, currently, efforts are being made to combine cisplatin with natural ingredients such as ethanol extract from duku leaves. Then extracted using ethanol as a solvent. The secondary metabolites of the extract were identified using LC-MS/MS with mobile phase A (0.1 percent formic acid in water) and phase B (0.1 percent formic acid in acetonitrile). The extract and cisplatin were determined by their IC50 values as the basis for carrying out the combination test using the MTT method. All data obtained were processed with Microsoft Excel and analyzed with SPSS 23. The ethanol extract of duku leaves contains about 15 compounds that cannot be clearly identified because they are not listed in the LC-MS/MS library used. Interestingly, there were 5 compounds that gave a sufficiently large absorption each at a retention time of 1.08; 5.18; 9.45; 9.57; 10.70; and 10.82. Cisplatin has stronger cytotoxic properties than the extract with IC50 values of 3.02±0.05 µg/mL and 28.61±0.13 µg/mL, respectively. The combination of these two substances is synergistic with a combination index <1. the combination of extract and cisplatin at doses of 1.75:0.75 and 1.75:0.375 had very strong synergy with a combination index of 0.01 (p>0.05). However, the mechanism of action of this combination is not yet known clearly, so further research is needed on it.

Combined Side and Base Resistance in Rock-Socketed Drilled Shafts – A State of the Art Consensus

Both side and base resistance contribute to drilled shaft rock socket axial resistance in most cases. While there are geological settings in which mobilization of side and/or base resistance may not be reliable, those situations are the exception, not the rule. The advent of bi-directional axial load testing of rock-socketed drilled shafts has resulted in a significant body of evidence regarding the independent behavior of side and base resistance mechanisms. Accordingly, over the last two decades, a wealth of data from these full-scale load tests of rock-socketed drilled shafts demonstrate this behavior when good design, construction and quality assurance/quality control (QA/QC) procedures are followed. The authors actively attempted to identify bi-directional test results to the contrary, including a survey of the entire Deep Foundations Institute (DFI) membership, but concluded there is a notable lack of evidence that side and base resistance do not mobilize simultaneously when proper design, construction and QA/QC procedures are followed in most geologic settings. Despite this fact, there are agencies and individual engineers that continue to disregard either side or base resistance for reasons that contradict available evidence, often resulting in excessive rock socket lengths that increase costs and the risk of problems during construction. The purpose of this document is to present a summary of the recent evidence indicating mobilization of combined side and base resistances at small, compatible displacements that are within the settlement tolerance of most structures in well-designed, constructed and inspected rock sockets. The recommended best practice for design of rock-socketed drilled shafts is to account for both side and base resistance unless there is a valid documented reason to disregard one or the other on a project-specific basis.

Recent Trends and Developments in Multifunctional Nanoparticles for Cancer Theranostics.

Conventional anticancer treatments, such as radiotherapy and chemotherapy, have significantly improved cancer therapy. Nevertheless, the existing traditional anticancer treatments have been reported to cause serious side effects and resistance to cancer and even to severely affect the quality of life of cancer survivors, which indicates the utmost urgency to develop effective and safe anticancer treatments. As the primary focus of cancer nanotheranostics, nanomaterials with unique surface chemistry and shape have been investigated for integrating cancer diagnostics with treatment techniques, including guiding a prompt diagnosis, precise imaging, treatment with an effective dose, and real-time supervision of therapeutic efficacy. Several theranostic nanosystems have been explored for cancer diagnosis and treatment in the past decade. However, metal-based nanotheranostics continue to be the most common types of nonentities. Consequently, the present review covers the physical characteristics of effective metallic, functionalized, and hybrid nanotheranostic systems. The scope of coverage also includes the clinical advantages and limitations of cancer nanotheranostics. In light of these viewpoints, future research directions exploring the robustness and clinical viability of cancer nanotheranostics through various strategies to enhance the biocompatibility of theranostic nanoparticles are summarised.

ANALISIS KINERJA LALU LINTAS JL. RAYA MR. MOCH. ICHSAN, KOTA SEMARANG (DEPAN PINTU KELUAR MASUK RS. PERMATA MEDIKA)

Semarang is one of the metropolitan. Traffic on Jl. Raya Mr Moch. Ichsan in front of the Permata Medika hospital, which is fairly crowded, is due to the influence of the hospital's activities. Many activities are seen at the entrance and exit of the hospital, including crossing. The purpose of this study was to analyze traffic performance, determine the factors that hinder traffic flow, determine the volume, travel time, and vehicle delay time due to u-turns at the median opening in front of the hospital entrance. Medical Gems. Traffic volume data collection was carried out for 3 days, namely weekdays, short days. and holidays using the 2014 PKJI method (referring to the reference to the 1997 MKJI basic rules). The results of the observations obtained are that the total current is 6201 cur/hour with the side resistance weight being at a moderate level. By following the 2014 PKJI guidelines, we get the adjustment values ​​for Free Flow Speed ​​(VB) = 61 km/hour and Capacity (C) = 7128 skr/hour. With a value of DJ = 0.869 cur/hour, it is at LOS level E which according to PKJI 2014 (referring to the reference to the 1997 MKJI basic rules) the level of road service is above the average for the maximum service level, namely levels A to D with a degree of saturation value of 0.00 - 0.84. Strict action from the relevant officers is needed by controlling existing traffic signs such as parking is prohibited in order to maximize the function of the existing road capacity.

ANALISIS KINERJA RUAS JALAN KELAPA 2 ENTROP JAYAPURA

Roads are a very important means of land transportation for people to connect one area to another. It also functions and plays a role in improving the regional economy, it is also needed for transportation activities to facilitate the safe and comfortable movement of goods and services. One of the factors is Jalan Kelapa 2 Entrop being the busiest road in Jayapura City because this road is a connecting road for the people of Keerom Regency and Jayapura City. The author conducted research by direct observation to the field and retrieved the data needed to support the research such as intersection geometry conditions, traffic volume, speed and side resistance. The data was then processed and analyzed using the 1997 Indonesian Highway Capacity Manual method. The research was carried out by observing for three days and carried out in the morning, afternoon and evening according to traffic congestion conditions. Based on the calculation results, a solution or alternative is obtained, namely prohibiting the entry and exit of vehicles on the side of the road and imposing a ban on parking on the east side of the road, also obtaining a road capacity value of 1312.84 pcu/hour, DS of 0.76 and FV 28.18 km/ hours, so that the degree of saturation is 0.76, so it still meets the normal limit requirements based on the 1997 Indonesian Road Capacity Manual.

Analisis Kinerja Ruas Jalan (Studi Kasus Jalan Tangkuban Perahu, Denpasar Barat)

Denpasar city is one of the big cities that has a very high population, it can be seen from the population of Denpasar city of 962,900.000 million people, (BPS, 2020). Over time, the traffic density on the road has increased, in addition to the increasing number of residents and the increasing number of private vehicle ownership, it is also caused by the location adjacent to shopping centers and restaurants. This research was conducted using primary data. Primary data was obtained from survey results in the form of traffic survey data,Road Capacity, Degree of Saturation, and Level of Service using the 2014 PKJI method. Based on the results of the discussion, it can be concluded that the performance of the Tangkuban Perahu road is at Level of Service F, which means it is very bad, with the following indicators. The peak hour volume is 2394 cur/hour. Capacity 2381 cur/hour. The side resistance is 98,4, for the side resistance class it is classified as very low, which is 0.96. The degree of saturation (DJ) > 1.00 is 101 cur/hour. The average travel speed of vehicles at a distance of 100m is 21,69 km/hour.

Synthesis and Anti-Leishmanial Properties of Quinolones Derived from Zanthosimuline.

Quinoline derivatives and especially quinolones are considered as privileged structures in medicinal chemistry and are often associated with various biological properties. We recently isolated a series of original monoterpenyl quinolones from the bark of Codiaeum peltatum. As this extract was found to have a significant inhibitory activity against a Leishmania species, we decided to study the anti-leishmanial potential of this type of compound. Leishmaniasis is a serious health problem affecting more than 12 million people in the world. Available drugs cause harmful side effects and resistance for some of them. With the aim of finding anti-leishmanial compounds, we developed a synthetic strategy to access natural quinolones and analogues derived from zanthosimuline. We showed the versatility of this natural compound toward cyclization conditions, leading to various polycyclic quinolone-derived structures. The natural and synthetic compounds were evaluated against amastigote forms of Leishmania infantum. The results obtained confirmed the interest of this family of natural compounds but also revealed promising activities for some intermediates deriving from zanthosimuline. Following the same synthetic strategy, we then prepared 14 new analogues. In this work, we identified two promising molecules with good activities against intramacrophage L. infantum amastigotes without any cytotoxicity. We also showed that slight changes in amide functional groups affect drastically their anti-parasitic activity.

Derivative Compounds of Chromanone As Candidates for Multiple Myeloma-Targeted Anticancer Drugs

Introduction: More than 70% of multiple myeloma (MM) cases occur in elderly patients over the age of 65 years, and the incidence of MM has remarkably increased in Korea over the past 20 years; thus, it is necessary to discover a new therapeutic agent that can be safely used in elderly patients. Lenalidomide-based therapeutics and proteasome inhibitors, which are currently used as the basis for the treatment of MM in clinical practice, have accompanying systemic side effects, such as pancytopenia, peripheral neuropathy, and severe skin lesions. Therefore, it is necessary to develop new therapeutic agents that can overcome the serious side effects, treatment tolerance, or resistance to these therapeutic agents. Methods: A chromanone-based (KBB-NX derivatives) low-molecular weight compound was synthesized by targeting prohibitin (PHB), which is our own companion diagnostic marker for hematologic cancers, such as MM. For the synthesized low-molecular weight synthetic substances, candidate synthetic compounds were identified through efficacy verification tests at the cell line level, blood stability tests, pharmacokinetic tests using laboratory animals, and single-dose toxicity tests. Further, after conducting an efficacy test using the mouse MM model that we built ourselves, we performed a study to discover a lead compound that can be used for non-clinical testing at the Good Laboratory Practices level. Results: In this study, 30 types of KBB-NX-based active substances that had an apoptotic effect on MM cells by blocking the PHB2 protein were obtained. When MM cells were treated with these active substances, the PHB2 function was inactivated to increase the intracellular reactive oxygen species (ROS) production, and then, proapoptotic and anti-proliferative effects were induced to kill MM cells. Among the discovered active substances, when a MM cell line was exposed to KBB-NX16, the amount of the target PHB2 protein was decreased by more than 90%, confirming the high molecular-target binding ability. Among the compounds synthesized by itself as a KBB-NX derivative, KBB-NX20 was found to have an IC50 of less than 1 μM. In the initial pharmacokinetic test for KBB-NX16 and KBB-NX20 compounds, which was conducted using rats, their half-lives were very short, less than 1 hour and 40 minutes; hence, there was a need for formulation studies. The need for early pharmacokinetic testing was increased. Conclusions: We identified effective substances from PHB-targeted chromanone compounds for the treatment of MM using an apoptosis mechanism through excessive production of intracellular ROS. These results suggested derivatives of PHB2 target chromanone compounds as candidates for MM-targeted anticancer drugs. Keywords: Multiple myeloma, PHB2, Targeted anticancer drugs, Chromanone compound Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Study on time effect of bearing capacity of Offshore Large Diameter Monopiles

In order to improve the evaluation ability of bearing capacity of offshore large-diameter monopile, the initial high strain detection and repeated high strain detection with an interval of 10-84 days were carried out on 6 large-diameter monopiles with a diameter of 7.2m-7.4m in the offshore wind field dominated by cohesive soil layer. The results show that the time-dependent increase of tip resistance, pile side resistance and total resistance of large-diameter monopiles in the same offshore wind farm has great discreteness, and the axial force increment of pile has a consistent change trend. This paper puts forward the prediction interval of 95% guarantee rate of bearing capacity increment of offshore large-diameter single pile based on depth, which provides a basis for the design of large-diameter monopile.

Anti-cancer effects of human placenta-derived amniotic epithelial stem cells loaded with paclitaxel on cancer cells

Available therapeutic strategies for cancers have developed side effects, resistance, and recurrence that cause lower survival rates. Utilizing targeted drug delivery techniques has opened up new hopes for increasing the efficacy of cancer treatment. The current study aimed to investigate the appropriate condition of primming human amniotic epithelial cells (hAECs) with paclitaxel as a dual therapeutic approach consisting of inherent anticancer features of hAECs and loaded paclitaxel. The effects of paclitaxel on the viability of hAECs were evaluated to find an appropriate loading period. The possible mechanism of hAECs paclitaxel resistance was assessed using verapamil. Afterward, the loading and releasing efficacy of primed hAECs were evaluated by HPLC. The anti-neoplastic effects and apoptosis as possible mechanism of conditioned media of paclitaxel-loaded hAECs were assessed on breast and cervical cancer cell lines. hAECs are highly resistant to cytotoxic effects of paclitaxel in 24 h. Evaluating the role of P-glycoproteins in hAECs resistance showed that they do not participate in hAECs resistance. The HPLC demonstrated that hAECs uptake/release paclitaxel with optimum efficacy in 8000 ng/ml treatment. Assessing the anti-proliferative effect of primed hAECs condition media on cancer cells showed that the secretome induced 3.3- and 4.8-times more potent effects on MCF-7 and HeLa, respectively, and enhanced the apoptosis process. These results suggest that hAECs could possibly be used as a drug delivery system for cancer treatment. Besides, inherent anticancer effects of hAECs were preserved during the modification process. Synergistic anticancer effects of paclitaxel and hAECs can be translated into clinical practice, which would be evaluated in the future studies.

Copper(II) Complex Containing 4-Fluorophenoxyacetic Acid Hydrazide and 1,10-Phenanthroline: A Prostate Cancer Cell-Selective and Low-Toxic Copper(II) Compound.

Prostate Cancer (PCa) is the second leading cause of cancer-related deaths among men worldwide. The treatment of advanced cases is based on chemotherapy, which lacks specificity and efficacy, due to severe side effects and resistance to the traditional drugs. Copper complexes have shown antitumoral efficacy and low toxicity, being considered a promising class of metal-based drugs for the treatment of malignant neoplasms. Thus, the present study aimed to evaluate the cellular effects of a copper(II) complex with 4-fluorophenoxyacetic acid hydrazide and 1,10-phenanthroline (1) on PCa cell lines, as well as the mutagenic/recombinogenic and anticarcinogenic potential of 1 in Drosophila melanogaster. PNT-2 (non-tumorigenic), LNCaP (hormone-responsive PCa) and PC-3 (androgen-independent PCa) cells were cultured, and cytotoxicity was assessed using the MTT assay. The expression levels of the proliferation markers Ki-67 and Cyclin D1 were analyzed by flow cytometry. Furthermore, the Somatic Mutation and Recombination Test (SMART) and the Epithelial Tumor Test (ETT) were performed. Complex 1 was selective to LNCaP cells, significantly reducing Ki-67 and Cyclin D1 expression levels. Sub-toxic concentrations of complex 1 were defined by the toxicity test in D. melanogaster, and no mutagenic/recombinogenic/carcinogenic effects were observed. Anticarcinogenic potential was observed in D. melanogaster, suggesting modulating activity of the complex 1 against Doxorubicin, a drug used as control by its carcinogenic properties. Therefore, complex 1 is a possible starting point for the development of new antitumor agents for the treatment of PCa.

Evaluation of Anti-leishmanial Effect of Selenium Nanoparticles on Leishmania major Promastigotes In Vitro

Background: Cutaneous leishmaniasis (CL) remains a major health threatening disease in Iran and many countries around the world. Antimony compounds are currently used to treat CL. Due to the side effects and high resistance, the use of alternative therapies, especially the use of nanoparticles, has been considered by researchers. The aim of this study was to investigate the anti-leishmanial activity of selenium nanoparticles (SeNPs) on Leishmania major in vitro. Methods: In this experimental study, the anti-leishmanial activity of the SeNPs was evaluated at concentrations of 1.25, 2.5, 5, 10, 25, 50, and 100 µg/mL at exposure times of 24, 48, and 72 hours on 106 live parasites. Then, the number of live parasites was counted by trypan blue using a neobar slide and light microscope (Hemocytometer method). Glucantime and distilled water were considered positive and negative controls, respectively. Then, 50% inhibitory concentration (IC50) values were calculated by SigmaPlot™ 13 software. All reactions were performed in triplicate, and the results were considered as average. Results: The results of this study revealed that all concentrations of SeNPs have anti-leishmanial activity. The concentration of 100 µg/mL of SeNPs had the highest anti-leishmanial effect (100%) after 72 hours of exposure. Further, the IC50 content of SeNPs on L. major after 24, 48, and 72 hours was calculated to be 42.76, 34.53, and 22.69 µg/mL, respectively. Conclusions: The results indicated that SeNPs in different concentrations has an inhibitory effect on the growth of L. major. However, further investigations are required to determine the efficacy of SeNPs in vivo.

Melanoma Management: From Epidemiology to Treatment and Latest Advances.

Simple SummaryMelanoma is a major public health issue that claims the lives of thousands of people every year. Furthermore, the outlook for the coming years is not encouraging with increasing morbidity and mortality trends. This review aims to offer an updated overview of various aspects related to cutaneous melanoma, from epidemiology, etiology, clinical presentation, prevention, diagnosis and staging. Moreover, conventional treatments currently available as well as the latest advances in clinical trials regarding new drugs and/or combinations, including nanotechnology-based strategies are also reviewed.Melanoma is the deadliest skin cancer, whose morbidity and mortality indicators show an increasing trend worldwide. In addition to its great heterogeneity, melanoma has a high metastatic potential, resulting in very limited response to therapies currently available, which were restricted to surgery, radiotherapy and chemotherapy for many years. Advances in knowledge about the pathophysiological mechanisms of the disease have allowed the development of new therapeutic classes, such as immune checkpoint and small molecule kinase inhibitors. However, despite the incontestable progress in the quality of life and survival rates of the patients, effectiveness is still far from desired. Some adverse side effects and resistance mechanisms are the main barriers. Thus, the search for better options has resulted in many clinical trials that are now investigating new drugs and/or combinations. The low water solubility of drugs, low stability and rapid metabolism limit the clinical potential and therapeutic use of some compounds. Thus, the research of nanotechnology-based strategies is being explored as the basis for the broad application of different types of nanosystems in the treatment of melanoma. Future development focus on challenges understanding the mechanisms that make these nanosystems more effective.

Combination treatment of hepatitis C virus-associated hepatocellular carcinoma by simultaneously blocking genes in multiple organelles via functionally engineered graphene oxide

Chemical reagents are widely used to block disease development, including tumor progression and increase in abnormal cell populations; however, their consistent usage is limited owing to drug-related side effects and resistance. Although strategies to enhance the intracellular delivery of anticancer drugs, even at low concentrations, and decrease their undesired side effects have been developed, practical approaches for liver cancer are still limited. Combination therapy has become a solution for improving chemotherapeutic efficacy. Here, we designed a dual-therapeutic platform by engineering graphene oxide (GO) as a multi-functional co-delivery carrier that targets multiple organelles in cells. It delivers two therapeutic reagents as a single vehicle while simultaneously blocking genes in the nucleus and cytoplasm. We adopted a xenograft mouse model of hepatitis C virus infection to verify the therapeutic efficacy of this combinatorial approach. Our strategy successfully suppressed tumor growth by enhancing the intracellular accumulation of anticancer drugs even at one-tenth of the conventional dosage of drugs. Simultaneously, the dual-treat method showed a twofold therapeutic efficiency compared with single-drug treatment. By facilitating a combination of individual pharmacological effects, the present functional GO-based delivery system could be a promising multimodal therapeutic platform owing to its high stability, biocompatibility, and multifunctionality.

Field Test Study on Vertical Bearing Characteristics of Coal Rock

Coal rock is rarely used as the foundation bearing strata. For buildings located on coal rock, it is a reasonable and feasible way to obtain the vertical bearing characteristics of coal rock through field tests. Three plate load tests and two bi-directional load tests were carried out, and the design parameters of the vertical bearing capacity of the shallow foundation and the deep foundation were obtained, respectively. The plate load test results show that the pressure–settlement curve of coal rock is a steep-drop-type, and the deformation modulus decreases with the increase of the pressure. The bi-directional load test results show that the unit tip resistance-displacement curve of coal rock is a steep-drop-type, and the load transfer function of the unit tip resistance is an ideal elastic–plastic curve, and the displacement value corresponding to the ultimate bearing capacity is about 1% of the pile diameter. The load transfer function of the unit side resistance of coal rock is a hyperbolic curve. The equivalent pile top load–settlement curve obtained according to the load transfer functions of the unit tip resistance and the unit side resistance is consistent with the equivalent conversion results of the bi-directional load test method.

Programmed Cell Death-Ligand-1 expression in Bladder Schistosomal Squamous Cell Carcinoma - There's room for Immune Checkpoint Blockage?

Schistosoma haematobium, the causative agent of urogenital schistosomiasis, is a carcinogen type 1 since 1994. It is strongly associated with bladder squamous-cell carcinoma in endemic regions, where it accounts for 53-69% of bladder-carcinoma cases. This histological subtype is associated with chronic inflammation being more aggressive and resistant to conventional chemo and radiotherapy. Immune-Checkpoint-Blockage (ICB) therapies targeting the Programmed-Cell-Death-Protein-1(PD-1)/Programmed-Cell-Death-Ligand-1(PD-L1) axis showed considerable success in treating advanced bladder urothelial carcinoma. PD-L1 is induced by inflammatory stimuli and expressed in immune and tumor cells. The binding of PD-L1 with PD-1 modulates immune response leading to T-cell exhaustion. PD-L1 presents in several isoforms and its expression is dynamic and can serve as a companion marker for patients’ eligibility, allowing the identification of positive tumors that are more likely to respond to ICB therapy. The high PD-L1 expression in bladder-urothelial-carcinoma and squamous-cell carcinoma may affect further ICB-therapy application and outcomes. In general, divergent histologies are ineligible for therapy. These treatments are expensive and prone to auto-immune side effects and resistance. Thus, biomarkers capable of predicting therapy response are needed. Also, the PD-L1 expression assessment still needs refinement. Studies focused on squamous cell differentiation associated with S. haematobium remain scarce. Furthermore, in low and middle-income-regions, where schistosomiasis is endemic, SCC biomarkers are needed. This mini-review provides an overview of the current literature regarding PD-L1 expression in bladder-squamous-cell-carcinoma and schistosomiasis. It aims to pinpoint future directions, controversies, challenges, and the importance of PD-L1 as a biomarker for diagnosis, disease aggressiveness, and ICB-therapy prognosis in bladder-schistosomal-squamous-cell carcinoma.

Rhodium-Tellurium Nanorod Synthesis Using Galvanic Replacement-Polyol Regrowth for Thermo-Dynamic Dual-Modal Cancer Phototherapy.

Rh is a noble metal introduced in bioapplications, including diagnosis and therapy, in addition to its consolidated utilization in organic catalysis and electrocatalysis. Herein, we designed the synthesis of highly crystalline Rh nanocrystal-decorated Rh-Te nanorods (RhTeNRs) through galvanic replacement of sacrificial Te nanorod (TeNR) templates and subsequent polyol regrowth. The obtained RhTeNRs showed excellent colloidal stability and efficient heat dissipation and photocatalytic activity under various laser irradiation wavelengths. Based on the confirmed biocompatibility, RhTeNRs were introduced into in vitro and in vivo cancer phototherapies. The results confirmed the selective physical death of cancer cells in the local area through laser irradiation. While chemotherapy does not guarantee successful treatment due to side effects and resistance, phototherapy using heat and reactive oxygen species generation of RhTeNRs induces physical death.

Antibiotic use numeracy: Developing the infectious numeracy test (INT).

Inadequate numeracy is a barrier to patients' understanding of their health. No measure of numeracy related to antibiotic use is available. to develop and validate a measure of numeracy of antibiotic use, and to make this measure available in the Arabic language and context. Best practices for developing, translating and validating scales were consulted to develop an anonymous survey administered on SurveyMonkey. Ten open-ended questions for which participants provided an answer assessed basic numeracy covering fractions, percentages, proportionality, measurement, and estimation, contextualized to real life situations. A panel of five experts, and 10 cognitive debriefings provided face and content validity for the tool. Individuals ≥18 years, who had mastery of Arabic or English were included. Exploratory factor analysis was performed to characterize the psychometric properties of the items, using principal-component analysis. Convergent validity was established by comparing numeracy scores with the antibiotic knowledge scale scores. Differences in numeracy scores according to sociodemographic variables were tested using multivariate analyses of variance. Two hundred fifty-four responses were obtained, giving a response rate of 63.5%. A two-factor structure which explained 44.2% of the variance evolved: "Mathematical knowledge and problem-solving skills" and "Numeracy-related practices and experience". An acceptable reliability of Cronbach's alpha coefficient=0.713. Higher numeracy scores were significantly correlated with the scores of the antibiotic knowledge (r=0.205, p<0.01) and factor one within the tool: "side effects and resistance" (r=0.162, p=0.05). Participants with University/College education presented higher levels of numeracy-related practices and experience than those with high-school education. Likewise, participants with medical insurance presented with higher numeracy scores than those without. A valid and reliable measure of antibiotic numeracy in English and Arabic was created. The tool could identify patients with low numeracy who are candidates for targeted interventions and intensive education on appropriate antibiotic use.

VALIDATION OF SCREENING MODELS OF EPILEPSY: A REVIEW

Epilepsy is a severe neurological illness characterized by abnormal, recurring, and synchronized brain discharges. Long-term recurring seizure attacks can cause substantial brain function loss, as seen in people with temporal lobe epilepsy. Controlling seizure events is critical for epilepsy therapy and prognosis. The disease is more common in developing countries than in developed countries. The causes of epilepsy include chemical imbalances such as low blood sugar or sodium, head injuries, drug abuse or withdrawal, alcohol withdrawal, stroke tumor affecting the blood vessels (vascular system) in the brain, hardening of the arteries (atherosclerosis) in the brain, brain tumours, and brain infections such as meningitis or encephalitis. Given the prevalence of epilepsy and the challenges associated with currently available antiepileptic medicines, such as side effects, resistance, safety concerns, and high cost, screening models are utilized in epilepsy analysis. Screening models for seizures and epilepsy have been critical in expanding our understanding of the fundamental mechanisms underlying ictogenesis and epileptogenesis, as well as in the discovery and preclinical development of novel antiepileptic medicines (AEDs). Diverse screening models of epilepsy have been developed in recent years to imitate various seizure forms, with no clear advantages or disadvantages. In this study, we will cover the numerous screening models for epilepsy, which will aid in gaining a better understanding of the disease.

Discovery of novel drugs for Chagas disease: is carbonic anhydrase a target for antiprotozoal drugs?

ABSTRACT Introduction Carbonic anhydrase (CA) arose significant interest as a potential new target for Chagas disease since its discovery in Trypanosoma cruzi in 2013. Benznidazole and Nifurtimox have been used for Chagas disease treatment for 60 years despite all efforts done for obtaining more efficient treatments, acting in the acute and chronic phases of illness, with fewer side effects and resistance induction. Areas covered We discuss the positive and negative aspects of T. cruzi CA (TcCA) studies as a target for developing new drugs. The current research discoveries and the classes of TcCA inhibitors are reviewed. The sulfonamides and their derivatives are the main inhibitor classes, but hydroxamates and the thiols, were investigated too. These compounds inhibited the growth of the evolutive forms of the parasite. A comparative analysis was done with CAs from other Trypanosomatids and protozoans. Expert opinion The search for new targets and drugs is a significant challenge worldwide, and TcCA is a potential candidate for developing new drugs. Several studied inhibitors were active against Trypanosoma cruzi, but their penetration and toxicity problems emerged. New approaches are in progress to obtain inhibitors with desired properties, allowing further steps such as tests using an adequate animal model and subsequent developments for the preclinical testing.