Development of new TAK-285 derivatives as potent EGFR/HER2 inhibitors possessing antiproliferative effects against 22RV1 and PC3 prostate carcinoma cell lines.

Epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) protein tyrosine kinases co-expressed in various cancers such as ovarian, breast, colon, and prostate subtypes. Herein, new TAK-285 derivatives (9a-h) were synthesised, characterised, and biologically evaluated as dual EGFR/HER2 inhibitors. Compound 9f exhibited IC50 values of 2.3 nM over EGFR and 234 nM over HER2, which is 38-fold of staurosporine and 10-fold of TAK-285 over EGFR. Compound 9f also showed high selectivity profile when tested over a small kinase panel. Compounds 9a-h showed IC50 values in the range of 1.0-7.3 nM and 0.8-2.8 nM against PC3 and 22RV1 prostate carcinoma cell lines, respectively. Cell cycle analysis, apoptotic induction, molecular docking, dynamics, and MM-GBSA studies confirmed the plausible mechanism(s) of compound 9f as a potent EGFR/HER2 dual inhibitor with an effective antiproliferative action against prostate carcinoma.

Therapeutic potential of natural products in inflammation: underlying molecular mechanisms, clinical outcomes, technological advances, and future perspectives.

Chronic inflammation is a common underlying factor in many major diseases, including heart disease, diabetes, cancer, and autoimmune disorders, and is responsible for up to 60% of all deaths worldwide. Metformin, statins, and corticosteroids, and NSAIDs (non-steroidal anti-inflammatory drugs) are often given as anti-inflammatory pharmaceuticals, however, often have even more debilitating side effects than the illness itself. The natural product-based therapy of inflammation-related diseases has no adverse effects and good beneficial results compared to substitute conventional anti-inflammatory medications. In this review article, we provide a concise overview of present pharmacological treatments, the pathophysiology of inflammation, and the signaling pathways that underlie it. In addition, we focus on the most promising natural products identified as potential anti-inflammatory therapeutic agents. Moreover, preclinical studies and clinical trials evaluating the efficacy of natural products as anti-inflammatory therapeutic agents and their pragmatic applications with promising outcomes are reviewed. In addition, the safety, side effects and technical barriers of natural products are discussed. Furthermore, we also summarized the latest technological advances in the discovery and scientific development of natural products-based medicine.

Physical properties and pharmacological applications of Co3O4, CuO, NiO and ZnO nanoparticles.

Nano materials have found developing interest in biogenic approaches in the present times. In this study, metal oxide nanoparticles (NPs) such as cobalt oxide (Co3O4), copper oxide (CuO), nickel oxide (NiO) and zinc oxide (ZnO), were synthesized using a convenient and rapid method. The structural features of synthesized metal oxide NPs were studied using various microscopic and spectroscopic techniques like SEM, TEM, XRD, FTIR and EDX. The characterization results confirmed that the prepared NPs possess highly pure, unique and crystalline geometry with size ranging between 10 and 20 nm. The synthesized nanoparticles were successfully employed for pharmacological applications. Enzyme inhibition potential of NPs was evaluated against the urease and tyrosinase enzymes. The percent inhibition for the urease enzyme was observed as 80 to 90% by using Co3O4, CuO, NiO and ZnO NPs while ZnO NPs were found to have best anti-urease and anti-tyrosinase activities. Moreover, effective inhibition was observed in the case of ZnO NPs at IC50 values of 0.0833 and 0.1732 for urease and tyrosinase enzymes which were comparable to reference drugs thiourea and kojic acid. The lower the IC50 value, higher the free radical scavenging power. Antioxidant activity by DPPH free radical scavenging method was found moderately high for the synthesized metal oxide NPs while best results were obtained for Co3O4 and ZnO NPs as compared to the standard ascorbic acid. Antimicrobial potential was also evaluated via the disc diffusion and well diffusion methods. CuO NPs show a better zone of inhibition at 20 and 27 mm by using both methods. This study proves that the novel metal oxide NPs can compete with the standard materials used in the pharmacological studies nowadays.

Risk analysis reveals global hotspots for marine debris ingestion by sea turtles.

Plastic marine debris pollution is rapidly becoming one of the critical environmental concerns facing wildlife in the 21st century. Here we present a risk analysis for plastic ingestion by sea turtles on a global scale. We combined global marine plastic distributions based on ocean drifter data with sea turtle habitat maps to predict exposure levels to plastic pollution. Empirical data from necropsies of deceased animals were then utilised to assess the consequence of exposure to plastics. We modelled the risk (probability of debris ingestion) by incorporating exposure to debris and consequence of exposure, and included life history stage, species of sea turtle and date of stranding observation as possible additional explanatory factors. Life history stage is the best predictor of debris ingestion, but the best-fit model also incorporates encounter rates within a limited distance from stranding location, marine debris predictions specific to the date of the stranding study and turtle species. There is no difference in ingestion rates between stranded turtles vs. those caught as bycatch from fishing activity, suggesting that stranded animals are not a biased representation of debris ingestion rates in the background population. Oceanic life-stage sea turtles are at the highest risk of debris ingestion, and olive ridley turtles are the most at-risk species. The regions of highest risk to global sea turtle populations are off of the east coasts of the USA, Australia and South Africa; the east Indian Ocean, and Southeast Asia. Model results can be used to predict the number of sea turtles globally at risk of debris ingestion. Based on currently available data, initial calculations indicate that up to 52% of sea turtles may have ingested debris.

Mistaken identity? Visual similarities of marine debris to natural prey items of sea turtles.

BACKGROUND: There are two predominant hypotheses as to why animals ingest plastic: 1) they are opportunistic feeders, eating plastic when they encounter it, and 2) they eat plastic because it resembles prey items. To assess which hypothesis is most likely, we created a model sea turtle visual system and used it to analyse debris samples from beach surveys and from necropsied turtles. We investigated colour, contrast, and luminance of the debris items as they would appear to the turtle. We also incorporated measures of texture and translucency to determine which of the two hypotheses is more plausible as a driver of selectivity in green sea turtles. RESULTS: Turtles preferred more flexible and translucent items to what was available in the environment, lending support to the hypothesis that they prefer debris that resembles prey, particularly jellyfish. They also ate fewer blue items, suggesting that such items may be less conspicuous against the background of open water where they forage. CONCLUSIONS: Using visual modelling we determined the characteristics that drive ingestion of marine debris by sea turtles, from the point of view of the turtles themselves. This technique can be utilized to determine debris preferences of other visual predators, and help to more effectively focus management or remediation actions.

Factors necessary for entrustment decision-making in surgical operating rooms: A modified Delphi study.

Objective: Resident autonomy in an operation theatre has been directly linked with patient safety in healthcare. The objective of this study was to identify the factors necessary for making resident-entrustment decisions from the perspective of a supervisor/consultant viewpoint. The second objective was to develop a checklist for assessing resident readiness for independent work. Materials and methods: This study employed a mixed-method Delphi approach. In the first stage, a comprehensive literature review and a qualitative exploratory study produced a list of factors related to residents. The second phase involved content validation by a panel of experts, followed by a two-round Delphi study with 20 expert panelists. Results: A total of 49 resident-related factors for entrustment were identified, which were reduced to 46 after content validation. During Delphi Round I, 17 factors were fully accepted, 7 were rejected and 22 items were partially accepted. Out of the 39 items sent to Delphi Round II, 23 items were accepted and 16 were rejected. A final 23-item checklist was formed based on the following factors; 6 Cognitive (knowledgeable, risk manager, safe doctor, general manager, field of interest, communicator), 5 Psychomotor (past performer, competent, ability to pick critical findings, ability to act situationally, decision maker) and 12 affective (responsible, leader, honest, empathetic, ethical, receptive, humble, emotionally intelligent, motivated, accountable, team player, disciplined) factors. Conclusion: The study resulted in the formation of a checklist based on the factors necessary for entrustment decision-making in surgical operating rooms. Some of the novel contextual factors were 'general manager', 'field of interest', 'ability to pick critical findings', 'accountable', 'risk manager', and 'past performer'. This framework offers a guideline for supervisors and residents to evaluate progress throughout the residency program. The developed tool demonstrates good content validity and is suitable for entrustment assessment following construct validation.

Prevalence of Overweight/Obesity Associated With Anemia Among Female Medical Students at Umm Al-Qura University in Makkah, Saudi Arabia: A Cross-Sectional Study.

Introduction The obesity epidemic has been linked to a wide range of health and nutritional problems, including anemia, which is often caused by impaired iron metabolism. The World Health Organization considers anemia and obesity to be global health issues among adolescent girls and women experiencing menstruation. This study aims to examine the association between iron deficiency anemia and obesity/overweight among female medical students. Methodology This cross-sectional descriptive study conducted as an online self-administered questionnaire. Furthermore, blood samples were collected from 206 students to evaluate the complete blood count, iron and lipid profile. Results The convenience sampling technique was used and a total of 206 students were enrolled in the study. The average body mass index (BMI) was 22.51 ± 3.25, with 83.5% (n = 172) falling within the normal weight range, 12.6% (n = 26) as overweight, and 3.9% (n = 8) as obese. Anemia was present in 16.0% (n = 33) of the participants overall. Higher prevalence of anemia was observed among overweight participants with 10 out of 26 (38.5%) subjects compared to obese with two out of eight (25.0%) and normal weight 21 out of 172 (12.2%); this difference was highly significant (P = 0.005). Individuals with anemia exhibited a significant association with those experiencing a diet full of unhealthy fats and carbohydrates (P = 0.05) and a diet containing all essential nutrients (P = 0.01). There is no statistically significant correlation between anemia prevalence and participants' response to the presence of signs of anemia, physical activity or other dietary habits. Obese participants had a significantly higher mean value of triglycerides (129.5 ± 20.5) compared to normal weight and overweight participants (74.5 ± 12.02 and 51.2 ± 15.04), respectively (P = 0.001). Conclusion A dependable assembly exists between obesity and overweight in cases of iron deficient anemia. The prevalence of iron deficiency anemia was substantially higher among overweight/obese females, highlighting that overweight/obesity signifies both quantitative and qualitative malnutrition. A high BMI was associated with elevated triglycerides, typically considered indicators of obesity. This association may suggest compromised iron homeostasis.

Awareness of Hepatitis C Among the General Population of Riyadh, KSA, in 2023: A Cross-Sectional Study.

Background Hepatitis C, a highly contagious viral infection transmitted through blood-to-blood contact, poses a significant threat to public health owing to its potential to induce extensive liver damage, leading to the development of life-threatening conditions such as liver cirrhosis and hepatocellular carcinoma, commonly known as liver cancer. Objective This cross-sectional study aims to assess the level of awareness of hepatitis C among the general population in Riyadh, Saudi Arabia. Methodology The study was conducted in Riyadh, Saudi Arabia. A national cross-sectional survey was conducted using a predesigned self-administered validated electronic questionnaire. The questionnaire was distributed electronically to the general population from April to September 2023. Results Out of the 800 participants, most were females (472, 59%), and the largest age group was between 23 and 29 years old (305, 38.1%). Saudi Arabians constituted the highest proportion of participants (609, 76.1%), and most participants were single (437, 54.6%). In terms of occupational status, 288 (36%) worked in occupations not listed. The study found that 463 (57.9%) participants had a low level of awareness about the global prevalence of hepatitis C. Additionally, 489 (61.1%) were aware that hepatitis C can cause both acute and chronic hepatitis, and 441 (55.1%) knew that most infected patients may develop chronic hepatitis. A majority (484, 60.5%) were aware of the importance of washing with soap and water after an accidental needle stick injury. Most participants (574, 71.8%) were aware of the common modes of hepatitis C transmission, such as unsterilized instruments, needle stick injuries, and sharing contaminated needles during drug use. Furthermore, 548 (73%) were aware of the transmission risk through unscreened blood transfusion, and 561 (70.1%) were aware of the higher risk of infection for individuals with multiple sexual partners. Conclusion The study highlights a low level of awareness among participants regarding the treatment and prevention of hepatitis C. To address the low level of awareness regarding the treatment and prevention of hepatitis C, targeted strategies and interventions are needed. This includes the development and implementation of public awareness campaigns, creation of informative educational materials, specialized training programs for healthcare professionals, establishment of support groups and counseling services for individuals living with hepatitis C, and continued support for research efforts and knowledge dissemination. By increasing awareness about hepatitis C, its treatment, and prevention, we can improve outcomes for individuals affected by the disease and reduce its overall burden on communities.

Experimental investigation into infrasonic emissions from atmospheric turbulence.

Clear air turbulence (CAT) is the leading cause of in-flight injuries and in severe cases can result in fatalities. The purpose of this work is to design and develop an infrasonic array network for early warning of clear air turbulence. The infrasonic system consists of an infrasonic three-microphone array, compact windscreens, and data management system. Past experimental efforts to detect acoustic emissions from CAT have been limited. An array of three infrasonic microphones, operating in the field at NASA Langley Research Center, on several occasions received signals interpreted as infrasonic emissions from CAT. Following comparison with current lidar and other past methods, the principle of operation, the experimental methods, and experimental data are presented for case studies and confirmed by pilot reports. The power spectral density of the received signals was found to fit a power law having an exponent of -6 to -7, which is found to be characteristics of infrasonic emissions from CAT, in contrast to findings of the past.

Novel Hybrid Indole-Based Caffeic Acid Amide Derivatives as Potent Free Radical Scavenging Agents: Rational Design, Synthesis, Spectroscopic Characterization, In Silico and In Vitro Investigations.

Antioxidant small molecules can prevent or delay the oxidative damage caused by free radicals. Herein, a structure-based hybridization of two natural antioxidants (caffeic acid and melatonin) afforded a novel hybrid series of indole-based amide analogues which was synthesized with potential antioxidant properties. A multiple-step scheme of in vitro radical scavenging assays was carried out to evaluate the antioxidant activity of the synthesized compounds. The results of the DPPH assay demonstrated that the indole-based caffeic acid amides are more active free radical scavenging agents than their benzamide analogues. Compared to Trolox, a water-soluble analogue of vitamin E, compounds 3a, 3f, 3h, 3j, and 3m were found to have excellent DPPH radical scavenging activities with IC50 values of 95.81 ± 1.01, 136.8 ± 1.04, 86.77 ± 1.03, 50.98 ± 1.05, and 67.64 ± 1.02 µM. Three compounds out of five (3f, 3j, and 3m) showed a higher capacity to neutralize the radical cation ABTS•+ more than Trolox with IC50 values of 14.48 ± 0.68, 19.49 ± 0.54, and 14.92 ± 0.30 µM, respectively. Compound 3j presented the highest antioxidant activity with a FRAP value of 4774.37 ± 137.20 µM Trolox eq/mM sample. In a similar way to the FRAP assay, the best antioxidant activity against the peroxyl radicals was demonstrated by compound 3j (10,714.21 ± 817.76 µM Trolox eq/mM sample). Taken together, compound 3j was validated as a lead hybrid molecule that could be optimized to maximize its antioxidant potency for the treatment of oxidative stress-related diseases.

Associated comorbidities in psoriasis and inflammatory bowel disease.

BACKGROUND: The association between psoriasis and inflammatory bowel disease (IBD) has been previously reported although a great deal remains unknown about associated comorbidities. OBJECTIVES: The aim of this study was to examine comorbidities in individuals diagnosed with both psoriasis and IBD, and to compare those with individuals diagnosed with psoriasis-only. We also looked at differences within the IBD group by clearly defining that cohort. METHODS: We included 146 patients diagnosed with both psoriasis and IBD and 146 controls diagnosed of psoriasis-only without previous records of IBD, matched by gender, ethnicity and age (±5 years). Patients were obtained from the research patient data repository of Brigham and Women's Hospital (BWH) and Massachusetts General Hospital. Controls were obtained from the psoriatic arthritis and psoriasis follow-up study (PAFS) at BWH. The comparison between the two groups included socio-demographics, comorbidities and laboratory inflammation parameters. RESULTS: Compared to individuals with psoriasis-only, patients with both psoriasis and IBD had significantly higher rates of autoimmune thyroiditis (2.1% vs. 6.8%), hepatitis (0.7 vs. 6.2%) and diabetes (11.0% vs. 26.7%). In addition, of the 146 patients with psoriasis and IBD, 60 (41.1%) were diagnosed with seronegative arthritis. The average C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) of the last visits in our clinics were significantly elevated compared to the individuals with psoriasis-only (ESR, 33.5 vs. 4.0 mm/h; CRP, 9.1 vs. 2.3 mg/L; both P-values <0.0001). CONCLUSIONS: We found that patients with both, psoriasis and IBD have a number of further associated comorbidities, some at significantly higher levels than individuals with psoriasis-only. Common inflammatory pathways and genetic predispositions for specific patterns in the immune response may play an important role in the evolution of associated conditions.

Cytotoxic activity of non-specific lipid transfer protein (nsLTP1) from Ajwain (Trachyspermum ammi) seeds.

BACKGROUND: Trachyspermum ammi, commonly known as Ajwain, is a member of the Apiaceae family. It is a therapeutic herbal spice with diverse pharmacological properties, used in traditional medicine for various ailments. However, all previous studies were conducted using small molecule extracts, leaving the protein's bioactivity undiscovered. AIM: The current study aimed to demonstrate the cytotoxic activity of Ajwain non-specific lipid transfer protein (nsLTP1) in normal breast (MCF10A), breast cancer (MCF-7), and pancreatic cancer (AsPC-1) cell lines. Also, to evaluate its structural stability in human serum as well as at high temperature conditions. METHODS: The cytotoxic activity of Ajwain nsLTP1 was evaluated in MCF-7 and AsPC-1 cell lines using MTT assay. Annexin V-FITC and PI staining were used to detect the early apoptotic and late apoptotic cells. The role of nsLTP1 in inducing apoptosis was further studied by quantifying Bcl-2, Bax, Caspase-3, Survivin, EGFR, and VEGF genes expression using RT-PCR. CD spectroscopy analyzed the nsLTP1 conformational changes after thermal treatment for structure stability determination. The RP-HPLC was used to analyze the nsLTP1 degradation rate in human serum at different time intervals incubated at 37 °C. RESULTS: Ajwain nsLTP1 showed a potent cytotoxic effect in MCF-7 and AsPC-1. The IC50 value obtained in MCF-7 was 8.21 µM, while for AsPC-1 4.17 µM. The effect of nsLTP1 on stimulating apoptosis revealed that the proportions of apoptotic cells in both cell lines were relatively increased depending on the concentration. The apoptotic cells percentage at 20 µM was in MCF-7 71% (***P < 0.001) and AsPC-1 88% (***P < 0.001). These results indicate that nsLTP1 might efficaciously induce apoptosis in multiple types of cancerous cells. Genes expression in MCF-7 and AsPC-1 showed significant upregulation in Bax and Caspase-3 and downregulation in Bcl-2, Survivin, EGFR, and VEGF protein. The CD analysis of nsLTP1 showed a significant thermostable property. In serum, nsLTP1 showed a slow degradation rate, indicating high stability with a half-life of ~ 8.4 h. CONCLUSION: Our results revealed the potential anticancer activity of Ajwain nsLTP1 and its mechanism in inducing apoptosis. It further exhibited thermostable properties at high temperatures and in human serum, which suggested this protein as a promising anticancer agent.

Real World Multiple Myeloma Registry from Jordan, a Developing Country.

Background and objective: Scanty reports from the middle east and north Africa (MENA) region have been published on multiple myeloma (MM). Multiple myeloma registry has been established at Jordan University Hospital (JUH) since 2009. Our work aims to review this Multiple Myeloma registry with data from 113 patients diagnosed with MM at JUH and analyze their management and course. Methods: This is a non-interventional and retrospective analysis of the MM registry from 2009-to 2016 involving 113 patients at JUH. Statistical analysis was done using the Statistical Package for the Social Sciences (SPSS). Overall survival (OS) was analyzed with the Kaplan-Meier method. P-value was considered significant if it was (<0.05). Results: We found no gender difference in this registry. The median age is 62 years. Most patients are in ISS stage II and III (36.28% for each). Immunoglobulin type G Kappa is the dominant subtype. Bone pain is the most common presenting symptom. The most common laboratory finding is anemia (45.6%). Most of our patients (85.2%) had received thalidomide and dexamethasone, while only 14.8% received bortezomib, thalidomide, and dexamethasone. Our patients' mean overall survival (OS) was 74 months, and the median survival was 38 months. For ISS stages I, II, and III, median OS was 96, 46, and 16 months. Conclusion: MM in a developing country presents a challenging disease compared to industrial countries in both epidemiology and management. An improved road map in the care of MM in these countries is needed. The use of three or four drugs combination upfront is warranted. However, this is limited because of the high cost of these drugs. We expect the following decade to show better survival and quality of life for MM patients once these drugs are widely used.

The use of advanced spectral imaging to reveal nanoparticle identity in biological samples.

Nanoparticles (NPs) have been used in drug delivery therapies, medical diagnostic strategies, and as current Covid-19 vaccine carriers. Many microscope-based imaging systems have been introduced to facilitate detection and visualization of NPs. Unfortunately, none can differentiate the core and the shell of NPs. Spectral imaging has been used to distinguish a drug molecule and its metabolite. We have recently integrated this technology to a resolution of 9 nm by using artificial intelligence-driven analyses. Such a resolution allowed us to collect many robust datapoints for each pixel of an image. Our analyses could recognize 45 spectral points within a pixel to detect unlabeled Ag-NPs and Au-NPs in single live cells and tissues (liver, heart, spleen and kidneys). The improved resolution and software provided a more specific fingerprinting for each single molecule, allowing simultaneous analyses of 990 complex interactions from the 45 points for each molecule within a pixel of an image. This in turn allowed us to detect surface-functionalization of Ag-NPs to distinguish the core from the shell of Ag-NPs for the first time. Our studies were validated using various laborious and time-consuming conventional techniques. We propose that spectral imaging has tremendous potential to study NP localization and identification in biological samples at a high temporal and spatial resolution, based primarily on spectral identity information.

Design, Synthesis, Biological Evaluation, and Molecular Dynamics Studies of Novel Lapatinib Derivatives.

Co-expression of the epidermal growth factor receptor (EGFR, also known as ErbB1) and human epidermal growth factor receptor 2 (HER2) has been identified as a diagnostic or prognostic sign in various tumors. Despite the fact that lapatinib (EGFR/HER2 dual inhibitor) has shown to be successful, many patients do not respond to it or develop resistance for a variety of reasons that are still unclear. As a result, new approaches and inhibitory small molecules are still needed for EGFR/HER2 inhibition. Herein, novel lapatinib derivatives possessing 4-anilinoquinazoline and imidazole scaffolds (6a-l) were developed and screened as EGFR/HER2 dual inhibitors. In vitro and in silico investigations revealed that compound 6j has a high affinity for the ATP-binding regions of EGFR and HER2. All of the designed candidates were predicted to not penetrate the BBB, raising the expectation for the absence of CNS side effects. At 10 µM, derivatives possessing 3-chloro-4-(pyridin-2-ylmethoxy)aniline moiety (6i-l) demonstrated outstanding ranges of percentage inhibition against EGFR (97.65-99.03%) and HER2 (87.16-96.73%). Compound 6j showed nanomolar IC50 values over both kinases (1.8 nM over EGFR and 87.8 nM over HER2). Over EGFR, compound 6j was found to be 50-fold more potent than staurosporine and 6-fold more potent than lapatinib. A kinase selectivity panel of compound 6j showed poor to weak inhibitory activity over CDK2/cyclin A, c-MET, FGFR1, KDR/VEGFR2, and P38a/MAPK14, respectively. Structure-activity relationship (SAR) that were obtained with different substitutions were justified. Additionally, molecular docking and molecular dynamics studies revealed insights into the binding mode of the target compounds. Thus, compound 6j was identified as a highly effective and dual EGFR/HER2 inhibitor worthy of further investigation.

Cleaner seas: reducing marine pollution.

In the age of the Anthropocene, the ocean has typically been viewed as a sink for pollution. Pollution is varied, ranging from human-made plastics and pharmaceutical compounds, to human-altered abiotic factors, such as sediment and nutrient runoff. As global population, wealth and resource consumption continue to grow, so too does the amount of potential pollution produced. This presents us with a grand challenge which requires interdisciplinary knowledge to solve. There is sufficient data on the human health, social, economic, and environmental risks of marine pollution, resulting in increased awareness and motivation to address this global challenge, however a significant lag exists when implementing strategies to address this issue. This review draws upon the expertise of 17 experts from the fields of social sciences, marine science, visual arts, and Traditional and First Nations Knowledge Holders to present two futures; the Business-As-Usual, based on current trends and observations of growing marine pollution, and a More Sustainable Future, which imagines what our ocean could look like if we implemented current knowledge and technologies. We identify priority actions that governments, industry and consumers can implement at pollution sources, vectors and sinks, over the next decade to reduce marine pollution and steer us towards the More Sustainable Future. Supplementary Information: The online version contains supplementary material available at 10.1007/s11160-021-09674-8.

Label-free spectral imaging to study drug distribution and metabolism in single living cells.

During drug development, evaluation of drug and its metabolite is an essential process to understand drug activity, stability, toxicity and distribution. Liquid chromatography (LC) coupled with mass spectrometry (MS) has become the standard analytical tool for screening and identifying drug metabolites. Unlike LC/MS approach requiring liquifying the biological samples, we showed that spectral imaging (or spectral microscopy) could provide high-resolution images of doxorubicin (dox) and its metabolite doxorubicinol (dox'ol) in single living cells. Using this new method, we performed measurements without destroying the biological samples. We calculated the rate constant of dox translocating from extracellular moiety into the cell and the metabolism rate of dox to dox'ol in living cells. The translocation rate of dox into a single cell for spectral microscopy and LC/MS approaches was similar (~ 1.5 pM min-1 cell-1). When compared to spectral microscopy, the metabolism rate of dox was underestimated for about every 500 cells using LC/MS. The microscopy approach further showed that dox and dox'ol translocated to the nucleus at different rates of 0.8 and 0.3 pM min-1, respectively. LC/MS is not a practical approach to determine drug translocation from cytosol to nucleus. Using various methods, we confirmed that when combined with a high-resolution imaging, spectral characteristics of a molecule could be used as a powerful approach to analyze drug metabolism. We propose that spectral microscopy is a new method to study drug localization, translocation, transformation and identification with a resolution at a single cell level, while LC/MS is more appropriate for drug screening at an organ or tissue level.

Calcium Dobesilate Versus Flavonoids for the Treatment of Early Hemorrhoidal Disease: A Randomized Controlled Trial.

Background and Aim Early hemorrhoidal disease is usually treated conservatively with fiber diet and medical therapy with flavonoids or calcium dobesilate. The purpose of this study was to compare the efficacy of these two agents in the treatment of early hemorrhoidal disease. Materials and Methods Patients having grade I and grade II hemorrhoidal disease were recruited in the study. One group received flavonoid therapy and the other group took calcium dobesilate treatment for three weeks. The symptoms and size of hemorrhoids were then assessed at the fourth week. Results  In this study, 70.2% of patients were male and 29.8% of patients were female. Of the total patients, 58.65% of patients were below 45 years of age and 41.34% of patients were above 45 years of age. Moreover, 83.65% of patients had grade II hemorrhoids, whereas 16.34% of patients had grade I hemorrhoids; 80.8% of patients showed a decrease in frequency and amount of bleeding after being treated by flavonoids, whereas 67.3% showed a decrease in frequency and amount of bleeding after administration of calcium dobesilate. A decrease in the size of hemorrhoids was seen in 67.3% of patients after treatment with flavonoids and 38.46% after giving calcium dobesilate. Conclusions Treatment of early hemorrhoidal with flavonoid therapy was more effective in improving the symptoms of disease as compared to calcium dobesilate treatment.

An Improved Marine Predators Algorithm With Fuzzy Entropy for Multi-Level Thresholding: Real World Example of COVID-19 CT Image Segmentation.

Medical imaging techniques play a critical role in diagnosing diseases and patient healthcare. They help in treatment, diagnosis, and early detection. Image segmentation is one of the most important steps in processing medical images, and it has been widely used in many applications. Multi-level thresholding (MLT) is considered as one of the simplest and most effective image segmentation techniques. Traditional approaches apply histogram methods; however, these methods face some challenges. In recent years, swarm intelligence methods have been leveraged in MLT, which is considered an NP-hard problem. One of the main drawbacks of the SI methods is when searching for optimum solutions, and some may get stuck in local optima. This because during the run of SI methods, they create random sequences among different operators. In this study, we propose a hybrid SI based approach that combines the features of two SI methods, marine predators algorithm (MPA) and moth-?ame optimization (MFO). The proposed approach is called MPAMFO, in which, the MFO is utilized as a local search method for MPA to avoid trapping at local optima. The MPAMFO is proposed as an MLT approach for image segmentation, which showed excellent performance in all experiments. To test the performance of MPAMFO, two experiments were carried out. The first one is to segment ten natural gray-scale images. The second experiment tested the MPAMFO for a real-world application, such as CT images of COVID-19. Therefore, thirteen CT images were used to test the performance of MPAMFO. Furthermore, extensive comparisons with several SI methods have been implemented to examine the quality and the performance of the MPAMFO. Overall experimental results confirm that the MPAMFO is an efficient MLT approach that approved its superiority over other existing methods.

Hydraulic transients: a seismic source in volcanoes and glaciers.

A source for certain low-frequency seismic waves is postulated in terms of the water hammer effect. The time-dependent displacement of a water-filled sub-glacial conduit is analyzed to demonstrate the nature of the source. Preliminary energy calculations and the observation of hydraulically generated seismic radiation from a dam indicate the plausibility of the proposed source.