Ambulatory Endoscopic Submucosal Dissection for Gastrointestinal Neoplasms: Trends and Associated Factors in the United States.

Endoscopic submucosal dissection (ESD) is a minimally invasive treatment for superficial gastrointestinal (GI) cancers.1,2 ESD practice is expanding significantly in the United States and Western countries. This is attributed to a shorter hospital stay, better quality of life, and fewer adverse events compared with surgery. In the United States, ESD usually is performed and managed in an outpatient setting (ambulatory ESD) or with an overnight hospital stay. This practice is in contrast to Eastern Asian countries, where 3 to 5 days of hospital stay is a routine process for observation after ESD. A Swedish study showed that patients with well-selected colorectal neoplasms (median tumor size, 37 mm) could be managed safely in an outpatient setting after ESD.3 A North American multicenter ESD study also reported that ambulatory ESD was safe and feasible in selected cases (noninvasive cancers, no adverse events, high-volume endoscopists with short procedure time).4 However, procedural and technical aspects that enable safe outpatient management of patients after ESD need to be investigated.

Characterization and genetic analysis of extensively drug-resistant hospital acquired Pseudomonas aeruginosa isolates.

BACKGROUND: The incidence of hospital-acquired infections in extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) has been increasing worldwide and is frequently associated with an increase in mortality and morbidity rates. The aim of this study was to characterize clinical XDR-PA isolates recovered during six months at three different hospitals in Egypt. RESULTS: Seventy hospital-acquired clinical isolates of P. aeruginosa were classified into multidrug-resistant (MDR), extensively drug-resistant (XDR) and pandrug-resistant (PDR), according to their antimicrobial resistance profile. In addition, the possession of genes associated with mobile genetic elements and genes encoding antimicrobial resistance determinants among isolates were detected using polymerase chain reaction. As a result, a significant percentage of the isolates (75.7%) were XDR, while 18.5% were MDR, however only 5.7% of the isolates were non-MDR. The phenotypic detection of carbapenemases, extended-spectrum ß-lactamases (ESBLs) and metallo ß-lactamase (MBL) enzymes showed that 73.6% of XDR-PA isolates were carbapenemases producers, whereas 75.5% and 88.7% of XDR-PA isolates produced ESBLs and MBL respectively. In addition, PCR screening showed that oxa gene was the most frequently detected gene of carbapenemases (91.4%), while aac(6')-lb gene was mostly detected (84.3%) among the screened aminoglycosides-resistance genes. Furthermore, the molecular detection of the colistin resistance gene showed that 12.9% of isolates harbored mcr-1 gene. Concerning mobile genetic element markers (intI, traA, tnp513, and merA), intI was the highest detected gene as it was amplified in 67 isolates (95.7%). Finally, phylogenetic and molecular typing of the isolates via ERIC-PCR analysis revealed 10 different ERIC fingerprints. CONCLUSION: The present study revealed a high prevalence of XDR-PA in hospital settings which were resistant to a variety of antibiotics due to several mechanisms. In addition, 98% of the XDR-PA clinical isolates contained at least one gene associated with movable genetic elements, which could have aided the evolution of these XDR-PA strains. To reduce spread of drug resistance, judicious use of antimicrobial agents and strict infection control measures are therefore essential.

The use of a self-assembling peptide gel for stricture prevention in the esophagus after endoscopic submucosal dissection: a U.S. multicenter prospective study (with video).

BACKGROUND AND AIMS: Postoperative stricture is a serious common adverse event after extensive endoscopic submucosal dissection (ESD) in the esophagus. Self-assembling peptide (SAP) gel has been shown to promote tissue healing and re-epithelialization. The aim of this study was to evaluate the effect of the SAP gel for esophageal stricture prevention after ESD. METHODS: This was a multicenter prospective study of patients who underwent esophageal ESD followed by SAP gel application between March 2022 and December 2023. Patients were included if the ESD mucosal defect involved ≥50% of the circumference of the esophagus. High-risk cases were defined as mucosal defects ≥75% of the circumference. Stricture was defined as the inability to pass an endoscope ≥8.9 mm in diameter or a narrow-caliber lumen in a patient with symptoms. RESULTS: A total of 43 patients (median age, 71 years; 81.4% male) underwent ESD (median resected specimen size, 50 mm) during the study period. SAP gel (median, 3 mL) was successfully applied in all cases (median time, 4 minutes). In aggregate, stricture occurred in 20.9% (9 of 43) of the cases. Stricture developed in 30.8% of the high-risk cases: 80% (4 of 5) after circumferential ESD and 19% (4 of 21) in those with defects ≥75% but <100% of the circumference. All cases of stricture resolved with endoscopic treatment. Three cases (6.9%) of postoperative bleeding occurred and were adequately managed endoscopically. CONCLUSIONS: We show that SAP gel application was easy, quick, and associated with a relatively low stricture rate comparable to other prophylactic methods. Additional comparative studies are needed to corroborate these preliminary findings.

More than just 'added value': The perils of not establishing shared core facilities in resource-constrained communities.

The accelerating pace of technological advancements necessitates specialised expertise and cutting-edge instruments to maintain competitive research in life sciences. Core facilities - collaborative laboratories equipped with state-of-the-art tools and staffed by expert personnel - are vital resources that support diverse scientific endeavours. However, their adoption in lower-income communities has been comparatively stagnant due to both financial and cultural challenges. This paper explores the perils of not supporting core facilities on national research enterprises, underscoring the need for balanced investments in discovery science and crucial infrastructure support. We explore the implications from the perspectives of funders, university leaders and lab heads. We advocate for a paradigm shift to recognise these facilities as essential components of national research efforts. Core facilities are positioned not as optional but as strategic investments that can catalyse breakthroughs, particularly in environments with limited resources.

Purification and characterization of the produced hyaluronidase by Brucella Intermedia MEFS for antioxidant and anticancer applications.

Hyaluronidase (hyase) is an endoglycosidase enzyme that degrades hyaluronic acid (HA) and is mostly known to be found in the extracellular matrix of connective tissues. In the current study, eleven bacteria isolates and one actinomycete were isolated from a roaster comb and screened for hyase production. Seven isolates were positive for hyase, and the most potent isolate was selected based on the diameter of the transparent zone. Based on the morphological, physiological, and 16 S rRNA characteristics, the most potent isolate was identified as Brucella intermedia MEFS with accession number OR794010. The environmental conditions supporting the maximum production of hyase were optimized to be incubation at 30 ºC for 48 h and pH 7, which caused a 1.17-fold increase in hyase production with an activity of 84 U/mL. Hyase was purified using a standard protocol, including precipitation with ammonium sulphate, DEAE as ion exchange chromatography, and size exclusion chromatography using Sephacryle S100, with a specific activity of 9.3-fold compared with the crude enzyme. The results revealed that the molecular weight of hyase was 65 KDa, and the optimum conditions for hyase activity were at pH 7.0 and 37 °C for 30 min. The purified hyase showed potent anticancer activities against colon, lung, skin, and breast cancer cell lines with low toxicity against normal somatic cells. The cell viability of hyase-treated cancer cells was found to be in a dose dependent manner. Hyase also controlled the growth factor-induced cell cycle progression of breast cancer cells and caused relative changes in angiogenesis-related genes as well as suppressed many pro-inflammatory proteins in MDA cells compared with 5-fluorouracil, indicating the significant role of hyase as an anticancer agent. In addition, hyase recorded the highest DPPH scavenging activity of 65.49% and total antioxidant activity of 71.84% at a concentration of 200 µg/mL.

Advances in the discovery of activin receptor-like kinase 5 (ALK5) inhibitors.

Activin receptor­like kinase-5 (ALK5) is an outstanding member of the transforming growth factor-ß (TGF-ß) family. (TGF-ß) signaling pathway integrates pleiotropic proteins that regulate various cellular processes such as growth, proliferation, and differentiation. Dysregulation within the signaling pathway can cause variety of diseases, such as fibrosis, cardiovascular disease, and especially cancer, rendering ALK5 a potential drug target. Hence, various small molecules have been designed and synthesized as potent ALK5 inhibitors. In this review, we shed light on the current ATP-competitive inhibitors of ALK5 through diverse heterocyclic based scaffolds that are in clinical or pre-clinical phases of development. Moreover, we focused on the binding interactions of the compounds to the ATP binding site and the structure-activity relationship (SAR) of each scaffold, revealing new scopes for designing novel candidates with enhanced selectivity and metabolic profiles.

Prevalence, genetic diversity, and antimicrobial susceptibility of Vibrio spp. infected gilthead sea breams from coastal farms at Damietta, Egypt.

BACKGROUND: Vibriosis is one of the most serious bacterial diseases and causes high morbidity and mortality among cultured sea breams. This study was undertaken to track the surveillance of Vibrio infection and its correlation to environmental factors. A total of 115 gilthead sea breams were collected seasonally from a private earthen pond fish farm in the Shatta area of Damietta, Egypt from September 2022 to July 2023. Physicochemical parameters of water were analyzed, and heavy metal levels were measured. The fish samples were subjected to clinical, bacteriological, Enterobacterial Repetitive Intergenic Consensus (ERIC) fingerprinting, and hematoxylin and Eosin histopathological staining. RESULTS: The results revealed significant variations in the water quality parameters over different seasons, in addition to an increase in heavy metals. Naturally infected fish showed external signs and postmortem lesions that were relevant to bacterial infection. Two dominant Vibrio subspecies of bacteria were identified: V. alginolyticus (205 isolates) and V. fluvialis (87 isolates). PCR confirmed the presence of V. alginolyticus using the species-specific primer collagenase at 737 bp. The highest prevalence of V. alginolyticus was detected during the summer season (57.72%), and the lowest prevalence was observed in autumn (39.75%). The correlation analysis revealed a positive relationship between V. alginolyticus and water temperature (r = 0.69). On the other hand, V. fluvialis showed a high prevalence during the autumn season (25.30%) and the lowest prevalence during the summer season (10.56%), where it was negatively correlated with water temperatures (r =-0.03). ERIC fingerprinting showed genetic variation within the Vibrio isolates. Antimicrobial susceptibility testing revealed sensitivity to ciprofloxacin and doxycycline, and resistance to amoxicillin and erythromycin. The multiple antibiotic resistance (MAR) index values for V. alginolyticus and V. fluvialis ranged from 0.3 to 0.7, with a multi-drug resistance pattern to at least three antibiotics. Histopathological alterations in the affected tissues revealed marked hemorrhage, vascular congestion, and hemosiderosis infiltration. CONCLUSION: This study provides insights into the potential propagation of waterborne diseases and antibiotic resistance in the environment. Ensuring that the environment does not serve as a reservoir for virulent and contagious Vibrio species is a critical concern for regional aquaculture industries. Therefore, we recommend implementing environmental context-specific monitoring and surveillance tools for microbial resistance.

A multidisciplinary study on Clinostomum infections in Nile tilapia: micro-morphology, oxidative stress, immunology, and histopathology.

Yellow grub disease, caused by Clinostomum metacercaria, is an endemic zoonotic infection in freshwater fish, responsible for Halzoun syndrome transmitted through the consumption of raw infected fish. This study aimed to conduct a multidisciplinary investigation integrating detailed morphology, oxidative stress, immunology, and histopathology alteration to advance our understanding of Clinostomum infection. In this annual study, 400 Nile tilapia (Oreochromis niloticus) were collected from the Nile River at Al Bahr Al Aazam, Giza Governorate to assess Clinostomum infection prevalence. Of the examined fish, 160 individuals (40.0%) harboured larval Clinostomum infections. Clinostomum metacercariae were observed in various anatomical locations, with 135 fish (33.8%) in buccal cavities, 21 fish (5.25%) in gill chambers, and 4 fish (1.0%) on the skin. Infection intensity ranged from 2 to 12 cysts per fish, averaging 5 cysts, notably with skin infections characterized by a single cyst in each fish. Macroscopic encysted metacercariae were collected from buccal cavities, gills, and skin. Micro-morphology revealed distinct features in C. complanatum, including an elliptical oral sucker with collar-like rings and large sensory papilla-like structures, contrasting with the absence of these features in C. phalacrocoracis. Oxidative stress, assessed through malondialdehyde (MDA) and nitric oxide levels, revealed an elevation in MDA to 35.13 ± 6 nmol/g and nitric oxide to 25.80 ± 3.12 µmol/g in infected fish. In infected fish, MHC-I gene expression increased approximately 13-fold, MHC-II peaked at 19-fold, and IL-1ß significantly upregulated by 17-fold, compared to control levels. Histopathology detailed associated lesions, such as cyst encapsulation and eosinophilic infiltration. Clinstomiasis and its impacts on fish hosts offer crucial insights to control this emerging fish-borne zoonotic disease, threatening wildlife, aquaculture, and human health.

Medical residents' perceptions of group biases in medical decision making: a qualitative study.

BACKGROUND: Systematic biases in group decision making (i.e., group biases) may result in suboptimal decisions and potentially harm patients. It is not well known how impaired group decision making in patient care may affect medical training. This study aimed to explore medical residents' experiences and perspectives regarding impaired group decision making and the role of group biases in medical decision making. METHODS: This study used a qualitative approach with thematic analysis underpinned by a social constructionist epistemology. Semi-structured interviews of medical residents were conducted at a single internal medicine residency program. Residents were initially asked about their experiences with suboptimal medical decision making as a group or team. Then, questions were targeted to several group biases (groupthink, social loafing, escalation of commitment). Interviews were transcribed and transferred to a qualitative data analysis software. Thematic analysis was conducted to generate major themes within the dataset. RESULTS: Sixteen interviews with residents revealed five major themes: (1) hierarchical influence on group decision making; (2) group decision making under pressure; (3) post-call challenges in decision making; (4) interactions between teamwork and decision making; and (5) personal and cultural influences in group decision making. Subthemes were also identified for each major theme. Most residents were able to recognize groupthink in their past experiences working with medical teams. Residents perceived social loafing or escalation of commitment as less relevant for medical team decision making. CONCLUSIONS: Our findings provide unique insights into the complexities of group decision making processes in teaching hospitals. Team hierarchy significantly influenced residents' experiences with group decision making-most group decisions were attributed to consultants or senior team members, while lower ranking team members contributed less and perceived fewer opportunities to engage in group decisions. Other factors such as time constraints on decision making, perceived pressures from other staff members, and challenges associated with post-call days were identified as important barriers to optimal group decision making in patient care. Future studies may build upon these findings to enhance our understanding of medical team decision making and develop strategies to improve group decisions, ultimately leading to higher quality patient care and training.

Design and synthesis of novel tetrabromophthalimide derivatives as potential tubulin inhibitors endowed with apoptotic induction for cancer treatment.

Although various approaches exist for treating cancer, chemotherapy continues to hold a prominent role in the management of this disease. Besides, microtubules serve as a vital component of the cellular skeleton, playing a pivotal role in the process of cell division making it an attractive target for cancer treatment. Hence, the scope of this work was adapted to design and synthesize new anti-tubulin tetrabromophthalimide hybrids (3-17) with colchicine binding site (CBS) inhibitory potential. The conducted in vitro studies showed that compound 16 displayed the lowest IC50 values (11.46 µM) at the FaDu cancer cell lines, whereas compound 17 exhibited the lowest IC50 value (13.62 µM) at the PC3 cancer cell line. However, compound 7b exhibited the lowest IC50 value (11.45 µM) at the MDA-MB-468 cancer cell line. Moreover, compound 17 was observed to be the superior antitumor candidate against all three tested cancer cell lines (MDA-MB-468, PC3, and FaDu) with IC50 values of 17.22, 13.15, and 13.62 µM, respectively. In addition, compound 17 showed a well-established upregulation of apoptotic markers (Caspases 3, 7, 8, and 9, Bax, and P53). Moreover, compound 17 induced downregulation of the antiapoptotic markers (MMP2, MMP9, and BCL-2). Furthermore, the colchicine binding site inhibition assay showed that compounds 15a and 17 exhibited particularly significant inhibitory potentials, with IC50 values of 23.07 and 4.25 µM, respectively, compared to colchicine, which had an IC50 value of 3.89 µM. Additionally, cell cycle analysis was conducted, showing that compound 17 could prompt cell cycle arrest at both the G0-G1 and G2-M phases. On the other hand, a molecular docking approach was applied to investigate the binding interactions of the examined candidates compared to colchicine towards CBS of the ß-tubulin subunit. Thus, the synthesized tetrabromophthalimide hybrids can be regarded as outstanding anticancer candidates with significant apoptotic activity.

The pulmonary protective potential of vanillic acid-loaded TPGS-liposomes: modulation of miR-217/MAPK/NF-κb signalling pathway.

The aim is to investigate the possible pulmonary protective effect of vanillic acid (VA) in liposome-TPGS nanoparticles, to overcome VA's poor bioavailability. VA was successfully extracted. Liposomes were prepared using thin film hydration. Central composite design was adopted for optimisation of liposomes to get the maximum entrapment efficiency (EE%) and the minimum mean diameter, where the liposomes were further modified with TPGS, and tested for PDI, zeta-potential, and in-vitro drug release. In-vivo study on mice with LPS-acute pulmonary toxicity was tested. TPGS-modified VA-liposomes showed EE% of 69.35 ± 1.23%, PS of 201.7 ± 3.23 nm, PDI of 0.19 ± 0.02, and zeta-potential of -32.2 ± 0.32 mv. A sustained drug release of the TPGS-modified VA-liposomes was observed compared to standard VA, and a pulmonary-protective effect through decreasing miR-217 expression with subsequent anti-inflammatory effect through suppression of MAPK and PI3K/NF-κB pathways was also demonstrated in the current study. TPGS-modified VA-liposomes showed an enhanced bioavailability and a sustained drug release with promising pulmonary protective effects against acute pulmonary injury diseases.

Molecular and immunological studies on Theileria equi and its vector in Egypt.

Equine piroplasmosis is not fully understood regarding pathogenicity, prophylaxis, host immune response expression, and specific vectors. Accurately identifying the parasite vector is crucial for developing an effective control plan for a particular infection. This study focused on morphologically identifying two Hyalomma species (H. anatolicum and H. marginatum) and one Rhipicephalus annulatus (R. annulatus) at the species level. The identification process was followed by phylogenetic analysis using the neighbor-joining method based on the cytochrome oxidase subunit 1 (COXI) gene as a specific vector for Theileria equi (T. equi) in horses. T. equi was diagnosed morphologically and molecularly from infected blood samples and crushed tick species using conventional PCR. Subsequently, phylogenetic analysis based on the amplification of the 18 S rRNA gene was conducted. The obtained sequence data were evaluated and registered in GenBank under accession numbers OR064161, OR067911, OR187727, and OR068139, representing the three tick species and the isolated T. equi, respectively. The study demonstrated that T. equi infection leads to immune system suppression by significantly increasing the levels of oxidative stress markers (CAT, GPx, MDA, and SOD) (P ≤ 0.0001), with this elevation being directly proportional to parasitemia levels in infected blood cells. Furthermore, a correlation was observed between parasitemia levels and the expression of immune response infection genes (IFN-gamma, TGF-ß1, and IL-1ß cytokines) in infected horses compared to non-infected equine. Common macroscopic symptoms indicating T. equi infection in horses include intermittent fever, enlarged lymph nodes (LN), and tick infestation.

Designing Potent Anti-Cancer Agents: Synthesis and Molecular Docking Studies of Thieno[2,3-d][1,2,4]triazolo[1,5-a]pyrimidine Derivatives.

A new series of thieno[2,3-d][1,2,4]triazolo[1,5-a]pyrimidines was designed and synthesized using readily available starting materials, specifically, ß-enaminoester. Their cytotoxicity was screened against three cancer cell lines, namely, MCF-7, HCT-116, and PC-3. 2-(4-bromophenyl)triazole 10b and 2-(anthracen-9-yl)triazole 10e afforded excellent potency against MCF-7 cell lines (IC50 = 19.4 ± 0.22 and 14.5 ± 0.30 µM, respectively) compared with doxorubicin (IC50 = 40.0 ± 3.9 µM). The latter derivatives 10b and 10e were further subjected to in silico ADME and docking simulation studies against EGFR and PI3K and could serve as ideal leads for additional modification in the field of anticancer research.

Alternative treatment modality for severe aplastic anemia in a resource-limited setting: a single-institution prospective cohort study from Upper Egypt.

This study compared the efficacy and safety of CsA monotherapy with eltrombopag (E-PAG) + CsA combined treatment in children with severe aplastic anemia (SAA). The study including 30 children had SAA. Ten were a retrospective cohort treated with CsA monotherapy. The other 20 were prospective cohort received E-PAG + CsA. All patients were evaluated for partial (PR) and complete (CR) hematological response at 3, 6, and 12 months. overall response (OR), overall survival rates (OS), and treatment safety. OR for the E-PAG patients was 40% after 3 months of therapy. At 6 months, this had increased to 75% with significantly higher CR rate (40%) than in the CsA group (p = 0.0001). After a year of treatment, the CR for the E-PAG + CsA regimen had increased to 50% and the OR to 85%, compared to 20% in the CsA group (p = 0.0001). The OS at 12 months was 100% in the E-PAG+ CsA group compared to 80% in the CsA cohort. At 24 months, the OS in the E-PAG + CsA group was 90%. In conclusion, E-PAG+ CsA was found to be a safe and effective alternative treatment for children with SAA particularly in countries with limited resources.

F18-FET PET in pediatric brain tumors: integrative analysis of image derived parameters and clinico-pathological data.

BACKGROUND: F18-FET PET has an established diagnostic role in adult brain gliomas. In this study we analyzed image derived static and dynamic parameters with available conventional MRI, histological, clinical and follow-up data in assessment of pediatric brain tumor patients at different stages of the disease. METHODS: Forty-four pediatric patients with median age 7 years, diagnosed with brain tumors and underwent forty-seven 18F-FET PET scans either initially (20 scans) or post-therapy (27 scans) were enrolled. Standardized analysis of summed FET PET images early from 10-20 min and late from 30-40 min post-injection were used for static (mean and maximum tumor to brain ratio [TBR] and biological tumor volume [BTV]) parameters evaluation as well as the time activity curve [TAC]. RESULTS: Nineteen out of 20 initially assessed patients had pathologically and/or clinico-radiologically proven neoplastic lesions and one patient had pathologically proven abscess. Receiver operator curve (ROC) marked early TBR max 2.95, early TBR mean 1.76, late TBR max 2.5 and late TBR mean 1.74 as discriminator points with diagnostic accuracy reaching 90% when TBR max was combined with dynamic parameters. Significant association was found between initial FET scans, early and late BTV and event free survival (EFS) (P value=0.042 and 0.005 respectively). In post-therapy assessment, the diagnostic accuracy of conventional MRI was 81.48% when used alone and 96.30% when combined with F18-FET PET scan findings. A cutoff point of 3.2 cm3 for late BTV, in post-therapy scans, was successfully marked as a predictor for therapy response (P value 0.042) and was significantly associated with EFS (P value 0.002). In FET-avid / MRI non-enhancing lesions, early TBR max was able to detect highly malignant processes (high-grade tumors in initial scans and residue/recurrence in post-therapy scans) with 80% sensitivity and 100% specificity when cutoff value of 2.25 was used (P value=0.024). In patients with FET-avid brainstem lesions, whether enhancing or non-enhancing in MRI scans, 81.8% were associated with high risk diagnoses and 68.2% of them were associated with poor therapy outcome. The degree of FET uptake matched tumor-grading, but did not show significant association with OS or EFS (P value>0.05). CONCLUSIONS: F18-FET PET seems to be an evolving pediatric neuro-imaging technique with valuable diagnostic and prognostic information at initial and post-therapy evaluation.

Breast Imaging and Intervention during Pregnancy and Lactation.

Physiologic changes that occur in the breast during pregnancy and lactation create challenges for breast cancer screening and diagnosis. Despite these challenges, imaging evaluation should not be deferred, because delayed diagnosis of pregnancy-associated breast cancer contributes to poor outcomes. Both screening and diagnostic imaging can be safely performed using protocols based on age, breast cancer risk, and whether the patient is pregnant or lactating. US is the preferred initial imaging modality for the evaluation of clinical symptoms in pregnant women, followed by mammography if the US findings are suspicious for malignancy or do not show the cause of the clinical symptom. Breast MRI is not recommended during pregnancy because of the use of intravenous gadolinium-based contrast agents. Diagnostic imaging for lactating women is the same as that for nonpregnant nonlactating individuals, beginning with US for patients younger than 30 years old and mammography followed by US for patients aged 30 years and older. MRI can be performed for high-risk screening and local-regional staging in lactating women. The radiologist may encounter a wide variety of breast abnormalities, some specific to pregnancy and lactation, including normal physiologic changes, benign disorders, and malignant neoplasms. Although most masses encountered are benign, biopsy should be performed if the imaging characteristics are suspicious for cancer or if the finding does not resolve after a short period of clinical follow-up. Knowledge of the expected imaging appearance of physiologic changes and common benign conditions of pregnancy and lactation is critical for differentiating these findings from pregnancy-associated breast cancer. ©RSNA, 2023 Online supplemental material is available for this article. Quiz questions for this article are available through the Online Learning Center.

Community-based Participatory Research: A Practical Guide for Radiologists.

Community-based participatory research (CBPR) is defined by the Kellogg Community Health Scholars Program as a collaborative process that equitably involves all partners in the research process and recognizes the unique strengths that each community member brings. The CBPR process begins with a research topic of importance to the community, with the goal of combining knowledge and action with social change to improve community health and eliminate health disparities. CBPR engages and empowers affected communities to collaborate in defining the research question; sharing the study design process; collecting, analyzing, and disseminating the data; and implementing solutions. A CBPR approach in radiology has several potential applications, including removing limitations to high-quality imaging, improving secondary prevention, identifying barriers to technology access, and increasing diversity in the research participation for clinical trials. The authors provide an overview with the definitions of CBPR, explain how to conduct CBPR, and illustrate its applications in radiology. Finally, the challenges of CBPR and useful resources are discussed in detail. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.

A Turn-On-Type Fluorescence Resonance Energy Transfer Eco-friendly Method for Nitazoxanide Quantification in Pharmaceutical Dosage Form and Spiked Plasma: Evaluation of Greenness Profile Using Different Assessment Tools.

A brand-new class of anti-infective drugs that work against bacteria, viruses, and protozoan parasites is nitazoxanide and related thiazolides. Thiazolides have also been shown to cause cell cycle arrest and apoptotic cell death in cancer cells in recent years. In this study, an eco-friendly, spectrofluorimetric technique that is verified, easy, and sensitive has been proposed for quantifying nitazoxanide (NTZ), a broad-spectrum antiparasitic drug. When NTZ is reduced with zinc (Zn) powder in an acidic media, a highly fluorescent product is produced. To get the highest sensitivity, different experimental conditions impacting the response were examined and optimized. Following excitation at 299 nm, scanning of the fluorescent product was done at 440 nm. The intensity of the fluorescence was proportional to the drug concentration in the range of 0.1-0.6 µg/mL. The approach was validated according to International Conference on Harmonization (ICH) guidelines, and the outcome was satisfactory. The detection and quantitation limits were calculated to be 0.013 and 0.038 µg/mL, respectively. The suggested technique was successful in analyzing commercially available NTZ dosage forms. Furthermore, the proposed technique was used to assess NTZ levels in human plasma and it was bio-analytically validated according to European Medicines Agency (EMA) guidelines. The suggested method can be used in quality control laboratories as well as in pharmacokinetic studies. In order to picture the green profile of the developed method, four greenness assessment tools have been applied. National Environmental Methods Index (NEMI), analytical Eco-Scale Assessment (ESA), Green Analytical Procedure Index (GAPI) and Analytical Greenness metric (AGREE) are the relatively most widely used metrics. So, they were utilized to perform a detailed greenness comparison between the proposed method and some of the reported methods for the determination of NTZ. The developed method was found to be an excellent green method with the highest AGREE score.

Acovenoside A as a novel therapeutic approach to boost taxol and carboplatin apoptotic and antiproliferative activities in NSCLC: Interplay of miR-630/miR-181a and apoptosis genes.

The aim of the present study is to explore the potential anticancer effect of the cardenolide; acovenoside A against non-small cell lung cancer (NSCLC), understand its molecular mechanism in inducing apoptosis and show the effect of its combination with carboplatin and taxol. MTT assay showed that the combination of acovenoside A with taxol and carboplatin caused 78.9% cytotoxicity reflecting the synergistic effect. The triple combination showed the best growth inhibition efficiency where the number of cells at the G2/M phase was decreased and boosted up apoptotic and necrotic activity. The combination also showed the most remarkable increase in gene expression of Bax and p53 and the least level of Bcl2. The gene expression of miRNA181a and miRNA630 was significantly upregulated in cell lines treated with the combination. The present study has proven that the underlying mechanism of acovenoside A is partially attributed to the upregulation of miR-630 and miR-181a gene expressions which in turn targets the intrinsic apoptosis genes as p53, Bax and Bcl2 as well as caspase 3. The present study is the first to address the valuable effect of using acovenoside A together with carboplatin and taxol in the treatment of NSCLC via exerting apoptotic, antiproliferative, and cytotoxic effects..

Novel topoisomerase II/EGFR dual inhibitors: design, synthesis and docking studies of naphtho[2',3':4,5]thiazolo[3,2-a]pyrimidine hybrids as potential anticancer agents with apoptosis inducing activity.

Topoisomerases II are ubiquitous enzymes with significant genotoxic effects in many critical DNA processes. Additionally, epidermal growth factor receptor (EGFR) plays pivotal role in tumour growth and angiogenesis. A novel series of naphtho[2',3':4,5]thiazolo[3,2-a]pyrimidine hybrids have been designed, synthesised and evaluated for their topo IIα/EGFR inhibitory and apoptotic inducer activities. Cytotoxicity of the synthesised hybrids was evaluated against MCF-7, A549 and HCT-116 cell lines. Of the synthesised hybrids, 6i, 6a and 6c experienced superior cytotoxic activity compared to doxorubicin and erlotinib against the tested cancer cells. The molecular mechanism of these hybrids revealed their ability to successfully inhibit topo IIα and EGFR activities in micromolar concentration and may serve as topo II catalytic inhibitor. Moreover, these hybrids significantly arrested cell cycle at G2/M phase together with increased p53, caspae-7, caspase-9 levels and Bax/Bcl-2 ratio. The synthesised hybrids showed efficient binding pattern in molecular docking study and have acceptable drug likeness characters.