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Introduction: Digital pathology artificial intelligence (AI) platforms have the capacity to improve over time through "deep machine learning." We have previously reported on the accuracy of peripheral white blood cell (WBC) differential and blast identification by Techcyte (Techcyte, Inc., Orem, UT, USA), a digital scanner‐agnostic web‐based system for blood film reporting. The aim of the current study was to compare AI protocols released over time to assess improvement in cell identification. Methods: WBC differentials were performed using Techcyte's online AI software on the same 124 digitized abnormal peripheral blood films (including 64 acute and 22 chronic leukaemias) in 2019 (AI1), 2020 (AI2), and 2022 (AI3), with no reassignment by a morphologist at any time point. AI results were correlated to the "gold standard" of manual microscopy, and comparison of Lin's concordance coefficients (LCC) and sensitivity and specificity of blast identification were used to determine the superior AI version. Results: AI correlations (r) with manual microscopy for individual cell types ranged from 0.50–0.90 (AI1), 0.66–0.86 (AI2) and 0.71–0.91 (AI3). AI3 concordance with manual microscopy was significantly improved compared to AI1 for identification of neutrophils (LCC AI3 = 0.86 vs. AI1 = 0.77, p = 0.03), total granulocytes (LCC AI3 = 0.92 vs. AI1 = 0.82, p = 0.0008), immature granulocytes (LCC AI3 = 0.67 vs. AI1 = 0.38, p = 0.0014), and promyelocytes (LCC AI3 = 0.53 vs. AI1 = 0.16, p = 0.0008). Sensitivity for blast identification (n = 65 slides) improved from 97% (AI1), to 98% (AI2), to 100% (AI3), while blast specificity decreased from 24% (AI1), to 14% (AI2) to 12% (AI3). Conclusion: Techcyte AI has shown significant improvement in cell identification over time and maintains high sensitivity for blast identification in malignant films. [ABSTRACT FROM AUTHOR]

Natural compounds, such as carotenoids, flavonoids, anthocyanins, or terpenoids, are physiologically active components found in plants (pigments), often known as phytochemicals or phytonutrients. The in vitro cytotoxic and anticolon cancer effects of biologically bavachin, bavachinin, artepillin C, and aromadendrin compounds against SW48, SNU‐C1, COLO 205, RKO, LS411N, and SW1417 cancer cell lines were assessed. Results of enzymes and antibacterial, antifungal were in level of micromolar that is good impacts. These natural compounds may be antidiabetic, anticancer, and antibacterial candidates for drug design. IC50 results were obtained between 14–19 and 5–119 µM for α‐amylase and α‐glucosidase, respectively. Good inhibitor Bavachinin was detected for both enzymes (IC50 for α‐amylase: 14.37 µM and IC50 for α‐glucosidase: 5.27 µM). The chemical activities of aromadendrin, artepillin C, bavachin, and bavachinin against pancreatic α‐amylase and α‐glucosidase were assessed by conducting the molecular docking study. The chemical activities of aromadendrin, artepillin C, bavachin, and bavachinin against some of the expressed surface receptor proteins (CD44, CD47, CXCR4, EGFR, folate receptor, HER2, and endothelin receptor) in the mentioned cell lines were investigated using the molecular docking calculations. The results illustrated the atomic‐level properties and potential interactions. These chemicals have high binding affinities to the enzymes and proteins, according to the docking scores. In addition, the compounds formed strong contacts with the enzymes and receptors. Thus, these compounds could be potential inhibitors for enzymes and cancer cells. [ABSTRACT FROM AUTHOR]

Objectives: To compare the safety and efficacy of oral apixaban with that of injectable enoxaparin after robot‐assisted radical cystectomy (RARC) for venous thromboembolism (VTE) thromboprophylaxis. Materials and Methods: We conducted a retrospective review of prospectively collected data for all RARC patients treated at our tertiary care centre between 2018 and 2022. The study included two groups: patients who were subject to a prospectively implemented protocol from October 2021 to the present, comprising a 21‐day postoperative course of apixaban 2.5 mg twice daily after discharge, and patients treated prior to October 2021 who received enoxaparin 40 mg daily. Baseline demographics and clinical characteristics, such as VTE (defined as deep vein thrombosis and pulmonary embolism), were analysed. The primary outcome was incidence of symptomatic VTE confirmed with definitive imaging within 90 days of RARC. Secondary outcomes included major bleeding, complications, readmission, and mortality within 30 days postoperatively. Descriptive statistics included baseline patient characteristics, operative information and complications. Differences in baseline characteristics and postoperative data were compared between groups. Multivariate logistic regression was used to determine associations between variables and the primary outcome. Results: A total of 124 patients received apixaban and 250 patients received enoxaparin prophylaxis. Ten patients (2.7%) experienced a VTE within 90 days postoperatively (two [1.6%] apixaban group vs eight [3.2%] enoxaparin group; P = 0.5). After patient stratification into European Association of Urology risk groups, no statistically significant difference in VTE rates was seen between groups in the apixaban (2.7% high‐ + intermediate‐risk group vs 1.1% low‐risk group; P = 0.5) and enoxaparin cohorts (4.3% high‐ + intermediate‐risk group vs 2.5% low‐risk group; P = 0.5). On multivariate logistic regression, no variables were associated with the development of the primary outcome. Conclusion: Prophylaxis with apixaban and enoxaparin showed no statistically significant differences in VTE rates among RARC patients. Apixaban appears to be safe and effective for VTE prophylaxis after RARC. [ABSTRACT FROM AUTHOR]

In this study, we worked on anticolon cancer effects and anti‐Alzheimer's disease with molecular docking studies. Hamamelitannin, flavokawain A, and triacetyl resveratrol compounds showed good inhibitory activities on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes. The inhibition effects of flavokawain A, hamamelitannin, and triacetyl resveratrol on AChE and BuChE enzymes were determined spectrophotometrically conforming to Ellman. IC50 values of these enzymes were ranging between 0.95 ± 0.12 and 93.27 ± 8.14 nM for AChE and 5.71 ± 0.77 and 52.10 ± 8.41 nM for BuChE. The inhibitory activities of some chemical compounds such as flavokawain A, hamamelitannin, and triacetyl resveratrol were assessed by performing the molecular docking study in the presence of AChE and BuChE. Also, the features of the ligand–enzyme complex had value of −7.722 kcal/mol for flavokawain A against AChE and −5.530 kcal/mol against BuChE. The molecular docking calculations indicated the probable interactions and their characteristics at an atomic level. Due to the outcomes gained from docking, the affinity of the chemical compounds to the enzymes was considerable. In vitro cell viabilities of flavokawain A, hamamelitannin, and triacetyl resveratrol with various concentrations on SW620, DLD‐1, HT29, HCT8, and HCT116 were investigated by MTT assay with Doxorubicin as the control compound. [ABSTRACT FROM AUTHOR]

The present work was designed to investigate the microscopic structure of the oesophagus in the southern white‐breasted hedgehog (Erinaceus concolor) using histochemical staining, Scanning electron microscope (SEM), and stereological procedures. Four adult males were included in our study. Serial sections of the entire length of the oesophagus were stained with aldehyde fuchsin, alcian blue (pH 2.5), Periodic acid Schiff (PAS), and Masson's trichrome. Then, the total volume of the oesophagus, and the total volume of its different layers, were estimated using Cavalieri's principle. The oesophageal epithelium was a non‐keratinized stratified squamous type. Muscularis mucosa was present as a thick layer between lamina propria and submucosa and its thickness was increased toward the stomach. Tunica submucosa was a loose connective tissue containing an oesophageal gland with PAS‐positive and AB‐positive reactions throughout the submucosa and become denser toward the stomach. The tunica muscularis consisted of two distinct striated muscle layers, and its thickness was decreased toward the stomach. On SEM images, the cervical and thoracic oesophagus showed shallow folding, while the abdominal part had deeper folds. The present findings indicate that the histological properties of the oesophagus in southern white‐breasted hedgehogs have slight similarities with rodents and considering its epithelium, submucosal glands and tunica muscularis more resemble with dog oesophagus. The obtained results may be quite helpful to improve the current knowledge of the histophysiology of the hedgehog gastrointestinal tract as a member of eulipotyplan mammals and as a pet for biologists and veterinarians. [ABSTRACT FROM AUTHOR]

Chloroxine (5,7‐dichloro‐8‐hydroxyquinoline) is a molecule utilized in some shampoos for the therapy of seborrheic dermatitis of the scalp and dandruff. In this study, we investigated the inhibition effects of 5,7‐dichloro‐8‐hydroxyquinoline and methyl 3,4,5‐trihydroxybenzoate compounds on the 3‐hydroxy‐3‐methylglutaryl coenzyme‐A (HMG‐CoA Reductase) and urease enzymes. We have obtained results for the HMG‐CoA Reductase and urease enzymes at the micromolar level. In our study, inhibition result of 5,7‐dichloro‐8‐hydroxyquinoline and Methyl 3,4,5‐trihydroxybenzoate on HMG‐CoA reductase showed lower values 2.28 ± 0.78 and 33.25 ± 5.04 µg/ml, respectively. Additionally, inhibition result of 5,7‐dichloro‐8‐hydroxyquinoline and methyl 3,4,5‐trihydroxybenzoate on urease showed lower values 6.18 ± 1.38 and 8.51 ± 1.35 µg/ml, respectively. Molecular docking calculations were made for their biological activities were compared. In the present work, the structures of the related compounds (1 and 2) were drawn using Gaussian 09 software and done geometry optimization at DFT/B3LYP/6‐31G* basis set with aforementioned program. Cytotoxicity potential of these compounds against human lung cancer demonstrated that these compounds had good cytotoxic effects. Both compounds significantly decreased lung cell viability from low doses. In addition, 100 µM dose of all compounds caused significant reductions in lung cell viability. In general, we can say that of the two tested compounds, 5,7‐dichloro‐8‐hydroxyquinoline and methyl 3,4,5‐trihydroxybenzoate have cytotoxic effects in all cell types, and this effect is particularly strong in lung cells. Activities were performed at concentrations of 10, 20, 50, 70, and 100 µl and we achieved good results. Lung cell viability (%) value was better at 100 µl concentration and IC50 of them were 54.28 and 48.05 µM. [ABSTRACT FROM AUTHOR]

Natural molecules that possess antibacterial and anticancer activity have received rising interest to be utilized as alternative drug. This compounds have capacity efficacy in the therapy of lung cancer with minimal side effects. Triacetyl resveratrol compound showed good inhibitory activities against some metabolic enzymes with IC50 values of 45.14±3.88 μM for collagenase, 5.20±0.65 μM for alpha amylase, 125.63±9.70 μM for HMG‐CoA reductase and 31.78±5.30 μM for elastase. Indeed, these molecules had good In vitro anti‐lung cancer activities. The molecular docking was conducted to assess the chemical activity of triacetyl resveratrol against HMG‐CoA reductase, alpha‐amylase, collagenase, and elastase. Based on the obtained results, this compound can target the crucial residues of the enzymes and decrease their activities. The docking score of triacetyl resveratrol is −4.385 kcal/mol against HMG‐CoA reductase and −3.890 kcal/mol against alpha amylase. This score for the compound against collagenase and elastase are −3.371 kcal/mol and −1.608 kcal/mol, respectively. Diverse interactions like hydrogen bonds and hydrophobic bonds with the key residues of the enzymes can affect their activities considerably. Inhibition of elastase and collagenase enzymes recorded as main aims in cosmetic industry for researches to discovery novel skin‐lightening and antiwrinkle molecules or extracts particularly with rich polyphenol contents as well as to prove their effectiveness. [ABSTRACT FROM AUTHOR]

This study was performed to investigate the gross anatomy, histochemistry, and immunohistochemistry of the stomach in the Caucasian squirrel. A total of five male squirrels were included. The obtained results showed that the shape of the stomach was acutely crescent and consisted of four regions namely; cardiac, fundus, body, and pylorus. The stomach glandular and its wall was consisted of four layers; serosa, muscularis, submucosa, and mucosa. All part of the mucosa was covered by a simple columnar epithelium. Furthermore, gastric glands were of the simple tubular type. The mucous cells of the fundic and body regions were PAS‐positive. In the lower third of the gastric glands, parietal, and chief cells were identified. The number of chief cells was increased toward the pyloric area. Scanning electron microscopy showed that the fundus region contained many plicae and grooves and each plica carried numerous glands opening. In the body region, cells were polygonal and formed network‐like structures. In the pyloric region, a mucosal ridge between the body and antrum and a thick mucosal crest on the lesser curvature were identified. Immunohistochemical staining showed that Sox9 was strongly expressed in the fundic region, however, its expression in the body and pylorus was moderate to weak. In conclusion, there are some similarities and differences between the stomach of the Caucasian squirrel and other mammals including rodents. The obtained results may enhance our basic knowledge regarding the feeding habits and digestive system histophysiology of this species. [ABSTRACT FROM AUTHOR]

The present investigations were designed to describe the ultrastructural properties of the eye of the golden gray mullet (Chelon aurata). For this purpose, the eyes were examined grossly, and by light and electron microscope. The external layer consists of the cornea and the sclera. Three layers compose the cornea; the anterior stratified cuboidal epithelial; the anterior limiting (Bowman) membrane; and the thick dermal layer of the stroma. The mucoidal layer has small collagen fiber bundles embedded in the CT layer and located between the anterior portion of the scleral cornea and the dermal stroma, (or "substancia propria"). The iridescent layer is thin at the center and thick at the periphery. It contains a pigmented layer with many ossicles. SEM analysis reveals that the cornea consists of undetermined shaped cells joined together by numerous thread‐like micro‐ridges, with several micro‐tubercles on the external surface. The photoreceptor layer had two types of cells: the rod‐shaped and the cone‐shaped cells. The cone cells differentiate into two types of cells: single and double cells. SEM analysis of the retina showed that rod cells appear as thin long uniform rod‐like, while the cone cells appear as rod cells with ovoid bases. SEM analysis demonstrates that the inner side of the retinal epithelium appears to be wrapped around itself. The morphological appearance of the eye adapts to life in superficial aquatic conditions. In conclusion, the current findings provide morphologic evidence to better understand the mechanism of fish vision adaptation to environmental conditions. Research Highlights: The transparent cornea composed of three layers; anterior stratified cuboidal epithelial, Bowman's membrane, and a thick dermal stromal layer. The mucoidal layer is formed from small collagen fibers bundles embedded in the CT layer and located between the anterior portion of the scleral cornea and the dermal stroma. There are two types of photoreceptor cells: rod and cone cells. Cone cells can be single and double cells. [ABSTRACT FROM AUTHOR]

The current study was designed to give microscopic view on the snout skin of the domestic pig (Sus scrofa domesticus) to clear its adaptations with the function of exploring for the food and pushing the objects. This study carried out on the snout skin of apparently healthy 1 year five pigs (Sus Scrofa) and examined under the light and transmission electron microscopy. Our results clarify that the snout skin cutis composed of the epidermis and the dermis. The epidermis consisted of stratum corneum, stratum granulosum, stratum spinosum, and stratum basale. The stratum corneum and the stratum spinosum appeared thicker than other parts. The dermis consisted of a reticular and a papillary dermis. For tightness junction between the dermis and the epidermis, the hemidesmosomes were observed, while the desmosomes were presented in abundant numbers at the level of stratum basale to ensure the adhesion between the keratinocytes. The merocrine sweat glands were observed in abundant numbers to provide the wetness of the snout to avoid its injury from friction during food exploring or pushing of the objects. We concluded that the adaptation of the snout skin with the environmental condition surrounding the studied domestic pig. [ABSTRACT FROM AUTHOR]

This study evaluated the protective effect of resolvin D1 (RVD1) against cadmium chloride (CdCl2)‐induced hippocampal damage and memory loss in rats and investigated if such protection is mediated by modulating the PTEN/PI3K/Akt/mTOR pathway. Adult male Wistar rats (n = 18/group) were divided as control, control + RVD1, CdCl2, CdCl2 + RVD1 and CdCl2 + RVD1 + bpV(pic), a PTEN inhibitor. All treatments were conducted for 4 weeks. Resolvin D1 improved the memory function as measured by Morris water maze (MWM), preserved the structure of CA1 area of the hippocampus, and increased hippocampal levels of RVD1 in the CdCl2‐treated rats. Resolvin D1 also suppressed the generation of reactive oxygen species (ROS), tumour necrosis factor‐α and interleukine‐6 (IL‐6), inhibited nuclear factor κB (NF‐κB) p65, stimulated levels of glutathione (GSH), manganese superoxide dismutase (MnSOD), and Bcl2 but reduced the expression of Bax and cleaved caspase 3 in hippocampi of CdCl2‐treated rats. Concomitantly, it stimulated levels and activity of PTEN and reduced the phosphorylation (activation) of PI3K, Akt and mTOR in hippocampi of CdCl2‐treated rats. In conclusion, RVD1 attenuates CdCl2‐induced memory loss and hippocampal damage in rats mainly by activating PTEN‐induced suppression of PI3K/Akt/mTOR, an effect that seems secondary to its' anti‐oxidant and anti‐inflammatory potential. [ABSTRACT FROM AUTHOR]

Background and aims: Opioid agonist treatment is effective but resource intensive to administer safely in custodial settings, leading to significant under‐treatment of opioid dependence in these settings world‐wide. This study assessed the safety of subcutaneous slow‐release depot buprenorphine in custody. Design Open‐label, non‐randomized trial. Setting: Correctional centres in New South Wales, Australia. Participants: Sixty‐seven men and women, aged ≥ 18 years of various security classifications with a diagnosis of moderate to severe DSM‐5 opioid use disorder currently serving a custodial sentence of ≥ 6 months were recruited between November 2018 and July 2019. Patients not in opioid agonist treatment at recruitment commenced depot buprenorphine; patients already stable on oral methadone treatment were recruited to the comparison arm. Intervention and comparator: Depot buprenorphine (CAM2038 weekly for 4 weeks then monthly) and daily oral methadone. Measurements Safety was assessed by adverse event (AE) monitoring and physical examinations at every visit. Participants were administered a survey assessing self‐reported diversion and substance use at baseline and weeks 4 and 16. Findings Retention in depot buprenorphine treatment was 92.3%. Ninety‐four per cent of patients reported at least one adverse event, typically mild and transient. No diversion was identified. The prevalence of self‐reported non‐prescribed opioid use among depot buprenorphine patients decreased significantly between baseline (97%) and week 16 (12%, odds ratio = 0.0035, 95% confidence interval = 0.0007–0.018, P < 0.0001). Conclusions: This first study of depot buprenorphine in custodial settings showed treatment retention and outcomes comparable to those observed in community settings and for other opioid agonist treatment used in custodial settings, without increased risk of diversion. [ABSTRACT FROM AUTHOR]

Introduction: Digital microscopy systems are beginning to replace traditional light microscopes for morphologic analysis of blood films, but these are geographically restricted to individual computers and technically limited by manufacturer's constraints. We explored the use of a scanner‐agnostic web‐based artificial intelligence (AI) system to assess the accuracy of white blood cell (WBC) differentials and blast identification in haematological malignancies. Methods: Digitized images of 20 normal and 124 abnormal peripheral blood films were uploaded to the web‐based platform (Techcyte©) and WBC differentials performed using the online AI software. Digital images were viewed for accuracy and manual cell reassignment was performed where necessary. Results were correlated to the 'gold standard' of manual microscopy for each WBC class, and sensitivity and specificity of blast identification were calculated. Results: The AI digital differential was very strongly correlated to microscopy (r >.8) for most normal cell types and did not require any manual reassignment. The AI digital differential was less reliable for abnormal blood films (r =.50‐.87), but could be greatly improved by manual assessment of digital images for most cell types (r >.95) with the exception of immature granulocytes (r =.62). For blast identification, initial AI digital differentials showed 96% sensitivity and 25% specificity, which was improved to 99% and 84%, respectively, after manual digital review. Conclusions: The Techcyte platform allowed remote viewing and manual analysis of digitized slides that was comparable to microscopy. The AI software produced adequate WBC differentials for normal films and had high sensitivity for blast identification in malignant films. [ABSTRACT FROM AUTHOR]

The current investigation gave a full ultrastructural and histological description of the oropharyngeal cavity of the rock-pigeon Columba livia dakhlae. Our study carried on 10 heads of adult rock pigeons by gross, scanning, and light microscopic examination, in addition to the immunohistochemical analysis of the cytokeratin of the dorsal surface mucosa epithelium and the proliferating cell nuclear antigen expression (PCNA) immunoreactivity. The pointed apex of the elongated tongue covered rostrally and laterally with numerous caudally directed scales-like papillae. The dorsal surface of the apex and body was covered with numerous caudally directed scales-like filiform papillae. The U-shaped transverse papillary crest carried caudally directed pointed triangular conical papillae with two giant papillae. The elevated caudal area of the lingual body contains little numbers of the opening of the lingual gland. The laryngeal mound is divided into two symmetrical halves by rostral fissure and caudal laryngeal fissure into the right and left half. There were four palatine ridges: two lateral, middle, and median ridges. The choanal field bounded by the two lateral palatine ridges and containing the median choanae. The rostral part of the palatine cleft bounded laterally by a line of the small caudally directed conical papillae, while the caudal part was free from these papillae. There was a little number of taste buds in the palate. The high magnification of the rostral part of the beak is covered with directed rods-like projections. In conclusion, the obtained results described the adaptations of the tongue and its belonged structures with the feeding demand of the rock-pigeon. [ABSTRACT FROM AUTHOR]

Background: Systemic responses to cytoreductive nephrectomy (CN) in the management of metastatic renal cell carcinoma (mRCC) are variable and difficult to anticipate. The authors aimed to determine the association of CN with modifiable International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk factors and oncological outcomes. Methods: Consecutive patients with mRCC referred for potential CN (2009‐2019) were reviewed. The primary outcome was overall survival (OS); variables of interest included undergoing CN and the baseline number of modifiable IMDC risk factors (anemia, hypercalcemia, neutrophilia, thrombocytosis, and reduced performance status). For operative cases, the authors evaluated the effects of IMDC risk factor dynamics, measured 6 weeks and 6 months after CN, on OS and postoperative treatment disposition. Results: Of 245 treatment‐naive patients with mRCC referred for CN, 177 (72%) proceeded to surgery. The CN cases had fewer modifiable IMDC risk factors (P =.003), including none in 71 of 177 patients (40.1%); fewer metastases (P =.011); and higher proportions of clear cell histology (P =.012). In a multivariable analysis, surgical selection, number of IMDC risk factors, metastatic focality, and histology were associated with OS. Total risk factors changed for 53.8% and 57.2% of the patients from the preoperative period to 6 weeks and 6 months after CN, respectively. Adjusted for preoperative IMDC risk scores, an increase in IMDC risk factors at 6 weeks and 6 months was associated with adverse OS (hazard ratio [HR], 1.57; 95% confidence interval [CI], 1.13‐2.19; P =.007; HR, 2.52; 95% CI, 1.74‐3.65; P <.001). Conclusions: IMDC risk factors are dynamic clinical variables that can improve after upfront CN in select patients, and this suggests a systemic benefit of cytoreduction, which may confer clinically meaningful prognostic implications. Cytoreductive nephrectomy modifies the overall systemic disease status. The changes have therapeutic and prognostic implications. [ABSTRACT FROM AUTHOR]

The current investigation represented the first anatomical description of the buccal cavity of the grey gurnard Eutrigla gurnardus. For the achievement of this study, 10 heads of mature fish were used for SEM examinations. The morphological characteristic appearance of the buccal cavity has shown several adaptations in relation concerning its feeding habits. The median fissure of the upper lip divided the upper lip into two halves, this fissure appeared to be formed from many micro‐tubercles with numerous taste buds which aid in holding mucus secretion to the cell surface, help in mucus spread, and provide mechanical protection to the epithelium. Velum had two regions: median and peripheral region. The epithelium covering of the median region of the upper velum had dots‐like epithelial protrusion that carrying numerous taste buds, meanwhile, the epithelium covering of the lower velum not carried taste buds but instead carried numerous small scales‐like structures. The palate is divided into two semicircular regions by small region of microridges into the anterior and posterior region. The slightly bifid tongue had a median tubercle with numerous small taste buds on its dorsal surface. Concluded, these data were necessary to understand the adaptation of fish to its habitat and in developing a new and better method for fishing of this type of fish. [ABSTRACT FROM AUTHOR]

This study investigated the nephroprotective role of acylated ghrelin (AG) against DOX‐induced nephropathy and examined whether the protection involves silent information regulator 1 (SIRT1). Rats were divided into control, control + AG, DOX, DOX + AG, DOX + AG + [D‐Lys3]‐GHRP‐6 (a ghrelin receptor antagonist), and DOX + AG + EX‐527 (a sirt1 inhibitor). DOX was given over the first 2 weeks. AG (10 ng/kg) and both inhibitors were given as 3 doses/wk for 5 weeks. AG improved the structure and the function of the kidneys; down‐regulated the renal expression of TGF‐β1, collagen 1A1 and α‐SMA; and inhibited the renal collagen deposition in the kidneys of DOX‐treated rats. Concomitantly, it reduced the renal levels of ROS, MDA, TNF‐α, and IL‐6 and protein levels of cytochrome‐c, TGF‐β1, Smad3 and α‐SMA in these rats. In both the control and DOX‐treated rats, AG significantly increased the renal levels of SOD and GSH, decreased the expression of cleaved caspase‐3 and Bax, increased the total levels and the nuclear activity of SIRT1 and reduced the deacetylation of p53, NF‐κB and FOXO‐31. All the effects were abolished by the concurrent administration of EX‐527 and [D‐Lys3]‐GHRP‐6. In conclusion, AG prevents DOX‐induced nephropathy in SIRT1 and GSHRa1‐dependent mechanism. [ABSTRACT FROM AUTHOR]

The aim of this descriptive and explorative study was to assess individual case safety reports of bisoprolol associated with tinnitus and investigate their added value in information about adverse drug reactions (ADRs) in relation to information provided in medicine labels. The global reports from VigiBase, the WHO database of individual case safety reports, as of May 3, 2020, were analyzed for information about bisoprolol associated with tinnitus as an ADR affecting the quality of life of the patients. There were 123 reports of the ADR tinnitus reported with intake of bisoprolol in VigiBase. These described experiences of tinnitus and how this impacted on patients' daily life, for example, it could be long‐lasting and may have negative impact on sleeping, and even ability to work and keep a job. There were also reports describing the management of the reaction, for example, recovery upon stopping the treatment, and improvement of the symptoms following a decreased dose or change of medicine batch. Based on reports in VigiBase, the ADR tinnitus associated with bisoprolol suggests vigilance for the onset of the event and that, if it occurs, a dose reduction or stopping the treatment could be necessary. The information provided in the reports shows the value of individual case safety reports collected post marketing, in providing descriptive information of the experience and management of the ADR. [ABSTRACT FROM AUTHOR]

The aim of the current study was to investigate antioxidant, anti‐inflammatory and anti‐apoptotic effects of Origanum vulgare on finasteride‐induced oxidative injury in mouse testis and sperm parameters. Thirty BALB/c mice were divided into 5 groups: negative control, received 0.5 ml/day distilled water; positive control, received 25 mg/kg finasteride orally; and three groups received 100, 200 and 400 mg/kg/day O. vulgare extract plus 25 mg kg−1 day−1 finasteride for 35 days. At day 36, serum luteinising hormone, follicle‐stimulating hormone and testosterone, inflammatory cytokines (IL‐6, TNF‐α, IL‐1β), glutathione peroxidase, superoxide dismutase and nitric oxide levels were assessed. Also, apoptotic changes investigated through genes expression and immunohistochemical staining. Finasteride in 35 days resulted in significant destructive alterations in the testis architecture, suppressed antioxidant enzymes and increased lipid peroxidation. The expression of Bcl‐2 was down‐regulated, whereas p53 and caspase‐3 were up‐regulated. Origanum vulgare improved the serum level of hormones and restored the antioxidant defence. 200 and 400 mg/kg/day of O. vulgare alleviated the testis structure and sperm parameters, up‐regulated the anti‐apoptotic gene Bcl‐2 and down‐regulated the p53, caspase‐3 genes in treated groups. The findings indicate that O. vulgare extract improved function and structure of testis tissue against finasteride‐induced testicular toxicity. [ABSTRACT FROM AUTHOR]

This study investigated the effect of ellagic acid (EA) on SKOV‐3 cell growth and invasiveness and tested if the underlying mechanism involves modulating autophagy. Cells were treated with EA in the presence or absence of chloroquine (CQ), an autophagy inhibitor, compound C (CC), an AMPK inhibitor, or an insulin‐like growth factor‐1 (IGF‐1), a PI3K/Akt activator. EA, at an IC50 of 36.6 µmol/L, inhibited cell proliferation, migration, and invasion and induced cell apoptosis in SKOV‐3 cells. These events were prevented by CQ. Also, EA increased levels of Beclin‐1, ATG‐5, LC3I/II, Bax, cleaved caspase‐3/8 and reduced those of p62 and Bcl‐2 in these cancer cells. Mechanistically, EA decreased levels of p‐S6K1 (Thr389) and 4EBP‐1 (Thr37/46), two downstream targets of mTORC1, and p‐Akt (Thr308) but increased levels of AMPK (Thr172) and p‐raptor (Ser792), a natural inhibitor of mTORC1. CC or IGF‐1 alone partially prevented the effect of EA on cell survival, cell invasions, and levels of LDH, Beclin‐1, and cleaved caspase‐3. In conclusion, EA can inhibit SKOV‐3 growth, migration, and invasion by activating cytotoxic autophagy mediated by inhibition of mTORC1 and Akt and activation of AMPK. [ABSTRACT FROM AUTHOR]

Exendin‐4, a glucagon‐like peptide‐1 receptor agonist, was shown to protect against cardiac ischaemia/reperfusion (I/R) injury by suppressing oxidative stress. p66Shc, a pro‐oxidant and an apoptotic protein, is activated in the infarcted left ventricles (LVs) after induction of I/R. This study investigated if the cardiac protective effect of Exendin‐4 against I/R injury in rats involves inhibition of p66Shc and to determine the underlying mechanisms behind this. Adult male rats (n = 12/group) were divided into four groups as a sham, a sham + Exendin‐4, an I/R, and an I/R + Exendin‐4. Exendin‐4 was administered to rats 7 days before the induction of I/R. Ischaemia was induced by ligating the left anterior descending (LAD) coronary artery for 40 minutes followed by reperfusion for 10 minutes. The infarct myocardium was used for further analysis. Exendin‐4 significantly reduced infarct area (by 62%), preserved LV function and lowered serum levels of LDH and CK‐MB in I/R‐induced rats. Also, it significantly reduced LV levels of ROS and MDA and protein levels of cytochrome‐c and cleaved caspase‐3 but significantly increased levels of glutathione (GSH) and manganese superoxide dismutase (MnSOD) in LVs of I/R rats indicating antioxidant and anti‐apoptotic effects. Furthermore, it inhibited JNK and p66Shc activation and downregulated protein levels of p66Shc and NADPH oxidase with no effect on protein levels/activity of p53 and PKCβII. Of note, Exendin‐4 also increased GSH and MnSOD in LVs of control rats. In conclusion, Exendin‐4 cardioprotective effect in I/R hearts is mediated mainly by antioxidant effect and inhibition of JNK/P66Shc/NADPH oxidase. [ABSTRACT FROM AUTHOR]

This study investigates the effect of chronic consumption of a high‐fat diet rich in corn oil (CO‐HFD) on atrial cells ultrastructure, antioxidant levels and markers of intrinsic cell death of both control and type 1 diabetes mellitus (T1DM)‐induced rats. Adult male rats (10 rats/group) were divided into four groups: control fed standard diet (STD) (3.82 kcal/g, 9.4% fat), CO‐HFD (5.4 kcal/g, 40% fat), T1DM fed STD, and T1DM + CO‐HFD. CO‐HFD and T1DM alone or in combination impaired systolic and diastolic functions of rats and significantly reduced levels of GSH and the activity of SOD, enhanced lipid peroxidation, increased protein levels of P53, Bax, cleaved caspase‐3, and ANF and decreased levels of Bcl‐2 in their atria. Concomitantly, atrial cells exhibited fragmentation of the myofibrils, disorganized mitochondria, decreased number of atrionatriuretic factor (ANF) granules, and loss of gap junctions accompanied by changes in capillary walls. Among all treatments, the severity of all these findings was more severe in T1DM and most profound in the atria of T1DM + CO‐HFD. In conclusion, chronic consumption of CO‐HFD by T1DM‐induced rats elicits significant biochemical and ultrastructural damage to rat atrial cells accompanied by elevated oxidative stress and mitochondria‐mediated cell death. [ABSTRACT FROM AUTHOR]

Autophagy promotes cell survival or induces apoptosis in cancer cells. While SIRT1 and AMPK induce autophagy in both normal and cancer cells, Akt and mTOR can inhibit it. Calycosin, a methoxyisoflavone, protects against several types of solid tumours including colorectal cancer. However, the mechanisms behind the antitumour effect of Calycosin remain largely unknown. This study investigates if autophagy mediates the anti‐tumourigenesis effect afforded by Calycosin and examines if this effect involves activation of SIRT1 and/or AMPK. Human colorectal (HT29) carcinoma cells were cultured under normal conditions with Calycosin (50 μmol/L) in the presence or absence of chloroquine (10 μmol/L), EX‐527 (100 nmol/L, SIRT1 inhibitor), or IGF‐1 (100 ng/mL, Akt/mTOR activator) for 48 hours. Calycosin inhibited cell growth, proliferation and invasion and increased protein levels of Beclin‐1 and LC3II, markers of autophagy. It significantly increased protein levels of cleaved caspase‐3, Bax, and SIRT1, and activity of AMPK and reduced those of Bcl‐2. These effects were parallel with concomitant reduction in protein levels p‐src, integrin‐β1 and Cyclin‐D1 and activities of Akt and mTOR. Inhibition of autophagy by CQ reversed all these effects except cell invasion. Interestingly, co‐incubating the cells with either EX‐527 or IGF‐1 completely prevented Calycosin‐induced autophagy and all other associated effects and increased cell invasion. Also, blockade of SIRT‐1 prevented the activation of AMPK, Akt, and mTOR, suggesting it to be an upstream regulator of these markers. In conclusion, Calycosin stimulates CRC cell apoptosis and inhibits their invasion by acting as SIRT1 activator which induces activation of AMPK‐induced inhibition of Akt/mTOR axis. [ABSTRACT FROM AUTHOR]

The aim of this study was to analyze prevalence and clinical outcomes of the following clinical conditions: normotension (NT; clinic BP < 140/90 mm Hg; 24-hour BP < 130/80 mm Hg), white-coat hypertension (WCHT; clinic BP ≥ 140 and/or ≥90 mm Hg; 24-hour BP < 130/80 mm Hg), masked hypertension (MHT; clinic BP < 140/90 mm Hg; 24-hour BP ≥ 130 and/or ≥80 mm Hg), and sustained hypertension (SHT; clinic BP ≥ 140 and/or ≥90 mm Hg; 24-hour BP ≥ 130 and/or ≥80 mm Hg) in a large cohort of adult untreated individuals. Systematic research throughout the medical database of Regione Lazio (Italy) was performed to estimate incidence of myocardial infarction (MI), stroke, and hospitalizations for HT and heart failure (HF). Among a total study sample of 2209 outpatients, 377 (17.1%) had NT, 351 (15.9%) had WCHT, 149 (6.7%) had MHT, and 1332 had (60.3%) SHT. During an average follow-up of 120.1 ± 73.9 months, WCHT was associated with increased risk of hospitalization for HT (OR 95% CI: 1.927 [1.233-3.013]; P = .04) and HF (OR 95% CI: 3.449 [1.321-9.007]; P = .011). MHT was associated with an increased risk of MI (OR 95% CI: 5.062 [2.218-11.550]; P < .001), hospitalization for HT (OR 95% CI: 2.553 [1.446-4.508]; P = .001), and for HF (OR 95% CI: 4.214 [1.449-12.249]; P = .008). These effects remained statistically significant event after corrections for confounding factors including age, BMI, gender, smoking, dyslipidaemia, diabetes, and presence of antihypertensive therapies. [ABSTRACT FROM AUTHOR]

Introduction: There is a growing interest in the study of radiation-induced secondary cancer. The aim of this work is (i) to estimate the peripheral doses attributable to intensity modulated radiotherapy (IMRT) and mega-voltage cone beam computed tomography (MV-CBCT) for some organs at risk (OARs) which surround the target being treated (Nasopharynx) in paediatric patients. (ii) To estimate the risk of radiation-induced secondary cancers attributable to patient setup verification imaging dose using MV-CBCT for Nasopharyngeal Carcinoma (NPC) in paediatric patients and comparing it with that attributable to the therapeutic dose using IMRT.Methods: Intensity modulated radiotherapy treatment planning of 10 NPC paediatric patients was carried out on KonRad release 2.2.23. The additional radiation doses to the patients attributable to MV-CBCT were calculated also using Xio Version 4.4. A paediatric phantom and thermoluminescent dosimeters (TLDs) were used to measure the patient doses attributable to IMRT. These doses were then compared with the calculated doses. The risk of induced secondary cancers attributable to IMRT and MV-CBCT was calculated and compared to each other.Results: The absorbed doses (mean dose) for the OARs (Brain, Brain stem, spinal cord, thyroid, oesophagus, mandible, heart, optic nerve, lung and eye) were higher for the therapeutic dose than for the imaging dose used in the verification of patient position before and during the treatment. The risk of induced secondary cancers in thyroid, oesophagus and lung (the only organs from the OARs which have tabulated values for risk calculations) was higher for therapeutic dose (7.29 ± 0.73%, 2.62 ± 0.17% and 6.76 ± 0.87%, respectively) than for verification imaging dose (0.14 ± 0.00%, 0.06 ± 0.00%, 0.10 ± 0.03% respectively).Conclusion: The risk of secondary cancers attributable to verification imaging dose using MV-CBCT is very small compared to therapeutic dose using IMRT. Therefore, it is important to focus on the risk of secondary cancers attributable to therapeutic dose especially when using IMRT, where the produced leakage radiation is considerably high compared to some other techniques (such as conformal radiotherapy). [ABSTRACT FROM AUTHOR]

Keeping up to date with research developments is a central activity of academic researchers, but researchers face difficulties in managing the rapid growth of available scientific information. This study examined how researchers stay up to date, using the information journey model as a framework for analysis and investigating which dimensions influence information behaviors. We designed a 2-round study involving semistructured interviews and prototype testing with 61 researchers with 3 levels of seniority ( PhD student to professor). Data were analyzed following a semistructured qualitative approach. Five key dimensions that influence information behaviors were identified: level of seniority, information sources, state of the project, level of familiarity, and how well defined the relevant community is. These dimensions are interrelated and their values determine the flow of the information journey. Across all levels of professional expertise, researchers used similar hard (formal) sources to access content, while soft (interpersonal) sources were used to filter information. An important 'pain point' that future information tools should address is helping researchers filter information at the point of need. [ABSTRACT FROM AUTHOR]

Among the various asset management functions that support capital renewal decisions, both inspection and fund-allocation are very challenging in terms of time, cost, and technology. To support these functions, this article introduces two unique techniques that can be implemented, individually or combined, into any asset management system: (1) Focused-Inspection Technique (FIT); and (2) Multiple Optimization and Segmentation Technique (MOST). FIT improves inspection by incorporating an analysis of reactive-maintenance data to predict components' conditions, thus saving the time and cost of indiscriminate inspections. The MOST technique, on the other hand, has a unique formulation for large-scale optimization involving thousands of assets simultaneously, thus maximizes the return of renewal dollars. The article provides a description of the MOST-FIT techniques and discusses their implementation in a prototype system that suits a large school board in North America. The proposed techniques are innovative and help organizations with large building assets improve the overall condition of their inventory with highest return on the limited renewal budget. [ABSTRACT FROM AUTHOR]

Objective Patients and Methods Results Conclusions To assess recurrence‐free survival (RFS) in patients with undetectable tumour‐informed circulating tumour DNA (ctDNA) before radical cystectomy (RC) and evaluate if those who converted from detectable to undetectable ctDNA status after RC have similar RFS outcomes as those with persistently undetectable ctDNA status.Patients who underwent RC had prospectively and longitudinally collected tumour‐informed ctDNA analyses during 2021–2023. ctDNA status was informed from the pre‐RC specimen. The minimal residual disease (MRD) window was defined as the initial 90 days after RC. RFS was evaluated using the Kaplan–Meier method. Cox regression analysis was performed to find predictors of disease recurrence.The cohort included 135 patients with 647 ctDNA analyses. The median (interquartile range [IQR]) age was 71 (63–77) years. Over a median (IQR) follow‐up of 11 (7–18) months, 41 patients (30%) had a recurrence. Pre‐RC undetectable ctDNA status was found in 54 patients (40%). The RFS rates at 6, 12, and 21 months were 98%, 93%, and 82%, respectively. Of 77 patients with undetectable ctDNA status at the MRD window available for conversion dynamics analysis, 43 had persistently undetectable ctDNA status (both at pre‐RC and MRD window) and 31 converted from pre‐RC detectable to MRD undetectable status (conversion group). The persistently undetectable group had significantly better RFS than the conversion group (log‐rank, P < 0.001), with 12‐month RFS rates of 97% vs 51%, and 18‐month RFS rates of 88% vs 51%, respectively. On Cox multivariate analysis, only the conversion group status predicted disease recurrence.Patients with undetectable pre‐RC ctDNA status have a favourable prognosis and may be candidates for treatment de‐escalation. Those with persistently undetectable ctDNA had superior RFS compared to the conversion group. Pre‐RC ctDNA status should be incorporated into trials examining ctDNA use in clinical decision‐making. [ABSTRACT FROM AUTHOR]

Analyzes a mixture of the fullerene derivative [sub 60]D[sub 36] by neutron diffraction techniques. Conversion of the diffraction data to a reduced density function by Fourier transformation; Description of the compound by a T symmetry isomer; Sample preparation.