Introduction: Patients undergoing heart valve surgery are predominantly transferred postoperatively to the intensive care unit (ICU) under continuous sedation. Volatile anaesthetics are an increasingly used treatment alternative to intravenous substances in the ICU. As subject to inhalational uptake and elimination, the resulting pharmacological benefits have been repeatedly demonstrated. Therefore, volatile anaesthetics appear suitable to meet the growing demands of fast-track cardiac surgery. However, their use requires special preparation at the bedside and trained medical and nursing staff, which might limit the pharmacological benefits. The aim of our work is to assess whether the temporal advantages of recovery under volatile sedation outweigh the higher effort of special preparation.

Methods and analysis: The study is designed to evaluate the differences between intravenous sedatives (n=48) and volatile sedatives (n=48) in continued intensive care sedation. This study will be conducted as a prospective, randomised, controlled, single-blinded, monocentre trial at a German university hospital in consenting adult patients undergoing heart valve surgery at a university hospital. This observational study will examine the necessary preparation time, staff consultation and overall feasibility of the chosen sedation method. For this purpose, the continuation of sedation in the ICU with volatile sedatives is considered as one study arm and with intravenous sedatives as the comparison group. Due to rapid elimination and quick awakening after the termination of sedation, closer consultation between the attending physician and the ICU nursing staff is required, in addition to a prolonged setup time. Study analysis will include the required setup time, time from admission to extubation as primary outcome and neurocognitive assessability. In addition, possible operation-specific (blood loss, complications), treatment parameters (catecholamine dosages, lung function) and laboratory results (acute kidney injury, acid base balance (lactataemia), liver failure) as influencing factors will be collected. The study-relevant data will be extracted from the continuous digital records of the patient data management system after the patient has been discharged from the ICU. For statistical evaluation, 95% CIs will be calculated for the median time to extubation and neurocognitive assessability, and the association will be assessed with a Cox regression model. In addition, secondary binary outcome measures will be evaluated using Fisher's exact tests. Further descriptive and exploratory statistical analyses are also planned.

Ethics and dissemination: The study was approved by the Institutional Ethics Board of the University of Frankfurt, Germany (#20-1050). Informed consent of all individual patients will be obtained before randomisation. Results will be disseminated via publication in peer-reviewed journals.

Trial registration number: Clinical trials registration (NCT04958668) was completed on 1 July 2021.

Keywords: adult intensive & critical care; cardiac surgery; health economics; thoracic surgery; valvular heart disease.

Objective: The aim of the study was to investigate the prevalence of metabolic syndrome (MetSyn), associated factors, and optimal waist circumference (WC) cut points in a subset of the elderly population in Asmara, Eritrea.

Design: A community-based cross-sectional study conducted between January and June 2018.

Setting: Asmara, Eritrea.

Participants: Demographic, clinical biochemistry and anthropometric information were collected from a total of 319 elderly participants of African lineage (54.5% men vs 45.5% women).

Main outcome measures: Lipid profiles, fasting plasma glucose (FPG), anthropometric data, clinical profiles and demographic characteristic of patients were described. MetSyn was defined according to the International Diabetes Federation harmonised criteria.

Results: The median age (IQR) of study participants was 67 (IQR: 63-72 years)-men 68 (IQR: 64-74) years versus women 65 (IQR: 62-70) years, p=0.002. The prevalence of MetSyn was 90 (28.4%). Abnormal values in MetSyn components were as follows: systolic blood pressure/diastolic blood pressure ≥130/85 mm Hg or use of hypertension medication 133 (41.7%); overweight/obesity, 55 (25.1%); abdominal obesity 129 (40.4); low-density lipoproptein cholesterol (LDL-C) >130 mg/dL, 139 (43.6%); total cholesterol >200 mg/dL, 152 (47.6%); non-high-density lipoproptein cholesterol (HDL-C)>130 mg/dL, 220 (69.0%) and FPG (≥100-125 mg/dL), 35 (12.7%) and FPG>125.17 (6.2%). Multivariate logistic regression analysis indicated that sex (females) (adjusted OR (aOR) 4.69, 95% CI 2.47 to 8.92); non-HDL-C (aOR 1.09, 95% CI 1.05 to 1.14); LDL-C >130 mg/dL (aOR 2.63, 95% CI 1.09 to 6.37) and body mass index (aOR 1.20, 95% CI 1.10 to 1.32) were independently associated with the presence of MetSyn. Optimal cut points for WC in men yielded a value of 85.50 cm, a sensitivity of 76.0%, a specificity of 61.0% and an area under receiver operating characteristics curve (AUROC) value of 74.0, 95% CI (65.7 to 82.4). For women, the WC at a cut point value of 80.50 cm yielded the highest Youden index (0.41) with a sensitivity of 80%, a specificity of 39%, and an AUROC of 73.4, 95% CI (64.8 to 82.5).

Conclusions: The MetSyn is highly prevalent in a subset of apparently healthy elderly population in Asmara, Eritrea. The findings support opportunistic and/or programmatic screening for CVD risk in the elderly during outpatient visits.

Keywords: cardiac epidemiology; epidemiology; general endocrinology; lipid disorders.

Introduction: Hand eczema (HE) is one of the most common skin disorders and an important cause for morbidity and occupational disability. The 1-year prevalence of HE is estimated to be up to 10% and it is estimated that 5%-7% of those develop severe chronic HE. However, current clinical evidence is not compelling enough to guide clinical practice. In a survey among 194 UK dermatologists the most frequent first choice approaches were psoralen combined with ultraviolet A (UVA) treatment (PUVA), oral steroids and alitretinoin (AL). When asked which strategy was most efficient for long-term outcome 20% of clinicians indicated they did not know; 43% of clinicians reported AL and 30% reported PUVA.

Methods and analysis: ALPHA is a multicentre, open, prospective, two-arm parallel group, randomised controlled trial comparing PUVA and AL with a planned sample size re-estimation. Between 500 and 780 participants will be randomised on a 1:1 basis. The physician's global assessment (PGA) will direct treatment after randomisation, non-responders will be treated according to usual clinical practice; providing valuable pilot data on second line therapeutic approaches to inform future trials.Assessments will be conducted up to 52 weeks post randomisation. The primary outcome measure is the Hand Eczema Severity Index at 12 weeks. Secondary outcome measures include modified Total Lesion Symptom Score, PGA, time to relapse, patient reported outcome measures and DNA extraction and assessment of genetic variants. A substudy on molecular inflammatory mediators will provide information on subgroup specific treatment responses. Photographs will be taken and HE severity assessed by a central review panel.

Ethics and dissemination: Ethics approval was obtained from Leeds West Research Ethics Committee (14/YH/1259).Trial results will be disseminated at relevant clinical conferences and societies, published in peer-reviewed journals and through relevant patient groups.

Trial registration number: ISRCTN80206075.

Keywords: dermatology; eczema; occupational dermatology; photodermatology.

Aim: This study was conducted to evaluate the marginal adaptation, marginal staining, and postoperative sensitivity of resin composite restorations after disinfection of class II cavities with NanoCare Gold and chlorhexidine in class II cavities immediately, after 6 months, 1, and 2 years using World Dental Federation (FDI) criteria for assessment of dental restorations.

Materials and methods: In this study, 19 participants were recruited, 3 carious lesions in each one. After preparation of these lesions, they were randomly allocated into three parallel groups according to the disinfection protocol. The first group was for NanoCare Gold, the second was for chlorhexidine, and the third was for the control. The three groups were evaluated clinically and radiographically using (FDI) criteria at different intervals till 2 years of clinical service.

Results: There was no statistically significant difference in age, gender, arch, and tooth type distribution among study groups. Regarding marginal adaptation, there was no statistically significant difference among the different groups but the difference was only statistically significant within each group after 2 years. Regarding the marginal staining, the difference was only significant between the NanoCare and the other groups after 2 years. In case of postoperative sensitivity, there was no statistically significant difference among the different groups and within each one at different intervals.

Conclusion: NanoCare Gold could be promising in durability preservation of direct tooth-colored restorations. Marginal staining and postoperative sensitivity are regulated by other factors than surface pretreatment.

Clinical significance: As long as restorations are inserted under rubber dam isolation, proper application steps, proper filling, and adequate finishing and polishing, the performance of the restorations would be satisfactory up to 1 year without any surface disinfection. However, after a longer follow-up, some changes may be noticed. NanoCare Gold and chlorhexidine are accepted as a cavity disinfectant without any negative effect on marginal adaptation of resin composite restorations.

Keywords: Chlorhexidine; Marginal adaptation; Marginal staining; NanoCare Gold Postoperative sensitivity..

Purpose: This study aims to determine if the presence of specific clinical and computed tomography (CT) patterns are associated with epidermal growth factor receptor (EGFR) mutation in patients with non-small cell lung cancer.

Methods: A systematic literature review and meta-analysis was carried out in 6 databases between January 2002 and July 2021. The relationship between clinical and CT patterns to detect EGFR mutation was measured and pooled using odds ratios (OR). These results were used to build several mathematical models to predict EGFR mutation.

Results: 34 retrospective diagnostic accuracy studies met the inclusion and exclusion criteria. The results showed that ground-glass opacities (GGO) have an OR of 1.86 (95%CI 1.34 -2.57), air bronchogram OR 1.60 (95%CI 1.38 - 1.85), vascular convergence OR 1.39 (95%CI 1.12 - 1.74), pleural retraction OR 1.99 (95%CI 1.72 - 2.31), spiculation OR 1.42 (95%CI 1.19 - 1.70), cavitation OR 0.70 (95%CI 0.57 - 0.86), early disease stage OR 1.58 (95%CI 1.14 - 2.18), non-smoker status OR 2.79 (95%CI 2.34 - 3.31), female gender OR 2.33 (95%CI 1.97 - 2.75). A mathematical model was built, including all clinical and CT patterns assessed, showing an area under the curve (AUC) of 0.81.

Conclusions: GGO, air bronchogram, vascular convergence, pleural retraction, spiculated margins, early disease stage, female gender, and non-smoking status are significant risk factors for EGFR mutation. At the same time, cavitation is a protective factor for EGFR mutation. The mathematical model built acts as a good predictor for EGFR mutation in patients with lung adenocarcinoma.

Keywords: ALK, anaplastic lymphoma kinase mutation; AUC, area under the curve; Biopsy; CT, computed tomography; Computed tomography; EGFR TKI, epidermal growth factor receptor tyrosine kinase inhibitors; EGFR mutation; EGFR, epidermal growth factor; FN, False negatives; FP, False positives; GGO, Ground glass opacities; KRAS, Kirsten rat sarcoma viral oncogene homolog; Lung adenocarcinoma; Lung cancer; NSCLC, non-small cell lung carcinoma; Non-small cell lung cancer; OR, Odds ratios; PRISMA, Preferred Reporting Items for Systematic Review and Meta-analysis; QUADAS-2, Quality Assessment of Diagnostic Accuracy Studies-2; ROC, Receiver Operating Characteristics; TN, True Negative; TP, True Positive.

Previous studies have shown that selenium possessed chemotherapeutic effect against multiple malignant cancers, inducing diverse stress responses including apoptosis and autophagy. Selenite was previously shown to induce apoptosis and autophagy in colorectal cancer cells. However, the relationship between selenite-induced apoptosis and autophagy was not fully understood. Our results revealed a pro-survival role of selenite-induced autophagy against apoptosis in colorectal cancer cells. Real-time PCR array of autophagy-related genes showed that GABARAPL-1 was significantly upregulated in colorectal cancer cells, which was confirmed by western blot and immunofluorescence results. Knockdown of GABARAPL-1 significantly inhibited selenite-induced autophagy and enhanced apoptosis. Furthermore, we found that selenite-induced upregulation of GABARAPL-1 was caused by upregulated p-AMPK and FoxO3a level. Their interaction was correlated with involved in regulation of GABARAPL-1. We observed that activation and inhibition of AMPK influenced both autophagy and apoptosis level via FoxO3a/ GABARAPL-1 signaling, implying the pro-survival role of autophagy against apoptosis. Importantly, we corroborated these findings in a colorectal cancer xenograft animal model with immunohistochemistry and western blot results. Collectively, these results show that sodium selenite could induce ROS/AMPK/FoxO3a/GABARAPL-1-mediated autophagy and downregulate apoptosis in both colorectal cancer cells and colon xenograft model. These findings help to explore sodium selenite as a potential anti-cancer drug in clinical practices.

Keywords: AMPK; Apoptosis; Autophagy; FoxO3a; Selenite.

Liver cancers, such as hepatocellular carcinoma (HCC), are a highly prevalent cause of cancer-related deaths. Current treatments to combat liver cancer are limited. (-)-Agelasidine A, a compound isolated from the methanol extract of Agelasnakamurai, a sesquiterpene guanidine derived from sea sponge, has antibacterial activity. We demonstrated its anticancer capabilities by researching the associated mechanism of (-)-agelasidine A in human liver cancer cells. We found that (-)-agelasidine A significantly reduced viability in Hep3B and HepG2 cells, and we determined that apoptosis was involved in the (-)-agelasidine A-induced Hep3B cell deaths. (-)-Agelasidine A activated caspases 9, 8, and 3, as well as PARP. This effect was reversed by caspase inhibitors, suggesting caspase-mediated apoptosis in the (-)-agelasidine A-treated Hep3B cells. Moreover, the reduced mitochondrial membrane potential (MMP) and the release of cytochrome c indicated that the (-)-agelasidine A-mediated mitochondrial apoptosis was mechanistic. (-)-Agelasidine A also increased apoptosis-associated proteins (DR4, DR5, FAS), which are related to extrinsic pathways. These events were accompanied by an increase in Bim and Bax, proteins that promote apoptosis, and a decrease in the antiapoptotic protein, Bcl-2. Furthermore, our results presented that (-)-agelasidine A treatment bridged the intrinsic and extrinsic apoptotic pathways. Western blot analysis of Hep3B cells treated with (-)-agelasidine A showed that endoplasmic reticulum (ER) stress-related proteins (GRP78, phosphorylated PERK, phosphorylated eIF2α, ATF4, truncated ATF6, and CHOP) were upregulated. Moreover, 4-PBA, an ER stress inhibitor, could also abrogate (-)-agelasidine A-induced cell viability reduction, annexin V+ apoptosis, death receptor (DR4, DR5, FAS) expression, mitochondrial dysfunction, and cytochrome c release. In conclusion, by activating ER stress, (-)-agelasidine A induced the extrinsic and intrinsic apoptotic pathways of human HCC.

Keywords: (−)-agelasidine A; apoptosis; caspase; death receptor; endoplasmic reticulum stress; hepatocellular carcinoma (HCC); mitochondrial membrane potential.

Phaeodactylum tricornutum is the marine diatom best known for high-value compounds that are useful in aquaculture and food area. In this study, fucoxanthin was first extracted from the diatom using supercritical fluid extraction (SFE) and then using the extracted diatom-like substrate to produce bioenergy through anaerobic digestion (AD) processes. Factors such as temperature (30 °C and 50 °C), pressure (20, 30, and 40 MPa), and ethanol (co-solvent concentration from 10% to 50% v/v) were optimized for improving the yield, purity, and recovery of fucoxanthin extracted using SFE. The highest yield (24.41% w/w) was obtained at 30 MPa, 30 °C, and 30% ethanol but the highest fucoxanthin purity and recovery (85.03mg/g extract and 66.60% w/w, respectively) were obtained at 30 MPa, 30 °C, and 40%ethanol. Furthermore, ethanol as a factor had the most significant effect on the overall process of SFE. Subsequently, P.tricornutum biomass and SFE-extracted diatom were used as substrates for biogas production through AD. The effect of fucoxanthin was studied on the yield of AD, which resulted in 77.15 ± 3.85 LSTP CH₄/kg volatile solids (VS) and 56.66 ± 1.90 LSTP CH₄/kg VS for the whole diatom and the extracted P.tricornutum, respectively. Therefore, P.tricornutuman can be considered a potential source of fucoxanthin and methane and both productions will contribute to the sustainability of the algae-biorefinery processes.

Keywords: Phaeodactylum tricornutum; algae biorefinery; anaerobic digestion; co-solvent; fucoxanthin; supercritical fluid extraction.

Left ventricular noncompaction (LVNC) is a type of cardiomyopathy characterized anatomically by prominent ventricular trabeculation and deep intertrabecular recesses. The mortality associated with LVNC ranges from 5% to 47%. The etiology of LVNC is yet to be fully understood, although decades have passed since its recognition as a clinical entity globally. Furthermore, critical questions, i.e., whether LVNC represents an acquired pathology or has a congenital origin and whether the reduced contractile function in LVNC patients is a cause or consequence of noncompaction, remain to be addressed. In this study, to answer some of these questions, we analyzed the clinical features of LVNC patients. Out of 9582 subjects screened for abnormal cardiac functions, 45 exhibit the characteristics of LVNC, and 1 presents right ventricular noncompaction (RVNC). We found that 40 patients show valvular regurgitation, 39 manifest reduced systolic contractions, and 46 out of the 46 present different forms of arrhythmias that are not restricted to be caused by the noncompact myocardium. This retrospective examination of LVNC patients reveals some novel findings: LVNC is associated with regurgitation in most patients and arrhythmias in all patients. The thickness ratio of the trabecular layer to compact layer negatively correlates with fractional shortening, and reduced contractility might result from LVNC. This study adds evidence to support a congenital origin of LVNC that might benefit the diagnosis and subsequent characterization of LVNC patients.

Keywords: arrythmia; left ventricular noncompaction; regurgitation; right ventricular noncompaction; trabeculation; ventricular contraction.

Quorum sensing (QS) can regulate the pathogenicity of bacteria and the production of some virulence factors. It is a promising target for screening to find anti-virulence agents in the coming post-antibiotics era. Cyclo (L-Trp-L-Ser), one variety of cyclic dipeptides (CDPs), isolated from a marine bacterium Rheinheimera aquimaris, exhibited anti-QS activity against Chromobacterium violaceum CV026 and Pseudomonas aeruginosa PAO1. Unlike the CDPs composed of phenylalanine or tyrosine, the anti-QS activity has been widely studied; however, cyclo (L-Trp-L-Ser) and derivatives, containing one tryptophan unit and one non-aromatic amino acid, have not been systematically explored. Herein, the cyclo (L-Trp-L-Ser) and seven derivatives were synthesized and evaluated. All tryptophane-contained CDPs were able to decrease the production of violacein in C.violaceum CV026 and predicted as binding within the same pocket of receptor protein CviR, but in lower binding energy compared with the natural ligand C₆HSL. As for P. aeruginosa PAO1, owning more complicated QS systems, these CDPs also exhibited inhibitory effects on pyocyanin production, swimming motility, biofilm formation, and adhesion. These investigations suggested a promising way to keep the tryptophan untouched and make modifications on the non-aromatic unit to increase the anti-QS activity and decrease the cytotoxicity, thus developing a novel CDP-based anti-virulence agent.

Keywords: Pseudomonas aeruginosa; anti-quorum sensing; bacterial adhesion; biofilm; cyclic dipeptides; tryptophane.

Our study aimed to evaluate the potential of prognostic nutritional index (PNI) and Brain natriuretic peptide (BNP) in predicting the prognosis of heart transplantation (HTx). We retrospectively investigated 489 patients undergoing HTx between 2015 and 2020 in our center. The relationship between preoperative index and prognosis was analyzed respectively, the optimal cut-off values for preoperative PNI and BNP level were evaluated with receiver operating curve analysis. Uni-variate analysis and multivariate analysis were used to compare baseline data (sex, age, diagnosis, etc.) of groups divided by the level of PNI and BNP. Propensity score matching (PSM) was applied to eliminate bias. We calculated the C-index from the prediction efficiency of PNI and BNP. During the period, 489 recipients undergoing HTx in our center were included according to the inclusion criteria; 383 (78.3%) males and 106 (21.7%) females were included in this study, with a median age of 47.57 years old. The ROC curve showed that the optimal cut-off values of each indicator were verified as 49.345 for PNI, and 4397.500 for BNP. The multivariate analyses indicated that PNI (p = 0.047), BNP (p = 0.024), age (p = 0.0023), and waiting time (p = 0.012) were risk factors for all-cause death after HTx. Propensity score matching generated 116 pairs based on PNI level and 126 pairs based on BNP level, and the results showed that OS (overall survival) was significantly correlated with PNI (n = 232, p = 0.0113) and BNP (n = 252, p = 0.0146). Our study implied that higher PNI and lower BNP level had direct correlation with better survival after HTx. Combining PNI and BNP together would be a potential clinical preoperative instrument to predict the survival of patients after HTx, especially in short-term survival.

Keywords: China; brain natriuretic peptide; heart transplantation; prognostic nutritional index; propensity score matching.

N-2-hydroxypropyltrimethyl ammonium chloride chitosan (HACC), a cationic quaternary ammonium salt polymer exhibiting good solubility in water, is widely used because of its low toxicity and good biocompatibility. Herein, through ion exchange reaction, we prepared N-2-hydroxypropyltrimethyl ammonium chitosan derivatives bearing amino acid Schiff bases with good biological activities. The accuracy of the structures was verified by FT-IR and ¹H NMR. The antibacterial activity, antifungal activity, and scavenging ability of DPPH radical and superoxide radical of HACC derivatives were significantly improved compared with that of HACC. In particular, HACGM (HACC-potassium 2-((2-hydroxy-3-methoxybenzylidene)amino)acetate) and HACGB (HACC-potassium 2-((5-bromo-2-hydroxybenzylidene)amino)acetate) showed good inhibitory effect on bacteria and fungi, including Staphylococcus aureus, Escherichia coli, Botrytis cinerea, and Fusarium oxysporum f. sp. cubense. The inhibition rate of HACGB on Staphylococcus aureus and Escherichia coli could reach 100% at the concentration of 0.1 mg/mL, and the inhibition rate of HACGM and HACGB on Botrytis cinerea and Fusarium oxysporum f. sp. cubense could also reach 100% at the concentration of 0.5 mg/mL. Improving antimicrobial and antioxidant activities of HACC could provide ideas and experiences for the development and utilization of chitosan derivatives.

Keywords: N-2-hydroxypropyltrimethyl ammonium chloride chitosan; amino acid Schiff bases; antimicrobial activity; antioxidant activity.

Due to their high biodiversity and adaptation to a mutable and challenging environment, aquatic lophotrochozoan animals are regarded as a virtually unlimited source of bioactive molecules. Among these, lectins, i.e., proteins with remarkable carbohydrate-recognition properties involved in immunity, reproduction, self/nonself recognition and several other biological processes, are particularly attractive targets for biotechnological research. To date, lectin research in the Lophotrochozoa has been restricted to the most widespread phyla, which are the usual targets of comparative immunology studies, such as Mollusca and Annelida. Here we provide the first overview of the repertoire of the secretory lectin-like molecules encoded by the genomes of six target rotifer species: Brachionus calyciflorus, Brachionus plicatilis, Proales similis (class Monogononta), Adineta ricciae, Didymodactylos carnosus and Rotaria sordida (class Bdelloidea). Overall, while rotifer secretory lectins display a high molecular diversity and belong to nine different structural classes, their total number is significantly lower than for other groups of lophotrochozoans, with no evidence of lineage-specific expansion events. Considering the high evolutionary divergence between rotifers and the other major sister phyla, their widespread distribution in aquatic environments and the ease of their collection and rearing in laboratory conditions, these organisms may represent interesting targets for glycobiological studies, which may allow the identification of novel carbohydrate-binding proteins with peculiar biological properties.

Keywords: C-type lectins; C1q domain-containing proteins; galectins; innate immunity; microbe-associated molecular patterns; pattern recognition receptors; rotifera.

Pore scale analysis of flow through porous media is of interest because it is essential for understanding internal erosion and piping, among other applications. Past studies have mainly focused on exploring macroscopic flow to infer microscopic phenomena. An innovative method is introduced in this study which permits visualization of interstitial fluid flow through the pores of a saturated synthetic transparent granular medium at the microscale. Several representative images of Ottawa sand were obtained using dynamic image analysis (DIA), for comparison with flow through perfect cylinders. Magnified transparent soil particles made of hydrogel were cast in 3D printed molds. Custom 3D printed jigs were employed for accurate positioning of the particles to ensure that particles have the same flow area within the soil. The pore fluid was embedded with silver-coated hollow microspheres that allowed for their florescence and tracking their movement within the model when illuminated by a laser light source. Images of the flow were captured from the model using a high-speed camera. This, along with particle image velocimetry (PIV) provided for the velocity and direction analysis of fluid flow movements within the pore space of a planar 2D model. Comparison of interstitial flow through homogeneous porosity-controlled Ottawa-shaped and cylindrical particles demonstrates that the magnitude of turbulence is related to particle roundness.

Keywords: granulometry; inter-particle; microscale; roundness; shape.

Cellular technologies are one of the most promising areas of biomedicine, which is based on the isolation of cells of various types, followed by their cultivation and use, or the use of their metabolic products, for medical purposes. Today, a significant part of biomedical research is carried out in vitro. On the other hand, organotypic culture can be used as a powerful model system and can complement cell culture and in vivo studies in different biomedical applications. Uterine leiomyoma (UL) is a very common benign tumor and often leads to many reproductive complications. Herein we describe a fast and reliable method of isolation and UL primary cells culturing along with the development of a UL organotypic model. We propose the usage of UL primary cells in experimental work at a first passage to prevent loss of driver mutations in MED12 and HMGA2 genes. New optimized conditions for the growth and maintenance of 2D and 3D models of uterine leiomyoma in vitro are suggested.

Keywords: HMGA2; MED12; cell model; organotypic model; uterine leiomyoma.

Objective: With the rising prevalence of diabetes worldwide, increased attention is focused on natural drug candidates that can treat diabetes with high efficacy but without undesired side effects. Lentinus edodes is an edible and medicinal fungus, whose polysaccharides are one of the main components that have been reported to have hypoglycemic ability. However, the detailed underlying hypoglycemic mechanism of Lentinus edodes polysaccharides is still unknown. In this study, we extracted and prepared a novel polysaccharide from Lentinus edodes, which was named LNT-1. Methods: The aim of this study was to evaluate the hypoglycemic effect of LNT-1 on mice with type 2 diabetes that was induced by a high fat and high sugar diet and streptozotocin. To explore the possible mechanism, metabolomics analysis based on UPLC-Q-TOF/MS and molecular methods were performed. Results: Data showed that treatment with LNT-1 could ameliorate the damage in diabetic mice, including physiological and biochemical indexes, oxidative parameters and histopathological changes. Moreover, 36 potential biomarkers were screened using metabolomics analysis based on UPLC-Q-TOF/MS. Among them, the main metabolic pathways were glycerophospholipid metabolism, arachidonic acid metabolism and arginine biosynthesis, thereby suggesting that oxidative stress may be involved in the occurrence of diabetes. Both the mRNA and protein expression of the Nrf2/HO-1 signaling pathway was upregulated after treatment with LNT-1, indicating that the hypoglycemic effect of LNT-1 may be related to the activation of the Nrf2/HO-1 pathway. Conclusion: LNT-1 may be a potential natural drug candidate for the prevention and treatment of diabetes by regulating the oxidative stress response. Our study aimed to provide new insights into the application of Lentinus edodes and its polysaccharide as a drug candidate and as an active ingredient in functional foods.

Aims: The impact of blood pressure (BP) levels on subclinical left ventricular (LV) dysfunction and possible sex-specific difference remains unclarified. This study investigated the relationship between BP categories given in the new 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guideline and subclinical LV dysfunction in subjects free of cardiac disease.

Methods and results: We examined antihypertensive medication-naive 858 individuals who underwent extensive cardiovascular health check-up. LV global longitudinal (LVGLS) and circumferential strain (LVGCS) were assessed by two-dimensional speckle-tracking echocardiography. Participants were categorized into four groups: normal BP, elevated BP, isolated diastolic hypertension (IDH), and systolic hypertension (SH). Among the 858 participants, 422 individuals had normal BP, 113 had elevated BP, 160 had IDH, and 163 had SH. Prevalence of abnormal LVGLS (>-18.6%) was greatest in SH (19.0%), followed by IDH (17.5%), elevated BP (14.2%), and normal BP (7.1%, P < 0.001); no significant differences were observed for LVGCS (P = 0.671). In the multivariable analyses, IDH and SH were associated with impaired LVGLS [adjusted odds ratio (OR) 2.69 and 2.66, P < 0.001], and borderline significance was observed for elevated BP (adjusted OR 1.90, P = 0.060); there was no significant association between any of the BP groups and LVGCS. In sex-stratified analysis, IDH and SH carried the significant risk of abnormal LVGLS in both sexes, while elevated BP was associated with LVGLS only in women.

Conclusions: Isolated diastolic hypertension and SH redefined by ACC/AHA guideline carried significant risk for LVGLS, but not LVGCS. Elevated BP was associated with LVGLS only in women. Our findings provide information on cardiac correlates of the newly established BP categories.

Keywords: Blood pressure; Left ventricular strain; Primary prevention; Sex difference; Speckle-tracking echocardiography.

Introduction: Correct and prompt diagnosis is essential for the appropriate management of patients. Often, children and their caretakers cannot provide a reliable history to allow clinicians to determine the cause of the pain. This study's objective was to find out the prevalence of abnormal ultrasonographic findings among referred patients with pain abdomen in the radiology department of a tertiary care center of Nepal.

Methods: A descriptive cross-sectional study was conducted among patients in the out-patient and emergency department with complaints of abdominal pain from 2021 April 5 to August 30 in a tertiary care hospital. Ethical clearance was taken from IRC (registration no: 423/2021). The convenience sampling method was used. Written informed consent was taken from each study participant. Collected data were entered and analyzed on Statistical Package for the Social Sciences version 20. Point estimate at 95% Confidence Interval was calculated along with frequency and percentage for binary data.

Results: Among 250 patients with pain abdomen referred to the department of radiology, 169 (67.6%) (61.80-73.40 at 95% Confidence Interval) had abnormal ultrasonographic findings. Mean age of the patients was 39.4±17.9 years. Initial clinical diagnosis was in agreement with the abdominal ultrasound diagnosis in 57 (22.8%) patients. For the remaining 193 patients, the diagnosis obtained from abdominal ultrasound differed from the initial clinical diagnosis.

Conclusions: Most of the cases of pain abdomen showed abnormalities in ultrasound. Clinical evaluation should be used together with ultrasound abdomen in order to arrive at a correct diagnosis.

Keywords: abdomen; pain; patients; radiology; ultrasonography..

The objective was to evaluate the correlation between N-terminal pro-atrial natriuretic peptide (NT-proANP), corin and the severity of target organ injury in hypertensive disorders of pregnancy. A total of 78 women with hypertensive disorders of pregnancy and 49 normotensive pregnancies were enrolled. The clinical characteristics, laboratory index and echocardiogram results were collected. NT-proANP, corin, sFlt-1 and PlGF levels were measured. A receiver's operating characteristics (ROC) curve was performed to evaluate the efficacy of predicting target organ injury in the HDP group. The NT-proANP, corin, and sFlt-1/PlGF ratio were increased in the HDP group (p < .05). The area under the curve (AUC) predicted by NT-proANP and corin were larger than sFlt-1/PlGF ratio (0.779, 0.867, and 0.766, respectively). The creatinine and urine protein were significantly increased, while the estimated glomerular filtration rate (eGFR) was dramatically decreased in the HDP group (p < .05 each). The left atrial diameter (LAD), left atrial volume index (LAVI), left ventricular posterior wall thickness (LVPWT), and left ventricular septal thickness (LVST) were larger in the HDP group (p < .001 each). The NT-proANP/corin levels were positively correlated with LAD, creatinine, and urine protein, and negatively correlated with eGFR in HDP group (p < .05 each). Multiple regressions demonstrated that NT-proANP was an independent risk factor of LAD and urine protein, and corin was an independent risk factor of creatinine and eGFR in HDP group. NT-proANP and corin may be reliable biomarkers for evaluating the severity of target organ damage in the hypertensive disorders of pregnant patients.

Keywords: N-terminal pro-atrial natriuretic peptide; corin; hypertensive disorders of pregnancy; placental growth factor; soluble FMS-like tyrosine kinase.

Two olean-27-carboxylic acid-type triterpenoids ( 1 and 2 ) were isolated from Saxifraga umbellulata (Saxifragaceae), representing the first case in the chemical discoveries of genus Saxifraga . Compound 1 was determined to be a new compound named 'Saxifragic acid' based on the comprehensive spectroscopic and X-ray crystallographic analyses. Compound 2 (deacetylated saxifragic acid) is a known compound reported before, but its absolute configuration through X-ray crystallographic analyses was first described here. In addition, their cytotoxicity against five digestive human cancer cell lines (BGC-823, GBC-SD, CCC-9810, HT-29, and HepG2) and hepatoprotective activity against CCl 4 -induced L-o2 cell injury in vitro were evaluated. Interestingly, UPLC-QTOFMS analysis showed that these two compounds could be used as chemical markers to discriminate between S . umbellulata and S. tangutica , both of which are used for the treatment of hepatobiliary diseases in traditional Tibetan medicine.

Keywords: Saxifraga umbellulata, triterpenoids, cytotoxicity, hepatoprotective, chemical markers.

Cortical amyloid deposition is one of the hallmark biomarkers of Alzheimer's disease (AD). However, given how cost- and time-intensive amyloid imaging can be, there is a continued need for a low-cost, non-invasive, and accessible enrichment strategy to pre-screen individuals for their likelihood of amyloid prior to imaging. Previous work supports the use of coordinated limb movement as a potential screening tool, even after controlling for cognitive and daily function. Thirty-six patients diagnosed with amnestic mild cognitive impairment over the age of 65 underwent 18F-Flutemetamol amyloid-positron emission tomography (PET) imaging and then completed a timed motor task involving upper limb coordination. This task takes ∼5 minutes to administer and score. Multivariate linear regression and receiver operator characteristic analyses showed that including motor task performance improved model prediction of amyloid burden. Results support the rationale for including functional upper extremity motor assessment as a cost- and time-effective means to screen participants for amyloid deposition.

Keywords: amyloid deposition; mild cognitive impairment; motor; positron emission tomography; upper-extremity.

Exquisite discoveries and new interpretations regarding an enigmatic group of cursorial avemetatarsalians led to a new phylogenetic hypothesis regarding pterosaur affinities. Previously thought to be dinosaur precursors, lagerpetids are now considered to be the closest relatives to pterosaurs. This new hypothesis sheds light on a new explorable field, especially regarding the character acquisition and evolution within the pterosaur lineage. In the present study, the morphospace occupation of distinct skeletal regions of lagerpetids withing the morphological spectrum of avemetatarsalians is investigated. This approach indicates which portions of the skeleton are more similar to the anatomy of pterosaurs and which portions present different homoplastic signals. The analyses demonstrates that the craniomandibular traits of lagerpetids are pterosaur-like, the pectoral girdle and forelimb are dinosauromorph-like and the axial skeleton and the pelvic girdle and hindlimb are unique and highly specialized among the analysed sample. So, despite the close phylogenetic relationships, the postcranial skeleton of lagerpetids and pterosaurs are very different. The occurrence of two distinct and highly specialized groups of pterosauromorphs coexisting with a wide ecological range of dinosauromorphs during Triassic suggests pressure for new niches occupation.

Keywords: Dinosauromorpha; Evolution; Lagerpetidae; Pterosauria; Pterosauromorpha.