Bioactive alkaloids from Nepalese Corydalis chaerophylla D.C. acting on the regulation of PCSK9 and LDL-R in vitro.

Four new alkaloids Chaeronepaline-A (1), Chaeronepaline-B (2), Chaeronepaline-C (3), and Chaeronepaline-D (4) were isolated from Corydalis chaerophylla D.C. collected from Nepal and their structures were elucidated by spectroscopic data, 1D, 2D NMR and mass spectrometry. The structures were established as 3,12- Dimethoxy-5,6-dihydroisoquinolino [2,1-b] isoquinolin- 7- ium- 2, 9- diol (1), 7-methyl-5, 6, 7, 8-tetrahydroisoquinoline- 2, 3- methylenedioxy- (8-> 9)- 10, 12- methylenedioxy- benzoic-16-acid (2), 7- methyl-5, 6, 7, 8- tetrahydro- 8H-spiro-9,14-dihydroxy-11,12-methylenedioxy-indane-isoquinoline (3) and 7- methyl-5, 6, 7, 8- tetrahydro- 8H-spiro-9,14-dihydroxy-11,12-methylenedioxy-indane-isoquinoline-N-oxide (4). The new alkaloids were tested in human hepatoma cell line to assess their ability to modulate the expression of low-density lipoprotein receptor (LDL-R), of proprotein convertase subtilisin/kexin 9 (PCSK9) and to affect cellular cholesterol biosynthesis with the aim to evaluate their potential hypocholesterolemic effect. Results indicated that compounds 2 and 3 upregulate the LDLR, and inhibited the cholesterol biosynthesis with compound 2, which also reduced the secretion of PCSK9 by Huh7 cells. These in vitro data indicated a potential hypocholesterolemic effect of compound 2 that requires further in vivo validation.

3D C-arm navigated acromioclavicular joint stabilization.

INTRODUCTION: Surgical treatment options for acromioclavicular joint separations are varied. Frequently, suspension devices (SD) are inserted for stabilization under arthroscopic view. This study investigates the feasibility and accuracy of three-dimensional (3D) digital-volume-tomography (DVT) C-arm navigated implantation with regard to the general trend toward increasingly minimally invasive procedures. MATERIALS AND METHODS: The implantation of a TightRope® suture button system (SD) via a navigated vertical drill channel through the clavicle and coracoid was investigated in 10 synthetic shoulder models with a mobile isocentric C-arm image intensifier setup in the usual parasagittal position. Thereby, in addition the placement of an additive horizontal suture cerclage via a navigated drill channel through the acromion was assessed. RESULTS: All vertical drill channels in the Coracoclavicular (CC) direction could be placed in a line centrally through the clavicle and the coracoid base. The horizontal drill channels in the Acromioclavicular (AC) direction ran strictly in the acromion, without affecting the AC joint or lateral clavicle. All SD could be well inserted and anchored. After tensioning and knotting of the system, the application of the horizontal AC cerclage was easily possible. The image quality was good and all relevant structures could be assessed well. CONCLUSION: Intraoperative 3D DVT imaging of the shoulder joint using a mobile isocentric C-arm in the usual parasagittal position to the patient is possible. Likewise, DVT navigated SD implantation at the AC joint in CC and AC direction on a synthetic shoulder model. By combining both methods, the application in vivo could be possible. Further clinical studies on feasibility and comparison with established methods should be performed.

Transcriptomic analysis reveals that Bacillomycin D-C16 induces multiple pathways of disease resistance in cherry tomato.

BACKGROUND: Bacillomycin D-C16 can induce resistance in cherry tomato against pathogens; however, the underlying molecular mechanism is poorly understood. Here, the effect of Bacillomycin D-C16 on induction of disease resistance in cherry tomato was investigated using a transcriptomic analysis. RESULTS: Transcriptomic analysis revealed a series of obvious enrichment pathways. Bacillomycin D-C16 induced phenylpropanoid biosynthesis pathways and activated the synthesis of defense-related metabolites including phenolic acids and lignin. Moreover, Bacillomycin D-C16 triggered a defense response through both hormone signal transduction and plant-pathogen interactions pathways, and increased the transcription of several transcription factors (e.g., AP2/ERF, WRKY and MYB). These transcription factors might contribute to the further activated the expression of defense-related genes (PR1, PR10 and CHI) and stimulated the accumulation of H2O2. CONCLUSION: Bacillomycin D-C16 can induce resistance in cherry tomato by activating the phenylpropanoid biosynthesis pathway, hormone signal transduction pathway and plant-pathogen interactions pathway, thus activating comprehensive defense reaction against pathogen invasion. These results provided a new insight into the bio-preservation of cherry tomato by the Bacillomycin D-C16.

Amyloid precursor protein 𝛽CTF accumulates in synapses in sporadic and genetic forms of Alzheimer's disease.

AIMS: Amyloid precursor protein (APP) 𝛽-C-terminal fragment (𝛽CTF) may have a neurotoxic role in Alzheimer's disease (AD). 𝛽CTF accumulates in the brains of patients with sporadic (SAD) and genetic forms of AD. Synapses degenerate early during the pathogenesis of AD. We studied whether the 𝛽CTF accumulates in synapses in SAD, autosomal dominant AD (ADAD) and Down syndrome (DS). METHODS: We used array tomography to determine APP at synapses in human AD tissue. We measured 𝛽CTF, A𝛽40, A𝛽42 and phosphorylated tau181 (p-tau181) concentrations in brain homogenates and synaptosomes of frontal and temporal cortex of SAD, ADAD, DS and controls. RESULTS: APP colocalised with pre- and post-synaptic markers in human AD brains. APP 𝛽CTF was enriched in AD synaptosomes. CONCLUSIONS: We demonstrate that 𝛽CTF accumulates in synapses in SAD, ADAD and DS. This finding might suggest a role for 𝛽CTF in synapse degeneration. Therapies aimed at mitigating 𝛽CTF accumulation could be potentially beneficial in AD.

Efficient H2 Evolution Coupled with Anodic Oxidation of Iodide over Defective Carbon-Supported Single-Atom Mo-N4 Electrocatalyst.

We successfully prepared nitrogen-doped defective carbon spheres (Mo-N4/d-C) with a high loading of 0.996 wt % via a designed vapor-deposition process for IOR-based hydrogen generation. The synthesized Mo-N4/d-C catalyst provides a record current density of 10 mA cm-2 at 0.77 V. Further, the Mo-N4/d-C catalyst shows a Tafel slope of 25.58 mV dec-1, exceptional stability over time in acidic media, a higher hydrogen generation rate of 0.1063 mL gcat-1 min-1, a high Faradaic efficiency of 99.8%, and a reduction of the energy consumption up to ∼50% for hydrogen evolution by anodic oxidation reaction of iodide (IOR) compared with the conventional OER-based electrolysis. Computational calculations demonstrate that the Mo-N4/d-C structure plays a vital effect on the activity of iodide oxidation, which is competitive with the Pt catalyst.

The cost of post-abortion care (PAC): a systematic review.

BACKGROUND: Despite the increasing trend of Postabortion Care (PAC) needs and provision, the evidence related to its cost is lacking. This study aims to review the costs of Postabortion Care (PAC) per patient at a national level. METHODS: A systematic review of literature related to PAC cost published in 1994 - October 2020 was performed. Electronic databases such as PubMed, Medline, The Cochrane Library, CINAHL, and PsycINFO were used to search the literature. Following the title and abstract screening, reporting quality was appraised using the Consolidates Health Economic Evaluation (CHEERS) checklist. PAC costs were extrapolated into US dollars ($US) and international dollars ($I), both in 2019. RESULTS: Twelve studies met the inclusion criteria. All studies reported direct medical cost per patient in accessing PAC, but only three of them included indirect medical cost. All studies reported either average or range of cost. In terms of range, the highest direct cost of PAC with MVA (Medical Vacuum Aspiration) services can be found in Colombia, between $US50.58-212.47, while the lowest is in Malawi ($US15.2-139.19). The highest direct cost of PAC with D&C (Dilatation and Curettage), services is in El Salvador ($US65.22-240.75), while the lowest is in Bangladesh ($US15.71-103.85). Among two studies providing average indirect cost data, Uganda with $US105.04 has the highest average indirect medical cost, while Rwanda with $US51.44 has the lowest. CONCLUSIONS: Our review shows variability in the cost of PAC across countries. This study depicts a clearer picture of how costly it is for women to access PAC services, although it is still seemingly underestimated. When a study compared the use of UE (Uterine Evacuation) method between MVA and D&C, it is confirmed that MVA treatments tend to have lower costs and potentially reduce a significant cost. Therefore, by looking at both clinical and economic perspectives, improving and strengthening the quality and accessibility of PAC with MVA is a priority.

Natural Products & Bioactivity Inspired Synthetic Pursuits Interfacing with Carbohydrates: Ongoing Journey with C-Glycosides.

Natural products, remains the most important source for the discovery of new drugs for the treatment of human diseases. This has inspired the synthetic community to design and develop mimics of natural products either to answer important questions in biology or to explore their therapeutic potentials. Glycosides present themselves abundantly in nature, right from the cell surface receptors to natural products of any origin. The O-Glycosides are hydrolytically less stable compared to C-glycosides and this feature has presented a great opportunity for drug discovery. The discovery of Dapagliflozin, an SGLT inhibitor and C-glucoside, for the treatment of diabetes is one such example. Aryl acyl-anion chemistry has been explored for the synthesis of 2-deoxy-C-aryl furanoside/pyranoside/septanosides. Besides success, the studies have provided valuable insight into the natural propensities of the architectural framework for the cascade to furan derivatives. The aryl acyl-anion chemistry has also enabled the synthesis of biologically active diaryl heptanoids. Inspired from sucesss of Dapagliflozin, new analogues have been synthesized with pyridine and isocoumarin heterocycle as the proximal ring. C-glucosides of isoliquiritigenin have been synthesized for the first time and evaluated as an efficient aldose reductase inhibitor. The synthesis and evaluation of acyl-C-ß-D-glucosides and benzyl-C-ß-D-glucoside as glucose-uptake promoters has revealed promise in small molecules. The concept of building blocks has been used to obtain natural oxylipins, D-xylo and L-xylo-configured alkane tetrols and novel lipophilic ketones with erythro/threo configured trihydroxy polar head-group as possible anti-mycobacterial agents.

Power and sample size calculation for the win odds test: application to an ordinal endpoint in COVID-19 trials.

The win odds is a distribution-free method of comparing locations of distributions of two independent random variables. Introduced as a method for analyzing hierarchical composite endpoints, it is well suited to be used in the analysis of ordinal scale endpoints in COVID-19 clinical trials. For a single outcome, we provide power and sample size calculation formulas for the win odds test. We also provide an implementation of the win odds analysis method for a single ordinal outcome in a commonly used statistical software to make the win odds analysis fully reproducible.

Structural determination of four manufacturing impurities of D&C Red No. 33.

Four manufacturing impurities of D&C Red No. 33 isolated by counter-current chromatography were analyzed by NMR and ESI mass spectrometry. Three of these impurities were reported previously with minimal details of structural determination. All four are structurally related to the main component of the dye. The fourth exhibited an unusual discrepancy between the NMR structure and its chemical formula suggested by ESI-MS results. Structural determination and assignment of the main component and four impurities are discussed as well as resolution of the discrepancy between the NMR and ESI-MS results of the fourth impurity.

Corneal Healing and Recovery of Ocular Crystallinity with a Dichloromethane Extract of Sedum dendroideum D.C. in a Novel Murine Model of Ocular Pterygium.

Pterygium is a corneal alteration that can cause visual impairment, which has been traditionally treated with the sap of Sedum dendroideum D.C. The pharmacological effect of a dichloromethane extract of S. dendroideum was demonstrated and implemented in a pterygium model on the healing process of corneal damage caused by phorbol esters. In mice of the ICR strain, a corneal lesion was caused by intravitreal injection of tetradecanoylphorbol acetate (TPA). The evolution of the corneal scarring process was monitored with vehicle, dexamethasone, and dichloromethane extract of S. dendroideum treatments by daily ophthalmic administration for fifteen days. The lesions were evaluated in situ with highlighted images of fluorescence of the lesions. Following treatment levels in eyeballs of IL-1α, TNF-α, and IL-10 cytokines were measured. The effective dose of TPA to produce a pterygium-like lesion was determined. The follow-up of the evolution of the scarring process allowed us to define that the treatment with S. dendroideum improved the experimental pterygium and had an immunomodulatory effect by decreasing TNF-α, IL-1α, and maintaining the level of IL-10 expression, without difference with respect to the healthy control. Traditional medical use of S. dendroideum sap to treat pterygium is fully justified by its compound composition.

Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in a Rapid-Initiation Model of Care for Human Immunodeficiency Virus Type 1 Infection: Primary Analysis of the DIAMOND Study.

BACKGROUND: Most guidelines recommend rapid treatment initiation for patients with newly diagnosed human immunodeficiency virus type 1 (HIV-1) infection, but prospective US data are limited. The DIAMOND (NCT03227861) study using darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg is a phase 3 prospective study evaluating efficacy/safety of a single-tablet regimen in a rapid-initiation model of care. METHODS: Adults aged ≥18 years began D/C/F/TAF ≤14 days from diagnosis without screening/baseline results; as results became available, participants not meeting predefined safety/resistance stopping rules continued. Primary endpoint was virologic response (HIV-1 RNA <50 copies/mL; intent-to-treat; US Food and Drug Administration [FDA] snapshot) at week 48; participant satisfaction was measured via the HIV Treatment Satisfaction Questionnaire status version (HIVTSQs). RESULTS: Of 109 participants, 87% were male, 32% black/African American, median (range) age was 28 (range, 19-66) years, 25% of participants had HIV-1 RNA ≥100 000 copies/mL, 21% had CD4+ cell count <200 cells/µL, and 31% enrolled ≤48 hours from diagnosis. At week 48, 97 (89%) participants completed the study and 92 (84%) achieved HIV-1 RNA <50 copies/mL (FDA snapshot). There were no protocol-defined virologic failures; incidences of adverse events (AEs) and adverse drug reactions (33%) were low, no serious AEs were study drug related, and 1 (<1%) participant discontinued due to study drug related AE(s). The overall HIVTSQs score at week 48 was 58 (maximum: 60). CONCLUSIONS: At week 48, a high proportion of participants starting D/C/F/TAF achieved HIV-1 RNA <50 copies/mL and very few discontinued therapy. D/C/F/TAF was well tolerated, no participants discontinued due to baseline resistance stopping criteria, and high treatment satisfaction among participants was recorded. CLINICAL TRIALS REGISTRATION: NCT03227861.

Racial disparities in breast cancer hereditary risk assessment referrals.

For poorly understood reasons, Black non-Hispanic (BNH) women meeting National Comprehensive Cancer Network (NCCN) criteria for genetic testing for breast cancer risk are less likely than White non-Hispanic (WNH) women to undergo testing (Armstrong, Micco, Carney, Stopfer, & Putt, JAMA, 293, 1729 and 2005). We compared physician referral rates and uptake for genetic testing of BNH and WNH women meeting select NCCN criteria (breast cancer under age 50, two primary breast cancers, triple-negative disease under age 60) in the Cancer Center at George Washington University (GWCC) between 2015 and 2018. Of the 723 BNH and WNH patients treated for breast cancer at GWCC, 28% met study criteria for genetic counseling referral (n = 252; BNH n = 115, WNH n = 137). Physician referral rates to genetic counseling differed significantly by race (BNH 75.7%, n = 87 and WNH 92.7%; n = 127; χ2  = 14.19, p-value < .01). Once referred, though, there was no significant difference in uptake of genetic counseling by race (BNH 95.4%, n = 83; WNH 97.6%, n = 124, χ2  = 1.33, p-value = .25) for patients appropriately referred.

Genetic analysis of the grapevine genotypes of the Russian Vitis ampelographic collection using iPBS markers.

Cultivated grapevine (Vitis vinifera L. ssp. sativa D.C.) is one of the oldest agricultural crops, each variety comprising an array of clones obtained by vegetative propagation from a selected vine grown from a single seedling. Most clones within a variety are identical, but some show a different form of accession, giving rise to new divergent phenotypes. Understanding the associations among the genotypes within a variety is crucial to efficient management and effective grapevine improvement. Inter-primer binding-site (iPBS) markers may aid in determining the new clones inside closely related genotypes. Following this idea, iPBS markers were used to assess the genetic variation of 33 grapevine genotypes collected from Russia. We used molecular markers to identify the differences among and within five grapevine clonal populations and analysed the variation, using clustering and statistical approaches. Four of a total of 30 PBS primers were selected, based on amplification efficiency. Polymerase chain reaction (PCR) with PBS primers resulted in a total of 1412 bands ranging from 300 to 6000 bp, with a polymorphism ratio of 44%, ranging from 58 to 75 bands per group. In total, were identified seven private bands in 33 genotypes. Results of molecular variance analysis showed that 40% of the total variation was observed within groups and only 60% between groups. Cluster analysis clearly showed that grapevine genotypes are highly divergent and possess abundant genetic diversities. The iPBS PCR-based genome fingerprinting technology used in this study effectively differentiated genotypes into five grapevine groups and indicated that iPBS markers are useful tools for clonal selection. The number of differences between clones was sufficient to identify them as separate clones of studied varieties containing unique mutations. Our previous phenotypic and phenological studies have confirmed that these genotypes differ from those of maternal plants. This work emphasized the need for a better understanding of the genotypic differences among closely related varieties of grapevine and has implications for the management of its selection processes.

A general double-proximal gradient algorithm for d.c. programming.

The possibilities of exploiting the special structure of d.c. programs, which consist of optimising the difference of convex functions, are currently more or less limited to variants of the DCA proposed by Pham Dinh Tao and Le Thi Hoai An in 1997. These assume that either the convex or the concave part, or both, are evaluated by one of their subgradients. In this paper we propose an algorithm which allows the evaluation of both the concave and the convex part by their proximal points. Additionally, we allow a smooth part, which is evaluated via its gradient. In the spirit of primal-dual splitting algorithms, the concave part might be the composition of a concave function with a linear operator, which are, however, evaluated separately. For this algorithm we show that every cluster point is a solution of the optimisation problem. Furthermore, we show the connection to the Toland dual problem and prove a descent property for the objective function values of a primal-dual formulation of the problem. Convergence of the iterates is shown if this objective function satisfies the Kurdyka-Lojasiewicz property. In the last part, we apply the algorithm to an image processing model.

3D conditional generative adversarial networks for high-quality PET image estimation at low dose.

Positron emission tomography (PET) is a widely used imaging modality, providing insight into both the biochemical and physiological processes of human body. Usually, a full dose radioactive tracer is required to obtain high-quality PET images for clinical needs. This inevitably raises concerns about potential health hazards. On the other hand, dose reduction may cause the increased noise in the reconstructed PET images, which impacts the image quality to a certain extent. In this paper, in order to reduce the radiation exposure while maintaining the high quality of PET images, we propose a novel method based on 3D conditional generative adversarial networks (3D c-GANs) to estimate the high-quality full-dose PET images from low-dose ones. Generative adversarial networks (GANs) include a generator network and a discriminator network which are trained simultaneously with the goal of one beating the other. Similar to GANs, in the proposed 3D c-GANs, we condition the model on an input low-dose PET image and generate a corresponding output full-dose PET image. Specifically, to render the same underlying information between the low-dose and full-dose PET images, a 3D U-net-like deep architecture which can combine hierarchical features by using skip connection is designed as the generator network to synthesize the full-dose image. In order to guarantee the synthesized PET image to be close to the real one, we take into account of the estimation error loss in addition to the discriminator feedback to train the generator network. Furthermore, a concatenated 3D c-GANs based progressive refinement scheme is also proposed to further improve the quality of estimated images. Validation was done on a real human brain dataset including both the normal subjects and the subjects diagnosed as mild cognitive impairment (MCI). Experimental results show that our proposed 3D c-GANs method outperforms the benchmark methods and achieves much better performance than the state-of-the-art methods in both qualitative and quantitative measures.

Cost-effectiveness analysis of biopsy strategies for endometrial cancer diagnosis in women with postmenopausal bleeding: Pipelle sampling curette versus dilatation & curettage.

BACKGROUND: Endometrial sampling is widely used for accurate diagnosis of endometrial cancer (EC), which is the most common gynecologic cancer in US women. The objective of this study was to explore the cost-effectiveness of two endometrial sampling procedures for diagnosing EC: (1) Pipelle endometrial sampling (Pipelle), and (2) dilatation & curettage (D&C), while accounting for sampling procedure failure rates and diagnostic accuracy in women with postmenopausal bleeding (PMB). METHOD: The decision analytic model was built to compare the cost-effectiveness of Pipelle and D&C strategies in a hypothetical cohort of PMB women. The analysis was performed from the perspective of a public healthcare payer (Medicare, US). We used 2017 Medicare reimbursement data for cost estimation. The effectiveness of these two diagnostic strategies was measured by analyzing the remaining life expectancy after EC diagnosis and subsequent treatment. RESULTS: The base case analysis suggested that Pipelle was not only equally effective (32.11 vs. 32.11 years of life), but also less costly ($1897.80 vs. $2999.11) based on Medicare reimbursement when compared to D&C. In one-way sensitivity analyses and Monte Carlo probabilistic sensitivity analysis, the Pipelle remained the more cost-effective sampling strategy even after accounting for sampling failure rate associated with each sampling strategy. CONCLUSION: The Pipelle is the more cost-effective sampling strategy compared to D&C for EC diagnosis in women with PMB. From the cost-effectiveness perspective, the higher sampling failure rate of Pipelle should not be regarded as a limitation in its clinical application.

ФC31 Integrase-Mediated Isolation and Characterization of Novel Safe Harbors for Transgene Expression in the Pig Genome.

Programmable nucleases have allowed the rapid development of gene editing and transgenics, but the technology still suffers from the lack of predefined genetic loci for reliable transgene expression and maintenance. To address this issue, we used ФC31 integrase to navigate the porcine genome and identify the pseudo attP sites suitable as safe harbors for sustained transgene expression. The combined ФC31 integrase mRNA and an enhanced green fluorescence protein (EGFP) reporter donor were microinjected into one-cell zygotes for transgene integration. Among the resulting seven EGFP-positive piglets, two had transgene integrations at pseudo attP sites, located in an intergenic region of chromosome 1 (chr1-attP) and the 6th intron of the TRABD2A gene on chromosome 3 (chr3-attP), respectively. The integration structure was determined by TAIL-PCR and Southern blotting. Primary fibroblast cells were isolated from the two piglets and examined using fluorescence-activated cell sorting (FACS) and enzyme-linked immunosorbent assay (ELISA), which demonstrated that the chr1-attP site was more potent than chr3-attP site in supporting the EGFP expression. Both piglets had green feet under the emission of UV light, and pelleted primary fibroblast cells were green-colored under natural light, corroborating that the two pseudo attP sites are beneficial to transgene expression. The discovery of these two novel safe harbors for robust and durable transgene expression will greatly facilitate the use of transgenic pigs for basic, biomedical and agricultural studies and applications.

Outcomes of nonsurgical versus surgical treatment of cesarean scar pregnancies in the first trimester.

PURPOSE: To compare outcomes of nonsurgical versus surgical treatment of Cesarean scar pregnancies (CSP) in the first trimester and identify optimal treatment methods for CSP. METHODS: Retrospective cohort study of all women diagnosed and treated with CSP in the first trimester at a single tertiary care center from 2000-2012. Main outcome measures were need for additional treatments, hemorrhage, or emergent hysterectomy. Future pregnancy outcomes were considered secondarily. RESULTS: Twenty-three cases of CSP treated in the first trimester were confirmed including 12 treated surgically and 11 treated nonsurgically. Of the nonsurgical patients, none treated with a combination of intrasac potassium chloride (KCl) and systemic methotrexate (MTX) required further treatment versus 5/8 (62%) of those treated with a single agent (p = 0.18). One patient who was treated with intrasac KCl alone experienced hemorrhage. Of the nine patients treated with suction dilation and curettage (D&C), two (22%) required additional intervention, but none experienced major complications. Nonsurgical therapy had a higher rate of needing further intervention (45%) than surgical therapy (17%) (p = 0.19). There was one recurrent CSP in 11 subsequent deliveries with no uterine ruptures or hysterectomies. CONCLUSIONS: We have described nonsurgical and surgical treatments of first trimester CSP with a low rate of major complications and no emergent hysterectomies. Of the nonsurgical therapies, single-agent treatment with either systemic MTX or intrasac KCl was associated with high rates of needing additional treatment and should be avoided. Our method of ultrasound-guided suction D&C resulted in no major hemorrhage and is a reasonable surgical treatment option.

One-stop clinical assessment of risk for endometrial hyperplasia (OSCAR-Endo): a fast-track protocol for evaluating endometrial pathologies.

PURPOSE: To evaluate a one-stop clinical assessment of risk for assessing endometrial pathologies (OSCAR-Endo), consisting of a fast-track protocol with hysteroscopy, dilation and curettage (D&C) with intraoperative frozen section analysis of the removed tissue in cases of hysteroscopic suspicion of malignancy. METHODS: In this prospective clinical trial, a total of 304 consecutive women with sonographically suspected endometrial hyperplasia and/or postmenopausal bleeding, underwent D&C with intraoperative frozen section analysis between May 2013 and September 2015. Based on the results of the hysteroscopy and/or frozen section, the OSCAR-Endo score was reported: negative, when no frozen section was regarded necessary or the frozen section yielded a negative result; equivocal, when the frozen section reported an equivocal result; positive, when frozen section reported either complex hyperplasia with atypia or cancer. RESULTS: Frozen sections were required by the surgeons in 59 (19.4%) of cases. When compared with the final histology after D&C, frozen section showed a sensitivity, specificity, PPV, NPV, and overall test accuracy of 91.3, 100, 100, 94.1, and 96.3% for predicting malignant disease, respectively. The OSCAR-Endo score showed a sensitivity, specificity, PPV, NPV, and overall test accuracy of 84, 100, 100, 98.6, and 98.7% for predicting malignant disease, respectively. CONCLUSION: The OSCAR-Endo protocol is easy to perform in daily clinical practice reaching an excellent test accuracy. It helps in immediate postoperative counseling of affected patients. Clinical Trial Registration http://www.clinicaltrials.gov ; NCT01961102.

Neuroprotective oleanane triterpenes from the roots of Bupleurum chinense.

The discovery of new natural compounds with pharmacological properties is an increasingly important field, and a continuous phytochemical investigation of the roots of Bupleurum chinense D.C. has led to the isolation of 17 triterpenoids, including three new oleanane triterpenes (1-3) together with 14 known ones. Their structures were determined on the basis of 1D and 2D NMR spectra as well as HR-ESI-MS data. The cytotoxicities of all compounds against five selected human cancer cell lines were assayed. Only compounds 9 and 14 exhibited moderate activities. Recently, a number of investigations have focused on the neuroprotective properties of triterpenoids in B. chinense. In order to expand our knowledge about this herb, the neuroprotective effects of compounds 1-17 against hydrogen peroxide (H2O2)-induced neuronal cell damage in human neuroblastoma SH-SY5Y cells were evaluated. Compounds 1-3, 6-7 showed significant neuroprotective effects against H2O2-induced SH-SY5Y cell death. Preliminary structure-activity relationships (SARs) between neuroprotective effects and the isolates were also discussed.