Reducing day 3 baseline monitoring bloodwork and ultrasound for patients undergoing timed intercourse and intrauterine insemination treatment cycles.

BACKGROUND: In the current context of a global pandemic it is imperative for fertility clinics to consider the necessity of individual tests and eliminate those that have limited utility and may impose unnecessary risk of exposure. The purpose of this study was to implement and evaluate a multi-modal quality improvement (QI) strategy to promote resource stewardship by reducing routine day 3 (d3) bloodwork and transvaginal ultrasound (TVUS) for patients undergoing intrauterine insemination (IUI) and timed intercourse (IC) treatment cycles. METHODS: After literature review, clinic stakeholders at an academic fertility centre met to discuss d3 testing utility and factors contributing to d3 bloodwork/TVUS in IC/IUI treatment cycles. Consensus was reached that it was unnecessary in patients taking oral/no medications. The primary intervention changed the default setting on the electronic order set to exclude d3 testing for IC/IUI cycles with oral/no medications. Exceptions required active test selection. Protocols were updated and education sessions were held. The main outcome measure was the proportion of cycles receiving d3 bloodwork/TVUS during the 8-week post-intervention period compared with the 8-week pre-intervention period. Balancing measures included provider satisfaction, pregnancy rates, and incidence of cycle cancellation. RESULTS: A significant reduction in the proportion of cycles receiving d3 TVUS (57.2% vs 20.8%, p < 0.001) and ≥ 1 blood test (58.6% vs 22.8%, p < 0.001) was observed post-intervention. There was no significant difference in cycle cancellation or pregnancy rates pre- and post-intervention (p = 0.86). Treatment with medications, cyst history, prescribing physician, and treatment centre were associated with receiving d3 bloodwork/TVUS. 74% of providers were satisfied with the intervention. CONCLUSION: A significant reduction in IC/IUI treatment cycles that received d3 bloodwork/TVUS was achieved without measured negative treatment impacts. During a pandemic, eliminating routine d3 bloodwork/TVUS represents a safe way to reduce monitoring appointments and exposure.

Salvianolic acid B inhibits Abeta fibril formation and disaggregates preformed fibrils and protects against Abeta-induced cytotoxicty.

One of the major pathological features of Alzheimer's disease (AD) is the appearance of senile plaques characterized by extracellular aggregation of amyloid beta-peptide (Abeta) fibrils. Inhibition of Abeta fibril aggregation is therefore viewed as one possible method to halt the progression of AD. Salvianolic acid B (Sal B) is an active ingredient isolated from Salvia miltiorrhiza, a Chinese herbal medicine commonly used for the treatment of cardiovascular and cerebrovascular disorders. Recent findings show that Sal B prevents Abeta-induced cytotoxicity in a rat neural cell line. To understand the mechanism of Sal B-mediated neuroprotection, its effects on the inhibition of Abeta1-40 fibril formation and destabilization of the preformed Abeta1-40 fibrils were studied. The results were obtained using Thioflavin T fluorescence assay and Abeta aggregating immunoassay. We found that Sal B can inhibit fibril aggregation (IC(50): 1.54-5.37 microM) as well as destabilize preformed Abeta fibril (IC(50): 5.00-5.19 microM) in a dose- and time-dependent manner. Sal B is a better aggregation inhibitor than ferulic acid but less active than curcumin in the inhibition of Abeta1-40 aggregation. In electron microscope study, Sal B-treated Abeta1-40 fibrils are seen in various stages of shortening or wrinkling with numerous deformed aggregates of amorphous structure. Circular dichroism data indicate that Sal B dose dependently prevents the formation of beta-structured aggregates of Abeta1-40. Addition of preincubated Sal B with Abeta1-42 significantly reduces its cytotoxic effects on human neuroblastoma SH-SY5Y cells. These results suggest that Sal B has therapeutic potential in the treatment of AD, and warrant its study in animal models.

Hospitals' internal accountability.

This study aimed to enhance understanding of the dimensions of accountability captured and not captured in acute care hospitals in Ontario, Canada. Based on an Ontario-wide survey and follow-up interviews with three acute care hospitals in the Greater Toronto Area, we found that the two dominant dimensions of hospital accountability being reported are financial and quality performance. These two dimensions drove both internal and external reporting. Hospitals' internal reports typically included performance measures that were required or mandated in external reports. Although respondents saw reporting as a valuable mechanism for hospitals and the health system to monitor and track progress against desired outcomes, multiple challenges with current reporting requirements were communicated, including the following: 58% of survey respondents indicated that performance-reporting resources were insufficient; manual data capture and performance reporting were prevalent, with the majority of hospitals lacking sophisticated tools or technology to effectively capture, analyze and report performance data; hospitals tended to focus on those processes and outcomes with high measurability; and 53% of respondents indicated that valuable cross-system accountability, performance measures or both were not captured by current reporting requirements.

In vitro screening on amyloid precursor protein modulation of plants used in Ayurvedic and traditional Chinese medicine for memory improvement.

ETHNOPHARMACOLOGICAL RELEVANCE: The 15 herbs for the screening have been traditionally used in Ayurvedic medicine or in Traditional Chinese medicine (TCM) for the treatment of cognitive disorders clinically. AIM OF THE STUDY: Fifteen plant species were investigated for the inhibition of amyloid peptide (Aß) production and modulation of amyloid precursor protein (APP) processing. MATERIALS AND METHODS: The selected plants were extracted successively with 70% ethyl alcohol and absolute alcohol concentrated with rotary evaporation then lyophilized. Using a mouse neuroblastoma cells expressing Swedish APP (N2a-SweAPP), MTT assay was performed to determine the toxicity concentration of each herbal extract. In order to evaluate the activity of ethanol extracts on Aß inhibition, the N2a-SweAPP cells were treated with a high and low dosage of different extracts for 24h, Aßs levels in the supernatant of conditioned media were assessed by ELISA. The most active extracts were then subjected to test the effect on APP modulation in N2a-SweAPP cells by determining their effect on sAPPα and sAPPß through western blot analysis. RESULTS: Among the screened herbal extracts, only Polygonum multiflorum Thunb. (root) and Convolvulus pluricaulis Choisy. (leaves) showed profound inhibition of Aß production. MTT assay demonstrated that the anti-Aß effect of these extracts was not a sequential consequence of their cytotoxicity. The extract of Polygonum multiflorum Thunb. (root) could reduce Aß production only through APP modulation, which was exhibited together with the up-regulation of sAPPα and down-regulation of sAPPß. CONCLUSION: The results show that extract of Polygonum multiflorum Thunb. (root) can lower Aß generation by modulating APP processing in the N2a-SwedAPP cell line. These results corroborate the traditional use of Polygonum multiflorum Thunb. (root) for the treatment of cognitive disorders including Alzheimer's disease (AD).

Stimulation of non-amyloidogenic processing of amyloid-ß protein precursor by cryptotanshinone involves activation and translocation of ADAM10 and PKC-α.

Cerebral deposition of amyloid-ß peptide (Aß) plaques is now considered the central feature of Alzheimer's disease. Recent studies suggest that cryptotanshinone (CTS) extracted from the root of Salvia miltiorrhiza Bunge could be used for the prevention and treatment of Alzheimer's disease. In this study, we investigated the role of CTS on non-amyloidogenic processing of amyloid-ß protein precursor (AßPP) as well as its regulation by protein kinase C (PKC). Treatment with CTS dose-dependently and significantly reduced both intracellular and secreted levels of Aß40 and Aß42 in N2a mouse neuroblastoma cells stably expressing human SwedishAßPP (N2a-SwedAßPP). Using N2a-SwedAßPP and human neuroblastoma SHSY5Y cells, it was demonstrated that CTS significantly and dose-dependently increased the production of sAßPPα and C-terminal fragment-α (CTF-α) from AßPP. At the same time, CTS specifically increased the maturation of "a disintegrin and metalloproteinase-10" (ADAM10), an α-secretase candidate. The increase of sAßPPα secretion by CTS was blocked by the hydroxamate-based inhibitors GI254023X and GW280264X, and by the PKC-α inhibitor GÖ6976, suggesting involvement of the ADAM10 and PKC-α in CTS-induced α-secretase cleavage. In other experiments, CTS induced the phosphorylation of PKC-α indicating that PKC-α is involved in CTS-induced sAßPPα secretion. Furthermore, treatment of neuroblastoma cells with CTS induced the co-translocation of ADAM10 and PKC-α to the cell membrane, the site at which AßPP was cleaved, and this translocation was significantly reduced by GÖ6976. These results suggest that CTS-induced sAßPPα secretion is regulated by a PKC-α and ADAM10 cascade in neuroblastoma cells and may be involved in the lowering of Aß production.

The effects of Boehmeria nivea (L.) Gaud. on embryonic development: in vivo and in vitro studies.

AIM OF THE STUDY: Boehmeria nivea (L.) Gaud. was commonly used to treat miscarriages clinically. The aim of this study was to examine its safety for embryonic development. MATERIALS AND METHODS: Pregnant mice were randomly assigned into 5 groups, i.e. mice were oral-treated with distilled water (G1), with Boehmeria nivea extract of 2, 8 or 32 g/kg/day (G2, G3 or G4), and with 3 doses of vitamin A of 200,000 IU/kg as positive controls (G5). Meanwhile, IC(50) values for both embryonic stem cells (ESCs) and 3T3 cells were detected by cytotoxicity assays. RESULTS: (1) The resorptions and malformed fetuses in G5 were significantly higher than G1 (P<0.001), whereas the maternal body-weight and uterus-weight were lower than G1 (P<0.05); (2) there was no difference in the fetal body-weight, maternal relative body-weight gain, liver-, kidney- or heart-weight, relative organ-weight, and histological examination among five groups; (3) there was no difference in IC(50) values between ESCs and 3T3 cells, but high concentration of Boehmeria nivea extract might significantly lower ESCs' viability (P<0.05). CONCLUSION: Boehmeria nivea extract at 32 g/kg/day did not cause significant embryotoxicity or maternal toxicity in mice, although it might cause cytotoxicity in cultured ESCs at a high dose.

The effect of salvianolic acid B combined with laminar shear stress on TNF-alpha-stimulated adhesion molecule expression in human aortic endothelial cells.

The study was conducted to investigate the effect of Salvianolic acid B (Sal B) on TNF-alpha-stimulated adhesion molecule expression i.e. vascular adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin in human aortic endothelial cells (HAECs) under laminar shear stress (LSS) condition. Exposure of HAECs to LSS (12 dynes/cm(2) for 6 h decreased the TNF-alpha-induced protein expression of adhesion molecules i.e. VCAM-1, ICAM-1 and E-selectin. Pre-treatment of HAECs with Sal B (10 microg/ml) then exposed to LSS (12 dynes/cm(2)) for 6 h significantly inhibited VCAM-1, ICAM-1 and E-selectin expression stimulated by TNF-alpha. Moreover, combined Sal B and LSS treatment inhibited the adhesiveness of monocytic U937 cells to TNF-alpha-stimulated HAECs. We further examined the molecular mechanisms and found that the combination of Sal B and LSS treatment dramatically inhibited TNF-alpha-induced NF-kappaB activation evidenced by IkappaBalpha degradation and p65 nuclear translocation in HAECs. This study provides the first biomechanopharmacological evidence that Sal B has a combination effect with LSS to reduce the expression of three adhesion molecules, leading to reduced monocyte adhesion to HAECs, at least in part, by inhibiting the NF-kappaB signaling pathway. Data from this study thus support the potential clinical application of Sal B in vascular inflammatory diseases.

Neuroprotective effects of Astragaloside IV in 6-hydroxydopamine-treated primary nigral cell culture.

Parkinson's disease (PD) is caused by a progressive degeneration of dopaminergic neurons in the substantia nigra. Oxidative stress and neural degeneration are suggested to be involved in the pathogenesis of Parkinson's disease. In the present study, Astragaloside IV (AS-IV) extracted from the dried root of Astragalus membranaceus, a well-known Chinese medicine used for the treatment of neurodegenerative diseases, was investigated for its capacity to protect dopaminergic neurons in experimental Parkinson's disease. By examining the effect of AS-IV on 6-hydroxydopamine (6-OHDA)-induced loss of dopaminergic neurons in primary nigral culture, we found that AS-IV pretreatment significantly and dose-dependently attenuated 6-OHDA-induced loss of dopaminergic neurons. Neuronal fiber length studies showed that massive neuronal cell death with degenerated neurons was observed in those cultures incubated with 6-OHDA, whereas in AS-IV co-treatments most dopaminergic neurons were seen to be intact and sprouting. In flow cytometric analysis, AS-IV resulted in a marked and dose-dependent rescue in tyrosine hydrolase (TH)-immunopositive cells from 6-OHDA-induced degeneration of dopaminergic neurons. Double immunofluorescence revealed that AS-IV treatment alone at concentrations of 100 and 200 microM increased the level of TH and NOS (nitrite oxide synthase) immunoreactivities; however, the protective effect of AS-IV on TH and NOS immunopositive cells in 6-OHDA treated nigral cell cultures was only seen at a concentration of 100 microM. These findings show that AS-IV can protect dopaminergic neurons against 6-OHDA-induced degeneration. Besides the neuroprotective effect, AS-IV alone promoted neurite outgrowth and increased TH and NOS immunoreactive of dopaminergic neurons. The neuroprotective and neurosprouting effects of AS-IV are specific for dopaminergic neurons and it has therapeutic potential in the treatment of PD.