Enhanced Efficiency and Stability of Sky Blue Perovskite Light-Emitting Diodes via Introducing Lead Acetate.

All-inorganic metal halide perovskite is promising for highly efficient and thermally stable perovskite light-emitting diodes (PeLEDs). However, there is still great room for improvement in the film quality, including low coverage and high trap density, which play a vital role in achieving high-efficiency PeLEDs. In this work, lead acetate (Pb(Ac)2) was introduced into the perovskite precursor solution as an additive. Experimental results show that perovskite films deposited from a one-step anti-solvent free solution process with increased surface coverage and reduced trap density were obtained, leading to enhanced photoluminescence (PL) intensity. More than that, the valence band maximum (VBM) of perovskite films was reduced, bringing about a better energy level matching the work function of the hole-injection layer (HIL) poly (3,4-ethylenedioxythiophene)-poly (styrene sulfonate) (PEDOT: PSS), which is facilitated for the hole injection, leading to a decrease in the turn-on voltage (Vth) of PeLEDs from 3.4 V for the control device to 2.6 V. Finally, the external quantum efficiency (EQE) of the sky blue PeLEDs (at 484 nm) increased from 0.09% to 0.66%. The principles of Pb(Ac)2 were thoroughly investigated by using X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR). This work provides a simple and effective strategy for improving the morphology of perovskite and therefore the performance of PeLEDs.

The length of the sanitary napkins can be used as a handier index than pictorial blood loss assessment chart to predict the heavy menstrual bleeding.

AIM: Many women with inherited bleeding disorders are not diagnosed because of a lack of appropriate indicators. This study aimed to assess the predictability of the pictorial blood loss assessment chart (PBAC) as an indicator of menorrhagia and identify an easy indicator of menorrhagia resulting from bleeding disorders. METHODS: A multicenter study enrolled 9 patients with von Willebrand disease (VWD), 23 hemophilia carriers, and 71 controls aged 20-45 years who completed PBACs for two menstrual cycles as well as questionnaires. RESULTS: The PBAC scores of the VWD were significantly higher than those of other groups, even in multivariate analysis with age and sanitary item factors (p = 0.014). A PBAC score of 100 was not an appropriate cutoff because of its low specificity (VWD: sensitivity, 100; specificity, 29.5; hemophilia carriers: 74 and 29.5, respectively). In the ROC analysis, the cutoff of optimal PBAC for VWD was 171 (sensitivity, 66.7; specificity, 72.3; AUC, 0.7296). As the pad length increased, the total length of the pads used during one menstrual period could be a new and easy indicator. However, the cutoff for VWD was 735 cm (sensitivity, 42.9; specificity, 94.3; AUC 0.6837). A threshold could not be established for the hemophilia carrier. Therefore, we multiplied the coefficient by the length of thick pads, which caused a lower PBAC. For the VWD, the sensitivity increased to 85.7 (specificity, 77.1). For the hemophilia carrier, sensitivity (66.7) and specificity (88.6) could be separated from the control. CONCLUSIONS: The total length of the pads with a thick-pad adjustment can be a simple method to identify bleeding disorders.

Evaluation of pharmacological interventions in the management of adenomyosis: a systematic review.

PURPOSE: Medical management of adenomyosis largely revolves around symptom management, with very few drugs having received regulatory approval for the disease. However, the level of evidence supporting the use of pharmacological interventions is low, making it difficult to establish their efficacy in the treatment of adenomyosis. Hence, the aim of our systematic review is to identify the strength of evidence currently available and evaluate the effectiveness of different medical interventions in the management of adenomyosis. METHODS: The search was performed in MEDLINE, Embase, Cochrane Library, CENTRAL and ClinicalTrials.gov. Articles published between 1 January 2010 and 30 November 2020 were considered. Randomized controlled trials and observational studies that assessed the efficacy of medical interventions in patients with adenomyosis were included. The quality of the data was analyzed using RevMan 5.3 software. RESULTS: LNG-IUS (levonorgestrel intrauterine system), dienogest and gonadotropin-releasing hormone (GnRH) analogues were effective in reducing pain, uterine volume and menstrual bleeding. However, these data were largely obtained in the non-trial setting and were fraught with issues that included patient selection, short duration of therapy, small sample size, and limited long-term safety and effectiveness data. CONCLUSIONS: Although LNG-IUS, dienogest and GnRH analogues have better evidence for effectiveness in adenomyosis, the need of the hour is to thoroughly evaluate other novel molecules for adenomyosis using well-designed randomized controlled trials.

Oxidative and salt stresses alter the 26S proteasome holoenzyme and associated protein profiles in Arabidopsis thaliana.

BACKGROUND: The 26S proteasome, canonically composed of multi-subunit 19S regulatory (RP) and 20S core (CP) particles, is crucial for cellular proteostasis. Proteasomes are re-modeled, activated, or re-localized and this regulation is critical for plants in response to environmental stresses. The proteasome holoenzyme assembly and dissociation are therefore highly dynamic in vivo. However, the stoichiometric changes of the plant proteasomes and how proteasome associated chaperones vary under common abiotic stresses have not been systematically studied. RESULTS: Here, we studied the impact of abiotic stresses on proteasome structure, activity, and interacting partners in Arabidopsis thaliana. We analyzed available RNA expression data and observed that expressions of proteasome coding genes varied substantially under stresses; however, the protein levels of a few key subunits did not change significantly within 24 h. Instead, a switch in the predominant proteasome complex, from 26S to 20S, occurs under oxidative or salt stress. Oxidative stress also reduced the cellular ATP content and the association of HSP70-family proteins to the 20S proteasome, but enhanced the activity of cellular free form CP. Salt stress, on the other hand, did not affect cellular ATP level, but caused subtle changes in proteasome subunit composition and impacted bindings of assembly chaperones. Analyses of an array of T-DNA insertional mutant lines highlighted important roles for several putative assembly chaperones in seedling establishment and stress sensitivity. We also observed that knockout of PBAC1, one of the α-ring assembly chaperones, resulted in reduced germination and tearing of the seed coat following sterilization. CONCLUSIONS: Our study revealed an evolutionarily conserved mechanism of proteasome regulation during oxidative stress, involving dynamic regulation of the holoenzyme formation and associated regulatory proteins, and we also identified a novel role of the PBAC1 proteasome assembly chaperone in seed coat development.

Mercury Chloride but Not Lead Acetate Causes Apoptotic Cell Death in Human Lung Fibroblast MRC5 Cells via Regulation of Cell Cycle Progression.

Heavy metals are important for various biological systems, but, in excess, they pose a serious risk to human health. Heavy metals are commonly used in consumer and industrial products. Despite the increasing evidence on the adverse effects of heavy metals, the detailed mechanisms underlying their action on lung cancer progression are still poorly understood. In the present study, we investigated whether heavy metals (mercury chloride and lead acetate) affect cell viability, cell cycle, and apoptotic cell death in human lung fibroblast MRC5 cells. The results showed that mercury chloride arrested the sub-G1 and G2/M phases by inducing cyclin B1 expression. In addition, the exposure to mercury chloride increased apoptosis through the activation of caspase-3. However, lead had no cytotoxic effects on human lung fibroblast MRC5 cells at low concentration. These findings demonstrated that mercury chloride affects the cytotoxicity of MRC5 cells by increasing cell cycle progression and apoptotic cell death.

Radiofrequency endometrial ablation with a novel endometrial tip for the management of heavy menstrual bleeding and abnormal uterine bleeding: a prospective study.

Aim: To evaluate the safety and efficacy of a radiofrequency ablation system with a novel endometrial tip (RFA-EMT) for the management of heavy menstrual bleeding (HMB) or abnormal uterine bleeding (AUB).Methods: This is a prospective study including a total of 38 premenopausal women with heavy menstrual bleeding (HMB) or abnormal uterine bleeding (AUB) that failed to respond to medical therapy. Hysteroscopic evaluation and curettage biopsy were performed just before the procedure. The procedure was timed to occur during the early proliferative phase (cycle days 4-10). RFA-EMT procedures were performed by a single surgeon with the patient under general anesthesia with a laryngeal mask airway. Primary outcome was reduction in bleeding, reported as amenorrhea, hypomenorrhea, and eumenorrhea, which were measured via hemoglobin level and pictorial blood assessment chart (PBAC) score. Secondary outcomes were adverse events, dysmenorrhea with numeric rating scale (NRS) score, and endometrial thickening in the early proliferative phase, as assessed by transvaginal ultrasonography.Results: There were no peri- or post-procedural complications. Combined amenorrhea, hypomenorrhea, and eumenorrhea rates at 3 and 6 months were 97.4% and 100%, respectively. The hemoglobin level was significantly increased, and the PBAC score, NRS score, and endometrial thickening were significantly decreased after 3 months. These trends were maintained for 6 months after the procedure.Conclusion: RFA-EMT, a new technique, is safe and effective for women with HMB or AUB for which medical therapy has failed.

Comparing the ICERs in Medicine Reimbursement Submissions to NICE and PBAC-Does the Presence of an Explicit Threshold Affect the ICER Proposed?

OBJECTIVES: The English National Institute for Health and Care Excellence (NICE) and the Australian Pharmaceutical Benefits Advisory Committee (PBAC) require evidence that a new medicine represents value for money before being publicly funded. NICE has an explicit threshold for cost effectiveness, whereas PBAC does not. We compared the initial incremental cost-effectiveness ratios (ICERs) presented by manufacturers in matched submissions to each decision-making body, with the aim of exploring the impact of an explicit threshold on these ICERs. METHODS: Data were extracted from matched submissions from 2005 to 2015. The ICERs in these submissions were compared within each pair and with respect to a cost-effectiveness threshold. RESULTS: Fifty-eight pairs of matched submissions were identified. The median difference between the ICERs ($2635/quality-adjusted life year [QALY]) was significantly greater than zero (Wilcoxon signed-rank test, P = 0.0299), indicating that the proposed ICERs in the submissions to NICE were higher than those in the matched submissions to PBAC. On 93% of occasions, NICE ICERs were within -$17,772 to +$48,422 of the corresponding PBAC ones (Bland-Altman analysis), demonstrating poor agreement. When an implicit threshold of AUD$50,000/QALY was assumed for PBAC decision making, only eight pairs of submissions had discordant ICERs falling above or below the respective threshold. CONCLUSIONS: The significantly higher ICERs in the submissions to NICE than those to PBAC may be a consequence of NICE's explicit willingness-to-pay threshold, and/or other health system factors. Industry may be assuming an implicit threshold for PBAC when constructing their ICERs despite the lack of acknowledgement of such a threshold.

A systematic review of methods to measure menstrual blood loss.

BACKGROUND: Since the publication over 50 years ago of the alkaline hematin method for quantifying menstrual blood loss (MBL) many new approaches have been developed to assess MBL. The aim of this systematic review is to determine for methods of measuring MBL: ability to distinguish between normal and heavy menstrual bleeding (HMB); practicalities and limitations in the research setting; and suitability for diagnosing HMB in routine clinical practice. METHODS: Embase®™, MEDLINE®, and ClinicalTrials.gov were screened for studies on the development/validation of MBL assessment methods in women with self-perceived HMB, actual HMB or uterine fibroids, or patients undergoing treatment for HMB. Studies using simulated menstrual fluid and those that included women with normal MBL as controls were also eligible for inclusion. Extracted data included study population, results of validation, and advantages/disadvantages of the technique. RESULTS: Seventy-one studies fulfilled the inclusion criteria. The sensitivity and/or specificity of diagnosing HMB were calculated in 16 studies of methods involving self-perception of MBL (11 pictorial), and in one analysis of the menstrual-fluid-loss (MFL) method; in 13 of these studies the comparator was the gold standard alkaline hematin technique. Sensitivity and specificity values by method were, respectively: MFL model, 89, 98%; pictorial blood loss assessment chart (PBAC), 58-99%, 7.5-89%; menstrual pictogram, 82-96%, 88-94%; models/questionnaires, 59-87%, 62-86%, and complaint of HMB, 74, 74%. The power of methods to identify HMB was also assessed using other analyses such as comparison of average measurements: statistical significance was reported for the PBAC, MFL, subjective complaint, and six questionnaires. In addition, PBAC scores, menstrual pictogram volumes, MFL, pad/tampon count, iron loss, and output from three questionnaires correlated significantly with values from a reference method in at least one study. In general, pictorial methods have been more comprehensively validated than questionnaires and models. CONCLUSIONS: Every method to assess MBL has limitations. Pictorial methods strike a good balance between ease of use and validated accuracy of MBL determination, and could complement assessment of HMB using quality of life (QoL) in the clinical and research setting. TRIAL REGISTRATION: PRISMA registration number: CRD42016032956 .

Hemin provides protection against lead neurotoxicity through heme oxygenase 1/carbon monoxide activation.

The neurotoxicity of lead (Pb) is well established, and oxidative stress is strongly associated with Pb-induced neurotoxicity. Heme oxygenase 1 (HO-1) is an important antioxidative enzyme for protection against oxidative stress in many disease models. In this study, we applied hemin, the substrate and a well-known inducer of HO-1, to investigate the possible role of HO-1 in protecting against Pb neurotoxicity. Hemin can significantly attenuate Pb acetate-induced cell death and oxidative stress in the hippocampus and frontal cortex of developmental rats. Consistent with in vivo results, the protective effects of hemin were also observed in SH-SY5Y cells after inducing cell survival and maintaining redox balance. However, knocking down HO-1 could significantly abolish the cytoprotective action of hemin against Pb toxicity, confirming HO-1 contributed to the protection. Finally, the HO-1-derived production of carbon monoxide, but not of bilirubin or Fe2+ , mediated the protective effects of HO-1 activation induced by hemin treatment against Pb-induced cell death and oxidative stress in SHSY5Y cells. Overall, this study showed that hemin provided protection against Pb neurotoxicity by HO-1/carbon monoxide activation.

Sparse canonical correlation analysis relates network-level atrophy to multivariate cognitive measures in a neurodegenerative population.

This study establishes that sparse canonical correlation analysis (SCCAN) identifies generalizable, structural MRI-derived cortical networks that relate to five distinct categories of cognition. We obtain multivariate psychometrics from the domain-specific sub-scales of the Philadelphia Brief Assessment of Cognition (PBAC). By using a training and separate testing stage, we find that PBAC-defined cognitive domains of language, visuospatial functioning, episodic memory, executive control, and social functioning correlate with unique and distributed areas of gray matter (GM). In contrast, a parallel univariate framework fails to identify, from the training data, regions that are also significant in the left-out test dataset. The cohort includes164 patients with Alzheimer's disease, behavioral-variant frontotemporal dementia, semantic variant primary progressive aphasia, non-fluent/agrammatic primary progressive aphasia, or corticobasal syndrome. The analysis is implemented with open-source software for which we provide examples in the text. In conclusion, we show that multivariate techniques identify biologically-plausible brain regions supporting specific cognitive domains. The findings are identified in training data and confirmed in test data.

An approach to outreach patients with von Willebrand disease in Egypt by targeting women with heavy menstrual bleeding and/or bleeding symptoms.

von Willebrand disease (VWD) is frequently ignored as a cause of menorrhagia. We investigated Egyptian women complaining of heavy menstrual bleeding (HMB) and/or other bleeding symptoms to detect potential VWD cases. Seventy-five female patients complaining of HMB and/or bleeding symptoms and 38 age-matched healthy female controls went through a family history questionnaire, a physical examination and were evaluated for bleeding score, pictorial blood assessment chart (PBAC), complete blood count, serum ferritin, blood group, prothrombin time, activated partial thromboplastin time, factor VIII (FVIII) activity, von Willebrand factor (VWF) ristocetin cofactor (RCo) activity, antigen (Ag), and RCo/Ag ratio. Sixty-eight of 75 patients presented with HMB, out of which 46 had no organic pathology and 7 presented other bleeding symptoms. Six patients were diagnosed with VWD, three with HMB, two with other bleeding symptoms and one with family history of VWD. Two related VWD patients were diagnosed in the control group. There were significant differences in bleeding and PBAC scores, ferritin level, FVIII activity, VWF:RCo and VWF:Ag between VWD patients and controls. This study indicated a high prevalence of VWD among patients with HMB without organic pathology (6.5%) and demonstrated the sensitivity of diagnostic parameters of VWD patients in an outreach campaign. The inexpensive bleeding and PBAC scoring systems are valuable to exclude cases without objective bleeding symptoms. Raising gynaecologists awareness about hereditary bleeding disorders is important to ensure a proper diagnosis and possible referral of these patients. Management of these patients with comprehensive medical care services under a multidisciplinary team would be ideal.

A quick method to customize pictorial blood assessment tools towards better measurement: Method development and validation.

OBJECTIVE: Identification of heavy menstrual bleeding (HMB) cases in primary care settings is often done by using pictorial blood assessment charts (PBAC). The study aims to highlight the challenge of assessing blood loss, to develop a standardized method to efficiently customize a patient-reported pictorial chart, to validate the tool produced with our proposed method, and to demonstrate the feasibility of using PBACs in settings where resources are scarce. MATERIALS AND METHODS: Using blood samples and feedback from 21 women aged 30-51 years, we followed guidelines suggested in the literature, developed a method to produce PBACs for regular, long and night sizes, and had 9 participants testuse them. Linear regression analysis was performed to determine the correlation between participants' scores and menstrual blood weight. RESULTS: The study demonstrated the feasibility of customizing product-sensitive and size-specific pictorial charts by adopting essential steps including collecting menstrual blood with menstrual cups, employing fluid application techniques, and using sanitary pads as icons for easy identification. Linear regression analyses of score versus blood weight showed that the recorded blood weight was around 95% of the scored values (R2 = 0.9428, 0.947, and 0.9508, respectively; p < 0.001). CONCLUSION: Valid patient-reported PBACs created by the proposed method provides an innovative women's healthcare solution to assist HMB identification and reduce health expenditure by preventing risks for HMB related complications in varying economic and technological contexts. Women's participation in tracking menstrual abnormalities may improve health literacy.

Making recommendations to subsidize new health technologies in Australia: A qualitative study of decision-makers' perspectives on committee processes.

OBJECTIVES: To explore experiences of, and perspectives on, health technology assessment (HTA) processes used to produce recommendations about subsidizing new medicines, and medical technologies in Australia, from the perspectives of those experienced in these processes. METHODS: Semi-structured interviews with a diverse group of 18 informants currently or previously members of the Pharmaceutical Benefits Advisory Committee (PBAC) or the Medical Services Advisory Committee (MSAC). Participants were interviewed September 2021-February 2022. Transcripts were analyzed using reflexive thematic analysis. RESULTS: 3 major themes were identified: contrasting technical and decision-making stages, resisting reductionist approaches, and navigating decision-making trade-offs. Participants discussed the complexities of the evaluative HTA process, especially when considering uncertainty in the evidence. As part of the current process, a deliberative decision-making stage was considered essential, allowing a flexible approach to decision making to consider factors beyond strength and quality of quantifiable data in the technical evaluation. Participants acknowledged these less-quantifiable factors were sometimes considered implicitly or were difficult to describe and this, paired with commercial in confidence requirements, presented challenges with respect to the desire to increase transparency. CONCLUSION (S): As HTA processes for new medicines and medical technologies in Australia continue to be reviewed, the balance between retaining flexibility during deliberation, confidentiality for sponsors and the public's desire for greater transparency may be a fruitful area for continuing research.

The critical adenosine triphosphate (ATP) concentration in treated ballast water.

Measuring Adenosine triphosphate (ATP) provides a proxy to check compliance with IMO's ballast water D-2 standard: <10 cells mL-1 in the 10-50 µm size class. Measured with standard boiling techniques the ATP concentration in aquatic eukaryotic microorganisms is 0.6 mol m-3. Model calculations with 10-50 µm spherical organisms show their ATP content is 0.2 to 20 pg cell-1, in line with several cell lysis data. However, at 10 cells mL-1, these ATP contents lead to a maximum of only 2 to 200 pg ATP mL-1, at least 7.5× below a D-2 test kit 1500 pg ATP mL-1 upper limit. Different cell shape and ATP extraction scenarios to reach 1500 pg ATP mL-1 are discussed but remain improbable. Because cell lysis data are inconclusive, and a novel phosphoric acid-benzalkonium chloride method indicates up to 3× higher ATP concentrations, an independent test kit validation and a comparison of all three techniques are recommended.

Appraisals by Health Technology Assessment Agencies of Economic Evaluations Submitted as Part of Reimbursement Dossiers for Oncology Treatments: Evidence from Canada, the UK, and Australia.

Publicly funded healthcare systems, including those in Canada, the United Kingdom (UK), and Australia, often use health technology assessment (HTA) to inform drug reimbursement decision-making, based on dossiers submitted by manufacturers, and HTA agencies issue publicly available reports to support funding recommendations. However, the level of information reported by HTA agencies in these reports may vary. To provide insights on this issue, we describe and assess the reporting of economic methods in recent oncology HTA recommendations from the Canadian Agency for Drugs and Technologies in Health (CADTH), National Institute for Health and Care Excellence (NICE), and Pharmaceutical Benefits Advisory Committee (PBAC). Publicly available HTA recommendations and reports for oncology drugs issued by CADTH over a 2-year period, 2019-2020, were identified and compared with the corresponding HTA documents from NICE and the PBAC. Reporting of key model characteristics and attributes, survival analysis methods, methodological criticisms, and re-assessment of the economic results were characterized using descriptive statistics. Dichotomous differences in the methodological criticisms observed between the three agencies were assessed using Cochran's Q tests and substantiated using pairwise McNemar tests. Chi-squared tests were used to assess the dichotomous differences in the reporting of methods and explore the potential relationships between categorical variables, where appropriate. HTAs published by CADTH, NICE, and the PBAC consistently reported a broad spectrum of descriptive information on the economic models submitted by manufacturers. While common economic evaluation attributes were well-reported across the three HTA agencies, significant differences in the reporting of survival analysis methods and methodological criticisms were observed. NICE consistently reported more comprehensive information, compared to either CADTH or PBAC. Despite these differences, broadly similar recommendation rates were observed between CADTH and NICE. The PBAC was found to be more restrictive. Based on our 2-year sample of oncology, the HTAs published by CADTH matched with the corresponding HTAs from NICE and PBAC; we observed important variations in the reporting of economic evidence, especially technical aspects, such as survival analysis, across the three agencies. In addition to guidelines for HTA submissions by manufacturers, the community of HTA agencies should also have common standards for reporting the results of their assessments, though the information and opinions reported may differ.

The effect of transcervical resection of submucous fibroids on menstrual blood loss: A prospective cohort study.

OBJECTIVES: Transcervical resection of myoma (TCRM) is a widely implemented treatment for submucous fibroids. The aim of this study is to evaluate the effect of TCRM on menstrual bleeding, fibroid related symptoms and quality of life and hemoglobin (Hb) levels. STUDY DESIGN: A prospective cohort study was conducted in three teaching hospitals and two academic hospitals in the Netherlands. Patients with HMB (PBAC score > 150) and submucous fibroids (type 0, 1, 2, 3, 4 and hybrid type 2-5) scheduled for TCRM were eligible. At baseline and 3 months after TCRM a Trans Vaginal Ultrasound (TVU) was performed and a Hb sample was taken. Patients filled out the Pictorial Blood Assessment Chart (PBAC) and the Uterine Fibroid Symptom and Quality of Life (UFS-QOL) questionnaire at baseline and up to 6 months after surgery. Primary outcome was improvement in PBAC score 6 months after surgery. Secondary outcomes were improvement in PBAC score and Hb level 3 months after surgery and UFS-QOL scores 3 and 6 months after surgery. RESULTS: 126 patients were included and 104 were operated. PBAC were obtained from 98 patients. Six months after surgery, 56.6% of patients went from HMB to normal menstrual bleeding (PBAC < 150). A significant reduction in median PBAC scores of 427 (IQR 198 - 1392) (p <.0001) was found (86% improvement). UFS-QOL scores were obtained from 91 patients. Symptom severity improved from a median of 54 on a scale of 100 (IQR 44-66) at baseline to 22 (IQR 9-41) after 6 months (p <.0001) (59% improvement). Health related quality of life (HRQOL) improved from a median score of 44 on a scale of 100 (IQR 33-62) to 89 (IQR 67-97) 6 months after surgery (p <.0001) (102% improvement). CONCLUSION: TCRM significantly reduces the amount of menstrual bleeding, severity of fibroid related symptoms and improves HRQOL in patients with submucous fibroids.

Uterine artery embolization or myomectomy for women with uterine fibroids: Four-year follow-up of a randomised controlled trial.

OBJECTIVE: To examine the quality of life experienced by women with symptomatic uterine fibroids who had been treated with UAE in comparison to myomectomy. We report the four-year follow-up of the FEMME randomised trial. Two-year follow-up data has been previously reported. STUDY DESIGN: Premenopausal women who had symptomatic uterine fibroids amenable to myomectomy or uterine artery embolization were recruited from 29 UK hospitals. Women were excluded if they had significant adenomyosis, any malignancy, pelvic inflammatory disease or had had a previous open myomectomy or uterine artery embolization.Participants were randomised to myomectomy or embolization in a 1:1 ratio using a minimisation algorithm. Myomectomy could be open abdominal, laparoscopic or hysteroscopic, according to clinician preference. Embolization of the uterine arteries was performed according to local practice, under fluoroscopic guidance.The primary outcome measure was the Uterine Fibroid Symptom Quality of Life questionnaire, adjusted for baseline score and reported here at four years post-randomisation. Subsequent procedures for fibroids, pregnancy and outcome were amongst secondary outcomes.Trial registration ISRCTN70772394 https://doi.org/10.1186/ISRCTN70772394. RESULTS: 254 women were randomized, 127 to myomectomy (105 underwent myomectomy) and 127 to uterine artery embolization (98 underwent embolization). At four years, 67 (53%) and 81 (64%) completed UFS-QoL quality of life scores. Mean difference in the UFS-QoL at 4 years was 5.0 points (95% CI -1.4 to 11.5; p = 0.13) in favour of myomectomy. There were 15 pregnancies in the UAE group and 7 in the myomectomy group, with a cumulative pregnancy rate to four years of 15% and 6% respectively (hazard ratio: 0.48; 95% CI 0.18-1.28). The cumulative repeat procedure rate to four years was 24% in the UAE group and 13% in the myomectomy group (hazard ratio: 0.53; 95% CI 0.27-1.05). CONCLUSIONS: Myomectomy resulted in greater improvement in quality of life compared with uterine artery embolization, although by four years, this difference was not statistically significant. Missing data may limit the generalisability of this result. The numbers of women becoming pregnant were too small draw a conclusion on the effect of the procedures on fertility.

Health Technology Assessment in Australia: The Pharmaceutical Benefits Advisory Committee and Medical Services Advisory Committee.

Health technology assessment (HTA) was introduced in Australia for the reimbursement of pharmaceuticals in 1992 and in the following years for procedures, diagnostic tests, and devices. The Australian health system is largely funded by the government. The Pharmaceutical Benefits Scheme is a national list of prescription pharmaceuticals for which the patient pays a small copayment. HTA submissions to the Pharmaceutical Benefits Scheme are assessed by the Pharmaceutical Benefits Advisory Committee. The Medical Benefits Scheme provides ambulatory medical services and HTA submissions are assessed by the Medical Services Advisory Committee. This article describes the processes of reimbursement in Australia as well as the special case of codependent technologies (eg, diagnostic test and a therapeutic drug) where a combined Medical Services Advisory Committee and Pharmaceutical Benefits Advisory Committee application is required. There are many future challenges for HTA in Australia, with growing pressure to provide early access to promising treatments and high cost personalized medicines looming on the horizon. However, Australia is well placed to deal with these issues as the early adoption of HTA and coexistence between industry, academia and the payer has proven to be a fertile environment for developing capacity to undertake and evaluate HTA.

PbAc Triggers Oxidation and Apoptosis via the PKA Pathway in NRK-52E Cells.

This study aimed to investigate the mechanism of the lead exposure-induced oxidative stress and apoptosis of renal tubular epithelial cells. We explored the effects of lead acetate (PbAc) on the oxidation and apoptosis of renal proximal tubular cells (NRK-52E) through in vitro experiments. Results showed that PbAc induced dose-dependent reactive oxygen species (ROS) accumulation in NRK-52E cells, and the activities of superoxide dismutase (SOD) and glutathione (GSH) decreased, whereas the malondialdehyde (MDA) content increased. Under the exposure of 40 and 80 µM PbAc, the mRNA level of B cell lymphoma-2 (Bcl-2) in the cells decreased, the mRNA levels of Bcl-2-associated X protein (Bax) and caspase-3 increased, and apoptosis was obvious. Furthermore, the nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4) activity was enhanced by PbAc in a dose-dependent manner. The mRNA levels of protein kinase A (PKA) were upregulated by PbAc. H-89, a PKA inhibitor, suppressed PKA activation, ROS accumulation, and Nox4 activity in NRK-52E cells. Our results indicated that PbAc potentially stimulated oxidative stress and apoptosis in NRK-52E cells by increasing Nox4-dependent ROS production via the PKA signaling pathway.

Microarray-based bioinformatics analysis of the combined effects of SiNPs and PbAc on cardiovascular system in zebrafish.

With rapid development of nanotechnology and growing environmental pollution, the combined toxic effects of SiNPs and pollutants of heavy metals like lead have received global attentions. The aim of this study was to explore the cardiovascular effects of the co-exposure of SiNPs and lead acetate (PbAc) in zebrafish using microarray and bioinformatics analysis. Although there was no other obvious cardiovascular malformation except bleeding phenotype, bradycardia, angiogenesis inhibition and declined cardiac output in zebrafish co-exposed of SiNPs and PbAc at NOAEL level, significant changes were observed in mRNA and microRNA (miRNA) expression patterns. STC-GO analysis indicated that the co-exposure might have more toxic effects on cardiovascular system than that exposure alone. Key differentially expressed genes were discerned out based on the Dynamic-gene-network, including stxbp1a, ndfip2, celf4 and gsk3b. Furthermore, several miRNAs obtained from the miRNA-Gene-Network might play crucial roles in cardiovascular disease, such as dre-miR-93, dre-miR-34a, dre-miR-181c, dre-miR-7145, dre-miR-730, dre-miR-129-5p, dre-miR-19d, dre-miR-218b, dre-miR-221. Besides, the analysis of miRNA-pathway-network indicated that the zebrafish were stimulated by the co-exposure of SiNPs and PbAc, which might cause the disturbance of calcium homeostasis and endoplasmic reticulum stress. As a result, cardiac muscle contraction might be deteriorated. In general, our data provide abundant fundamental research clues to the combined toxicity of environmental pollutants and further in-depth verifications are needed.