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The clinical importance of MDS stem cells has been highlighted through the demonstration of selective persistence of MDS stem cells in patients at complete remission in response to therapy. This implies that MDS stem cells might possess unique resistance mechanisms responsible for relapses following otherwise efficient treatments. Specific surveillance of MDS stem cells should be considered to assess the efficiency of therapies and as an early indicator of emerging relapses in patients in clinical remission. Moreover, further molecular characterization of purified MDS stem cells should facilitate identification and validation of improved and more stem cell-specific therapies for MDS.The interpretation of umbilical cord gases may not be straightforward following shoulder dystocia. We reviewed Perinatal and Maternal Mortality Review Committee data from New Zealand infants with moderate and severe neonatal encephalopathy (NE) for 2010-2017 inclusive. If one or more of pH of ≤7.1; base excess of ≤-12 mmol/L; or lactate of ≥6 mmol/L were present it was considered an abnormal result. One-third (12/36) of infants born following shoulder dystocia had documented umbilical cord gases within the normal range. It is important for clinicians to be aware of this possibility when assessing newborn infants with NE.The present study was designed to develop a self-emulsifying drug delivery system (SEDDS) of (R)-α-lipoic acid (RLA) to improve the physicochemical and nutraceutical properties of RLA. RLA/SEDDS was prepared using medium-chain triglycerides, Tween 80, and polyethylene glycol 400 as oil, surfactant, and co-surfactant, respectively. The preferable composition of SEDDS was selected according to a pseudo-ternary phase diagram for improved emulsification properties, and its physicochemical and pharmacokinetic properties were evaluated. RLA/SEDDS showed the immediate formation of fine micelles with a mean droplet size of approximately 260 nm when introduced into aqueous media. In simulated gastric fluid, this system could significantly improve the dissolution behavior of RLA and prevent the degradation of RLA, possibly due to the encapsulation of RLA into the emulsion structure. Following the oral administration of RLA/SEDDS (10 mg RLA/kg) in rats, systemic exposure to RLA and dihydrolipoic acid (DHLA), a reduced form of RLA, increased by 7- and 3-fold, respectively. The improved dissolution and gastric stability of RLA could contribute to enhancing systemic exposure to RLA and DHLA after oral administration. From these findings, RLA/SEDDS might be an efficacious dosage option for improving the oral bioavailability as well as nutraceutical properties of RLA.Because of the importance of providing the appropriate fluid consistency for effective management of swallowing problems (dysphagia) in infants, this project sought to determine the effect of three commercially available thickening agents on the resulting thickened consistencies of commonly prescribed, ready-to-feed infant formulas. Nine ready-to-feed infant formulas were thickened with three different thickening agents to nectar and honey consistencies following manufacturer's instructions and their resulting thickness was measured via line spread test (LST). The nine formulas with nothing added to them (thin liquids) and the 27 target-nectar and 27 target-honey samples together created 63 unique samples for comparison. A series of one-way analysis of variance analyses were conducted to determine if the resulting thickness (as measured by LST values) for target categories of nectar and honey consistencies was significantly influenced by the type of thickening agent used. The achieved thickness of the formula samples as measured by LST values was statistically significantly different for the three different types of thickening agents used to achieve a target nectar consistency, F (2, 24) = 15.55, p  less then  .001, η p 2 = .709. Additionally, the achieved thickness of the formula samples was statistically significantly different for the three different types of thickening agents used to achieve a target honey consistency, F (2, 24) = 16.18, p  less then  .001, η p 2 = .709. The results of this study reveal that the choice of thickening agent impacts the resulting thickness of ready-to-feed infant formula.Rechargeable magnesium batteries (RMBs) have been considered as a promising energy storage device due to their high energy density and high safety, but they still suffer from the lack of cathode with high-rate performance and cycle performance. Herein, CuCo 2 S 4 /Cu 7.2 S 4 composites with nano-sized were first synthesized by a facile solvothermal method in this work and the magnesium ion storage behaviour was discussed when applied in the cathode for RMBs. Electrochemical results demonstrated that the CuCo 2 S 4 /Cu 7.2 S 4 composites exhibit a high initial discharge capacity of 256 mAh g -1 at 10 mA g -1 and 123 mAh g -1 at 300 mA g -1 at room temperature and an outstanding long-term cyclic stability over 300 cycles at 300 mA g -1 . Furthermore, the electrochemical storage mechanism demonstrated that the storage process of magnesium ion in the CuCo 2 S 4 /Cu 7.2 S 4 cathode is mainly driven by the strong pseudocapacitive effects.Integrating risk assessment, economic evaluation, and uncertainty to inform policy decisions is a core challenge to risk analysis. In September 2019, the Harvard Center for Risk Analysis, with support from the Society for Risk Analysis Economics and Benefits Analysis Specialty Group and others, convened a workshop to address this issue. The workshop built in part on the recommendations of the 2009 National Research Council report, Science and Decisions Advancing Risk Assessment. It honored John S. Evans, whose thoughtful and innovative teaching and scholarship have significantly advanced thinking on these issues. This special issue features a profile of Dr. Evans and nine articles that build on work presented at the workshop.As the most abundant internal modification of mRNA, N6 -methyladenosine (m6 A) methylation of RNA is emerging as a new layer of epitranscriptomic gene regulation in cellular processes, including embryo development, flowering-time control, microspore generation and fruit ripening, in plants. find more However, the cellular role of m6 A in plant responses to environmental stimuli remains largely unexplored. In this study, we show that m6 A methylation plays an important role in salt stress tolerance in Arabidopsis. All mutants of m6 A writer components, including MTA, MTB, VIRILIZER (VIR) and HAKAI, displayed salt-sensitive phenotypes in an m6 A-dependent manner. The vir mutant, in which the level of m6 A was most highly reduced, exhibited salt-hypersensitive phenotypes. Analysis of the m6 A methylome in the vir mutant revealed a transcriptome-wide loss of m6 A modification in the 3' untranslated region (3'-UTR). We demonstrated further that VIR-mediated m6 A methylation modulates reactive oxygen species homeostasis by negatively regulating the mRNA stability of several salt stress negative regulators, including ATAF1, GI and GSTU17, through affecting 3'-UTR lengthening linked to alternative polyadenylation. Our results highlight the important role played by epitranscriptomic mRNA methylation in the salt stress response of Arabidopsis and indicate a strong link between m6 A methylation and 3'-UTR length and mRNA stability during stress adaptation.

People living with HIV who use drugs commonly experience chronic pain and often use illicit opioids to manage pain. Recent research suggests people living with HIV use cannabis for pain relief, including as an adjunct to opioids. This underscores the need to better understand how people living with HIV who use drugs use cannabis for pain management, particularly as cannabis markets are undergoing changes due to cannabis legalisation.

From September 2018 to April 2019, we conducted in-depth interviews with 25 people living with HIV who use drugs in Vancouver, Canada to examine experiences using cannabis to manage pain. Interviews were audio-recorded, transcribed and coded. Themes were identified using inductive and deductive approaches.

Most participants reported that using cannabis for pain management helped improve daily functioning. Some participants turned to cannabis as a supplement or periodic alternative to prescription and illicit drugs (e.g. benzodiazepines, opioids) used to manage pain and related symptoms. Nonetheless, participants' access to legal cannabis was limited and most continued to obtain cannabis from illicit sources, which provided access to cannabis that was free or deemed to be affordable.

Cannabis use may lead to reduced use of prescription and illicit drugs for pain management among some people living with HIV who use drugs. Our findings add to growing calls for additional research on the role of cannabis in pain management and harm reduction, and suggest the need for concrete efforts to ensure equitable access to cannabis.

Cannabis use may lead to reduced use of prescription and illicit drugs for pain management among some people living with HIV who use drugs. Our findings add to growing calls for additional research on the role of cannabis in pain management and harm reduction, and suggest the need for concrete efforts to ensure equitable access to cannabis.A pilot randomized controlled trial (RCT) was conducted in El Salvador of an intervention ('Thula Sana') previously shown to enhance maternal sensitivity and infant security of attachment in a South African sample. In El Salvador, trained community workers delivered the intervention from late pregnancy to 6 months postpartum as part of a home-visiting programme. The sample comprised 64 pregnant adolescent women, aged 14-19 years, living in predominantly rural settings. They were randomised to receive either the intervention or normal care. Demographic information was collected at baseline and, immediately post-intervention, blind assessments were made of parental sensitivity and infant emotion regulation. The intervention was found to have a substantial positive impact on maternal sensitivity. Further, compared to control group, infants in the intervention group showed more regulated behaviour in a social challenge task they showed more attempts to restore communication, and in a non-social challenge task they showed more social and goal-directed behaviour. This replication and extension of the South African findings in a small El Salvador sample shows promise and justifies the conduct of a large-scale RCT in a Central or South American context.The current diagnostic work-up of inborn errors of metabolism (IEM) is rapidly moving toward integrative analytical approaches. We aimed to develop an innovative, targeted urine metabolomics (TUM) screening procedure to accelerate the diagnosis of patients with IEM. Urinary samples, spiked with three stable isotope-labeled internal standards, were analyzed for 258 diagnostic metabolites with an ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) configuration run in positive and negative ESI modes. The software automatically annotated peaks, corrected for peak overloading, and reported peak quality and shifting. Robustness and reproducibility were satisfactory for most metabolites. Z-scores were calculated against four age-group-matched control cohorts. Disease phenotypes were scored based on database metabolite matching. Graphical reports comprised a needle plot, annotating abnormal metabolites, and a heatmap showing the prioritized disease phenotypes. In the clinical validation, we analyzed samples of 289 patients covering 78 OMIM phenotypes from 12 of the 15 society for the study of inborn errors of metabolism (SSIEM) disease groups.