Hydroxyapatite-based cements induce different apatite formation in radicular dentin

Objectives. To investigate crystallinity and ultrastructure of the formed hydroxyapatite at radicular cervical and apical dentin after being treated with three different canal sealers. Methods. Cervical and apical root dentin surfaces were treated with two experimental hydroxyapatite-based sealers, containing sodium hydroxide (calcypatite) or zinc oxide (oxipatite) and an epoxy resin-based canal sealer (AH Plus); gutta-percha without sealer was included as control. Dentin surfaces were studied by X-ray diffraction and transmission electron microscopy through selected area diffraction and bright-field imaging after 24 h and 12 m of storage. Results. Root cervical dentin treated with calcypatite and oxipatite produced poor crystallinity of new minerals, wide amorphous phase and non-stoichiometry. Reflections at the 002 plane and the corresponding diffraction rings attained lower values in the Scherrer equation and the Scherrer-Wilson equation in samples treated with both HAp-based sealers than in specimens without sealer or with AH Plus. At root cervical dentin treated with calcypatite, shorter and wider crystallite size formations and lower crystals grain size were found, if compared to those encountered at oxipatite treated dentin. Oxipatite attained improved crystallographic atomic order and less structural variation in both distances and angles. Apical dentin treated with oxipatite attained preferred grain orientation with polycrystalline lattices. Significance. The immature crystallites formed in dentin treated with calcypatite and oxipatite will account for high hydroxyapatite solubility and remineralizing activity. New polycrystalline formations encountered in apical dentin treated with oxipatite may also produce high mechanical performance.This work was supported by the Ministry of Economy and Competitiveness (MINECO) and European Regional Development Fund (FEDER) Project MAT2017-85999-P

What do healthcare professionals need to turn risk models for type 2 diabetes into usable computerized clinical decision support systems? Lessons learned from the MOSAIC project

[EN] Background To understand user needs, system requirements and organizational conditions towards successful design and adoption of Clinical Decision Support Systems for Type 2 Diabetes (T2D) care built on top of computerized risk models. Methods The holistic and evidence-based CEHRES Roadmap, used to create eHealth solutions through participatory development approach, persuasive design techniques and business modelling, was adopted in the MOSAIC project to define the sequence of multidisciplinary methods organized in three phases, user needs, implementation and evaluation. The research was qualitative, the total number of participants was ninety, about five-seventeen involved in each round of experiment. Results Prediction models for the onset of T2D are built on clinical studies, while for T2D care are derived from healthcare registries. Accordingly, two set of DSSs were defined: the first, T2D Screening, introduces a novel routine; in the second case, T2D Care, DSSs can support managers at population level, and daily practitioners at individual level. In the user needs phase, T2D Screening and solution T2D Care at population level share similar priorities, as both deal with risk-stratification. End-users of T2D Screening and solution T2D Care at individual level prioritize easiness of use and satisfaction, while managers prefer the tools to be available every time and everywhere. In the implementation phase, three Use Cases were defined for T2D Screening, adapting the tool to different settings and granularity of information. Two Use Cases were defined around solutions T2D Care at population and T2D Care at individual, to be used in primary or secondary care. Suitable filtering options were equipped with "attractive" visual analytics to focus the attention of end-users on specific parameters and events. In the evaluation phase, good levels of user experience versus bad level of usability suggest that end-users of T2D Screening perceived the potential, but they are worried about complexity. Usability and user experience were above acceptable thresholds for T2D Care at population and T2D Care at individual. Conclusions By using a holistic approach, we have been able to understand user needs, behaviours and interactions and give new insights in the definition of effective Decision Support Systems to deal with the complexity of T2D care.The research leading to these results has received funding from the European Commission under the European Union's Seventh Framework Programme (FP7/2007-2013) grant agreement no 600914.Fico, G.; Hernandez, L.; Cancela, J.; Dagliati, A.; Sacchi, L.; Martinez-Millana, A.; Posada, J.... (2019). What do healthcare professionals need to turn risk models for type 2 diabetes into usable computerized clinical decision support systems? 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Silencing alanine transaminase 2 in diabetic liver attenuates hyperglycemia by reducing gluconeogenesis from amino acids

Hepatic gluconeogenesis from amino acids contributes significantly to diabetic hyperglycemia, but the molecular mechanisms involved are incompletely understood. Alanine transaminases (ALT1 and ALT2) catalyze the interconversion of alanine and pyruvate, which is required for gluconeogenesis from alanine. We find that ALT2 is overexpressed in the liver of diet-induced obese and db/db mice and that the expression of the gene encoding ALT2 (GPT2) is downregulated following bariatric surgery in people with obesity. The increased hepatic expression of Gpt2 in db/db liver is mediated by activating transcription factor 4, an endoplasmic reticulum stress-activated transcription factor. Hepatocyte-specific knockout of Gpt2 attenuates incorporation o

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Measurement of the W-boson mass in pp collisions at √s=7 TeV with the ATLAS detector

A measurement of the mass of the W boson is presented based on proton–proton collision data recorded in 2011 at a centre-of-mass energy of 7 TeV with the ATLAS detector at the LHC, and corresponding to 4.6 fb−1 of integrated luminosity. The selected data sample consists of 7.8×106 candidates in the W→μν channel and 5.9×106 candidates in the W→eν channel. The W-boson mass is obtained from template fits to the reconstructed distributions of the charged lepton transverse momentum and of the W boson transverse mass in the electron and muon decay channels, yielding mW=80370±7 (stat.)±11(exp. syst.) ±14(mod. syst.) MeV =80370±19MeV, where the first uncertainty is statistical, the second corresponds to the experimental systematic uncertainty, and the third to the physics-modelling systematic uncertainty. A measurement of the mass difference between the W+ and W−bosons yields mW+−mW−=−29±28 MeV

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years