387 research outputs found
Synthesis of oxindoles and benozfuranones via oxidation of 2-heterocyclic BMIDAs
The synthesis of functionalized oxindoles and benzofuranones via oxidation of 2-BMIDA indoles and benzofurans, respectively, is described. Interconversion of boron species (BMIDAÃ BF3K) was necessary to enable oxidation and overcome boronic acid stability issues associated with a difficult BMIDA hydrolysis. Overall, a robust process was developed that allowed access to a small library of oxindole and benzofuranone products and facilitated the step-efficient synthesis of biologically-active compounds containing the oxindole pharmacophore
Sodium-glucose cotransporter 2 inhibitor effects on heart failure hospitalization and cardiac function: systematic review
Aims:
To systematically review randomized controlled trials assessing effects of sodium–glucose cotransporter 2 inhibitors (SGLT2is) on hospitalization for heart failure (HHF) and cardiac structure/function and explore randomized controlled trial (RCT)-derived evidence for SGLT2i efficacy mechanisms in heart failure (HF).
Methods and results:
Systematic searches of Medline and Embase were performed. In seven trials [3730–17 160 patients; low risk of bias (RoB)], SGLT2is significantly reduced the relative risk of HHF by 27–39% vs. placebo, including in two studies in patients with HF with reduced ejection fraction with or without type-2 diabetes mellitus (T2DM). Improvements in conventional cardiovascular risk factors, including glycaemic levels, cannot account for these effects. Five trials (56–105 patients; low RoB) assessed the effects of 6–12 months of SGLT2i treatment on left ventricular structure/function; four reported significant improvements vs. placebo, and one did not. Five trials (low RoB) assessed SGLT2i treatment effects on serum N-terminal pro B-type natriuretic peptide levels; significant reductions vs. placebo were reported after 8–12 months (two studies; 3730–4744 patients) but not ≤12 weeks (three studies; 80–263 patients). Limited available RCT-derived evidence suggests various possible cardioprotective SGLT2i mechanisms, including improved haemodynamics (natriuresis and reduced interstitial fluid without blood volume contraction/neurohormonal activation) and vascular function, enhanced erythropoiesis, reduced tissue sodium and epicardial fat/inflammation, decreased sympathetic tone, and beneficial changes in cellular energetics.
Conclusions:
Sodium–glucose cotransporter 2 inhibitors reduce HHF regardless of T2DM status, and reversal of adverse left ventricular remodelling likely contributes to this efficacy. Hypothesis-driven mechanistic trials remain sparse, although numerous trials are planned or ongoing
Systematic review of the effects of sodium-glucose cotransporter 2 inhibitors on hospitalization for heart failure and cardiac structure or function, and exploratory assessment of potential mechanisms
In the past 5 years, there has been a profound shift in the therapeutic focus of trials of sodium-glucose cotransporter 2 inhibitors (SGLT2is).
Although initially explored and introduced as glucose-lowering agents for patients with type 2 diabetes mellitus (T2DM), 1 clinical investigation of these molecules has evolved towards heart failure (HF) and chronic kidney disease (CKD) outcomes in patients with and without T2DM.
We systematically reviewed randomized controlled trial (RCT) data assessing the effects of SGLT2 is compared with placebo on hospitalization for HF (HHF), cardiac structure and cardiac function, in a PRISMA-compliant manner.
We also reviewed, in an exploratory manner, mechanistic evidence for how SGLT2 is may exert their benefits
Direct Light-Enabled Access to α-Boryl Radicals: Application in the Stereodivergent Synthesis of Allyl Boronic Esters
Operationally simple strategies to assemble boron containing organic frameworks are highly enabling in organic synthesis. While conventional retrosynthetic logic has engendered many platforms focusing on the direct formation of C−B bonds, α-boryl radicals have recently reemerged as versatile open-shell alternatives to access organoborons via adjacent C−C bond formation. Direct light-enabled α-activation is currently contingent on photo- or transition metal-catalysis activation to efficiently generate radical species. Here, we disclose a facile activation of α-halo boronic esters using only visible light and a simple Lewis base to enable homolytic scission. Intermolecular addition to styrenes facilitates the rapid construction of highly versatile E-allylic boronic esters. The simplicity of activation permits the strategic merger of this construct with selective energy transfer catalysis to enable the complimentary stereodivergent synthesis of Z-allylic boronic esters
Chemoselective oxidation of aryl organoboron systems enabled by boronic acid-selective phase transfer
We report the direct chemoselective Brown-type oxidation of aryl organoboron systems containing two oxidizable boron groups. Basic biphasic reaction conditions enable selective formation and phase transfer of a boronic acid trihydroxyboronate in the presence of boronic acid pinacol (BPin) esters, while avoiding speciation equilibria. Spectroscopic investigations validate a base-promoted phase-selective discrimination of organoboron species. This phenomenon is general across a broad range of organoboron compounds and can also be used to invert conventional protecting group strategies, enabling chemoselective oxidation of BMIDA species over normally more reactive BPin substrates. We also demonstrate the selective oxidation of diboronic acid systems with chemoselectivity predictable a priori. The utility of this method is exemplified through the development of a chemoselective oxidative nucleophile coupling
Characterizing the Initial Phase of Epidemic Growth on some Empirical Networks
A key parameter in models for the spread of infectious diseases is the basic
reproduction number , which is the expected number of secondary cases a
typical infected primary case infects during its infectious period in a large
mostly susceptible population. In order for this quantity to be meaningful, the
initial expected growth of the number of infectious individuals in the
large-population limit should be exponential.
We investigate to what extent this assumption is valid by performing repeated
simulations of epidemics on selected empirical networks, viewing each epidemic
as a random process in discrete time. The initial phase of each epidemic is
analyzed by fitting the number of infected people at each time step to a
generalised growth model, allowing for estimating the shape of the growth. For
reference, similar investigations are done on some elementary graphs such as
integer lattices in different dimensions and configuration model graphs, for
which the early epidemic behaviour is known.
We find that for the empirical networks tested in this paper, exponential
growth characterizes the early stages of the epidemic, except when the network
is restricted by a strong low-dimensional spacial constraint, such as is the
case for the two-dimensional square lattice. However, on finite integer
lattices of sufficiently high dimension, the early development of epidemics
shows exponential growth.Comment: To be included in the conference proceedings for SPAS 2017
(International Conference on Stochastic Processes and Algebraic Structures),
October 4-6, 201
Coagulation profiles are associated with early clinical outcomes in neonatal encephalopathy
Introduction: Neonatal encephalopathy (NE) is associated with coagulation abnormalities. We aimed to investigate the serial alterations in coagulation profiles in term infants with NE and correlate with their clinical outcomes. This was a prospective cohort study in a tertiary referral, university-affiliated maternity hospital. Neonates exposed to perinatal asphyxia were recruited (n = 82) and 39 received therapeutic hypothermia. Infants had serial coagulation tests including platelets, prothrombin time (PT), activated partial thromboplastin time (aPTT) and fibrinogen in the first week of life. The main outcome measures included MRI brain and EEG seizures. Our results show that mortality was predicted on day 1 by decreased Fibrinogen (AUC = 0.95, p = 0.009) and by PT on day 2 with a cutoff of 22 s. An abnormal MRI was predicted by Fibrinogen on day 3 with a cut-off value of 2 g/L. For prediction of grade II/III NE, PT on day 2 of life was strongest with a cut-off value of 14 s. Only elevated APTT levels on day 1 of life were predictive of seizures (AUC = 0.65, p = 0.04). Conclusion: Coagulation parameters are strong predictors of outcomes such as abnormal NE grade, seizures, and mortality
A randomized controlled multimodal behavioral intervention trial for improving antiepileptic drug adherence
Purpose: Medication nonadherence is one of the most important reasons for treatment failure in patients with
epilepsy. The present study investigated the effectiveness of a multicomponent intervention to improve adherence
to antiepileptic drug (AED) medication in patients with epilepsy.
Methods: In a prospective, randomizedmulticenter trial, three sessions of face-to-facemotivational interviewing
(MI) in combination with complementary behavior change techniques were compared with standard care.Motivational
interviewing prompted change talk and self-motivated statements from the patients, planning their
own medication intake regimen and also identifying and overcoming barriers thatmay prevent adherence. Participants
were provided with calendars to self-monitor their medication taking behavior. A family member and
the health-care teamwere invited to attend the last session ofMI in order to improve the collaboration and communication
between patients, their caregiver or family member, and their health-care provider. At baseline and
6-month follow-up, psychosocial variables and medical adherence were assessed.
Results: In total, 275 participantswere included in the study. Comparedwith the active control group, patients in
the intervention group reported significantly highermedication adherence, aswell as stronger intention and perceptions
of control for taking medication regularly. The intervention group also reported higher levels of action
planning, coping planning, self-monitoring, and lower medication concerns.
Conclusions: This study shows that MI can be effective in clinical practice to improvemedication adherence in patientswith
epilepsy. It also provides evidence that combining volitional interventions, including action planning,
coping planning, and self-monitoring withmotivational interviewing can promote the effectiveness of the medical
treatments for epilepsy by improving adherenc
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