129 research outputs found
Rapid multistep kinetic model generation from transient flow data
Today, the generation of kinetic models is still seen as a resource intensive and specialised activity. We report an efficient method of generating reaction profiles from transient flows using a state-ofthe-art continuous-flow platform. Experimental data for multistep aromatic nucleophilic substitution reactions are collected from an automated linear gradient flow ramp with online HPLC at the reactor outlet. Using this approach, we generated 16 profiles, at 3 different inlet concentrations and 4 temperatures, in less than 3 hours run time. The kinetic parameters, 4 rate constants and 4 activation energies were fitted with less than 4% uncertainty. We derived an expression for the error in the observed rate constants due to dispersion and showed that such error is 5% or lower. The large range of operational conditions prevented the need to isolate individual reaction steps. Our approach enables early identification of the sensitivity of product quality to parameter changes and early use of unit operation models to identify optimal processequipment combinations in silico, greatly reducing scale up risks
A polymeric nanomedicine diminishes inflammatory events in renal tubular cells
The polyglutamic acid/peptoid 1 (QM56) nanoconjugate inhibits apoptosis by interfering with Apaf-1 binding to
procaspase-9. We now describe anti-inflammatory properties of QM56 in mouse kidney and renal cell models.
In cultured murine tubular cells, QM56 inhibited the inflammatory response to Tweak, a non-apoptotic stimulus. Tweak
induced MCP-1 and Rantes synthesis through JAK2 kinase and NF-kB activation. Similar to JAK2 kinase inhibitors, QM56
inhibited Tweak-induced NF-kB transcriptional activity and chemokine expression, despite failing to inhibit NF-kB-p65
nuclear translocation and NF-kB DNA binding. QM56 prevented JAK2 activation and NF-kB-p65(Ser536) phosphorylation.
The anti-inflammatory effect and JAK2 inhibition by QM56 were observed in Apaf-12/2 cells.
In murine acute kidney injury, QM56 decreased tubular cell apoptosis and kidney inflammation as measured by downmodulations
of MCP-1 and Rantes mRNA expression, immune cell infiltration and activation of the JAK2-dependent
inflammatory pathway. In conclusion, QM56 has an anti-inflammatory activity which is independent from its role as
inhibitor of Apaf-1 and apoptosis and may have potential therapeutic relevance.This work was supported by grants from the Instituto de Salud Carlos III (www.isciii.es), FIS: PI07/0020, CP08/1083, PS09/00447 and ISCIII-RETICS
REDINREN RD 06/0016; Sociedad Española de Nefrología (www.senefro.org). Álvaro Ucero, Sergio Berzal and Carlos Ocaña supported by Fundacion Conchita
Rabago (www.fundacionconchitarabago.net), Alberto Ortiz by the Programa de Intensificación de la Actividad Investigadora in the Sistema Nacional de Salud of
the Instituto de Salud Carlos III and the Agencia ‘‘Pedro Lain Entralgo’’ of the Comunidad de Madrid and CIFRA S-BIO 0283/2006 www.madrid.org/lainentralgo)
and Adrián Ramos, by FIS (Programa Miguel Servet)
Anthropogenic reaction parameters - the missing link between chemical intuition and the available chemical space
How do skilled synthetic chemists develop
such a good intuitive expertise
?
Why can we
only access such a small amount of the available chemical space
—
both in terms of the
re
actions used and the chemical scaffolds we make?
We argue here that these
seemingly
unrelated
questions
have a common root and
are strongly
interdependent
.
We performed a
comprehensive analysis of organic reaction parameters dating back to 1771 and discove
red
that
there are several
anthropogenic
factors
that limit the
reaction parameters and thus the
scop
e of synthetic
chemistry.
Nevertheless,
many of the anthropogenic limitations such as
the
narrow parameter space and the opportunity of the rapid and clear
feedback on the progress of
reactions appear to be crucial for the acquisition of valid and reliable chemical intuition.
In
parallel, however, all of these
same
factors represent limitations
for the
exploration of
available chemistry space and
we argue
th
at these
are thus at least partly responsible for
limited access to new chemistries. We advocate, therefore, that the present
anthropogenic
boundaries can be expanded by a more conscious expl
oration of “off
-
road” chemistry that
would also
extend the intuit
ive knowledge of trained chemists
Evolving trends in the management of acute appendicitis during COVID-19 waves. The ACIE appy II study
Background: In 2020, ACIE Appy study showed that COVID-19 pandemic heavily affected the management of patients with acute appendicitis (AA) worldwide, with an increased rate of non-operative management (NOM) strategies and a trend toward open surgery due to concern of virus transmission by laparoscopy and controversial recommendations on this issue. The aim of this study was to survey again the same group of surgeons to assess if any difference in management attitudes of AA had occurred in the later stages of the outbreak.
Methods: From August 15 to September 30, 2021, an online questionnaire was sent to all 709 participants of the ACIE Appy study. The questionnaire included questions on personal protective equipment (PPE), local policies and screening for SARS-CoV-2 infection, NOM, surgical approach and disease presentations in 2021. The results were compared with the results from the previous study.
Results: A total of 476 answers were collected (response rate 67.1%). Screening policies were significatively improved with most patients screened regardless of symptoms (89.5% vs. 37.4%) with PCR and antigenic test as the preferred test (74.1% vs. 26.3%). More patients tested positive before surgery and commercial systems were the preferred ones to filter smoke plumes during laparoscopy. Laparoscopic appendicectomy was the first option in the treatment of AA, with a declined use of NOM.
Conclusion: Management of AA has improved in the last waves of pandemic. Increased evidence regarding SARS-COV-2 infection along with a timely healthcare systems response has been translated into tailored attitudes and a better care for patients with AA worldwide
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