18 research outputs found
Evaluación de la adecuación del calendario de vacunaciones y el cumplimiento de las recomendaciones adicionales, por su patología de base, en niños con problemas complejos de salud
Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Pediatría. Fecha de lectura: 22-09-2017Esta tesis tiene embargado el acceso al texto completo hasta el 22-03-201
Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries
Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely
Nanostructuration by Self-Assembly in <i>N</i>‑Alkyl Thiazolium and Triazolium Side-Chain Polymethacrylates
Amphiphilic polymers are tunable
systems to construct supramolecular hierarchically self-assembled
structures. Six families of heterocyclic polymethacrylates (PMTAs)
bearing 1,3-thiazole and 1,2,3-triazole pendant groups with alkyl
and succinate spacers were chemically modified by quaternization reaction
of the azole heterocycles with five alkylating agents (methyl, butyl,
octyl, dodecyl, and hexadecyl iodide) leading to a library of 30 different
amphiphilic poly(ionic liquid)s (PMTAs-RI). These polymers have been
characterized in bulk by small- and wide-angle X-ray scattering (SAXS,
WAXS) and differential scanning calorimetry (DSC). Quaternization
induces a dramatic effect (increase) on the glass-transition temperature <i>T</i><sub>g</sub>, being strongest for methyl iodide members.
Increasing the length of the quaternizing agent, plasticization is
first observed, followed by a further increase of <i><i>T</i></i><sub>g</sub>. This effect, together with evidence
of a second <i>T</i><sub>g</sub> and crystallization for
the members with the longest quaternizing agents, could be attributed
to the presence of well-developed alkyl nanodomains evidenced by the
structural investigation. WAXS and SAXS results have been consistently
interpreted by assuming nanostructuration driven by the amphiphilicity
balance of poly(ionic liquid)s. The different morphologies revealed
by SAXS have been characterized, assigning a plausible chemical nature
to the phases involved in each case. The nonpolar fraction has been
considered as the control parameter defining the main features of
the achieved morphology. By increasing this parameter, structures
ranging from hexagonally packed nonpolar cylinders in a polar matrix
to the inverse situation have been found, passing through lamellar
phases. Under some conditions, within the polar lamellae a third phase
formed by cylinders of heterocycles has even been determined. We have
checked the validity of the scenario proposed by comparing the sizes
deduced from the SAXS analysis with the expected characteristic lengths
of the associated moieties, inferring thereby how alkyl side groups
arrange within the nanodomains. On the basis of the complete picture
achieved, the type of nanostructures formed by this class of polymers
can be predicted, if the chemical composition including the quaternization
degree is known
Probing Carbohydrate-Lectin Recognition in Heterogeneous Environments with Monodisperse Cyclodextrin-Based Glycoclusters
A series of β-cyclodextrin (βCD)-scaffolded
glycoclusters
exposing heterogeneous yet perfectly controlled displays of α-mannosyl
(α-Man) and β-lactosyl (β-Lact) antennas were synthesized
to probe the mutual influence of varying densities of the saccharide
motifs in the binding properties toward different plant lectins. Enzyme-linked
lectin assay (ELLA) data indicated that the presence of β-Lact
residues reinforced binding of α-Man to the mannose-specific
lectin concanavalin A (Con A) even though homogeneous β-Lact
clusters are not recognized at all by this lectin, supporting the
existence of synergic recognition mechanisms (<i>heterocluster
effect</i>). Conversely, the presence of α-Man motifs in
the heteroglycoclusters also resulted in a binding-enhancing effect
of β-Lact toward peanut agglutinin (PNA), a lectin strongly
binding multivalent lactosides but having no detectable affinity for
α-mannopyranosides, for certain architectural arrangements.
Two-site, sandwich-type ELLA data corroborated the higher lectin clustering
efficiency of heterogeneous glycoclusters compared with homogeneous
displays of the putative sugar ligand with identical valency. A turbidity
assay was also consistent with the previous observations. Most revealingly,
the lectin cross-linking ability of heterogeneous glycoclusters was
sensitive to the presence of high concentrations of the non-ligand
sugar, strongly suggesting that “mismatching” saccharide
motifs may modulate carbohydrate-lectin specific recognition in a
lectin-dependent manner when present in highly dense displays together
with the “matching” ligand, a situation frequently encountered
in biological systems
Effect of glycounits on the antimicrobial properties and toxicity behavior of polymers based on quaternized DMAEMA
Polymers
with quaternary ammonium groups such as quaternized poly(2-(dimethylamino)ethyl
methacrylate) (PDMAEMAQ) have been used as antimicrobial agents because
of their demonstrated good antimicrobial activities against a huge
number and types of microbes, although their cytotoxicity is also
well-known. In this work block copolymers based on PDMAEMAQ were synthesized
containing hydrophobic segments of poly(butyl methacrylate) to improve
the antimicrobial activity and glycomonomer units with the aim of
decreasing the cytotoxicity of the polymers. Hydrophobic butyl methacrylate
(BMA) blocks were chain extended by statistical and block copolymers
of DMAEMA and 2-{[(d-glucosamin-2-<i>N</i>-yl)carbonylethyl
methacrylate (HEMAGl) glycomonomer of different compositions. In order
to find the balance between antimicrobial activity and cytotoxicity,
the selectivity index of each polymer was obtained from minimum inhibitory
concentrations (MIC) and white and red blood cells toxicity measurements
Formation of Multigradient Porous Surfaces for Selective Bacterial Entrapment
Herein we describe the preparation
of multigradient porous platforms
by using the breath figures approach. In a single and straightforward
step, we prepared porous surfaces in which three different parameters
vary gradually from the edge of the sample to the center in a radial
manner. Thus, we evidenced the gradual variation of the pore size
and the shape of the pores that can be varied, depending on the sample
concentration, but also depending on their radial position within
the same sample. In addition, we succeeded in the control over the
chemical composition inside and outside the pores as well as the variation
of the concentration of block copolymer inside the pores as a function
of their radial position. Moreover, the chemical composition and the
variable cavity size of porous surfaces have been evaluated to analyze
the influence of these variables on the selective bacterial immobilization.
To the best of our knowledge this is the first example in which, by
using a simple one-step strategy, a multigradient surface can be obtained.
These initial results can be the base to construct platforms for selective
immobilization and isolation of bacteria
Cryoconservation of Peptide Extracts from Trypsin Digestion of Proteins for Proteomic Analysis in a Hospital Biobank Facility
We
tested a semiautomated protocol for the proper storage and conservation
in a hospital biobank of tryptic peptide extracts coming from samples
with low and high protein complexity for subsequent mass spectrometry
analysis. Low-complexity samples (serum albumin, serotransferrin.
and alpha-S1-casein) were loaded in replicates in SDS-PAGE and subjected
to standard in-gel trypsin digestion. For LC–MALDI–TOF/TOF
analysis, purified β-galactosidase and human serum samples were
in-solution digested following standard procedures and desalted with
C18 stage-tips. In both cases, peptides extracts were aliquoted in
individually 2D coded tubes, vacuum-dried, barcode-read, and stored
in an automated −20 °C freezer in the Biobank facility.
Samples were kept dried at −20 °C until the corresponding
time-point of analysis, then reconstituted in the proper buffer and
analyzed by either MALDI-TOF/TOF (peptide fingerprinting and MS/MS)
or LC–MALDI-TOF/TOF following a highly reproducible pattern
to ensure the reproducibility of the results. Protein identification
was done with either Mascot or Protein Pilot as search engines using
constant parameters. Over a period of 1 year we checked six different
time points at days 0, 7, 30, 90, 180, and 365. We compared MS and
MS/MS protein score, number of identified peptides, and coverage of
the identified proteins. In the low complexity samples, the number
of peptides detected gradually decreased over time, especially affecting
the MS score. However, two of the three proteins – serum albumin
and serotransferrin – were identified by both PMF and MS/MS
at day 90. By day 180, only MS/MS identification in some replicates
was possible. By LC–MS/MS, β-galactosidase and the most
abundant serum proteins were identified with good scores at all time
points even by day 365, with no detectable peptide loss or decrease
in the fragmentation efficiency, although a progressive decrease in
peptide intensity indicates that detection of low abundant proteins
could not be optimal after very long periods of time. Our results
encourage us to use the biobank facility in the future for long-term
storage – up to 3 months – of dried peptide extracts
Cryoconservation of Peptide Extracts from Trypsin Digestion of Proteins for Proteomic Analysis in a Hospital Biobank Facility
We
tested a semiautomated protocol for the proper storage and conservation
in a hospital biobank of tryptic peptide extracts coming from samples
with low and high protein complexity for subsequent mass spectrometry
analysis. Low-complexity samples (serum albumin, serotransferrin.
and alpha-S1-casein) were loaded in replicates in SDS-PAGE and subjected
to standard in-gel trypsin digestion. For LC–MALDI–TOF/TOF
analysis, purified β-galactosidase and human serum samples were
in-solution digested following standard procedures and desalted with
C18 stage-tips. In both cases, peptides extracts were aliquoted in
individually 2D coded tubes, vacuum-dried, barcode-read, and stored
in an automated −20 °C freezer in the Biobank facility.
Samples were kept dried at −20 °C until the corresponding
time-point of analysis, then reconstituted in the proper buffer and
analyzed by either MALDI-TOF/TOF (peptide fingerprinting and MS/MS)
or LC–MALDI-TOF/TOF following a highly reproducible pattern
to ensure the reproducibility of the results. Protein identification
was done with either Mascot or Protein Pilot as search engines using
constant parameters. Over a period of 1 year we checked six different
time points at days 0, 7, 30, 90, 180, and 365. We compared MS and
MS/MS protein score, number of identified peptides, and coverage of
the identified proteins. In the low complexity samples, the number
of peptides detected gradually decreased over time, especially affecting
the MS score. However, two of the three proteins – serum albumin
and serotransferrin – were identified by both PMF and MS/MS
at day 90. By day 180, only MS/MS identification in some replicates
was possible. By LC–MS/MS, β-galactosidase and the most
abundant serum proteins were identified with good scores at all time
points even by day 365, with no detectable peptide loss or decrease
in the fragmentation efficiency, although a progressive decrease in
peptide intensity indicates that detection of low abundant proteins
could not be optimal after very long periods of time. Our results
encourage us to use the biobank facility in the future for long-term
storage – up to 3 months – of dried peptide extracts
Stellatolides, a New Cyclodepsipeptide Family from the Sponge Ecionemia acervus: Isolation, Solid-Phase Total Synthesis, and Full Structural Assignment of Stellatolide A
The
marine environment is a rich source of metabolites with potential
therapeutic properties and applications for humans. Here we describe
the first isolation, solid-phase total synthesis, and full structural
assignment of a new class of cyclodepsipeptides from the Madagascan
sponge Ecionemia acervus that shows
in vitro cytotoxic activities at submicromolar concentrations. Seven
structures belonging to a new family of compounds, given the general
name stellatolides, were characterized. The sequence and stereochemistry
of all the amino acids in these molecules were established by a combination
of spectroscopic analysis, chemical degradation, and derivatization
studies. Furthermore, the complete structure of stellatolide A was
confirmed by an efficient solid-phase method for the first total synthesis
and the full structural assignment of this molecule, including the
asymmetric synthesis of the unique β-hydroxy acid moiety (<i>Z</i>)-3-hydroxy-6,8-dimethylnon-4-enoic acid