68 research outputs found
Overproduction of threonine by Saccharomyces cerevisiae mutants resistant to hydroxynorvaline
In
this
work,
we
isolated
and
characterized
mutants
that
overproduce
threonine
from
Saccharomyces
cerevisiae.
The
mutants
were
selected
for
resistance
to
the
threonine
analog
a-amino-13-hydroxynorvalerate
(hydroxynorvaline),
and,
of
these,
the
ones
able
to
excrete
threonine
to
the
medium
were
chosen.
The
mutant
strains
produce
between
15
and
30
times
more
threonine
than
the
wild
type
does,
and,
to
a
lesser
degree,
they
also
accumulate
isoleucine.
Genetic
and
biochemical
studies
have
revealed
that
the
threonine
overproduction
is,
in
all
cases
studied,
associated
with
the
presence
in
the
strain
of
a
HOM3
allele
coding
for
a
mutant
aspartate
kinase
that
is
totally
or
partially
insensitive
to
feedback
inhibition
by
threonine.
This
enzyme
seems,
therefore,
to
be
crucial
in
the
regulation
of
threonine
biosynthesis
in
S.
cerevisiae.
The
results
obtained
suggest
that
this
strategy
could
be
efficiently
applied
to
the
isolation
of
threonine-overproducing
strains
of
yeasts
other
than
S.
cerevisiae,
even
those
used
industrially
Sequential oral antibiotic in uncomplicated Staphylococcus aureus bacteraemia: a propensity-matched cohort analysis
Objectives: We aimed to analyse the efficacy and safety of oral sequential therapy (OST) in uncomplicated Staphylococcus aureus bacteraemia (SAB). Methods: Single-centre observational cohort at a tertiary hospital in Spain, including all patients with the first SAB episode from January 2015 to December 2020. We excluded patients with complicated SAB and those who died during the first week. Patients were classified into the OST group (patients who received oral therapy after initial intravenous antibiotic therapy [IVT]), and IVT group (patients who received exclusively IVT). We performed a propensity-score matching to balance baseline differences. The primary composite endpoint was 90-day mortality or microbiological failure. Secondary endpoints included 90-day SAB relapse. Results: Out of 407 SAB first episodes, 230 (56.5%) were included. Of these, 112 (n = 48.7%) received OST and 118 (51.3%) IVT exclusively. Transition to oral therapy was performed after 7 days (interquartile range, 4–11). The primary endpoint occurred in 10.7% (11/112) in OST vs. 30.5% (36/118) in IVT (p < 0.001). SAB relapses occurred in 3.6% (4/112) vs. 1.7% (2/118) (p 0.436). None of the deaths in OST were related to SAB or its complications. After propensity-score matching, the primary endpoint was not more frequent in the OST group (relative risk, 0.42; 95% CI, 0.22–0.79). Ninety-day relapses occurred similarly in both groups (relative risk, 1.35; 95% CI, 0.75–2.39). Discussion: After an initial intravenous antibiotic, patients with uncomplicated SAB can safely be switched to oral antibiotics without apparent adverse outcomes. This strategy could save costs and complications of prolonged hospital stays. Prospective randomized studies are needed
Usefulness of 18 F-FDG PET-CT for the management of invasive fungal infections: A retrospective cohort from a tertiary university hospital
Background: 18F-FDG PET-CT is a potentially useful technique to help manage invasive fungal infection (IFI), but information on this topic is scarce. Objectives: To describe our experience using 18F-FDG PET-CT for IFI management. Patients/Methods: Retrospective cohort of IFI episodes in a university hospital from 2018 to 2023 with a18F-FDG PET-CT performed during the episode. We analysed its impact on IFI management compared to conventional imaging. Results: Thirty-five patients diagnosed with 36 episodes of IFI (52.8% moulds, 44.4% yeasts and 2.8% Pneumocystis) underwent 55 18F-FDG PET-CT. 74.3% were immunocompromised, including 45.7% solid organ transplant recipients. Indications for 18F-FDG PET-CT were diagnostic (10.9%), staging (47.3%) and follow-up (41.8%). Altogether 18F-FDG PET-CT added value to IFI management in 50.9% episodes. In 26 patients who had both staging 18F-FDG PET-CT and conventional imaging, sites of IFI dissemination were detected in 53.8% and 19.2%, respectively. Staging 18F-FDG PET-CT unveiled occult sites in 34.6%, uncovering unknown dissemination in 19.2%. In the evaluation of endocarditis in patients with fungemia, it contributed in at least 38.5%. Follow-up 18F-FDG PET-CTs had an added value in 47.8% episodes. They were allowed to de-escalate antifungal therapy in 26.1%. There were discordant findings between 18F-FDG PET-CT and CT follow-up in 40% cases. Conclusions: Overall, 18F-FDG PET-CT added value to IFI management in more than 50% of the episodes. It increased the diagnosis of occult sites, unveiled disseminated disease missed out by conventional imaging, and contributed to diagnose or rule out endocarditis in fungemia. Follow-up 18F-FDG PET-CT helped adjust the treatment duration and deserves further stud
Epidemiology and risk factors of mycotic aneurysm in patients with infective endocarditis and the impact of its rupture in outcomes. Analysis of a national prospective cohort
Background: Several aspects of the occurrence and management of mycotic aneurysm (MA) in patients with infective endocarditis (IE) have not been studied. Objectives: To determine the incidence and factors associated with MA presence and rupture and to assess the evolution of those initially unruptured MA. Methods: Prospective multicenter cohort including all patients with definite IE between January 2008 and December 2020. Results: Of 4548 IE cases, 85 (1.9%) developed MA. Forty-six (54.1%) had intracranial MA and 39 (45.9%) extracranial MA. Rupture of MA occurred in 39 patients (45.9%). Patients with ruptured MA had higher 1-year mortality (hazard ratio, 2.33; 95% confidence interval, 1.49-3.67). Of the 55 patients with initially unruptured MA, 9 (16.4%) presented rupture after a median of 3 days (interquartile range, 1-7) after diagnosis, being more frequent in intracranial MA (32% vs 3.3%, P = .004). Of patients with initially unruptured MA, there was a trend toward better outcomes among those who received early specific intervention, including lower follow-up rupture (7.1% vs 25.0%, P = .170), higher rate of aneurysm resolution in control imaging (66.7% vs 31.3%, P = .087), lower MA-related mortality (7.1% vs 16.7%, P = .232), and lower MA-related sequalae (0% vs 27.8%, P = .045). Conclusions: MA occurred in 2% of the patients with IE. Half of the Mas occurred in an intracranial location. Their rupture is frequent and associated with poor prognosis. A significant proportion of initially unruptured aneurysms result from rupture during the first several days, being more common in intracranial aneurysms. Early specific treatment could potentially lead to better outcomes.No funding was received for this article
Safety and effectiveness of isavuconazole in real-life non-neutropenic patients
Objectives: Information is scarce on clinical experiences with non-neutropenic patients with invasive fungal infection (IFI) receiving isavuconazole. We aimed to report the safety and effectiveness of this drug as a first-line treatment or rescue in real life. Methods: A retrospective, observational multicentric study of non-neutropenic patients who received isavuconazole as an IFI treatment at 12 different university hospitals (January 2018-2022). All patients met criteria for proven, probable or possible IFI according to EORTC-MSG. Results: A total of 238 IFIs were treated with isavuconazole during the study period. Combination therapy was administered in 27.7% of cases. The primary IFI was aspergillosis (217, 91.2%). Other IFIs treated with isavuconazole were candidemia (n = 10), mucormycosis (n = 8), histoplasmosis (n = 2), cryptococcosis (n = 2), and others (n = 4). Median time of isavuconazole treatment was 29 days. Only 5.9% (n = 14) of cases developed toxicity, mainly hepatic-related (10 patients, 4.2%). Nine patients (3.8%) had treatment withdrawn. Successful clinical response at 12 weeks was documented in 50.5% of patients. Conclusion: Isavuconazole is an adequate treatment for non-neutropenic patients with IFIs. Toxicity rates were low and its effectiveness was comparable to other antifungal therapies previously reported. (c) 2024 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/
Corporate social responsibility, engagement, burnout and satisfaction with life in an NGO in Colombia
La salud mental es una de las principales áreas de
interés en el marco de bienestar social y en el contexto
organizacional. En este sentido, se ha convertido en un
reto para las organizaciones no gubernamentales que
contribuyen al sector de economía de los servicios
sociales, alcanzar un equilibrio entre dos aspectos
íntimamente relacionados como lo son la salud y el
servicio a la comunidad. Este artículo tuvo como
objetivo describir la responsabilidad social corporativa,
el engagement y la satisfacción con la vida en una
muestra de 57 colaboradores de una ONG colombiana.
Los participantes completaron el Maslach Burnout
Inventory, la Escala de Satisfacción con la Vida y la
Encuesta de Adicción al Trabajo. Los resultaron
arrojaron que el engagement en el trabajo, está
directamente relacionado con actitudes positivas hacia
las tareas laborales y en la satisfacción de vida.Mental health is one of the main areas of interest within the framework of social welfare and the organizational
context. In this sense, it has become a challenge for non-governmental organizations that contribute to the
social services economy sector, striking a balance between two closely related aspects such as health and
community service. This article aimed to describe corporate social responsibility, engagement and
satisfaction with life in a sample of 57 employees of a Colombian NGO. Participants filled the Maslach Burnout
Inventory, Life Satisfaction Scale and Work Addiction Survey. The results showed that engagement at work is
directly related to positive attitudes towards work tasks and the satisfaction with life
Bioactive characterization of Persea americana Mill. by-products: A rich source of inherent antioxidants
[EN] Avocado (Persea americana Mill.) is a worldwide consumed fruit, with great interest for cosmetic and pharmaceutical industries; however, 30% of avocado fruits are bio-wastes (peels and kernels), converting them into a potential source of bioactive compounds, such as phenolic compounds. Therefore, the hydroethanolic extracts of peels and kernels of Persea america Mill. var. Hass were analysed regarding their individual phenolic profile by HPLC-DAD/ESI-MS and correlated with their antioxidant, antimicrobial and cytotoxic activities. Avocado by-products presented a very distinct phenolic profile, presenting higher concentration in peels (227.9 mg/g of extract for total phenolic content), mainly in (epi)catechin derivatives (175 mg/g of extract), followed by chlorogenic derivatives (42.9 mg/g of extract). In this study hydrophilic and lipophilic antioxidant assays were performed together for the first time in P. americana by-products, and although kernels showed a great antioxidant potential (EC50 values ranging from 18.1 to 276 mu g/mL), peels presented the highest potential (EC50 ranging from 11.7 to 152 mu g/mL), mainly due to the presence of phenolic compounds, and an overall better performance in the antibacterial assays. Further studies needs to be conducted to better understand the correlation between the presence of phenolic compounds and bioactivities, however, the main objective is to implement these biocompounds in different products and industries, due to results obtained, P. americana peels could be a great alternative in the substitution of synthetic antioxidants.The authors are grateful to the Foundation for Science and Technology(FCT, Portugal) and FEDER under Program PT2020 for financial support to CIMO (UID/AGR/00690/2013) and L. Barros contract. The authors would like to thank the Interreg Espana-Portugal for financial support through the project 0377_Iberphenol_6_E. B. Melgar thanks CONACyT for his grant (No. 329930). The authors are also grateful to the Serbian Ministry of Education, Science and Technological Development, grant number 173032 for financial support.Melgar-Castañeda, B.; Dias, MI.; Ciric, A.; Sokovic, M.; Garcia-Castello, EM.; Rodríguez López, AD.; Barros, L.... (2018). Bioactive characterization of Persea americana Mill. by-products: A rich source of inherent antioxidants. Industrial Crops and Products. 111:212-218. https://doi.org/10.1016/j.indcrop.2017.10.024S21221811
Uso de Twitter y la gamificación para fomentar el análisis crítico del conocimiento científico y las vías para su comunicación en estudiantes del Grado de Medicina
El objetivo del proyecto de innovación docente que se presenta fue mejorar la capacidad de análisis crítico del conocimiento científico en el alumnado del Grado de Medicina a través del uso de Twitter. Los estudiantes de la asignatura de Fisiología Humana compartieron a través de Twitter noticias científicas relacionadas con la asignatura. Tras una selección previa, el profesorado publicó un periódico online y los alumnos presentaron una de las noticias publicadas. Se realizó una encuesta online de evaluación del proyecto utilizando escalas de Likert (1-10). Los estudiantes respondieron que el proyecto había aumentado su capacidad de análisis crítico de la investigación biomédica (7,65; ds=1,71) y que la metodología había aumentado su interés por la asignatura (8,05; ds=1,69). La utilización de Twitter combinada con la exposición de noticias científicas resultó útil para mejorar la capacidad de análisis crítico de la evidencia científica biomédica, competencia básica del Grado de Medicina
Anti-Spike antibodies 3 months after SARS-CoV-2 mRNA vaccine booster dose in patients on hemodialysis: the prospective SENCOVAC study
Background: Patients on hemodialysis are at high-risk for complications derived from coronavirus disease 2019 (COVID-19). The present analysis evaluated the impact of a booster vaccine dose and breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections on humoral immunity 3 months after the booster dose. Methods: This is a multicentric and prospective study assessing immunoglobulin G anti-Spike antibodies 6 and 9 months after initial SARS-CoV-2 vaccination in patients on hemodialysis that had also received a booster dose before the 6-month assessment (early booster) or between the 6- and 9-month assessments (late booster). The impact of breakthrough infections, type of vaccine, time from the booster and clinical variables were assessed. Results: A total of 711 patients [67% male, median age (range) 67 (20-89) years] were included. Of these, 545 (77%) received an early booster and the rest a late booster. At 6 months, 64 (9%) patients had negative anti-Spike antibody titers (3% of early booster and 29% of late booster patients, P =. 001). At 9 months, 91% of patients with 6-month negative response had seroconverted and there were no differences in residual prevalence of negative humoral response between early and late booster patients (0.9% vs 0.6%, P =. 693). During follow-up, 35 patients (5%) developed breakthrough SARS-CoV-2 infection. Antibody titers at 9 months were independently associated with mRNA-1273 booster (P =. 001), lower time from booster (P =. 043) and past breakthrough SARS-CoV-2 infection (P <. 001). Conclusions: In hemodialysis patients, higher titers of anti-Spike antibodies at 9 months were associated with mRNA-1273 booster, lower time from booster and past breakthrough SARS-CoV-2 infectionThe present project has been supported by Fresenius Medical Care, Diaverum, Vifor Pharma, Vircell, Fundación Renal Iñigo Álvarez de Toledo and ISCIII FEDER funds RICORS2040 (RD21/0005
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