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BACKGROUND: Pseudomonas aeruginosa bloodstream infections (PA-BSIs) are a serious disease and a therapeutic challenge due to increasing resistance to carbapenems. Our objectives were to describe the prevalence and risk factors associated with carbapenem resistance (CR) and mortality in children with PA-BSI. METHODS: A retrospective, multi-centre study was carried out, including patients aged <20 years with PA-BSI in four tertiary hospitals in Madrid (Spain) during 2010-2020. Risk factors for CR PA-BSIs and 30-day mortality were evaluated in a multi-variable logistic regression model. RESULTS: In total, 151 patients with PA-BSI were included, with a median age of 29 months (interquartile range: 3.5-87.1). Forty-five (29.8%) cases were CR, 9.9% multi-drug resistant and 6.6% extensively drug resistant. The prevalence of CR remained stable throughout the study period, with 26.7% (12/45) of CR mediated by VIM-type carbapenemase. Patients with BSIs produced by CR-PA were more likely to receive inappropriate empiric treatment (53.3% vs 5.7%, P<0.001) and to have been previously colonized by CR-PA (8.9% vs 0%, P=0.002) than BSIs caused by carbapenem-susceptible P. aeruginosa. CR was associated with carbapenem treatment in the previous month (adjusted odds ratio (aOR) 11.15) and solid organ transplantation (aOR 7.64). The 30-day mortality was 23.2%, which was associated with mechanical ventilation (aOR 4.24), sepsis (aOR 5.72), inappropriate empiric antibiotic therapy (aOR 5.86), and source control as a protective factor (aOR 0.16). CONCLUSION: This study shows a concerning prevalence of CR in children with PA-BSIs, leading to high mortality. Inappropriate empiric treatment and sepsis were associated with mortality. The high prevalence of CR with an increased risk of inappropriate empiric treatment should be closely monitored.
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Bacteriemia , Carbapenémicos , Infecciones por Pseudomonas , Pseudomonas aeruginosa , Humanos , Infecciones por Pseudomonas/mortalidad , Infecciones por Pseudomonas/epidemiología , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/microbiología , Preescolar , Niño , Factores de Riesgo , Masculino , Femenino , Pseudomonas aeruginosa/efectos de los fármacos , Estudios Retrospectivos , Lactante , Carbapenémicos/farmacología , Carbapenémicos/uso terapéutico , Adolescente , Bacteriemia/mortalidad , Bacteriemia/microbiología , Bacteriemia/epidemiología , Bacteriemia/tratamiento farmacológico , España/epidemiología , Prevalencia , Centros de Atención Terciaria/estadística & datos numéricos , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Análisis de Supervivencia , Resistencia betalactámicaRESUMEN
Estrogen receptors (ERs) are thought to be the ancestor of all steroid receptors and are present in most lophotrochozoans studied to date, including molluscs, annelids, and rotifers. A number of studies have investigated the functional role of estrogen receptors in invertebrate species, although most are in molluscs, where the receptor is constitutively active. In vitro experiments provided evidence for ligand-activated estrogen receptors in annelids, raising important questions about the role of estrogen signalling in lophotrochozoan lineages. Here, we review the concordant and discordant evidence of estradiol receptor signalling in lophotrochozoans, with a focus on annelids and rotifers. We explore the de novo synthesis of estrogens, the evolution and expression of estrogen receptors, and physiological responses to activation of estrogen receptors in the lophotrochozoan phyla Annelida and Rotifera. Key data are missing to determine if de novo biosynthesis of estradiol in non-molluscan lophotrochozoans is likely. For example, an ortholog for the CYP11 gene is present, but confirmation of substrate conversion and measured tissue products is lacking. Orthologs CYP17 and CYP19 are lacking, yet intermediates or products (e.g. estradiol) in tissues have been measured. Estrogen receptors are present in multiple species, and for a limited number, in vitro data show agonist binding of estradiol and/or transcriptional activation. The expression patterns of the lophotrochozoan ERs suggest developmental, reproductive, and digestive roles but are highly species dependent. E2 exposures suggest that lophotrochozoan ERs may play a role in reproduction, but no strong dose-response relationship has been established. Therefore, we expect most lophotrochozoan species, outside of perhaps platyhelminths, to have an ER but their physiological role remains elusive. Mining genomes for orthologs gene families responsible for steroidogenesis, coupled with in vitro and in vivo studies of the steroid pathway are needed to better assess whether lophotrochozoans are capable of estradiol biosynthesis. One major challenge is that much of the data are divided across a diversity of species. We propose that the polychaetes Capitella teleta or Platyneris dumerilii, and rotifer Brachionus manjavacas may be strong species choices for studies of estrogen receptor signalling, because of available genomic data, established laboratory culture techniques, and gene knockout potential.
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Transducción de Señal , Animales , Transducción de Señal/fisiología , Transducción de Señal/genética , Receptores de Estradiol/metabolismo , Receptores de Estradiol/genética , Anélidos/metabolismo , Anélidos/genética , Receptores de Estrógenos/metabolismo , Receptores de Estrógenos/genética , Rotíferos/metabolismo , Rotíferos/genética , Estradiol/metabolismoRESUMEN
The preservation of the nuclear genome's integrity is paramount for the viability and overall health of cells, tissues, and organisms. DNA, being susceptible to damage under physiological conditions and vulnerable to both endogenous and environmental factors, faces constant threats. To assess DNA damage and repair within individual eukaryotic cells, the comet assay presents itself as a versatile, gel electrophoresis-based, relatively simple, and highly sensitive method. Originally designed to monitor DNA damage and repair within populations of mammalian cells, the comet assay has now found applications across diverse domains, including yeast, protozoa, plants, and invertebrates. This technique has proven invaluable in cryopreservation studies, serving as a valuable adjunct for determining suitable cryopreservation protocols. These protocols encompass choices related to cryoprotectants, sample preparation, as well as storage conditions in terms of time and temperature. In the realm of animal cryopreservation research, the comet assay stands as a gold-standard method for assessing DNA integrity. Nevertheless, when applied in plant-oriented investigations, additional efforts are essential due to the distinct nature of plant cells and associated technical challenges. This review elucidates the fundamental principles underlying the comet assay, discusses its current iterations, and delineates its applications in the cryopreservation of both animal and plant specimens. Moreover, we delve into the primary challenges confronting the comet assay's utility as a monitoring tool in the context of plant sample cryopreservation. https://doi.org/10.54680/fr24110110112.
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Criopreservación , Daño del ADN , Animales , Ensayo Cometa/métodos , Criopreservación/métodos , Crioprotectores/farmacología , ADN , Mamíferos/genéticaRESUMEN
The present study aimed to evaluate the feasibility of using near-infrared hyperspectral imaging (NIR-HSI) and chemometrics for classification of individual wheat kernels according to their deoxynivalenol (DON) level. In total, 600 wheat kernels from samples naturally contaminated over the maximum EU level were collected, and the DON content in each individual wheat kernel was analyzed by UHPLC. Linear discriminant analysis (LDA) was employed for building classification models of DON using the EU maximum level as cut off level, and they were tested on balanced and imbalanced test sets. The results showed that the models presented a balanced accuracy of 0.71, that would allow to obtain safe batches from contaminated batches once the unsafe kernels had been rejected, but often more than 30% of the batch would be rejected. The work confirmed that NIR-HSI could be a feasible method for monitoring DON in individual kernels and removing highly contaminated kernels prior to food chain entry.
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Tricotecenos , Triticum , Imágenes Hiperespectrales , Contaminación de Alimentos/análisis , Tricotecenos/análisisRESUMEN
Controlling molecular reactivity by shaped laser pulses is a long-standing goal in chemistry. Here, we suggest a direct optimal control approach that combines external pulse optimization with other control parameters arising in the upcoming field of vibro-polaritonic chemistry for enhanced controllability. The direct optimal control approach is characterized by a simultaneous simulation and optimization paradigm, meaning that the equations of motion are discretized and converted into a set of holonomic constraints for a nonlinear optimization problem given by the control functional. Compared with indirect optimal control, this procedure offers great flexibility, such as final time or Hamiltonian parameter optimization. A simultaneous direct optimal control theory will be applied to a model system describing H-atom transfer in a lossy Fabry-Pérot cavity under vibrational strong coupling conditions. Specifically, optimization of the cavity coupling strength and, thus, of the control landscape will be demonstrated.
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PURPOSE: After standard treatment for glioblastoma, perfusion MRI remains challenging for differentiating tumor progression from post-treatment changes. Our objectives were (1) to correlate rCBV values at diagnosis and at first tumor progression and (2) to analyze the relationship of rCBV values at tumor recurrence with enhancing volume, localization of tumor progression, and time elapsed since the end of radiotherapy in tumor recurrence. METHODS: Inclusion criteria were (1) age > 18 years, (2) histologically confirmed glioblastoma treated with STUPP regimen, and (3) tumor progression according to RANO criteria > 12 weeks after radiotherapy. Co-registration of segmented enhancing tumor VOIs with dynamic susceptibility contrast perfusion MRI was performed using Olea Sphere software. For tumor recurrence, we correlated rCBV values with enhancing tumor volume, with recurrence localization, and with time elapsed from the end of radiotherapy to progression. Analyses were performed with SPSS software. RESULTS: Sixty-four patients with glioblastoma were included in the study. Changes in rCBV values between diagnosis and first tumor progression were significant (p < 0.001), with a mean and median decreases of 32% and 46%, respectively. Mean rCBV values were also different (p < 0.01) when tumors progressed distally (radiation field rCBV values of 1.679 versus 3.409 distally). However, changes and, therefore, low rCBV values after radiotherapy in tumor recurrence were independent of time. CONCLUSION: Chemoradiation alters tumor perfusion and rCBV values may be decreased in the setting of tumor progression. Changes in rCBV values with respect to diagnosis, with low rCBV in tumor progression, are independent of time but related to the site of recurrence.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Adulto , Persona de Mediana Edad , Glioblastoma/diagnóstico por imagen , Glioblastoma/radioterapia , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/radioterapia , Recurrencia Local de Neoplasia/diagnóstico por imagen , Medios de Contraste , Quimioradioterapia , Imagen por Resonancia Magnética/métodosRESUMEN
BACKGROUND: Hearing loss impacts health-related quality of life and general well-being and was identified in a Lancet report as one of the largest potentially modifiable factors for the prevention of age-related dementia. There is a lack of robust data on how cochlear implant treatment in the elderly impacts quality of life. The primary objective was to measure the change in health utility following cochlear implantation in individuals aged ≥ 60 years. METHODS: This study uniquely prospectively recruited a large multinational sample of 100 older adults (mean age 71.7 (SD7.6) range 60-91 years) with severe to profound hearing loss. In a repeated-measures design, pre and post implant outcome measures were analysed using mixed-effect models. Health utility was assessed with the Health Utilities Index Mark III (HUI3). Subjects were divided into groups of 60-64, 65-74 and 75 + years. RESULTS: At 18 months post implant, the mean HUI3 score improved by 0.13 (95%CI: 0.07-0.18 p < 0.001). There was no statistically significant difference in the HUI3 between age groups (F[2,9228] = 0.53, p = 0.59). The De Jong Loneliness scale reduced by an average of 0.61 (95%CI: 0.25-0.97 p < 0.014) and the Lawton Instrumental Activities of Daily Living Scale improved on average (1.25, 95%CI: 0.85-1.65 p < 0.001). Hearing Handicap Inventory for the Elderly Screening reduced by an average of 8.7 (95%CI: 6.7-10.8, p < 0.001) from a significant to mild-moderate hearing handicap. Age was not a statistically significant factor for any of the other measures (p > 0.20). At baseline 90% of participants had no or mild depression and there was no change in mean depression scores after implant. Categories of Auditory perception scale showed that all subjects achieved a level of speech sound discrimination without lip reading post implantation (level 4) and at least 50% could use the telephone with a known speaker. CONCLUSIONS: Better hearing improved individuals' quality of life, ability to communicate verbally and their ability to function independently. They felt less lonely and less handicapped by their hearing loss. Benefits were independent of age group. Cochlear implants should be considered as a routine treatment option for those over 60 years with bilateral severe to profound hearing loss. TRIAL REGISTRATION: ClinicalTrials.gov ( http://www. CLINICALTRIALS: gov/ ), 7 March 2017, NCT03072862.
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Implantación Coclear , Implantes Cocleares , Sordera , Pérdida Auditiva , Percepción del Habla , Anciano , Anciano de 80 o más Años , Humanos , Actividades Cotidianas , Sordera/cirugía , Pérdida Auditiva/diagnóstico , Pérdida Auditiva/terapia , Calidad de Vida , Resultado del Tratamiento , Persona de Mediana EdadRESUMEN
BACKGROUND: Voluntary post-mortem donation to science (PDS) is the most appropriate source for body dissection in medical education and training, and highly useful for biomedical research. In Mexico, unclaimed bodies are no longer a legal source, but PDS is legally possible, although scarcely facilitated, and mostly ignored by the general population. Therefore, we aimed to evaluate the attitude and willingness for PDS and to identify a sociodemographic profile of people with willingness toward PDS. METHODS: A validated on-line survey was distributed by the convenience method via the social networks of a Catholicism-inspired, private university in northern Mexico. Frequency analyses of all variables and coded free comments were complemented with association studies. RESULTS: Although the responder cohort (n = 143) was too small and biased to be representative of the university community (n = 13,500), willingness to post-mortem organ donation was 90.7% and to PDS 70.7%. In this cohort, PDS willingness had the strongest association with mature age (> 40 years old; P, 0.0008). Among young adults, willingness to PDS was the lowest among volunteers from technical and business schools and the highest among those from the social sciences (P, 0.009). Respondents from the social sciences were also the most consistent between attitude and behavior with respect to organ donation. A free comment option revealed respondents were interested in the unusual taboo topic. CONCLUSIONS: A small, but sufficiently large proportion expressed willingness toward PDS. In our university cohort, which was biased in higher education and altruism, mature age and social interest were associated with PDS willingness.
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Donantes de Tejidos , Obtención de Tejidos y Órganos , Adulto Joven , Humanos , Adulto , Universidades , México , Encuestas y Cuestionarios , Conocimientos, Actitudes y Práctica en SaludRESUMEN
Antecedentes y objetivo Los nódulos tiroideos se encuentran entre las dolencias más frecuentes, con un 10% de riesgo de malignidad. El objetivo es describir la frecuencia de las características demográficas, clínicas y ecográficas de la enfermedad de nódulos tiroideos en adultos y explorar la relación con la malignidad del tumor. Métodos Estudio transversal analítico, retrospectivo, en adultos con nódulos tiroideos y aspiración con aguja fina nodular realizada en pacientes adultos de un centro de referencia colombiano entre 2009-2019. Los datos se obtuvieron de la historia clínica y se estimaron medidas descriptivas de las variables demográficas, clínicas y ecográficas de los pacientes y se exploró su relación con la malignidad del tumor. Resultados Se incluyeron 445 pacientes y 515 nódulos. La mediana de edad fue de 55 años (RIQ 44-64), 86,8% mujeres, 54,8% tenía lesión única. El 80,2 y el 19,8% eran nódulos benignos y malignos, con una mediana de 15,7mm (RIQ 11-25) y 12,7mm (RIQ 8,5-18,3), respectivamente (p<0,001). El hipotiroidismo y el consumo de levotiroxina fueron mayores en quienes tenían nódulos malignos, (p<0,001). Las características ecográficas fueron diferentes estadísticamente entre los nódulos: en los malignos hubo mayor frecuencia de composición sólida, hipoecogenicidad y margen irregular, mientras que en los benignos se destacó la ausencia de foco ecogénico (p<0,001). Conclusión Las características ecográficas son fundamentales para definir el riesgo de malignidad de un nódulo tiroideo, por lo cual, considerar las más frecuentes puede ayudar en el abordaje más adecuado desde la atención primaria (AU)
Background and objective Thyroid nodules are among the most frequent conditions, with a 10% risk of malignancy. The objective is to describe the frequency of demographic, clinical, and ultrasonographic characteristics of thyroid nodule pathology in adults and to explore the relationship with tumor malignancy. Methods An analytical, retrospective cross-sectional study in adults with thyroid nodules and nodular fine-needle aspiration performed in adult patients from a Colombian reference center between 2009-2019. Data were obtained from the clinical history, descriptive measures of the patient's demographic, clinical, and ultrasound variables were estimated, and their relationship with the malignancy of the tumor was explored. Results A total of 445 patients and 515 nodules were included. The median age was 55 years (IQR 44-64), 86.8% of women, and 54.8% had a single lesion. Percentages of 80.2 and 19.8 were benign and malignant nodules, with a median of 15.7mm (IQR 11-25) and 12.7mm (IQR 8.5-18.3), respectively (p<0.001). Hypothyroidism and levothyroxine consumption were higher in those with malignant nodules (p<0.001). The echographic characteristics were statistically different between the nodules. In the malignant ones, there was a higher frequency of solid composition, hypoechogenicity, and irregular margins. In contrast, in the benign ones, the absence of echogenic focus stood out (p<0.001). Conclusion The ultrasound characteristics are essential to define the risk of malignancy of a thyroid nodule. Therefore, considering the most frequent ones can help in the most appropriate approach to primary care (AU)
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Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/epidemiología , Nódulo Tiroideo/diagnóstico por imagen , Nódulo Tiroideo/epidemiología , Estudios Transversales , Estudios Retrospectivos , Colombia/epidemiología , Factores Socioeconómicos , Neoplasias de la Tiroides/patología , Nódulo Tiroideo/patología , UltrasonografíaRESUMEN
Iberian lacustrine sediments are a valuable archive to document environmental changes since the last glacial termination, seen as key for anticipating future climate/environmental changes and their far-reaching implications for generations to come. Herein, multi-proxy-based indicators of a mountain lake record from Serra da Estrela were used to reconstruct atmospheric (in)fluxes and associated climatic/environmental changes over the last â¼13.5 ka. Depositions of long-range transported dust (likely from the Sahara) and halogens (primarily derived from seawater) were higher for the pre-Holocene, particularly in the late Bølling-Allerød-Younger Dryas period, compared to the Holocene. This synchronous increase could be related to a recognized dust-laden atmosphere, along with the combined effect of (i) an earlier proposed effective transport of Sahara dust for higher latitudes during cold periods and (ii) the progressive Polar Front expansion southwards, with the amplification of halogen activation reactions in lower latitudes due to greater closeness to snow/sea ice (halide-laden) surfaces. Additionally, the orographic blocking of Serra da Estrela may have played a critical role in increasing precipitation of Atlantic origin at higher altitudes, with the presence of snow prompting physical and chemical processes involving halogen species. In the Late Holocene, the dust proxy records highlighted two periods of enhanced input to Lake Peixão, the first (â¼3.5-2.7 ka BP) after the end of the last African Humid Period and the second, from the 19th century onwards, agreeing with the advent of commercial agriculture, and human contribution to land degradation and dust emission in the Sahara/Sahel region. The oceanic imprints throughout the Holocene matched well with North Atlantic rapid climatic changes that, in turn, coincided with ice-rafted debris or Bond events and other records of increased storminess for the European coasts. Positive parallel peaks in halogens were found in recent times, probably connected to fire extinction by halogenated alkanes and roadway de-icing.
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OBJECTIVES: Paid leave is essential for public health in order to prevent presenteeism (i.e., working while sick), provide an economic safety net for workers when ill, and promote family well-being through parental leave. While racial and ethnic disparities in unmet paid leave (or needing but not being able to take paid leave) are well documented, little evidence of the intersecting role of citizenship status exists. This study examined disparities in unmet paid leave across race, ethnicity and citizenship status. STUDY DESIGN: This was a cross-sectional study of employed adults in California, USA. METHODS: Weighted, multivariable logistic regressions were used to assess disparities in unmet needed paid leave across race, ethnicity and citizenship status categories, including non-citizen, naturalised, and citizen Latinx and Asian respondents, and naturalised and non-citizen White respondents, relative to US-born White respondents, controlling for demographic, familial, health-related and work-related covariates. This study examined a representative sample of Californian adults using the 2021 California Health Interview Survey (CHIS). A total of 24,453 people completed the CHIS from March to October 2021. This analysis was restricted to individuals who had complete data, were employed at the time of the survey and were part of the study race and ethnic groups of interest, leading to an analytical sample of 12,485 respondents. RESULTS: While 16.9% of employed Californians reported forgoing needed paid leave, disparities across race, ethnicity and citizenship status were evident. Specifically, 31.8% of non-citizen Latinx respondents, compared to 11% of US-born White respondents, did not use paid leave when they needed it due to fear of job loss, fear of negative impacts on job advancement, employers denying it, lack of information or knowledge regarding the process or ineligibility. In the fully adjusted analyses, respondents identifying as non-citizen Latinx (adjusted odds ratio [aOR] = 2.57, 95% confidence interval [CI] = 1.94-3.40), naturalised Latinx (aOR = 1.90, 95% CI = 1.46-2.48), US-born Latinx (OR = 1.30, 95% CI = 1.06-1.60), non-citizen Asian (aOR = 2.34, 95% CI = 1.69-3.23) and naturalised Asian (aOR = 1.78, 95% CI = 1.35-2.34) had a statistically significantly higher likelihood of experiencing unmet needed paid leave compared to US-born White respondents. CONCLUSIONS: Despite its importance for health, disparities across race, ethnicity and citizenship status exist in those who experience unmet paid leave. It is recommended that the administrative and enforcement agencies in California further communicate eligibility, facilitate the application process and enforce equitable access to paid leave for all workers.
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Empleo , Etnicidad , Hispánicos o Latinos , Salarios y Beneficios , Adulto , Humanos , Ciudadanía , Estudios Transversales , Necesidades y Demandas de Servicios de Salud , Asiático , BlancoRESUMEN
INTRODUCTION: Cerebral amyloid angiopathy-related inflammation (CAA-ri) is an entity characterised by an inflammatory response to ß-amyloid deposition in the walls of cerebral microvessels. METHODS: We conducted a retrospective review of a series of patients with a diagnosis of CAA-ri according to histopathological study findings or clinical-radiological diagnostic criteria. RESULTS: The study included 7 patients (5 men) with a mean age of 79 years. Disease onset was acute or subacute in 6 patients. The most frequent symptoms were cognitive impairment (nâ¯=â¯6), behavioural alterations (nâ¯=â¯5), epileptic seizures (nâ¯=â¯5), focal neurological signs (nâ¯=â¯4), and headache (nâ¯=â¯2). Cerebrospinal fluid was abnormal in 3 patients (lymphocytic pleocytosis and high protein levels). The most frequent MRI findings were microbleeds (nâ¯=â¯7), subcortical white matter hyperintensities on T2-FLAIR sequences (nâ¯=â¯7), and leptomeningeal enhancement (nâ¯=â¯6). Lesions were bilateral in 3 patients and most frequently involved the parieto-occipital region (nâ¯=â¯5). Amyloid PET studies were performed in 2 patients, one of whom showed pathological findings. Two patients underwent brain biopsy, which confirmed diagnosis. All patients received immunosuppressive therapy. An initially favourable clinical-radiological response was observed in all cases, with 2 patients presenting radiological recurrence after treatment withdrawal, with a subsequent improvement after treatment was resumed. CONCLUSIONS: Early diagnosis of CAA-ri is essential: early treatment has been shown to improve prognosis and reduce the risk of recurrence. Although a histopathological study is needed to confirm diagnosis, clinical-radiological criteria enable diagnosis without biopsy.