Clinical course of neonatal acute kidney injury: multi-center prospective cohort study.

BACKGROUND: Neonatal acute kidney injury (AKI) has been associated with unfavorable outcomes, including increased mortality. We aimed to describe the clinical course and outcomes during the first 7 days after diagnosis in newborns with AKI in three neonatal intensive care units in Popayán-Colombia. METHODS: Multi-center prospective cohort study conducted between June 2019 and December 2020 in three NICUs after ethical approval. We included newborns between 2 and 28 days of life, first diagnosed with AKI using the KDIGO classification modified for newborns which consider increased serum creatinine values over baseline values as well as urine output over time in hours or both. Patients with chromosomal abnormalities, major kidney malformations, and complex congenital heart disease were excluded. Patients were followed for up to 7 days after diagnosis and the maximum KDIGO stage, recovery of kidney function, need for renal replacement therapy and cumulative incidence of death were evaluated. RESULTS: Over the 18 months of the study, 4132 newborns were admitted to the NICUs, and 93 patients (2.25, 95% CI 1.82-2.75%) developed neonatal AKI. 59.1% of the newborns were premature and there were no differences in severity according to gestational age. During follow-up, the maximum KDIGO was 64.5% for AKI-stage 1, 11.8% for AKI-stage 2, and 23.7% for AKI-stage 3. Kidney function recovery was higher in AKI-stage 1 patients vs. AKI-severe (AKI-stage 2 and 3) (95% vs. 48.5%). Five patients (5.4%) received renal replacement therapy and 15 died (16.1%), four in AKI-stage 1 vs. 11 in AKI-severe (6.7% vs 33.3%). CONCLUSIONS: Newborns admitted to the NICUs can develop AKI regardless of gestational age, and it is more frequent between the second and ninth days of life. More patients whit AKI-stage 1 recover and die less than those in a severe stage.

Perspectives of intensive care nurses on open visits in an ICU.

OBJECTIVE: To determine the attitude of the nursing professionals of an Intensive Care Unit regarding the effects of open visiting on the daily activities of the patient, their family and professionals, and also to determine their contribution to the current open visiting policy. METHOD: A cross-sectional descriptive study was performed, with a non-probabilistic discretionary sampling. The sample comprised nursing professionals of the aforementioned Unit. They were given a questionnaire with 26 items and an open question to evaluate their suggestions. RESULTS: 101 nursing professionals took part in the study, of the 120 working in the Unit under study. Seventy-five point two percent state that the nursing team has to postpone or modify their work due to the presence of the family and 89.9% that their presence produces a physical and psychological burden on the staff. Eighty percent think that the visit exhausts the family and 84.2% that the family feels obliged to remain with the patient. Ninety-four percent think that the effect of the presence of the family depends on the patient and the family. CONCLUSIONS: Most of professionals have a negative opinion about the policy of open visits, showing some reluctance when it comes to flexible visiting hours, although they admit that an unrestricted schedule in this type of units implies some benefit for the patient and the family.

Perspectives of intensive care nurses on open visits in an ICU. / Perspectivas de los profesionales de enfermería de cuidados intensivos sobre las visitas abiertas en una UCI.

OBJECTIVE: To determine the attitude of the nursing professionals of an Intensive Care Unit regarding the effects of open visiting on the daily activities of the patient, their family and professionals, and also to determine their contribution to the current open visiting policy. METHOD: A cross-sectional descriptive study was performed, with a non-probabilistic discretionary sampling. The sample comprised nursing professionals of the aforementioned Unit. They were given a questionnaire with 26 items and an open question to evaluate their suggestions. RESULTS: 101 nursing professionals took part in the study, of the 120 working in the Unit under study. Seventy-five point two percent state that the nursing team has to postpone or modify their work due to the presence of the family and 89.9% that their presence produces a physical and psychological burden on the staff. Eighty percent think that the visit exhausts the family and 84.2% that the family feels obliged to remain with the patient. Ninety-four percent think that the effect of the presence of the family depends on the patient and the family. CONCLUSIONS: Most of professionals have a negative opinion about the policy of open visits, showing some reluctance when it comes to flexible visiting hours, although they admit that an unrestricted schedule in this type of units implies some benefit for the patient and the family.

Machine learning applied to atopic dermatitis transcriptome reveals distinct therapy-dependent modification of the keratinocyte immunophenotype.

BACKGROUND: Atopic dermatitis (AD) arises from a complex interaction between an impaired epidermal barrier, environmental exposures, and the infiltration of T helper (Th)1/Th2/Th17/Th22 T cells. Transcriptomic analysis has advanced our understanding of gene expression in cells and tissues. However, molecular quantitation of cytokine transcripts does not predict the importance of a specific pathway in AD or cellular responses to different inflammatory stimuli. OBJECTIVES: To understand changes in keratinocyte transcriptomic programmes in human cutaneous disease during development of inflammation and in response to treatment. METHODS: We performed in silico deconvolution of the whole-skin transcriptome. Using co-expression clustering and machine-learning tools, we resolved the gene expression of bulk skin (seven datasets, n = 406 samples), firstly, into keratinocyte phenotypes identified by unsupervised clustering and, secondly, into 19 cutaneous cell signatures of purified populations from publicly available datasets. RESULTS: We identify three unique transcriptomic programmes in keratinocytes - KC1, KC2 and KC17 - characteristic of immune signalling from disease-associated Th cells. We cross-validate those signatures across different skin inflammatory conditions and disease stages and demonstrate that the keratinocyte response during treatment is therapy dependent. Broad-spectrum treatment with ciclosporin ameliorated the KC17 response in AD lesions to a nonlesional immunophenotype, without altering KC2. Conversely, the specific anti-Th2 therapy, dupilumab, reversed the KC2 immunophenotype. CONCLUSIONS: Our analysis of transcriptomic signatures in cutaneous disease biopsies reveals the effect of keratinocyte programming in skin inflammation and suggests that the perturbation of a single axis of immune signal alone may be insufficient to resolve keratinocyte immunophenotype abnormalities.

SLX4 interacts with RTEL1 to prevent transcription-mediated DNA replication perturbations.

The SLX4 tumor suppressor is a scaffold that plays a pivotal role in several aspects of genome protection, including homologous recombination, interstrand DNA crosslink repair and the maintenance of common fragile sites and telomeres. Here, we unravel an unexpected direct interaction between SLX4 and the DNA helicase RTEL1, which, until now, were viewed as having independent and antagonistic functions. We identify cancer and Hoyeraal-Hreidarsson syndrome-associated mutations in SLX4 and RTEL1, respectively, that abolish SLX4-RTEL1 complex formation. We show that both proteins are recruited to nascent DNA, tightly co-localize with active RNA pol II, and that SLX4, in complex with RTEL1, promotes FANCD2/RNA pol II co-localization. Importantly, disrupting the SLX4-RTEL1 interaction leads to DNA replication defects in unstressed cells, which are rescued by inhibiting transcription. Our data demonstrate that SLX4 and RTEL1 interact to prevent replication-transcription conflicts and provide evidence that this is independent of the nuclease scaffold function of SLX4.

Publisher Correction: SLX4 interacts with RTEL1 to prevent transcription-mediated DNA replication perturbations.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Author Correction: SLX4 interacts with RTEL1 to prevent transcription-mediated DNA replication perturbations.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

[Congenital radial head dislocation: report of two cases]. / Luxación congénita de cabeza radial: reporte de dos casos.

INTRODUCTION: Congenital dislocation of the Radial head is a condition that has been described in a few cases in the international literature, the anterior and lateral dislocation were the less frequent forms of presentation with 15% of cases, each, and the posterior dislocation the most frequent with 70% of the total cases reported. However, this pathology is considered the most frequent congenital pathology of the elbow in children. The present study describes the case of a patient with congenital dislocation of elbow anterior variety and another case with dislocation lateral variety, both diagnosed at an early age, in which it has been decided for conservative management and an annual follow-up. A bibliographic review of the subject is also carried out. DISCUSSION: The congenital elbow dislocation usually has a benign evolution, being painless and not very limiting for the patient, so it can be managed conservatively. Pain and limited movement are indicative of surgical treatment. There are multiple surgical treatments for this entity, however they are not widely accepted due to the complications and poor results presented by them.

INTRODUCCIÓN: La luxación congénita de cabeza radial es un padecimiento que se ha descrito en contados casos en la literatura internacional, siendo la luxación anterior y lateral las formas de presentación menos frecuentes con 15% de los casos cada una y la luxación posterior la más frecuente con 70% del total de los casos reportados. Sin embargo, esta patología es considerada la patología congénita más frecuente del codo en el niño. Se presenta el caso de un paciente con luxación congénita de codo variedad anterior y otro caso con luxación variedad lateral, ambos diagnosticados a temprana edad, en los que se decidió realizar un manejo conservador y un seguimiento anual. Asimismo, se hizo una revisión bibliográfica del tema. DISCUSIÓN: La luxación congénita de codo tiene por lo general una evolución benigna, siendo indolora y poco limitante para el paciente, por lo que puede ser manejada de manera conservadora. El dolor y la limitación de movimientos son indicativos de un tratamiento quirúrgico; sin embargo, no son ampliamente aceptados debido a las complicaciones y resultados deficientes que presentan.

Manejo ortopédico de la esclerodermia lineal localizada en niños: reporte de un caso / Orthopedic management of localized linear scleroderma in children: a case report

Resumen: Introducción: La esclerodermia localizada es la forma de presentación de esclerosis más frecuente en niños; tiene una incidencia de 2.7 por cada 100,000 habitantes, con predilección por la raza caucásica y el sexo femenino con relación de 2.4 a 4.1 por cada varón. El común denominador es la afección a nivel de tejido conectivo, genera una variedad de presentación clínica que va desde placas escleróticas localizadas circunscritas que afectan la piel hasta afecciones más profundas que atacan al tejido muscular y óseo, dejando secuelas estéticas y/o deformidades incapacitantes en el paciente. Objetivo: Presentación de caso y su manejo quirúrgico. Los datos expuestos se obtuvieron del expediente clínico físico y electrónico, entrevista directa con paciente y familiares y seguimiento y valoración de estudios radiográficos, desde Enero de 2012 hasta Noviembre de 2017. Discusión: El tratamiento quirúrgico está indicado cuando las deformidades y contracturas condicionan incapacidad en el paciente. Los mejores resultados se obtendrán una vez que la enfermedad haya dejado de progresar.

Abstract: Introduction: Localized scleroderma is the most common form of sclerosis in children; it has an incidence of 2.7 per 100,000 inhabitants, with a predilection for the Caucasian and female races of 2.4 to 4.1 per male. The common denominator is the connective tissue-level condition, causing a variety of clinical presentation ranging from localized sclerotic circumscribed plaques affecting the skin, to deeper conditions that attack muscle and bone tissue, leaving aesthetic consequences and/or disabling deformities in the patient. Objective: Case presentation and surgical management. The data presented were obtained from the physical and electronic clinical record, direct interview with patients and family members and monitoring and evaluation of radiographic studies, from January 2012 to November 2017. Discussion: Surgical treatment is indicated when deformities and contractures condition incapacity in the patient. The best results will be obtained once the disease has stopped progressing.

Switching to dual antiretroviral regimens is associated with improvement or no changes in activation and inflammation markers in virologically suppressed HIV-1-infected patients: the TRILOBITHE pilot study.

OBJECTIVES: While the use of dual antiretroviral therapies could reduce the toxicity of antiretroviral treatment in treatment-experienced HIV-1-infected patients, it is crucial to know if reducing the number of drugs could lead to an adverse increase in inflammation and activation markers. METHODS: This was a cross-sectional pilot study conducted at the HIV-1 Unit at the Tertiary University Hospital in Madrid, Spain, evaluating biomarkers of activation [interferon-γ-induced protein 10 (IP10), high-sensitivity C-reactive protein (hs-CRP), soluble CD14 (sCD14) and sCD163], inflammation [interleukin-6 (IL-6)], blood coagulation (d-dimer), and immune response [interferon (IFN)-γ, tumour necrosis factor (TNF)-α and IL-4] in three groups of suppressed HIV-1-infected patients: patients continuing on triple therapy (26 patients), and patients who switched from triple to dual therapy, at 24 or 48 weeks after switching (13 and 36 patients, respectively). RESULTS: Demographic and immunovirological parameters were similar in the three groups of patients. IL-6 and sCD14 levels were lower in patients at 48 weeks after switching to dual therapy compared with those found in patients who continued to receive triple therapy (P = 0.012 and P = 0.001, respectively), with no differences in the levels of the remaining biomarkers. Among patients with nadir CD4 count ≤ 200 cells/µL, sCD14 levels were lower in patients who had been on dual therapy for 48 weeks (14 patients) compared with those found in patients who received ongoing triple therapy (11 patients; P = 0.029), with no differences in the levels of the other biomarkers. CONCLUSIONS: HIV-1-infected patients receiving dual regimens showed similar or even lower levels of inflammatory and activation markers compared with those found in patients who received ongoing triple therapy. Of note, similar data were obtained in patients with low nadir CD4 count.

Luxación congénita de cabeza radial: reporte de dos casos / Congenital radial Head dislocation: report of two cases

Resumen: Introducción: La luxación congénita de cabeza radial es un padecimiento que se ha descrito en contados casos en la literatura internacional, siendo la luxación anterior y lateral las formas de presentación menos frecuentes con 15% de los casos cada una y la luxación posterior la más frecuente con 70% del total de los casos reportados. Sin embargo, esta patología es considerada la patología congénita más frecuente del codo en el niño. Se presenta el caso de un paciente con luxación congénita de codo variedad anterior y otro caso con luxación variedad lateral, ambos diagnosticados a temprana edad, en los que se decidió realizar un manejo conservador y un seguimiento anual. Asimismo, se hizo una revisión bibliográfica del tema. Discusión: La luxación congénita de codo tiene por lo general una evolución benigna, siendo indolora y poco limitante para el paciente, por lo que puede ser manejada de manera conservadora. El dolor y la limitación de movimientos son indicativos de un tratamiento quirúrgico; sin embargo, no son ampliamente aceptados debido a las complicaciones y resultados deficientes que presentan.

Abstract: Introduction: Congenital dislocation of the Radial head is a condition that has been described in a few cases in the international literature, the anterior and lateral dislocation were the less frequent forms of presentation with 15% of cases, each, and the posterior dislocation the most frequent with 70% of the total cases reported. However, this pathology is considered the most frequent congenital pathology of the elbow in children. The present study describes the case of a patient with congenital dislocation of elbow anterior variety and another case with dislocation lateral variety, both diagnosed at an early age, in which it has been decided for conservative management and an annual follow-up. A bibliographic review of the subject is also carried out. Discussion: The congenital elbow dislocation usually has a benign evolution, being painless and not very limiting for the patient, so it can be managed conservatively. Pain and limited movement are indicative of surgical treatment. There are multiple surgical treatments for this entity, however they are not widely accepted due to the complications and poor results presented by them.

[Orthopedic management of localized linear scleroderma in children: a case report]. / Manejo ortopédico de la esclerodermia lineal localizada en niños: reporte de un caso.

INTRODUCTION: Localized scleroderma is the most common form of sclerosis in children; it has an incidence of 2.7 per 100,000 inhabitants, with a predilection for the Caucasian and female races of 2.4 to 4.1 per male. The common denominator is the connective tissue-level condition, causing a variety of clinical presentation ranging from localized sclerotic circumscribed plaques affecting the skin, to deeper conditions that attack muscle and bone tissue, leaving aesthetic consequences and/or disabling deformities in the patient. OBJECTIVE: Case presentation and surgical management. The data presented were obtained from the physical and electronic clinical record, direct interview with patients and family members and monitoring and evaluation of radiographic studies, from January 2012 to November 2017. DISCUSSION: Surgical treatment is indicated when deformities and contractures condition incapacity in the patient. The best results will be obtained once the disease has stopped progressing.

INTRODUCCIÓN: La esclerodermia localizada es la forma de presentación de esclerosis más frecuente en niños; tiene una incidencia de 2.7 por cada 100,000 habitantes, con predilección por la raza caucásica y el sexo femenino con relación de 2.4 a 4.1 por cada varón. El común denominador es la afección a nivel de tejido conectivo, genera una variedad de presentación clínica que va desde placas escleróticas localizadas circunscritas que afectan la piel hasta afecciones más profundas que atacan al tejido muscular y óseo, dejando secuelas estéticas y/o deformidades incapacitantes en el paciente. OBJETIVO: Presentación de caso y su manejo quirúrgico. Los datos expuestos se obtuvieron del expediente clínico físico y electrónico, entrevista directa con paciente y familiares y seguimiento y valoración de estudios radiográficos, desde Enero de 2012 hasta Noviembre de 2017. DISCUSIÓN: El tratamiento quirúrgico está indicado cuando las deformidades y contracturas condicionan incapacidad en el paciente. Los mejores resultados se obtendrán una vez que la enfermedad haya dejado de progresar.

The effect of local antibiotic prophylaxis when treating open limb fractures: A systematic review and meta-analysis.

OBJECTIVES: As well as debridement and irrigation, soft-tissue coverage, and osseous stabilization, systemic antibiotic prophylaxis is considered the benchmark in the management of open fractures and considerably reduces the risk of subsequent fracture-related infections (FRI). The direct application of antibiotics in the surgical field (local antibiotics) has been used for decades as additional prophylaxis in open fractures, although definitive evidence confirming a beneficial effect is scarce. The purpose of the present study was to review the clinical evidence regarding the effect of prophylactic application of local antibiotics in open limb fractures. METHODS: A comprehensive literature search was performed in PubMed, Web of Science, and Embase. Cohort studies investigating the effect of additional local antibiotic prophylaxis compared with systemic prophylaxis alone in the management of open fractures were included and the data were pooled in a meta-analysis. RESULTS: In total, eight studies which included 2738 patients were eligible for quantitative synthesis. The effect of antibiotic-loaded poly(methyl methacrylate) beads was investigated by six of these studies, and two studies evaluated the effect of local antibiotics applied without a carrier. Meta-analysis showed a significantly lower infection rate when local antibiotics were applied (4.6%; 91/1986) than in the control group receiving standard systemic prophylaxis alone (16.5%; 124/752) (p < 0.001) (odds ratio 0.30; 95% confidence interval 0.22 to 0.40). CONCLUSION: This meta-analysis suggests a risk reduction in FRI of 11.9% if additional local antibiotics are given prophylactically for open limb fractures. However, due to limited quality, heterogeneity, and considerable risk of bias, the pooling of data from primary studies has to be interpreted with caution.Cite this article: M. Morgenstern, A. Vallejo, M. A. McNally, T. F. Moriarty, J. Y. Ferguson, S. Nijs, WJ. Metsemakers. Bone Joint Res 2018;7:447-456. The effect of local antibiotic prophylaxis when treating open limb fractures: A systematic review and meta-analysis. DOI: 10.1302/2046-3758.77.BJR-2018-0043.R1.

In Vivo Imaging of Venous Side Cerebral Small-Vessel Disease in Older Adults: An MRI Method at 7T.

BACKGROUND AND PURPOSE: Traditional neuroimaging markers of small-vessel disease focus on late-stage changes. We aimed to adapt a method of venular assessment at 7T for use in older adults. We hypothesized that poorer venular morphologic characteristics would be related to other small-vessel disease neuroimaging markers and a higher prevalence of small-vessel disease-Alzheimer disease risk factors. MATERIALS AND METHODS: Venules were identified in periventricular ROIs on SWI and defined as tortuous or straight. The tortuosity ratio was defined as total tortuous venular length divided by total straight venular length. White matter hyperintensity burden (visually rated from 0 to 3) and the number of microbleeds (0, 1, >1) were determined. Differences in tortuous and straight venular lengths were evaluated. Relationships with demographic variables, allele producing the e4 type of apolipoprotein E (APOE4), growth factors, pulse pressure, physical activity, and Modified Mini-Mental State Examination were assessed via Spearman correlations. RESULTS: Participants had 42% more tortuous venular tissue than straight (median, 1.42; 95% CI, 1.13-1.62). APOE4 presence was associated with a greater tortuosity ratio (ρ = 0.454, P = .001), and these results were robust to adjustment for confounders and multiple comparisons. Associations of the tortuosity ratio with sex and vascular endothelial growth factor did not survive adjustment. Associations of the tortuosity ratio with other variables of interest were not significant. CONCLUSIONS: Morphologic measures of venules at 7T could be useful biomarkers of the early stages of small-vessel disease and Alzheimer disease. Longitudinal studies should examine the impact of apolipoprotein E and vascular endothelial growth factor on the risk of venular damage.

Tetraphasic polar organic chemical integrative sampler for the determination of a wide polarity range organic pollutants in water. The use of performance reference compounds and in-situ calibration.

In the present work, a homemade polar organic chemical integrative sampler (POCIS) was studied for the determination of 16 target analytes. The suitability of the combination of triphasic mixture (used in so called pesticides-POCIS) and octadecyl-functionalized silica gel (C18) as sorbent for POCIS was evaluated for the determination of alkylphenols (APs), several hormones, bisphenol-A (BPA), synthetic musk fragrances and herbicides such as trifluralin (Tri) and alachlor (Ala). With this purpose, POCIS laboratory calibration study, using a continuous-flow calibration system, was carried out in order to determine the uptake behavior and sampling rate (Rs) values for each target analyte. While the most hydrophobic compounds, (synthetic musk fragrances, some APs and Tri), showed poor linearity and low accumulation, a linear accumulation was observed for compounds whose logarithmic octanol-water partition coefficient (log Kow) ranged from 5.3 (4-tert-octylphenol, 4t-OP) to 3.1 (cis-androsterone, ADT). The Rs values obtained ranged from 0.190Lday-1 (4t-OP) to 0.042Lday-1 (BPA and equilin, EQ). The addition of C18 to the commonly used triphasic mixture increased the applicability of the POCIS sampler to compounds slightly more non-polar, such as 4t-OP. As far as we know, this is the first time that a combination of tetraphasic sorbent composed by the commercially available triphasic sorbent (Isolute ENV+polystyrene divinylbenzene and Ambersorb 1500 carbon dispersed on S-X3 Biobeads) and C18 was evaluated for passive sampling of the target analytes. The developed POCIS samplers were applied in field experiments from Halle (Germany) wastewater treatment plant (WWTP) effluent. Concerning the calculation of Rs values, the time weighted average (TWA) water concentration CWTWA values were determined considering three different approaches: (i) Rs from laboratory calibration (ii) Rs from laboratory calibration corrected with the use of performance reference compounds (PRCs) and (iii) Rs derived from field experiments or in-situ calibration. Several deuterated compounds such as, [2H3]-17ß-estradiol ([2H3]-E2), [2H4]-nonylphenol ([2H4]-NP), [2H4]-equilin ([2H4]-EQ), [2H3]-tonalide ([2H3]-AHTN) and [2H15]-musk xylene ([2H15]-MX) were also studied for their applicability as PRCs. Finally, a reasonable agreement between grab sampling and CWTWA was found when results from in-situ calibration were considered, but not when PRCs were used for correction.

The effects of prebiotics on microbial dysbiosis, butyrate production and immunity in HIV-infected subjects.

Altered interactions between the gut mucosa and bacteria during HIV infection seem to contribute to chronic immune dysfunction. A deeper understanding of how nutritional interventions could ameliorate gut dysbiosis is needed. Forty-four subjects, including 12 HIV+ viremic untreated (VU) patients, 23 antiretroviral therapy-treated (ART+) virally suppressed patients (15 immunological responders and 8 non-responders) and 9 HIV- controls (HIV-), were blindly randomized to receive either prebiotics (scGOS/lcFOS/glutamine) or placebo (34/10) over 6 weeks in this pilot study. We assessed fecal microbiota composition using deep 16S rRNA gene sequencing and several immunological and genetic markers involved in HIV immunopathogenesis. The short dietary supplementation attenuated HIV-associated dysbiosis, which was most apparent in VU individuals but less so in ART+ subjects, whose gut microbiota was found more resilient. This compositional shift was not observed in the placebo arm. Significantly, declines in indirect markers of bacterial translocation and T-cell activation, improvement of thymic output, and changes in butyrate production were observed. Increases in the abundance of Faecalibacterium and Lachnospira strongly correlated with moderate but significant increases of butyrate production and amelioration of the inflammatory biomarkers soluble CD14 and high-sensitivity C-reactive protein, especially among VU. Hence, the bacterial butyrate synthesis pathway holds promise as a viable target for interventions.

Analysis of needs of the critically ill relatives and critical care professional's opinion. / Análisis de las necesidades de la familia del paciente crítico y la opinión de los profesionales de la unidad de cuidados intensivos.

OBJECTIVE: To describe the needs of the families of patients admitted to the Intensive Care Unit (ICU) and the opinion of ICU professionals on aspects related to the presence of patient relatives in the unit. DESIGN: A prospective descriptive study was carried out between March and June 2015. SETTING: Polyvalent ICU of León University Healthcare Complex (Spain). PARTICIPANTS: Two samples of volunteers were studied: one comprising the relatives emotionally closest to the primarily non-surgical patients admitted to the Unit for over 48hours, and the other composed of ICU professionals with over three months of experience in the ICU. INTERVENTION: One self-administered questionnaire was delivered to each relative and another to each professional. MAIN VARIABLES OF INTEREST: Sociodemographic data were collected. The variables in the questionnaire for relatives comprised the information received, closeness to the patient, safety of care, the support received, and comfort. In turn, the questionnaire for professionals addressed empathy and professional relationship with the family, visiting policy, and the effect of the family upon the patient. RESULTS: A total of 59% of the relatives (35/61) answered the questionnaire. Of these subjects, 91.4% understood the information received, though 49.6% received no information on nursing care. A total of 82.9% agreed with the visiting policy applied (95.2% were patient offspring; P<.05). Participation on the part of the professionals in turn reached 76.3% (61/80). A total of 59.3% would flexibilize the visiting policy, and 78.3% considered that the family afforded emotional support for the patient, with no destabilizing effect. On the other hand, 62.3% routinely informed the family, and 88% considered training in communication skills to be needed. CONCLUSIONS: Information was adequate, though insufficient in relation to nursing care. The professionals pointed to the need for training in communication skills.

Inactivation of p53 Is Sufficient to Induce Development of Pulmonary Hypertension in Rats.

OBJECTIVE: Pulmonary artery smooth muscle cells (PA-SMCs) in pulmonary arterial hypertension (PAH) show similarities to cancer cells. Due to the growth-suppressive and pro-apoptotic effects of p53 and its inactivation in cancer, we hypothesized that the p53 pathway could be altered in PAH. We therefore explored the involvement of p53 in the monocrotaline (MCT) rat model of pulmonary hypertension (PH) and the pathophysiological consequences of p53 inactivation in response to animal treatment with pifithrin-α (PFT, an inhibitor of p53 activity). METHODS AND RESULTS: PH development was assessed by pulmonary arterial pressure, right ventricular hypertrophy and arterial wall thickness. The effect of MCT and PFT on lung p53 pathway expression was evaluated by western blot. Fourteen days of daily PFT treatment (2.2 mg/kg/day), similar to a single injection of MCT (60 mg/kg), induced PH and aggravated MCT-induced PH. In the first week after MCT administration and prior to PH development, p53, p21 and MDM2 protein levels were significantly reduced; whereas PFT administration effectively altered the protein level of p53 targets. Anti-apoptotic and pro-proliferative effects of PFT were revealed by TUNEL and MTT assays on cultured human PA-SMCs treated with 50 µM PFT. CONCLUSIONS: Pharmacological inactivation of p53 is sufficient to induce PH with a chronic treatment by PFT, an effect related to its anti-apoptotic and pro-proliferative properties. The p53 pathway was down-regulated during the first week in the rat MCT model. These in vivo experiments implicate the p53 pathway at the initiation stages of PH pathogenesis.

The A2B adenosine receptor colocalizes with adenosine deaminase in resting parietal cells from gastric mucosa.

The A2B adenosine receptor (A2BR) mediates biological responses to extracellular adenosine in a wide variety of cell types. Adenosine deaminase (ADA) can degrade adenosine and bind extracellularly to adenosine receptors. Adenosine modulates chloride secretion in gastric glands and gastric mucosa parietal cells. A close functional link between surface A2BR and ADA has been found on cells of the immune system, but whether this occurs in the gastrointestinal tract is unknown. The goal of this study was to determine whether A2BR and ADA are coexpressed at the plasma membrane of the acid-secreting gastric mucosa parietal cells. We used isolated gastric parietal cells after purification by centrifugal elutriation. The membrane fraction was obtained by sucrose gradient centrifugation. A2BR mRNA expression was analyzed by RT-PCR. The surface expression of A2BR and ADA proteins was evaluated by Western blotting, flow cytometry and confocal microscopy. Our findings demonstrate that A2BR and ADA are expressed in cell membranes isolated from gastric parietal cells. They show a high degree of colocalization that is particularly evident in the surface of contact between parietal cells. The confocal microscopy data together with flow cytometry analysis suggest a tight association between A2BR and ADA that might be specifically linked to glandular secretory function.