Loss of KEAP1 causes an accumulation of nondegradative organelles

KEAP1 is a cytoplasmic protein that functions as an adaptor for the Cullin-3-based ubiquitin E3 ligase system, which regulates the degradation of many proteins, including NFE2L2/NRF2 and p62/SQSTM1. Loss of KEAP1 leads to an accumulation of protein ubiquitin aggregates and defective autophagy. To better understand the role of KEAP1 in the degradation machinery, we investigated whether Keap1 deficiency affects the endosome-lysosomal pathway. We used KEAP1-deficient mouse embryonic fibroblasts (MEFs) and combined Western blot analysis and fluorescence microscopy with fluorometric and pulse chase assays to analyze the levels of lysosomal-endosomal proteins, lysosomal function, and autophagy activity. We found that the loss of keap1 downregulated the protein levels and activity of the cathepsin D enzyme. Moreover, KEAP1 deficiency caused lysosomal alterations accompanied by an accumulation of autophagosomes. Our study demonstrates that KEAP1 deficiency increases nondegradative lysosomes and identifies a new role for KEAP1 in lysosomal function that may have therapeutic implications

Interleukin 27 could be useful in the diagnosis of tuberculous pleural effusions

BACKGROUND: The diagnosis of tuberculous pleural effusion (TBPE) has some limitations. We studied the efficacy of interleukin-27 (IL-27) in the diagnosis of TBPE. METHODS: We measured IL-27, adenosine deaminase (ADA), ADA-2, interferon-gamma (IFNgamma), and the ADA.IL-27 and ADA-2.IL-27 products in all the pleural effusion fluids. The diagnostic yield of IL-27 was evaluated with receiver operating characteristic curves. RESULTS: Of 431 pleural effusions, 70 were tuberculous, 146 were neoplastic, 58 were parapneumonic, 28 were empyemas, 88 were transudates, and 41 were other types. With a cutoff point of 0.55 ng/mL, IL-27 had a sensitivity of 91.4% and a specificity of 85.1%, which were significantly less than ADA, ADA-2, IFNgamma, ADA.IL-27, or ADA-2.IL-27. The area under the receiver operating characteristic curve for IL-27 (0.963) was also significantly lower than that for the other markers, except for IFNgamma. However, IL-27 improved the sensitivity of ADA and ADA-2 through ADA.IL-27 and ADA-2.IL-27 products (100% for both). CONCLUSIONS: IL-27 is less efficient than ADA and ADA-2 in the diagnosis of TBPE. However, ADA.IL-27 and ADA-2.IL-27 improve the diagnostic sensitivity of ADA and ADA-2, and thus could be useful in situations of high clinical suspicion and low ADA level. A value above the cutoff point of the latter is practically diagnostic of TBPE

Immunomodulatory properties of carvone inhalation and Its effects on contextual fear memory in mice

A complex network of interactions exists between the immune, the olfactory, and the central nervous system (CNS). Inhalation of different fragrances can affect immunological reactions in response to an antigen but also may have effects on the CNS and cognitive activity. We performed an exploratory study of the immunomodulatory ability of a series of compounds representing each of the 10 odor categories or clusters described previously. We evaluated the impact of each particular odor on the immune response after immunization with the model antigen ovalbumin in combination with the TLR3 agonist poly I:C. We found that some odors behave as immunostimulatory agents, whereas others might be considered as potential immunosuppressant odors. Interestingly, the immunomodulatory capacity was, in some cases, strain-specific. In particular, one of the fragrances, carvone, was found to be immunostimulatory in BALB/c mice and immunosuppressive in C57BL/6J mice, facilitating or impairing viral clearance, respectively, in a model of a viral infection with a recombinant adenovirus. Importantly, inhalation of the odor improved the memory capacity in BALB/c mice in a fear-conditioning test, while it impaired this same capacity in C57BL/6J mice. The improvement in memory capacity in BALB/c was associated with higher CD3+ T cell infiltration into the hippocampus and increased local expression of mRNA coding for IL-1β, TNF-α, and IL-6 cytokines. In contrast, the memory impairment in C57BL/6 was associated with a reduction in CD3 numbers and an increase in IFN-γ. These data suggest an association between the immunomodulatory capacity of smells and their impact on the cognitive functions of the animals. These results highlight the potential of studying odors as therapeutic agents for CNS-related diseases

Spanish adaptation and validation of the empowerment of parents in the intensive care-neonatology (EMPATHIC-N) questionnaire

Introduction Parental satisfaction is rarely measured in the neonatal intensive care unit due to a lack of specific assessment tools. The Empowerment of Parents in The Intensive Care-Neonatology (EMPATHIC-N) questionnaire is an instrument to assess satisfaction in relation to family-centred care that has been validated in several countries, but not Spain. Objectives To perform the translation and cultural adaptation of the EMPATHIC-N to Spanish followed by its validation for the purpose of assessing satisfaction in parents with children admitted to the neonatal intensive care unit. Material and methods The questionnaire first underwent forward and backward translation and transcultural adaptation by a panel of experts through a standardized process based on the Delphi method, followed by a pilot study in 8 parents and then a cross-sectional study in the neonatal intensive care unit of a tertiary care hospital to assess the reliability and converging validity of the Spanish version. Results The study proved the comprehensibility, validity, feasibility, applicability and usefulness of the Spanish version of the EMPATHIC-N in the field of paediatric health after being evaluated by 19 professionals and 60 parents. The content validity was found to be excellent (0.93). The reliability and convergent validity of the Spanish version of the EMPHATIC-N was analysed in a sample of 65 completed questionnaires. The Cronbach α for each domain was greater than 0.7, indicating a high internal consistency. We assessed validity by analysing the correlation of the 5 domains with the with the 4 general satisfaction items. The validity was found to be adequate (rs, 0.4−0.76; P < .01). Conclusions The Spanish version of the EMPATHIC-N questionnaire is a comprehensible, useful, valid and reliable instrument to measure satisfaction in the parents of children admitted to neonatal care units

Adaptación y validación espanola ˜ del Empowerment of Parents in the Intensive Care-Neonatology (EMPATHIC-N)

Introduction Parental satisfaction is rarely measured in the neonatal intensive care unit due to a lack of specific assessment tools. The EMpowerment of PArents in THe Intensive Care-Neonatology (EMPATHIC-N) questionnaire is an instrument to assess satisfaction in relation to family-centred care that has been validated in several countries, but not Spain. Objectives To perform the translation and cultural adaptation of the EMPATHIC-N to Spanish followed by its validation for the purpose of assessing satisfaction in parents with children admitted to the neonatal intensive care unit. Material and methods The questionnaire first underwent forward and backward translation and transcultural adaptation by a panel of experts through a standardized process based on the Delphi method, followed by a pilot study in 8 parents and then a cross-sectional study in the neonatal intensive care unit of a tertiary care hospital to assess the reliability and converging validity of the Spanish version. Results The study proved the comprehensibility, validity, feasibility, applicability and usefulness of the Spanish version of the EMPATHIC-N in the field of paediatric health after being evaluated by 19 professionals and 60 parents. The content validity was found to be excellent (0.93). The reliability and convergent validity of the Spanish version of the EMPHATIC-N was analysed in a sample of 65 completed questionnaires. The Cronbach α for each domain was greater than 0.7, indicating a high internal consistency. We assessed validity by analysing the correlation of the 5 domains with the with the 4 general satisfaction items. The validity was found to be adequate (rs, 0.4-0.76; P < .01). Conclusions The Spanish version of the EMPATHIC-N questionnaire is a comprehensible, useful, valid and reliable instrument to measure satisfaction in the parents of children admitted to neonatal care units

Activation of the Fas/Fas ligand pathway in hypertensive renal disease in Dahl/Rapp rats

BACKGROUND: Hypertensive nephrosclerosis is the second most common cause of end-stage renal failure in the United States. The mechanism by which hypertension produces renal failure is incompletely understood. Recent evidence demonstrated that an unscheduled and inappropriate increase in apoptosis occurred in the Dahl/Rapp rat, an inbred strain of rat that uniformly develops hypertension and hypertensive nephrosclerosis; early correction of the hypertension prevents the renal injury. The present study examined the role of the Fas/FasL pathway in this process. METHODS: Young male Dahl/Rapp salt-sensitive (S) and Sprague-Dawley rats were fed diets that contained 0.3% or 8.0% NaCl diets. Kidneys were examined at days 7 and 21 of the study. RESULTS: An increase in Fas and FasL expression was observed in glomerular and tubular compartments of kidneys of hypertensive S rats, whereas dietary salt did not change expression of either of these molecules in normotensive Sprague-Dawley rats. Associated with this increase was cleavage of Bid and activation of caspase-8, the initiator caspase in this apoptotic pathway, by day 21 of the study. CONCLUSIONS: Augmented expression of apoptotic signaling by the Fas/FasL pathway occurred during development of end-stage renal failure in this model of hypertensive nephrosclerosis

Burden of herpes zoster requiring hospitalization in Spain during a seven-year period (1998–2004)

<p>Abstract</p> <p>Background</p> <p>A thorough epidemiological surveillance and a good understanding of the burden of diseases associated to VZV are crucial to asses any potential impact of a prevention strategy. A population-based retrospective epidemiological study to estimate the burden of herpes zoster requiring hospitalization in Spain was conducted.</p> <p>Methods</p> <p>This study was conducted by using data from the national surveillance system for hospital data, Conjunto Mínimo Básico de Datos (CMBD). Records of all patients admitted to hospital with a diagnosis of herpes zoster (ICD-9-MC codes 053.0–053.9) during a 7-year period (1998–2004) were selected.</p> <p>Results</p> <p>A total of 23,584 hospitalizations with a primary or secondary diagnosis of herpes zoster in patients ≥ 30 years of age were identified during the study period. Annually there were 13.4 hospitalizations for herpes zoster per 100,000 population in patients ≥ 30 years of age. The rate increases with age reaching a maximum in persons ≥ 80 years of age (54.3 admissions per 100,000 population >80 years of age). The mean cost of a hospitalization for herpes zoster in adult patients was 3,720 €. The estimated annual cost of hospitalizations for herpes zoster in patients ≥ 30 years of age in Spain was 12,731,954 €.</p> <p>Conclusion</p> <p>Herpes zoster imposes an important burden of hospitalizations and result in large cost expenses to the Spanish National Health System, especially in population older than 50 years of age</p

Real-time incidence of travel-related symptoms through a smartphone-based app remote monitoring system: a pilot study

Trip Doctor(R), a Smartphone-based app monitoring system, was developed to detect infections among travelers in real-time. For testing, 106 participants were recruited (62.2% male, mean age 36 years (SD = 11)). Majority of trips were for tourism and main destinations were in South East Asia. Mean travel duration was 14 days (SD = 10). Diarrhea was the most frequently reported symptom (15.5%). The system demonstrated adequate usability and is ready to be used on a larger scale

Small Bowel Enteroscopy - A Joint Clinical Guideline by the Spanish and Portuguese Small-Bowel Study Groups

The present evidence-based guidelines are focused on the use of device-assisted enteroscopy in the management of small-bowel diseases. A panel of experts selected by the Spanish and Portuguese small-bowel study groups reviewed the available evidence focusing on the main indications of this technique, its role in the management algorithm of each indication, and its diagnostic and therapeutic yield. A set of recommendations was issued accordingly.info:eu-repo/semantics/publishedVersio