Airway Hyperresponsiveness, Inflammation, and Pulmonary Emphysema in Rodent Models Designed to Mimic Exposure to Fuel Oil-Derived Volatile Organic Compounds Encountered during an Experimental Oil Spill.

BACKGROUND: Fuel oil-derived volatile organic compounds (VOCs) inhalation is associated with accidental marine spills. After the Prestige petroleum tanker sank off northern Spain in 2002 and the Deepwater Horizon oil rig catastrophe in 2009, subjects involved in environmental decontamination showed signs of ongoing or residual lung disease up to 5 y after the exposure. OBJECTIVES: We aimed at investigating mechanisms driving persistent respiratory disease by developing an animal model of inhalational exposure to fuel oil-derived VOCs. METHODS: Female Wistar and Brown Norway (BN) rats and C57BL mice were exposed to VOCs produced from fuel oil mimicking the Prestige spill. Exposed animals inhaled the VOCs 2 h daily, 5 d per week, for 3 wk. Airway responsiveness to methacholine (MCh) was assessed, and bronchoalveolar lavage (BAL) and lung tissues were analyzed after the exposure and following a 2-wk washout. RESULTS: Consistent with data from human studies, both strains of rats that inhaled fuel oil-derived VOCs developed airway hyperresponsiveness that persisted after the washout period, in the absence of detectable inflammation in any lung compartment. Histopathology and quantitative morphology revealed the development of peripherally distributed pulmonary emphysema, which persisted after the washout period, associated with increased alveolar septal cell apoptosis, microvascular endothelial damage of the lung parenchyma, and inhibited expression of vascular endothelial growth factor (VEGF). DISCUSSION: In this rat model, fuel oil VOCs inhalation elicited alveolar septal cell apoptosis, likely due to DNA damage. In turn, the development of a peculiar pulmonary emphysema pattern altered lung mechanics and caused persistent noninflammatory airway hyperresponsiveness. Such findings suggest to us that humans might also respond to VOCs through physiopathological pathways different from those chiefly involved in typical cigarette smoke-driven emphysema in chronic obstructive pulmonary disease (COPD). If so, this study could form the basis for a novel disease mechanism for lasting respiratory disease following inhalational exposure to catastrophic fuel oil spills. https://doi.org/10.1289/EHP4178.

Mass Spectrometry Analysis of the Exhaled Breath Condensate and Proposal of Dermcidin and S100A9 as Possible Markers for Lung Cancer Prognosis.

INTRODUCTION: New sampling techniques to analyse lung diseases, such as exhaled breath condensate (EBC), are a breakthrough in research field since they are less invasive and less traumatic for the patients compared to lung biopsies. Nevertheless, there is an increasing need to optimize not only the sampling protocols but the storage and processing of specimens to get accurate results. METHODS: Exhaled breath condensate was sampled employing the ECoScreen device. Concentrated protein was obtained after ultracentrifugation, lyophilization and reversed-phase chromatography. MALDI-time of flight (TOF)/TOF mass spectrometry (MS) was applied to determine the protein profile in EBC. Commercially available ELISA kits were used to detect the selected biomarker in the EBC after MALDI-MS proteins identification. RESULTS: The obtained EBC volume after two periods of 10 min doubled the amount obtained after 20 min. One hundred peptides were detected by MALDI-MS, and 18 proteins were identified after reversed-phase chromatography concentration. Dermcidin (P81605), S100A9 (P06702) and Cathepsin G (P08311) were selected to be analysed by ELISA. Dermcidin and S100A9 expression were statistically higher in lung cancer versus healthy volunteers. VEGF concentrations decreased, respectively, by 5.94 and 11.42-fold after 1 and 2 years of frozen EBC preservation in parallel with the declined number of proteins identified by MALDI-MS. CONCLUSION: Exhaled breath condensate analysis combined with MS technique may become a valuable method for lung cancer screening and Dermcidin and S100A9 may serve as biomarkers for lung cancer diagnosis or prognosis.

Allogeneic Adipose-Derived Mesenchymal Stem Cells (Horse Allo 20) for the Treatment of Osteoarthritis-Associated Lameness in Horses: Characterization, Safety, and Efficacy of Intra-Articular Treatment.

Osteoarthritis commonly causes lameness in the horse and has a great impact in performance animals. Due to the limitations of current medical therapies, allogenic mesenchymal stem cells (MSCs) may become an alternative method to control inflammation, reduce tissue damage and pain, and therefore improve lameness. We present the results of a regulatory clinical trial testing adipose-derived MSCs (Horse Allo 20) in veterinary (Agencia Española del Medicamento y Productos Sanitarios, Spanish Medicines Agency, Reference number 325/ECV) involving a total number of 80 participants and with 90 days of follow-up period. The manufacturing process of Horse Allo 20 was robust with no influence of the adipose tissue donor (gender, age, or breed), sample origin (intraperitoneal or subcutaneous), or storage conditions (fresh vs. frozen product presentations) on the quality, safety, and efficacy of the drug product. An in vivo safety study showed that local and systemic tolerance was safe even after repeated intra-articular administration (three injections). An in vivo efficacy study demonstrated the efficacy of the treatment after one or two injections by a reduction in lameness (P < 0.05) for an extended period of time (90 days), decreasing the need for prolonged local and/or systemic anti-inflammatory therapies and their well-known deleterious effects and toxicities.

The Opinion of Professional Caregivers About The Platform UnderstAID for Patients with Dementia.

BACKGROUND The person with dementia should be treated as an unique person regarding symptoms directly associated with dementia, such as problems with memory, hallucinations, and delusions, as well as other physical, mental, or neurological deficits. The symptoms not directly typical of dementia, such as musculoskeletal disorders or depression, should be also be considered in order to improve the quality of life of a person with dementia. That is why professional caregivers have to broaden their current knowledge not only of medical symptoms but also of the patient's psychosocial condition and increase their inquisitiveness about the individual condition of the patient. The aim of the study was to get to know the opinion of professional caregivers about the UnderstAID platform and its usefulness for informal caregivers. MATERIAL AND METHODS Participants in the study group consisted of professional caregivers: nurses, sociologists, psychologists, physiotherapists, and occupational therapists, all of whom specialized in geriatrics and had experience in working with people with dementia. All professional caregivers answered 24 questions that refer to positive and negative aspects of the UnderstAID platform. RESULTS The study group of professional caregivers highly appreciated that the application could give support to caregivers (mean score of 4.78; 5 points means that they totally agreed, and 1 point means that they totally disagreed) and that a wide range of multimedia materials helped the informal caregivers to gain a better understanding of the contents (mean score of 4.78). There was a statistically significant correlation between the age of the professional caregivers and the frequency of positive opinions that the UnderstAID application gave support to caregivers of relatives with dementia (p=0.028) and the opinion that videos, photos, and pictures may help the informal caregivers to gain a better understanding of the contents (p=0.028). CONCLUSIONS A group of professional caregivers positively assessed the UnderstAID platform. Caregivers, especially older caregivers, highly appreciated the usefulness of videos, photos, and pictures for gaining a better understanding of the contents.

UnderstAID, an ICT Platform to Help Informal Caregivers of People with Dementia: A Pilot Randomized Controlled Study.

Information and communications technology (ICT) could support ambient assisted living (AAL) based interventions to provide support to informal caregivers of people with dementia, especially when they need to cope with their feelings of overburden or isolation. An e-learning platform (understAID application) was tested by informal caregivers from Denmark, Poland, and Spain to explore the technical and the pedagogical specifications, as well as evaluating the impact of its use on the psychological status of the participants. 61 informal caregivers completed the study taking part in the experimental (n = 30) or control (n = 31) groups. 33.3% of the caregivers were satisfied with the application and around 50% of the participants assessed it as technically and pedagogically acceptable. After using understAID the caregivers in the experimental group significantly decreased their depressive symptomatology according to the Center for Epidemiologic Studies Depression scale, but a possible benefit on their feelings of competence and satisfaction with the caring experience was also observed. The low scores obtained for satisfaction were highlighting issues that need to be modified to meet the informal caregivers' needs in national, social, and cultural context. Some possible biases are also considered and discussed to be taken into account in future improvements of understAID application.

Efficacy of a computerized cognitive training application on cognition and depressive symptomatology in a group of healthy older adults: A randomized controlled trial.

OBJECTIVE: The purpose of this study was to evaluate the efficacy of a multimedia and interactive cognitive program on cognition and depressive symptomatology in healthy older adults. METHODS: Adults aged ≥65 years were randomly assigned to two groups: the experimental group in which the participants received a computerized cognitive training application; and the control group in which the participants received no intervention during the protocol. Performance on the mini-mental state examination (MMSE) and the short-form of the geriatric depression scale (GDS-SF) were analysed using a three-way repeated-measure analysis of variance. RESULTS: To determine cognition after the training, the cognitive program was used and the results were assessed using the MMSE, indicating that the significant time effects within the groups reflected the score for cognitive assessment that was significantly better after the intervention in the experimental group. No significant differences were observed with regard to the depressive symptomatology or between the groups according to sex or educational level on the two dimensions previously established (cognition and depressive symptomatology). CONCLUSION: The development of technological applications for intervention in older adults is increasing. Based on the established objective, we can conclude that the computerized intervention may constitute a good alternative to enhance the cognitive status in older people.

The impact of hearing loss on language performance in older adults with different stages of cognitive function.

PURPOSE: The possible relationship between audiometric hearing thresholds and cognitive performance on language tests was analyzed in a cross-sectional cohort of older adults aged ≥65 years (N=98) with different degrees of cognitive impairment. MATERIALS AND METHODS: Participants were distributed into two groups according to Reisberg's Global Deterioration Scale (GDS): a normal/predementia group (GDS scores 1-3) and a moderate/moderately severe dementia group (GDS scores 4 and 5). Hearing loss (pure-tone audiometry) and receptive and production-based language function (Verbal Fluency Test, Boston Naming Test, and Token Test) were assessed. RESULTS: Results showed that the dementia group achieved significantly lower scores than the predementia group in all language tests. A moderate negative correlation between hearing loss and verbal comprehension (r=-0.298; P<0.003) was observed in the predementia group (r=-0.363; P<0.007). However, no significant relationship between hearing loss and verbal fluency and naming scores was observed, regardless of cognitive impairment. CONCLUSION: In the predementia group, reduced hearing level partially explains comprehension performance but not language production. In the dementia group, hearing loss cannot be considered as an explanatory factor of poor receptive and production-based language performance. These results are suggestive of cognitive rather than simply auditory problems to explain the language impairment in the elderly.

Predictors of caregiving satisfaction in informal caregivers of people with dementia.

OBJECTIVE: The prevalence of dementia is increasing and consequently the demands from families, institutions and healthcare system. Although a substantial amount of research on caregiving has emphasized the negative aspects of caregiving, specifically on caregiver burden and depression, less attention has been paid to the positive aspects of caregiving. The aim of the present work was to study the phenomenon of caregiving satisfaction in informal caregivers of people with dementia by assessing their likely predictors. METHODS: A stress process model was used to study caregiver's satisfaction (measured using the Revised Caregiving Satisfaction Scale) on 101 informal caregivers of patients with dementia in relation to the caregiver's background and context, stress-related factors, and mediators. RESULTS: The regression model has an adjusted R(2) of 0.20, which indicates that having a consanguinity relationship with the care recipient, suffering from lower levels of subjective burden, and managing individuals with severe cognitive impairment are the most important predictors of higher caregiving satisfaction. CONCLUSION: Interventions focused on the enhancement of the caregiving satisfaction by increasing the understanding of the disease, should be especially addressed to caregivers without a consanguinity relationship and with high levels of subjective burden, and to those managing care recipients with mild or moderate stages of dementia.

Verbal fluency, naming and verbal comprehension: three aspects of language as predictors of cognitive impairment.

OBJECTIVES: To establish the possible relationship among three components of language (verbal fluency, naming and comprehension) and cognitive impairment as well as to determine the usefulness of language assessment tests to predict or monitor the development of cognitive impairment. METHOD: A comparative, descriptive and cross-sectional study was performed on 82 subjects ≥ 65 years of age who were cognitively assessed with the Mini Mental State Examination and were divided into two groups: Group A comprised of subjects classified as levels 1, 2 and 3 on the Reisberg's Global Deterioration Scale (GDS) and group B comprised of subjects at levels 4 and 5 of the GDS. Language skills were assessed by the Verbal Fluency Test, Boston Naming Test and Token Test. RESULTS: An inverse relationship between performance on language tests and cognitive impairment level was observed with a more pronounced effect observed on fluency and comprehension tests. CONCLUSION: Language assessments, especially fluency and comprehension, were good indicators of cognitive impairment. The use of these assessments as predictors of the degree of cognitive impairment is discussed in-depth.

Efficacy of a computerized cognitive training application for older adults with and without memory impairments.

BACKGROUND/AIMS: It has been shown that cognitive training might help to protect against age-related cognitive decline. Our aim was to evaluate the efficacy of a computerized cognitive training application and its near transfer effects on the cognitive status of older adults. METHODS: Performance on the 7-Minute Screen at baseline and at the end of the program was analyzed by using a pre-post design. Adults aged 55 and older (n = 101; mean age ± standard deviation: 68.97 ± 5.81 years) with and without memory impairments were trained. RESULTS: Significant improvements after the training program were found in memory, visuo-spatial and verbal fluency abilities, regardless of age, gender or education. Moreover, participants without significant memory impairments and those with Age-Associated Memory Impairment gained from the program more than subjects with mild cognitive impairment. CONCLUSION: Computerized cognitive training programs, such as Telecognitio®, may be used as a practical and valuable tool in clinic to improve cognitive status.

Determination of ELISA reproducibility to detect protein markers in exhaled breath condensate.

Exhaled breath condensate (EBC) is a representative sample from the lungs that may be used to detect different markers, but the reproducibility of these determinations is unknown over time. The aim of this paper is to assess the reproducibility of protein marker determination in EBC using samples collected at two different time points. EBC and blood were collected from 16 healthy subjects, smokers and non-smokers by using the ECoScreen device. EBC was collected on two separate occasions within ten days. Enzyme-linked immunosorbent assay (ELISA) was performed to measure angiogenesis and hypoxia markers. Blood and EBC samples were analyzed by ELISA to detect angiogenesis markers: vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and endostatin. A hypoxia marker, the anhydrase IX, was also determined. Biomarker concentration was higher in plasma samples compared to EBC. bFGF determination was higher in women (39.47 ± 3.914 versus 27.15 ± 3.145; p < 0.05). There were no significant differences among the averages of detection for any of the markers. The Bland-Altman method showed that the average of the differences or biases in EBC for every biomarker was close to zero, indicating a good reproducibility of the measurements. Nevertheless, the VEGF showed wide limits of agreement. EBC is suitable to detect biomarkers by ELISA and the measurements are reproducible over time. Nevertheless, some factors such as sex should be taken into account when analyzing the results.

[Development of a murine model of airway inflammation and remodeling in experimental asthma]. / Desarrollo de un modelo murino de inflamación y remodelación de vías respiratorias en asma experimental.

BACKGROUND AND OBJECTIVE: Experimental animal models are necessary for studying asthma disease mechanisms and for identifying new therapeutic targets. We present a murine model of experimental asthma that allows integrated, quantitative assessment of airway inflammation and remodeling. MATERIAL AND METHODS: BALB/c mice were sensitized to ovalbumin (OVA) and challenged with OVA or vehicle 3 times per week for 12 weeks. RESULTS: On bronchoalveolar lavage, the OVA-sensitized mice had significantly higher total leukocyte counts, with a median (Q25-Q75) of 670.0 cells/mL x 10(3) (376.2, 952.5) in comparison with 40.0 cells/mL x 10(3) (60.0-85.0) in controls (P=.001), and higher eosinophil and differential lymphocyte counts. In sagittal sections of lungs inflated to a standard pressure, the OVA-sensitized animals showed goblet cell hyperplasia in the respiratory epithelium (periodic acid-Schiff staining, 53.89 [36.26-62.84]cells/mm(2) vs 0.66 [0.00-1.06]cells/mm(2), P<.001), dense mononuclear and eosinophilic inflammatory infiltrates (hematoxylin-eosin, 32.87 [27.34-37.13]eosinophils/mm(2) vs 0.06 [0.00-0.20]eosinophils/mm(2), P=.002), subepithelial infiltration by mast cells (toluidine blue, 2.88 [2.00-3.28] mast cells/mm(2) vs 0.28 [0.15-0.35] mast cells/mm(2), P<.001), increased contractile tissue mass (immunofluorescence analysis for alpha-smooth-muscle actin, 2.60 [2.28-2.98] vs 1.08 [0.93-1.16], dimensionless, P<.001) and enhanced extracellular matrix deposition (Masson's trichrome, 2.18 [1.85-2.80] vs 0.50 [0.37-0.65], dimensionless, P<.001). CONCLUSIONS: Our dataset describes an experimental model of asthma which is driven by prolonged allergen exposure and in which airway inflammation and remodeling develop and are assessed together.