Could a Tailored Exercise Intervention for Hospitalised Older Adults Have a Role in the Resolution of Delirium? Secondary Analysis of a Randomised Clinical Trial.

Delirium is a transient neurocognitive disorder. Nonpharmacological measures can be efficient in reducing the incidence and intensity of delirium, but there is a paucity of evidence when using a physical exercise program exclusively. This was a secondary analysis of a randomised clinical trial that provided evidence on the functional and cognitive benefits of an individualised exercise intervention in hospitalised older adults. Of the 370 patients who participated in the trial, 17.1% in the intervention group had delirium and 12.1% in the control group. After the exercise intervention, 84.6% of the patients in the intervention group showed improvement in delirium compared to 68.4% of patients in the control group. Despite the fluctuating nature of delirium,we show that it is feasible to establish individualised exercise interventions in hospitalised geriatric patients in the periods when patients are able to cooperate. Baseline functional status, measured by the Barthel Index, is a clinical marker that could help to identify those who will benefit most.

Vaginal neutrophil infiltration is contingent on ovarian cycle phase and independent of pathogen infection.

The mucosa of the female reproductive tract must reconcile the presence of commensal microbiota and the transit of exogenous spermatozoa with the elimination of sexually transmitted pathogens. In the vagina, neutrophils are the principal cellular arm of innate immunity and constitute the first line of protection in response to infections or injury. Neutrophils are absent from the vaginal lumen during the ovulatory phase, probably to allow sperm to fertilize; however, the mechanisms that regulate neutrophil influx to the vagina in response to aggressions remain controversial. We have used mouse inseminations and infections of Neisseria gonorrhoeae, Candida albicans, Trichomonas vaginalis, and HSV-2 models. We demonstrate that neutrophil infiltration of the vaginal mucosa is distinctively contingent on the ovarian cycle phase and independent of the sperm and pathogen challenge, probably to prevent sperm from being attacked by neutrophils. Neutrophils extravasation is a multi-step cascade of events, which includes their adhesion through selectins (E, P and L) and integrins of the endothelial cells. We have discovered that cervical endothelial cells expressed selectin-E (SELE, CD62E) to favor neutrophils recruitment and estradiol down-regulated SELE expression during ovulation, which impaired neutrophil transendothelial migration and orchestrated sperm tolerance. Progesterone up-regulated SELE to restore surveillance after ovulation.

Efficacy of Antiresorptive Treatment in Osteoporotic Older Adults: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

OBJECTIVES: To investigate concerns surrounding the benefits of antiresorptive drugs in older adults, a systematic review was carried out to evaluate the efficacy of these treatments in the prevention of osteoporotic hip fractures in older adults. DESIGN: a systematic review and meta-analysis of randomized clinical trials. SETTING AND PARTICIPANTS: older adults ≥65 years with osteoporosis, with or without a previous fragility fracture. Studies with cancer-related and corticosteroid-induced osteoporosis, participants <65 years and no reported hip fracture were not included. METHODS: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ISI Web of Science and Scopus databases were searched. The primary outcome was hip fracture, and subgroup analysis (≥75 years, with different drug types and secondary prevention) and sensitivity analysis was carried out using a GRADE evaluation. Secondary outcomes were any type of fractures, vertebral fracture, bone markers and adverse events. The risk of bias was assessment with the Cochrane risk of bias tool. RESULTS: A total of 12 randomised controlled trials (RCTs) qualified for this meta-analysis, with 36,196 participants. Antiresorptive drugs have a statistically significant effect on the prevention of hip fracture (RR=0.70; 95%CI 0.60 to 0.81), but with a moderate GRADE quality of evidence and a high number needed to treat (NNT) of 186. For other outcomes, there is a statistically significant effect, but with a low to moderate quality of evidence. Antiresorptives showed no reduction in the risk of hip fracture in people ≥75 years. The results for different drug types, secondary prevention and sensitivity analysis are similar to the main analyses and have the same concerns. CONCLUSIONS: Antiresorptive drugs have a statistically significant effect on preventing hip fracture but with a moderate quality (unclear/high risk of bias) and high NNT (186). This small benefit disappears in those ≥75 years, but increases in secondary prevention. More RCTs in very old osteoporotic adults are needed.

Cobalamin cbiP mutant shows decreased tolerance to low temperature and copper stress in Listeria monocytogenes.

BACKGROUND: Listeria monocytogenes is a foodborne pathogen that causes listeriosis in humans. This pathogen activates multiple regulatory mechanisms in response to stress, and cobalamin biosynthesis might have a potential role in bacterial protection. Low temperature is a strategy used in the food industry to control bacteria proliferation; however, L. monocytogenes can grow in cold temperatures and overcome different stress conditions. In this study we selected L. monocytogenes List2-2, a strain with high tolerance to the combination of low temperature + copper, to understand whether the cobalamin biosynthesis pathway is part of the tolerance mechanism to this stress condition. For this, we characterized the transcription level of three cobalamin biosynthesis-related genes (cbiP, cbiB, and cysG) and the eutV gene, a transcriptional regulator encoding gene involved in ethanolamine metabolism, in L. monocytogenes strain List2-2 growing simultaneously under two environmental stressors: low temperature (8 °C) + copper (0.5 mM of CuSO4 × 5H2O). In addition, the gene cbiP, which encodes an essential cobyric acid synthase required in the cobalamin pathway, was deleted by homologous recombination to evaluate the impact of this gene in L. monocytogenes tolerance to a low temperature (8 °C) + different copper concentrations. RESULTS: By analyzing the KEGG pathway database, twenty-two genes were involved in the cobalamin biosynthesis pathway in L. monocytogenes List2-2. The expression of genes cbiP, cbiB, and cysG, and eutV increased 6 h after the exposure to low temperature + copper. The cobalamin cbiP mutant strain List2-2ΔcbiP showed less tolerance to low temperature + copper (3 mM) than the wild-type L. monocytogenes List2-2. The addition of cyanocobalamin (5 nM) to the medium reverted the phenotype observed in List2-2ΔcbiP. CONCLUSION: These results indicate that cobalamin biosynthesis is necessary for L. monocytogenes growth under stress and that the cbiP gene may play a role in the survival and growth of L. monocytogenes List2-2 at low temperature + copper.

A comprehensive approach using multiple biomarkers to detect damage induced by pesticides in broad-snouted caiman (Caiman latirostris) under ex-situ conditions.

Caiman latirostris is one of the two species of the order Crocodylia that inhabit Argentina and is considered a species of vital ecological and economic importance in the north-east of Argentina. In this region, pesticides are the most common contaminants in natural environments and wild caiman populations are subject to this contamination constantly. The aim of this study was to evaluate the effects the main pesticides used in the region: glyphosate (GLY), cypermethrin (CYP) and chlorpyrifos (CPF) -based formulations, as well as the mixture of them, on C. latirostris juveniles under semi-controlled condition of exposure (ex-situ) during 75 days. One hundred yearling caimans (10-month-old) were equally distributed into five experimental groups (20 animals per group): a negative control (NC -tap water), GLY 2% (Roundup® Full II formulation -RU), CYP 0.12% (Atanor® formulation), CPF 0.8% (Lorsban® formulation), and a mixture of the three pesticides (Mx3: GLY 2% + CYP 0.12% + CPF 0.8%). We applied early warning biomarkers to detect damage induced by these chemicals in peripheral blood: activity of the antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD), analysis of lipid peroxidation (LPO) by the thiobarbituric acid reactive substances (TBARS), DNA damage and specific base oxidation through the standard and modified comet assay (CA), chromosome damage by micronucleus (MN) test and other nuclear abnormalities (NAs), hematological and growth parameters. Results showed a statistically significant increase in MN and NAs frequency, DNA damage, with an important contribution of base oxidation for all exposed groups compared to the NC. Total white blood cells count (TWBCC), and growth parameters showed effects mainly at the Mx3. The principal component analysis (PCA) demonstrated more sensitivity for biomarkers associated to genetic damage, including base oxidation to DNA than LPO, antioxidant enzyme modulation, immunotoxicity or growth parameters, to detect pesticides effects, applied under conditions similar to that found in natural environments.

Cobalamin cbiP mutant shows decreased tolerance to low temperature and copper stress in Listeria monocytogenes

BACKGROUND: Listeria monocytogenes is a foodborne pathogen that causes listeriosis in humans. This pathogen activates multiple regulatory mechanisms in response to stress, and cobalamin biosynthesis might have a potential role in bacterial protection. Low temperature is a strategy used in the food industry to control bacteria proliferation; however, L. monocytogenes can grow in cold temperatures and overcome different stress conditions. In this study we selected L. monocytogenes List2-2, a strain with high tolerance to the combination of low temperature +copper, to understand whether the cobalamin biosynthesis pathway is part of the tolerance mechanism to this stress condition. For this, we characterized the transcription level of three cobalamin biosynthesis related genes ( cbiP , cbiB, and cysG ) and the eutV gene, a transcriptional regulator encoding gene involved in ethanolamine metabolism, in L. monocytogenes strain List2-2 growing simultaneously under two environmental stressors: low temperature (8 °C) +copper (0.5 mM of CuSO4 ×5H2O). In addition, the gene cbiP , which encodes an essential cobyric acid synthase required in the cobalamin pathway, was deleted by homologous recombination to evaluate the impact of this gene in L. monocytogenes tolerance to a low temperature (8 °C) +different copper concentrations. RESULTS: By analyzing the KEGG pathway database, twenty-two genes were involved in the cobalamin biosynthesis pathway in L. monocytogenes List2-2. The expression of genes cbiP , cbiB, and cysG, and eutV increased 6 h after the exposure to low temperature +copper. The cobalamin cbiP mutant strain List2-2Δ cbiP showed less tolerance to low temperature +copper (3 mM) than the wild type L. monocytogenes List2-2. The addition of cyanocobalamin (5 nM) to the medium reverted the phenotype observed in List2-2Δ cbiP . CONCLUSION: These results indicate that cobalamin biosynthesis is necessary for L. monocytogenes growth under stress and that the cbiP gene may play a role in the survival and growth of L. monocytogenes List2-2 at low temperature +copper.

Biomechanical consequences of compromised elastic fiber integrity and matrix cross-linking on abdominal aortic aneurysmal enlargement.

Abdominal aortic aneurysms (AAAs) are characterized histopathologically by compromised elastic fiber integrity, lost smooth muscle cells or their function, and remodeled collagen. We used a recently introduced mouse model of AAAs that combines enzymatic degradation of elastic fibers and blocking of lysyl oxidase, and thus matrix cross-linking, to study progressive dilatation of the infrarenal abdominal aorta, including development of intraluminal thrombus. We quantified changes in biomaterial properties and biomechanical functionality within the aneurysmal segment as a function of time of enlargement and degree of thrombosis. Towards this end, we combined multi-modality imaging with state-of-the art biomechanical testing and histology to quantify regional heterogeneities for the first time and we used a computational model of arterial growth and remodeling to test multiple hypotheses, suggested by the data, regarding the degree of lost elastin, accumulation of glycosaminoglycans, and rates of collagen turnover. We found that standard histopathological findings can be misleading, while combining advanced experimental and computational methods revealed that glycosaminoglycan accumulation is pathologic, not adaptive, and that heightened collagen deposition is ineffective if not cross-linked. In conclusion, loss of elastic fiber integrity can be a strong initiator of aortic aneurysms, but it is the rate and effectiveness of fibrillar collagen remodeling that dictates enlargement. STATEMENT OF SIGNIFICANCE: Precise mechanisms by which abdominal aortic aneurysms enlarge remain unclear, but a recent elastase plus ß-aminopropionitrile mouse model provides new insight into disease progression. As in the human condition, the aortic degeneration and adverse remodeling are highly heterogeneous in this model. Our multi-modality experiments quantify and contrast the heterogeneities in geometry and biomaterial properties, and our computational modeling shows that standard histopathology can be misleading. Neither accumulating glycosaminoglycans nor frustrated collagen synthesis slow disease progression, thus highlighting the importance of stimulating adaptive collagen remodeling to limit lesion enlargement.

Psychological Contract Mutuality and Work-related Outcomes: Testing a Mediation Model.

Psychological contract (PC) describes the labor relationships through the different promises made by the employer towards the employees and the promises made by employees to their employer. PC mutuality is defined as the agreement about whether these promises were actually made. Mutuality is a key element in PC theory. The aim of this study is to test a mediation model of relationships between PC mutuality and work related outcomes, through PC fulfillment. We analyze whether PC mutuality regarding promises made by the employer are significantly related to employees' affective, attitudinal, and behavioral work-related outcomes, and whether fulfillment of PC promises mediates these relationships. The sample was composed of 942 employees and their HR managers from 47 organizations in three sectors (food, education, and sales). Mediation model is tested, using the bootstrapping technique developed by Hayes (2009). The study provides support for the hypothesized mediation model. Results show that PC mutuality predicts work-related outcomes such as job satisfaction, well-being, organizational commitment, intention to quit, in-role perceived performance, and perceptions of PC violation, and that PC fulfillment partially mediates these relationships. These findings provide theoretical insights into PC theory, highlighting the relevance of PC mutuality. They offer practical suggestions for companies about the importance of achieving mutuality in their relationships with employees in order to increase positive work-related outcomes.

Vaginal neutrophils eliminate sperm by trogocytosis.

STUDY QUESTION: What is the vaginal polymorphonuclear (PMN) spermicidal mechanism to reduce the excess of sperm? SUMMARY ANSWER: We show that PMNs are very efficient at killing sperm by a trogocytosis-dependent spermicidal activity independent of neutrophil extracellular traps (NETs). WHAT IS KNOWN ALREADY: Trogocytosis has been described as an active membrane exchange between immune cells with a regulatory purpose. Recently, trogocytosis has been reported as a mechanism which PMNs use to kill tumour cells or Trichomonas vaginalis. STUDY DESIGN, SIZE, DURATION: We used in vivo murine models and human ex vivo sperm and PMNs to investigate the early PMN-sperm response. PARTICIPANTS/MATERIALS, SETTING, METHODS: We set up a live/dead sperm detection system in the presence of PMNs to investigate in vivo and ex vivo PMN-spermicidal activity by confocal microscopy, flow cytometry and computer-assisted sperm analysis (SCA). MAIN RESULTS AND THE ROLE OF CHANCE: We revealed that PMNs are highly efficient at killing sperm by way of a NETs-independent, contact-dependent and serine proteases-dependent engulfment mechanism. PMNs 'bite' sperm and quickly reduce sperm motility (within 5 min) and viability (within 20 min) after contact. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: This study was conducted using murine models and healthy human blood PMNs; whether it is relevant to human vaginal PMNs or to cases of infertility is unknown. WIDER IMPLICATIONS OF THE FINDINGS: Vaginal PMNs attack and immobilize excess sperm in the vagina by trogocytosis because sperm are exogenous and may carry pathogens. Furthermore, this mechanism of sperm regulation has low mucosal impact and avoids an exacerbated inflammatory response that could lead to mucosal damage or infertility. STUDY FUNDING/COMPETING INTEREST(S): This work was partially supported by Ministry of Economy and Competitiveness ISCIII-FIS grants, PI16/00050, and PI19/00078, co-financed by ERDF (FEDER) Funds from the European Commission, 'A way of making Europe' and IiSGM intramural grant II-PI-MRC-2017. M.R. holds a Miguel Servet II contract (CPII14/00009). M.C.L. holds IiSGM intramural contract. There are no competing interests.

Numerical knockouts-In silico assessment of factors predisposing to thoracic aortic aneurysms.

Myriad risk factors-including uncontrolled hypertension, aging, and diverse genetic mutations-contribute to the development and enlargement of thoracic aortic aneurysms. Detailed analyses of clinical data and longitudinal studies of murine models continue to provide insight into the natural history of these potentially lethal conditions. Yet, because of the co-existence of multiple risk factors in most cases, it has been difficult to isolate individual effects of the many different factors or to understand how they act in combination. In this paper, we use a data-informed computational model of the initiation and progression of thoracic aortic aneurysms to contrast key predisposing risk factors both in isolation and in combination; these factors include localized losses of elastic fiber integrity, aberrant collagen remodeling, reduced smooth muscle contractility, and dysfunctional mechanosensing or mechanoregulation of extracellular matrix along with superimposed hypertension and aortic aging. In most cases, mild-to-severe localized losses in cellular function or matrix integrity give rise to varying degrees of local dilatations of the thoracic aorta, with enlargement typically exacerbated in cases wherein predisposing risk factors co-exist. The simulations suggest, for the first time, that effects of compromised smooth muscle contractility are more important in terms of dysfunctional mechanosensing and mechanoregulation of matrix than in vessel-level control of diameter and, furthermore, that dysfunctional mechanobiological control can yield lesions comparable to those in cases of compromised elastic fiber integrity. Particularly concerning, therefore, is that loss of constituents such as fibrillin-1, as in Marfan syndrome, can compromise both elastic fiber integrity and mechanosensing.

Paradoxical aortic stiffening and subsequent cardiac dysfunction in Hutchinson-Gilford progeria syndrome.

Hutchinson-Gilford progeria syndrome (HGPS) is an ultra-rare disorder with devastating sequelae resulting in early death, presently thought to stem primarily from cardiovascular events. We analyse novel longitudinal cardiovascular data from a mouse model of HGPS (LmnaG609G/G609G) using allometric scaling, biomechanical phenotyping, and advanced computational modelling and show that late-stage diastolic dysfunction, with preserved systolic function, emerges with an increase in the pulse wave velocity and an associated loss of aortic function, independent of sex. Specifically, there is a dramatic late-stage loss of smooth muscle function and cells and an excessive accumulation of proteoglycans along the aorta, which result in a loss of biomechanical function (contractility and elastic energy storage) and a marked structural stiffening despite a distinctly low intrinsic material stiffness that is consistent with the lack of functional lamin A. Importantly, the vascular function appears to arise normally from the low-stress environment of development, only to succumb progressively to pressure-related effects of the lamin A mutation and become extreme in the peri-morbid period. Because the dramatic life-threatening aortic phenotype manifests during the last third of life there may be a therapeutic window in maturity that could alleviate concerns with therapies administered during early periods of arterial development.

The protective effect of extra-virgin olive oil in the experimental model of multiple sclerosis in the rat.

This study has evaluated the effect of EVOO (Extra-Virgin olive oil), OA (oleic acid) and HT (hydroxytyrosol) in an induced model of MS through experimental autoimmune encephalomyelitis (EAE).Dark Agouti 2-month old rats (25 males) were divided into five groups: (i) control group, (ii) EAE group, (iii) EAE+EVOO, (iv) EAE+HT, and (v) EAE+OA. At 65 days, the animals were sacrificed and the glutathione redox system and bacterial lipopolysaccharide (LPS) and LPS-binding protein (LBP) products of the microbiota in brain, spinal cord, and blood were evaluated.Gastric administration of EVOO, OA, and HT reduced the degree of lipid and protein oxidation, and increased glutathione peroxidase, making it a diet-based mechanism for enhancing protection against oxidative damage. In addition, it reduced the levels of LPS and LBP, which appeared as being increased in the EAE correlated with the oxidative stress produced by the disease.

Psychological contract mutuality and work-related outcomes: testing a mediation model

Psychological contract (PC) describes the labor relationships through the different promises made by the employer towards the employees and the promises made by employees to their employer. PC mutuality is defined as the agreement about whether these promises were actually made. Mutuality is a key element in PC theory. The aim of this study is to test a mediation model of relationships between PC mutuality and work related outcomes, through PC fulfillment. We analyze whether PC mutuality regarding promises made by the employer are significantly related to employees' affective, attitudinal, and behavioral work-related outcomes, and whether fulfillment of PC promises mediates these relationships. The sample was composed of 942 employees and their HR managers from 47 organizations in three sectors (food, education, and sales). Mediation model is tested, using the bootstrapping technique developed by Hayes (2009). The study provides support for the hypothesized mediation model. Results show that PC mutuality predicts work-related outcomes such as job satisfaction, well-being, organizational commitment, intention to quit, in-role perceived performance, and perceptions of PC violation, and that PC fulfillment partially mediates these relationships. These findings provide theoretical insights into PC theory, highlighting the relevance of PC mutuality. They offer practical suggestions for companies about the importance of achieving mutuality in their relationships with employees in order to increase positive work-related outcomes

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European Countries: Does common legislation guarantee better hazardous waste performance for European Union member states?

The study of efficiency in hazardous waste management has been proved to be a driving factor for sustainable development (SD). This study focuses on a performance assessment of European countries, most of them European Union (EU) member states and candidate countries that share a common legislative framework through European regulations, in order to provide a general understanding of hazardous waste performance. In this paper, we use Data Envelopment Analysis (DEA) to examine the efficiency of 32 countries in Europe by using novel input/output environmental parameters to study the efficiency of the different waste management operations from an environmental point of view. This analysis contrasts the efficiency in the management of total waste versus hazardous waste and studies three operations with hazardous wastes: incineration and incineration with energy recovery, disposal and recovery. Results show that there are differences in the achievement of efficiency, not only among countries, but also among the different waste management operations analysed.

Eosinophilic granulomatosis with polyangiitis and laryngeal involvement: review of the literature and a cross-sectional prospective experience.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis and granulomatosis with polyangiitis show variable otorhinolaryngological involvement. Up to 14 per cent of granulomatosis with polyangiitis patients have subglottis involvement; little is known about the laryngeal involvement in eosinophilic granulomatosis with polyangiitis. METHOD: A literature review was conducted, together with a prospective cross-sectional analysis of 43 eosinophilic granulomatosis with polyangiitis patients. All patients underwent fibre-optic laryngoscopy with narrow-band imaging, and completed health-related questionnaires. RESULTS: The literature review showed only two cases of laryngeal involvement in eosinophilic granulomatosis with polyangiitis; in our cohort, no cases of subglottis stenosis were found, but local signs of laryngeal inflammation were present in 72 per cent of cases. Of the patients, 16.2 per cent had a pathological Reflux Finding Score (of 7 or higher). CONCLUSION: Laryngeal inflammation in eosinophilic granulomatosis with polyangiitis is frequent. It is possibly due more to local factors than to eosinophilic granulomatosis with polyangiitis itself. However, ENT evaluation is needed to rule out possible subglottis inflammation. These findings are in line with current literature and worthy of confirmation in larger cohorts.

Factors reducing omalizumab response in severe asthma.

BACKGROUND: Despite adding Omalizumab to conventional therapy, several severe asthmatics still show poor disease control. We investigated the factors that may affect a reduced Omalizumab response in a large population of severe asthmatics. METHODS: 340 patients were retrospectively evaluated. FEV1%, FVC%, Asthma Control Test (ACT), fractional exhaled nitric oxide (FENO), possible step-downs/step-ups of concomitant therapies, exacerbations, disease control levels, ICS doses and SABA use, observed at the end of treatment, were considered as a response to Omalizumab. RESULTS: Age was an independent risk factor for a reduced response concerning FEV1%, FVC%, ACT and for a lower asthma control. Obesity (vs normal weight) was a determinant condition for exacerbations (OR:3.114[1.509-6.424], p = 0.002), for a disease partial/no control (OR:2.665[1.064-6.680], p = 0.036), for excessive SABA use (OR:4.448[1.837-10.768], p = 0.002) and for an unchanged/increased level of concomitant asthma medications. Furthermore, obesity also reduced the response in FEV1 (ß = -6.981,p = 0.04), FVC (ß = -11.689,p = 0.014) and ACT (ß = -2.585, p = 0.027) and was associated with a higher FENO level (ß = 49.045,p = 0.040). Having at least one comorbidity was a risk factor for exacerbations (OR:1.383[1.128-1.697], p = 0.008) and for an ACT <20 (OR:2.410[1.071-3.690], p = 0.008). Specifically, chronic heart disease was associated with both a lower ACT and FVC% whereas gastroesophageal reflux with a partial/no asthma control. Nasal polyps were a predisposing factor leading both to exacerbations and to the use of higher inhaled corticosteroids doses. Moreover, smoking habits, pollen or dog/cat dander co-sensitizations may negatively influence Omalizumab response. CONCLUSION: Age, obesity, comorbidities, smoking habits, nasal polyps, allergic poly-sensitization might reduce Omalizumab effectiveness independently to other asthma-influencing factors.

RItA: The Italian severe/uncontrolled asthma registry.

BACKGROUND: The Italian severe/uncontrolled asthma (SUA) web-based registry encompasses demographic, clinical, functional, and inflammatory data; it aims to raise SUA awareness, identifying specific phenotypes and promoting optimal care. METHODS: Four hundred and ninety three adult patients from 27 Italian centers (recruited in 2011-2014) were analyzed. RESULTS: Mean age was 53.8 years. SUA patients were more frequently female (60.6%), with allergic asthma (83.1%). About 30% showed late onset of asthma diagnosis/symptoms (>40 years); the mean age for asthma symptoms onset was 30.2 years and for asthma diagnosis 34.4 years. 97.1% used ICS (dose 2000 BDP), 93.6% LABA in association with ICS, 53.3% LTRAs, 64.1% anti-IgE, 10.7% theophylline, and 16.0% oral corticosteroids. Mean FEV1 % pred of 75.1%, median values of 300/mm3 of blood eosinophil count, 323 kU/L of serum total IgE, and 24 ppb of FENO were shown. Most common comorbidities were allergic rhinitis (62.4%), gastroesophageal reflux (42.1%), sinusitis (37.9%), nasal polyposis (30.2%), and allergic conjunctivitis (30.2%). 55.7% of SUA patients had exacerbations in the last 12 months, 9.7% emergency department visits, and 7.3% hospitalizations. Factors associated with exacerbation risk were obesity (OR, 95% CI 2.46, 1.11-5.41), psychic disorders (2.87, 0.89-9.30-borderline), nasal polyps (1.86, 0.88-3.89-borderline), partial/poor asthma treatment adherence (2.54, 0.97-6.67-borderline), and anti-IgE use in a protective way (0.26, 0.12-0.53). Comparisons to severe asthma multicenter studies and available registries showed data consistency across European and American populations. CONCLUSIONS: An international effort in the implementation of SUA patients' registries could help to better understand the clinical features and to manage severe asthma, representing a non-negligible socioeconomic burden for health services.

Effect of feeding a high-carbohydrate or a high-fat diet on subsequent food intake and blood concentration of satiety-related hormones in dogs.

Although studies in rodents and humans have evidenced a weaker effect of fat in comparison to carbohydrates on the suppression of food intake, very few studies have been carried out in this field in dogs. This study investigates the effects of a high-carbohydrate (HC) and a high-fat (HF) diets on subsequent food intake and blood satiety-related hormones in dogs. Diets differed mainly in their starch (442 vs. 271 g/kg dry matter) and fat (99.3 vs. 214 g/kg dry matter) contents. Twelve Beagle dogs received the experimental diets at maintenance energy requirements in two experimental periods, following a cross-over arrangement. In week 7 of each period, blood concentrations of active ghrelin, glucagon-like peptide (GLP-1), peptide YY, insulin, and glucose were determined before and at 30, 60, 120, 180, and 360 min post-feeding. The following week, intake of a challenge food offered 180 min after the HC and HF diets was recorded over two days. In comparison to the dogs on the HC diet, those on the HF diet had a higher basal concentration of GLP-1 (p = .010) and a higher total area under the curve over 180 min post-prandial (tAUC0-180 ) (p = .031). Dogs on the HC diet showed a higher elevation of ghrelin at 180 min (p = .033) and of insulin at 360 min (p = .041), although ghrelin and insulin tAUC0-180 did not differ between the two diets (p Ëƒ .10). Diet had no effect on challenge food intake (p Ëƒ .10), which correlated with the tAUC0-180 of ghrelin (r = .514, p = .010), insulin (r = -.595, p = .002), and glucose (r = -.516, p = .010). Feeding a diet high in carbohydrate or fat at these inclusion levels does not affect the feeding response at 180 min post-prandial, suggesting a similar short-term satiating capacity.