Neurofilament light compared to neuron-specific enolase as a predictor of unfavourable outcome after out-of-hospital cardiac arrest.

AIM: We compared the prognostic abilities of neurofilament light (NfL) and neuron-specific enolase (NSE) in patients resuscitated from out-of-hospital cardiac arrest (OHCA) of various aetiologies. METHODS: We analysed frozen blood samples obtained at 24 and 48 hours from OHCA patients treated in 21 Finnish intensive care units in 2010 and 2011. We defined unfavourable outcome as Cerebral Performance Category (CPC) 3-5 at 12 months after OHCA. We evaluated the prognostic ability of the biomarkers by calculating the area under the receiver operating characteristic curves (AUROCs [95% confidence intervals]) and compared these with a bootstrap method. RESULTS: Out of 248 adult patients, 12-month outcome was unfavourable in 120 (48.4%). The median (interquartile range) NfL concentrations for patients with unfavourable and those with favourable outcome, respectively, were 689 (146-1804) pg/mL vs. 31 (17-61) pg/mL at 24 h and 1162 (147-4360) pg/mL vs. 36 (21-87) pg/mL at 48 h, p < 0.001 for both. The corresponding NSE concentrations were 13.3 (7.2-27.3) µg/L vs. 8.5 (5.8-13.2) µg/L at 24 h and 20.4 (8.1-56.6) µg/L vs. 8.2 (5.9-12.1) µg/L at 48 h, p < 0.001 for both. The AUROCs to predict an unfavourable outcome were 0.90 (0.86-0.94) for NfL vs. 0.65 (0.58-0.72) for NSE at 24 h, p < 0.001 and 0.88 (0.83-0.93) for NfL and 0.73 (0.66-0.81) for NSE at 48 h, p < 0.001. CONCLUSION: Compared to NSE, NfL demonstrated superior accuracy in predicting long-term unfavourable outcome after OHCA.

Unraveling Brazilian bioethanol yeasts as novel starters for high-gravity brewing.

High-gravity (HG) brewing has broader application to succeed on beer differentiation and production optimization. However, such process imposes a handicap to yeasts, which must be able to deal with stressful conditions in fermentation. In this work, we assessed different physiological traits of 24 Saccharomyces cerevisiae strains isolated from Brazilian bioethanol distilleries for the selection of novel starters for HG brewing. Five yeast strains were selected with ability to overcome different stressors under HG beer fermentation, showing high fermentability rates, resilience to ethanol stress, low production of foam and hydrogen sulfide, as well as similar flocculation rates to brewer's yeasts. After five fermentation recycles, most strains sustained a viability rate higher than 90% and were able to efficiently accumulate trehalose and glycogen, besides presenting no detectable petite mutants at the final stage. In the sensory analysis, the beers obtained from the five selected strains showed greater aromatic complexity, with predominance of 'spicy', 'dried' and 'fresh fruits' descriptors. In conclusion, this study sheds light on the potential of yeast strains from Brazilian bioethanol process to produce distinctive specialty beers, aside from proposing an effective selection methodology based on relevant physiological attributes for HG brewing process.

Arylsulfonyl histamine derivatives as powerful and selective α-glucosidase inhibitors.

A series of simple N-arylbenzenesulfonyl histamine derivatives were prepared and screened against α-glucosidase. Inhibition was in the micromolar range for several N α,N τ-di-arylsulfonyl compounds, with N α,N τ-di-4-trifluorobenzenesulfonyl histamine (IId) being the best inhibitor. Compound IId is a reversible and competitive α-glucosidase inhibitor, and presented good selectivity with respect to other target enzymes, including ß-glucosidase and α-amylase, and interesting predicted physicochemical properties. Docking studies have been run to postulate ligand-enzyme interactions to account for the experimental results. In vivo, compound IId produced a similar hypoglycemic effect to acarbose with half of its dose.

Effects of different classroom temperatures on cardiac autonomic control and cognitive performances in undergraduate students.

OBJECTIVE: Indoor microclimate may affect students' wellbeing, cardiac autonomic control and cognitive performance with potential impact on learning capabilities. To assess the effects of classroom temperature variations on the autonomic profile and students' cognitive capabilities. APPROACH: Twenty students attending Humanitas University School, (14M, age 21 ± 3 years) underwent a single-lead ECG continuous recording by a portable device during a 2 h lecture when classroom temperature was set 'neutral' (20 °C-22 °C, Day 1) and when classroom temperature was set to 24 °C-26 °C (Day 2). ECGs were sent by telemetry to a server for off-line analysis. Spectral analysis of RR variability provided indices of cardiac sympathetic (LFnu), vagal (HF, HFnu) and cardiac sympatho-vagal modulation (LF/HF). Symbolic analysis of RR variability provided the percentage of sequences of three heart periods with no significant change in RR interval (0V%) and with two significant variations (2V%) reflecting cardiac sympathetic and vagal modulation, respectively. Students' cognitive performance (memory, verbal comprehension and reasoning) was assessed at the end of each lecture using the Cambridge Brain Sciences cognitive evaluation tool. MAIN RESULTS: Classroom temperature and CO2 were assessed every 5 min. Classroom temperatures were 22.4 °C ± 0.1 °C (Day 1) and 26.2 °C ± 0.1 °C (Day 2). Student's thermal comfort was lower during Day 2 compared to Day 1. HR, LF/HF and 0V% were greater during Day 2 (79.5 ± 12.1 bpm, 6.9 ± 7.1 and 32.8% ± 10.3%) than during Day 1 (72.6 ± 10.8 bpm, 3.4 ± 3.7, 21.4% ± 9.2%). Conversely, 2V% was lower during Day 2 (23.1% ± 8.1%) than during Day 1 (32.3% ± 11.4%). Short-term memory, verbal ability and the overall cognitive C-score scores were lower during Day 2 (10.3 ± 0.3; 8.1 ± 1.2 and 10.9 ± 2.0) compared to Day 1 (11.7 ± 2.1; 10.7 ± 1.7 and 12.6 ± 1.8). SIGNIFICANCE: During Day 2, a shift of the cardiac autonomic control towards a sympathetic predominance was observed compared to Day 1, in the presence of greater thermal discomfort. Furthermore, during Day 2 reduced cognitive performances were found.

Acquired neuromyotonia in thymoma-associated myasthenia gravis: a clinical and serological study.

BACKGROUND AND PURPOSE: Acquired neuromyotonia can occur in patients with thymoma, alone or in association with myasthenia gravis (MG), but the clinical prognostic significance of such comorbidity is largely unknown. The clinico-pathological features were investigated along with the occurrence of neuromyotonia as predictors of tumour recurrence in patients with thymoma-associated myasthenia. METHODS: A total number of 268 patients with thymomatous MG were studied retrospectively. Patients with symptoms of spontaneous muscle overactivity were selected for autoantibody testing using immunohistology for neuronal cell-surface proteins and cell-based assays for contactin-associated protein 2 (CASPR2), leucine-rich glioma inactivated 1 (LGI1), glycine receptor and Netrin-1 receptor antibodies. Neuromyotonia was diagnosed according to the presence of typical electromyography abnormalities and/or autoantibodies against LGI1/CASPR2. RESULTS: Overall, 33/268 (12%) MG patients had a thymoma recurrence. Five/268 (2%) had neuromyotonia, four with typical autoantibodies, including LGI1 (n = 1), CASPR2 (n = 1) or both (n = 2). Three patients had Netrin-1 receptor antibodies, two with neuromyotonia and concomitant CASPR2+LGI1 antibodies and one with spontaneous muscle overactivity without electromyography evidence of neuromyotonia. Thymoma recurrence was more frequent in those with (4/5, 80%) than in those without (28/263, 10%, P < 0.001) neuromyotonia. Neuromyotonia preceded the recurrence in 4/5 patients. In univariate analysis, predictors of thymoma recurrence were age at thymectomy [odds ratio (OR) 0.95, 95% confidence interval (CI) 0.93-0.97], Masaoka stage ≥IIb (OR 10.73, 95% CI 2.38-48.36) and neuromyotonia (OR 41.78, 95% CI 4.71-370.58). CONCLUSIONS: De novo occurrence of neuromyotonia in MG patients with previous thymomas is a rare event and may herald tumour recurrence. Neuronal autoantibodies can be helpful to assess the diagnosis. These observations provide pragmatic risk stratification for tumour vigilance in patients with thymomatous MG.

A randomized clinical trial evaluating maxillary sinus augmentation with different particle sizes of demineralized bovine bone mineral: histological and immunohistochemical analysis.

This study was performed to investigate sinus floor augmentation with two different particle sizes of demineralized bovine bone mineral (DBBM) by means of histological and immunohistochemical (IHC) analysis. A randomized clinical trial was conducted involving 10 individuals requiring two-stage bilateral maxillary sinus augmentation for implant installation. The patients were randomly divided into two groups following a split-mouth design: the maxillary sinus on one side was filled with small-sized particles (0.25-1mm) and on the contralateral side with large-sized particles (1-2mm). After a healing period of 8 months, 25 implants were placed. During implant site preparation, bone biopsies were obtained from each sinus, perpendicular to the long axis of the implant (buccal-palatal direction), for descriptive and histomorphometric analyses. IHC staining for protein expression of osteocalcin (OCN), vascular endothelial growth factor (VEGF), and tartrate-resistant acid phosphatase (TRAP) was also performed. Histomorphometric analysis revealed no statistically significant difference in the percentage of biomaterial (32.4±8.56% and 38.0±6.92%), newly formed bone (36.1±9.60% and 36.7±5.79%), or connective tissue (30.4±8.63% and 23.8±6.16%) between the small- and large-sized particle groups, respectively. IHC analysis did not reveal differences in the expression of OCN, VEGF, or TRAP. These findings suggest that both particle sizes of DBBM are effective for bone augmentation in the maxillary sinus.

Tongue pressure measurement in children with mouth-breathing behaviour.

The tongue plays an important role in oral functions. Reduced tongue strength is often noted among children with mouth-breathing behaviour. The purposes of this study were to measure the tongue pressure in children with mouth-breathing behaviour, to compare these values to those of children with nasal-breathing behaviour and to analyse the relationship between age and tongue pressure in children with a mouth-breathing pattern and in children with a nasal-breathing pattern. In this cross-sectional analytical observational study, we enroled 40 children aged 5-12 years who either exhibited mouth-breathing behaviour (n = 20) or nasal-breathing behaviour (gender- and age-matched [±2 years] controls; n = 20). Tongue pressure was evaluated using the Iowa Oral Performance Instrument; 3 measurements were recorded for each participant, with a 30-seconds rest interval. The average tongue pressure in the mouth-breathing group was lower than that in the nasal-breathing group. There was no difference in tongue pressure between genders. There was a strong and direct correlation between tongue pressure and age in the nasal-breathing group. The breathing pattern impacts tongue pressure development.

Poultry rearing on perforated plastic floors and the effect on air quality, growth performance, and carcass injuries - Experiment 2: Heat stress situation.

Previously, we reported the effect of rearing conditions (plastic floors and air quality) on carcass injury development of broiler chickens at thermal comfort. In this study, the same rearing conditions were tested at thermal stress. The birds were reared in 2 climatic chambers, and the experiment followed a completely randomized design with one factor, flooring material: wood shaving or perforated plastic. The birds were divided into 16 experimental pens, being 8 females and 8 males. The studied parameters were the same as the previous study (ammonia concentration, carbon dioxide, performance, carcass yield, and variability, and scores of hygiene, gait and chest, and hocks and footpad lesions). Higher ammonia (15 ppm vs. 4 ppm) and carbon dioxide (1,000 ppm vs. 850 ppm) concentration was seen at d 42 for the wood shavings floor as compared to the perforated plastic floor, respectively. Regarding gender, males had better performance than females at 42 d of age on both floor types. Males reared on wood shavings showed a higher meat production (29.049 kg/m2) than females (24.700 kg/m2). There were observed breast lesion incidences of 10.4% (score 1) in males reared on the plastic floor, as well higher incidence of hock injury and footpad dermatitis. Chickens reared on plastic flooring showed better hygiene than chickens reared on wood shavings. Our findings revealed that the use of perforated plastic flooring in a heat stress situation can improve the air quality (less CO2 and NH3 concentration) and bird cleanliness. On the other hand, chickens are more susceptible to develop lesions in the breast, hock, and footpad. We conclude that the use of plastic flooring in heat stress conditions needs more attention, since chickens are more susceptible to develop lesions on the carcass, being a source of pain, impairing bird wellbeing and causing losses in meat production.

N α-arylsulfonyl histamines as selective ß-glucosidase inhibitors.

N α-benzenesulfonylhistamine, a new semi-synthetic ß-glucosidase inhibitor, was obtained by bioactivity-guided isolation from a chemically engineered extract of Urtica urens L. prepared by reaction with benzenesulfonyl chloride. In order to identify better ß-glucosidase inhibitors, a new series of N α,N τ-di-arylsulfonyl and N α-arylsulfonyl histamine derivatives was prepared. Biological studies revealed that the ß-glucosidase inhibition was in a micromolar range for several N α-arylsulfonyl histamine compounds of the series, N α-4-fluorobenzenesulfonyl histamine being the most powerful compound. Besides, this reversible and competitive inhibitor presented a good selectivity for ß-glucosidase with respect to other target enzymes including α-glucosidase.

Multiple biomarkers improve the prediction of multiple sclerosis in clinically isolated syndromes.

OBJECTIVES: Since its introduction, MRI had a major impact on the early and more precise diagnosis of multiple sclerosis (MS), and the 2010 diagnostic criteria even allow a diagnosis to be made just after a single attack if stringent MRI criteria are met. Several other clinical and paraclinical markers have been reported to be associated with an increased risk of MS independently of MRI in patients with clinically isolated syndromes (CIS), but the incremental usefulness of adding them to the current criteria has not been evaluated. In this study, we determined whether multiple biomarkers improved the prediction of MS in patients with CIS in a real-world clinical practice. MATERIALS AND METHODS: This was a retrospective study involving patients with CIS admitted to our department between 2000 and 2013. We evaluated baseline clinical, MRI, neurophysiological, and cerebrospinal fluid (CSF) data. RESULTS: During follow-up (median, 7.2 years), 127 of 243 participants (mean age, 31.6 years) developed MS. Cox proportional-hazards models adjusted for established MRI criteria, age at onset, number of T1 lesions, and presence of CSF oligoclonal bands significantly predicted the risk of developing MS at 2 and 5 years. The use of multiple biomarkers led to 29% net reclassification improvement at 2 years (P<.001) and 30% at 5 years (P<.001). CONCLUSIONS: The simultaneous addition of several biomarkers significantly improved the risk stratification for MS in patients with CIS beyond that of a model based only on established MRI criteria.

Interference of age and supplementation of direct-fed microbial and essential oil in the activity of digestive enzymes and expression of genes related to transport and digestion of carbohydrates and proteins in the small intestine of broilers.

The objectives of this study were to describe alterations that age and dietary inclusion of direct-fed microbial (DFM) Bacillus subtilis (BS) and a specific essential oil (EO) blend (carvacrol, cinnamaldehyde, cineol, and pepper extract) causes in the activity of digestive enzymes (maltase: MALT; aminopeptidase-N: APN; intestinal alkaline phosphate: IAP) and expression patterns of genes related to transport (oligopeptide transporter gene: SLC15A1; Na+-dependent glucose and galactose transporter gene: SLC5A1; Na+-independent glucose, galactose, and fructose transporter gene: SLC2A2; ATPase, Na+/K+ transporting gene: ATP1A1) and digestion (aminopeptidase-N gene: ANPEP; maltase-glucoamylase gene: MGAM; Sucrase-isomaltase gene: SI) of carbohydrates and proteins in the small intestine of broilers. Also, the objective was to analyze if growth performance of broilers is affected by supplementation (BS and EO blend). Day-old male broiler chicks (n = 1,320) were assigned to 5 treatments. Diets included a basal diet (BD) as a negative control (CON); experimental diets were BD + BS; BD + BS + EO; BD + EO; BD + antibiotic growth promoter (AGP) avilamycin was the positive control. Performance was evaluated between 1 to 42 d. Transcript abundance of transport-related genes and digestion-related genes were assayed by RT-qPCR and determined at d 7, 21, and 42. MALT-, APN-, and IAP-specific activities were determined at d 7, 21, and 42. Broilers fed BS had greater SLC15A1 mRNA abundance compared to CON, while EO and AGP were related to higher activities of IAP and APN. Analysis over time revealed higher abundance of MGAM, SLC2A2, SLC15A1, SLC5A1 and SI mRNA at d 42 when compared to d 7. Activity of IAP decreased after d 7 and activity of MALT increased with age. The current study suggests that age had effect over carbohydrate and protein transport and carbohydrate digestion. The supplementation of BS DFM hade evident effect over protein transport and that the use of EO in the diet enhanced the activities of carbohydrate and protein digestion, reflecting improvement in digestive and transport physiology of birds. Changes performed by BS DFM and EO did not favor performance.

Subclinical central inflammation is risk for RIS and CIS conversion to MS.

BACKGROUND: Subtle diffuse intrathecal inflammation is undetectable by conventional neuroimaging, and could influence multiple sclerosis (MS) disease course. OBJECTIVE: To explore the role of subclinical persisting intrathecal inflammation in radiologically isolated syndrome (RIS) or clinically isolated syndrome (CIS) conversion to MS, and in early MS disease reactivation. METHODS: One-hundred ninety-three subjects with RIS, CIS, relapsing-remitting (RR), or primary progressive (PP) MS were included, along with 76 matched controls. Cerebrospinal fluid (CSF) levels of interleukin-8 (IL-8), a major proinflammatory cytokine, were measured as a biomarker of intrathecal inflammation. Patients were followed up for 2 years. Clinical and imaging measures of disease progression were recorded. RESULTS: High central contents of IL-8 were associated to clinical progression in subjects with RIS, and to the risk of conversion to MS in subjects with CIS. Asymptomatic intrathecal inflammation placed subjects at risk for MS conversion, even regardless lesion load. CSF IL-8 levels were higher in RR MS with high disease activity. Higher number of relapses in the first two years since diagnosis and shorter first inter-attack intervals were observed in patients with high levels of IL-8. CONCLUSION: IL-8 might provide utility in determining the presence of active intrathecal inflammation, and could be important in diagnostically undefined cases.

Adherence to prophylaxis is associated with better outcomes in moderate and severe haemophilia: results of a patient survey.

Severe haemophilia is associated with bleeding into joints and development of arthropathy. Prophylactic treatment with infusion of replacement clotting factor is known to prevent bleeding, preserve joint functioning and result in higher health-related quality of life (HRQoL) than episodic treatment; however, adhering to standard prophylaxis schedules can be difficult, and little is known about the relationship between adherence to prophylactic treatment and outcomes. The aim of this study was to assess the relationship between self-reported adherence to prophylaxis and health outcomes, including HRQoL and bleeding episodes. Adults with haemophilia (n = 55) and caregivers of children with haemophilia (n = 55) in Australia, Canada, and the United States completed an online questionnaire which included measures of HRQoL (SF-12v2 for adults and SF-10 for caregivers of children), self-reported bleeding episodes, and the VERITAS-Pro measure of adherence to prophylaxis in haemophilia. Regression analysis was used to test the association between VERITAS-Pro total score and outcomes. Poorer adherence (higher VERITAS-Pro scores) was associated with a greater number of self-reported bleeding episodes in the past year among adults (p < 0.01), more days of work/school missed among paediatric patients (p < 0.01), and lower physical health status scores among paediatric patients (p < 0.05). This study highlights the benefits of adherence to prophylaxis among those with severe haemophilia and provides evidence for the utility of the VERITAS-Pro by demonstrating a relationship between adherence and outcomes.

Increased M1/decreased M2 signature and signs of Th1/Th2 shift in chronic patients with bipolar disorder, but not in those with schizophrenia.

We here present data on immune gene expression of chemokines, chemokine receptors, cytokines and regulatory T-cell (T-reg) markers in chronic patients suffering from either schizophrenia (SCZ, N=20) or bipolar disorder (BD=20) compared with healthy controls (HCs, N=20). We extracted RNA from peripheral blood mononuclear cells and performed real-time (RT)-PCR to measure mRNA levels of chemokines, chemokine receptors, cytokines and T-reg markers. All the analyses were Bonferroni-corrected. The classical monocyte activation (M1) markers il6, ccl3 were significantly increased in BD as compared with both HC and SCZ patients (P=0.03 and P=0.002; P=0.024 and P=0.021, respectively), whereas markers of alternative (M2) monocyte activation ccl1, ccl22 and il10 were coherently decreased (controls: P=0.01, P=0.001 and P=0.09; SCZ subjects: P=0.02, P=0.05 and P=0.011, respectively). Concerning T-cell markers, BD patients had compared with HC downregulated ccr5 (P=0.02) and upregulated il4 (P=0.04) and compared with both healthy and SCZ individuals downregulated ccl2 (P=0.006 and P=0.003) and tgfß (P=0.004 and P=0.007, respectively). No significant associations were found between any immune gene expression and clinical variables (prior hospitalizations, Brief Psychiatric Rating Scale, medications' dosages and lifetime administration). Although some markers are expressed by different immune cell types, these findings suggest a coherent increased M1/decrease M2 signature in the peripheral blood of BD patients with potential Th1/Th2 shift. In contrast, all the explored immune marker levels were preserved in SCZ. Further larger studies are needed to investigate the relevance of inflammatory response in BD, trying to correlate it to psychopathology, treatment and outcome measures and, possibly, to brain connectivity.

Interleukin-8 is associated with acute and persistent dysfunction after optic neuritis.

BACKGROUND: Acute optic neuritis is often in association with multiple sclerosis (MS). Proinflammatory cytokines trigger neuronal damage in neuroinflammatory disorders but their role in optic neuritis is poorly investigated. OBJECTIVE: The objective of this work is to investigate the associations of intrathecal contents of proinflammatory cytokines with transient and persistent dysfunctions after optic neuritis. METHODS: In 50 MS patients followed for up to six months, cerebrospinal fluid (CSF) levels of IL-1ß, TNF and IL-8 were determined, along with clinical, neurophysiological and morphological measures of optic neuritis severity. RESULTS: Visual impairment, measured by high- and low-contrast visual acuity, and delayed visual-evoked potential (VEP) latencies were significantly correlated to IL-8 levels during optic neuritis. IL-8 at the time of optic neuritis was also associated with persistent demyelination and final axonal loss, inferred by VEP and optical coherence tomography measures, respectively. Contents of IL-8 were correlated to functional visual outcomes, being higher among patients with incomplete recovery. Multivariate analysis confirmed that IL-8 significantly predicted final visual acuity, at equal values of demographics and baseline visual scores. CONCLUSION: Our study points to IL-8 as the main inflammatory cytokine associated with demyelination and secondary neurodegeneration in the optic nerve after optic neuritis.

Microglia convert aggregated amyloid-ß into neurotoxic forms through the shedding of microvesicles.

Alzheimer's disease (AD) is characterized by extracellular amyloid-ß (Aß) deposition, which activates microglia, induces neuroinflammation and drives neurodegeneration. Recent evidence indicates that soluble pre-fibrillar Aß species, rather than insoluble fibrils, are the most toxic forms of Aß. Preventing soluble Aß formation represents, therefore, a major goal in AD. We investigated whether microvesicles (MVs) released extracellularly by reactive microglia may contribute to AD degeneration. We found that production of myeloid MVs, likely of microglial origin, is strikingly high in AD patients and in subjects with mild cognitive impairment and that AD MVs are toxic for cultured neurons. The mechanism responsible for MV neurotoxicity was defined in vitro using MVs produced by primary microglia. We demonstrated that neurotoxicity of MVs results from (i) the capability of MV lipids to promote formation of soluble Aß species from extracellular insoluble aggregates and (ii) from the presence of neurotoxic Aß forms trafficked to MVs after Aß internalization into microglia. MV neurotoxicity was neutralized by the Aß-interacting protein PrP and anti-Aß antibodies, which prevented binding to neurons of neurotoxic soluble Aß species. This study identifies microglia-derived MVs as a novel mechanism by which microglia participate in AD degeneration, and suggest new therapeutic strategies for the treatment of the disease.

Predictive accuracy of triage nurses evaluation in risk stratification of syncope in the emergency department.

BACKGROUND: Syncope is a common clinical problem that accounts for 1-3% of all emergency department (ED) visits. Its prognosis is extremely variable with a 1-year mortality that may reach 30%. There are no available data about the accuracy of nursing triage in identifying high-risk syncope. The aim of our study was to evaluate the predictive accuracy of nursing triage in identifying high-risk syncope. METHODS: We conducted a retrospective study on 678 consecutive patients who presented with syncope at four EDs. For each patient, nursing triage, comorbidities, clinical features and adverse events that occurred both in the ED and at 10-day follow-up were assessed. Adverse events included death, readmission to ED, need for major therapeutic procedures, cardiopulmonary resuscitation, intensive care unit admittance, acute antiarrhythmic therapy and major causes of syncope identified during the ED evaluation. Predictive accuracy of nursing triage was evaluated. RESULTS: We observed a total of 55 (8.1%) adverse events. Eight of them (9.4%) occurred among the 85 patients who were identified as high priority by nursing triage. Sensitivity (Sn) and specificity (Sp) of urgent nursing triage in identifying adverse outcomes in the ED (19 patients) were 21% (95% CI 3% to 39%) and 88% (95% CI 85% to 90%), while the positive likelihood ratio (LR+) and negative likelihood ratio (LR-) were 1.7 and 0.9, respectively. Sn and Sp for 10-day adverse events were 15% (95% CI 5% to 24%) and 88% (95% CI 85% to 90%), respectively, with a LR+ of 1.18 and a LR- of 0.98. CONCLUSIONS: Nursing triage was characterised by a low predictive accuracy in identifying high-risk individuals.

Effects of corn replacement by sorghum in broiler diets on performance and intestinal mucosa integrity.

The effect of replacing corn with low-tannin sorghum on broiler performance, carcass yield, integrity of mucosa of small intestine segments, and activity of membrane enzymes of the jejunum is investigated. A total of 594 male Cobb-500 broiler chicks were randomly assigned to 3 dietary treatments: 100% corn (control), 50% corn replacement with low-tannin sorghum (low sorghum), and 100% corn replacement with low-tannin sorghum (high sorghum). Body weight gain, feed consumption, feed conversion, and carcass yield were determined at 7, 21, and 42 d, and segments of the small intestine were collected. Feed conversion and weight gain were impaired at d 42 in broilers fed the high-sorghum diet, but no differences were observed for carcass yield among the treatments (P > 0.05). Crypt cell mitotic index of the jejunum and ileum at d 21 and 42 was lower in broilers fed the control diet than in those fed low- and high-sorghum diets (P < 0.05). Aminopeptidase activity was higher in broilers fed the control diet than in those fed low- and high-sorghum diets irrespective of age (P < 0.05). Conversely, intestinal alkaline phosphatase activity in the small intestine did not differ among the dietary treatments (P > 0.05). Our results indicate that 50% corn replacement with low-tannin sorghum is suitable for broiler diets, whereas 100% corn replacement with low-tannin sorghum had negative effects on the intestinal mucosa and performance of broilers at 42 d.

Lentiviral-mediated administration of IL-25 in the CNS induces alternative activation of microglia.

Interleukin-25 (IL-25) is the only anti-inflammatory cytokine of the IL-17 family, and it has been shown to be efficacious in inhibiting neuroinflammation. Known for its effects on cells of the adaptive immune system, it has been more recently described to be effective also on cells of the innate immune system, namely macrophages. We used a lentiviral-mediated gene therapy approach to deliver IL-25 to the central nervous system (CNS) in two mouse models of neuroinflammation, entorhinal cortex lesion and experimental autoimmune encephalomyelitis. In both, we found that IL-25 gene therapy was able to modulate CNS myeloid cells, either infiltrating macrophages or resident microglia, towards an anti-inflammatory, tissue-protective phenotype, as testified by the increase in markers such as Arginase-1 (Arg1), Mannose receptor 1 (CD206) and Chitinase 3-like 3 (Ym1). As a consequence, neuroinflammation was partly inhibited and the CNS protected from immune-mediated damage. To our knowledge, this is the first example of M2 shift (alternative activation) induced in vivo on CNS-resident myeloid cells by gene therapy, and may constitute a promising strategy to investigate the potential role of protective microglia in neurological disorders.

Abnormal NMDA receptor function exacerbates experimental autoimmune encephalomyelitis.

BACKGROUND AND PURPOSE: Glutamate transmission is dysregulated in both multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), the animal model of MS. A characteristic of EAE is increased glutamate transmission associated with up-regulation of AMPA receptors. However, little is known about the role of NMDA receptors in the synaptic modifications induced by EAE. EXPERIMENTAL APPROACH: The contribution of NMDA receptors to the alterations of glutamate transmission and disease severity in EAE mice was assessed by means of neurophysiological, morphological, Western blot, metabolic and clinical score assessments. KEY RESULTS: In our EAE mice, there was an NMDA receptor-dependent increase of glutamate release, associated with marked activation of the astroglia. Presynaptic NMDA receptors became overactive during EAE, increasing synaptic glutamate release by a mechanism dependent on voltage-gated sodium channels. By means of NAD(P)H autofluorescence analysis, we also found that EAE has a glutamate and NMDA receptor-dependent dysfunction of mitochondrial activity, which is known to contribute to the neurodegenerative damage of MS and EAE. Furthermore, pharmacological blockade of NMDA receptors in vivo ameliorated both synaptic transmission defects and of the clinical disease course of EAE mice, while EAE induced in mice with a genetically enhanced NMDA receptor signalling had opposite effects. CONCLUSIONS AND IMPLICATIONS: Our data, showing both sensitization of NMDA receptors and their involvement in the progression of the EAE disease, supggest that pharmacological impairment of NMDA receptor signalling would be a component of a neuroprotection strategy in MS.