Spectral Signatures of Feedforward and Recurrent Circuitry in Monkey Area MT

Recordings of local field potential (LFP) in the visual cortex can show rhythmic activity at gamma frequencies (30-100 Hz). While the gamma rhythms in the primary visual cortex have been well studied, the structural and functional characteristics of gamma rhythms in extrastriate visual cortex are less clear. Here, we studied the spatial distribution and functional specificity of gamma rhythms in extrastriate middle temporal (MT) area of visual cortex in marmoset monkeys. We found that moving gratings induced narrowband gamma rhythms across cortical layers that were coherent across much of area MT. Moving dot fields instead induced a broadband increase in LFP in middle and upper layers, with weaker narrowband gamma rhythms in deeper layers. The stimulus dependence of LFP response in middle and upper layers of area MT appears to reflect the presence (gratings) or absence (dot fields and other textures) of strongly oriented contours. Our results suggest that gamma rhythms in these layers are propagated from earlier visual cortex, while those in the deeper layers may emerge in area MT

Inhibitors of inflammation and endogenous surfactant pool size as modulators of lung injury with initiation of ventilation in preterm sheep

<p>Abstract</p> <p>Background</p> <p>Increased pro-inflammatory cytokines in tracheal aspirates correlate with the development of BPD in preterm infants. Ventilation of preterm lambs increases pro-inflammatory cytokines and causes lung inflammation.</p> <p>Objective</p> <p>We tested the hypothesis that selective inhibitors of pro-inflammatory signaling would decrease lung inflammation induced by ventilation in preterm newborn lambs. We also examined if the variability in injury response was explained by variations in the endogenous surfactant pool size.</p> <p>Methods</p> <p>Date-mated preterm lambs (n = 28) were operatively delivered and mechanically ventilated to cause lung injury (tidal volume escalation to 15 mL/kg by 15 min at age). The lambs then were ventilated with 8 mL/kg tidal volume for 1 h 45 min. Groups of animals randomly received specific inhibitors for IL-8, IL-1, or NF-κB. Unventilated lambs (n = 7) were the controls. Bronchoalveolar lavage fluid (BALF) and lung samples were used to quantify inflammation. Saturated phosphatidylcholine (Sat PC) was measured in BALF fluid and the data were stratified based on a level of 5 μmol/kg (~8 mg/kg surfactant).</p> <p>Results</p> <p>The inhibitors did not decrease the cytokine levels or inflammatory response. The inflammation increased as Sat PC pool size in BALF decreased. Ventilated lambs with a Sat PC level > 5 μmol/kg had significantly decreased markers of injury and lung inflammation compared with those lambs with < 5 μmol/kg.</p> <p>Conclusion</p> <p>Lung injury caused by high tidal volumes at birth were decreased when endogenous surfactant pool sizes were larger. Attempts to decrease inflammation by blocking IL-8, IL-1 or NF-κB were unsuccessful.</p

Development and testing of an online community care platform for frail older adults in the Netherlands: a user-centred design

Background Recent transitions in long-term care in the Netherlands have major consequences for community-dwelling older adults. A new paradigm expects them to manage and arrange their own care and support as much as possible. Technology can support this shift. A study has been conducted to explore the needs of community-dwelling frail older adults with regard to an online platform. An existing platform was subsequently modified, based upon these needs, resulting in an online community care platform (OCC-platform) comprising of care, health, and communication functions. The purpose of this platform was to support frail older adults in their independence and functioning, by stimulating self-care and providing reliable information, products and services. Methods The study used a User-Centred Design. The development processes involved the following steps: Step 1) Identification of the User Requirements. To assess the user requirements, direct observations (N = 3) and interviews (N = 14) were performed. Step 2) Modification of an Existing Online Platform. Based upon Step 1, available online platforms were explored to determine whether an existing useful product was available. Two companies collaborated in modifying such a platform; Step 3) Testing the Modified Platform. A total of 73 older adults were invited to test a prototype of the OCC-platform during 6 months, which comprised of two phases: (1) a training phase; and (2) a testing phase. Results An iterative process of modifications resulted in an interactive software concept on a Standard PC, containing 11 Functions. The Functions of ‘contacts’, ‘services’ and ‘messaging’, were by far, the most frequently used. The use was at its highest during the first 2 weeks of the testing and then its use steadily declined. The vast majority of the subjects (94%) were positive about the usability of the platform. Only a minority of the subjects (27%) indicated that the platform had added value for them. Conclusion The overall prospect was that an OCC-platform can contribute to the social participation and the self-management competencies of frail older adults, together with their social cohesion in the community. In order to validate these prospects, further research is needed on the characteristics and the impact of online platforms

A comparison of the performance of the ice and ocean tracking modes of the ERS‐1 radar altimeter over non‐ocean surfaces

The European Space Agency's ERS-1 radar altimeter is the first to include separate operating modes to optimise performance over both ocean and non-ocean surfaces. As part of the ERS-1 commissioning activities, we have carried out a study of the tracking performance of this instrument over non-ocean surfaces. Statistics for land ice, sea ice, arid lands, and inland water are presented. Performance in both operating modes is shown to be better than that of previous missions

Antenatal and postnatal corticosteroid and resuscitation induced lung injury in preterm sheep

<p>Abstract</p> <p>Background</p> <p>Initiation of ventilation using high tidal volumes in preterm lambs causes lung injury and inflammation. Antenatal corticosteroids mature the lungs of preterm infants and postnatal corticosteroids are used to treat bronchopulmonary dysplasia.</p> <p>Objective</p> <p>To test if antenatal or postnatal corticosteroids would decrease resuscitation induced lung injury.</p> <p>Methods</p> <p>129 d gestational age lambs (n = 5-8/gp; term = 150 d) were operatively delivered and ventilated after exposure to either 1) no medication, 2) antenatal maternal IM Betamethasone 0.5 mg/kg 24 h prior to delivery, 3) 0.5 mg/kg Dexamethasone IV at delivery or 4) Cortisol 2 mg/kg IV at delivery. Lambs then were ventilated with no PEEP and escalating tidal volumes (<it>V</it>_T) to 15 mL/kg for 15 min and then given surfactant. The lambs were ventilated with <it>V</it>_T8 mL/kg and PEEP 5 cmH₂0 for 2 h 45 min.</p> <p>Results</p> <p>High V_Tventilation caused a deterioration of lung physiology, lung inflammation and injury. Antenatal betamethasone improved ventilation, decreased inflammatory cytokine mRNA expression and alveolar protein leak, but did not prevent neutrophil influx. Postnatal dexamethasone decreased pro-inflammatory cytokine expression, but had no beneficial effect on ventilation, and postnatal cortisol had no effect. Ventilation increased liver serum amyloid mRNA expression, which was unaffected by corticosteroids.</p> <p>Conclusions</p> <p>Antenatal betamethasone decreased lung injury without decreasing lung inflammatory cells or systemic acute phase responses. Postnatal dexamethasone or cortisol, at the doses tested, did not have important effects on lung function or injury, suggesting that corticosteroids given at birth will not decrease resuscitation mediated injury.</p

Proinflammatory genotype is associated with the frailty phenotype in the English Longitudinal Study of Ageing

Background: Frailty is a state of increased vulnerability to poor resolution of homeostasis after a stressor event, which increases the risk of adverse outcomes including falls, disability and death. The underlying pathophysiological pathways of frailty are not known but the hypothalamic–pituitary–adrenal axis and heightened chronic systemic inflammation appear to be major contributors. Methods: We used the English Longitudinal Study of Ageing dataset of 3160 individuals over the age of 50 and assessed their frailty status according to the Fried-criteria. We selected single nucleotide polymorphisms in genes involved in the steroid hormone or inflammatory pathways and performed linear association analysis using age and sex as covariates. To support the biological plausibility of any genetic associations, we selected biomarker levels for further analyses to act as potential endophenotypes of our chosen genetic loci. Results: The strongest association with frailty was observed in the Tumor Necrosis Factor (TNF) (rs1800629, P = 0.001198, β = 0.0894) and the Protein Tyrosine Phosphatase, Receptor type, J (PTPRJ) (rs1566729, P = 0.001372, β = 0.09397) genes. Rs1800629 was significantly associated with decreased levels of high-density lipoprotein (HDL) (P = 0.00949) and cholesterol levels (P = 0.00315), whereas rs1566729 was associated with increased levels of HDL (P = 0.01943). After correcting for multiple testing none of the associations remained significant. Conclusions: We provide potential evidence for the involvement of a multifunctional proinflammatory cytokine gene (TNF) in the frailty phenotype. The implication of this gene is further supported by association with the endophenotype biomarker results

Advances in the treatment of chronic myeloid leukemia

Although imatinib is firmly established as an effective therapy for newly diagnosed patients with chronic myeloid leukemia (CML), the field continues to advance on several fronts. In this minireview we cover recent results of second generation tyrosine kinase inhibitors in newly diagnosed patients, investigate the state of strategies to discontinue therapy and report on new small molecule inhibitors to tackle resistant disease, focusing on agents that target the T315I mutant of BCR-ABL. As a result of these advances, standard of care in frontline therapy has started to gravitate toward dasatinib and nilotinib, although more observation is needed to fully support this. Stopping therapy altogether remains a matter of clinical trials, and more must be learned about the mechanisms underlying the persistence of leukemic cells with treatment. However, there is good news for patients with the T315I mutation, as effective drugs such as ponatinib are on their way to regulatory approval. Despite these promising data, accelerated or blastic phase disease remains a challenge, possibly due to BCR-ABL-independent resistance

Stress-Induced Reinstatement of Drug Seeking: 20 Years of Progress

In human addicts, drug relapse and craving are often provoked by stress. Since 1995, this clinical scenario has been studied using a rat model of stress-induced reinstatement of drug seeking. Here, we first discuss the generality of stress-induced reinstatement to different drugs of abuse, different stressors, and different behavioral procedures. We also discuss neuropharmacological mechanisms, and brain areas and circuits controlling stress-induced reinstatement of drug seeking. We conclude by discussing results from translational human laboratory studies and clinical trials that were inspired by results from rat studies on stress-induced reinstatement. Our main conclusions are (1) The phenomenon of stress-induced reinstatement, first shown with an intermittent footshock stressor in rats trained to self-administer heroin, generalizes to other abused drugs, including cocaine, methamphetamine, nicotine, and alcohol, and is also observed in the conditioned place preference model in rats and mice. This phenomenon, however, is stressor specific and not all stressors induce reinstatement of drug seeking. (2) Neuropharmacological studies indicate the involvement of corticotropin-releasing factor (CRF), noradrenaline, dopamine, glutamate, kappa/dynorphin, and several other peptide and neurotransmitter systems in stress-induced reinstatement. Neuropharmacology and circuitry studies indicate the involvement of CRF and noradrenaline transmission in bed nucleus of stria terminalis and central amygdala, and dopamine, CRF, kappa/dynorphin, and glutamate transmission in other components of the mesocorticolimbic dopamine system (ventral tegmental area, medial prefrontal cortex, orbitofrontal cortex, and nucleus accumbens). (3) Translational human laboratory studies and a recent clinical trial study show the efficacy of alpha-2 adrenoceptor agonists in decreasing stress-induced drug craving and stress-induced initial heroin lapse

A liver fibrosis cocktail? Psoriasis, methotrexate and genetic hemochromatosis

BACKGROUND: Pathologists are often faced with the dilemma of whether to recommend continuation of methotrexate therapy for psoriasis within the context of an existing pro-fibrogenic risk factor, in this instance, patients with genetic hemochromatosis. CASE PRESENTATIONS: We describe our experience with two male psoriatic patients (A and B) on long term methotrexate therapy (cumulative dose A = 1.56 gms and B = 7.88 gms) with hetero- (A) and homozygous (B) genetic hemochromatosis. These patients liver function were monitored with routine biochemical profiling; apart from mild perivenular fibrosis in one patient (B), significant liver fibrosis was not identified in either patient with multiple interval percutaneous liver biopsies; in the latter instance this patient (B) had an additional risk factor of partiality to alcohol. CONCLUSION: We conclude that methotrexate therapy is relatively safe in patients with genetic hemochromatosis, with no other risk factor, but caution that the risk of fibrosis be monitored, preferably by non-invasive techniques, or by liver biopsy

Early Respiratory Management of Respiratory Distress Syndrome in Very Preterm Infants and Bronchopulmonary Dysplasia: A Case-Control Study

BACKGROUND: In the period immediately after birth, preterm infants are highly susceptible to lung injury. Early nasal continuous positive airway pressure (ENCPAP) is an attempt to avoid intubation and may minimize lung injury. In contrast, ENCPAP can fail, and at that time surfactant rescue can be less effective. OBJECTIVE: To compare the pulmonary clinical course and outcome of very preterm infants (gestational age 25–32 weeks) with respiratory distress syndrome (RDS) who started with ENCPAP and failed (ECF group), with a control group of infants matched for gestational age, who were directly intubated in the delivery room (DRI group). Primary outcome consisted of death during admission or bronchopulmonary dysplasia (BPD). RESULTS: 25 infants were included in the ECF group and 50 control infants matched for gestational age were included in the DRI group. Mean gestational age and birth weight in the ECF group were 29.7 weeks and 1,393 g and in the DRI group 29.1 weeks and 1,261 g (p = NS). The incidence of BPD was significantly lower in the ECF group than in the DRI group (4% vs. 35%; P<0.004; OR 12.6 (95% CI 1.6–101)). Neonatal mortality was similar in both groups (4%). The incidence of neonatal morbidities such as severe cerebral injury, patent ductus arteriosus, necrotizing enterocolitis and retinopathy of prematurity, was not significantly different between the two groups. CONCLUSION: A trial of ENCPAP at birth may reduce the incidence of BPD and does not seem to be detrimental in very preterm infants. Randomized controlled trials are needed to test whether early respiratory management of preterm infants with RDS plays an important role in the development of BPD