Pharmacotherapy in patients with epilepsy and psychosis.

The recognition and treatment of psychosis in persons with epilepsy (PWE) is recommended with the apparent dilemma between treating psychosis and opening the possibility of exacerbating seizures. The pooled prevalence estimate of psychosis in PWE is 5.6%. It has been proposed that a 'two hit' model, requiring both aberrant limbic activity and impaired frontal control, may account for the wide range of clinical phenotypes. The role of antiepileptic drugs in psychosis in PWE remains unclear. Alternating psychosis, the clinical phenomenon of a reciprocal relationship between psychosis and seizures, is unlikely to be an exclusively antiepileptic drug-specific phenomenon but rather, linked to the neurobiological mechanisms underlying seizure control. Reevaluation of antiepileptic treatment, including the agent/s being used and degree of epileptic seizure control is recommended. The authors found very few controlled studies to inform evidence-based treatment of psychosis in PWE. However, antipsychotics and benzodiazepines are recommended as the symptomatic clinical treatments of choice for postictal and brief interictal psychoses. The general principle of early symptomatic treatment of psychotic symptoms applies in epilepsy-related psychoses, as for primary psychotic disorders. In the authors' experience, low doses of antipsychotic medications do not significantly increase clinical risk of seizures in PWE being concurrently treated with an efficacious antiepileptic regimen

Tendinopathy—from basic science to treatment

Chronic tendon pathology (tendinopathy), although common, is difficult to treat. Tendons possess a highly organized fibrillar matrix, consisting of type I collagen and various 'minor' collagens, proteoglycans and glycoproteins. The tendon matrix is maintained by the resident tenocytes, and there is evidence of a continuous process of matrix remodeling, although the rate of turnover varies at different sites. A change in remodeling activity is associated with the onset of tendinopathy. Major molecular changes include increased expression of type III collagen, fibronectin, tenascin C, aggrecan and biglycan. These changes are consistent with repair, but they might also be an adaptive response to changes in mechanical loading. Repeated minor strain is thought to be the major precipitating factor in tendinopathy, although further work is required to determine whether it is mechanical overstimulation or understimulation that leads to the change in tenocyte activity. Metalloproteinase enzymes have an important role in the tendon matrix, being responsible for the degradation of collagen and proteoglycan in both healthy patients and those with disease. Metalloproteinases that show increased expression in painful tendinopathy include ADAM (a disintegrin and metalloproteinase)-12 and MMP (matrix metalloproteinase)-23. The role of these enzymes in tendon pathology is unknown, and further work is required to identify novel and specific molecular targets for therapy

Synchronisation of egg hatching of brown hairstreak (Thecla betulae) and budburst of blackthorn (Prunus spinosa) in a warmer future

Synchronisation of the phenology of insect herbivores and their larval food plant is essential for the herbivores’ fitness. The monophagous brown hairstreak (Thecla betulae) lays its eggs during summer, hibernates as an egg, and hatches in April or May in the Netherlands. Its main larval food plant blackthorn (Prunus spinosa) flowers in early spring, just before the leaves appear. As soon as the Blackthorn opens its buds, and this varies with spring temperatures, food becomes available for the brown hairstreak. However, the suitability of the leaves as food for the young caterpillars is expected to decrease rapidly. Therefore, the timing of egg hatch is an important factor for larval growth. This study evaluates food availability for brown hairstreak at different temperatures. Egg hatch and budburst were monitored from 2004 to 2008 at different sites in the Netherlands. Results showed ample food availability at all monitored temperatures and sites but the degree of synchrony varied strongly with spring temperatures. To further study the effect of temperature on synchronisation, an experiment using normal temperatures of a reference year (T) and temperatures of T + 5°C was carried out in climate chambers. At T + 5°C, both budburst and egg hatch took place about 20 days earlier and thus, on average, elevated temperature did not affect synchrony. However, the total period of budburst was 11 days longer, whereas the period of egg hatching was 3 days shorter. The implications for larval growth by the brown hairstreak under a warmer climate are considered.

Longevity - Extending the lifespan of long-lived mice

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62803/1/414412a0.pd

Brane-world black holes and the scale of gravity

A particle in four dimensions should behave like a classical black hole if the horizon radius is larger than the Compton wavelength or, equivalently, if its degeneracy (measured by entropy in units of the Planck scale) is large. For spherically symmetric black holes in 4 + d dimensions, both arguments again lead to a mass threshold MC and degeneracy scale Mdeg of the order of the fundamental scale of gravity MG. In the brane-world, deviations from the Schwarzschild metric induced by bulk effects alter the horizon radius and effective four-dimensional Euclidean action in such a way that MC \simeq Mdeg might be either larger or smaller than MG. This opens up the possibility that black holes exist with a mass smaller than MG and might be produced at the LHC even if M>10 TeV, whereas effects due to bulk graviton exchanges remain undetectable because suppressed by inverse powers of MG. Conversely, even if black holes are not found at the LHC, it is still possible that MC>MG and MG \simeq 1TeV.Comment: 4 pages, no figur

Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium.

BACKGROUND: Invasive fungal diseases (IFDs) remain important causes of morbidity and mortality. The consensus definitions of the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group have been of immense value to researchers who conduct clinical trials of antifungals, assess diagnostic tests, and undertake epidemiologic studies. However, their utility has not extended beyond patients with cancer or recipients of stem cell or solid organ transplants. With newer diagnostic techniques available, it was clear that an update of these definitions was essential. METHODS: To achieve this, 10 working groups looked closely at imaging, laboratory diagnosis, and special populations at risk of IFD. A final version of the manuscript was agreed upon after the groups' findings were presented at a scientific symposium and after a 3-month period for public comment. There were several rounds of discussion before a final version of the manuscript was approved. RESULTS: There is no change in the classifications of "proven," "probable," and "possible" IFD, although the definition of "probable" has been expanded and the scope of the category "possible" has been diminished. The category of proven IFD can apply to any patient, regardless of whether the patient is immunocompromised. The probable and possible categories are proposed for immunocompromised patients only, except for endemic mycoses. CONCLUSIONS: These updated definitions of IFDs should prove applicable in clinical, diagnostic, and epidemiologic research of a broader range of patients at high-risk

Water- and nutrient-dependent effects of dietary restriction on Drosophila lifespan

Dietary restriction (DR) is a widely conserved intervention leading to lifespan extension. Despite considerable effort, the mechanisms underlying DR remain poorly understood. In particular, it remains unclear whether DR prolongs life through conserved mechanisms in different species. Here, we show that, in the most common experimental conditions, lifespan extension by DR is abolished by providing Drosophila with ad libitum water, without altering food intake, indicating that DR, as conventionally studied in flies, is fundamentally different from the phenomenon studied in mammals. We characterize an alternative dietary paradigm that elicits robust lifespan extension irrespective of water availability, and thus likely represents a more relevant model for mammalian DR. Our results support the view that protein:carbohydrate ratio is the main dietary determinant of fly lifespan. These findings have broad implications for the study of lifespan and nutrition

Neonatal seizures in a rural Kenyan District Hospital: aetiology, Incidence and outcome of hospitalization

<p>Abstract</p> <p>Background</p> <p>Acute seizures are common among children admitted to hospitals in resource poor countries. However, there is little data on the burden, causes and outcome of neonatal seizures in sub-Saharan Africa. We determined the minimum incidence, aetiology and immediate outcome of seizures among neonates admitted to a rural district hospital in Kenya.</p> <p>Methods</p> <p>From 1^stJanuary 2003 to 31^stDecember 2007, we assessed for seizures all neonates (age 0-28 days) admitted to the Kilifi District Hospital, who were resident in a defined, regularly enumerated study area. The population denominator, the number of live births in the community on 1 July 2005 (the study midpoint) was modelled from the census data.</p> <p>Results</p> <p>Seizures were reported in 142/1572 (9.0%) of neonatal admissions. The incidence was 39.5 [95% confidence interval (CI) 26.4-56.7] per 1000 live-births and incidence increased with birth weight. The main diagnoses in neonates with seizures were sepsis in 85 (60%), neonatal encephalopathy in 30 (21%) and meningitis in 21 (15%), but only neonatal encephalopathy and bacterial meningitis were independently associated with seizures. Neonates with seizures had a longer hospitalization [median period 7 days - interquartile range (IQR) 4 to10] -compared to 5 days [IQR 3 to 8] for those without seizures, <it>P </it>= 0.02). Overall, there was no difference in inpatient case fatality between neonates with and without seizures but, when this outcome was stratified by birth weight, it was significantly higher in neonates ≥ 2.5 kg compared to low birth weight neonates [odds ratio 1.59 (95%CI 1.02 to 2.46), <it>P </it>= 0.037]. Up to 13% of the surviving newborn with seizures had neurological abnormalities at discharge.</p> <p>Conclusion</p> <p>There is a high incidence of neonatal seizures in this area of Kenya and the most important causes are neonatal encephalopathy and meningitis. The high incidence of neonatal seizures may be a reflection of the quality of the perinatal and postnatal care available to the neonates.</p

Novel Protein Kinase Signaling Systems Regulating Lifespan Identified by Small Molecule Library Screening Using Drosophila

Protein kinase signaling cascades control most aspects of cellular function. The ATP binding domains of signaling protein kinases are the targets of most available inhibitors. These domains are highly conserved from mammals to flies. Herein we describe screening of a library of small molecule inhibitors of protein kinases for their ability to increase Drosophila lifespan. We developed an assay system which allowed screening using the small amounts of materials normally present in commercial chemical libraries. The studies identified 17 inhibitors, the majority of which targeted tyrosine kinases associated with the epidermal growth factor receptor (EGFR), platelet-derived growth factor (PDGF)/vascular endothelial growth factor (VEGF) receptors, G-protein coupled receptor (GPCR), Janus kinase (JAK)/signal transducer and activator of transcription (STAT), the insulin and insulin-like growth factor (IGFI) receptors. Comparison of the protein kinase signaling effects of the inhibitors in vitro defined a consensus intracellular signaling profile which included decreased signaling by p38MAPK (p38), c-Jun N-terminal kinase (JNK) and protein kinase C (PKC). If confirmed, many of these kinases will be novel additions to the signaling cascades known to regulate metazoan longevity