The relationship between the time of cerebral desaturation episodes and outcome in aneurysmal subarachnoid haemorrhage: a preliminary study.

In this preliminary study we investigated the relationship between the time of cerebral desaturation episodes (CDEs), the severity of the haemorrhage, and the short-term outcome in patients with aneurysmal subarachnoid haemorrhage (aSAH). Thirty eight patents diagnosed with aneurysmal subarachnoid haemorrhage were analysed in this study. Regional cerebral oxygenation (rSO2) was assessed using near infrared spectroscopy (NIRS). A CDE was defined as rSO2 < 60% with a duration of at least 30 min. The severity of the aSAH was assessed using the Hunt and Hess scale and the short-term outcome was evaluated utilizing the Glasgow Outcome Scale. CDEs were found in 44% of the group. The total time of the CDEs and the time of the longest CDE on the contralateral side were longer in patients with severe versus moderate aSAH [h:min]: 8:15 (6:26-8:55) versus 1:24 (1:18-4:18), p = 0.038 and 2:05 (2:00-5:19) versus 0:48 (0:44-2:12), p = 0.038. The time of the longest CDE on the ipsilateral side was longer in patients with poor versus good short-term outcome [h:min]: 5:43 (3:05-9:36) versus 1:47 (0:42-2:10), p = 0.018. The logistic regression model for poor short-term outcome included median ABP, the extent of the haemorrhage in the Fisher scale and the time of the longest CDE. We have demonstrated that the time of a CDE is associated with the severity of haemorrhage and short-term outcome in aSAH patients. A NIRS measurement may provide valuable predictive information and could be considered as additional method of neuromonitoring of patients with aSAH

Activity and regulation by growth factors of calmodulin-dependent protein kinase III (elongation factor 2-kinase) in human breast cancer

Calmodulin-dependent protein kinase III (CaM kinase III, elongation factor-2 kinase) is a unique member of the Ca2+/CaM-dependent protein kinase family. Activation of CaM kinase III leads to the selective phosphorylation of elongation factor 2 (eEF-2) and transient inhibition of protein synthesis. Recent cloning and sequencing of CaM kinase III revealed that this enzyme represents a new superfamily of protein kinases. The activity of CaM kinase III is selectively activated in proliferating cells; inhibition of the kinase blocked cells in G0/G1-S and decreased viability. To determine the significance of CaM kinase III in breast cancer, we measured the activity of the kinase in human breast cancer cell lines as well as in fresh surgical specimens. The specific activity of CaM kinase III in human breast cancer cell lines was equal to or greater than that seen in a variety of cell lines with similar rates of proliferation. The specific activity of CaM kinase III was markedly increased in human breast tumour specimens compared with that of normal adjacent breast tissue. The activity of this enzyme was regulated by breast cancer mitogens. In serum-deprived MDA-MB-231 cells, the combination of insulin-like growth factor I (IGF-I) and epidermal growth factor (EGF) stimulated cell proliferation and activated CaM kinase III to activities observed in the presence of 10% serum. Inhibition of enzyme activity blocked cell proliferation induced by growth factors. In MCF-7 cells separated by fluorescence-activated cell sorting, CaM kinase III was increased in S-phase over that of other phases of the cell cycle. In summary, the activity of Ca2+/CaM-dependent protein kinase III is controlled by breast cancer mitogens and appears to be constitutively activated in human breast cancer. These results suggest that CaM kinase III may contribute an important link between growth factor/receptor interactions, protein synthesis and the induction of cellular proliferation in human breast cancer. © 1999 Cancer Research Campaig

The practical politics of sharing personal data

The focus of this paper is upon how people handle the sharing of personal data as an interactional concern. A number of ethnographic studies of domestic environments are drawn upon in order to articulate a range of circumstances under which data may be shared. In particular a distinction is made between the in situ sharing of data with others around you and the sharing of data with remote parties online. A distinction is also drawn between circumstances of purposefully sharing data in some way and circumstances where the sharing of data is incidental or even unwitting. On the basis of these studies a number of the organisational features of how people seek to manage the ways in which their data is shared are teased out. The paper then reflects upon how data sharing practices have evolved to handle the increasing presence of digital systems in people’s environments and how these relate to the ways in which people traditionally orient to the sharing of information. In conclusion a number of ways are pointed out in which the sharing of data remains problematic and there is a discussion of how systems may need to adapt to better support people’s data sharing practices in the future

Distribution and correlates of plantar hyperkeratotic lesions in older people

<p>Abstract</p> <p>Background</p> <p>Plantar hyperkeratotic lesions are common in older people and are associated with pain, mobility impairment and functional limitations. However, little has been documented in relation to the frequency or distribution of these lesions. The aim of this study was to document the occurrence of plantar hyperkeratotic lesions and the patterns in which they occur in a random sample of older people.</p> <p>Methods</p> <p>A medical history questionnaire was administered to a random sample of 301 people living independently in the community (117 men, 184 women) aged between 70 and 95 years (mean 77.2, SD 4.9), who also underwent a clinical assessment of foot problems, including the documentation of plantar lesion locations, toe deformities and the presence and severity of hallux valgus.</p> <p>Results</p> <p>Of the 301 participants, 180 (60%) had at least one plantar hyperkeratotic lesion. Those with plantar lesions were more likely to be female (χ²= 18.75, <it>p </it>< 0.01; OR = 2.86), have moderate to severe hallux valgus (χ²= 6.15, <it>p </it>< 0.02; OR = 2.95), a larger dorsiflexion range of motion at the ankle (39.4 ± 9.3 <it>vs </it>36.3 ± 8.4°; <it>t </it>= 2.68, <it>df </it>= 286, <it>p </it>< 0.01), and spent more time on their feet at home (5.1 ± 1.0 <it>vs </it>4.8 ± 1.3 hours, <it>t </it>= -2.46, <it>df </it>= 299, <it>p </it>= 0.01). No associations were found between the presence of plantar lesions and body mass index, obesity, foot posture, dominant foot or forefoot pain. A total of 53 different lesions patterns were observed, with the most common lesion pattern being "roll-off" hyperkeratosis on the medial aspect of the 1^stmetatarsophalangeal joint (MPJ), accounting for 12% of all lesion patterns. "Roll-off" lesions under the 1^stMPJ and interphalangeal joint were significantly associated with moderate to severe hallux valgus (<it>p </it>< 0.05), whereas lesions under the central MPJs were significantly associated with deformity of the corresponding lesser toe (<it>p </it>< 0.05). Factor analysis indicated that 62% of lesion patterns could be grouped under three broad categories, relating to medial, central and lateral locations.</p> <p>Conclusion</p> <p>Plantar hyperkeratotic lesions affect 60% of older people and are associated with female gender, hallux valgus, toe deformity, increased ankle flexibility and time spent on feet, but are not associated with obesity, limb dominance, forefoot pain or foot posture. Although there are a wide range of lesion distribution patterns, most can be classified into medial, central or lateral groups. Further research is required to determine whether these patterns are related to the dynamic function of the foot or other factors such as foot pathology or morphology.</p

Retinal Degeneration Progression Changes Lentiviral Vector Cell Targeting in the Retina

In normal mice, the lentiviral vector (LV) is very efficient to target the RPE cells, but transduces retinal neurons well only during development. In the present study, the tropism of LV has been investigated in the degenerating retina of mice, knowing that the retina structure changes during degeneration. We postulated that the viral transduction would be increased by the alteration of the outer limiting membrane (OLM). Two different LV pseudotypes were tested using the VSVG and the Mokola envelopes, as well as two animal models of retinal degeneration: light-damaged Balb-C and Rhodopsin knockout (Rho-/-) mice. After light damage, the OLM is altered and no significant increase of the number of transduced photoreceptors can be obtained with a LV-VSVG-Rhop-GFP vector. In the Rho-/- mice, an alteration of the OLM was also observed, but the possibility of transducing photoreceptors was decreased, probably by ongoing gliosis. The use of a ubiquitous promoter allows better photoreceptor transduction, suggesting that photoreceptor-specific promoter activity changes during late stages of photoreceptor degeneration. However, the number of targeted photoreceptors remains low. In contrast, LV pseudotyped with the Mokola envelope allows a wide dispersion of the vector into the retina (corresponding to the injection bleb) with preferential targeting of Müller cells, a situation which does not occur in the wild-type retina. Mokola-pseudotyped lentiviral vectors may serve to engineer these glial cells to deliver secreted therapeutic factors to a diseased area of the retina

Polymorphism of the Tryptophan Hydroxylase 2 (TPH2) Gene Is Associated with Chimpanzee Neuroticism

In the brain, serotonin production is controlled by tryptophan hydroxylase 2 (TPH2), a genotype. Previous studies found that mutations on the TPH2 locus in humans were associated with depression and studies of mice and studies of rhesus macaques have shown that the TPH2 locus was involved with aggressive behavior. We previously reported a functional single nucleotide polymorphism (SNP) in the form of an amino acid substitution, Q468R, in the chimpanzee TPH2 gene coding region. In the present study we tested whether this SNP was associated with neuroticism in captive and wild-born chimpanzees living in Japan and Guinea, respectively. Even after correcting for multiple tests (Bonferroni p = 0.05/6 = 0.008), Q468R was significantly related to higher neuroticism (β = 0.372, p = 0.005). This study is the first to identify a genotype linked to a personality trait in chimpanzees. In light of the prior studies on humans, mice, and rhesus macaques, these findings suggest that the relationship between neuroticism and TPH2 has deep phylogenetic roots

Improvement of attention span and reaction time with hyperbaric oxygen treatment in patients with toxic injury due to mold exposure

It is, by now, well established that mold toxins (mycotoxins) can cause significant adverse health effects. In this study, 15 subjects who developed an attention deficit disorder (ADD) and slowing of reaction time at the time of exposure to mold toxins were identified. Deficits in attention span and reaction time were documented not only by taking a careful history, but also by performing a Test of Variables of Attention (TOVA). The TOVA test provides an objective measure of these two variables. It was found that mold-exposed subjects show statistically significant decreases in attention span and significant increases in reaction time to stimuli compared to controls. After ten sessions of hyperbaric oxygen treatment (HBOT), a statistically significant improvement was seen in both measures. This preliminary study suggests promising outcomes in treating mold-exposed patients with hyperbaric oxygen

Carcass persistence and detectability : reducing the uncertainty surrounding wildlife-vehicle collision surveys

Carcass persistence time and detectability are two main sources of uncertainty on roadkill surveys. In this study, we evaluate the influence of these uncertainties on roadkill surveys and estimates. To estimate carcass persistence time, three observers (including the driver) surveyed 114km by car on a monthly basis for two years, searching for wildlife-vehicle collisions (WVC). Each survey consisted of five consecutive days. To estimate carcass detectability, we randomly selected stretches of 500m to be also surveyed on foot by two other observers (total 292 walked stretches, 146 km walked). We expected that body size of the carcass, road type, presence of scavengers and weather conditions to be the main drivers influencing the carcass persistence times, but their relative importance was unknown. We also expected detectability to be highly dependent on body size. Overall, we recorded low median persistence times (one day) and low detectability (<10%) for all vertebrates. The results indicate that body size and landscape cover (as a surrogate of scavengers' presence) are the major drivers of carcass persistence. Detectability was lower for animals with body mass less than 100g when compared to carcass with higher body mass. We estimated that our recorded mortality rates underestimated actual values of mortality by 2±10 fold. Although persistence times were similar to previous studies, the detectability rates here described are very different from previous studies. The results suggest that detectability is the main source of bias across WVC studies. Therefore, more than persistence times, studies should carefully account for differing detectability when comparing WVC studies

Differential serotonin transport is linked to the rh5-HTTLPR in peripheral blood cells

The human serotonin transporter (SERT) gene possesses a 43-base pair (bp) insertion-deletion promoter polymorphism, the h5-HTTLPR. Genotype at this locus correlates with variation in anxiety-related personality traits and risk for major depressive disorder in many studies. Yet, the complex effects of the h5-HTTLPR, in combination with closely associated single-nucleotide polymorphisms (SNPs), continue to be debated. Moreover, although SERT is of high clinical significance, transporter function in vivo remains difficult to assess. Rhesus express a promoter polymorphism related to the h5-HTTLPR. The rh5-HTTLPR has been linked to differences in stress-related behavior and cognitive flexibility, although allelic variations in serotonin uptake have not been investigated. We studied the serotonin system as it relates to the 5-HTTLPR in rhesus peripheral blood cells. Sequencing of the rh5-HTTLPR revealed a 23-bp insertion, which is somewhat longer than originally reported. Consistent with previous reports, no SNPs in the rh5-HTTLPR and surrounding genomic regions were detected in the individuals studied. Reductions in serotonin uptake rates, cell surface SERT binding, and 5-hydroxyindoleacetic acid/serotonin ratios, but not SERT mRNA levels, were associated with the rh5-HTTLPR short allele. Thus, serotonin uptake rates are differentiable with respect to the 5-HTTLPR in an easily accessible native peripheral tissue. In light of these findings, we foresee that primary blood cells, in combination with high sensitivity functional measurements enabled by chronoamperometry, will be important for investigating alterations in serotonin uptake associated with genetic variability and antidepressant responsiveness in humans

GFAP-Driven GFP Expression in Activated Mouse Muller Glial Cells Aligning Retinal Blood Vessels Following Intravitreal Injection of AAV2/6 Vectors

Background: Muller cell gliosis occurs in various retinal pathologies regardless of the underlying cellular defect. Because activated Muller glial cells span the entire retina and align areas of injury, they are ideal targets for therapeutic strategies, including gene therapy.Methodology/Principal Findings: We used adeno-associated viral AAV2/6 vectors to transduce mouse retinas. The transduction pattern of AAV2/6 was investigated by studying expression of the green fluorescent protein (GFP) transgene using scanning-laser ophthalmoscopy and immuno-histochemistry. AAV2/6 vectors transduced mouse Muller glial cells aligning the retinal blood vessels. However, the transduction capacity was hindered by the inner limiting membrane (ILM) and besides Muller glial cells, several other inner retinal cell types were transduced. To obtain Muller glial cell-specific transgene expression, the cytomegalovirus (CMV) promoter was replaced by the glial fibrillary acidic protein (GFAP) promoter. Specificity and activation of the GFAP promoter was tested in a mouse model for retinal gliosis. Mice deficient for Crumbs homologue 1 (CRB1) develop gliosis after light exposure. Light exposure of Crb1(-/-) retinas transduced with AAV2/6-GFAP-GFP induced GFP expression restricted to activated Muller glial cells aligning retinal blood vessels.Conclusions/Significance: Our experiments indicate that AAV2 vectors carrying the GFAP promoter are a promising tool for specific expression of transgenes in activated glial cells