Therapeutic Hypothermia Reduces Intracranial Pressure and Partial Brain Oxygen Tension in Patients with Severe Traumatic Brain Injury:Preliminary Data from the Eurotherm3235 Trial

Traumatic brain injury (TBI) is a significant cause of disability and death and a huge economic burden throughout the world. Much of the morbidity associated with TBI is attributed to secondary brain injuries resulting in hypoxia and ischemia after the initial trauma. Intracranial hypertension and decreased partial brain oxygen tension (P(bt)O(2)) are targeted as potentially avoidable causes of morbidity. Therapeutic hypothermia (TH) may be an effective intervention to reduce intracranial pressure (ICP), but could also affect cerebral blood flow (CBF). This is a retrospective analysis of prospectively collected data from 17 patients admitted to the Western General Hospital, Edinburgh. Patients with an ICP >20 mmHg refractory to initial therapy were randomized to standard care or standard care and TH (intervention group) titrated between 32°C and 35°C to reduce ICP. ICP and P(bt)O(2) were measured using the Licox system and core temperature was recorded through rectal thermometer. Data were analyzed at the hour before cooling, the first hour at target temperature, 2 consecutive hours at target temperature, and after 6 hours of hypothermia. There was a mean decrease in ICP of 4.3±1.6 mmHg (p<0.04) from 15.7 to 11.4 mmHg, from precooling to the first epoch of hypothermia in the intervention group (n=9) that was not seen in the control group (n=8). A decrease in ICP was maintained throughout all time periods. There was a mean decrease in P(bt)O(2) of 7.8±3.1 mmHg (p<0.05) from 30.2 to 22.4 mmHg, from precooling to stable hypothermia, which was not seen in the control group. This research supports others in demonstrating a decrease in ICP with temperature, which could facilitate a reduction in the use of hyperosmolar agents or other stage II interventions. The decrease in P(bt)O(2) is not below the suggested treatment threshold of 20 mmHg, but might indicate a decrease in CBF

Can standardized patients replace physicians as OSCE examiners?

BACKGROUND: To reduce inter-rater variability in evaluations and the demand on physician time, standardized patients (SP) are being used as examiners in OSCEs. There is concern that SP have insufficient training to provide valid evaluation of student competence and/or provide feedback on clinical skills. It is also unknown if SP ratings predict student competence in other areas. The objectives of this study were: to examine student attitudes towards SP examiners; to compare SP and physician evaluations of competence; and to compare predictive validity of these scores, using performance on the multiple choice questions examination (MCQE) as the outcome variable. METHODS: This was a cross-sectional study of third-year medical students undergoing an OSCE during the Internal Medicine clerkship rotation. Fifty-two students rotated through 8 stations (6 physician, 2 SP examiners). Statistical tests used were Pearson's correlation coefficient, two-sample t-test, effect size calculation, and multiple linear regression. RESULTS: Most students reported that SP stations were less stressful, that SP were as good as physicians in giving feedback, and that SP were sufficiently trained to judge clinical skills. SP scored students higher than physicians (mean 90.4% +/- 8.9 vs. 82.2% +/- 3.7, d = 1.5, p < 0.001) and there was a weak correlation between the SP and physician scores (coefficient 0.4, p = 0.003). Physician scores were predictive of summative MCQE scores (regression coefficient = 0.88 [0.15, 1.61], P = 0.019) but there was no relationship between SP scores and summative MCQE scores (regression coefficient = -0.23, P = 0.133). CONCLUSION: These results suggest that SP examiners are acceptable to medical students, SP rate students higher than physicians and, unlike physician scores, SP scores are not related to other measures of competence

Morphological and Geochemical Evidence of Eumelanin Preservation in the Feathers of the Early Cretaceous Bird, Gansus yumenensis

Recent studies have shown evidence for the preservation of colour in fossilized soft tissues by imaging melanosomes, melanin pigment containing organelles. This study combines geochemical analyses with morphological observations to investigate the preservation of melanosomes and melanin within feathers of the Early Cretaceous bird, Gansus yumenensis. Scanning electron microscopy reveals structures concordant with those previously identified as eumelanosomes within visually dark areas of the feathers but not in lighter areas or sedimentary matrices. Fourier transform infrared analyses show different spectra for the feathers and their matrices; melanic functional groups appear in the feather including carboxylic acid and ketone groups that are not seen in the matrix. When mapped, the carboxylic acid group absorption faithfully replicates the visually dark areas of the feathers. Electron Paramagnetic Resonance spectroscopy of one specimen demonstrates the presence of organic signals but proved too insensitive to resolve melanin. Pyrolysis gas chromatography mass spectrometry shows a similar distribution of aliphatic material within both feathers that are different from those of their respective matrices. In combination, these techniques strongly suggest that not only do the feathers contain endogenous organic material, but that both geochemical and morphological evidence supports the preservation of original eumelanic pigment residue

Mating alters gene expression patterns in Drosophila melanogaster male heads

<p>Abstract</p> <p>Background</p> <p>Behavior is a complex process resulting from the integration of genetic and environmental information. <it>Drosophila melanogaster </it>rely on multiple sensory modalities for reproductive success, and mating causes physiological changes in both sexes that affect reproductive output or behavior. Some of these effects are likely mediated by changes in gene expression. Courtship and mating alter female transcript profiles, but it is not known how mating affects male gene expression.</p> <p>Results</p> <p>We used <it>Drosophila </it>genome arrays to identify changes in gene expression profiles that occur in mated male heads. Forty-seven genes differed between mated and control heads 2 hrs post mating. Many mating-responsive genes are highly expressed in non-neural head tissues, including an adipose tissue called the fat body. One fat body-enriched gene, <it>female-specific independent of transformer </it>(<it>fit</it>), is a downstream target of the somatic sex-determination hierarchy, a genetic pathway that regulates <it>Drosophila</it> reproductive behaviors as well as expression of some fat-expressed genes; three other mating-responsive loci are also downstream components of this pathway. Another mating-responsive gene expressed in fat, <it>Juvenile hormone esterase </it>(<it>Jhe</it>), is necessary for robust male courtship behavior and mating success.</p> <p>Conclusions</p> <p>Our study demonstrates that mating causes changes in male head gene expression profiles and supports an increasing body of work implicating adipose signaling in behavior modulation. Since several mating-induced genes are sex-determination hierarchy target genes, additional mating-responsive loci may be downstream components of this pathway as well.</p

Loss of DNMT1o Disrupts Imprinted X Chromosome Inactivation and Accentuates Placental Defects in Females

The maintenance of key germline derived DNA methylation patterns during preimplantation development depends on stores of DNA cytosine methyltransferase-1o (DNMT1o) provided by the oocyte. Dnmt1omat-/- mouse embryos born to Dnmt1Δ1o/Δ1o female mice lack DNMT1o protein and have disrupted genomic imprinting and associated phenotypic abnormalities. Here, we describe additional female-specific morphological abnormalities and DNA hypomethylation defects outside imprinted loci, restricted to extraembryonic tissue. Compared to male offspring, the placentae of female offspring of Dnmt1Δ1o/Δ1o mothers displayed a higher incidence of genic and intergenic hypomethylation and more frequent and extreme placental dysmorphology. The majority of the affected loci were concentrated on the X chromosome and associated with aberrant biallelic expression, indicating that imprinted X-inactivation was perturbed. Hypomethylation of a key regulatory region of Xite within the X-inactivation center was present in female blastocysts shortly after the absence of methylation maintenance by DNMT1o at the 8-cell stage. The female preponderance of placental DNA hypomethylation associated with maternal DNMT1o deficiency provides evidence of additional roles beyond the maintenance of genomic imprints for DNA methylation events in the preimplantation embryo, including a role in imprinted X chromosome inactivation. © 2013 McGraw et al

When Less Is Best: Female Brown-Headed Cowbirds Prefer Less Intense Male Displays

Sexual selection theory predicts that females should prefer males with the most intense courtship displays. However, wing-spread song displays that male brown-headed cowbirds (Molothrus ater) direct at females are generally less intense than versions of this display that are directed at other males. Because male-directed displays are used in aggressive signaling, we hypothesized that females should prefer lower intensity performances of this display. To test this hypothesis, we played audiovisual recordings showing the same males performing both high intensity male-directed and low intensity female-directed displays to females (N = 8) and recorded the females' copulation solicitation display (CSD) responses. All eight females responded strongly to both categories of playbacks but were more sexually stimulated by the low intensity female-directed displays. Because each pair of high and low intensity playback videos had the exact same audio track, the divergent responses of females must have been based on differences in the visual content of the displays shown in the videos. Preferences female cowbirds show in acoustic CSD studies are correlated with mate choice in field and captivity studies and this is also likely to be true for preferences elucidated by playback of audiovisual displays. Female preferences for low intensity female-directed displays may explain why male cowbirds rarely use high intensity displays when signaling to females. Repetitive high intensity displays may demonstrate a male's current condition and explain why these displays are used in male-male interactions which can escalate into physical fights in which males in poorer condition could be injured or killed. This is the first study in songbirds to use audiovisual playbacks to assess how female sexual behavior varies in response to variation in a male visual display

Intravenous injection of neural progenitor cells improved depression-like behavior after cerebral ischemia

Poststroke depression (PSD) occurs in approximately one-third of stroke survivors and is one of the serious sequelae of stroke. The onset of PSD causes delayed functional recovery by rehabilitation and also increases cognitive impairment. However, appropriate strategies for the therapy against ischemia-induced depression-like behaviors still remain to be developed. Such behaviors have been associated with a reduced level of brain-derived neurotrophic factor (BDNF). In addition, accumulating evidence indicates the ability of stem cells to improve cerebral ischemia-induced brain injuries. However, it remains to be clarified as to the effect of neural progenitor cells (NPCs) on PSD and the association between BDNF level and PSD. Using NPCs, we investigated the effect of intravenous injection of NPCs on PSD. We showed that injection of NPCs improved ischemia-induced depression-like behaviors in the forced-swimming test and sucrose preference test without having any effect on the viable area between vehicle- and NPC-injected ischemic rats. The injection of NPCs prevented the decrease in the level of BDNF in the ipsilateral hemisphere. The levels of phosphorylated CREB, ERK and Akt, which have been implicated in events downstream of BDNF signaling, were also decreased after cerebral ischemia. NPC injection inhibited these decreases in the phosphorylation of CREB and ERK, but not that of Akt. Our findings provide evidence that injection of NPCs may have therapeutic potential for the improvement of depression-like behaviors after cerebral ischemia and that these effects might be associated with restoring BDNF-ERK-CREB signaling

Environmentally Realistic Exposure to the Herbicide Atrazine Alters Some Sexually Selected Traits in Male Guppies

Male mating signals, including ornaments and courtship displays, and other sexually selected traits, like male-male aggression, are largely controlled by sex hormones. Environmental pollutants, notably endocrine disrupting compounds, can interfere with the proper functioning of hormones, thereby impacting the expression of hormonally regulated traits. Atrazine, one of the most widely used herbicides, can alter sex hormone levels in exposed animals. I tested the effects of environmentally relevant atrazine exposures on mating signals and behaviors in male guppies, a sexually dimorphic freshwater fish. Prolonged atrazine exposure reduced the expression of two honest signals: the area of orange spots (ornaments) and the number of courtship displays performed. Atrazine exposure also reduced aggression towards competing males in the context of mate competition. In the wild, exposure levels vary among individuals because of differential distribution of the pollutants across habitats; hence, differently impacted males often compete for the same mates. Disrupted mating signals can reduce reproductive success as females avoid mating with perceptibly suboptimal males. Less aggressive males are at a competitive disadvantage and lose access to females. This study highlights the effects of atrazine on ecologically relevant mating signals and behaviors in exposed wildlife. Altered reproductive traits have important implications for population dynamics, evolutionary patterns, and conservation of wildlife species