Use of LigaSure vessel sealing system versus conventional axillary dissection in breast cancer patients: a retrospective comparative study.

BACKGROUND: In locally advanced breast cancer, axillary lymph node dissection remains a pivotal component of surgical therapy. Apart from this, it has been mostly replaced by sentinel node biopsy. Complications after axillary dissection include wound infection, neuropathy, lymphedema and-most frequently-seroma. In this retrospective multi-centre study, we compared the use of LigaSureTM with monopolar electrocautery regarding perioperative outcome. METHODS: A retrospective data analysis from female breast cancer patients who underwent axillary dissection at two breast centres in Austria that are using two different surgical techniques was performed for this study. We compared the rate of complications and re-operations, length of hospital stay, time to drain removal, total drain fluid, seroma formation after drain removal, number of seroma aspirations and total seroma fluid. RESULTS: Seventy one female patients with a median age of 63 (30-83) were included in this study. In 35 patients LigaSureTM and in 36 monopolar cautery was used for axillary dissection. There was no significant difference regarding intraoperative complications and rate of re-operations between the two groups (2.9 vs. 5.6%; p = 1 and 2.9 vs. 13.9%; p = 0.199). The time to drain removal and the length of hospital stay was similar in both groups. A significant difference in the occurence of postoperative wound infection could also not be shown. However, we found a significantly smaller total drain fluid in the LigaSureTM-group compared to the cautery-group (364.6 ml vs. 643.4 ml; p = 0.004). Seroma formation after drain removal was more frequent in the LigaSureTM-group (68.6 vs. 41.7%; p = 0.032) with a higher number of outpatient seroma aspirations (2.0 vs. 0.9; p = 0.005). CONCLUSION: LigaSureTM and monopolar cautery provide equivalent techniques in axillary lymph node dissection with comparable postoperative outcomes.

A Strong and Fortuitous Case of Dyspnea.

CASE: A 48 year-old man with no past medical history was sent to our emergency department (ED); from a primary care clinic for hypertensive urgency of 200/130. The man reported an intermittent non-productive cough of approximately one year's duration and worsening dyspnea on exertion and orthopnea over the last month with lower extremity swelling. Of note, he emigrated from Honduras twenty years ago. Blood pressure normalized with administration of Lasix in the ED. Physical exam revealed rales in lung bases bilaterally, jugular venous distension, lower extremity pitting edema with serpiginous patches of erythema and excoriation, and a cardiac gallop. Labs showed peripheral eosinophilia, thrombocytopenia, elevated creatinine, hyperbilirubinemia, hyperglycemia, and mild transaminitis. Transthoracic echocardiogram revealed a dilated left ventricle with global hypokinesis and severely depressed systolic function with an ejection fraction less than 15 percent . The patient was diuresed, and subsequent left and right heart catheterizations were normal. CT chest showed a small nodule in the right upper lobe. Tests for Coccidiosis, Trypanosoma cruzi, and Mycobacterium tuberculosis were negative; however the acid fast bacilli culture grew Mycobacterium fortuitum. A Strongyloides stercoralis antibody test was positive, and the patient was treated with two doses of oral ivermectin with one dose of intravenous ceftriaxone, and discharged. Two months later, his eosinophilia resolved, but he remained symptomatic with productive cough and weight loss, and was started on an outpatient course of oral ciprofloxacin and trimethoprim-sulfamethozole for M. fortuitum. DISSCUSION: Strongyloides-infected patients may carry the parasite for years without prominent symptoms. Endemic throughout South America, Strongyloides persists in its hosts through a lifecycle of autoinfection, which, over time, increases parasite burden and can lead to a hyperinfection syndrome whereby filiariform larvae penetrate organ tissue, most commonly: heart, central nervous system, lungs and liver. We suspect chronic eosinophilia and disseminated filiaria to be the etiology of the non-ischemic dilated cardiomyopathy in this patient. Standard treatment of strongyloidiasis is ivermectin, however, mortality owing to transient bacteremia in the setting of hyperinfection syndrome is high. Therefore, bacteremia prophylaxis with gram negative rod coverage should be considered before antiparasitic agent initiation.

Observation and Structure Determination of an Oxide Quasicrystal Approximant.

We report on the first observation of an approximant structure to the recently discovered two-dimensional oxide quasicrystal. Using scanning tunneling microscopy, low-energy electron diffraction, and surface x-ray diffraction in combination with ab initio calculations, the atomic structure and the bonding scheme are determined. The oxide approximant follows a 3^{2}.4.3.4 Archimedean tiling. Ti atoms reside at the corners of each tiling element and are threefold coordinated to oxygen atoms. Ba atoms separate the TiO_{3} clusters, leading to a fundamental edge length of the tiling 6.7 Å.

Screening for chromosomal abnormalities by first trimester combined screening and noninvasive prenatal testing.

PURPOSE: To examine combined first trimester screening (FTS), noninvasive prenatal testing (NIPT) and a two-step policy that combines FTS and NIPT in screening for aneuploidy. MATERIALS AND METHODS: Retrospective study involving 21,052 pregnancies where FTS was performed at the Praxis Praenatal.de in Duesseldorf, Germany. In each case, the sum risk of trisomy 21, 18 and 13 was computed. We assumed that NIPT detects 99 %, 98 %, 90 % and 99 % of cases with trisomy 21, 18, 13 and sex chromosomal abnormalities and that the false-positive rate is 0.5 %. The following screening policies were examined: NIPT or FTS with sum risk cut-offs of 1 in 50 and 1 in 250 in all patients or a two-step-policy with FTS in all patients followed by NIPT in the intermediate sum risk group. For the intermediate risk group, sum risk cut-offs of 1 in 50 and 1 in 1000 and 1 in 150 and 1 in 500 were used. RESULTS: There were 127, 34, 13 and 15 pregnancies with trisomy 21, 18, 13 and sex chromosomal abnormalities. 23 fetuses had other chromosomal abnormalities with an increased risk for adverse outcome that are not detectable by NIPT. 20,840 pregnancies were classified as normal as ante- and postnatal examinations did not show any signs of clinically significant chromosomal abnormalities. FTS with a sum risk cut-off of 1 in 50 and 1 in 250 detects 81 % and 91 % for all aneuploidies. NIPT detects 88 % of the respective pregnancies. The 2-step approach with sum risk cut-offs of 1 in 50 and 1 in 1000 detects 94 % of all aneuploidies. With sum risk cut-offs of 1 in 150 and 1 in 500, the detection rate is 93 %. CONCLUSION: A 2-step policy with FTS for all patients and NIPT in the intermediate risk group results in the highest detection rate of all aneuploidies.

Neurotrophins in the ventral tegmental area: Role in social stress, mood disorders and drug abuse.

This review discusses the impact of neurotrophins and other trophic factors, including fibroblast growth factor and glial cell line-derived neurotrophic factor, on mood disorders, weight regulation and drug abuse, with an emphasis on stress- and drug-induced changes in the ventral tegmental area (VTA). Neurotrophins, comprising nerve growth factor, brain-derived neurotrophic factor (BDNF), and neurotrophins 3 and 4/5 play important roles in neuronal plasticity and the development of different psychopathologies. In the VTA, most research has focused on the role of BDNF, because other neurotrophins are not found there in significant quantities. BDNF originating in the VTA provides trophic support to dopamine neurons. The diverse intracellular signaling pathways activated by BDNF may underlie precise physiological functions specific to the VTA. In general, VTA BDNF expression increases after psychostimulant exposures, and enhanced BDNF level in the VTA facilitates psychostimulant effects. The impact of VTA BDNF on the behavioral effects of psychostimulants relies primarily on its action within the mesocorticolimbic circuit. In the case of opiates, VTA BDNF expression and effects seem to be dependent on whether an animal is drug-naïve or has a history of drug use, only the latter of which is related to dopamine mechanisms. Social defeat stress that is continuous in mice or intermittent in rats increases VTA BDNF expression, and is associated with depressive and social avoidance behaviors. Intermittent social defeat stress induces persistent VTA BDNF expression that triggers psychostimulant cross-sensitization. Understanding the cellular and molecular substrates of neurotrophin effects may lead to novel therapeutic approaches for the prevention and treatment of substance use and mood disorders.

[Information seeking on the internet: what information are pregnant women seeking?]. / Recherche d'informations sur internet: quels sont les usages des femmes enceintes?

In the literature, uses of the internet by patients are interpreted either as a resource supporting their autonomy, or as a source of perturbation in the doctor-patient relationship. Analysing 50 interviews with pregnant women, this article aims at describing the different uses made during pregnancy. Some women mostly aim at sharing their experience in their use of internet. Others are looking for specialised information, by curiosity, to complement the information received in medical visits or, more rarely, as a result of a lack of information in their exchanges with professionals. Uses of internet by patients will develop in the future and it is important that professionals take into account these different forms of internet use in their practices.

Fetal gastroschisis: a comparison of second vs. third-trimester bowel dilatation for predicting bowel atresia and neonatal outcomes.

PURPOSE: To compare various gestational ages and thresholds for diagnosing bowel dilatation in fetuses with gastroschisis and to evaluate the prognostic value of bowel dilatation for predicting postnatal bowel atresia and neonatal outcomes. MATERIALS AND METHODS: This was a retrospective observational study conducted from March 1997 to September 2009 that included 78 pregnancies with fetal gastroschisis. The predictive value of prenatal bowel dilatation for neonatal bowel atresia and postnatal complications was investigated in three subgroups: those with bowel dilatations ≥ 10 mm at a gestational age < 27 + 0 weeks, ≥ 10 mm at a gestational age < 30 + 0 weeks and ≥ 18 mm at a gestational age ≥ 30 weeks. RESULTS: Prenatally, 6 %, 81 % and 13 % of the bowel malformations were identified in the first, second and third trimesters, respectively. There were three stillbirths and three neonatal deaths, and the mean gestational age at delivery was 35.4 weeks (range 31 + 4 to 41 + 6). Bowel atresia was significantly correlated with prenatal bowel dilatation in all three subgroups. Bowel dilatations of ≥ 10 mm before 30 + 0 gestational weeks achieved the best performance in predicting bowel atresia, with a sensitivity of 89 % (8 / 9) and a specificity of 79 % (30 / 38). A prenatal bowel diameter ≥ 10 mm through 30 completed weeks was also the best predictor of a prolonged neonatal hospital stay ≥ 8 weeks (sensitivity = 61.1, 11 / 18, p = 0.002). CONCLUSION: Fetuses with isolated gastroschisis successfully underwent postnatal surgery in most cases (93.2 %), except for one termination, one intrauterine death and 3 cases of neonatal death. A fetal bowel dilatation > 10 mm before 30 + 0 weeks had the highest predictive value for postnatal bowel complications.

Intermittent social defeat stress enhances mesocorticolimbic ΔFosB/BDNF co-expression and persistently activates corticotegmental neurons: implication for vulnerability to psychostimulants.

Intermittent social defeat stress exposure augments behavioral response to psychostimulants in a process termed cross-sensitization. Brain-derived neurotrophic factor (BDNF) mediates synaptic plasticity and cellular responses to stress and drugs of abuse. We previously showed that repeated social defeat stress persistently alters BDNF and activates ΔFosB expression in mesocorticolimbic regions. Here, we hypothesized that social defeat stress would increase ΔFosB expression in BDNF-containing mesocorticolimbic neurons at a time when cross-sensitization is evident. Because the ventral tegmental area (VTA) is critical for cross-sensitization, we similarly hypothesized that repeated social defeat stress would induce ΔFosB in neurons of mesocorticolimbic terminal regions that innervate the VTA. We induced social defeat stress in rats by short confrontations with an aggressive resident rat every third day for 10 days. Control rats were handled according to the same schedule. Defeated rats exhibited sensitized locomotor response to amphetamine (1.0mg/kg, i.p.) 10 days after termination of stress exposure. Separate rats, which underwent stress procedures without amphetamine challenge, were used for histological assessments. Rats received intra-VTA infusion of the retrograde tracer, Fluorogold (FG), and brain tissue was collected 10 days after stress or handling for immunohistochemistry. Stress exposure increased BDNF immunoreactivity in anterior cingulate, prelimbic and infralimbic regions of the prefrontal cortex (PFC), medial amygdala (AMY), nucleus accumbens (NAc) and VTA; ΔFosB labeling in anterior cingulate cortex (ACG) and nucleus accumbens; and ΔFosB/BDNF co-expression in prelimbic cortex (PL), nucleus accumbens and medial amygdala. Infralimbic ΔFosB-labeling was enhanced by stress in neurons innervating the VTA. Increased ΔFosB/BDNF co-expression and persistent functional activation of corticolimbic neurons after stress may contribute to mechanisms underlying cross-sensitization to psychostimulants.

Comparative analysis of SV40 17kT and LT function in vivo demonstrates that LT's C-terminus re-programs hepatic gene expression and is necessary for tumorigenesis in the liver.

Transformation by Simian Virus 40 (SV40) large T antigen (LT) is mediated in large part by its interaction with a variety of cellular proteins at distinct binding domains within LT. While the interaction of LT's N-terminus with the tumor suppressor Rb is absolutely required for LT-dependent transformation, the requirement for the interaction of LT's C-terminus with p53 is less clear and cell- and context-dependent. Here, we report a line of transgenic mice expressing a doxycycline-inducible liver-specific viral transcript that produces abundant 17kT, a naturally occurring SV40 early product that is co-linear with LT for the first 131 amino acids and that binds to Rb, but not p53. Comparative analysis of livers of transgenic mice expressing either 17kT or full length LT demonstrates that 17kT stimulates cell proliferation and induces hepatic hyperplasia but is incapable of inducing hepatic dysplasia or promoting hepatocarcinogenesis. Gene expression profiling demonstrates that 17kT and LT invoke a set of shared molecular signatures consistent with the action of LT's N-terminus on Rb-E2F-mediated control of hepatocyte transcription. However, 17kT also induces a unique set of genes, many of which are known transcriptional targets of p53, while LT actively suppresses them. LT also uniquely deregulates the expression of a subset of genes within the imprinted network and rapidly re-programs hepatocyte gene expression to a more fetal-like state. Finally, we provide evidence that the LT/p53 complex provides a gain-of-function for LT-dependent transformation in the liver, and confirm the absolute requirement for LT's C-terminus for liver tumor development by demonstrating that phosphatase and tensin homolog (PTEN)-deficiency readily cooperates with LT, but not 17kT, for tumorigenesis. These results confirm independent and inter-dependent functions for LT's N- and C-terminus and emphasize differences in the requirements for LT's C-terminus in cell-type dependent transformation.

Impact of maternal obesity and maternal overweight on the detection rate of fetal heart defects and the image quality of prenatal echocardiography.

PURPOSE: The purpose of this study was to compare the prenatal detection of four congenital heart defects (CHDs) and the image quality of five corresponding ultrasound planes among obese, overweight and normal-weight women. MATERIALS AND METHODS: This was a retrospective cohort study of 54,846 pregnancies undergoing fetal echocardiography between 18 and 37 weeks of gestation in the years from 2000 to 2007. The women were categorized according to pre-pregnancy body mass index (BMI) as normal-weight (BMI < 25), overweight (BMI 25 - 29.9) and obese (BMI ≥ 30). Image quality and prenatal detection of atrioventricular septal defect (AVSD), double outlet right ventricle (DORV), tetralogy of fallot (TOF) and dextro transposition of the great arteries (D-TGA) were evaluated in the BMI strata. RESULTS: 108 cases with one of the considered CHDs were identified. The prevalence was significantly higher (relative risk = 2.04) in overweight or obese women (57/19,404 vs. 51/35,442, p < 0.0002) than in normal-weight women. In total 86.1% of CHDs were correctly identified prenatally (93/108, CI: 79.6%-92.6%), 84.3% (43/51) in the normal weight group, 88.6% (39/44) in the overweight group and 84.6% (11/13) in the obese group. The rate of insufficient ultrasound images increased from 6.4% in normal-weight patients to 17.4% in obese women within the 108 CHD cases. CONCLUSION: The prenatal detection of fetal AVSD, DORV, TOF and D-TGA was also satisfactory in overweight and obese patients, but image quality substantially decreases with an increasing maternal BMI. If there is a BMI-associated difference in the detection rate, it probably will not exceed 20%.

[DLys(6)]-luteinizing hormone releasing hormone-curcumin conjugate inhibits pancreatic cancer cell growth in vitro and in vivo.

Pancreatic ductal adenocarcinomas are invariably lethal, and developing effective treatments that have minimal side effects is a challenge. Previous studies from our laboratory have shown that conjugates of cell membrane disrupting lytic peptides and luteinizing hormone releasing hormone (LHRH) target and destroy human prostate and breast cancer cells in xenografts in the nude mouse model (Hansel et al., Mol Cell Endocrinol 2007;260-262:183-9; Hansel et al., Mol Cell Endocrinol 2007;269:26-33), which express LHRH receptors. The objectives of our study were to synthesize a bioconjugate of LHRH analog ([DLys(6)]-LHRH) and a dietary microchemical (curcumin) and test the hypothesis that [DLys(6)]-LHRH-curcumin targets and inhibits pancreatic cancer cell growth in vitro and in vivo. In in vitro studies, we determined by confocal microscopy, flow cytometry analysis and reverse transcriptase-polymerase chain reaction that MIAPaCa-2, Panc-1 and BxPC-3 pancreatic cancer cell lines express LHRH receptors. [DLys(6)]-LHRH-curcumin inhibited cell proliferation of pancreatic cancer cell lines and induced apoptotic cell death (p < 0.05). Apoptosis was induced by cleavage of polyadenosine-5'-diphosphate-ribose-polymerase and caspase-3. The activity of [DLys(6)]-LHRH-curcumin was equal to free curcumin at equimolar concentrations in vitro. Unlike curcumin itself, the [DLys(6)]-LHRH-curcumin conjugate is water soluble which allows its intravenous administration. In two in vivo studies, [DLys(6)]-LHRH-curcumin given intravenously caused a significant (p < 0.01) reduction in tumor weights and volumes, and free curcumin given by gavage at an equal dose failed to cause a significant reduction in tumor weights and volumes in the nude mouse pancreatic cancer model. [DLys(6)]-LHRH-curcumin treatment enhanced apoptosis compared to [DLys(6)]-LHRH and vehicle-treated controls in tumor tissue. In conclusion, [DLys(6)]-LHRH-curcumin may be useful in treating pancreatic cancer.

Assessment of the ductus venosus, tricuspid blood flow and the nasal bone in second-trimester screening for trisomy 21.

OBJECTIVE: To examine the prevalence of reversed a-wave in the ductus venosus, tricuspid regurgitation and absent nasal bone, in a second-trimester population undergoing amniocentesis, after exclusion of major fetal defects and to estimate the performance in screening for trisomy 21 based on maternal age and these markers in a general population. METHODS: This was a retrospective study involving pregnancies undergoing amniocentesis due to increased risk for trisomy 21, mainly because of advanced maternal age. Before the invasive procedure, an ultrasound examination was carried out to exclude major fetal defects and to examine the ductus venosus, tricuspid blood flow and the presence of the fetal nasal bone. Modeling techniques were used based on 20 000 euploid pregnancies and 20 000 pregnancies with trisomy 21 to assess the screening performance in a general population. RESULTS: The study population consisted of 3613 euploid pregnancies and 35 cases with trisomy 21. In the euploid group, reversed flow in the ductus venosus, tricuspid regurgitation and an absent nasal bone was observed in 1.7%, 1.5% and 0.1% of cases, respectively. In the trisomic group, these markers were found in 14.3%, 11.4% and 14.3% of cases, respectively. For a 5% false-positive rate, the detection rate in screening for trisomy 21, based on maternal age and either ductus venosus, tricuspid blood flow or nasal bone would be 33.8%, 32.4% or 31.4%, respectively. Screening by maternal age alone would detect 29.0% of the fetuses with trisomy 21. Receiver-operating characteristics curve analysis showed a slight but significant improvement in screening performance for trisomy 21 based on the inclusion of these markers. CONCLUSION: Second-trimester ultrasound screening for trisomy 21 based on maternal age with additional assessment of the ductus venosus, tricuspid blood flow and the fetal nasal bone in otherwise normal-appearing fetuses is only marginally better than is screening by maternal age alone.

Short- and long-term effects of intermittent social defeat stress on brain-derived neurotrophic factor expression in mesocorticolimbic brain regions.

Social defeat stress is an ethologically salient stressor which activates dopaminergic areas and, when experienced repeatedly, has long-term effects on dopaminergic function and related behavior. The mechanism for these long-lasting consequences remains unclear. A potential candidate for mediating these effects is brain-derived neurotrophic factor (BDNF), a neurotrophin involved in synaptic plasticity and displaying alterations in dopaminergic regions in response to various types of stress. In this study, we sought to determine whether repeated social defeat stress altered BDNF mRNA and protein expression in dopaminergic brain regions either immediately after the last stress exposure or 4 weeks later. Male Sprague-Dawley rats were subjected to social defeat stress consisting of brief confrontation with an aggressive male rat every third day for 10 days; control rats were handled according to the same schedule. Animals were euthanized either 2 h or 28 days after the last stress or handling episode. Our results show that 2 h after stress, BDNF protein and mRNA expression increased in the medial prefrontal cortex. At this time-point, BDNF mRNA increased in the amygdala and protein expression increased in the substantia nigra. Twenty-eight days after stress, BDNF protein and mRNA expression were elevated in the medial amygdala and ventral tegmental area. Given the role of BDNF in neural plasticity, BDNF alterations that are long-lasting may be significant for neural adaptations to social stress. The dynamic nature of BDNF expression in dopaminergic brain regions in response to repeated social stress may therefore have implications for lasting neurochemical and behavioral changes related to dopaminergic function.

Genomic survey of prepulse inhibition in mouse chromosome substitution strains.

Prepulse inhibition (PPI) is a measure of sensorimotor gating, a pre-attentional inhibitory brain mechanism that filters extraneous stimuli. Prepulse inhibition is correlated with measures of cognition and executive functioning, and is considered an endophenotype of schizophrenia and other psychiatric illnesses in which patients show PPI impairments. As a first step toward identifying genes that regulate PPI, we performed a quantitative trait locus (QTL) screen of PPI phenotypes in a panel of mouse chromosome substitution strains (CSSs). We identified five CSSs with altered PPI compared with the host C57BL/6J strain: CSS-4 exhibited decreased PPI, whereas CSS-10, -11, -16 and -Y exhibited higher PPI compared with C57BL/6J. These data indicate that A/J chromosomes 4, 10, 11, 16 and Y harbor at least one QTL region that modulates PPI in these CSSs. Quantitative trait loci for the acoustic startle response were identified on seven chromosomes. Like PPI, habituation of the startle response is also disrupted in schizophrenia, and in the present study CSS-7 and -8 exhibited deficits in startle habituation. Linkage analysis of an F(2) intercross identified a highly significant QTL for PPI on chromosome 11 between positions 101.5 and 114.4 Mb (peak LOD = 4.54). Future studies will map the specific genes contributing to these QTLs using congenic strains and other genomic approaches. Identification of genes that modulate PPI will provide insight into the neural mechanisms underlying sensorimotor gating, as well as the psychopathology of disorders characterized by gating deficits.

PP2A-dependent disruption of centrosome replication and cytoskeleton organization in Drosophila by SV40 small tumor antigen.

Viruses of the DNA tumor virus family share the ability to transform vertebrate cells through the action of virus-encoded tumor antigens that interfere with normal cell physiology. They accomplish this very efficiently by inhibiting endogenous tumor suppressor proteins that control cell proliferation and apoptosis. Simian virus 40 (SV40) encodes two oncoproteins, large tumor antigen, which directly inhibits the tumor suppressors p53 and Rb, and small tumor antigen (ST), which interferes with serine/threonine protein phosphatase 2A (PP2A). We have constructed a Drosophila model for SV40 ST expression and show that ST induces supernumerary centrosomes, an activity we also demonstrate in human cells. In early Drosophila embryos, ST also caused increased microtubule stability, chromosome segregation errors, defective assembly of actin into cleavage furrows, cleavage failure, a rise in cyclin E levels and embryonic lethality. Using ST mutants and genetic interaction experiments between ST and PP2A subunit mutations, we show that all of these phenotypes are dependent on ST's interaction with PP2A. These analyses demonstrate the validity and utility of Drosophila as a model for viral oncoprotein function in vivo.

[Evaluation of malformations of the fetal central nervous system using fetal MRI]. / Das fetale MRT in der pränatalen Beurteilung von ZNS-Störungen.

PURPOSE: Ultrasound as the primary prenatal screening modality is used to detect fetal anomalies. Aim of the study was to prove the additional value of fetal magnetic resonance imaging (MRI). MATERIALS AND METHODS: In 25 pregnant women (age 30.6 +/- 4.8; 24 single and one twin pregnancy) with pathologic findings of the central nervous system detected by obstetric ultrasound, a fetal MRI was performed. All sequences (T2w-HASTE, TRUEFISP, T 1w-FLASH 2D, DWI) were performed using the breath-hold technique. The results were compared to postnatal MRI or ultrasound scan findings and tested for correlation with the clinical course and development of these children. RESULTS: Three to seven days after ultrasound, an MRI of all 26 fetuses without sedation was performed (26.6 +/- 4.0 GW). One healthy twin was not included in this study. MRI confirmed the ultrasonographic diagnosis in 7 cases. Compared to ultrasound, an additional pathology could be detected by MRI in 8 cases. In 10 cases ultrasound diagnosis was overruled by MRI. Prenatal MRI findings were confirmed by postnatal imaging in 18 children. The clinical course was predictable in 8 of 15 cases, depending on the pathology detected. Three newborns died in the perinatal period. CONCLUSION: Our results showed that fetal MRI has a high impact as an addition to ultrasound in evaluating congenital CNS pathology. Fetal MRI has become a helpful device for advising parents. However, clinical course and development still cannot be predicted based on MRI findings alone.

Associations of forest bird species richness with housing and landscape patterns across the USA.

In the United States, housing density has substantially increased in and adjacent to forests. Our goal in this study was to identify how housing density and human populations are associated with avian diversity. We compared these associations to those between landscape pattern and avian diversity, and we examined how these associations vary across the conterminous forested United States. Using data from the North American Breeding Bird Survey, the U.S. Census, and the National Land Cover Database, we focused on forest and woodland bird communities and conducted our analysis at multiple levels of model specificity, first using a coarse-thematic resolution (basic models), then using a larger number of fine-thematic resolution variables (refined models). We found that housing development was associated with forest bird species richness in all forested ecoregions of the conterminous United States. However, there were important differences among ecoregions. In the basic models, housing density accounted for < 5% of variance in avian species richness. In refined models, 85% of models included housing density and/or residential land cover as significant variables. The strongest guild response was demonstrated in the Adirondack-New England ecoregion, where 29% of variation in richness of the permanent resident guild was associated with housing density. Model improvements due to regional stratification were most pronounced for cavity nesters and short-distance migrants, suggesting that these guilds may be especially sensitive to regional processes. The varying patterns of association between avian richness and attributes associated with landscape structure suggested that landscape context was an important mediating factor affecting how biodiversity responds to landscape changes. Our analysis suggested that simple, broadly applicable, land use recommendations cannot be derived from our results. Rather, anticipating future avian response to land use intensification (or reversion to native vegetation) has to be conditioned on the current landscape context and the species group of interest. Our results show that housing density and residential land cover were significant predictors of forest bird species richness, and their prediction strengths are likely to increase as development continues.

Improved solid-phase synthesis of alpha,alpha-dialkylated amino acid-rich peptides with antimicrobial activity.

A homologous series of nonapeptides and their acetylated versions were successfully prepared using solid-phase synthetic techniques. Each nonapeptide was rich in alpha,alpha-dialkylated amino acids [one 4-aminopiperidine-4-carboxylic acid (Api) and six alpha-aminoisobutyric acid (Aib) residues] and also included lysines or lysine analogs (two residues). The incorporation of the protected dipeptide 9-fluorenylmethyloxycarbonyl (Fmoc)-Aib-Aib-OH improved the purity and overall yields of these de novo designed peptides. The helix preference of each nonapeptide was investigated in six different solvent environments, and each peptide's antimicrobial activity and cytotoxicity were studied. The 3(10)-helical, amphipathic design of these peptides was born out most prominently in the N-terminally acetylated peptides. Most of the peptides exhibited modest activity against Escherichia coli and no activity against Staphylococcus aureus. The nonacetylated peptides (concentrations < or =100 microM) and the acetylated peptides (concentrations < or = 200 microM) did not exhibit any significant cytotoxicity with normal (nonactivated) murine macrophages.

Long-term behavioral and neuronal cross-sensitization to amphetamine induced by repeated brief social defeat stress: Fos in the ventral tegmental area and amygdala.

Repeated exposure to stress induces cross-sensitization to psychostimulants. The present study assessed functional neural activation during social defeat stress-induced sensitization to a subsequent amphetamine challenge. Social defeat stress was induced in intruder rats during short confrontations with an aggressive resident rat once every third day during the course of 10 days. Rats received d-amphetamine injections (1 mg/kg, i.p.) 17 or 70 days after the first social defeat stress exposure. Amphetamine administration induced a significantly higher frequency of locomotor activity in stressed animals than in handled control rats, which was still evident 2 months after the last social stress exposure. Immunohistochemistry for Fos-like proteins was used to detect activated neural profiles in the striatum, nucleus accumbens (NAc), prefrontal cortex, amygdala, and ventral tegmental area (VTA). Repeated social defeat stress significantly increased Fos-like immunoreactive (Fos-LI) labeling 17 days after the start of stress exposure in the prelimbic and infralimbic cortical regions, NAc shell and core, medial, central and basolateral amygdala, and VTA, which probably represented the expression of chronic Fos-related antigens. Amphetamine augmented stress-induced Fos-LI labeling 17 days after the first stress episode in the dorsal striatum, NAc core, and medial amygdala, reflecting a cross-sensitization of Fos response. Amphetamine challenge 70 days after social stress exposures revealed sensitized Fos-LI labeling in the VTA and the amygdala. These data suggest that episodes of repeated social stress induce a long-lasting neural change that leads to an augmented functional activation in the VTA and amygdala, which might represent a neurobiological substrate for long-lasting cross-sensitization of repeated social defeat stress with psychostimulant drugs.