Single institutional experience of radiation therapy for angiosarcoma of the scalp without cervical lymph node metastases: Impact of concurrent chemoradiation with maintenance chemotherapy using taxanes on patient prognosis.
Cutaneous angiosarcoma is a rare aggressive malignant tumor. Concurrent chemoradiation (CCRT) with maintenance chemotherapy using taxanes is one of the primary treatments. The aim of the present study was to retrospectively analyze the efficacy of CCRT with maintenance chemotherapy using taxanes in localized angiosarcoma of the scalp without cervical lymph node metastases. A total of 19 patients treated with radiation therapy for localized angiosarcomas of the scalp without cervical lymph node metastases were enrolled. The overall survival (OS), progression-free survival (PFS), and local control (LC) rates were calculated using Kaplan-Meier analysis. Univariate analyses were performed for various potential prognostic factors for OS, PFS, and LC. The median radiation dose was 70 Gy (range, 60-70 Gy), and the fractional dose was 2 Gy. Radiation therapy alone, radiation therapy + interleukin-2, surgery + CCRT with maintenance chemotherapy, CCRT with maintenance chemotherapy, and CCRT without maintenance chemotherapy were administered to 2, 4, 2, 9 and 2 patients, respectively. The 1- and 3-year OS, PFS, and LC rates were 88 and 52%, 47 and 33%, and 74 and 56%, respectively. CCRT with maintenance chemotherapy and surgery were significant prognostic factors for PFS (P=0.036 and 0.025, respectively). Therefore, CCRT with maintenance chemotherapy using taxanes might be effective in treating localized angiosarcomas of the scalp without cervical lymph node metastases.


Noninvasive in vivo liver fibrosis evaluation using supersonic shear imaging: a clinical study on 113 hepatitis C virus patients.
Supersonic shear imaging (SSI) has recently been demonstrated to be a repeatable and reproducible transient bidimensional elastography technique. We report a prospective clinical evaluation of the performances of SSI for liver fibrosis evaluation in 113 patients with hepatitis C virus (HCV) and a comparison with FibroScan (FS). Liver elasticity values using SSI and FS ranged from 4.50 kPa to 33.96 kPa and from 2.60 kPa to 46.50 kPa, respectively. Analysis of variance (ANOVA) shows a good agreement between fibrosis staging and elasticity assessment using SSI and FS (p < 10(-5)). The areas under receiver operating characteristic (ROC) curves for elasticity values assessed from SSI were 0.948, 0.962 and 0.968 for patients with predicted fibrosis levels F ≥ 2, F ≥ 3 and F = 4, respectively. These values are compared with FS area under the receiver operating characteristic curve (AUROC) of 0.846, 0.857 and 0.940, respectively. This comparison between ROC curves is particularly significant for mild and intermediate fibrosis levels. SSI appears to be a fast, simple and reliable method for noninvasive liver fibrosis evaluation.


Symptom Burden in Advanced Soft-Tissue Sarcoma.
There is little information on symptom prevalence and severity in advanced soft-tissue sarcoma (STS). Understanding symptom burden will aid clinical consultations, clarify which symptom interventions are needed, and better define optimum timings of palliative and supportive care referrals. To describe symptom prevalence and severity in patients undergoing different treatment options for advanced STS: 1) first-line palliative chemotherapy (FLC), 2) active surveillance (AS) pre- and post-FLC, and 3) palliative care (PC) alone. Cross-sectional survey in one sarcoma center using the patient-reported Memorial Symptom Assessment Scale-Short Form (MSAS-SF). Symptom prevalence, severity, and MSAS-SF subscales were recorded before commencing a new treatment. Our results were compared with other MSAS-SF cancer and noncancer data. One-hundred and thirteen patients (mean age, 59 years) were recruited. Forty-two commenced FLC, 27 started AS pre-FLC, 24 AS post-FLC, and 20 PC alone. Median overall number of reported symptoms was 11 (range 1-31): which when stratified by treatment meant AS pre-FLC < AS post-FLC < FLC < PC alone (most symptomatic). The commonest physical symptoms were pain (77%; 95% CI 68-84), lack of energy (73%; CI 63-81) difficulty sleeping (56%; CI 46-65), feeling bloated (49%; CI 39-58), and dyspnea (49%; CI 39-58). Distress levels were commensurated with prevalence except for dyspnea, which was disproportionally less distressing. Psychological distress was moderate (mean MSAS-PSYCH: 1.39) but higher than comparative cancer data. Advanced STS patients have a clinically important symptom burden comparable to other cancers. Common symptoms should be screened and addressed appropriately, including timely PC involvement.


Holographic otoscope using dual-shot-acquisition for the study of eardrum biomechanical displacements.
Recently an optoelectronic holography system was deployed in the clinic with the purpose of quantifying the tympanic membrane (TM) displacements of various mammal species, the objective being the understanding of their middle ear biomechanics. The optoelectronic holography system has an in-line configuration where the data gathered is decoded using lensless digital holography with the Fresnel approximation. This paper presents quantitative data obtained from an acoustically excited postmortem chinchilla's TM. To achieve this we used a robust customized windowed unwrapping method to unwrap the noisy optical phase obtained by subtracting phase maps of two recorded holograms and the results were compared with those obtained when using the unwrapping branch-cut algorithm. Additionally, phase maps obtained by the phase-stepping technique were compared applying both unwrapping methods. For in vivo applications particular emphasis is made on post-processing dual-shot-acquisition of holograms as one of various acquisition strategies and algorithms to diminish measurement error due to heartbeat, breathing, and patient's head motion as well as environment induced mechanical disturbances present in a noncontrolled environment, such as in a clinic. By recording only two holograms representing a stationary and deformed state of eardrum, respectively, we can increase the acquisition speed of the camera used to record faster events happening on the TM surface.


Identification and functional characterisation of novel glucokinase mutations causing maturity-onset diabetes of the young in Slovakia.
Heterozygous glucokinase (GCK) mutations cause a subtype of maturity-onset diabetes of the young (GCK-MODY). Over 600 GCK mutations have been reported of which ∼65% are missense. In many cases co-segregation has not been established and despite the importance of functional studies in ascribing pathogenicity for missense variants these have only been performed for <10% of mutations. The aim of this study was to determine the minimum prevalence of GCK-MODY amongst diabetic subjects in Slovakia by sequencing GCK in 100 Slovakian probands with a phenotype consistent with GCK-MODY and to explore the pathogenicity of identified variants through family and functional studies. Twenty-two mutations were identified in 36 families (17 missense) of which 7 (I110N, V200A, N204D, G258R, F419S, c.580-2A>C, c.1113-1114delGC) were novel. Parental DNA was available for 22 probands (covering 14/22 mutations) and co-segregation established in all cases. Bioinformatic analysis predicted all missense mutations to be damaging. Nine (I110N, V200A, N204D, G223S, G258R, F419S, V244G, L315H, I436N) mutations were functionally evaluated. Basic kinetic analysis explained pathogenicity for 7 mutants which showed reduced glucokinase activity with relative activity indices (RAI) between 0.6 to <0.001 compared to wild-type GCK (1.0). For the remaining 2 mutants additional molecular mechanisms were investigated. Differences in glucokinase regulatory protein (GKRP) -mediated-inhibition of GCK were observed for both L315H & I436N when compared to wild type (IC(50) 14.6±0.1 mM & 20.3±1.6 mM vs.13.3±0.1 mM respectively [p<0.03]). Protein instability as assessed by thermal lability studies demonstrated that both L315H and I436N show marked thermal instability compared to wild-type GCK (RAI at 55°C 8.8±0.8% & 3.1±0.4% vs. 42.5±3.9% respectively [p<0.001]). The minimum prevalence of GCK-MODY amongst Slovakian patients with diabetes was 0.03%. In conclusion, we have identified 22 GCK mutations in 36 Slovakian probands and demonstrate that combining family, bioinformatic and functional studies can aid the interpretation of variants identified by molecular diagnostic screening.


The scent of senescence: age-dependent changes in the composition of the cephalic gland secretion of the male European beewolf, Philanthus triangulum.
The process of aging inevitably leads to changes in physiology, performance and fertility of eukaryotic organisms and results in trade-offs in the resource allocation between current and future reproduction and longevity. Such constraints may also affect the production of complex and costly signals used for mate attraction and might therefore be important in the context of mate choice. We investigated age-related changes in the amount and composition of the cephalic gland secretion that male European beewolves, Philanthus triangulum (Hymenoptera, Crabronidae) use to mark their territories. The secretion mainly consists of eleven long-chain compounds with large proportions of a carbon acid, a ketone and two alcohols, and small proportions of several alkanes and alkenes. Both the total amount and the composition of the gland content varied with age. The four compounds with functional groups were present in much lower proportions in very young and very old males compared to middle-aged males, suggesting that these components may be more costly than the alkanes and alkenes. Thus, physiological constraints may cause the delayed onset and early decline of these substances in the cephalic gland. There were also minor but significant changes in four components among the middle-aged males. These age-related changes in the amount and composition of the male marking secretion might provide reliable indicators for female choice.


Anopheles gambiae immune responses to Sephadex beads: involvement of anti-Plasmodium factors in regulating melanization.
We have performed a global genome expression analysis of mosquito responses to CM-25 Sephadex beads and identified 27 regulated immune genes, including several anti-Plasmodium factors and other components with likely roles in melanization. Silencing of two bead injection responsive genes, TEP1 and LRIM1, which encode proteins known to mediate Plasmodium killing, significantly compromised the ability to melanize the beads. In contrast, silencing of two Plasmodium protective c-type lectins, CTL4 and CTLMA2, did not affect bead melanization. This data suggest that the anti-Plasmodium factors have dual functions, as determinants of both Plasmodium killing and melanization of the parasite and other foreign bodies, while the Plasmodium protective factors are specifically utilized by the parasite for evasion of mosquito defense mechanisms.


Hypnosis reduces distress and duration of an invasive medical procedure for children.
Voiding cystourethrography (VCUG) is a commonly performed radiologic procedure in children that can be both painful and frightening. Given the distress that some children experience during the VCUG and the need for children to be alert and cooperative during the procedure, finding a psychological intervention that helps children to manage anxiety, distress, and pain is clearly desirable. This study was designed to examine whether relaxation and analgesia facilitated with hypnosis could reduce distress and procedure time for children who undergo this procedure. Forty-four children who were scheduled for an upcoming VCUG were randomized to receive hypnosis (n = 21) or routine care (n = 23) while undergoing the procedure. The sample consisted of 29 (66%) girls and 15 (34%) boys with a mean age of 7.6 years (SD: 2.5; range: 4-15 years). Ethnic/racial backgrounds were 72.7% white, 18.2% Asian, 4.5% Latino, 2.3% black, and 2.3% Filipino. The mean number of previous VCUGs was 2.95 (SD: 2.51; mode: 2; range: 1-15). Potential participants were identified through computerized hospital records of upcoming VCUGs. Parents were contacted by telephone and invited to participate if their child was eligible. To be eligible for the study, the child must have undergone at least 1 previous VCUG, been at least 4 years of age at that time, and experienced distress during that procedure, and both the child and the participating parent had to be English speaking. Each eligible child and parent met with the research assistant (RA) before the day of the scheduled procedure for an initial assessment. Children were queried regarding the degree of crying, fear, and pain that they had experienced during their most recent VCUG. Parents completed a series of parallel questions. Immediately after this assessment, those who were randomized to the hypnosis condition were given a 1-hour training session in self-hypnotic visual imagery by a trained therapist. Parents and children were instructed to practice using the imaginative self-hypnosis procedure several times a day in preparation for the upcoming procedure. The therapist was also present during the procedure to conduct similar exercises with the child. The majority (83%) of those who were randomized to the routine care control group chose to participate in a hospital-provided recreation therapy program (offered as part of routine care). The program includes demonstration of the procedure with dolls, relaxation and breath work training, and assistance during the procedure. On the day of the VCUG, the RA met the family at the clinic before the procedure, and both the child and the parent rated the child's present level of fearfulness. During the procedure, the RA recorded observational ratings of the child's emotional tone and behavior and timed the overall procedure and its phases. Immediately after the VCUG, the child was asked how much crying, fear, and pain he or she had experienced during the procedure; the parent rated the child's experience on the same dimensions and also how traumatic the procedure had been (both generally and compared with their previous one), and the medical staff rated the degree of procedural difficulty. Outcomes included child reports of distress during the procedure, parent reports of how traumatic the present VCUG was compared with the previous one, observer ratings of distress during the procedure, medical staff reports of the difficulty of the procedure overall, and total procedural time. Results indicate significant benefits for the hypnosis group compared with the routine care group in the following 4 areas: (1) parents of children in the hypnosis group compared with those in the routine care group reported that the procedure was significantly less traumatic for their children compared with their previous VCUG procedure; (2) observational ratings of typical distress levels during the procedure were significantly lower for children in the hypnosis condition compared with those in the routine care condition; (3) medical staff reported a significant difference between groups in the overall difficulty of conducting the procedure, with less difficulty reported for the hypnosis group; and (4) total procedural time was significantly shorter-by almost 14 minutes-for the hypnosis group compared with the routine care group. Moderate to large effect sizes were obtained on each of these 4 outcomes. Hypnotic relaxation may provide a systematic method for improving the overall medical care of children with urinary tract abnormalities and may be beneficial for children who undergo other invasive medical procedures. Because the VCUG is an essential part of the evaluation of urinary tract infections and vesicoureteral reflux in children, lower distress during the procedure may improve patient and family compliance with initial as well as follow-up evaluations. These findings augment the accumulating literature demonstrating the benefits of using hypnosis to reduce distress in the pediatric setting. The present findings are noteworthy in that this study was a controlled, randomized trial conducted in a naturalistic medical setting. In this context, we achieved a convergence of subjective and objective outcomes with moderate to large effect sizes, including those that may have an impact on patient care and procedure cost, that were consistently supportive of the beneficial effects of hypnosis-a noninvasive intervention with minimal risk. The findings, therefore, have immediate implications for pediatric care. Limitations of this study include the lack of participant and staff blindness to the child's condition assignment, which could have introduced bias into reports. However, the objective procedural time differences between groups were consistent with the other, more subjective outcome findings. The sample was also small and primarily white in ethnic/racial makeup, which may have restricted our ability to detect some differences and may limit the generalizability of findings to more representative samples. In addition, the sample comprised children who had already undergone at least 1 VCUG during which they had had difficulty. Consequently, additional research is needed to determine whether hypnosis would be helpful to those who are undergoing their first VCUG. Additional limitations, clinical observations, and directions for future research are also discussed.


Sensorimotor learning configures the human mirror system.
Cells in the "mirror system" fire not only when an individual performs an action but also when one observes the same action performed by another agent [1-4]. The mirror system, found in premotor and parietal cortices of human and monkey brains, is thought to provide the foundation for social understanding and to enable the development of theory of mind and language [5-9]. However, it is unclear how mirror neurons acquire their mirror properties -- how they derive the information necessary to match observed with executed actions [10]. We address this by showing that it is possible to manipulate the selectivity of the human mirror system, and thereby make it operate as a countermirror system, by giving participants training to perform one action while observing another. Before this training, participants showed event-related muscle-specific responses to transcranial magnetic stimulation over motor cortex during observation of little- and index-finger movements [11-13]. After training, this normal mirror effect was reversed. These results indicate that the mirror properties of the mirror system are neither wholly innate [14] nor fixed once acquired; instead they develop through sensorimotor learning [15, 16]. Our findings indicate that the human mirror system is, to some extent, both a product and a process of social interaction.


Bombesin-like peptides: studies on food intake and social behaviour with receptor knock-out mice.
Bombesin (BN)-like peptides and receptors for these peptides are widely distributed in mammalian peripheral tissues and the central nervous system. The physiological and behavioural functions of these peptides have been clarified by both in vivo and in vitro studies. In spite of intensive investigations, the functions of endogenous BN-like peptides remain unclear. In order to specify these functions, our group and another laboratory generated by gene targeting mutant mice that lack one of the three BN-like peptide receptors found in mammals, ie neuromedin B receptor (NMB-R; BB1), gastrin-releasing peptide receptor (GRP-R; BB2), or bombesin receptor subtype-3 (BRS-3; BB3). Using these mutant mouse, we have found unexpected phenotypes, such as hyperphagia and obesity in the BRS-3-deficient mouse, and abnormal social behaviour in the GRP-R-deficient mouse. In the present study, we present our most recent findings in addition to previous studies and discuss the functions of BN-like peptides related to feeding and social behaviour from the point of view of knock-out mice studies.


Is Ki-67 a better proliferative marker in the colon than proliferating cell nuclear antigen?
Endogenous markers of proliferating cells have increasingly supplanted the use of incubation of biopsy tissues in vitro with tritiated thymidine or with bromodeoxyuridine, thus avoiding the potential variation resulting from the incubation procedure. Antibodies to proliferating cell nuclear antigen (PCNA) such as PC10 have been promoted as optimal for this purpose, although considerable variation in colonic proliferating cells with this antibody has been reported. We have compared the detection of colonic proliferating cells in normal mucosa and adenomata using the PC10 monoclonal antibody (mAb) to PCNA and the Mib-1 mAb to Ki-67 in formalin-fixed tissues using antigen retrieval solutions with microwaving. The PC10 antibody showed variable immunostaining of proliferating and nonproliferating cells with minor changes in primary antibody concentration or microwave conditions and between normal and adenomatous tissue. In contrast, Mib-1 immunostaining was quite constant with differing antigen retrieval and antibody conditions and similar staining of proliferating cells in colonic adenomas. Some loss of immunoreactivity occurred if the cut sections were not immunostained within approximately 1 week. These data suggest that whereas PCNA immunohistochemistry is satisfactory when carefully controlled in large chemopreventive studies, the Mib-1 mAb to Ki-67 is superior to PCNA antibodies in immunostaining proliferating cells in the formalin-fixed human colon.


C-Reactive Protein as a Therapeutic Target in Age-Related Macular Degeneration.
Age-related macular degeneration (AMD), a retinal degenerative disease, is the leading cause of central vision loss among the elderly population in developed countries and an increasing global burden. The major risk is aging, compounded by other environmental factors and association with genetic variants for risk of progression. Although the etiology of AMD is not yet clearly understood, several pathogenic pathways have been proposed, including dysfunction of the retinal pigment epithelium, inflammation, and oxidative stress. The identification of AMD susceptibility genes encoding complement factors and the presence of complement and other inflammatory mediators in drusen, the hallmark deposits of AMD, support the concept that local inflammation and immune-mediated processes play a key role in AMD pathogenesis that may be accelerated through systemic immune activation. In this regard, increased levels of circulating C-reactive protein (CRP) have been associated with higher risk of AMD. Besides being a risk marker for AMD, CRP may also play a role in the progression of the disease as it has been identified in drusen, and we have recently found that its monomeric form (mCRP) induces blood retinal barrier disruption in vitro. In this review, we will address recent evidence that links CRP and AMD pathogenesis, which may open new therapeutic opportunities to prevent the progression of AMD.


Peritoneal cytology in patients with potentially resectable adenocarcinoma of the pancreas.
The prognostic significance of malignant cells in the peritoneal washings of patients with pancreatic adenocarcinoma remains poorly defined. Prior reports suggest that positive peritoneal cytology (PPC) is associated with advanced disease and reduced survival. To determine the prognostic value of PPC in patients with pancreatic cancer, we retrospectively reviewed our database between July 1987 and September 2002 and identified 168 patients who had undergone exploration for potentially resectable pancreatic cancer with peritoneal washings performed at the time of exploration. One hundred thirty-five patients underwent resection; 33 were considered unresectable. PPC was reported for 27 patients (16.1%): 13 (9.6%) in the resected and 14 (42.4%) in the unresected group. Median time to macroscopically detected recurrence in the resected group was not significantly different in the PPC versus negative peritoneal cytology (NPC) patients (10 vs 12 months, P = 0.46). Median overall survival of patients with PPC versus NPC approached, but did not reach, significance (15 vs 19 months, P = 0.055). Peritoneal cytology status was not associated with administration of chemoradiation, margin status, antecedent fine-needle aspiration, stage, or site of recurrence. These data suggest that malignant cells in peritoneal washings of patients with potentially resectable pancreatic adenocarcinoma should not preclude resection. Long-term survival may be achieved, therefore aggressive treatment should strongly be considered.


Infusion device standardisation and dose error reduction software.
In 2004, the National Patient Safety Agency (NPSA) released a safety alert relating to the management and use of infusion devices in England and Wales. The alert called for the standardisation of infusion devices and a consideration of using centralised equipment systems to manage device storage. There has also been growing interest in smart-pump technology, such as dose error reduction software (DERS) as a way to reduce IV medication errors. However, questions remain about the progress that has been made towards infusion device standardisation and the adoption of DERS. In this article, the authors report the results of a survey investigating the extent to which the standardisation of infusion devices has occurred in the last 10 years and centralised equipment libraries are being used in practice, as well as the prevalence of DERS use within the UK. Findings indicate that while reported standardisation levels are high, use of centralised equipment libraries remains low, as does DERS usage.


Attitudes and the environment as determinants of active travel in adults: what do and don't we know?
Walking and cycling for transport, or 'active travel,' has the potential to contribute to overall physical activity levels. However, a wide range of factors are hypothesized to be associated with adult's active travel behavior. This paper describes current knowledge of the psychological and environmental determinants of active travel in adults, and considers ways in which the 2 domains can be better integrated. Quantitative studies were reviewed which examined psychological and environmental influences on active travel in an adult population. Studies were classified according to whether they examined psychological, environmental or both types of factor. Fourteen studies were identified which examined psychological correlates of active travel behavior in adults, and 36 which examined environmental correlates. Seven studies were identified which considered both domains, of which only 2 of explored the interactions between personal, social and environmental factors. The majority of the evidence is helpful in identifying correlates rather than determinants of active travel behavior. To further our understanding of the influences of active travel, there is a need for more research which integrates both individual and environmental domains and examines how they interact.


Characterization of the Complete Genome and P0 Protein for a Previously Unreported Genotype of Cotton Leafroll Dwarf Virus, an Introduced Polerovirus in the United States.
Virus-like disease symptoms consisting of leaf cupping, shortened internodes, and overall stunting were observed in commercial cotton fields in Alabama in 2017 to 2018. To determine the complete genome sequence of the suspected causal polerovirus, symptomatic leaf samples were collected in Macon County, Alabama, and subjected to Illumina RNA sequencing. Based on BLASTn analysis, the Illumina contig of 5,771 nt shared the highest nucleotide identity (approximately 95%) with members of the species Cotton leafroll dwarf virus (CLRDV) (genus Polerovirus; family Luteoviridae) from Argentina and Brazil. The full-length viral genome sequence was verified by reverse transcription (RT)-PCR amplification, cloning, and Sanger sequencing. The complete CLRDV genome of 5,865 nt in length shared 94.8 to 95.2% nucleotide identity with six previously reported CLRDV isolates. The genome of the CLRDV isolate amplified from Alabama samples (CLRDV-AL) has seven predicted open reading frames (ORFs). Viral proteins 1 to 5 (P1 to P5) shared 91.9 to 99.5% amino acid identity with the six CLRDV isolates from Argentina and Brazil. However, P0, the suppressor of host gene silencing, shared 82.4 to 88.5% pairwise amino acid identity with the latter CLRDV isolates. Phylogenetic analysis of the seven full-length CLRDV genomes resolved three sister clades: CLRDV-AL, CLRDV-typical, and CLRDV-atypical, respectively. Three recombination events were detected by the recombination detection program among the seven CLRDV isolates with breakpoints occurring along the genome. Pairwise nucleotide identity comparisons of ORF0 sequences for the three CLRDV-AL field isolates indicated that they were >99% identical, suggesting that this previously unknown CLRDV genotype represents a single introduction to Alabama.


Angiogenic factors stimulate tubular branching morphogenesis of sonic hedgehog-deficient lungs.
Sonic Hedgehog (Shh)-deficient mice have a severe lung branching defect. Recent studies have shown that hedgehog signaling is involved in vascular development and it is possible that the diminished airway branching in Shh-deficient mice is due to abnormal pulmonary vasculature formation. Therefore, we investigated the role of Shh in pulmonary vascular development using Shh/Tie2lacZ compound mice, which exhibit endothelial cell-specific LacZ expression, and Pecam-1 immunohistochemistry. In E11.5-13.5 Shh-deficient mice, the pulmonary vascular bed is decreased, but appropriate to the decrease in airway branching. However, when E12.5 Shh-deficient lungs were cultured for 4-6 days, the vascular network deteriorated compared to wild-type lungs. The expression of vascular endothelial growth factor (Vegf) or its receptor Vegfr2 (KDR/Flk-1) was not different between E12.5-13.5 Shh-deficient and wild-type lungs. In contrast, angiopoietin-1 (Ang1), but not Ang2 or the angiopoietin receptor Tie2, mRNA expression was downregulated in E12.5-E13.5 lungs of Shh null mutants. Recombinant Ang1 alone was unable to restore in vitro branching morphogenesis in Shh-deficient lungs. Conversely, the angiogenic factor fibroblast growth factor (Fgf)-2 alone or in combination with Ang1, increased vascularization and tubular growth and branching of Shh-deficient lungs in vitro. The angiogenic factors did not overcome the reduced smooth muscle cell differentiation in the Shh null lungs. These data indicate that early vascular development, mediated by Vegf/Vegfr2 signaling proceeds normally in Shh-deficient mice, while later vascular development and stabilization of the primitive network mediated by the Ang/Tie2 signaling pathway are defective, resulting in an abnormal vascular network. Stimulation of vascularization with angiogenic factors such as Fgf2 and Ang1 partially restored tubular growth and branching in Shh-deficient lungs, suggesting that vascularization is required for branching morphogenesis.


Salivary testosterone does not predict mental rotation performance in men or women.
Multiple studies report relationships between circulating androgens and performance on sexually differentiated spatial cognitive tasks in human adults, yet other studies find no such relationships. Relatively small sample sizes are a likely source of some of these discrepancies. The present study thus tests for activational effects of testosterone (T) using a within-participants design by examining relationships between diurnal fluctuations in salivary T and performance on a male-biased spatial cognitive task (Mental Rotation Task) in the largest sample yet collected: 160 women and 177 men. T concentrations were unrelated to within-sex variation in mental rotation performance in both sexes. Further, between-session learning-related changes in performance were unrelated to T levels, and circadian changes in T were unrelated to changes in spatial performance in either sex. These results suggest that circulating T does not contribute substantially to sex differences in spatial ability in young men and women. By elimination, the contribution of androgens to sex differences in human performance on these tasks may be limited to earlier, organizational periods.


Intracellular digestion of reovirus particles requires a low pH and is an essential step in the viral infectious cycle.
Lysosomotropic drugs such as NH4Cl have been useful for studying the role of low pH in early events in virus infection. NH4Cl blocks the production of infectious progeny virus in mammalian reovirus-infected cells. The inhibitory effect of NH4Cl is mediated by an inhibition of intracellular digestion of reovirus outer capsid proteins. In vitro digestion of viral outer capsid proteins produces infectious partially uncoated particles, called intermediate subviral particles, which are no longer inhibited by the presence of NH4Cl. These results indicate that proteolytic processing of reovirus outer capsid proteins takes place in a low pH compartment of the cell and is an essential step in the viral infectious cycle.


Structural Order in Cellulose Thin Films Prepared from a Trimethylsilyl Precursor.
Biopolymer cellulose is investigated in terms of the crystallographic order within thin films. The films were prepared by spin-coating of a trimethylsilyl cellulose precursor followed by an exposure to HCl vapors; two different source materials were used. Careful precharacterization of the films was performed by infrared spectroscopy and atomic force microscopy. Subsequently, the films were investigated by grazing incidence X-ray diffraction using synchrotron radiation. The results showed broad diffraction peaks, indicating a rather short correlation length of the molecular packing in the range of a few nanometers. The analysis of the diffraction patterns was based on the known structures of crystalline cellulose, as the observed peak pattern was comparable to cellulose phase II and phase III. The dominant fraction of the film is formed by two different types of layers, which are oriented parallel to the substrate surface. The stacking of the layers results in a one-dimensional crystallographic order with a defined interlayer distance of either 7.3 or 4.2 Å. As a consequence, two different preferred orientations of the polymer chains are observed. In both cases, polymer chain axes are aligned parallel to the substrate surface, and the orientation of the cellulose molecules are concluded to be either edge-on or flat-on. A minor fraction of the cellulose molecules form nanocrystals that are randomly distributed within the films. In this case, the molecular packing density was found to be smaller in comparison to the known crystalline phases of cellulose.


[Effects of intramuscular and perineural clonidine on sciatic nerve block with 0.5% ropivacaine.].
This study evaluated the effects of clonidine on anesthesia onset, quality and duration of analgesia of sciatic nerve block using 0.5% ropivacaine. Forty adult patients scheduled for foot or lateral aspect of the ankle procedures under combined anterior femoral/sciatic nerves block were randomly assigned to group 1, receiving 25 mL of 0.5% ropivacaine plus placebo perineurally, group 2, receiving intramuscular 2 microg.kg-1 clonidine and perineural 25 mL of 0.5% ropivacaine and group 3, receiving perineural 2 microg.kg-1 clonidine and 25 mL of 0.5% ropivacaine injected after motor responses were obtained with stimulations between 0.2 and 0.5 mA. Sensory and motor blocks were assessed for 30 minutes after blockade. A total block effectiveness score was calculated. The quality of surgical anesthesia was classified as success or failure according to the need for systemic intraoperative supplementation. Duration of anesthesia was defined as time from blockade placement until the first analgesic request. Median onset times were 5, 12.5, and 17.5 minutes for groups 1, 2 and 3, respectively (p = 0.11). Success rates were 100%, 93% and 75% (p = 0.12), and postoperative analgesia duration was 14.5, 13.5 and 13.75 hours (p = 0.15) for groups 1, 2 and 3, respectively. Intramuscular or perineural clonidine has not affected anesthetic onset, quality or the duration of postoperative analgesia of 0.5% ropivacaine-induced sciatic nerve block.


Internet gaming disorder and online gambling disorder: Clinical and personality correlates.
Background and aims The recent growth of Internet use has led to an increase of potentially problematic behaviors that can be engaged online, such as online gambling or Internet gaming. The aim of this study is to better conceptualize Internet gaming disorder (IGD) by comparing it with gambling disorder (GD) patients who only gamble online (online GD). Methods A total of 288 adult patients (261 online GD and 27 IGD) completed self-reported questionnaires for exploring psychopathological symptoms, food addiction (FA), and personality traits. Results Both clinical groups presented higher psychopathological scores and less functional personality traits when compared with a normative Spanish population. However, when comparing IGD to online GD, some singularities emerged. First, patients with IGD were younger, more likely single and unemployed, and they also presented lower age of disorder onset. In addition, they displayed lower somatization and depressive scores together with lower prevalence of tobacco use but higher FA scores and higher mean body mass index. Finally, they presented lower novelty seeking and persistence traits. Discussion GD is fully recognized as a behavioral addiction, but IGD has been included in the Appendix of DSM-5 as a behavioral addiction that needs further study. Our findings suggest that IGD and online GD patients share some emotional distress and personality traits, but patients with IGD also display some differential characteristics, namely younger age, lower novelty seeking scores and higher BMI, and FA scores. Conclusions IGD presents some characteristics that are not extensive to online GD. These specificities have potential clinical implications and they need to be further studied.


Antibiotics for the treatment of dysentery in children.
Ciprofloxacin, ceftriaxone and pivmecillinam are the antibiotics currently recommended by the World Health Organization (WHO) for the treatment of dysentery in children; yet there have been no reviews of the clinical effectiveness of these antibiotics in recent years. We reviewed all literature reporting the effect of ciprofloxacin, ceftriaxone and pivmecillinam for the treatment of dysentery in children in the developing countries. We used a standardized abstraction and grading format and performed meta-analyses to determine the effect of treatment with these antibiotics on rates of treatment failure, bacteriological failure and bacteriological relapse. The CHERG Standard Rules were applied to determine the final effect of treatment with these antibiotics on diarrhoea mortality. Eight papers were selected for abstraction. Treatment with ciprofloxacin, ceftriaxone or pivmecillinam resulted in a cure rate of >99% while assessing clinical failure, bacteriological failure and bacteriological relapse. The antibiotics recommended by the WHO--ciprofloxacin, ceftriaxone and pivmecillinam--are effective in reducing the clinical and bacteriological signs and symptoms of dysentery and thus can be expected to decrease diarrhoea mortality attributable to dysentery.


The potential for interaction of tolbutamide with pomegranate juice against diabetic induced complications in rats.
Pomegranate can inhibit cytochrome P450 (CYP) 2C9 activity, which is largely responsible for the metabolism of sulfonylureas. The present study was undertaken to evaluate the pharmacokinetic and pharmacodynamic interaction of pomegranate and tolbutamide (TOL) against diabetic-induced complications. Diabetes was induced via administration of alloxan (150 mg/kg, intraperitoneally). Rats (n = 8) were treated with pomegranate juice (PJ) [3 mL/animal, per os (p.o.)], TOL (20 mg/kg, p.o.), and their combination for 4 weeks. Twenty-four hours after the last treatment, the pharmacodynamic interaction of PJ and TOL was evaluated by antinociceptive activity, electrocardiographic parameters, serum glucose, biomarkers, and lipid profile values. The influence of PJ on the pharmacokinetics of TOL was studied using the high performance liquid chromatography method. The combination of PJ and TOL resulted in a significant improvement against diabetic complications compared to the group treated with TOL alone. The combination group was found to be the best protective group by significant improvement of antinociceptive activity, restoration of electrocardiographic parameters, serum glucose, biomarkers, and lipid profile compared to the group treated with TOL alone. Results of the pharmacokinetic study revealed that PJ increases bioavailability and half-life, along with a decrease in clearance and elimination rate of TOL. From this study, it can be concluded that the combination of PJ and TOL exhibited profound protection compared to TOL alone against diabetic complications. The findings of pharmacokinetic interaction justified the results of pharmacodynamic interaction.


SHP2 is required for growth of KRAS-mutant non-small-cell lung cancer in vivo.
RAS mutations are frequent in human cancer, especially in pancreatic, colorectal and non-small-cell lung cancers (NSCLCs)1-3. Inhibition of the RAS oncoproteins has proven difficult4, and attempts to target downstream effectors5-7 have been hampered by the activation of compensatory resistance mechanisms8. It is also well established that KRAS-mutant tumors are insensitive to inhibition of upstream growth factor receptor signaling. Thus, epidermal growth factor receptor antibody therapy is only effective in KRAS wild-type colon cancers9,10. Consistently, inhibition of SHP2 (also known as PTPN11), which links receptor tyrosine kinase signaling to the RAS-RAF-MEK-ERK pathway11,12, was shown to be ineffective in KRAS-mutant or BRAF-mutant cancer cell lines13. Our data also indicate that SHP2 inhibition in KRAS-mutant NSCLC cells under normal cell culture conditions has little effect. By contrast, SHP2 inhibition under growth factor-limiting conditions in vitro results in a senescence response. In vivo, inhibition of SHP2 in KRAS-mutant NSCLC also provokes a senescence response, which is exacerbated by MEK inhibition. Our data identify SHP2 inhibition as an unexpected vulnerability of KRAS-mutant NSCLC cells that remains undetected in cell culture and can be exploited therapeutically.


Elevated C-reactive protein levels may be a predictor of persistent unfavourable symptoms in patients with mild traumatic brain injury: a preliminary study.
The pathogenesis of persistent unfavourable outcomes following mild traumatic brain injury (mTBI) are not fully understood. Low-grade systemic inflammation might contribute to the development of persistent unfavourable outcomes in patients with mTBI. We used plasma high-sensitivity C-reactive protein (CRP) levels as the biomarker of systemic inflammation to investigate whether elevated CRP levels were associated with persistent adverse outcomes in these patients. A total of 213 consecutive patients with mTBI were identified in our study. Plasma high-sensitivity CRP levels were measured at baseline, 1month, 2months and 3months after initial traumatic brain injury. The study endpoints included persistent postconcussion syndrome (PCS), persistent psychological problems (depression and anxiety), persistent physiological problems (frequent headache, nausea, insomnia, dizziness and fatigue) and persistent cognitive impairment, which were screened by International Classification of Diseases (ICD-10), diagnostic and statistical manual of mental disorders (DSM-IV), Beck anxiety inventory (BAI), Beck depression inventory (BDI) and montreal cognitive assessment (MoCA) 3months post-injury. The associations between baseline CRP levels and persistent unfavourable outcomes were estimated from multiple regression models adjusting for various confounding covariates. Elevated baseline CRP levels were associated with a significant increase in the incidence of persistent PCS (odds ratio [OR], 2.719; 95% confidence interval [CI], 1.609-4.594; p=0.000), persistent psychological problems (OR, 1.535; 95% CI, 1.063-2.216; p=0.022), and persistent cognitive impairment (OR, 1.687; 95% CI, 1.135-2.507; p=0.010). However, elevated CRP levels were not associated with persistent physiological problems (OR, 1.330; 95% CI, 0.905-1.956; p=0.146). Furthermore, three adjusted models did not essentially affect the OR of elevated CRP levels for these persistent unfavourable outcomes. Among patients with mTBI, baseline elevated CRP levels may be an independent predictor of persistent persistent PCS, psychological problems and cognitive impairment.


Expression of pancreatic trypsinogen in human extrapancreatic gastrointestinal carcinomas.
Pancreatic trypsinogen expression in 149 surgically resected extrapancreatic gastrointestinal neoplasms was evaluated immunohistochemically. Immunohistochemistry was performed using a monoclonal antibody against human pancreatic trypsinogen. Pancreatic trypsinogen expression was detected in 28 of 55 gastric carcinomas (50.9%), 22 of 44 colorectal cancers (50%), 12 of 20 gallbladder cancers (60%), nine of 10 extrahepatic bile duct cancers (90%), and none of 20 hepatocellular carcinomas. The intensity of immunoreactivity in the tumor area varied from specimen to specimen, and from area to area within the same specimen. In most cases, however, immunoreactivity was more pronounced at the infiltrative margin of the tumor. Additionally, the highly differentiated carcinoma cells tended to display a focal, fine granular immunoreactive pattern, usually present in the supranuclear cytoplasm, while the poorly differentiated carcinoma cells displayed a fine granular pattern, usually present over the entire cytoplasm. These findings suggest that some extrapancreatic gastrointestinal neoplasms express pancreatic trypsinogen immunoreactive peptides, raising the possibility that secreted pancreatic trypsinogen plays a role in carcinoma invasion and metastasis, as has been shown for other classes of proteases.


Experimental test of self-shielding in vacuum ultraviolet photodissociation of CO.
Self-shielding of carbon monoxide (CO) within the nebular disk has been proposed as the source of isotopically anomalous oxygen in the solar reservoir and the source of meteoritic oxygen isotopic compositions. A series of CO photodissociation experiments at the Advanced Light Source show that vacuum ultraviolet (VUV) photodissociation of CO produces large wavelength-dependent isotopic fractionation. An anomalously enriched atomic oxygen reservoir can thus be generated through CO photodissociation without self-shielding. In the presence of optical self-shielding of VUV light, the fractionation associated with CO dissociation dominates over self-shielding. These results indicate the potential role of photochemistry in early solar system formation and may help in the understanding of oxygen isotopic variations in Genesis solar-wind samples.


A Nanodot Array Modulates Cell Adhesion and Induces an Apoptosis-Like Abnormality in NIH-3T3 Cells.
Micro-structures that mimic the extracellular substratum promote cell growth and differentiation, while the cellular reaction to a nanostructure is poorly defined. To evaluate the cellular response to a nanoscaled surface, NIH 3T3 cells were grown on nanodot arrays with dot diameters ranging from 10 to 200 nm. The nanodot arrays were fabricated by AAO processing on TaN-coated wafers. A thin layer of platinum, 5 nm in thickness, was sputtered onto the structure to improve biocompatibility. The cells grew normally on the 10-nm array and on flat surfaces. However, 50-nm, 100-nm, and 200-nm nanodot arrays induced apoptosis-like events. Abnormality was triggered after as few as 24 h of incubation on a 200-nm dot array. For cells grown on the 50-nm array, the abnormality started after 72 h of incubation. The number of filopodia extended from the cell bodies was lower for the abnormal cells. Immunostaining using antibodies against vinculin and actin filament was performed. Both the number of focal adhesions and the amount of cytoskeleton were decreased in cells grown on the 100-nm and 200-nm arrays. Pre-coatings of fibronectin (FN) or type I collagen promoted cellular anchorage and prevented the nanotopography-induced programed cell death. In summary, nanotopography, in the form of nanodot arrays, induced an apoptosis-like abnormality for cultured NIH 3T3 cells. The occurrence of the abnormality was mediated by the formation of focal adhesions.


Clinical significance of NCOA5 gene rs2903908 polymorphism in Behçet's disease.
Behçet's disease (BD) is an autoimmune multisystemic disease. The precise etiology of BD is not fully understood; however, it is thought that interactions between genetic and environmental factors play an essential role in its pathogenesis. The nuclear receptor coactivator-5 (NCOA5) gene encodes a coregulator for nuclear receptor subfamily 1 group D member 2 (NR1D2) and estrogen receptor 1 and 2 (ESR1 and ESR2). Also, the NCOA5 gene insufficiency leads to an elevated expression of IL-6, and increased levels of IL-6 were found to be related to the pathogenesis of BD. In this study, we aimed to clarify the impact of the NCOA5 rs2903908 polymorphism on susceptibility and clinical findings of BD. This study included 671 participants (300 BD patients and 371 healthy controls). The analyses of NCOA5 rs2903908 polymorphism was performed by using the TaqMan allelic discrimination assay. The frequency of TT genotype of the NCOA5 rs2903908 polymorphism was found significantly higher in BD patients compared to those in healthy controls (p=0.016, OR=1.46, 95 % CI=1.08-1.99). Also, the frequencies of CT genotype was observed significantly higher in BD patients with genital ulceration and uveitis than without genital ulceration and uveitis (p=0.002 and p=0.005, respectively). The most significant association was found between C allele frequencies of BD patients with and without uveitis (p=0.0001). Our study represents for the first time that the NCOA5 rs2903908 polymorphism seemed to be linked to BD susceptibility and clinical findings.


Determination of thin film optical parameters from photometric measurements: an algebraic solution for the (T,R(f),R(b)) method.
A new method of analysis for the simultaneous determination of the optical constants and the thickness of thin films is proposed. It requires measurements under normal incidence of the transmission and of the reflections from both sides of a thin film deposited on a nonabsorbing sbstrate. An algebraic inversion technique is developed involving a numerical interpolation procedure in the last step. There are no missing solutions. The physical solution can be isolated by a comparison with some film thickness estimates or by measurements in a wavelength range.


The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report.
"The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure" provides a new guideline for hypertension prevention and management. The following are the key messages(1) In persons older than 50 years, systolic blood pressure (BP) of more than 140 mm Hg is a much more important cardiovascular disease (CVD) risk factor than diastolic BP; (2) The risk of CVD, beginning at 115/75 mm Hg, doubles with each increment of 20/10 mm Hg; individuals who are normotensive at 55 years of age have a 90% lifetime risk for developing hypertension; (3) Individuals with a systolic BP of 120 to 139 mm Hg or a diastolic BP of 80 to 89 mm Hg should be considered as prehypertensive and require health-promoting lifestyle modifications to prevent CVD; (4) Thiazide-type diuretics should be used in drug treatment for most patients with uncomplicated hypertension, either alone or combined with drugs from other classes. Certain high-risk conditions are compelling indications for the initial use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, calcium channel blockers); (5) Most patients with hypertension will require 2 or more antihypertensive medications to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg for patients with diabetes or chronic kidney disease); (6) If BP is more than 20/10 mm Hg above goal BP, consideration should be given to initiating therapy with 2 agents, 1 of which usually should be a thiazide-type diuretic; and (7) The most effective therapy prescribed by the most careful clinician will control hypertension only if patients are motivated. Motivation improves when patients have positive experiences with and trust in the clinician. Empathy builds trust and is a potent motivator. Finally, in presenting these guidelines, the committee recognizes that the responsible physician's judgment remains paramount.


moCluster: Identifying Joint Patterns Across Multiple Omics Data Sets.
Increasingly, multiple omics approaches are being applied to understand the complexity of biological systems. Yet, computational approaches that enable the efficient integration of such data are not well developed. Here, we describe a novel algorithm, termed moCluster, which discovers joint patterns among multiple omics data. The method first employs a multiblock multivariate analysis to define a set of latent variables representing joint patterns across input data sets, which is further passed to an ordinary clustering algorithm in order to discover joint clusters. Using simulated data, we show that moCluster's performance is not compromised by issues present in iCluster/iCluster+ (notably, the nondeterministic solution) and that it operates 100× to 1000× faster than iCluster/iCluster+. We used moCluster to cluster proteomic and transcriptomic data from the NCI-60 cell line panel. The resulting cluster model revealed different phenotypes across cellular subtypes, such as doubling time and drug response. Applying moCluster to methylation, mRNA, and protein data from a large study on colorectal cancer patients identified four molecular subtypes, including one characterized by microsatellite instability and high expression of genes/proteins involved in immunity, such as PDL1, a target of multiple drugs currently in development. The other three subtypes have not been discovered before using single data sets, which clearly illustrates the molecular complexity of oncogenesis and the need for holistic, multidata analysis strategies.


Characterization of a novel deletion causing beta-thalassemia major in an Afghan family.
We have identified and characterized a novel beta-globin gene deletion mutation in a family of Afghan ancestry. The proband was a 10-year-old transfusion-dependent female with the phenotype of beta-thalassemia major (beta-TM). DNA sequencing of the beta-globin gene showed no abnormalities. Multiplex ligation-dependent probe amplification (MLPA) showed reduced/absent probe height of the probe covering the 5' end of the beta-globin gene indicating a possible deletion. Gap-polymerase chain reaction (gap-PCR) produced junctional fragments and direct sequencing of the product revealed that the 5' breakpoint was 478 nucleotides upstream of the Cap site and the 3' breakpoint was in the second exon of the beta-globin gene, giving a deletion size of 909 bp. The proband was homozygous and the parents were heterozygous for the deletion. This is the first report of a large beta-thalassemia (beta-thal) deletion mutation in this ethnic group.


Time differences in the formation of meteorites as determined from the ratio of lead-207 to lead-206.
Measurements of the lead isotopic composition and the uranium, thorium, and lead concentrations in meteorites were made in order to obtain more precise radiometric ages of these members of the solar system. The newly determined value of the lead isotopic composition of Canyon Diablo troilite is as follows: (206)Pb/(204)Pb = 9.307, (207)Pb/(2O4)Pb = 10.294, and (208)Pb/(204)Pb = 29.476. The leads of Angra dos Reis, Sioux County, and Nuevo Laredo achondrites are very radiogenic, the (206)Pb/(204)Pb values are about 200, and the uranium-thorium-lead systems are nearly concordant. The ages of the meteorites as calculated from a single-stage (207)Pb/(206)Pb isochron based on the newly determined primordial lead value and the newly reported (235)U and (838)U decay constants, are 4.528 x 10(9) years for Sioux County and Nuevo Laredo and 4.555 x 10(9) years for Angra dos Reis. When calculated with the uranium decay constants used by Patterson, these ages are 4.593 x 10(9) years and 4.620 x 10(9) years, respectively, and are therefore 40 to 70 x 10(6) years older than the 4.55 x 10(9) years age Patterson reported. The age difference of 27 x 10(6) years between Angra dos Reis and the other two meteorites is compatible with the difference between the initial (87)Sr/(86)Sr ratio of Angra dos Reis and that of seven basaltic achondrites observed by Papanastassiou and Wasserburg. The time difference is also comparable to that determined by (129)1-(129)Xe chronology. The ages of ordinary chondrites (H5 and L6) range from 4.52 to 4.57 x 10(9) years, and, here too, time differences in the formation of the parent bodies or later metamorphic events are indicated. Carbonaceous chondrites(C2 and C3) appear to contain younger lead components.


Crustacean cardioactive peptides: Expression, localization, structure, and a possible involvement in regulation of egg-laying in the cuttlefish Sepia officinalis.
The cuttlefish (Sepia officinalis) is a cephalopod mollusk distributed on the western European coast, in the West African Ocean and in the Mediterranean Sea. On the Normandy coast (France), cuttlefish is a target species of professional fishermen, so its reproduction strategy is of particular interest in the context of stock management. Egg-laying, which is coastal, is controlled by several types of regulators among which neuropeptides. The cuttlefish neuropeptidome was recently identified by Zatylny-Gaudin et al. (2016). Among the 38 neuropeptide families identified, some were significantly overexpressed in egg-laying females as compared to mature males. This study is focused on crustacean cardioactive peptides (CCAPs), a highly expressed neuropeptide family strongly suspected of being involved in the control of egg-laying. We investigated the functional and structural characterization and tissue mapping of CCAPs, as well as the expression patterns of their receptors. CCAPs appeared to be involved in oocyte transport through the oviduct and in mechanical secretion of capsular products. Immunocytochemistry revealed that the neuropeptides were localized throughout the central nervous system (CNS) and in the nerve endings of the glands involved in egg-capsule synthesis and secretion, i.e. the oviduct gland and the main nidamental glands. The CCAP receptor was expressed in these glands and in the subesophageal mass of the CNS. Multiple sequence alignments revealed a high level of conservation of CCAP protein precursors in Sepia officinalis and Loligo pealei, two cephalopod decapods. Primary sequences of CCAPs from the two species were fully conserved, and cryptic peptides detected in the nerve endings were also partially conserved, suggesting biological activity that remains unknown for the time being.


[The origins of the Renal Immunopathology Group of the Italian Society of Nephrology].
This article describes the birth and development of the Renal Immunopathology Group of the Italian Society of Nephrology. It collects the stories of nephrologists and pathologists who, since the early Seventies up to the first decade of this century, devoted their professional lives to the study of renal pathology with a strong personal involvement, characterized by enthusiasm, commitment, ability, strong spirit of cooperation, and friendship. All this enabled the Group to: propose the criteria for a standardized histological and immuno-histological examination of renal biopsies and reporting; produce several multicenter studies, whose results were also published in important international journals; to set up a national registry of renal biopsies; to organize a number of courses, some of which were associated with the publication of monographs, on various renal diseases. This article also traces the history of renal pathology in Italy from the second half of the Sixties - when young Italian nephrologists and pathologists from different institutions moved to French laboratories to learn new techniques to apply to renal biopsies - up to the present days. It also shows us how Italian renal pathology has been an essential tool for the development of the nephrological clinical practice and the advancement of scientific research.


Recovery: conceptual and ethical aspects.
To examine recent publications on implications of recovery for the provision of mental health services. Predominantly, the concept of recovery, implications for professional mental health services, and the impact of peer workers on the provision of healthcare are discussed. Recovery in the context of mental health issues refers to multiple dimensions of the individual's development. According to recent publications, the dimension of an individual journey, measurable through subjective parameters and accounts, is complementary to the traditional objectives of symptom reduction, improvement of functioning, and social inclusion. To foster recovery orientation in mental health services subjective measures should be included in clinical practice, research, and teaching. Moreover, services striving to support recovery need to implement strategies in terms of policy, concepts, structures, and professional attitude. This challenging paradigm shift is claimed to be supported by the integration of peer workers with own lived experience in the provision of mental healthcare. Some exponents of the social recovery movement criticize this recent international development to implement recovery into traditional services, as it would uphold the established structures of power and control. Questions of impaired legal capacity, involuntary admissions and risk assessment related to recovery are rarely discussed.


The intersection of cancer and aging: establishing the need for breast cancer rehabilitation.
The increasing success of treatments for common cancers has resulted in growing awareness of the unique health care needs of cancer survivors. Cancer treatments can be toxic and have long-lasting effects on health, potentially accelerating the aging process and producing associated declines in physical function. In this synthesis of the literature, we critically examine the strength of existing evidence that breast cancer diagnosis and treatment are associated with a disproportionate decline in physical function compared with the effects of living without cancer for the same number of years. There is some observational epidemiologic evidence that women treated for breast cancer report greater declines in physical function than their peers. Discerning the factors associated with such declines and their clinical significance remains to be addressed. Physiologic, psychological, and behavioral changes associated with both aging and cancer treatment are reviewed. Parallels are proposed between existing preventive and rehabilitative programs and possibilities for similar interventions aimed at preventing, reversing, or halting declines in physical function in cancer survivors. Finally, a program of research is proposed to evaluate whether there is some subset of breast cancer survivors for whom prevention or rehabilitation of functional status declines is needed, as well as development of targeted, mechanistically driven interventions.


In vivo fate of the inflammatory macrophage during the resolution of inflammation: inflammatory macrophages do not die locally, but emigrate to the draining lymph nodes.
The resolution of acute inflammation requires bulk clearance of extravasated inflammatory cells in an ordered manner. Neutrophils undergo apoptosis and are ingested by macrophages (M psi) via a novel recognition mechanism that fails to provoke proinflammatory responses. Thereafter, the fate of inflammatory M psi themselves remains unclear. We investigated this in vivo, developing a semiallogeneic adoptive transfer system to track the fate of inflammatory M psi in a murine model of resolving peritonitis. Fluorescently labeled M psi from H-2k/d mice were transferred into the peritoneal cavity of H-2k mice at the same stage of resolving inflammation as the donor mice. Dual color flow cytometry permitted discrimination among donor cells, recipient cells, and donor cells that had been phagocytosed by recipient M psi. Despite the absence of significant local phagocytosis, the number of transferred M psi free in the peritoneum of recipient mice declined rapidly, being undetectable by 96 h. These data suggest that inflammatory M psi normally emigrate rapidly from the peritoneal cavity during the resolution of inflammation, contrasting with resident M psi, which persist in the noninflamed peritoneum for weeks. Accordingly, labeled nonphagocytosed cells were detected in the draining lymph nodes, but not in a variety of other tissues. Thus, unlike the polymorphonuclear leukocyte, which dies by apoptosis and is ingested by M psi, the inflammatory M psi itself does not die locally. Having performed its acute inflammatory and scavenging roles, it emigrates in a nonrandom fashion to the draining lymph node, where it may play an important part in the presentation of Ags from the inflamed site.


One hundred fascia-sparing myocutaneous rectus abdominis flaps: An update.
Major efforts have been undertaken to reduce donor-site morbidity after abdominal flaps, which eventually culminated in the introduction of the deep inferior epigastric perforator (DIEP) flap. However, due to anatomical variations (absence of dominant perforators) and the risk of ischaemic complications, the selection of patients qualifying for a DIEP flap is limited. Furthermore, DIEP flaps can only be used as free flaps. We present our long-term experience with a dissection technique of rectus abdominis myocutaneous (RAM) flaps that was developed to circumvent these drawbacks. The dissection is characterised by preventing to sacrifice any perforators nourishing the flap and by fully preserving the anterior rectus sheath, but not the muscle. The study comprises a consecutive series of prospectively assessed patients, treated between February 2000 and April 2008. A total of 100 fascia-sparing RAM flaps were operated on 97 patients (age 22-84 years, median 64 years). Free flaps were mainly used for breast reconstruction (47 flaps/24 patients), and cranially (34) or caudally (19) pedicled flaps for soft-tissue coverage after sternectomy, urogenital tumour resection or rectum amputation. Eighty patients had a total of 213 risk factors, such as cardiovascular diseases, obesity, hyperlipidaemia, diabetes mellitus, smoking or steroid medication. Partial tissue loss (skin or fat necrosis) occurred in 13 flaps, out of which seven required surgical revision. The ischaemic complications were evenly distributed between the patient subsets. At a follow-up of 2-89 months (median 20 months), one patient showed a flap harvest-related abdominal bulge after bilateral-free transverse rectus abdominis myocutaneous (TRAM) flap. We conclude that the present dissection technique provides maximal perforator-related perfusion and minimal donor-site morbidity even in pedicled flaps and high-risk patients. In free flaps, it may, therefore, be recommended as an alternative to the DIEP flap.


Focused Proteomics Revealed a Novel Rho-kinase Signaling Pathway in the Heart.
Protein phosphorylation plays an important role in the physiological regulation of cardiac function. Myocardial contraction and pathogenesis of cardiac diseases have been reported to be associated with adaptive or maladaptive protein phosphorylation; however, phosphorylation signaling in the heart is not fully elucidated. We recently developed a novel kinase-interacting substrate screening (KISS) method for exhaustive screening of protein kinase substrates, using mass spectrometry and affinity chromatography. First, we examined protein phosphorylation by extracellular signal-regulated kinase (ERK) and protein kinase A (PKA), which has been relatively well studied in cardiomyocytes. The KISS method showed that ERK and PKA mediated the phosphorylation of known cardiac-substrates of each kinase such as Rps6ka1 and cTnI, respectively. Using this method, we found about 330 proteins as Rho-kinase-mediated substrates, whose substrate in cardiomyocytes is unknown. Among them, CARP/Ankrd1, a muscle ankyrin repeat protein, was confirmed as a novel Rho-kinase-mediated substrate. We also found that non-phosphorylatable form of CARP repressed cardiac hypertrophy-related gene Myosin light chain-2v (MLC-2v) promoter activity, and decreased cell size of heart derived H9c2 myoblasts more efficiently than wild type-CARP. Thus, focused proteomics enable us to reveal a novel signaling pathway in the heart.


The CGView Server: a comparative genomics tool for circular genomes.
The CGView Server generates graphical maps of circular genomes that show sequence features, base composition plots, analysis results and sequence similarity plots. Sequences can be supplied in raw, FASTA, GenBank or EMBL format. Additional feature or analysis information can be submitted in the form of GFF (General Feature Format) files. The server uses BLAST to compare the primary sequence to up to three comparison genomes or sequence sets. The BLAST results and feature information are converted to a graphical map showing the entire sequence, or an expanded and more detailed view of a region of interest. Several options are included to control which types of features are displayed and how the features are drawn. The CGView Server can be used to visualize features associated with any bacterial, plasmid, chloroplast or mitochondrial genome, and can aid in the identification of conserved genome segments, instances of horizontal gene transfer, and differences in gene copy number. Because a collection of sequences can be used in place of a comparison genome, maps can also be used to visualize regions of a known genome covered by newly obtained sequence reads. The CGView Server can be accessed at http://stothard.afns.ualberta.ca/cgview_server/


Myostatin-induced inhibition of the long noncoding RNA Malat1 is associated with decreased myogenesis.
Myostatin, a member of the transforming growth factor-β (TGF-β) superfamily of secreted proteins, is a potent negative regulator of myogenesis. Free myostatin induces the phosphorylation of the Smad family of transcription factors, which, in turn, regulates gene expression, via the canonical TGF-β signaling pathway. There is, however, emerging evidence that myostatin can regulate gene expression independent of Smad signaling. As such, we acquired global gene expression data from the gastrocnemius muscle of C57BL/6 mice following a 6-day treatment with recombinant myostatin compared with vehicle-treated animals. Of the many differentially expressed genes, the myostatin-associated decrease (-11.20-fold; P < 0.05) in the noncoding metastasis-associated lung adenocarcinoma transcript 1 (Malat1) was the most significant and the most intriguing because of numerous reports describing its novel role in regulating cell growth. We therefore sought to further characterize the role of Malat1 expression in skeletal muscle myogenesis. RT-PCR-based quantification of C2C12 and primary human skeletal muscle cells revealed a significant and persistent upregulation (4- to 7-fold; P < 0.05) of Malat1 mRNA during the differentiation of myoblasts into myotubes. Conversely, targeted knockdown of Malat1 using siRNA suppressed myoblast proliferation by arresting cell growth in the G(0)/G(1) phase. These results reveal Malat1 as novel downstream target of myostatin with a considerable ability to regulate myogenesis. The identification of new targets of myostatin will have important repercussions for regenerative biology through inhibition and/or reversal of muscle atrophy and wasting diseases.


Collagen and Elastic Fiber Content Correlation Analysis between Horizontal and Vertical Orientations of Skin Samples of Human Body.
Background. Unequal distribution of dermal collagen and elastic fibers in different orientations of skin is reported to be one of the multifocal causes of scar related complications. Present study is to understand the correlation pattern between collagen in horizontal (CH) and in vertical (CV) directions as well as that of elastic in horizontal (EH) and vertical (EV) directions. Materials and Method. A total of 320 skin samples were collected in two orientations from suprascapular, anterior chest, lateral chest, anterior abdominal wall, and inguinal regions of 32 human cadavers. Spearman correlation coefficient (r) was calculated between the variables (CH, CV, EH, and EV). Results. Significant positive correlation between CH and CV, and between EH and EV observed in all 5 areas tested. A negative correlation between CV and EV at suprascapular, lateral chest, and inguinal regions and negative correlation between CH and EH at anterior chest and anterior abdominal wall have been identified. Conclusion. Knowledge of asymmetric content of dermal collagen and elastic fibers together with the varied strength and degree of association in the given area provides guidelines to the dermatologists and aesthetic surgeons in placing elective incisions in the direction maximally utilizing the anatomical facts for aesthetically pleasing result.


Comparison of Trunk Flexion Proprioception Between Healthy Athletes and Athletes With Patellofemoral Pain.
Patellofemoral pain (PFP) is the most commonly reported musculoskeletal overuse injury in active individuals, such as athletes, and is a multifactorial problem with no definite cause identified to date. Some studies have shown a relationship between impaired core and trunk sensorimotor control and knee disorders, especially PFP. The aim of this study was to evaluate trunk flexion proprioception by comparing the repositioning error between healthy athletes and athletes with PFP. Cross-sectional case-control study. Rehabilitation sciences research center. Twenty healthy athletes and 20 athletes with PFP. To examine proprioception of trunk flexors, the absolute active and passive repositioning error at 30° and 60° trunk flexion were evaluated with isokinetic dynamometry. The results were compared between the two groups. In the PFP group, the active trunk repositioning error at 30° flexion was significantly greater than in the healthy individuals (P < .001). The mean absolute active repositioning error at 30° flexion was 3.04° (1.37°) in the PFP group and 1.50° (0.70°) in the control group. There was no significant difference between groups in the active trunk repositioning error at 60° flexion (P = .066). The mean absolute active repositioning error at 60° flexion was 2.96° (1.26°) in the PFP group and 2.18° (0.99°) in the control group. The passive trunk repositioning error at 30° and 60° flexion was significantly greater in the PFP group (P = .013 and P = .004, respectively). The mean absolute passive repositioning error at 30° and 60° flexion in the PFP group was 2.94° (0.80°) and 3.13° (1.19°), respectively, and was 2.08° (1.08°) and 1.96° (0.71°), respectively, in the control group. The calculated eta-squared value showed that joint repositioning errors had large effect sizes (0.15-0.32). Trunk proprioception in the flexion direction may be impaired in patients with PFP. This finding suggests that trunk proprioception training may be important in rehabilitation for athletes with PFP.


Kinetics of iron oxidation by Leptospirillum ferriphilum dominated culture at pH below one.
The kinetics of ferrous iron oxidation by Leptospirillum ferriphilum (L. ferriphilum) dominated culture was studied in the concentration range of 0.1-20 g Fe(2+)/L and the effect of ferric iron (0-60 g Fe(3+)/L) on Fe(2+) oxidation was investigated at pH below one. Denaturing gradient gel electrophoresis of PCR amplified 16S rRNA genes followed by partial sequencing confirmed that the bacterial community was dominated by L. ferriphilum. In batch assays, Fe(2+) oxidation started without lag phase and the oxidation was completed within 1 to 60 h depending on the initial Fe(2+) concentration. The specific Fe(2+) oxidation rates increased up to around 4 g/L and started to decrease at above 4 g/L. This implies substrate inhibition of Fe(2+) oxidation at higher concentrations. Haldane equation fitted the experimental data reasonably well (R(2) = 0.90). The maximum specific oxidation rate (q(m)) was 2.4 mg/mg VS . h, and the values of the half saturation (K(s)) and self inhibition constants (K(i)) were 413 and 8,650 mg/L, respectively. Fe(2+) oxidation was competitively inhibited by Fe(3+) and the competitive inhibition constant (K(ii)) was 830 mg/L. The time required to reach threshold Fe(2+) concentration was around 1 day and 2.3 days with initial Fe(3+) concentration of 5 and 60 g/L, respectively. The threshold Fe(2+) concentration, below which no further Fe(2+) oxidation occurred, linearly increased with increasing initial Fe(2+) and Fe(3+) concentrations. Fe(2+) oxidation proceeds by L. ferriphilum dominated culture at pH below 1 even in the presence of 60 g Fe(3+)/L. This indicates potential of using and biologically regenerating concentrated Fe(3+) sulfate solutions required, for example, in indirect tank leaching of ore concentrates.


The Marine Strategy Framework Directive and the ecosystem-based approach – pitfalls and solutions.
The European Marine Strategy Framework Directive aims at good environmental status (GES) in marine waters, following an ecosystem-based approach, focused on 11 descriptors related to ecosystem features, human drivers and pressures. Furthermore, 29 subordinate criteria and 56 attributes are detailed in an EU Commission Decision. The analysis of the Decision and the associated operational indicators revealed ambiguity in the use of terms, such as indicator, impact and habitat and considerable overlap of indicators assigned to various descriptors and criteria. We suggest re-arrangement and elimination of redundant criteria and attributes avoiding double counting in the subsequent indicator synthesis, a clear distinction between pressure and state descriptors and addition of criteria on ecosystem services and functioning. Moreover, we suggest the precautionary principle should be followed for the management of pressures and an evidence-based approach for monitoring state as well as reaching and maintaining GES.


Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Severe Sepsis and Septic Shock: A Retrospective Before-After Study.
The global burden of sepsis is estimated as 15 to 19 million cases annually, with a mortality rate approaching 60% in low-income countries. In this retrospective before-after clinical study, we compared the outcome and clinical course of consecutive septic patients treated with intravenous vitamin C, hydrocortisone, and thiamine during a 7-month period (treatment group) with a control group treated in our ICU during the preceding 7 months. The primary outcome was hospital survival. A propensity score was generated to adjust the primary outcome. There were 47 patients in both treatment and control groups, with no significant differences in baseline characteristics between the two groups. The hospital mortality was 8.5% (4 of 47) in the treatment group compared with 40.4% (19 of 47) in the control group (P < .001). The propensity adjusted odds of mortality in the patients treated with the vitamin C protocol was 0.13 (95% CI, 0.04-0.48; P = .002). The Sepsis-Related Organ Failure Assessment score decreased in all patients in the treatment group, with none developing progressive organ failure. All patients in the treatment group were weaned off vasopressors, a mean of 18.3 ± 9.8 h after starting treatment with the vitamin C protocol. The mean duration of vasopressor use was 54.9 ± 28.4 h in the control group (P < .001). Our results suggest that the early use of intravenous vitamin C, together with corticosteroids and thiamine, are effective in preventing progressive organ dysfunction, including acute kidney injury, and in reducing the mortality of patients with severe sepsis and septic shock. Additional studies are required to confirm these preliminary findings.


Kelp carbon sink potential decreases with warming due to accelerating decomposition.
Cycling of organic carbon in the ocean has the potential to mitigate or exacerbate global climate change, but major questions remain about the environmental controls on organic carbon flux in the coastal zone. Here, we used a field experiment distributed across 28° of latitude, and the entire range of 2 dominant kelp species in the northern hemisphere, to measure decomposition rates of kelp detritus on the seafloor in relation to local environmental factors. Detritus decomposition in both species were strongly related to ocean temperature and initial carbon content, with higher rates of biomass loss at lower latitudes with warmer temperatures. Our experiment showed slow overall decomposition and turnover of kelp detritus and modeling of coastal residence times at our study sites revealed that a significant portion of this production can remain intact long enough to reach deep marine sinks. The results suggest that decomposition of these kelp species could accelerate with ocean warming and that low-latitude kelp forests could experience the greatest increase in remineralization with a 9% to 42% reduced potential for transport to long-term ocean sinks under short-term (RCP4.5) and long-term (RCP8.5) warming scenarios. However, slow decomposition at high latitudes, where kelp abundance is predicted to expand, indicates potential for increasing kelp-carbon sinks in cooler (northern) regions. Our findings reveal an important latitudinal gradient in coastal ecosystem function that provides an improved capacity to predict the implications of ocean warming on carbon cycling. Broad-scale patterns in organic carbon decomposition revealed here can be used to identify hotspots of carbon sequestration potential and resolve relationships between carbon cycling processes and ocean climate at a global scale.


Mediators of the relation between war experiences and suicidal ideation among former child soldiers in Northern Uganda: the WAYS study.
Globally, suicide is a public health burden especially in the aftermath of war. Understanding the processes that define the path from previous war experiences (WE) to current suicidal ideation (SI) is crucial for defining opportunities for interventions. We assessed the extent to which different types of previous WE predict current SI and whether post-war hardships and depression mediate the relations between WE and SI among former child soldiers (FCS) in Northern Uganda. We performed cross-sectional analyses with a sample of 539 FCS (61% male) participating in an on-going longitudinal study. The influence of various types of previous WE on current SI and mediation by post-war hardships and depression were assessed by regression analyses. The following types of war experiences: "witnessing violence", "direct personal harm", "deaths", "Involvement in hostilities", "sexual abuse" and "general war experiences" significantly predicted current SI in a univariable analyses whereas "direct personal harm", "involvement in hostilities", and "sexual abuse" independently predicted current SI in a multivariable analyses. General WE were linked to SI (β = 0.18 (95% CI 0.10 to 0.25)) through post-war hardships (accounting for 69% of the variance in their relationship) and through depression/anxiety (β = 0.17 (95% CI 0.12 to 0.22)) accounting for 65% of the variance in their relationship. The direct relationship between previous WE and current SI reduced but remained marginally significant (β = .08, CI: (.01, .17) for depression/anxiety but not for post-war hardships (β = .09, CI: (-.03, .20). Types of WE should be examined when assessing risks for SI. Interventions to reduce SI should aim to alleviate post-war hardships and treat depression/anxiety.


Emergency medicine residency applicant views on the interview day process.
Emergency medicine (EM) residency programs spend significant time and money offering an interview day experience for their applicants. The day may include a range of activities, although which are most important from the applicants' point of view are not known. An anonymous web-based survey was sent to all applicants to an EM residency program from the 2006/07 cycle. The study assessed factors about the interview day that were most helpful to applicants in assessing goodness of fit and preparing their rank list of programs. When considering whether a program was a good fit for them, the respondents chose (from most to least important) how happy the residents seem, faculty-resident relationships, how well the residents work together, resident and faculty values match my own, the residents spend time together outside of the residency, and the residents share my outside interests. Applicants most value assessing program "personality," informal off-campus gatherings with residents, and interviewing with the program director as ways to decide where a program will reside on their rank list. Touring off-campus emergency departments and off-service facilities received the lowest rating averages. Residency programs have the opportunity to control two of the three most important ways in which applicants use the interview day to assess programs by offering off-campus gatherings with residents and ensuring that every candidate interviews with the program director. Residency programs may use this knowledge to optimize interview day resources.


Prevalence of dyslipidaemia and associated risk factors in a rural population in South-Western Uganda: a community based survey.
The burden of dyslipidaemia is rising in many low income countries. However, there are few data on the prevalence of, or risk factors for, dyslipidaemia in Africa. In 2011, we used the WHO Stepwise approach to collect cardiovascular risk data within a general population cohort in rural south-western Uganda. Dyslipidaemia was defined by high total cholesterol (TC) ≥ 5.2 mmol/L or low high density lipoprotein cholesterol (HDL-C) <1 mmol/L in men, and <1.3 mmol/L in women. Logistic regression was used to explore correlates of dyslipidaemia. Low HDL-C prevalence was 71.3% and high TC was 6.0%. In multivariate analysis, factors independently associated with low HDL-C among both men and women were: decreasing age, tribe (prevalence highest among Rwandese tribe), lower education, alcohol consumption (comparing current drinkers to never drinkers: men adjusted (a)OR=0.44, 95%CI=0.35-0.55; women aOR=0.51, 95%CI=0.41-0.64), consuming <5 servings of fruit/vegetable per day, daily vigorous physical activity (comparing those with none vs those with 5 days a week: men aOR=0.83 95%CI=0.67-1.02; women aOR=0.76, 95%CI=0.55-0.99), blood pressure (comparing those with hypertension to those with normal blood pressure: men aOR=0.57, 95%CI=0.43-0.75; women aOR=0.69, 95%CI=0.52-0.93) and HIV infection (HIV infected without ART vs. HIV negative: men aOR=2.45, 95%CI=1.53-3.94; women aOR=1.88, 95%CI=1.19-2.97). The odds of low HDL-C was also higher among men with high BMI or HbA1c ≤ 6%, and women who were single or with abdominal obesity. Among both men and women, high TC was independently associated with increasing age, non-Rwandese tribe, high waist circumference (men aOR=5.70, 95%CI=1.97-16.49; women aOR=1.58, 95%CI=1.10-2.28), hypertension (men aOR=3.49, 95%CI=1.74-7.00; women aOR=1.47, 95%CI=0.96-2.23) and HbA1c >6% (men aOR=3.00, 95%CI=1.37-6.59; women aOR=2.74, 95%CI=1.77-4.27). The odds of high TC was also higher among married men, and women with higher education or high BMI. Low HDL-C prevalence in this relatively young rural population is high whereas high TC prevalence is low. The consequences of dyslipidaemia in African populations remain unclear and prospective follow-up is required.


Early extrastriate activity without primary visual cortex in humans.
Damage to the primary visual cortex (V1) destroys the major source of anatomical input to extrastriate cortical areas (V2, V3, V4 and V5) and produces cortical blindness--an absence of any sensation of light and colour--in the visual field contralateral to the side of the lesion. Neuroimaging studies, nevertheless, have recently demonstrated dorsal and ventral extrastriate activation for stationary stimuli presented to the blind visual field in the absence of V1 activity in human subjects. To clarify the moment in time that visual information reaches extrastriate areas, by means of event-related potentials (ERPs) we tracked the temporal course of responses to complex visual stimuli (faces) presented in the blind field of a hemianopic patient. Stimulation of the normal visual field elicited a positive occipital deflection (P1) at 140 ms. A P1 response was also observed with stimulation of the blind field, although slightly delayed (20 ms) and reduced. Its topography and timing demonstrate that early neural activity for stationary stimuli takes place within extrastriate regions despite V1 denervation.


Histopathological implications of ventricle wall 5-aminolevulinic acid-induced fluorescence in the absence of tumor involvement on magnetic resonance images.
During 5-aminolevulinic acid (ALA)-guided glioblastoma multiforme (GBM) surgery, we encountered fluorescence in ventricular walls that lacked enhancement on magnetic resonance (MR) images and were free of macroscopic invasion of tumor cells. However, the meaning of ventricular wall fluorescence during 5-ALA-guided surgery is still unknown. The aim of this study was to investigate the relationship between intraoperative 5-ALA fluorescence and histopathological findings of ventricular walls free of enhancement on MR images. Nineteen patients with newly diagnosed GBM located near the lateral ventricle underwent 5‑ALA fluorescence‑guided surgery. During the surgery, the ventricle wall was opened and investigated with the aid of a surgical microscope equipped with optical filters to examine 5‑ALA fluorescence of the ventricular wall. Twenty‑five ventricular wall tissues that were apparently free of tumor involvement by MR imaging and macroscopic observation were obtained during surgery. Among the 19 cases with brightly fluorescing tumor masses, 11 patients (57.9%) exhibited 5‑ALA‑induced fluorescence in the ventricular wall. Of the 25 ventricular wall samples, 11 exhibited 5‑ALA‑induced fluorescence; upon pathologic examination, tumors were present in 5 samples (45.5%), but the remaining 6 (54.5%) were free of tumor cells. A pathologic examination revealed no tumor cells in the 14 samples that lacked 5‑ALA‑induced fluorescence. Our data suggest the possibility that glioma cells exhibiting 5‑ALA fluorescence are present in the ventricle wall, despite no signs of tumor involvement in MR images. Further investigation of non‑tumor cells from tissues with 5‑ALA fluorescence is needed to understand the nature of this unexpected ventricular wall fluorescence.


Omentin-A Novel Adipokine in Respiratory Diseases.
Adipokines, secreted by the adipose tissue, are extensively involved in the regulation and maintenance of various physiological and pathological processes, including insulin sensitivity, energy expenditure, glucose and lipid metabolism, inflammatory activity, neuroendocrine activity, immunity, cancer, homeostasis, angiogenesis, cardiovascular function, breeding and bone metabolism, and all functions of the endocrine-reproductive system axis. Omentin is a recently identified adipokine, which has become a research hotspot due to its pleiotropic effects on various diseases. However, the specific receptor for omentin has not been identified so far. In this study, we report that omentin levels fluctuate in various diseases. In addition, we have focused on the pleiotropic roles of omentin in pulmonary diseases, as it may act as a biomarker for malignant pleural mesothelioma (MPM) and is related to disease severity. Omentin may play significant roles in other pulmonary diseases, such as asthma, obstructive sleep apnea syndrome (OSAS), pulmonary arterial hypertension (PAH), acute respiratory distress syndrome (ARDS), and chronic obstructive pulmonary disease (COPD). This review summarizes the advances in current knowledge and future trends, which may provide a concise and general view on omentin and its effects on pulmonary biology.


Knockdown of RNA Interference Pathway Genes in Western Corn Rootworms (Diabrotica virgifera virgifera Le Conte) Demonstrates a Possible Mechanism of Resistance to Lethal dsRNA.
RNA interference (RNAi) is being developed as a potential tool for insect pest management. Increased understanding of the RNAi pathway in target insect pests will provide information to use this technology effectively and to inform decisions related to resistant management strategies for RNAi based traits. Dicer 2 (Dcr2), an endonuclease responsible for formation of small interfering RNA's and Argonaute 2 (Ago2), an essential catalytic component of the RNA-induced silencing complex (RISC) have both been associated with the RNAi pathway in a number of different insect species including the western corn rootworm, Diabrotica virgifera virgifera (Coleoptera: Chrysomelidae). We identified both genes from a transcriptome library generated from different tissues and developmental stages of the western corn rootworm, an important target pest for transgenic plants expressing dsRNA targeting essential genes. The expression of these genes was suppressed by more than 90% after injecting gene specific dsRNA into adult rootworms. The injected beetles were then fed vATPase A dsRNA which has previously been demonstrated to cause mortality in western corn rootworm adults. The suppression of both RNAi pathway genes resulted in reduced mortality after subsequent exposure to lethal concentrations of vATPase A dsRNA as well as increased vATPase A expression relative to control treatments. Injections with dsRNA for a non-lethal target sequence (Laccase 2) did not affect mortality or expression caused by vATPase A dsRNA indicating that the results observed with Argo and Dicer dsRNA were not caused by simple competition among different dsRNA's. These results confirm that both genes play an important role in the RNAi pathway for western corn rootworms and indicate that selection pressures that potentially affect the expression of these genes may provide a basis for future studies to understand potential mechanisms of resistance.


Comprehensive multi-modality assessment of regional and global arterial structure and function in adults born preterm.
Preterm birth is associated with higher blood pressure, which could be because preterm birth alters early aortic elastin and collagen development to cause increased arterial stiffness. We measured central and conduit artery size and multiple indices of arterial stiffness to define the extent and severity of macrovascular changes in individuals born preterm. A total of 102 young adults born preterm and 102 controls who were born after an uncomplicated pregnancy underwent cardiovascular magnetic resonance on a Siemens 1.5 T scanner to measure the aortic cross-sectional area in multiple locations. Ultrasound imaging with a Philips CX50 and linear array probe was used to measure carotid and brachial artery diameters. Carotid-femoral pulse wave velocity and the augmentation index were measured by SphygmoCor, brachial-femoral pulse wave velocity by Vicorder and aortic pulse wave velocity by cardiovascular magnetic resonance. The cardio-ankle vascular index (CAVI) was used as a measurement of global stiffness, and ultrasound was used to assess peripheral vessel distensibility. Adults born preterm had 20% smaller thoracic and abdominal aortic lumens (2.19 ± 0.44 vs. 2.69 ± 0.60 cm(2), P<0.001; 1.25 ± 0.36 vs. 1.94 ± 0.45 cm(2), P<0.001, respectively) but similar carotid and brachial diameters to adults born at term. Pulse wave velocity was increased (5.82 ± 0.80 vs. 5.47 ± 0.59 m s(-1), P<0.01, 9.06 ± 1.25 vs. 8.33 ± 1.28 m s(-1), P=0.01, 5.23 ± 1.19 vs. 4.75 ± 0.91 m s(-1), P<0.01) and carotid distensibility was decreased (4.75 ± 1.31 vs. 5.60 ± 1.48 mm Hg(-1)10(3), P<0.001) in this group compared with the group born at term. However, the global and peripheral arterial stiffness measured by CAVI and brachial ultrasound did not differ (5.95 ± 0.72 vs. 5.98 ± 0.60, P=0.80 and 1.07 ± 0.48 vs. 1.19 ± 0.54 mm Hg(-1)10(3), P=0.12, respectively). Adults who are born preterm have significant differences in their aortic structure from adults born at term, but they have relatively small differences in central arterial stiffness that may be partially explained by blood pressure variations.


Ion mobility-mass spectrometry and orthogonal gas-phase techniques to study amyloid formation and inhibition.
Amyloidogenic peptide oligomers are responsible for a variety of neurodegenerative disorders such as Alzheimer's and Parkinson's disease. Due to their dynamic, polydisperse, and polymorphic nature, these oligomers are very challenging to characterize using traditional condensed-phase methods. In the last decade, ion mobility-mass spectrometry (IM-MS) and related gas-phase techniques have emerged as a powerful alternative to disentangle the structure and assembly characteristics of amyloid forming systems. This review highlights recent advances in which IM-MS was used to characterize amyloid oligomers and their underlying assembly pathway. In addition, we summarize recent studies in which IM-MS was used to size- and mass-select species for a further spectroscopic investigation and outline the potential of IM-MS as a tool for the screening of amyloid inhibitors.