[Recurrent benign intrahepatic cholestasis. A case report].
A case of benign and recurrent intrahepatic cholestasis in a 46 year old female is presented. This patient, who correctly coincided with the diagnosis criteria, had 2 episodes of jaundice and pruritus over a period of 4 years. The diagnosis criteria, clinical features, blood tests, etiopathogenesis and treatment are reviewed.


Nonlinear visual mapping model for 3-D visual tracking with uncalibrated eye-in-hand robotic system.
A new control scheme for uncalibrated robotic visual tracking problem is proposed that compromises the computational expenses of overall system with offline modeling and online control. A nonlinear visual mapping model for the uncalibrated hand-eye coordination is first proposed with an artificial neural network implementation. An online visual tracking controller is then developed together with a real-time motion planner. To improve the system performance, the control scheme is also integrated with a feedforward controller to compensate unknown object motions. Extensive simulations and experiments demonstrate the effectiveness of the proposed control scheme.


A first-principles study of weakly bound molecules using exact exchange and the random phase approximation.
We present a study of the binding energy (BE) curves of rare gas and alkaline-earth dimers using an energy functional that includes exact exchange (EXX) and correlation energies within the random phase approximation (RPA). Our results for the equilibrium positions and long range behavior of the potential energy curves show great improvements over those obtained at the density functional theory level, within local and semilocal approximations. BEs are improved as well in the case of rare gas dimers. For Ar and Kr, the accuracy of our results is comparable to that of so-called van der Waals density functionals, although EXX/RPA yields BE curves that agree better with experiment for large separation distances, as expected. We also discuss shortcomings of the EXX/RPA perturbative approach and analyze possible sources of error in the description of the potential energy curve of alkaline-earth dimers, in particular, Be(2), exhibiting an unphysical maximum at large separations. We suggest that the lack of self-consistency in current EXX/RPA approaches might be largely responsible for most of the observed shortcomings. Finally, we present a tight-binding approach to obtain the eigenvalues of the dielectric matrix entering the calculation of the RPA correlation energy that greatly improves the efficiency of EXX/RPA calculations.


Facile cleavage of triethylsilyl (TES) ethers using o-iodoxybenzoic acid (IBX) without affecting tert-butyldimethylsilyl (TBS) ethers.
[reaction: see text] In DMSO cleavage of triethylsilyl (TES) ethers by o-iodoxybenzoic acid (IBX) was significantly faster than cleavage of tert-butyldimethylsilyl (TBS) ethers or further oxidation into carbonyl compounds. In most cases, TES protecting groups could be removed in good to excellent yields within 1 h, whereas similar TBS protecting groups remained intact under the same conditions. The procedure also could be adapted for direct one-pot conversion of TES ethers into carbonyl compounds.


Apigenin potentiates the growth inhibitory effects by IKK-β-mediated NF-κB activation in pancreatic cancer cells.
Apigenin is a potential chemopreventive agent for cancer prevention. Because of the central role of transcription factor nuclear factor-κB (NF-κB) in pancreatic cancer, we investigated the roles of NF-κB in apigenin-induced growth inhibition in pancreatic cancer cells. It showed that apigenin reduced cell growth and induced apoptosis in the cells. Apigenin treatment down-regulated not only basal but also TNF-α-induced NF-κB DNA binding activity, NF-κB transcription activity, inhibitor of κB (IκB)-α phosphorylation together with translocation of p65 and p50, and it accompanied with the blockade of IκB kinase (IKK)-β activity. Moreover, IKK blockage potentiated the anticancer efficacy of apigenin and IKK-β overexpression attenuated the apigenin-induced cell growth inhibition. Additionally, apigenin (30 mg/kg) administration suppressed pancreatic cancer growth and IKK-β activation in nude mice xenograft. These results indicated that apigenin had a potential to inhibit IKK-β-mediated NF-κB activation, and was a valuable agent for the pancreatic cancer treatment.


Cd²⁺-induced alteration of the global proteome of human skin fibroblast cells.
Cadmium (Cd(2+)) is a toxic heavy metal and a well-known human carcinogen. The toxic effects of Cd(2+) on biological systems are diverse and thought to be exerted through a complex array of mechanisms. Despite the large number of studies aimed to elucidate the toxic mechanisms of action of Cd(2+), few have been targeted toward investigating the ability of Cd(2+) to disrupt multiple cellular pathways simultaneously and the overall cellular responses toward Cd(2+) exposure. In this study, we employed a quantitative proteomic method, relying on stable isotope labeling by amino acids in cell culture (SILAC) and LC-MS/MS, to assess the Cd(2+)-induced simultaneous alterations of multiple cellular pathways in cultured human skin fibroblast cells. By using this approach, we were able to quantify 2931 proteins, and 400 of them displayed significantly changed expression following Cd(2+) exposure. Our results unveiled that Cd(2+) treatment led to the marked upregulation of several antioxidant enzymes (e.g., metallothionein-1G, superoxide dismutase, pyridoxal kinase, etc.), enzymes associated with glutathione biosynthesis and homeostasis (e.g., glutathione S-transferases, glutathione synthetase, glutathione peroxidase, etc.), and proteins involved in cellular energy metabolism (e.g., glycolysis, pentose phosphate pathway, and the citric acid cycle). Additionally, we found that Cd(2+) treatment resulted in the elevated expression of two isoforms of dimethylarginine dimethylaminohydrolase (DDAH I and II), enzymes known to play a key role in regulating nitric oxide biosynthesis. Consistent with these findings, we observed elevated formation of nitric oxide in human skin (GM00637) and lung (IMR-90) fibroblast cells following Cd(2+) exposure. The upregulation of DDAH I and II suggests a role of nitric oxide synthesis in Cd(2+)-induced toxicity in human cells.


Cooperation and conflict between women in the family.
Here I review recent research on reproductive conflict between females in families and how it influences their reproductive behaviour. Kin selection can favor cooperation between parent and offspring, siblings, or unrelated co-residents who share interests in other family members such as grand-offspring. However, these are also the individuals most likely to be sharing resources, and so conflict can also emerge. While substantial interest has arisen in evolutionary anthropology, especially over the last two decades, in the possibility of cooperative breeding in humans, less attention has been paid to reproductive conflict among female kin. Communal breeding in animals is generally understood as emerging from competition over the resources needed to breed. Competition for household resources is a problem that also faces human families. Models suggest that in some circumstances, inclusive fitness can be maximized by sharing reproduction rather than harming relatives by fighting with them, even if the shares that emerge are not equal. Thus, competition and cooperation turn out to be strongly related to each other. Reproductive competition within and between families may have underpinned the biological evolution of fertility patterns (such as menopause) and the cultural evolution of marriage, residence, and inheritance norms (such as late male marriage or primogeniture), which can enhance cooperation and minimize the observed incidence of such conflicts.


[Cutaneous angiolipoleiomyoma: a case report and literature review].
The Authors describe a rare case of cutaneous angiolipoleiomyoma in an acral location together with a brief literature review. A 62-year-old male presented with a slow-growing asymptomatic nodule, 2.2 cm in diameter, located in the subcutaneous tissue of the left calf. Ten months after surgical excision, the patient is alive and free of disease. Histologically, the lesion was well-circumscribed and contained three components: areas of mature fat tissue were intermingled with cellular areas of spindle eosinophilic cells, reminiscent of smooth muscle cells, and a complex mixture of vessels of different types and sizes. Immunohistochemically, the cellular spindle component was positive for vimentin and smooth muscle actin, and negative for S-100, HMB-45, MART-1 and oestrogen and progesterone receptors. The Authors discuss differential diagnosis with other benign lesions such as angioleiomyoma and subcutaneous angiomyolipoma.


Where We Work, Play, And Live: Health Equity and the Physical Environment.
The physical environment in which we live, work, and play has everything to do with our overall well-being and health. This issue of the North Carolina Medical Journal focuses on those physical structures, environmental factors, and access issues that impact North Carolinians' ability to make healthy choices and the policy changes that could improve indicators like access to healthy food, exercise opportunities, and secure and safe housing.


Warfarin Adherence Among Patients with Atrial Fibrillation in Rural Area of Dongyang, China: A Questionnaire-Based Study.
Adherence to warfarin is associated with improved outcome in patients with atrial fibrillation (AF), but the adherence status of patients in rural areas of China is not known. A questionnaire-based study evaluating warfarin adherence of rural residents with AF was carried out in Dongyang, China. Potentially eligible patients were screened and contacted by telephone, and their demographic characteristics were collected. Illness perception was assessed using the Brief Illness Perception Questionnaire (BIPQ), and warfarin adherence was assessed using a Chinese-version adherence scale. Univariate and multivariate analyses were conducted to identify factors associated with unsatisfactory adherence. A total of 201 patients (male, n=99; mean age, 70.3±8.12 years) were included, among whom 95 (47.3%) patients showed good adherence and 63 (31.3%) poor adherence. Number of co-dispensed drugs (multivariate analysis: odds ratio [OR]=3.64, 95% confidence interval [CI] 1.35-9.81, p=0.011) and BIPQ score (OR=1.25, 95% CI 1.17-1.33, p<0.001) were identified as factors associated with good adherence. Medical adherence to warfarin needs to improve in rural patients with AF. Efforts that can reduce the number of co-dispensed drugs and increase illness perception may improve warfarin adherence. This study may benefit future management of warfarin administration to rural patients with AF.


Functional analysis of putative adhesion factors in Lactobacillus acidophilus NCFM.
Lactobacilli are major inhabitants of the normal microflora of the gastrointestinal tract, and some select species have been used extensively as probiotic cultures. One potentially important property of these organisms is their ability to interact with epithelial cells in the intestinal tract, which may promote retention and host-bacterial communication. However, the mechanisms by which they attach to intestinal epithelial cells are unknown. The objective of this study was to investigate cell surface proteins in Lactobacillus acidophilus that may promote attachment to intestinal tissues. Using genome sequence data, predicted open reading frames were searched against known protein and protein motif databases to identify four proteins potentially involved in adhesion to epithelial cells. Homologous recombination was used to construct isogenic mutations in genes encoding a mucin-binding protein, a fibronectin-binding protein, a surface layer protein, and two streptococcal R28 homologs. The abilities of the mutants to adhere to intestinal epithelial cells were then evaluated in vitro. Each strain was screened on Caco-2 cells, which differentiate and express markers characteristic of normal small-intestine cells. A significant decrease in adhesion was observed in the fibronectin-binding protein mutant (76%) and the mucin-binding protein mutant (65%). A surface layer protein mutant also showed reduction in adhesion ability (84%), but the effect of this mutation is likely due to the loss of multiple surface proteins that may be embedded in the S-layer. This study demonstrated that multiple cell surface proteins in L. acidophilus NCFM can individually contribute to the organism's ability to attach to intestinal cells in vitro.


Comparison of the effects of a truncating and a missense MYBPC3 mutation on contractile parameters of engineered heart tissue.
Hypertrophic cardiomyopathy (HCM) is a cardiac genetic disease characterized by left ventricular hypertrophy, diastolic dysfunction and myocardial disarray. The most frequently mutated gene is MYBPC3, encoding cardiac myosin-binding protein-C (cMyBP-C). We compared the pathomechanisms of a truncating mutation (c.2373_2374insG) and a missense mutation (c.1591G>C) in MYBPC3 in engineered heart tissue (EHT). EHTs enable to study the direct effects of mutants without interference of secondary disease-related changes. EHTs were generated from Mybpc3-targeted knock-out (KO) and wild-type (WT) mouse cardiac cells. MYBPC3 WT and mutants were expressed in KO EHTs via adeno-associated virus. KO EHTs displayed higher maximal force and sensitivity to external [Ca(2+)] than WT EHTs. Expression of WT-Mybpc3 at MOI-100 resulted in ~73% cMyBP-C level but did not prevent the KO phenotype, whereas MOI-300 resulted in ≥95% cMyBP-C level and prevented the KO phenotype. Expression of the truncating or missense mutation (MOI-300) or their combination with WT (MOI-150 each), mimicking the homozygous or heterozygous disease state, respectively, failed to restore force to WT level. Immunofluorescence analysis revealed correct incorporation of WT and missense, but not of truncated cMyBP-C in the sarcomere. In conclusion, this study provides evidence in KO EHTs that i) haploinsufficiency affects EHT contractile function if WT cMyBP-C protein levels are ≤73%, ii) missense or truncating mutations, but not WT do not fully restore the disease phenotype and have different pathogenic mechanisms, e.g. sarcomere poisoning for the missense mutation, iii) the direct impact of (newly identified) MYBPC3 gene variants can be evaluated.


Artificial impaction in hip fracture. By F. J. Cotton, 1911.
Frederic Jay Cotton (Fig. 1) was born in Prescott, Wisconsin, and educated at Harvard. After postgraduate study in New York and in Europe, he returned to Boston where he had an association with most of the important hospitals. In addition to great surgical talent, he also was an able administrator and medical politician. He is remembered primarily for his work on fractures, which is summarized in his book, Dislocations and Joint Fractures. The two editions of this book were illustrated by many of the author's own drawings. Cotton was a founder of the American College of Surgeons and served as Regent of the College as well as on the Committee on Fractures. He served in both the Spanish American War and World War I. In the summer of 1918, he was the Chief of Surgery at Walter Reed Army Hospital in Washington, D.C. This article on "Artificial Impaction in Hip Fracture" is an example of the application of a clinical observation to the development of an improvement in the care of patients. It had been known for a long time that impacted fractures of the neck of the femur healed, while displaced fractures did not. Cotton was the first to suggest that impaction, after reduction of the fracture, would be of value. Cotton published three additional papers on the use of impaction in the treatment of hip fractures, the last in 1938, the year of his death. Impaction of fractures of the neck of the femur after reduction of the displacement was rapidly incorporated into all of the procedures for internal fixation of such injuries.


Prevention of oculopharyngeal muscular dystrophy-associated aggregation of nuclear polyA-binding protein with a single-domain intracellular antibody.
Oculopharyngeal muscular dystrophy (OPMD) belongs to the group of protein aggregation disorders and is caused by extensions of the N-terminal polyalanine stretch of the nuclear polyA-binding protein 1 (PABPN1). The presence of PABPN1-containing intranuclear aggregates in skeletal muscle is unique for OPMD and is also observed in transgenic mouse and cell models for OPMD. These models consistently support a direct role for the protein aggregation in OPMD pathogenesis. We have isolated and characterized a diverse panel of single-domain antibody reagents (VHH), recognizing different epitopes in PABPN1. The antibody reagents specifically detect endogenous PABPN1 in cell lysates on western blot and label PABPN1 in cultured cells and muscle sections. When expressed intracellularly as intrabodies in a cellular model for OPMD, aggregation of PABPN1 was prevented in a dose-dependent manner. More importantly yet, these intrabodies could also reduce the presence of already existing aggregates. Given the domain specificity of VHH-mediated aggregation interference, this approach at least allows the definition of the nucleation kernel in aggregation-prone proteins, thus facilitating etiological insight into this and other protein aggregation disorders, and ultimately, it may well provide useful therapeutic agents.


Effect of diazepam on brain neurotransmitters, plasma corticosterone, and the immune system of stressed rats.
Rats were treated with injections of diazepam (1 or 10 mg/kg) and stressed by restraint lasting 3 hours. This was performed once or, in animals immunized with sheep erythrocytes, repeatedly for 4 consecutive days. After repeated stress and/or diazepam treatment, the levels of brain noradrenalin decreased in all treated groups. Although both treatments (stress and diazepam) diminished the 5-hydroxytryptamine (5-HT)/5-hydroxyindoleacetic acid (5-HIAA) ratio, treatment with either dose of diazepam prevented the stress-induced fall of this ratio. The activity of hypothalamic glutamate decarboxylase, the enzyme taking part in GABA synthesis, was affected neither by the acute nor by repeated stress and/or diazepam treatment. The levels of plasma corticosterone were enhanced in all stressed rats, with and without drug. This finding was in accordance with the enhanced weights of adrenal glands in repeatedly stressed rats. The tendency to a corticosterone rise after repeated treatment with diazepam, 10 mg/kg, coincided with the enhanced weights of adrenal glands in these animals. The plaque-forming cell (PFC) response was reduced in all stressed animals and in animals treated with diazepam, 10 mg/kg. Accordingly, high doses of diazepam given repeatedly to rats are immunosuppressive, achieving this effect presumably by an enhancement of glucocorticoid secretion. Neither the low nor the high doses of diazepam affect the stress-induced enhancement of hypothalamohypophysial-adrenal axis activity and consecutive immunosuppression.


Phylogeographic and phylogenetic analysis for Tripterygium species delimitation.
Tripterygium wilfordii (Celastraceae) is a traditional Chinese medicine; and the dried root and rhizome constitute the main officinal parts. Tripterygium wilfordii has been identified as a potential candidate for the treatment of systemic lupus erythematosus, rheumatoid arthritis, nephritis, asthma, leprosy, and cancer. The phylogenetic relationships within the Tripterygium genus are ambiguous; thus, our aim is to clarify the relationships within this genus using phylogeographic and phylogenetic analyses. Here, we first sequenced three plastid DNA regions (i.e., psbA-trnH, rpl32-trnL, and trnL-trnF) and found that Tripterygium hypoglaucum and T. wilfordii were clustered together based on the strength of the topology in the phylogenetic analysis: T. hypoglaucum is polyphyletic, and T. wilfordii is paraphyletic. A spatial analysis of molecular variance showed that the best group value is 4, and the groups were almost consistent with the topology of in the phylogenetic analysis. The Mantel analyses of Tripterygium using IBD web showed statistically significant relationships between genetic and geographical distance distributions (r = .3479, p < .0001). The molecular dating using Fossil calibration indicated that the divergence in Tripterygium was approximately 8.13 Ma. Furthermore, we also analyzed four DNA regions (i.e., ITS2, psbA-trnH, matK, and rbcL) that were obtained from the NCBI nucleotide database; these results showed that T. wilfordii and T. hypoglaucum clustered together, while Tripterygium regelii represented a separate cluster. Tripterygium hypoglaucum and T. wilfordii were never distinct lineages, and the species circumscriptions are artificial. We propose that T. wilfordii and T. hypoglaucum are conspecific, while T. regelii likely constitutes a separate species.


Regulation of Chloroplast Development by Nitrogen Source and Growth Conditions in a Chlorella protothecoides Strain.
Chlorella strain (UTEX 27) maintains optimal photosynthetic capacity when growing photoautotrophically in the presence of ammonium. Nitrate-grown photoautotrophic cells, however, show a drastic loss of chlorophyll content and ribulose-1,6-bisphosphate carboxylase/oxygenase activity, resulting in a greater than 10-fold decrease in photosynthetic capacity and growth rate. Nitrate-grown cells are not deficient in protein content, and under mixotrophic and heterotrophic conditions, the alga can utilize nitrate as well as it does ammonium. The alga metabolizes both glucose and acetate in the dark with a doubling time of 5 to 6 hours. However, its growth on acetate is inhibited by light. Ribulose-1,6-biphosphate carboxylase/oxygenase activity correlates well with photosynthetic capacity, and glucose 6-phosphate dehydrogenase and hexokinase activities are altered in a manner consistent with the availability of glucose in growing cells. The alga appears to assimilate ammonium under photoautotrophic conditions primarily via the glutamine synthetase pathway, and shows an induction of both NADH and NADPH dependent glutamate dehydrogenase pathways under mixotrophic and heterotrophic conditions. Multiple isoforms are present only for hexokinase and glucose 6-phosphate dehydrogenase. Etiolated nitrate-grown cells resume greening and increase their photosynthetic capacity after about 6 hours of incubation in the presence of ammonium under photoautotrophic conditions. Similarly, the loss of photosynthetic capacity in ammonium-grown photoautotrophic cells commence about 9 hours after their transfer to heterotrophic nitrate containing media.


Using Mixed-Methods Research to Adapt and Evaluate a Family Strengthening Intervention in Rwanda.
Research in several international settings indicates that children and adolescents affected by HIV and other compounded adversities are at increased risk for a range of mental health problems including depression, anxiety, and social withdrawal. More intervention research is needed to develop valid measurement and intervention tools to address child mental health in such settings. This article presents a collaborative mixed-methods approach to designing and evaluating a mental health intervention to assist families facing multiple adversities in Rwanda. Qualitative methods were used to gain knowledge of culturally-relevant mental health problems in children and adolescents, individual, family and community resources, and contextual dynamics among HIV-affected families. This data was used to guide the selection and adaptation of mental health measures to assess intervention outcomes. Measures were subjected to a quantitative validation exercise. Qualitative data and community advisory board input also informed the selection and adaptation of a family-based preventive intervention to reduce the risk for mental health problems among children in families affected by HIV.. Community-based participatory methods were used to ensure that the intervention targeted relevant problems manifest in Rwandan children and families and built on local strengths. Qualitative data on culturally-appropriate practices for building resilience in vulnerable families has enriched the development of a Family-Strengthening Intervention (FSI). Input from community partners has also contributed to creating a feasible and culturally-relevant intervention. Mental health measures demonstrate strong performance in this population. The mixed-methods model discussed represents a refined, multi-phase protocol for incorporating qualitative data and community input in the development and evaluation of feasible, culturally-sound quantitative assessments and intervention models. The mixed-methods approach may be applied to research in other parts of sub-Saharan Africa and beyond.


Improving a natural CaMKII inhibitor by random and rational design.
CaM-KIIN has evolved to inhibit stimulated and autonomous activity of the Ca(2+)/calmodulin (CaM)-dependent protein kinase II (CaMKII) efficiently, selectively, and potently (IC50 ∼100 nM). The CN class of peptides, derived from the inhibitory region of CaM-KIIN, provides powerful new tools to study CaMKII functions. The goal of this study was to identify the residues required for CaMKII inhibition, and to assess if artificial mutations could further improve the potency achieved during evolution. First, the minimal region with full inhibitory potency was identified (CN19) by determining the effect of truncated peptides on CaMKII activity in biochemical assays. Then, individual residues of CN19 were mutated. Most individual Ala substitutions decreased potency of CaMKII inhibition, however, P3A, K13A, and R14A increased potency. Importantly, this initial Ala scan suggested a specific interaction of the region around R11 with the CaMKII substrate binding site, which was exploited for further rational mutagenesis to generate an optimized pseudo-substrate sequence. Indeed, the potency of the optimized peptide CN19o was >250fold improved (IC50 <0.4 nM), and CN19o has characteristics of a tight-binding inhibitor. The selectivity for CaMKII versus CaMKI was similarly improved (to almost 100,000fold for CN19o). A phospho-mimetic S12D mutation decreased potency, indicating potential for regulation by cellular signaling. Consistent with importance of this residue in inhibition, most other S12 mutations also significantly decreased potency, however, mutation to V or Q did not. These results provide improved research tools for studying CaMKII function, and indicate that evolution fine-tuned CaM-KIIN not for maximal potency of CaMKII inhibition, but for lower potency that may be optimal for dynamic regulation of signal transduction.


Disseminated infection due to Mycobacterium avium subsp. avium in an Asian elephant (Elephas maximus).
A disseminated infection caused by Mycobacterium avium subspecies avium (MAA) was diagnosed in a 57-yr-old male Asian elephant (Elephas maximus) housed at the Seoul Zoo, Gyeonggi, Republic of Korea. An apparent granulomatous inflammation with central caseous necrosis was evident in the lung sections. To confirm mycobacterial infection, polymerase chain reaction-restriction enzyme polymorphism analysis (PCR-RFLP) of the rpoB and hsp65 genes was performed from multiple organs and cultured bacteria. The PCR-RFLP revealed a M. avium subspecies. MAA was identified by multiplex PCR for detection of IS901 and IS1311. Thus, it is believed that MAA caused the disseminated infection in this case. Although the source of infection was not determined, the elephant may have become infected through contamination of soil and feed by free-living birds infected with MAA. This is the first reported case of disseminated infection due to MAA in a captive elephant in the Republic of Korea.


Tweezing of Magnetic and Non-Magnetic Objects with Magnetic Fields.
Although strong magnetic fields cannot be conveniently "focused" like light, modern microfabrication techniques enable preparation of microstructures with which the field gradients - and resulting magnetic forces - can be localized to very small dimensions. This ability provides the foundation for magnetic tweezers which in their classical variant can address magnetic targets. More recently, the so-called negative magnetophoretic tweezers have also been developed which enable trapping and manipulations of completely nonmagnetic particles provided that they are suspended in a high-magnetic-susceptibility liquid. These two modes of magnetic tweezing are complimentary techniques tailorable for different types of applications. This Progress Report provides the theoretical basis for both modalities and illustrates their specific uses ranging from the manipulation of colloids in 2D and 3D, to trapping of living cells, control of cell function, experiments with single molecules, and more.


A critical role for the protein tyrosine phosphatase receptor type Z in functional recovery from demyelinating lesions.
Several lines of evidence suggest that tyrosine phosphorylation is a key element in myelin formation, differentiation of oligodendrocytes and Schwann cells, and recovery from demyelinating lesions. Multiple sclerosis is a demyelinating disease of the human central nervous system, and studies of experimental demyelination indicate that remyelination in vivo requires the local generation, migration or maturation of new oligodendrocytes, or some combination of these. Failure of remyelination in multiple sclerosis could result from the failure of any of these processes or from the death of oligodendrocytes. Ptprz encodes protein tyrosine phosphatase receptor type Z (Ptpz, also designated Rptpbeta), which is expressed primarily in the nervous system but also in oligodendrocytes, astrocytes and neurons. Here we examine the susceptibility of mice deficient in Ptprz to experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. We observe that mice deficient in Ptprz show impaired recovery from EAE induced by myelin oligodendrocyte glycoprotein (MOG) peptide. This sustained paralysis is associated with increased apoptosis of mature oligodendrocytes in the spinal cords of mutant mice at the peak of inflammation. We further demonstrate that expression of PTPRZ1, the human homolog of Ptprz, is induced in multiple sclerosis lesions and that the gene is specifically expressed in remyelinating oligodendrocytes in these lesions. These results support a role for Ptprz in oligodendrocyte survival and in recovery from demyelinating disease.


Lymphomatoid papulosis and cutaneous CD30+ lymphoma.
Lymphomatoid papulosis and cutaneous CD30+ lymphoma are closely related conditions in which large atypical lymphocytes that have similar immunophenotypic features occur. In lymphomatoid papulosis, the lesions are papules and nodules that spontaneously involute. There are two polar histologic patterns, type A and B, in which the large atypical cells resemble those of Hodgkin's disease and mycosis fungoides, respectively, but in many cases, features of both types are present, either separately or in the same lesions. Variants of lymphomatoid papulosis include cases with a perifollicular distribution and those with lymphocytic vasculitis or dermal mucin deposits. Clinical lesions that tend to be stable, a monomorphous cellular composition, and in the case of immunocompromised patients, the presence of Epstein-Barr viral genome characterize cutaneous CD30+ lymphoma. A loss of response to transforming growth factor-beta, which normally dampens cellular proliferation, may differentiate CD30+ lymphoma from lymphomatoid papulosis.


Biogenic Amine Degradation by Bacillus Species Isolated from Traditional Fermented Soybean Food and Detection of Decarboxylase-Related Genes.
Biogenic amines in some food products present considerable toxicological risks as potential human carcinogens when consumed in excess concentrations. In this study, we investigated the degradation of the biogenic amines histamine and tyramine and the presence of genes encoding histidine and tyrosine decarboxylases and amine oxidase in Bacillus species isolated from fermented soybean food. No expression of histidine and tyrosine decarboxylase genes (hdc and tydc) were detected in the Bacillus species isolated (B. subtilis HJ0-6, B. subtilis D'J53-4, and B. idriensis RD13-10), although substantial levels of amine oxidase gene (yobN) expression were observed. We also found that the three selected strains, as non-biogenic amineproducing bacteria, were significantly able to degrade the biogenic amines histamine and tyramine. These results indicated that the selected Bacillus species could be used as a starter culture for the control of biogenic amine accumulation and degradation in food. Our study findings also provided the basis for the development of potential biological control agents against these biogenic amines for use in the food preservation and food safety sectors.


A Model to Predict the Expansion of Trioza erytreae throughout the Iberian Peninsula Using a Pest Risk Analysis Approach.
Assessing the potential of spread of an introduced crop pest in a new country is crucial to anticipating its effects on crop production and deriving phytosanitary management toward reducing potential negative effects. Citrus production represents a key agricultural activity throughout the Mediterranean basin. The African citrus psyllid Trioza erytreae (del Guercio, 1918) (Hemiptera: Triozidae) is a natural vector of Candidatusliberibacter spp., the causal agent of the harmful disease huanglongbing (HLB) or "citrus greening disease". In continental Europe, T. erytreae was detected for the first time in northwestern Spain in 2014. Pest risk analysis (PRA) approaches, such as modeling, consider both time and space components to predict the potential distribution of pests in a given region. In this work, we aim to parameterize a model able to predict the expected spread of T. erytreae in the Iberian Peninsula using three types of PRA models. The kernel model with two hypothetical entry points accurately predicted the distribution of T. erytreae with respect to latitude. This model should be further refined and validated to support decision-makers in the adoption of timely and successful management and regulatory measures against the spread of T. erytreae to other citrus-producing areas in Europe.


Stimulatory effects on lactotrophs and crop-sac of interleukin-1 and interleukin-2 in pigeons (Columba livia).
The ultrastructural effects of human-recombinant interleukin-1 beta (IL-1 beta) and human-recombinant interleukin-2 (IL-2) on the crop-sac (the target organ for prolactin secretion in birds) and the anterior pituitary lactotrophs, were studied in pigeons (Columba livia). The intraventricular microinfusion of the two interleukins produced maximal crop-sac stimulation with milk-like secretion, as demonstrated by the observation of ultrastructural changes in the lactiferous areas through scanning and transmission electron microscopy of crop-sac mucosa. A marked activation of the anterior pituitary lactotrophs was also observed. Crop-sac and pituitary lactotrophs stimulatory effects were prevented by a previous intraventricular treatment with monoclonal antibodies for IL-1 beta and IL-2 receptors, but not by an intraperitoneal administration of naloxone. The present results show that interleukins possess in pigeons marked stimulatory effects on prolactin secretion and that these are mediated by specific receptors.


Tympanic and transtympanic electrocochleography in acoustic neuroma and vestibular nerve section surgery.
Eighth nerve action potential (AP) amplitudes and latencies and cochlear microphonic (CM) amplitudes were compared using tympanic and transtympanic electrocochleography (ECOG) in two patient groups. Tympanic ECOG was performed with a wick electrode placed on the tympanic membrane (TM). Transtympanic ECOG was performed with a needle electrode placed on the promontory of the anesthetized patient. Eighteen subjects were tested by tympanic ECOG as part of a preoperative assessment for either acoustic neuroma removal or transection of the vestibular portion of the eighth cranial nerve. Surgery occurred within 1 week of the preoperative evaluation. Intraoperative auditory monitoring was performed using transtympanic ECOG. Baseline recordings were compared to the preoperative tympanic ECOG data. Stimuli were condensation and rarefaction clicks and tone bursts, presented by an insert earphone. As expected, the two methods resulted in essentially identical response latencies and large amplitude differences, although the response amplitudes were extremely variable. The AP amplitude and the CM amplitude did not increase by the same factor with the transtympanic (TT) electrode compared to the tympanic electrode. On comparison of preoperative and intraoperative response amplitudes with regard to stimulus polarity, tympanic electrocochleography appears to be a useful method of gathering preliminary information on the status of the patient's auditory system. In this study, tympanic ECOG was found to have some predictive value when trying to ascertain the best intraoperative monitoring situation.


Spray washing of tomatoes with chlorine dioxide to minimize Salmonella on inoculated fruit surfaces and cross-contamination from revolving brushes.
Chlorine dioxide (ClO(2)) is an antimicrobial agent available for commercial produce washing. This study examined the efficacy of ClO(2) at 5 parts per million (ppm) during spray washing of tomatoes (5.0 ml/s per fruit) for preventing Salmonella enterica transfer from inoculated roller brushes to fruit and wash runoff. Furthermore, the sanitizing effects of ClO(2) during spray washing at low and high flow rates (5.0 and 9.3 ml/s per fruit, respectively) on tomato surfaces (nonstem scar areas) with either newly introduced (wet) or overnight air-dried Salmonella inocula were investigated. Salmonella transfer from contaminated brushes to fruit surfaces was reduced 2.1 +/- 0.6 or 4.7 +/- 0.2 log cycles after spray washing with water for 40 s or with the ClO(2) solution for 10 s, respectively. Cross-contamination of Salmonella from brushes to wash runoff during fruit washing for 60 s decreased 5.9 +/- 0.3 log cycles when ClO(2) was used. Fruit washing using contaminated brushes and low flow-rate washing with either water or ClO(2) solution for 10 s reduced newly introduced Salmonella on fruit surfaces by 1.7 +/- 0.6 or 5.1 +/- 0.3 log cycles, respectively. For fruit surfaces with air-dried inocula, washing with water and using uncontaminated brushes for 10 to 40 s reduced Salmonella by 3.2 +/- 0.3 to 3.4 +/- 0.4 log cycles; and the reduction was significantly improved by using ClO(2), high flow rate, or a longer washing time. Washing with ClO(2) at tested flow rates for 10 to 60 s resulted in a 4.4 +/- 0.6 to 5.2 +/- 0.1 log reduction of air-dried Salmonella on fruit surfaces.


A radical procedure of circumferential spinal cord decompression through a modified posterior approach for thoracic myelopathy caused by severely impinging anterior ossification.
Thoracic myelopathy caused by an anterior, massive ossified plaque is often progressive and responds poorly to conservative treatment. Direct removal of the compressing ossification is the optimal procedure for a spinal cord that is severely impinged anteriorly. However, both anterior and posterior decompressive manipulations have caused catastrophic iatrogenic spinal cord injuries. A comprehensive treatment method for severe thoracic myelopathy that enables a sufficient and safe decompression of the spinal cord is needed. The purpose of this study is to demonstrate the efficacy, safety, and results of a one-stage circumferential decompressive procedure using a modified posterior approach in patients with severe thoracic myelopathy resulting from anterior spinal compression. A modified procedure of circumferential spinal cord decompression for thoracic myelopathy is described. A retrospective study was conducted to investigate the clinical outcomes of 23 sequentially treated patients. Twenty-three patients were treated sequentially with a modified procedure for circumferential spinal cord decompression for thoracic myelopathy. Outcomes were assessed using the Japanese Orthopedic Association (JOA) score, modified Frankel classification, Hirabayashi recovery rate, and a general assessment of complications. Twenty-three patients with thoracic myelopathy caused by a massive, anterior ossified structure were treated with an extensive posterior laminectomy, anterior removal of the ossification, and interbody fusion with kyphosis-reversing stabilization through a modified posterolateral approach. The neurologic outcomes are evaluated according to the JOA and the modified Frankel classification before surgery, 2 weeks after surgery, 1 year after surgery, and at the final follow-up visit. The surgical outcomes are also described using the Hirabayashi recovery rate. Radiographs, computed tomography (CT), and magnetic resonance imaging were performed before and after surgery. A postoperative CT scan was obtained to determine the efficacy of the decompression. Operative time, intraoperative blood loss, and complications were reviewed from the medical records. In addition, a 48-year-old man who presented with severe thoracic myelopathy resulting from anterior impingement with multiple osteophytes is described as an illustrative patient. The sites of ossification in this series were distributed widely, from T4-T12. The anterior ossified plaques of all patients were resected completely. Five patients who had intraoperative evidence of dural ossification required resection of the ossified dura matter. The average operating time was 276 minutes. Mean intraoperative blood loss was 1,350 mL. The postoperative follow-up ranged from 2.5 to 6 years, with an average of 4.6 years. The average preoperative JOA score was 4.3±1.5 points, and it improved to 6.1±1.9 points 2 weeks postoperatively, to 8.1±1.8 points 1 year postoperatively, and to 8.5±1.9 points at the most recent follow-up. The overall Hirabayashi recovery rate at the final examination averaged 63.6±22.4%. Eight patients were graded as excellent, 10 as good, 4 as fair, and 1 as unchanged. No patient was graded as deteriorated. The paralysis improved by at least 1 grade in 22 patients (95.7%). Transient deterioration of thoracic myelopathy occurred immediately after surgery in three patients (13%). Cerebrospinal fluid leakage occurred in six patients (26.1%). One patient sustained severe bilateral groin pain, three had unilateral intercostal neuralgia, and pleura tear occurred in one patient. One-stage posterior decompression, anterior extirpation of the ossification, and interbody fusion with instrumentation via a modified posterior approach is a safe and effective treatment for severe thoracic myelopathy resulting from prominent anterior impingement. This procedure is technically demanding, and the indications are limited to thoracic myelopathy caused by severe anterior impingement of various etiologies from T4-T12.


Adenylyl cyclase isoforms in pregnant and non-pregnant human myometrium.
The precise factors involved in the transition of the relaxed pregnant uterus to the contractile state at the onset of parturition remain unclear, but it is accepted that cAMP-generating pathways contribute to uterine relaxation. We have previously reported an increased expression of the adenylyl cyclase (AC)-stimulating protein Galphas in human myometrium during gestation, with a corresponding increase in GTP-stimulated AC activity. However, little is known about the predominating AC isoforms expressed during pregnancy. This information is important, because although all AC isoforms are stimulated by Galphas, their regulation by other signalling molecules is very different. In the present study we have identified the isoforms of AC expressed in both pregnant and non-pregnant myometrium by mRNA analysis and immunoblotting. mRNA encoding for AC I, II, III, VIII and IX was present in non-pregnant and pregnant myometrium, and in cultured myometrial cells. Differing levels of AC protein could be detected in myometrial plasma membranes, with decreased levels of Group 1 (isoforms I, III and VIII) and Group 4 (IX) ACs allied with increased levels of Group 2 (II, IV and VII) and 3 (V and VI) ACs during pregnancy. These findings imply a role for Group 2-activating pathways, e.g. G-protein betagamma-subunits and protein kinase C, in the maintenance of uterine quiescence, whilst suggesting a lesser involvement of calcium-calmodulin complex, an activator of Group 1 AC isoforms, in uterine relaxation during gestation. These data may provide an alternative pharmacological approach for the attenuation of preterm labour.


Antibiotic resistance of faecal Escherichia coli in poultry, poultry farmers and poultry slaughterers.
The percentage of faecal samples containing resistant Echerichia coli and the proportion of resistant faecal E. coli were determined in three poultry populations: broilers and turkeys commonly given antibiotics, and laying hens treated with antibiotics relatively infrequently. Faecal samples of five human populations were also examined: turkey farmers, broiler farmers, laying-hen farmers, broiler slaughterers and turkey slaughterers. The MICs of antibiotics commonly used in poultry medicine were also determined. Ciprofloxacin-resistant isolates from these eight populations and from turkey meat were genotyped by pulsed-field gel electrophoresis (PFGE) after SmaI digestion. The proportion of samples containing resistant E. coli and the percentages of resistant E. coli were significantly higher in turkeys and broilers than in the laying-hen population. Resistance to nearly all antibiotics in faecal E. coli of turkey and broiler farmers, and of turkey and broiler slaughterers, was higher than in laying-hen farmers. Multiresistant isolates were common in turkey and broiler farmers but absent in laying-hen farmers. The same resistance patterns were found in turkeys, turkey farmers and turkey slaughterers and in broiler, broiler farmers and broiler slaughterers. The PFGE patterns of the isolates from the eight populations were quite heterogeneous, but E. coli with an identical PFGE pattern were isolated at two farms from a turkey and the farmer, and also from a broiler and a broiler farmer from different farms. Moreover, three E. coli isolates from turkey meat were identical to faecal isolates from turkeys. The results of this study strongly indicate that transmission of resistant clones and resistance plasmids of E. coli from poultry to humans commonly occurs.


PlantTFDB 3.0: a portal for the functional and evolutionary study of plant transcription factors.
With the aim to provide a resource for functional and evolutionary study of plant transcription factors (TFs), we updated the plant TF database PlantTFDB to version 3.0 (http://planttfdb.cbi.pku.edu.cn). After refining the TF classification pipeline, we systematically identified 129 288 TFs from 83 species, of which 67 species have genome sequences, covering main lineages of green plants. Besides the abundant annotation provided in the previous version, we generated more annotations for identified TFs, including expression, regulation, interaction, conserved elements, phenotype information, expert-curated descriptions derived from UniProt, TAIR and NCBI GeneRIF, as well as references to provide clues for functional studies of TFs. To help identify evolutionary relationship among identified TFs, we assigned 69 450 TFs into 3924 orthologous groups, and constructed 9217 phylogenetic trees for TFs within the same families or same orthologous groups, respectively. In addition, we set up a TF prediction server in this version for users to identify TFs from their own sequences.


Novel pathogenic mutations and skin biopsy analysis in Knobloch syndrome.
To facilitate future diagnosis of Knobloch syndrome (KS) and better understand its etiology, we sought to identify not yet described COL18A1 mutations in KS patients. In addition, we tested whether mutations in this gene lead to absence of the COL18A1 gene product and attempted to better characterize the functional effect of a previously reported missense mutation. Direct sequencing of COL18A1 exons was performed in KS patients from four unrelated pedigrees. We used immunofluorescent histochemistry in skin biopsies to evaluate the presence of type XVIII collagen in four KS patients carrying two already described mutations: c.3277C>T, a nonsense mutation, and c.3601G>A, a missense mutation. Furthermore, we determined the binding properties of the mutated endostatin domain p.A1381T (c.3601G>A) to extracellular matrix proteins using ELISA and surface plasmon resonance assays. We identified four novel mutations in COL18A1, including a large deletion involving exon 41. Skin biopsies from KS patients revealed lack of type XVIII collagen in epithelial basement membranes and blood vessels. We also found a reduced affinity of p.A1381T endostatin to some extracellular matrix components. COL18A1 mutations involved in Knobloch syndrome have a distribution bias toward the coding exons of the C-terminal end. Large deletions must also be considered when point mutations are not identified in patients with characteristic KS phenotype. We report, for the first time, lack of type XVIII collagen in KS patients by immunofluorescent histochemistry in skin biopsy samples. As a final point, we suggest the employment of this technique as a preliminary and complementary test for diagnosis of KS in cases when mutation screening either does not detect mutations or reveals mutations of uncertain effect, such as the p.A1381T change.


Epigenetics and Vascular Senescence-Potential New Therapeutic Targets?
Epigenetics is defined as the heritable alterations of gene expression without changes to the coding sequence of DNA. These alterations are mediated by processes including DNA methylation, histone modifications, and non-coding RNAs mechanisms. Vascular aging consists of both structural and functional changes in the vasculature including pathological processes that drive progression such as vascular cell senescence, inflammation, oxidation stress, and calcification. As humans age, these pathological conditions gradually accumulate, driven by epigenetic alterations, and are linked to various aging-related diseases. The development of drugs targeting a spectrum of epigenetic processes therefore offers novel treatment strategies for the targeting of age-related diseases. In our previous studies, we identified HDAC4, JMJD3, Fra-1, and GATA4 as potential pharmacological targets for regulating vascular inflammation, injury, and senescence.


Clinical impact of K-ras mutation in colorectal cancer patients treated with adjuvant FOLFOX.
K-ras proto-oncogene is commonly mutated in colorectal cancer (CRC) and has been associated with predictive markers for anti-EGFR (epidermal growth factor receptor) therapy. However, the prognostic role of K-ras status is still unclear. The aim of this study was to evaluate the association between k-ras status and addition of oxaliplatin to fluorouracil plus leucovorin (FOLFOX) chemotherapy in CRC patients with curative surgical resection. Sixty-six patients with stage II or III CRC were treated with FOLFOX or fluorouracil plus leucovorin (FL) followed by curative surgery between January 2004 and October 2007. K-ras status was assessed by direct sequencing. Fifteen patients (22.7%) had K-ras mutations of codon 12 (11/15) or codon 13 (4/15). There were no significant differences in clinicopathological parameters, such as age, sex, stage, or adjuvant regimen between the wild-type K-ras and mutant K-ras. With a median follow-up of 41.6 months (range 25.1-72.3 months), median disease-free survival (DFS) and overall survival (OS) were not reached. With regard to K-ras status, DFS and OS were not statistically different (P = 0.269 and P = 0.917, respectively). Even in the group treated with FOLFOX only, neither DFS (P = 0.651) nor OS (P = 0.265) was significantly different according to K-ras status. With the exception of tumor location in DFS and OS, no differences in other variables were observed. Proximal colon cancer patients had a longer DFS than distal CRC patients (P = 0.079); this trend was maintained only in the wild-type K-ras group (P = 0.051). These results showed that K-ras status was not associated with clinical outcome in patients treated with adjuvant FOLFOX.


Inconsistent contraceptive use among female college students: implications for intervention.
The authors evaluated the longitudinal consistency of use of contraceptive and barrier methods among female college students attending a student health clinic. The majority of students using unreliable methods of contraception during follow-up did not report unreliable contraceptive use at the baseline observation. Of 213 women who participated, 33% used unreliable contraception; 9% only at baseline, 14% only during 6-month follow-up, and 9% at both. Selection of a contraceptive method varied considerably over time. Of those using the oral contraceptive pill at baseline, 31% did not use this method during follow-up, and 43% of those using condoms at baseline had intercourse without a condom during follow-up. Single observations are inadequate to detect unreliable contraceptive use in this population; cross-sectional studies will fail to detect important transitions in contraceptive use. Interventions to prevent pregnancy and sexually transmitted disease among female college students should include a focus on the consistency of contraceptive use.


Ceramide and sphingosine-1 phosphate in COPD lungs.
Studies of chronic obstructive pulmonary disease (COPD) using animal models and patient plasma indicate dysregulation of sphingolipid metabolism, but data in COPD lungs are sparse. Mass spectrometric and immunostaining measurements of lungs from 69 COPD, 16 smokers without COPD and 13 subjects with interstitial lung disease identified decoupling of lung ceramide and sphingosine-1 phosphate (S1P) levels and decreased sphingosine kinase-1 (SphK1) activity in COPD. The correlation of ceramide abundance in distal COPD lungs with apoptosis and the inverse correlation between SphK1 activity and presence of emphysema suggest that disruption of ceramide-to-S1P metabolism is an important determinant of emphysema phenotype in COPD.


US Pharmacopeial Convention safety evaluation of menaquinone-7, a form of vitamin K.
Vitamin K plays important biological roles in maintaining normal blood coagulation, bone mineralization, soft tissue physiology, and neurological development. Menaquinone-7 is a form of vitamin K2 that occurs naturally in some animal-derived and fermented foods. It is also available as an ingredient of dietary supplements. Menaquinone-7 has greater bioavailability than other forms of vitamin K, which has led to increasing sales and use of menaquinone-7 supplements. This special article reviews the chemistry, nomenclature, dietary sources, intake levels, and pharmacokinetics of menaquinones, along with the nonclinical toxicity data available and the data on clinical outcomes related to safety (adverse events). In conclusion, the data reviewed indicate that menaquinone-7, when ingested as a dietary supplement, is not associated with any serious risk to health or with other public health concerns. On the basis of this conclusion, US Pharmacopeia monographs have been developed to establish quality standards for menaquinone-7 as a dietary ingredient and as a dietary supplement in various dosage forms.


Training simulation for helicopter navigation by characterizing visual scan patterns.
Helicopter overland navigation is a cognitively complex task that requires continuous monitoring of system and environment parameters and years of training. This study investigated potential improvements to training simulation by analyzing the influences of flight expertise on visual scan patterns. There were 12 military officers who varied in flight expertise as defined by total flight hours who participated in overland navigation tasks. Their gaze parameters were tracked via two eye tracking systems while subjects were looking at out-the-window (OTW) and topographic Map views in a fixed based helicopter simulator. Flight performance measures were not predicted by the expertise level of pilots. However, gaze parameters and scan management skills were predicted by the expertise level. For every additional 1000 flight hours, on average, the model predicted the median dwell will decrease 28 ms and the number of view changes will increase 33 times. However, more experienced pilots scanned more OTW than novice pilots, which was contrary to our expectation. A visualization tool (FEST: Flight and Eye Scan visualization Tool) to replay navigation tasks and corresponding gaze data was developed. Qualitative analysis from FEST revealed visual scan patterns of expert pilots not only looking ahead on the map, but also revisiting areas on the map they just flew over to retain confidence in their orientation. Based on the analysis provided above, this work demonstrates that neurophysiological markers, such as eye movements, can be used to indicate the aspects of a trainee's cognitive state that are useful for cuing an instructional system.


Copepod feeding currents: flow patterns, filtration rates and energetics.
Particle image velocimetry was used to construct a quasi 3-dimensional image of the flow generated by the feeding appendages of the calanoid copepod Temora longicornis. By scanning layers of flow, detailed information was obtained on flow velocity and velocity gradients. The flow around feeding T. longicornis was laminar, and was symmetrical viewed dorsally, but highly asymmetrical viewed laterally, with high levels of vorticity on the ventral side. The flow rate through the feeding appendages varied between 77 and 220 ml day(-1) per individual. The morphology of the flow field ensured that water was entrained over the full length of the first antennae. These were kept out of areas with high velocity gradients that could interfere with distant mechano- or chemoreception. The volume of influence, i.e. the volume of water around the foraging copepod, where shear rates were significantly higher than background levels, was calculated. Implications for encounter probability and mechanoreception are discussed. The average rate of energy dissipation within the copepod's volume of influence is several times higher than the levels of turbulent energy dissipation these animals are likely to encounter in their environment. Even in highly turbulent environments, adult T. longicornis will not experience very significant effects of turbulence. Within the volume of influence of the copepods the energy dissipation due to viscous friction varied between 6.6 x 10(-11) and 2.3 x 10(-10)W. Taking mechanical efficiency and muscle efficiency into account, this results in a total energetic cost of the feeding current of 1.6 x 10(-9)W per copepod. This value represents only a small percentage of the total energy budget of small calanoid copepods.


Normal levels of inflammatory markers in treated patients with familial hypercholesterolaemia: a cross-sectional study.
To assess the relationship of levels of inflammatory risk markers to presence of clinical coronary artery disease (CAD) in patients with treated heterozygous familial hypercholesterolaemia. A cross-sectional study of patients on the Simon Broome Familial Hyperlipidaemia Register. Six hospital outpatient clinics in the UK. A total of 211 men and 199 women with heterozygous familial hypercholesterolaemia. Analysis of conventional risk factors and concentrations of high-sensitivity C-reactive protein (hsCRP), lipoprotein(a), serum intercellular adhesion molecule (sICAM), interleukin-6 (IL-6) and lipoprotein-associated phospholipase A2 (LpPLA2) mass. CAD was present in 104 men and in 55 women; the mean ages of onset were 43.1 and 46.5 years, respectively. On univariate analysis there was a positive relationship of CAD with age, male sex, smoking, IL-6 and sICAM, and an inverse relationship with low-density lipoprotein (LDL) and LpPLA2. On multivariate analysis, age, smoking, low LDL and low LpPLA2 were associated with CAD. When LpPLA2 values were adjusted for apoB and aspirin usage, there was no significant difference between those with and without CAD. Only age and smoking were independently associated with CAD in men, and IL-6 and lipoprotein(a) in women. Although on univariate analysis inflammatory marker levels were associated with CAD in these patients, the majority of the associations, including that for hsCRP, disappeared when corrected for smoking and apoB. This may be because atherosclerotic plaques in these statin-treated patients were quiescent or an effect of aspirin usage. In this observational study newer risk markers were not usefully associated with the presence or absence of symptomatic CAD.


The duration of REM sleep epic, odes in normal sleep.
The distributions of the durations of the first 3 REM sleep episodes have been analysed using a total of 134 overnight sleep recordings from 10 subjects. From investigation of the length of uninterrupted episodes of stage REM, it is shown that arousals to stage 0/1 could play an important part in the process of REM exit, and that by the middle of the sleep period, these arousals probably occur according to a Poisson process. During the first and second REM episodes a more complex process appears to be at work, which could reflect increased pressure for slow wave sleep. These findings suggest that the duration of a REM episode is determined by a process that has a large stochastic element, which is not necessarily tied to REM entry.


Sequential shape similarity for active contour based left ventricle segmentation in cardiac cine MR image.
Delineation of the boundaries of the Left Ventricle (LV) in cardiac Magnetic Resonance Images (MRI) is a hot topic due to its important diagnostic power. In this paper, an approach is proposed to extract the LV in a sequence of MR images. In the proposed paper, all images in the sequence are segmented simultaneously and the shape of the LV in each image is supposed to be similar to that of the LV in nearby images in the sequence. We coined the novel shape similarity constraint, and it is called sequential shape similarity (SSS in short). The proposed segmentation method takes the Active Contour Model as the base model and our previously proposed Gradient Vector Convolution (GVC) external force is also adopted. With the SSS constraint, the snake contour can accurately delineate the LV boundaries. We evaluate our method on two cardiac MRI datasets and the Mean Absolute Distance (MAD) metric and the Hausdorff Distance (HD) metric demonstrate that the proposed approach has good performance on segmenting the boundaries of the LV.


[Therapeutic esophagoscopy based on a portal and preportal block in hemorrhaging varices of the esophagus and portal hypertension].
Parallel with the hitherto known methods of treatment of bleeding esophageal varicosities in portal hypertension with Seinkstaken-Blackmore's probe and by surgical approaches for controlling the hemorrhage from ruptured esophageal varicosities, such as Cryle's and Linton's operations, azigoportal deconnection by Tanner's technique, splenectomy, omentohepatoplexy, Sugiura's operation, esophagus ligation by the method of Fosschulte and V. Mateev (1983), the authors apply the method of transendoscopic sclerosification of bleeding varicosities in adults and children with cirrhosis of the liver and prehepatic block. The indications and contraindications of the method and the etiologic factors underlying portal and preportal block in adults and children (in adults--cirrhosis of the liver, in children--mostly preportal block secondary to portal vein thrombosis dating back to early childhood after exchange transfusion through the umbilical vein) are discussed. Of 11 sclerosified children 3 to 14 years of age, 10 are still alive (100 per cent survival of living patients). For the period 1985-1990 a total of 60 adult patients with bleeding ulcers were sclerosified and resclerosified. Hemostasis attempted in 11 patients provided successful obliteration in 42 per cent; endoscopic failure--in 15 patients (57.69 per cent). Seven patients were operated, 5 of them died. Fourty-off of 53 nonoperated patients died. Overall case fatality rate was 78.33 per cent, operative case fatality rate--71.42 per cent. Fifteen of the deceased nonoperated patients died of uncontrollable persistent bleeding, 27 of severe hepatic failure, progressive jaundice, ascites hepatorenal insufficiency and hepatargia.(ABSTRACT TRUNCATED AT 250 WORDS)


Prospective trial registration for clinical research: what is it, what is it good for, and why do I care?
Optimizing evidence-based medicine--and therefore the care of our patients--requires a public record of both the benefits and the risks of various medical interventions. Unfortunately, available evidence is often skewed because some clinical trials are withheld from publication; only selected data are reported, and statistical techniques are often inappropriately determined following data analysis. Prospective clinical trial registration (PCTR) is the public documentation of trial protocols--today primarily on the Internet--before data analysis (and ideally before trial commencement). The primary goals of PCTR are to reduce selective reporting and improve data analysis transparency, but it may also promote trial awareness for the public and other investigators. Prospective clinical trial registration is certainly not without problems, but many have been resolved, and the remainder is relatively minor in nature and easily overcome. Multiple organizations endorse (in some cases mandate) PCTR, including prominent committees of medical editors, the World Health Organization, the World Medical Association (responsible for the Helsinki Declaration), and, more recently, the US Food and Drug Administration. Although Regional Anesthesia and Pain Medicine does not currently require registration for published articles, PCTR in this and other anesthesiology and pain journals may become mandatory within the next few years. Potential authors/investigators will therefore benefit from becoming familiar with PCTR before mandatory registration implementation, and familiarity among readers may improve interpretation and understanding of clinical research results.


Influenza vaccination and intention to receive the pandemic H1N1 influenza vaccine among healthcare workers of British Columbia, Canada: a cross-sectional study.
To assess healthcare workers' attitudes and concerns regarding seasonal and pandemic influenza vaccines in order to improve vaccination campaign communications. Cross-sectional survey. All 6 health authorities in British Columbia, Canada. An anonymous, self-administered online survey was conducted from August 30 through September 30, 2009. Question topics included demographic characteristics, factors influencing acceptance of seasonal influenza vaccine, factors influencing intentions to accept pandemic H1N1 influenza vaccine, and knowledge and concerns regarding the effect of the influenza pandemic. All 96,217 British Columbia healthcare workers were eligible to participate. A volunteer sample of 4,046 healthcare workers returned the survey; 3,563 (88%) were women, 58% were under 50 years old (mean age + or - standard deviation, 45.3 + or - 10.9 years), 3,152 of 4,023 (79%) had 5 or more years of experience in their profession, 1,853 of 4,023 (46%) were nurses, and 2,833 (70%) had been vaccinated against seasonal influenza the previous year. Two thousand eight hundred (69%) respondents reported intending to receive the pandemic H1N1 vaccine. The most important predictor of this intention was having received the seasonal vaccine the previous year (odds ratio [OR], 6.25 [95% confidence interval {CI}, 5.39-7.26]). Worry about making loved ones ill was the only attitude associated with intention to receive the pandemic H1N1 vaccine (adjusted OR, 1.38 [95% CI, 1.27-1.50]). Concerns with vaccine safety (adjusted OR, 0.31 [95% CI, 0.25-0.39]) and belief "that H1N1 is not severe enough" (adjusted OR, 0.29 [95% CI, 0.26-0.32]) were independently associated with the intention to reject the pandemic H1N1 vaccine. Vaccination campaigns for pandemic H1N1 vaccine should use messages that emphasize the risk of illness among younger people and the opportunity to protect loved ones by getting the vaccine and should address concerns about the safety and effectiveness of the vaccine.


Of mice and models: improved animal models for biomedical research.
The ability to engineer the mouse genome has profoundly transformed biomedical research. During the last decade, conventional transgenic and gene knockout technologies have become invaluable experimental tools for modeling genetic disorders, assigning functions to genes, evaluating drugs and toxins, and by and large helping to answer fundamental questions in basic and applied research. In addition, the growing demand for more sophisticated murine models has also become increasingly evident. Good state-of-principle knowledge about the enormous potential of second-generation conditional mouse technology will be beneficial for any researcher interested in using these experimental tools. In this review we will focus on practice, pivotal principles, and progress in the rapidly expanding area of conditional mouse technology. The review will also present an internet compilation of available tetracycline-inducible mouse models as tools for biomedical research (http://www.zmg.uni-mainz.de/tetmouse/).


Baseline screening for the presence of antimicrobial resistance in E. coli isolated from Kuwait's marine environment.
Here we present the findings of a study where 598 isolates of Escherichia coli (351 derived from seawater; 247 derived from the Venus clam, Circenita callipyga) were obtained from Kuwait's marine environment. Isolates were screened for their potential resistance to an array of 23 commonly deployed frontline antibiotics. Results demonstrate the resistant was widespread across all sites with high-levels of resistance (seawater: summer 89-64%; winter 90-57% and biota: summer 77%; winter 88%) observed to at least 1 of the 23 antibiotics tested. Resistance to Ampicillin was by far the most widely observed profile in seawater and biota across both summer and winter seasons, with 55.9 to 70.9% isolates displaying resistance to this antibiotic. This study demonstrates the potential of AMR screening to be used in Kuwait to detect issues related to water quality and the consequences it may pose for human health.


Differential expression of genes mapping to recurrently abnormal chromosomal regions characterize neuroblastic tumours with distinct ploidy status.
Neuroblastic tumours (NBTs) represent a heterogeneous spectrum of neoplastic diseases associated with multiple genetic alterations. Structural and numerical chromosomal changes are frequent and are predictive parameters of NBTs outcome. We performed a comparative analysis of the biological entities constituted by NBTs with different ploidy status. Gene expression profiling of 49 diagnostic primary NBTs with ploidy data was performed using oligonucleotide microarray. Further analyses using Quantitative Real-Time Polymerase Chain Reaction (Q-PCR); array-Comparative Genomic Hybridization (aCGH); and Fluorescent in situ Hybridization (FISH) were performed to investigate the correlation between aneuploidy, chromosomal changes and gene expression profiles. Gene expression profiling of 49 primary near-triploid and near-diploid/tetraploid NBTs revealed distinct expression profiles associated with each NBT subgroup. A statistically significant portion of genes mapped to 1p36 (P = 0.01) and 17p13-q21 (P < 0.0001), described as recurrently altered in NBTs. Over 90% of these genes showed higher expression in near-triploid NBTs and the majority are involved in cell differentiation pathways. Specific chromosomal abnormalities observed in NBTs, 1p loss, 17q and whole chromosome 17 gains, were reflected in the gene expression profiles. Comparison between gene copy number and expression levels suggests that differential expression might be only partly dependent on gene copy number. Intratumoural clonal heterogeneity was observed in all NBTs, with marked interclonal variability in near-diploid/tetraploid tumours. NBTs with different cellular DNA content display distinct transcriptional profiles with a significant portion of differentially expressed genes mapping to specific chromosomal regions known to be associated with outcome. Furthermore, our results demonstrate that these specific genetic abnormalities are highly heterogeneous in all NBTs, and suggest that NBTs with different ploidy status may result from different mechanisms of aneuploidy driving tumourigenesis.


Allelic imbalances of the egfr gene as key events in breast cancer progression--the concept of committed progenitor cells.
The introduction of concepts proposing multiple cellular subgroups in the normal female breast leads to the hypothesis that distinct cellular phenotypes in the female breast give rise to different subtypes of breast carcinomas e.g. expressing ER, HER2 and EGFR differentially. Therefore, origin of breast carcinoma types may be based on the formation of a cancer prone field in which the committed progenitor cells pass mutations to their progenies, glandular as well as myoepithelial cells. The existence of such field within the human breast was inferred from the results on primary breast cancer obtained by PCR-based microsatellite analysis of allelic imbalance (AI) of the EGF receptor gene. Here, normal breast tissue shows egfr AI adjacent to breast cancer tissue also harboring egfr gene AI. The therapeutic implications of such a model are fundamental, as tumors may display different phenotypes which arise from transformation of different progenitor cells as well as from transformation of more differentiated progenies within a cancer prone field. Thereby they may show up with different clinical courses of the disease, higher rates of metastases and responses to therapy. In this review, we discuss this mechanism focusing on the EGF receptor as an example for regulators of progenitor cell growth in many tissues. Phylloides tumors serve as a putative model for embryonic differentiation stage ruled by EGFR signaling and give insights into the tumor-host-interaction. The inhibition of the EGF receptor by specific monoclonal antibodies (e.g. Erbitux) will give an answer in as far EGFR-signaling is decisive for the development of an invasive breast cancer. For this purpose new models have been inaugurated which vary in the EGF receptor gene dosage and protein expression. Moreover, we discuss the EGF receptor as a target for the treatment of pre-malignant lesions with a high risk for malignant growth, e.g. DCIS, which certainly will be detected more frequently by mammography screening programs soon.


Identification of protein binding surfaces using surface triplet propensities.
The ability to reliably predict protein-protein and protein-ligand interactions is important for identifying druggable binding sites and for understanding how proteins communicate. Most currently available algorithms identify cavities on the protein surface as potential ligand recognition sites. The method described here does not explicitly look for cavities but uses small surface patches consisting of triplets of adjacent surface atomic groups that can be touched simultaneously by a probe sphere representing a solvent molecule. A total of 455 different types of triplets can be identified. A training set of 309 protein-ligand protein X-ray structures has been used to generate interface propensities for the triplets, which can be used to predict their involvement in ligand-binding interactions. The success rate for locating protein-ligand binding sites on protein surfaces using this new surface triplet propensities (STP) algorithm is 88% which compares well with currently available grid-based and energy-based approaches. Q-SiteFinder's dataset (Laurie and Jackson, 2005. Bioinformatics, 21, 1908-1916) was used to show the favorable performance of STP. An analysis of the different triplet types showed that higher ligand binding propensity is related to more polarizable surfaces. The interaction statistics between triplet atoms on the protein surface and ligand atoms have been used to estimate statistical free energies of interaction. The ΔG(stat) for halogen atoms interacting with hydrophobic triplets is -0.6 kcal/mol and an estimate of the maximal ΔG(stat) for a ligand atom interacting with a triplet in a binding pocket is -1.45 kcal/mol. Freely available online at http://opus.bch.ed.ac.uk/stp. Website implemented in Php, with all major browsers supported. firstname.lastname@example.com Supplementary data are available at Bioinformatics online.


Baboon-like syndrome in children.
Baboon syndrome is a combination of diffuse symmetrical erythema on the major flexural areas and V-shaped erythema on both upper anteromedial thighs. Infectious agents have been described as possible triggers. We describe for the first time baboon syndrome in a child induced by a coinfection with Epstein-Barr virus and cytomegalovirus.


Illuminating the theoretical components of alexithymia using bifactor modeling and network analysis.
Alexithymia is a multifaceted personality construct that reflects deficits in affect awareness (difficulty identifying feelings, DIF; difficulty describing feelings, DDF) and operative thinking (externally oriented thinking, EOT; restricted imaginal processes, IMP), and is associated with several common psychiatric disorders. Over the years, researchers have debated the components that comprise the construct with some suggesting that IMP and EOT may reflect constructs somewhat distinct from alexithymia. In this investigation, we attempt to clarify the components and their interrelationships using a large heterogeneous multilanguage sample (N = 839), and an interview-based assessment of alexithymia (Toronto Structured Interview for Alexithymia; TSIA). To this end, we used 2 distinctly different but complementary methods, bifactor modeling and network analysis. Results of the confirmatory bifactor model and related reliability estimates supported a strong general factor of alexithymia; however, the majority of reliable variance for IMP was independent of this general factor. In contrast, network analysis results were based on a network comprised of only substantive partial correlations among TSIA items. Modularity analysis revealed 3 communities of items, where DIF and DDF formed 1 community, and EOT and IMP formed separate communities. Network metrics supported that the majority of central items resided in the DIF/DDF community and that IMP items were connected to the network primarily through EOT. Taken together, results suggest that IMP, at least as measured by the TSIA, may not be as salient a component of the alexithymia construct as are the DIF, DDF, and EOT components. (PsycINFO Database Record


Effects of healthy aging measured by intracranial compartment volumes using a designed MR brain database.
A publicly available database of high-quality, multi-modal MR brain images of carefully screened healthy subjects, equally divided by sex, and with an equal number of subjects per age decade, would be of high value to investigators interested in the statistical study of disease. This report describes initial use of an accumulating healthy database currently comprising 50 subjects aged 20-72. We examine changes by age and sex to the volumes of gray matter, white matter and cerebrospinal fluid for subjects within the database. We conclude that traditional views of healthy aging should be revised. Significant atrophy does not appear in healthy subjects 60 or 70 years old. Gray matter loss is not restricted to senility, but begins in early adulthood and is progressive. The percentage of white matter increases with age. A carefully-designed healthy database should be useful in the statistical analysis of many age- and non-age-related diseases.


[Methods for in vivo measurement of light transparency in the human crystalline lens].
A method for the in vivo measurement of light transparency of the human crystalline lens, based on the measurement of the blue and red light threshold radiance, in presented. The threshold limit values for radiances of 477 nm (blue) and 620 nm (red) were measured for people at age from 17 to 66 years old without cataract. The people recognised the geometric figures by left and right eye separately, after being adapted to darkness. The radiance of the figures was changed smoothly by ADM adaptometer. The threshold limit values were measured several times for each eye. For each eye the average of the threshold limit values for radiances of 620 nm and 477 nm and their quotient were calculated. Values of these quotients practically did not change for young eyes (to 32 years old) and they decreased for older eyes. These results indicate the increase of the threshold radiance of 477 nm in relation to threshold radiance of 620 nm for older people, and this means the reduction of the crystalline lens transparency for blue light in relation to red one as they grow old. It seems that the reduction should precede the development of cataractous changes and this fact may be used in the diagnostics of precataractous states.


Sensitivity, specificity, and predictive value of fecal occult blood testing (Hemoccult II) for colorectal neoplasia in symptomatic patients: a prospective study with total colonoscopy.
To evaluate the specificity, sensitivity, and positive predictive value of fecal occult blood testing (FOBT) in symptomatic patients, with colonoscopy as the gold standard, and to assess the usefulness of FOBT as an ancillary examination in symptomatic patients for whom total colonoscopy is indicated. We studied 439 consecutive patients who underwent Hemoccult II testing before total colonoscopy. The sensitivity, specificity, and positive predictive value for colorectal neoplasia (cancer and adenomatous polyps) was 76.5%, 56.7%, and 27.6%, respectively. The sensitivity, specificity, and positive predictive value for colorectal cancer were 69.2%, 73.2%, and 7.3%, respectively. The sensitivity, specificity, and positive predictive value of FOBT are difficult to estimate from screening programs, because Hemoccult-negative individuals do not undergo examination of the colon, and many of the Hemoccult-positive cases do not undergo total colonoscopy. With total colonoscopy serving as the gold standard, FOBT does not appear to be of much value as an ancillary examination in patients with symptoms potentially attributable to the lower gastrointestinal tract.


Quality assessment in rehabilitation centres: the indicator system 'Quality Profile'.
An indicator system for measuring the quality of rehabilitation centres ('Quality Profile' of rehabilitation centres) is presented. The implementation of the concept is explained with the aid of results regarding structural, process and outcome quality in 26 cardiac and orthopaedic rehabilitation centres. In each centre, structural, process and outcome quality, including patient and employee satisfaction, are measured. Process quality is determined by means of a peer review procedure that includes examination of 20 randomly selected cases on the basis of discharge reports and therapy plans. The medical outcome is measured by a prospective study with three measurement time points and a sample of approx. N=200 patients per centre. Overall, the level of quality of the medical rehabilitation in the institutions participating in the study must be considered high. However, on almost all quality dimensions, even after a risk adjustment there are clear differences between centres, which point to the usefulness of benchmarking analyses and the need for improvements in quality in some centres. The indicator system presented is a starting-point for comprehensive, comparative measurement of the quality of in-patient rehabilitation centres that, with regard to its principles, also appears applicable to other areas of health care.


Dextropropoxyphene poisoning: problems with interpretation of analytical data.
Difficulties in the estimation and interpretation of dextropropoxyphene and norpropoxyphene analyses have added to the controversy concerning the toxicity of these compounds. Poor performance in external proficiency assessment trials reflects the unsatisfactory state of many dextropropoxyphene and norpropoxyphene analyses in general use. There is substantial overlap between blood concentrations of dextropropoxyphene and norpropoxyphene encountered in chronic therapeutic dose and those associated with acute toxicity. As dextropropoxyphene and norpropoxyphene are often taken in overdose with other drugs, their blood concentrations must be interpreted in the context of careful identification and quantitation of such agents. The present availability of accurate methods for measurement of parent drug and metabolite should now make anecdotal reports unsupported by analytical data entirely superfluous.


Carotid artery stenting in patients at surgical high risk: clinical and ultrasound findings.
Angioplasty and stenting (A/S) provide an alternative for patients with simultaneous severe cardiac and cerebrovascular disease, or with medical illnesses which carry a high perioperative risk. We conducted A/S in 20 high-risk patients (15 males, 5 females, mean age = 64.5 years, range = 49-83 years) with symptomatic (n = 16) and asymptomatic (n = 4) high-grade stenosis (>70%, NASCET criterion) of the internal carotid artery. Patients had neurological examinations before, during and after the procedure. Color-coded duplex sonography was performed before and 24 h and every 3 months after the procedure; the 3-month examination also included cerebral angiography. The mean degree of stenosis was reduced from 85.75 +/- 7.47 to 8.0 +/- 22.09% in angiography. In an 18-month follow-up with color-coded duplex sonography the effects of the A/S could be visualized effectively: 2 with local, transient vasospasms, 1 with asymptomatic occlusion, 2 carotid arteries with remaining stenosis of 50% and 2 with minimal hyperplasia within the stent. In conclusion, in patients with a high perioperative risk, A/S is a therapeutic alternative to surgery.


Implementation of real-time ultrasound in a thoracic surgery practice.
The purpose of this study was to implement real-time transthoracic ultrasound in a thoracic surgery and lung transplant practice. Ultrasound units that are light, small, robust, and portable are now available. Obstacles to use include demarcation issues between specialties, training, and a perception that basic ultrasound may be difficult to use. The experience of implementing this is described. After a training period, 62 studies were performed in 4 months. Patients and clinicians gave positive feedback. The learning time was short, and with ultrasonic guidance, all interventional procedures were successful at the first attempt, without any complications. Basic transthoracic ultrasound was found to be easy to learn and use by thoracic surgeons, fellows, and specialist nurses. Patients were appreciative. Real-time use may have genuine advantages to patient care.


Association Between Influenza Vaccination During Pregnancy and Breastfeeding Duration.
Background: Prenatal vaccination and breastfeeding are both health promotional behaviors. The benefits of breastfeeding are widely investigated and well established, as well as the effectivity and the safety of the influenza vaccination. This study aimed to investigate the association between the prenatal health behavior of influenza vaccination and breastfeeding duration for at least 3 months in the United States. Methods: A secondary data analysis was conducted using 2016-2019 Pregnancy Risk Assessment and Monitoring System data consisting of 83,976 postpartum women. Results: Overall, 68.3% (n = 57,269) breastfed for at least 3 months and 56.6% (n = 48,834) received the influenza vaccine during pregnancy. Women who did not receive the influenza vaccine during pregnancy were significantly less likely to breastfeed compared with women who received the vaccine during pregnancy (64.5% versus 71.1%; p < 0.001). Significant covariates associated with ≥3-month breastfeeding duration included maternal sociodemographic factors, infant factors, maternal health factors, and prenatal health behaviors. In the multivariable logistic regression analyses, the odds of breastfeeding at least 3 months were significantly lower in women who did not receive the influenza vaccine during pregnancy compared with those who were vaccinated (odds ratio, 0.92; 95% confidence interval, 0.88-0.98; p = 0.005). Discussion: Findings from this large, nationally representative sample of U.S. mothers indicate an association between the health-promotional behaviors of prenatal influenza vaccination and breastfeeding duration postpartum. Recommendations and education by health care providers should include a focus on maternal health behaviors to support positive maternal-infant health outcomes including reduced risk of infection and extended breastfeeding duration.


Bilateral symmetry detection: testing a 'callosal' hypothesis.
At the end of the 19th century Mach observed that vertical symmetry is more easily perceived than is symmetry at other orientations, and proposed this resulted from bilateral symmetry in the visual system. Numerous studies of symmetry detection have been conducted, but none has been concentrated on Mach's proposal. Recent interpretations of Mach's hypothesis suggest the corpus callosum mediates the vertical-symmetry advantage. In this 'callosal' hypothesis it is suggested that the detectability of symmetry should be narrowly tuned around vertical, and that presentation of patterns away from fixation should disrupt the vertical advantage. We found that the vertical advantage was disrupted by presentation of patterns 1.2 deg from fixation, while detection of symmetry at other orientations was not disrupted. At fixation the orientation tuning was at least within +/- 10 degrees of vertical. The detection of vertical symmetry at fixation was found to be anomalous in two subjects born without a corpus callosum as compared with controls, but relatively normal for presentation off fixation. The three experiments reported are in agreement with some of the predictions derived from the callosal hypothesis. It appears that the callosal hypothesis may account for the relative advantage of vertical symmetry at fixation, but other mechanisms must operate to detect symmetry at other orientations and positions.


Comparison of prognostic value of Roper Hall and Dua classification systems in acute ocular burns.
To compare the predictive outcome of ocular burns using two different prognostic classification systems, that is, Dua and Roper Hall classification. In a prospective, randomised, controlled clinical trial, the extent of acute ocular burns in 100 patients was graded by Roper Hall and Dua classifications. Patients were randomised in two groups of 50 each to receive conventional medical therapy alone or additional amniotic membrane transplantation (AMT). Moderate burns were graded similarly (grade II and III) under both systems, while severe burns were classified differently and compared further. Baseline parameters (size of epithelial defect, corneal haze, limbal ischaemia, conjunctival involvement and visual acuity) and outcome variables (healing of epithelial defect, corneal clarity, corneal vascularisation, visual outcome and symblepharon) after 1 year were noted and compared. There was no difference in terms of time taken and rate of healing of epithelial defect, but there was a significant difference in extent of corneal vascularisation between grades IV, V and VI (p<0.05). In patients who received AMT in addition to medical therapy, the degree of corneal clarity achieved was significantly better in patients with grade IV burns than either grade V (p=0.045) or grade VI (p=0.024) burns, and final visual acuity was significantly better in these patients (p=0.043). On comparison of patients with grade IV burns (with and without AMT), the outcome in terms of extent of corneal vascularisation was significantly better (p=0.0124) in patients who received AMT. Dua classification by providing further subclassification of grade IV ocular burns by Roper Hall into three separate grades has a superior prognostic predictive value in severe ocular burns.


LMI approach for stationary oscillation of interval neural networks with discrete and distributed time-varying delays under impulsive perturbations.
In this paper, a class of impulsive interval neural networks with discrete and distributed time-varying delays is discussed. Several new sufficient conditions are obtained ensuring the existence, uniqueness, and global exponential stability of periodic solution (i.e., stationary oscillation) for the addressed models based on inequality analysis techniques. The obtained results can be checked easily by the linear matrix inequality control toolbox in MATLAB. Finally, two numerical examples are given to show the effectiveness of our results.


Interventions among adolescents who were violently injured and those who attempted suicide.
To examine responses to the psychological needs of adolescent injury victims, the records of all adolescents hospitalized at an urban trauma center during a one-year period for injury by gunshots, stabbings, and physical assaults (N = 59) were compared with the records of adolescents admitted that year for attempting suicide (N = 28). Victims of intentional injuries received significantly lower levels of psychosocial interventions than suicide attempters, and access to such interventions appeared to be influenced by gender and race. Intentionally injured adolescents may not receive available interventions for the psychosocial consequences of their injuries.


Effect of market competition on hospital performance for heart failure.
To investigate whether market competition is a potential driver of hospital performance on the key evidence-based Joint Commission heart-failure (HF) quality indicators of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker prescribed, left ventricular function assessment, smoking-cessation counseling, and discharge instructions. Retrospective multivariate analysis. Hospital performance data for HF was obtained from The Joint Commission's ORYX program from 2003 to 2006. The performance data were linked with hospital characteristics from the American Hospital Association Annual Survey and area-level sociodemographic information from the Area Resource File. Healthcare markets were defined as hospital referral regions (HRRs) and market competition intensity was defined by the Herfindahl-Hirschman Index. Hospital-level and HRR-level ordinary least squares fixed effects regression models were used to estimate the relationship between market competition and performance. A paired comparison indicated that there was a significant change in the mean hospital-level performance over time on all of the HF quality indicators. From the multivariate analyses, hospitals in the least competitive markets (Quintile 5) performed slightly better (2.9%) than the most competitive markets (Quintile 1) for left ventricular function assessment (P <.01). At the HRR level, however, the least competitive markets (Quintile 5) performed moderately worse (5.1%) on the discharge-instructions quality indicator compared with the most competitive markets (Quintile 1) (P = .05). Market competition intensity was associated with only small differences in hospital performance. The level of market competitiveness may produce only marginal incremental benefits to inpatient HF care.


Oesophageal carcinoma: the need for screening.
Oesophageal cancer is a substantial cause of mortality in the Western world and recent data indicate that the incidence is increasing. Despite better understanding of the pathogenesis and in the surgical management of the disease, little improvement in the survival rates has been achieved anywhere in the world, especially because screening for detection of premalignant lesions cannot, at present, be adequately applied to populations at risk. The present review summarizes current knowledge of the use of conventional screening methods as well as possible applications of new techniques to targeted populations to permit earlier diagnosis of premalignant lesions of the oesophagus.


Magnetic Resonance Imaging Exploration of the Human Brain During 10 kHz Spinal Cord Stimulation for Failed Back Surgery Syndrome: A Resting State Functional Magnetic Resonance Imaging Study.
Apart from the clinical efficacy of high frequency spinal cord stimulation at 10 kHz, the underlying mechanism of action remains unclear. In parallel with spinal or segmental theories, supraspinal hypotheses have been recently proposed. In order to unveil hidden altered brain connectome patterns, a resting state functional magnetic resonance imaging (rsfMRI) protocol was performed in subjects routinely treated for back and/or leg pain with high-frequency spinal cord stimulation (HF-SCS) HF-SCS at 10 kHz. RsfMRI imaging was obtained from ten patients with failed back surgery syndrome who were eligible for HF-SCS at 10 kHz. Specifically-chosen regions of interest with different connectivity networks have been investigated over time. Baseline measurements were compared with measurements after 1 month and 3 months of HF-SCS at 10 kHz. Additionally, clinical parameters on pain intensity, central sensitization, pain catastrophizing, and sleep quality were correlated with the functional connectivity strengths. The study results demonstrate an increased connectivity over time between the anterior insula (affective salience network) and regions of the frontoparietal network and the central executive network. After 3 months of HF-SCS, the increased strength in functional connectivity between the left dorsolateral prefrontal cortex and the right anterior insula was significantly correlated with the minimum clinically important difference (MCID) value of the Pittsburgh sleep quality index. These findings support the hypothesis that HF-SCS at 10 kHz might influence the salience network and therefore also the emotional awareness of pain.