Dissociation between seeing and acting: insights from common marmosets (Callithrix jacchus).
Perception-based measures often reveal much earlier competencies than action-based approaches. We explored this phenomenon generally labeled as "knowledge dissociation" in 28 common marmoset monkeys (Callithrix jacchus) using a paradigm where subjects had to localize a food item dropped down an opaque tube. Experiments 1 and 2 assessed common marmoset monkeys' gravity bias in an action based version of the tubes task. Experiments 3 and 4 investigated whether marmosets' performance increases in an action-free task context where they simply look at objects falling down a tube. The results suggest that common marmosets have some intuition of continuity/solidity constraints when tested with perception based measures even though these principles do not appear to guide their search for falling objects.


The flexibility in the proline ring couples to the protein backbone.
In proteins, the proline ring exists predominantly in two discrete states. However, there is also a small but significant amount of flexibility in the proline ring of high-resolution protein structures. We have found that this side-chain flexibility is coupled to the backbone conformation. To study this coupling, we have developed a model that is simply based on geometric and steric factors and not on energetics. We show that the coupling between phi and chi1 torsions in the proline ring can be described by an analytic equation that was developed by Bricard in 1897, and we describe a computer algorithm that implements the equation. The model predicts the observed coupling very well. The strain in the C(gamma)-C(delta)-N angle appears to be the principal barrier between the UP and DOWN pucker. This strain is relaxed to allow the proline ring to flatten in the rare PLANAR conformation.


5'-triphosphate-siRNA activates RIG-I-dependent type I interferon production and enhances inhibition of hepatitis B virus replication in HepG2.2.15 cells.
Hepatitis B virus (HBV) infection often results in acute or chronic viral hepatitis and other liver diseases including cirrhosis and hepatocellular carcinoma. Current therapies for HBV usually have severe side effects and can cause development of drug-resistant mutants. An alternative and safe immunotherapeutic approach for HBV infection is urgently needed for effective anti-HBV therapy. In this study, we propose a new strategy for anti-HBV therapy that activates type-I interferon (IFN) antiviral innate immunity through stimulating pattern-recognition receptors with RNA interference (RNAi) using a 5'-end triphosphate-modified small interfering RNA (3p-siRNA). We designed and generated a 3p-siRNA targeting overlapping region of S gene and P gene of the HBV genome at the 5'-end of pregenomic HBV RNA. Our results demonstrated that 3p-siRNA induced a RIG-I-dependent antiviral type-I IFN response when transfected into HepG2.2.15 cells that support HBV replication. The 3p-siRNA significantly inhibited HBsAg and HBeAg secretion from HepG2.2.15 cells in a RIG-I-dependent manner, and the antiviral effect of 3p-siRNA was superior to that of siRNA. Furthermore, 3p-siRNA had more pronounced inhibition effects on the replication of HBV DNA and the transcription of mRNA than that of siRNA. Finally, 3p-siRNA displayed antiviral activity with long-term suppression of HBV replication. In conclusion, our findings suggest that 3p-siRNA could act as a powerful bifunctional antiviral molecule with potential for developing a promising therapeutic against chronic HBV infection.


Functional load and the lexicon: Evidence that syntactic category and frequency relationships in minimal lemma pairs predict the loss of phoneme contrasts in language change.
All languages use individually meaningless, contrastive categories in combination to create distinct words. Despite their central role in communication, these "phoneme" contrasts can be lost over the course of language change. The century-old functional load hypothesis proposes that loss of a phoneme contrast will be inhibited in relation to the work that it does in distinguishing words. In a previous work we showed for the first time that a simple measure of functional load does significantly predict patterns of contrast loss within a diverse set of languages: the more minimal word pairs that a phoneme contrast distinguishes, the less likely those phonemes are to have merged over the course of language change. Here, we examine several lexical properties that are predicted to influence the uncertainty between word pairs in usage. We present evidence that (a) the lemma rather than surface-form count of minimal pairs is more predictive of merger; (b) the count of minimal lemma pairs that share a syntactic category is a stronger predictor of merger than the count of those with divergent syntactic categories, and (c) that the count of minimal lemma pairs with members of similar frequency is a stronger predictor of merger than that of those with more divergent frequencies. These findings support the broad hypothesis that properties of individual utterances influence long-term language change, and are consistent with findings suggesting that phonetic cues are modulated in response to lexical uncertainty within utterances.


Rapid detection and curation of conserved DNA via enhanced-BLAT and EvoPrinterHD analysis.
Multi-genome comparative analysis has yielded important insights into the molecular details of gene regulation. We have developed EvoPrinter, a web-accessed genomics tool that provides a single uninterrupted view of conserved sequences as they appear in a species of interest. An EvoPrint reveals with near base-pair resolution those sequences that are essential for gene function. We describe here EvoPrinterHD, a 2nd-generation comparative genomics tool that automatically generates from a single input sequence an enhanced view of sequence conservation between evolutionarily distant species. Currently available for 5 nematode, 3 mosquito, 12 Drosophila, 20 vertebrate, 17 Staphylococcus and 20 enteric bacteria genomes, EvoPrinterHD employs a modified BLAT algorithm [enhanced-BLAT (eBLAT)], which detects up to 75% more conserved bases than identified by the BLAT alignments used in the earlier EvoPrinter program. The new program also identifies conserved sequences within rearranged DNA, highlights repetitive DNA, and detects sequencing gaps. EvoPrinterHD currently holds over 112 billion bp of indexed genomes in memory and has the flexibility of selecting a subset of genomes for analysis. An EvoDifferences profile is also generated to portray conserved sequences that are uniquely lost in any one of the orthologs. Finally, EvoPrinterHD incorporates options that allow for (1) re-initiation of the analysis using a different genome's aligning region as the reference DNA to detect species-specific changes in less-conserved regions, (2) rapid extraction and curation of conserved sequences, and (3) for bacteria, identifies unique or uniquely shared sequences present in subsets of genomes. EvoPrinterHD is a fast, high-resolution comparative genomics tool that automatically generates an uninterrupted species-centric view of sequence conservation and enables the discovery of conserved sequences within rearranged DNA. When combined with cis-Decoder, a program that discovers sequence elements shared among tissue specific enhancers, EvoPrinterHD facilitates the analysis of conserved sequences that are essential for coordinate gene regulation.


The genetics of neuroendocrine prostate cancers: a review of current and emerging candidates.
Prostate cancer (PC) displays a strong familial link and genetic factors; genes regulating inflammation may have a pivotal role in the disease. Epigenetic changes control chromosomal integrity, gene functions, and, ultimately, carcinogenesis. The most widely studied epigenetic event in PC is aberrant DNA methylation (hypo- and hypermethylation); besides this, chromatin remodeling and micro RNA (miRNA) are other studied alterations in PC. These all lead to genomic instability and inappropriate gene expression. Causative dysfunction of histone modifying enzymes results in generic and locus-specific changes in chromatin remodeling. miRNA deregulation also contributes to prostate carcinogenesis, including interference with androgen-receptor signaling and apoptosis. These epigenetic alterations have the potential to act as biomarkers for PC for screening and diagnosis as well as prognosis and follow-up. The variable biological potential for a newly diagnosed PC is one of the biggest challenges. The other major clinical problem is in the management of castration-resistant PC. Neuroendocrine (NE) differentiation is one of the putative explanations for the development of castration-resistant disease. Most advanced and poorly differentiated cancer does not produce prostate-specific antigen (PSA) in response to disease progression. Circulating and tissue biomarkers like chromogranin A (CgA) thus become important tools. There is the potential to use various genetic and epigenetic alterations and NE differentiation as therapeutic targets in the management of PC. However, we are still some distance from developing clinically effective tools. Valuable insights into the nature of NE differentiation in PC have been gained in the last decades, but additional understanding of its pathogenetic mechanisms is needed. This will help in devising novel therapeutic strategies to develop targeted therapies. CgA has the potential to become an important marker of advanced castration-resistant PC in cases where prostate-specific antigen can no longer be relied upon. Aberrant androgen-receptor signaling at various levels provides evidence of the importance of this pathway for the development of castration-resistant PC. Many epigenetic influences - in particular, the role of changing miRNA expression - provide valuable insights. Currently, massive sequencing efforts are underway to define important somatic genetic alterations (amplifications, deletions, point mutations, translocations) in PC, and these alterations hold great promise as prognostic markers and for predicting response to therapy.


Does Sex Really Matter? Examining the Connections Between Spouses' Nonsexual Behaviors, Sexual Frequency, Sexual Satisfaction, and Marital Satisfaction.
We examined the interplay between husbands' and wives' positive and negative nonsexual interpersonal behaviors, frequency of sexual intercourse, sexual satisfaction, and feelings of marital satisfaction. To do this, we conducted an in-depth face-to-face interview and completed a series of telephone diaries with 105 couples during their second, third, and fourteenth years of marriage. Consistent with the argument that women's sexual response is tied to intimacy (Basson, 2000), multilevel analyses revealed that husbands' positive interpersonal behaviors directed toward their wives-but not wives' positivity nor spouses' negative behaviors (regardless of gender)-predicted the frequency with which couples engaged in intercourse. The frequency of sexual intercourse and interpersonal negativity predicted both husbands' and wives' sexual satisfaction; wives' positive behaviors were also tied to husbands' sexual satisfaction. When spouses' interpersonal behaviors, frequency of sexual intercourse, and sexual satisfaction were considered in tandem, all but the frequency of sexual intercourse were associated with marital satisfaction. When it comes to feelings of marital satisfaction, therefore, a satisfying sex life and a warm interpersonal climate appear to matter more than does a greater frequency of sexual intercourse. Collectively, these findings shed much-needed light on the interplay between the nonsexual interpersonal climate of marriage and spouses' sexual relationships.


Wnt3a regulates the development of cardiac neural crest cells by modulating expression of cysteine-rich intestinal protein 2 in rhombomere 6.
The cardiac neural crest is a subpopulation of neural crest cells (NCCs) that originates from the dorsal neural tube and later migrates to the heart and pharyngeal arch (PA), where they contribute to distinct aspects of cardiogenesis and PA patterning. Wnt family members have been implicated in general neural crest induction; however, the molecular mechanisms underlying the specification of distinct cell types such as cardiac NCCs remain unclear. Here, we have identified cysteine-rich intestinal protein 2 (crip2), a gene encoding for a LIM domain-containing protein, as a novel marker for cardiac NCCs in zebrafish. We observed a dynamic expression pattern for crip2, with expression being detected in the premigratory NCCs in rhombomere 6 (r6), migrating NCCs, ventricular cardiomyocytes, and aortic vessels in PAs 3 to 6. Interestingly, expression of wnt3a was detected in regions of the dorsal neural tube encompassing r6, and reduction of wnt3a led to disrupted expression of crip2 in r6, abnormal migration of NCCs, and defective cardiac function, as well as PA development. Furthermore, these phenotypes could be recapitulated by reduction of crip2 and rescued by overexpression of crip2. In summary, our data suggest a specific role for Wnt3a in the development of cardiac NCCs. We propose that this function of wnt3a in r6 is partially mediated by crip2 expression in the premigratory cardiac NCCs, which subsequently affects cardiac function and PA patterning.


Success of MRSA eradication in hospital routine: depends on compliance.
To prevent transmission of MRSA, eradication by antiseptic washings and nasal ointment is recommended. There are few studies, which investigated the success of eradication of MRSA carriage during everyday clinical working conditions and results are controversial. We wanted to assess the effectiveness of MRSA eradication procedures--especially octenidine whole body washings and mupirocin nasal ointment--under conditions of everyday life. We retrospectively analyzed the files of all patients who were admitted to the medical department of a tertiary care hospital between 1999 and 2004 and who were infected or colonized by MRSA. According to hospital's standards of care patients should have been washed with octenidine and should have got mupirocin nasal ointment only in case of nasal carriage. Patients were regarded as MRSA-eradicated when swabs taken on three consecutive days, earliest, three days after discontinuation of antiseptic and antiinfective procedures were without proof of MRSA. Only 6% of patients were eradicated. MRSA could be cultured from swabs taken on dismissal of 60% of patients. Fifteen percent of patients had only one or two negative series of swabs. In 19% of patients success of eradication remained unknown. Besides we found that under every day clinical working conditions compliance with several tasks of the eradication protocol was insufficient. Under every day clinical working conditions MRSA eradication is successful only in few patients. Whole body washings should be tested in detailed studies before they should become a recommendation for eradication of MRSA.


Building diversity in a complex academic health center.
For 30 years, the many diversity-related health sciences programs targeting the University of Pittsburgh undergraduate campus, school of medicine, schools of the health sciences, clinical practice plan, and medical center were run independently and remained separate within the academic health center (AHC). This lack of coordination hampered their overall effectiveness in promoting diversity and inclusion. In 2007, a group of faculty and administrators from the university and the medical center recognized the need to improve institutional diversity and to better address local health disparities. In this article, the authors describe the process of linking the efforts of these institutions in a way that would be successful locally and applicable to other academic environments. First, they engaged an independent consultant to conduct a study of the AHC's diversity climate, interviewing current and former faculty and trainees to define the problem and identify areas for improvement. Next, they created the Physician Inclusion Council to address the findings of this study and to coordinate future efforts with institutional leaders. Finally, they formed four working committees to address (1) communications and outreach, (2) cultural competency, (3) recruitment, and (4) mentoring and retention. These committees oversaw the strategic development and implementation of all diversity and inclusion efforts. Together these steps led to structural changes within the AHC and the improved allocation of resources that have positioned the University of Pittsburgh to achieve not only diversity but also inclusion and to continue to address the health disparities in the Pittsburgh community.


The Primary Care Research Landscape and its Relationship with Clinical Practice: A Scientometric Analysis.
It is unclear if research published in primary care journals aligns with the broad spectrum of problems managed in primary care practice. The aim of this study was to analyse publication trends concerning the burden of medical conditions reported in primary care journals, and to compare these findings with the burden of problems seen in clinical practice, in order to identify research gaps. Scientometric tools were used to analyse 9956 articles of primary care journals indexed in MEDLINE. Through keyword analysis, a relations map was built. Literature review and a primary care database were used to identify active problems and reasons for visiting a family physician. Rankings and frequencies of research output and conditions were compared. Keyword analysis identified five clusters of publication trends: cardiovascular conditions and conditions related with unhealthy lifestyles; mental disorders; infections; oncology and health management. By comparing publications with clinical problems, the fields of orthopaedics, endocrinology/metabolism, gastroenterology/hepatology, dermatology, ophthalmology, and the respiratory system show the biggest gaps. Through the relations map, more concrete potential research topics were identified such as palliative care, chronic pain, insomnia, antibiotic prescribing, burnout, osteoporosis, osteoarthritis, and COVID-19. The present study acknowledged potential research and publication gaps in Primary Care journals. The findings might help to direct continuing medical education and help with guideline development. The distribution of publications in primary care journals is distinct from the burden of problems faced in clinical practice and reasons for visiting a family physician. The use of scientometric tools to identify publication trends and their comparison with common problems could be a strategy to identify areas with research gaps in primary care.


Vascularized composite allograft tolerance across MHC barriers in a large animal model.
Vascularized composite allograft (VCA) transplantation can restore form and function following severe craniofacial injuries, extremity amputations or massive tissue loss. The induction of transplant tolerance would eliminate the need for long-term immunosuppression, realigning the risk-benefit ratio for these life-enhancing procedures. Skin, a critical component of VCA, has consistently presented the most stringent challenge to transplant tolerance. Here, we demonstrate, in a clinically relevant miniature swine model, induction of immunologic tolerance of VCAs across MHC barriers by induction of stable hematopoietic mixed chimerism. Recipient conditioning consisted of T cell depletion with CD3-immunotoxin, and 100 cGy total body irradiation prior to hematopoietic cell transplantation (HCT) and a 45-day course of cyclosporine A. VCA transplantation was performed either simultaneously to induction of mixed chimerism or into established mixed chimeras 85-150 days later. Following withdrawal of immunosuppression both VCAs transplanted into stable chimeras (n=4), and those transplanted at the time of HCT (n=2) accepted all components, including skin, without evidence of rejection to the experimental end point 115-504 days posttransplant. These data demonstrate that tolerance across MHC mismatches can be induced in a clinically relevant VCA model, providing proof of concept for long-term immunosuppression-free survival.


[Effect of passive smoking on pulmonary function in the asthmatic child].
Few studies refer to pulmonary function in asthmatic children exposed to environmental tobacco smoke (ETS). Some authors have found lower FEV1 and FEF25-75 values in asthmatic children exposed to ETS. The objective of this study was to evaluate pulmonary function parameters between asthmatic children exposed and not exposed to ETS. A case-control study in children between 3 and 19 years of age, with a ratio of 1:1 of cases versus control, was carried out. Cases were defined as asthmatic children with at least one of the following criteria: FVC < 85%, FEV1 < 85%, PEF < 85% or FEF25-75 < 60%. Controls were asthmatic children with none of the above mentioned criteria. Measurement of exposure was carried out both directly by assessment of capillary blood COHb in both parents and the child and indirectly through a questionnaire about smoking habits. Measurement of effect was by pulmonary function (forced spirometry) and a scale of clinical symptoms. The statistics used included descriptive statistics, Chi square test, Student's-t and ANOVA. Three hundred and twelve children were studied (mean age 9.01 +/- 3.45 years). Parental CoHb results correlated with the number of cigarettes smoked (p < 0.01). ETS exposure correlated with the children's COHb values (p < 0.01). ETS exposed children had lower pulmonary function values, OR for exposure was 1.84 (1.12-3.03). 1) We have validated a questionnaire about smoking habits. Smokers have higher COHb values. 2) We found a weak correlation between exposure to ETS (number of cigarettes and maternal COHb) and the child's COHb. 3) Pulmonary function in asthmatic children is influenced by parental smoking habits.


Chronic vascular risk factors (cholesterol, homocysteine, ethanol) impair spatial memory, decline cholinergic neurons and induce blood-brain barrier leakage in rats in vivo.
Epidemiological studies show that vascular risk factors (e.g. atherosclerosis, diabetes, homocysteine, hypertension or cholesterol) may play a role in the development of Alzheimer's disease. Animal models may help to discover the role of vascular risk factors on cognition. In the present project we treated male Sprague Dawley rats with a diet containing homocysteine (hyperhomocysteinemia) or cholesterol (hypercholesterolemia) for 5 months or exposed the rats to ethanol (20% in drinking water) or a combination of cholesterol+ethanol (mix) for 12 months. Our experiments show that all 3 treatments (homocysteine, cholesterol, ethanol) declined spatial memory in the 8-arm radial maze, reduced the number of cholinergic neurons and induced blood-brain barrier leakage in the cortex. Rats treated with cholesterol also displayed markedly enhanced inflammation in the cortex. Levels of amyloid precursor protein, beta-amyloid((1-42)), as well as tau and phospho-tau 181 were significantly enhanced in the cortex of cholesterol-fed rats. A combination of ethanol and cholesterol did not further potentiate the effects on spatial memory, cholinergic neurons and blood-brain barrier leakage. The data suggest that chronic mild vascular risk factors over months induce small lesions of the brain capillaries in the cortex, which may contribute to the development of vascular dementia or also Alzheimer's disease.


The product of the herpes simplex virus type 1 UL25 gene is required for encapsidation but not for cleavage of replicated viral DNA.
The herpes simplex virus type 1 (HSV-1) UL25 gene contains a 580-amino-acid open reading frame that codes for an essential protein. Previous studies have shown that the UL25 gene product is a virion component (M. A. Ali et al., Virology 216:278-283, 1996) involved in virus penetration and capsid assembly (C. Addison et al., Virology 138:246-259, 1984). In this study, we describe the isolation of a UL25 mutant (KUL25NS) that was constructed by insertion of an in-frame stop codon in the UL25 open reading frame and propagated on a complementing cell line. Although the mutant was capable of synthesis of viral DNA, it did not form plaques or produce infectious virus in noncomplementing cells. Antibodies specific for the UL25 protein were used to demonstrate that KUL25NS-infected Vero cells did not express the UL25 protein. Western immunoblotting showed that the UL25 protein was associated with purified, wild-type HSV A, B, and C capsids. Transmission electron microscopy indicated that the nucleus of Vero cells infected with KUL25NS contained large numbers of both A and B capsids but no C capsids. Analysis of infected cells by sucrose gradient sedimentation analysis confirmed that the ratio of A to B capsids was elevated in KUL25NS-infected Vero cells. Following restriction enzyme digestion, specific terminal fragments were observed in DNA isolated from KUL25NS-infected Vero cells, indicating that the UL25 gene was not required for cleavage of replicated viral DNA. The latter result was confirmed by pulsed-field gel electrophoresis (PFGE), which showed the presence of genome-size viral DNA in KUL25NS-infected Vero cells. DNase I treatment prior to PFGE demonstrated that monomeric HSV DNA was not packaged in the absence of the UL25 protein. Our results indicate that the product of the UL25 gene is required for packaging but not cleavage of replicated viral DNA.


A calcaneus attributable to the primitive late Eocene anthropoid Proteopithecus sylviae: phenetic affinities and phylogenetic implications.
A well-preserved calcaneus referrable to Proteopithecus sylviae from the late Eocene Quarry L-41 in the Fayum Depression, Egypt, provides new evidence relevant to this taxon's uncertain phylogenetic position. We assess morphological affinities of the new specimen using three-dimensional geometric morphometric analyses with a comparative sample of primate calcanei representing major extinct and extant radiations (n = 58 genera, 106 specimens). Our analyses reveal that the calcaneal morphology of Proteopithecus is most similar to that of the younger Fayum parapithecid Apidium. Principal components analysis places Apidium and Proteopithecus in an intermediate position between primitive euprimates and crown anthropoids, based primarily on landmark configurations corresponding to moderate distal elongation, a more distal position of the peroneal tubercle, and a relatively "unflexed" calcaneal body. Proteopithecus and Apidium are similar to cercopithecoids and some omomyiforms in having an ectal facet that is more tightly curved, along with a larger degree of proximal calcaneal elongation, whereas other Fayum anthropoids, platyrrhines and adapiforms have a more open facet with less proximal elongation. The similarity to cercopithecoids is most plausibly interpreted as convergence given the less tightly curved ectal facets of stem catarrhines. The primary similarities between Proteopithecus and platyrrhines are mainly in the moderate distal elongation and the more distal position of the peroneal tubercle, both of which are not unique to these groups. Proteopithecus and Apidium exhibit derived anthropoid features, but also a suite of primitive retentions. The calcaneal morphology of Proteopithecus is consistent with our cladistic analysis, which places proteopithecids as a sister group of Parapithecoidea.


Structure of the Rna15 RRM-RNA complex reveals the molecular basis of GU specificity in transcriptional 3'-end processing factors.
Rna15 is a core subunit of cleavage factor IA (CFIA), an essential transcriptional 3'-end processing factor from Saccharomyces cerevisiae. CFIA is required for polyA site selection/cleavage targeting RNA sequences that surround polyadenylation sites in the 3'-UTR of RNA polymerase-II transcripts. RNA recognition by CFIA is mediated by an RNA recognition motif (RRM) contained in the Rna15 subunit of the complex. We show here that Rna15 has a strong and unexpected preference for GU containing RNAs and reveal the molecular basis for a base selectivity mechanism that accommodates G or U but discriminates against C and A bases. This mode of base selectivity is rather different to that observed in other RRM-RNA structures and is structurally conserved in CstF64, the mammalian counterpart of Rna15. Our observations provide evidence for a highly conserved mechanism of base recognition amongst the 3'-end processing complexes that interact with the U-rich or U/G-rich elements at 3'-end cleavage/polyadenylation sites.


[Immunity against tetanus in childhood].
In order to evaluate the programs of vaccination against tetanus, we have studied the presence of specific antibodies in a sample of children and adolescents from our region. We used a passive hemagglutination test, corroborating the results by a biological assay based on toxin-neutralization. Among the subjects investigated, 93.2% (551/591) had neutralizing toxin-antibodies at a protective level (> or = 0.01 ui/ml). The younger children were more protected (97.5% in children from 1 to 5 years old, and 79.2% in children from 16 to 19 years of age), (X2 = 25.39, p = 0.000-). We did not find any significant differences between the sexes in the degree of protection. Among protected subjects, the higher antibody titers were observed in children from 6 to 10 years old, coinciding with the age of a booster vaccine. The results show an excellent immunization coverage among the childhood population in our region. They also confirm the high effectiveness of this vaccine. However, this high protection was not found among people above the adolescent period.


[Acute kidney injury caused by hantavirus in the Netherlands].
Although unusual in the Netherlands, acute kidney injury is sometimes caused by infection with Hantavirus, a zoonosis transmitted by rodents. Hantavirus infections can cause a syndrome known as 'haemorrhagic fever with renal syndrome', characterized by fever, acute kidney injury and thrombocytopenia. Recovery is spontaneous and treatment is mostly supportive. We describe two cases of otherwise healthy men presenting with fever and acute kidney injury. Laboratory tests revealed raised inflammatory parameters and thrombocytopenia. Urine analysis revealed proteinuria, microscopic haematuria and cell casts. Despite treatment with fluids, renal function declined and oliguria and fluid retention developed in one patient. Dialysis could be avoided, with spontaneous recovery of renal function in both cases. Serological testing revealed acute Hantavirus infection. Acute kidney injury caused by Hantavirus infections is rare in the Netherlands, but should be suspected in any patient presenting with renal failure and a history of viral infection.


Employment-based health benefits under universal coverage.
In the context of proposals for universal coverage, a key emerging issue is the role of employer-sponsored coverage. Such coverage has been slowly eroding and has been criticized for providing little meaningful plan choice. Increased reliance on the individual insurance market in its present form is unlikely to meet society's goals, but directing those without access to employer coverage who receive subsidies to regional insurance exchanges could make such coverage much more attractive. But real-world experience with such a reform is needed before considering the substitution of individual coverage for employer-based coverage.


Salmonella enterica induces and subverts the plant immune system.
Infections with Salmonella enterica belong to the most prominent causes of food poisoning and infected fruits and vegetables represent important vectors for salmonellosis. Although it was shown that plants raise defense responses against Salmonella, these bacteria persist and proliferate in various plant tissues. Recent reports shed light into the molecular interaction between plants and Salmonella, highlighting the defense pathways induced and the means used by the bacteria to escape the plant immune system and accomplish colonization. It was recently shown that plants detect Salmonella pathogen-associated molecular patterns (PAMPs), such as the flagellin peptide flg22, and activate hallmarks of the defense program known as PAMP-triggered immunity (PTI). Interestingly, certain Salmonella strains carry mutations in the flg22 domain triggering PTI, suggesting that a strategy of Salmonella is to escape plant detection by mutating PAMP motifs. Another strategy may rely on the type III secretion system (T3SS) as T3SS mutants were found to induce stronger plant defense responses than wild type bacteria. Although Salmonella effector delivery into plant cells has not been shown, expression of Salmonella effectors in plant tissues shows that these bacteria also possess powerful means to manipulate the plant immune system. Altogether, these data suggest that Salmonella triggers PTI in plants and evolved strategies to avoid or subvert plant immunity.


Effect of soybean variety on anti-nutritional factors content, and growth performance and nutrients metabolism in rat.
The present study was undertaken to evaluate the effects of soybean varieties on content of anti-nutritional factors, growth, and nutrient digestibility in rat. For this purpose, the content of trypsin inhibitor and lectin was firstly measured in five soybean varieties. Then sixty male Wistar rats were randomly divided into six groups and fed on different diets as follows: groups 1 to 5 were fed on treatment diets containing five different varieties of soybean flour; group 6 was fed on a control diet containing casein. All animals were fed for four weeks. During this period, faeces and urine were collected to determine the nutritional efficiency of diets and body weight were measured weekly on ten rats from each group. The results showed that trypsin inhibitor and lectin content of Jilin45 was the highest, and those of Jinong7 were the lowest of the soybean varieties. In comparison, all measured parameters, that is including gain in body weight, feed utilization efficiency, nutrient digestibility, nitrogen balance and nitrogen retention, were markedly different among the five groups of animals, but were significantly lower than the control group. These findings show that soybean varieties could significantly affect trypsin inhibitor and lectin content in soybean.


Conservation of Ovary-Specific Genes, Foxl2, Aromatase, and Rspo1, in the Common Indian Garden Lizard, Calotes versicolor, That Lacks Chromosomal or Temperature-Dependent Sex Determination.
Foxl2,Rspo1, and Aromatase are genes important in the ovary developmental pathway in mammals and birds. Here, we show their presence in the lizard, Calotes versicolor, which is known to lack a chromosomal as well as a temperature-dependent mode of sex determination and has an indeterminate, bipotential gonad throughout embryonic development. The expression of the 3 genes, as well as that of CvSox9 and Wnt4 - the known testis and ovary pathway genes - was studied by RT-PCR and whole tissue RNA in situ hybridization (WRISH) on the developing mesonephros gonadal complex (MGC). The expression of all 3 genes was initiated in the gonad shortly after its evagination from the mesonephros (day 5 onwards). CvFoxl2 generally was expressed in those MGCs in which CvSox9 was either not expressed or lowly expressed and vice versa. On the other hand, CvArom was expressed rather sporadically and randomly, showing no association with CvFoxl2, CvRspo1, or CvSox9, though in later stages WRISH preparations showed its coincidence with CvWnt4. CvRspo1 was expressed in almost all embryos right from day 5. Immunofluorescence localization of Rspo1 and Foxl2 proteins showed their presence in the gonads from day 10 onwards, and by day 25 it was primarily confined to the cortex but away from the coelomic epithelium of the gonadal cortex. Apparently both proteins were localized in the pregranulosa cells, Rspo1 in the cytoplasm and Foxl2 in the nucleus. Thus, it is clear that both CvFoxl2 and CvRspo1 are active in ovary formation, but whether they are expressed in the same or different cells is unknown. Though the transcription pattern of CvArom remains circumspect for its role in differentiation of the ovary, earlier evidence on aromatase inhibitor-induced reversal to the male sex indicates its importance in ovary function.


Roles of the cyclooxygenase 2 matrix metalloproteinase 1 pathway in brain metastasis of breast cancer.
Brain is one of the major sites of metastasis in breast cancer; however, the pathological mechanism of brain metastasis is poorly understood. One of the critical rate-limiting steps of brain metastasis is the breaching of blood-brain barrier, which acts as a selective interface between the circulation and the central nervous system, and this process is considered to involve tumor-secreted proteinases. We analyzed clinical significance of 21 matrix metalloproteinases on brain metastasis-free survival of breast cancer followed by verification in brain metastatic cell lines and found that only matrix metalloproteinase 1 (MMP1) is significantly correlated with brain metastasis. We have shown that MMP1 is highly expressed in brain metastatic cells and is capable of degrading Claudin and Occludin but not Zo-1, which are key components of blood-brain barrier. Knockdown of MMP1 in brain metastatic cells significantly suppressed their ability of brain metastasis in vivo, whereas ectopic expression of MMP1 significantly increased the brain metastatic ability of the cells that are not brain metastatic. We also found that COX2 was highly up-regulated in brain metastatic cells and that COX2-induced prostaglandins were directly able to promote the expression of MMP1 followed by augmenting brain metastasis. Furthermore, we found that COX2 and prostaglandin were able to activate astrocytes to release chemokine (C-C motif) ligand 7 (CCL7), which in turn promoted self-renewal of tumor-initiating cells in the brain and that knockdown of COX2 significantly reduced the brain metastatic ability of tumor cells. Our results suggest the COX2-MMP1/CCL7 axis as a novel therapeutic target for brain metastasis.


Nordic Pharmacy Students' Opinions of their Patient Communication Skills Training.
Objective. To describe Nordic pharmacy students' opinions of their patient communication skills training (PCST), and the association between course leaders' reports of PCST qualities and students' perceptions of their training. Secondary objective was to determine what factors influence these associations. Methods. A cross-sectional questionnaire-based study was performed. The various curricula were categorized into three types (basic, intermediate and innovative training) and students were divided into three groups according to the type of training they had received. Multivariable logistic regression models were fitted with different opinions as outcomes and three types of training as exposure, using generalized estimation equations. Results. There were 370 students who responded (response rate: 77%). Students within the innovative group were significantly more likely to agree that they had received sufficient training, and to agree with the assertion that the pharmacy school had contributed to their level of skills compared to students in the basic group. Conclusion. There appears to be an association between larger and varied programs of training in patient communication skills and positive attitudes toward this training on the part of the students, with students reporting that they received sufficient training, which likely enhanced their skills.


The respiratory quotient has little value in evaluating the state of feeding in burn patients.
The respiratory quotient (RQ) is frequently used to predict over or under feeding in burn patients. The purpose of our study was to evaluate the usefulness of RQ obtained from indirect calorimetry to assess feeding adequacy in pediatric burn Intensive Care Unit patients. We evaluated pediatric patients who received enteral nutrition by continuous duodenal tube feeding at a calculated goal rate in the burn intensive care unit from January 2003 to March 2006. RQ lower than 0.85 indicated underfeeding and RQ greater than 1.0 indicated overfeeding. Actual energy intake was recorded and compared with the energy intake divided by measured resting energy expenditure. Underfeeding was defined as a nutritional regimen providing <90% of caloric requirement; appropriate feeding was provision of within +/-10% of caloric requirements and overfeeding was provision of >110% of caloric requirements. On the basis of regression analysis, there was no relationship between energy intake divided by measured resting energy expenditure and RQ (R2 = 0.0059). There was also no relationship between measured RQ and the degree of feeding (N = 222). RQ <0.85 as an indicator of underfeeding had a low sensitivity of 40% and specificity of 77%. RQ >1.0 as an indicator of overfeeding had a poor sensitivity of 23% and a specificity of 85%. The RQ, used in isolation, is a poor method to assess over or underfeeding. Future prospective studies are needed to determine the optimal methodology for the assessment of nutritional needs in children with burn injury.


Dependence of Ca2+-induced contraction on ATP in alpha-toxin-permeabilized preparations of rat femoral artery.
Effects of various concentrations of ATP on Ca(2+)-induced contraction were studied in alpha-toxin-permeabilized preparations obtained from the rat femoral artery. The contractile magnitude was highest in the presence of 1 mM ATP and decreased with both increasing and decreasing the concentration, suggesting the presence of an optimum ATP concentration in inducing contraction. The magnitude of the contractions in various concentrations of ATP correlated with the extent of the phosphorylated myosin light chain (MLC). The rate of contractions in the presence of 1 mM ATP under an inhibition of MLC phosphatase was faster than in the presence of 4 mM ATP, suggesting that the increased phosphorylation of MLC at 1 mM ATP results from an increased activity of MLC kinase. On the other hand, MLC phosphatase activity appeared unchanged, because the rates of relaxations under the inhibition of MLC kinase were not different in the presence of either 1 or 4 mM ATP. The high sensitivity to 1 mM ATP was absent in the preparations that were permeabilized with beta-escin or Triton X-100, suggesting the existence of an intracellular factor required for the increased activity of MLC kinase to ATP in the alpha-toxin-permeabilized preparations of the rat femoral artery.


Clinical course of spontaneous spinal epidural haematoma mimicking Guillain-Barré syndrome in a child: a case report and literature review.
We describe a 9-year-old female with thoracic epidural haematoma. The clinical course simulated Guillain-Barré syndrome (GBS) so intravenous immunoglobulin therapy was started at the paediatric clinic. Magnetic resonance imaging (MRI) 3 days after admission showed thoracic epidural haematoma between T2 and T8. An emergency laminectomy was performed and the patient's neurological symptoms began to improve immediately after surgery and she made a full recovery during the 2 weeks of follow-up. Time is a very important factor in achieving reversibility of symptoms of compressive cord lesions, such as spinal epidural haematoma, and MRI is mandatory for patients with progressive paraplegia, even though the signs and symptoms might suggest GBS.


Sequence and transcription patterns of 60S ribosomal protein P0, a diapause-regulated AP endonuclease in the flesh fly, Sarcophaga crassipalpis.
We have isolated and sequenced a 1308bp clone from a pupal brain cDNA library of the flesh fly, Sarcophaga crassipalpis, showing 97% amino acid (aa) sequence similarity to Ceratitis capitata 60S acidic ribosomal protein P0 (CcP0) and 93% aa sequence similiarity to Drosophila melanogaster P0 (DmP0). DmP0 is a multifunctional protein necessary for efficient protein translation of the 60S ribosome as well as DNA repair via AP3 endonuclease activity. In this study, we observed that S. crassipalpis P0 (ScP0) is cyclically regulated throughout the fly's overwintering pupal diapause. Expression of ScP0 cycles out of phase with the 4day cycles of O(2) consumption: the peak day of O(2) consumption is characterized by low ScP0 expression, while high expression is noted during the trough of the O(2) consumption cycle. The O(2) cycles, which are in turn driven by cycles of juvenile hormone (JH), can be eliminated by application of a JH analog (JHA). Pupae rendered acyclic with a JHA application consume O(2) at a constant high rate and ScP0 is consistently downregulated. Our findings thus suggest that the cyclic nature of ScP0 regulation during pupal diapause is linked to the JH-mediated metabolic cycles characteristic of this species.


Macrophage-stimulating protein and calcium homeostasis in zebrafish.
To systematically identify novel gene functions essential for osteogenesis and skeletal mineralization, we performed a forward genetic mutagenesis screen in zebrafish and isolated a mutant that showed delayed skeletal mineralization. Analysis of the mutant phenotype in an osterix:nuclear-GFP transgenic background demonstrated that mutants contain osterix-expressing osteoblasts comparable to wild-type embryos. Positional cloning revealed a premature stop mutation in the macrophage-stimulating protein (msp) gene, predicted to result in a biologically inactive protein. Analysis of the embryonic expression pattern for the receptor for Msp, Ron, shows specific expression in the corpuscles of Stannius, a teleost-specific organ that produces stanniocalcin, a pivotal hormone in fish calcium homeostasis. Knockdown of Ron resulted in identical phenotypes as observed in msp mutants. Msp mutant embryos could be rescued by excess calcium. Consistent with a role for Msp/Ron in calcium homeostasis, calcium-regulating factors, such as pth1, pth2, stc1l, and trpv5/6 were significantly affected in msp mutant larvae. While Msp and Ron have previously been shown to play a critical role in a wide variety of biological processes, we introduce here the Msp/Ron signaling axis as a previously unappreciated player in calcium homeostasis and embryonic skeletal mineralization.


Identification of novel antigen candidates for a tuberculosis vaccine in the adult zebrafish (Danio rerio).
Tuberculosis (TB) remains a major global health challenge and the development of a better vaccine takes center stage in fighting the disease. For this purpose, animal models that are capable of replicating the course of the disease and are suitable for the early-stage screening of vaccine candidates are needed. A Mycobacterium marinum infection in adult zebrafish resembles human TB. Here, we present a pre-clinical screen for a DNA-based tuberculosis vaccine in the adult zebrafish using an M. marinum infection model. We tested 15 antigens representing different types of mycobacterial proteins, including the Resuscitation Promoting factors (Rpf), PE/PPE protein family members, other membrane proteins and metabolic enzymes. The antigens were expressed as GFP fusion proteins, facilitating the validation of their expression in vivo. The efficiency of the antigens was tested against a low-dose intraperitoneal M. marinum infection (≈ 40 colony forming units), which mimics a primary M. tuberculosis infection. While none of the antigens was able to completely prevent a mycobacterial infection, four of them, namely RpfE, PE5_1, PE31 and cdh, led to significantly reduced bacterial burdens at four weeks post infection. Immunization with RpfE also improved the survival of the fish against a high-dose intraperitoneal injection with M. marinum (≈ 10.000 colony forming units), resembling the disseminated form of the disease. This study shows that the M. marinum infection model in adult zebrafish is suitable for the pre-clinical screening of tuberculosis vaccines and presents RpfE as a potential antigen candidate for further studies.


Combined effect of body mass index and metabolic status on the risk of prevalent and incident chronic kidney disease: a systematic review and meta-analysis.
The risk of chronic kidney disease (CKD) differs in the normal weight, overweight, and obese individuals owing to metabolic abnormality. We aimed to determine the combined effects of body mass index (BMI) and metabolic status on the risk of the prevalence and incidence of CKD. Pubmed, Scopus, Web of science, and abstracts from recently relevant meetings prior to April 2016 were searched to identify eligible studies. Pooled relative risks (RR) and 95% confidence intervals (CI) were calculated using a random effects model. Eight cross-sectional studies and four longitudinal follow-up studies with a total of 14787 and 166718 participants were separately included in present study. Compared with metabolically healthy normal weight individuals, metabolically healthy obese individuals showed increased risk for CKD, with RR of 1.235 (95%CI: 1.027 to 1.484), while metabolically health overweight individuals still presented in a healthy pattern, RR=1.094(95%CI: 0.774 to 1.547). In addition, metabolically abnormal groups had much higher risk for CKD, with RR of 1.572 (95%CI: 1.373 to 1.801), 1.652(95%CI: 1.139 to 2.397) and 1.898(95%CI: 1.505 to 2.395) across metabolically unhealthy normal weight, overweight and obese individuals respectively. Individuals with abnormal metabolic status are at a significantly elevated risk for CKD, regardless of BMI. For metabolically healthy individuals, CKD risk increases with the growth of BMI, and obese persons eventually have a higher risk.


The influence of inhomogeneous volume conductor models on the ECG and the MCG.
The authors investigated the influence of human body inhomogeneities such as the lungs, blood masses and the skeletal muscle layer on the electrical body surface potential and the magnetic field. The surface potentials and magnetic fields are calculated using a boundary element method. As a rule the blood masses have a large influence on both potential and magnetic field amplitude as well as on the potential and magnetic field map orientation, but the influence on the topology of the map is less in the electric case than in the magnetic case. The single-dipole reconstruction was applied to estimate the error caused by neglecting inner inhomogeneities in source localization. The neglect of lungs and blood masses results in a localization error of less than 1 cm in the electric case but more than 1 cm for deep sources at the posterior side of the heart in the magnetic case. The authors tried to assess the influence of the skeletal muscle layer by both an analytical two-layered anisotropic half-space model and the torso extension method. The skeletal muscle layer causes a smoothing effect on the electrical surface potential and to a lesser extent on the magnetic field, leading to an overestimation of the actual source depth of about 1-2 cm. In principle this can be reduced by taking data from all over the thoracic surface. The authors designed experiments for simultaneous measurement of body surface potential and extracorporeal magnetic field from the same subject. The evaluation of data from two patients showing Wolff-Parkinson-White syndrome has shown that localization results from electric potential data and magnetocardiographic data are consistent.


An online adolescent message board discussion about the internet: Use for pain.
Health-care systems seek to advance their care to adolescents through the online provision of information and support. An online, moderated, asynchronous discussion board called Let's Chat Pain was created to recruit adolescent users of online content for pain to a discussion about pain coping and associated Internet use. Participants were asked about everyday pain coping and the role they judge online information to play in this coping. They were asked about determinations of website reliability and validity for health but especially for help with pain problems. Themes around adolescent trust in online websites for pain and research are explored, in addition to inhibiting and disinhibiting factors associated with the Internet use for health. We found users to mistrust online content even when they know it to be valid. Further study is needed to assess if there are ways of instilling confidence in pain information presented online for this group.


Saccade trajectory deviations and inhibition-of-return: Measuring the amount of attentional processing.
This study used a classic exogenous cueing task in which an abrupt onset cue indicated the target location at chance level. When there was a delay between the cue and the target, observers responded slower and less accurate to the target presented at cued than at uncued locations, signifying the occurrence of inhibition-of-return (IOR). On some trials, instead of a manual response, participants had to move their eyes to a location in space. Our findings show no saccade deviation away from the location that was inhibited due to IOR unless participants had to process the target letter presented at the inhibited location. Our findings are consistent with the notion that inhibition resulting in IOR does not occur at the saccade map level but IOR seems to reduce the input of signals going into the saccade map. We show that the strength of saccade deviation is an important measure which can reveal the amount of attentional processing taking place at any particular location in time.


Analysis of signal transducing mechanisms in CD3+ CD4- CD8- cells expressing the putative T cell receptor gamma gene product.
The signal transducing mechanisms, involved in the activation of CD3+ WT31- cells bearing the putative products of T cell receptor gamma genes, have been investigated. After stimulation with phytohemagglutinin or with monoclonal antibodies directed against CD2 or CD3 surface molecules, a rapid increase in free cytoplasmic Ca2+ concentration rise was detected in one representative CD3+ WT31- clone and in PEER cell line. Experiments performed in the presence of the Ca2+ chelator EGTA indicated that the free cytoplasmic Ca2+ concentration rise was consequent to an early release of Ca2+ from internal stores, followed by a sustained Ca2+ influx from the extracellular compartment. Moreover, increased levels of inositol-3-phosphate (the putative mobilizer of Ca2+ from the intracellular stores) were observed after stimulation, thus suggesting that activation of this cell subset occurs via the classical inositol-lipid metabolic pathway.


Early maternal psychosocial factors are predictors for adolescent caries.
Few studies have investigated the role of early maternal enabling and psychosocial factors on subsequent adolescent caries experience. In this retrospective cohort study of 224 adolescents, we hypothesized that the causal pathway between early maternal enabling factors (education, cognitive abilities, psychological distress) and adolescent caries experience (DMFT) at age 14 yrs is mediated by maternal psychosocial factors (stress, coping, social support) and adolescent dental behavior/access. Maternal data on socio-demographic, medical, and psychosocial variables were measured when the child was 3, 8, and 14 yrs old. A structural equations model (SEM) evaluated the causal pathway, with latent variables for maternal enabling factors (MEF), stress, coping, and social support. Poor MEF was associated with increased stress and poorer coping when the child was 3 yrs old, which in turn affected adolescent dental visits and behavior. Greater social support at child's age 3 was directly associated with lower mean DMFT in adolescence. Maternal psychosocial factors measured when children are young are important mediators for adolescent mean DMFT, but these factors measured when children are adolescents are not. Better early and concurrent MEF, however, was associated directly/indirectly (through dental visits and insurance) with adolescent DMFT. Early maternal factors are important predictors for adolescent caries.


Therapy of nonalcoholic fatty liver disease: current status.
Nonalcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome, has become a common entity in clinical practice. In most of the patients it presents as simple steatosis with nonprogressive clinical course. However, some patients have progressive form of NAFLD, nonalcoholic steatohepatitis (NASH), and are at increased risk of developing cirrhosis and hepatocellular carcinoma. NAFLD treatment includes lifestyle modifications and pharmacotherapy aiming at increasing insulin sensitivity, and attenuating inflammation and hepatic fibrosis. Weight reduction has consistently been shown to reduce levels of liver enzymes and insulin resistance. Although dietary intervention and exercise remain the first-line therapy, due to low patients compliance to these measures pharmacotherapy or surgical approaches are often required. Metformin and thiazolidinediones may improve insulin sensitivity, serum aminotransferase level and liver histology. However, little evidence exists regarding their sustained effects after drug discontinuation which, together with their side effects, limits their widespread use in clinical practice. Statins appear to be safe agents for the treatment of hyperlipidemia, although trials documenting their efficacy in NAFLD are scarce. Based on the recent clinical trials, weight loss medication orlistat, ursodeoxycholic acid and antioxidant agents could potentially be used as adjunctive therapy. Considering still largely controversial clinical data regarding pharmacological agents, their high cost and known side-effects, lifestyle modifications at present remain the only essential considerations in the NAFLD treatment.


GTP-bound Rab3A exhibits consecutive positive and negative roles during human sperm dense-core granule exocytosis.
Exocytosis of mammalian sperm dense-core secretory granule relies on the same fusion molecules as all other secretory cells; one such molecule is the small GTPase Rab3A. Here, we report an in-depth biochemical characterization of the role of Rab3A in secretion by scrutinizing the exocytotic response of streptolysin O-permeabilized human sperm to the acute application of a number of Rab3A-containing constructs and correlating the findings with those gathered with the endogenous protein. Full length, geranylgeranylated, and active Rab3A elicited human sperm exocytosis per se. With Rab3A/Rab22A chimeric proteins, we demonstrated that the carboxy-terminal domain of the Rab3A molecule was necessary and sufficient to promote exocytosis, whereas its amino-terminus prevented calcium-triggered secretion. Interestingly, full length Rab3A halted secretion when added after the docking of the acrosome to the plasma membrane. This effect depended on the inability of Rab3A to hydrolyze GTP. We combined modified immunofluorescence and acrosomal staining protocols to detect membrane fusion and the activation status of endogenous Rab3 simultaneously in individual cells, and found that GTP hydrolysis on endogenous Rab3 was mandatory for fusion pores to open. Our findings contribute to establishing that Rab3 modulates regulated exocytosis differently depending on the nucleotide bound and the exocytosis stage under study.


Estimation of direct and correlated responses to selection using univariate animal models.
Analytic results obtained using simple models show that estimates of selection response of univariate experiments using animal models are completely dependent on the heritability used as prior when fixed effects are nested within generations, and both on the prior and on the true heritability parameter when fixed effects overlap across generations. Univariate animal model estimators of correlated changes of a trait not selected directly are usually biased. The absolute value of the estimate of the correlated response is smaller than the true value when the traits are only genetically correlated and larger than the expected value of zero when they are only environmentally correlated. The validity of the results derived from the analysis of simple models is confirmed using computer simulations, which illustrate the magnitude of the bias. It is emphasized that use of univariate animal models to estimate response in breeding programs whose breeding objectives include several correlated traits may lead to erroneous conclusions.


Assessment of hydrocarbon degradation potentials in a plant-microbe interaction system with oil sludge contamination: A sustainable solution.
A pot culture experiment was conducted for 90 days for the evaluation of oil and total petroleum hydrocarbon (TPH) degradation in vegetated and non-vegetated treatments of real-field oil-sludge-contaminated soil. Five different treatments include (T1) control, 2% oil-sludge-contaminated soil; (T2), augmentation of microbial consortium; (T3), Vertiveria zizanioides; (T4), bio-augmentation along with V. zizanioides; and (T5), bio-augmentation with V. zizanioides and bulking agent. During the study, oil reduction, TPH, and degradation of its fractions were determined. Physico-chemical and microbiological parameters of soil were also monitored simultaneously. At the end of the experimental period, oil content (85%) was reduced maximally in bio-augmented rhizospheric treatments (T4 and T5) as compared to control (27%). TPH reduction was observed to be 88 and 89% in bio-augmented rhizospheric soil (T4 and T5 treatments), whereas in non-rhizospheric and control (T2 and T1), TPH reduction was 78 and 37%, respectively. Degradation of aromatic fraction after 90 days in bio-augmented rhizosphere of treatments T4 and T5 was found to 91 and 92%, respectively. In microbial (T2) and Vertiveria treatments (T3), degradation of aromatic fraction was 83 and 68%, respectively. A threefold increase in soil dehydrogenase activity and noticeable changes in organic carbon content and water-holding capacity were also observed which indicated maximum degradation of oil and its fractions in combined treatment of plants and microbes. It is concluded that the plant-microbe soil system helps to restore soil quality and can be used as an effective tool for the remediation of oil-sludge-contaminated sites.


Prevention and treatment of cardiovascular instability during spinal anaesthesia for caesarean section.
Spinal anaesthesia is the method of choice for caesarean section. There is however a significant associated morbidity and mortality in South Africa, particularly in inexperienced hands. This review provides recommendations for safe practice for anaesthetists at all levels of expertise, with particular reference to the management of haemodynamic instability.


Prevalence of hearing disorders in Singapore military conscripts: a role for routine audiometry screening?
To determine the prevalence of hearing disorders in Singapore military conscripts and describe the profile of hearing loss and associated risk factors. Population-based descriptive analysis of randomised cohort of 818 Singapore military conscripts presenting for medical examination, using self-administered questionnaire and pure tone audiometry performed for both ears. Main outcome measures are prevalence rate of hearing loss and relative risk of hearing loss by demographic factors and surrogates for noise exposure. Prevalence of hearing loss was 36.7 per 1,000 (95% CI 24.8, 51.9). Of 30 subjects with hearing loss, 19 (63.3%) had loss at high frequency, 7 (23.3%) at low frequency, and 4 (13.4%) in both ranges. Hearing loss was unilateral in 17 (56.7%) subjects and bilateral in 13 (43.3%). Relative risk of hearing loss did not differ by age group, education level, race or frequency of personal stereo use. Relative risk of hearing loss is higher in subjects with frequent discotheque visits compared to those who never do so (RR = 2.72, 95%CI 1.09, 6.76). The high prevalence of hearing loss in Singapore military conscripts points to the need for routine audiometry screening prior to enlistment. This will be useful in assigning military vocations, in clinical case management, and for assessing cases of noise-induced hearing loss attributable to military service.


Structure determination of bound nitrogen-based adducts with copper(II) acetylacetonato; an EPR, ENDOR and DFT study.
The adducts of bis(acetylacetonato)–copper(II), [Cu(acac)2], formed with a range of nitrogen heterocycles including pyridine (2), methylpyridines (3,4,5), amino-methylpyridines (6,7) and diazines (8,9,10) were investigated in frozen solution using X-band EPR and 1H ENDOR spectroscopy. The small perturbations to the EPR spin Hamiltonian parameters (g and CuA) were consistent with the axial coordination of the nitrogen bases to Cu(II), and found to be dependent on both the basicity and steric influence of the coordinating substrate. The detailed structure of two adducts was then investigated by angular selective (1)H ENDOR and DFT. For the [Cu(acac)2](pyridine) adduct, axial coordination of the substrate was found to occur via the pyridine nitrogen as expected, producing a characteristic (1)H hyperfine coupling ((H)Ai = −2.6, −2.04, 4.7 MHz; β = 36°; aiso = 0.2 MHz) arising from the ortho-(1)H in the ring 2 or 6 position. These results were confirmed by DFT. However, in the [Cu(acac)2](2-amino-6-methyl-pyridine) adduct, the ENDOR data revealed a substantially different (1)H hyperfine coupling ((H)Ai = −4.52, −3.35, 6.47 MHz; β = 14°; aiso = −0.47 MHz) arising from the –NH2 amino protons. Analysis of this experimentally derived tensor in conjunction with the calculated DFT tensors, revealed that the 2-amino-6-methyl-pyridine substrate binds to Cu(II) via the exocyclic amino pyridine nitrogen, but with a tilt angle of 20° of the pyridine ring away from the geometry optimised structure. These results reveal how important structural information on the coordination geometry of Cu(II) adducts can be obtained by (1)H ENDOR, but only when the complete angular dependency profile of the ENDOR data is thoroughly considered.


A Profile of Knee Injuries Suffered by Australian Army Reserve Soldiers.
Despite having to perform the same occupational tasks as full-time soldiers, part-time soldiers may have lower levels of physical conditioning and report higher rates of injury per unit exposure to active service. The purpose of this study was to profile the leading body site of injury occurring in part-time soldiers to inform injury prevention strategies. Injury data from the Australian Army Reserve (ARES) spanning a two-year period were obtained from the Department of Defence Workplace Health, Safety, Compensation and Reporting database pertaining to locations, nature, mechanisms, and the activity being performed at the time of injury. Among the 1434 injuries reported by ARES personnel, the knee was the most common injury site (n = 228, 16%). Soft tissue injury due to trauma or unknown causes was the most common nature of knee injury (n = 177, 78%). Combat training was the most common activity being performed when soft tissue injuries occurred at the knee (n = 73, 42%), with physical training the second most common (n = 51, 30%), due to muscular stress (n = 36, 71%) and falls (n = 8, 16%). Targeted intrinsic and extrinsic approaches to injury minimization strategies for soft tissue knee injuries during combat and physical training should be designed.


[Leiomyosarcoma of the tongue].
We report on a 48-year old female patient presenting with a spherical firm tumour that developed within a period of about three weeks. No causative trauma could be assessed. The tumour was surgically removed and turned out to be a leiomyosarcoma of the tongue. Probably the tumour originated from the vascular smooth muscle cells. Clinically this very rare tumour of the tongue must be differentiated from various benign and malignant mesenchymal neoplasms. Therapeutic considerations and differential diagnosis are discussed in reviewing the literature.


Adaptation of the Quality Indicator for Rehabilitative Care (QuIRC) for use in mental health supported accommodation services (QuIRC-SA).
No standardised tools for assessing the quality of specialist mental health supported accommodation services exist. To address this, we adapted the Quality Indicator for Rehabilitative care-QuIRC-that was originally developed to assess the quality of longer term inpatient and community based mental health facilities. The QuIRC, which is completed by the service manager and gives ratings of seven domains of care, has good psychometric properties. Focus groups with staff of the three main types of supported accommodation in the UK (residential care, supported housing and floating outreach services) were carried out to identify potential amendments to the QuIRC. Additional advice was gained from consultation with three expert panels, two of which comprised service users with lived experience of mental health and supported accommodation services. The amended QuIRC (QuIRC-SA) was piloted with a manager of each of the three service types. Item response variance, inter-rater reliability and internal consistency were assessed in a random sample of 52 services. Factorial structure and discriminant validity were assessed in a larger random sample of 87 services. The QuIRC-SA comprised 143 items of which only 18 items showed a narrow range of response and five items had poor inter-rater reliability. The tool showed good discriminant validity, with supported housing services generally scoring higher than the other two types of supported accommodation on most domains. Exploratory factor analysis showed that the QuIRC-SA items loaded onto the domains to which they had been allocated. The QuIRC-SA is the first standardised tool for quality assessment of specialist mental health supported accommodation services. Its psychometric properties mean that it has potential for use in research as well as audit and quality improvement programmes. A web based application is being developed to make it more accessible which will produce a printable report for the service manager about the performance of their service, comparison data for similar services and suggestions on how to improve service quality.


Universal screening for alcohol misuse in acute medical admissions is feasible and identifies patients at high risk of liver disease.
Many people who die from alcohol related liver disease (ARLD) have a history of recurrent admissions to hospital, representing potential missed opportunities for intervention. Universal screening for alcohol misuse has been advocated but it is not known if this is achievable or effective at detecting individuals at high risk of ARLD. We systematically screened all admissions to the Acute Medical Unit (AMU) of a large acute hospital using an electronic data capture system in real time. Patients at an increasing risk of alcohol harm were referred for either brief intervention (BI) or further assessment by an Alcohol Specialist Nursing Service (ASNS). Additional data were recorded on admission diagnoses, alcohol unit consumption, previous attendances, previous admissions, length of stay and mortality. Between July 2011 and March 2014, there were 53,165 admissions and 48,211 (90.68%) completed screening. Of these, 1,122 (2.3%) were classified as "increasing", and 1,921 (4.0%) as "high" risk of alcohol harm. High risk patients had more hospital admissions in the three previous years (average 4.74) than the low (3.00) and increasing (2.92) risk groups (p<0.001). The high risk patients also had more frequent emergency department (ED) attendances (7.68) than the lower (2.64) and increasing (3.81) groups (p<0.001 for both). A total of 1,396 (72.6%) of the high risk group were seen by the ASNS and 1,135 (81.2%) had an Alcohol Use Disorders Identification Test (AUDIT) score over 20 with 527 (37.8%) recording the maximum value of 40. Compared to the other groups, high risk patients had a distinct profile of admissions with the most common diagnoses being mental health disorders, gastro-intestinal bleeding, poisoning and liver disease. Universal screening of admissions for alcohol misuse is feasible and identifies a cohort with frequent ED attendances, recurrent admissions and an elevated risk of ARLD. An additional group of patients at an increasing risk of alcohol harm can be identified in a range of common presentations. These patients can be targeted with interventions to reduce the burden of alcohol related harm. Lay summary: Many people who die from alcohol related liver disease (ARLD) have a recent history of recurrent admissions to hospital. These admissions may represent missed opportunities to intervene earlier and offer effective therapies for alcohol misuse. Unfortunately, we know that patients are often missed because medical staff may not routinely ask about alcohol consumption. In our study of over 50,000 admissions, we have demonstrated the feasibility of offering screening for alcohol misuse to all medical admissions to hospital and delivered this 24hours a day, 7days a week, with automatic referral to treatment services. We have shown that it is possible to identify those people who are at the highest risk of dependency, those who have attended the emergency department the most and those who are at an increased risk of ARLD. We hope this study will lead to improved detection and management of alcohol problems in acute hospitals.


Years of life lost from suicide in China, 1990-2000.
Suicide is an important public health problem in China: It is the fifth leading cause of death in China, and suicide in China accounts for over 30% of the world's overall suicide deaths. The substantial burden due to suicide has not been well recognized. This study aims to provide an estimate of the socioeconomic burden of the suicide problem in China in terms of years of life lost (YLL) and to discuss its implications. Suicide rates and the related YLL by age, gender, and region (urban/rural) from 1990 to 2000 were estimated using the most recent data from the Ministry of Health of China. The suicide rate in rural China was three times higher than that in urban areas. Suicide completers in rural areas shared 90% of total YLL. Rural women aged 25-39 years contributed the largest share of YLL. Our results show that some population subgroups contributed a disproportionate share to the disease burden of suicide. National strategies for suicide prevention should include targeted programs in catering the need of these specified subgroups in China.


Barriers to performing stretching exercises among Korean-Chinese female migrant workers in Korea.
The purpose of this study was to investigate the barriers to performing stretching exercise experienced by Korean-Chinese female migrant workers during a community-based 12-week stretching exercise intervention trial. Qualitative secondary data analysis was conducted using telephone counseling interview transcripts from 27 middle-aged, Korean-Chinese migrant women workers. A semistructured interview question asking barriers to performing stretching exercise was given to women who did not adhere to recommended stretching exercise. During the 12-week home-based stretching exercise intervention trial, six telephone calls were made to participants biweekly to elicit barriers to performing stretching exercise. Directed content analysis approach was utilized using three barrier categories: intrapersonal, interpersonal, and work-related environmental factors based on the ecological model. Participants experienced an average of 2.5 barriers during the study period. Intrapersonal barriers included lack of time and lack of motivation, and interpersonal barriers included no family to provide support and also a feeling resistance from coworkers. Work-related environmental barriers included frequent job changes, long working hours, lack of rest time, and unpredictable job demands. The findings highlight that migrant workers in Korea face unique work-related difficulties which present barriers to exercise.


[Effects of glyphosate on apoptosis and expressions of androgen-binding protein and vimentin mRNA in mouse Sertoli cells].
To investigate the effect of different doses of glyphosate on apoptosis and expressions of androgen-binding protein (ABP) and vimentin mRNA in mouse Sertoli cells. Primarily cultured mouse Sertoli cells incubated with different doses of glyphosate (60, 90, 120, 150 and 180 mg/L) for 24 h. The growth and morphological alterations in the cells were observed under inverted microscope, and the cell proliferation rate was evaluated withMTT assay. Hoechst 33342 staining was used to detect cell apoptosis after the treatment, and RT-PCR was performed to examine the changes in the expression of ABP and vimentin mRNAs. Sertoli cells exposed to glyphosate showed a reduced cell volume, cell dissociation with occasional cell disruption. The proliferation of the exposed was suppressed with an increased rate of cell apoptosis and lowered expressions of ABP and vimentin mRNAs (P<0.05). GLY can cause cellular damages, inhibit cell proliferation, induce cell apoptosis, and decrease expression of ABP and vimentin mRNAs in mouse Sertoli cells in vitro.


Hippo and rassf1a Pathways: A Growing Affair.
First discovered in Drosophila, the Hippo pathway regulates the size and shape of organ development. Its discovery and study have helped to address longstanding questions in developmental biology. Central to this pathway is a kinase cascade leading from the tumor suppressor Hippo (Mst1 and Mst2 in mammals) to the Yki protein (YAP and TAZ in mammals), a transcriptional coactivator of target genes involved in cell proliferation, survival, and apoptosis. A dysfunction of the Hippo pathway activity is frequently detected in human cancers. Recent studies have highlighted that the Hippo pathway may play an important role in tissue homoeostasis through the regulation of stem cells, cell differentiation, and tissue regeneration. Recently, the impact of RASSF proteins on Hippo signaling potentiating its proapoptotic activity has been addressed, thus, providing further evidence for Hippo's key role in mammalian tumorigenesis as well as other important diseases.


Factors associated with the onset and progression of neurotrauma: A systematic review of systematic reviews and meta-analyses.
Neurotrauma, including traumatic brain injury (TBI) and spinal cord injury (SCI), is a preventable condition that imposes an important burden on the Canadian society. In this study, the current evidence on risk factors for the onset and progression of neurotrauma is systematically reviewed and synthesized. Searches of the Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects (DARE), Medline and Medline in Process (via OVID), EMBASE and PsycINFO from inception to February 2013 were conducted to identify relevant systematic reviews and meta-analyses published in English or French. Two referees screened and assessed the quality of the studies using the AMSTAR tool. Thirty-two studies examined at least one risk factor for the onset of neurotrauma. Thirteen studies passed the quality assessment and the majority evaluated the impact of protective equipment in sports. Helmets effectively reduce TBI from bicycling, skiing, snowboarding, ice hockey and motorcycling. There was no evidence of a protective effect of helmets for SCI. No studies contributed evidence on risk factors for the onset of SCI. Of two studies examining risk factors for the progression of neurotrauma, only injury severity was found to be associated with poorer post-injury outcomes. Substantial evidence supports the use of helmets for the prevention of TBI in sports and motorcycling and face shields in ice hockey. Addressing bicycle helmet legislation across Canada may be an effective option for reducing TBI caused by bicycle accidents. Limited evidence on relevant risk factors for spinal cord injuries and neurotrauma progression was available.


Working with the family: the role of values.
In this paper, we have examined that ethical aspect of working with families which stresses the relevance of values. Given that values are at the heart of both the family's and the therapists's view of the world, we see it as crucial for them to be addressed in the course of assessment and treatment. A variety of approaches have been adopted by clinicians ranging from those who regard ethics as a cornerstone of therapy to more compartmentalized positions, whereby specific sociopolitical themes like racism, poverty, and sexism are highlighted. Whatever model is preferred, the essential task is to accept that values are a necessary feature of therapeutic work and require negotiation. Failure to do so may have adverse repercussions on the therapist-family relationship, even to the point of jeopardizing therapy. Guidelines can be articulated to forestall such unfortunate consequences. We have attempted to identify these in the hope of clarifying for therapists the necessary steps they need to take to safeguard the family's interests and achieve an optimal ethical (and clinical) outcome.


Sex differences in exertional dyspnea in patients with mild COPD: physiological mechanisms.
The purpose of this study was to evaluate the physiological basis for sex-differences in exercise-induced dyspnea in patients with mild COPD. We compared operating lung volumes, breathing pattern and dyspnea during incremental cycling in 32 men (FEV(1)=86±10% predicted) and women (FEV(1)=86±12% predicted) with mild COPD and 32 age-matched controls. There were no sex differences in dyspnea in the control group at any work-rate or ventilation (V(E)). Women with COPD had significantly greater dyspnea than men at 60 and 80 W. At 80 W, dyspnea ratings were 5.7±2.3 and 3.3±2.5 Borg units (P<0.05) and the V(E) to maximal ventilatory capacity ratio was 72% and 55% in women and men, respectively (P<0.05). Comparable increases in dynamic hyperinflation were seen in both male and female COPD groups at symptom limitation but women reached tidal volume constraints at a lower work rate and V(E) than men. Superimposing mild COPD on the normal aging effects had greater sensory consequences in women because of their naturally reduced ventilatory reserve.


Diallyl trisulfide-induced apoptosis of bladder cancer cells is caspase-dependent and regulated by PI3K/Akt and JNK pathways.
Diallyl trisulfide (DATS) is one of the major organosulfur components of garlic (Allium sativum L.), which inhibits the proliferation of various cancer cells, but the exact mechanisms of this action in human bladder cancer cells still remain largely unresolved. In this study, we investigated how DATS induces apoptosis in T24 human bladder cancer cells in vitro. Treatment of T24 cells with DATS resulted in potent anti-proliferative activity. Additionally, some typical apoptotic characteristics, such as chromatin condensation and an increase in the population of sub-G1 hypodiploid cells, were observed. With respect to the mechanism underlying the induction of apoptosis, DATS reduced the expression of anti-apoptotic Bcl-2 and Bcl-xL, and inhibitor of apoptosis protein family proteins, but the expression of pro-apoptotic Bax and death receptor-related proteins was increased compared with the controls. DATS also activated caspase-8 and -9, the respective initiator caspases of the extrinsic and the intrinsic apoptotic pathways. The increase in mitochondrial membrane depolarization was correlated with activation of effector caspase-3 and cleavage of poly-ADP-ribose polymerase, a vital substrate of activated caspase-3. Blockage of caspase activation through treatment with a pan-caspase inhibitor consistently inhibited apoptosis and abrogated growth inhibition in DATS-treated T24 cells. The study further investigated the roles of the phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein kinases (MAPKs) pathways with respect to the apoptotic effect of DATS, and showed that DATS deactivates Akt. Additionally, DATS activates extracellular signal-regulated kinase (ERK) and c-Jun N-terminal protein kinase (JNK), but not p38 MAPK, in T24 cells. Unlike ERK, JNK inhibitors reversed DATS-induced apoptosis and growth inhibition; however, inhibition of PI3K/Akt notably enhanced the apoptotic action of DATS. The results suggest that the pro-apoptotic activity of DATS is probably regulated by a caspase-dependent cascade through the activation of both intrinsic and extrinsic signaling pathways, which is mediated through the blocking of PI3K/Akt and the activation of the JNK pathway.


Acute cellulitis: an unusual manifestation of meningococcal disease.
We describe 2 patients who both developed cellulitis due to Neisseria meningitidis and review 8 other cases reported since 1966. Female patients outnumbered male patients by 8 to 2, and there were 5 children and 5 adults. Four cases were caused by the serogroup C meningococcus, 2 cases by serogroup B and 2 others by serogroup Y (the nature of the meningococcal group was not available in 2 cases). Diverse medical underlying conditions were present in 4 of the adult patients. The periorbital region (in all 5 children), limb (in 3 adults), neck (in 1 adult) and face and neck (in 1 adult) were the locations of the meningococcal cellulitis. In all 10 patients, a favorable clinical response to the antibiotic therapy was documented and no relapses occurred. These cases indicate that N. meningitidis should be considered as a causative agent of cellulitis in the appropriate clinical setting, particularly in children with signs of periorbital infection or adults with underlying diseases.


Finite Element Analysis Generates an Increasing Interest in Dental Research: A Bibliometric Study.
The purpose was to provide a longitudinal overview of published studies that use finite element analysis in dental research, by using the SCI-expanded database of Web of Science(®) (Thomson Reuters). Eighty publications from 1999-2000 and 473 from 2009-2010 were retrieved. This literature grew faster than the overall dental literature. The number of publishing countries doubled. The main journals were American or English, and dealt with implantology. For the top 10 journals publishing dental finite element papers, the mean impact factor increased by 75% during the decade. Finite elements generate an increasing interest from dental authors and publishers worldwide.


An analysis of variance of the pubertal and midgrowth spurts for length and width.
Using data from the first Zurich Longitudinal Growth Study characteristics of the growth of six variables--bihumeral width, biiliac width, standing height, sitting height, leg height and arm length--are studied. The main interest is in differences between boys and girls, and across variables and in particular in whether there are sex differences that are specific for some variables. For each child and variable, individual velocity and acceleration curves are estimated using a kernal smoother. From these curves, parameters characterizing the midgrowth spurt (MS) and the pubertal spurt (PS) are estimated: timings, durations and intensities. The level of childhood velocity is used for characterizing early growth. These parameters are analysed using a repeated measures analysis of variance (ANOVA) to assess the statistical significance of differences between boys and girls and across variables. This necessitates some kind of standardization and two types of standardization are used here. The MS shows negligible or small differences between boys and girls, and the same is true for velocity in childhood. Differences across variables during the MS are much more pronounced: with respect to intensity, bihumeral width has an MS about six times more intense than height. The PS is later for boys (as is well known), and there are significant differences across variables: bihumeral width and sitting height are late while legs are early. With the exception of biiliac width, the duration of the PS (which has been subdivided into three phases-early, middle and late) is slightly longer for boys for all variables: boys have a longer starting phase, the middle phase is about equal in length for both boys and girls, and girls have a slightly longer late phase. Leg height and height experience a PS of short duration while bihumeral and biiliac width experience a long one and these differences are highly statistically significant. For all variables, with the exception of biiliac width, boys have a more intense PS (in terms of maximal acceleration), even having adjusted for their larger adult size. Differences in intensity are also marked across variables, bihumeral width and sitting height having the highest intensity and legs the lowest. Differences between sexes and across variables are much smaller for the stopping intensity, characterized by maximal deceleration.


Survival and functional demonstration of interregional pathways in fore/midbrain slice explant cultures.
An important general question in neurobiology concerns the development and expression of the rich context of neuronal phenotypes, especially in relation to the diverse patterns of connectivity. Organotypic cultures of brain slices may offer distinct advantages for such studies if such a preparation survives, maintains a wide diversity of neuronal phenotypes and displays appropriate synaptic connections between regions. To address these requirements, we utilized long-term organotypic cultures of intact horizontal slices of rat forebrain and midbrain and assessed a variety of markers of phenotype in combination with functional tests of connectivity. This explant preparation displayed a distinct viability requirement such that the greatest explant survival was seen in slices taken from pups of less than postnatal day 7 and was independent of N-methyl-D-aspartate channel blockade. The anatomical features of the major brain regions (e.g., neocortex, striatum, septum, hippocampus, diencephalon and midbrain) were observed in their normal boundaries. The presence of cholinergic and catecholaminergic neurons was demonstrated with acetylcholinesterase histochemistry and tyrosine hydroxylase immunohistochemistry. Labelled neurons displayed multiple, regionally-appropriate cytoarchitectures and, in some cases, could be seen to project to brain regions in a manner quite similar to that seen in vivo. Finally, the direct demonstration of spontaneous and evoked interregional excitatory synaptic transmission was made using whole-cell patch-clamp recordings from striatal neurons which revealed an intact glutamate-using corticostriatal pathway. This simple explant preparation appears to contain a rich diversity of neuronal types and synaptic organization. Therefore, this preparation appears to have several distinct advantages for basic neurobiologic research since it combines long-term culture viability and many features of mature brain including complex interregional neuronal systems.


[Acute effects of tobacco and vascular risk modulated by genetic factors].
Most studies regarding the acute effects of cigarette smoking refer to the higher sympathetic and adrenomedullary activity as a result of sympathetic ganglia and adrenal medulla nicotinic receptor activation. Although it is reasonable to suppose that the renin-angiotensin system might be activated, this possible effect of nicotine has not been studied. We have studied the effects of cigarette smoking on blood pressure, cardiac output, pulse pressure, renin-angiotensin system, kinins-NO, oxidative stress and insulin. Also, we have investigated if the variability of the biochemical parameters was dependent on genetic polymorphisms of the angiotensin converting enzyme and the acute phase protein haptoglobin. 39 normotensive individuals, 18 males and 21 females, of mean age 35.4 +/- 8.9 years were included in this study. Oxidative stress was dependent on the ACE I/D and Hp1/2 polymorphisms, with the ACE DD genotype and the Hp2-2 phenotype not showing variation in the anti-oxidant defense systems, and the ACE II-ID genotypes and Hp1-1 + 2-2 phenotypes showing a higher anti-oxidant response, hence a lower cardiovascular risk being predictable in the latter individuals.


Polymer Nanorings with Uranium Specific Clefts for Selective Recovery of Uranium from Acidic Effluents via Reductive Adsorption.
Nanostructured polymeric materials, functionalized with an appropriate receptor, have opened up newer possibilities for designing a reagent that shows analyte-specific recognition and efficient scavenging of an analyte that has either a detrimental influence on human physiology and environment or on its recovery for further value addition. Higher active surface area, morphological diversity, synthetic tunability for desired surface functionalization, and the ease of regeneration of a nanostructured material for further use have provided such materials with a distinct edge over conventional reagents. The use of a biodegradable polymeric backbone has an added significance owing to the recent concern over the impact of polymers on the environment. Functionalization of biodegradable sodium alginate with AENA (6.85% grafting) as the receptor functionality led to a unique open framework nanoring (NNRG) morphology with a favorable spatial orientation for specific recognition and efficient binding to uranyl ions (U) in an aqueous medium over a varied pH range. Nanoring morphology was confirmed by transmission electron microscopy and atomic force microscopy images. The nanoscale design maximizes the surface area for the molecular scavenger. A combination of all these features along with the reversible binding phenomenon has made NNRG a superior reagent for specific, efficient uptake of UO22+ species from an acidic (pH 3-4) solution and compares better than all existing UO22+-scavengers reported till date. This could be utilized for the recovery of uranyl species from a synthetic acidic effluent of the nuclear power. The results of the U uptake experiments reveal a maximum adsorption capacity of 268 mg of U per g of NNRG in a synthetic nuclear effluent. X-ray photoelectron spectroscopy studies revealed a reductive complexation process and stabilization of U(IV)-species in adsorbed uranium species (U@NNRG).


Cell-ECM traction force modulates endogenous tension at cell-cell contacts.
Cells in tissues are mechanically coupled both to the ECM and neighboring cells, but the coordination and interdependency of forces sustained at cell-ECM and cell-cell adhesions are unknown. In this paper, we demonstrate that the endogenous force sustained at the cell-cell contact between a pair of epithelial cells is approximately 100 nN, directed perpendicular to the cell-cell interface and concentrated at the contact edges. This force is stably maintained over time despite significant fluctuations in cell-cell contact length and cell morphology. A direct relationship between the total cellular traction force on the ECM and the endogenous cell-cell force exists, indicating that the cell-cell tension is a constant fraction of the cell-ECM traction. Thus, modulation of ECM properties that impact cell-ECM traction alters cell-cell tension. Finally, we show in a minimal model of a tissue that all cells experience similar forces from the surrounding microenvironment, despite differences in the extent of cell-ECM and cell-cell adhesion. This interdependence of cell-cell and cell-ECM forces has significant implications for the maintenance of the mechanical integrity of tissues, mechanotransduction, and tumor mechanobiology.


Neuroradiological Findings in the Spinocerebellar Ataxias.
The spinocerebellar ataxias (SCAs) are a group of autosomal dominant degenerative diseases characterized by cerebellar ataxia. Classified according to gene discovery, specific features of the SCAs - clinical, laboratorial, and neuroradiological (NR) - can facilitate establishing the diagnosis. The purpose of this study was to review the particular NR abnormalities in the main SCAs. We conducted a literature search on this topic. The main NR characteristics of brain imaging (magnetic resonance imaging or computerized tomography) in SCAs were: (1) pure cerebellar atrophy; (2) cerebellar atrophy with other findings (e.g., pontine, olivopontocerebellar, spinal, cortical, or subcortical atrophy; "hot cross bun sign", and demyelinating lesions); (3) selective cerebellar atrophy; (4) no cerebellar atrophy. The main NR abnormalities in the commonest SCAs, are not pathognomonic of any specific genotype, but can be helpful in limiting the diagnostic options. We are progressing to a better understanding of the SCAs, not only genetically, but also pathologically; NR is helpful in the challenge of diagnosing the specific genotype of SCA.


A computational model for gonadotropin releasing cells in the teleost fish medaka.
Pituitary endocrine cells fire action potentials (APs) to regulate their cytosolic Ca2+ concentration and hormone secretion rate. Depending on animal species, cell type, and biological conditions, pituitary APs are generated either by TTX-sensitive Na+ currents (INa), high-voltage activated Ca2+ currents (ICa), or by a combination of the two. Previous computational models of pituitary cells have mainly been based on data from rats, where INa is largely inactivated at the resting potential, and spontaneous APs are predominantly mediated by ICa. Unlike in rats, spontaneous INa-mediated APs are consistently seen in pituitary cells of several other animal species, including several species of fish. In the current work we develop a computational model of gonadotropin releasing cells in the teleost fish medaka (Oryzias latipes). The model stands out from previous modeling efforts by being (1) the first model of a pituitary cell in teleosts, (2) the first pituitary cell model that fires sponateous APs that are predominantly mediated by INa, and (3) the first pituitary cell model where the kinetics of the depolarizing currents, INa and ICa, are directly fitted to voltage-clamp data. We explore the firing properties of the model, and compare it to the properties of previous models that fire ICa-based APs. We put a particular focus on how the big conductance K+ current (IBK) modulates the AP shape. Interestingly, we find that IBK can prolong AP duration in models that fire ICa-based APs, while it consistently shortens the duration of the predominantly INa-mediated APs in the medaka gonadotroph model. Although the model is constrained to experimental data from gonadotroph cells in medaka, it may likely provide insights also into other pituitary cell types that fire INa-mediated APs.