Community health center provider and staff's Spanish language ability and cultural awareness.
Many community health center providers and staff care for Latinos with diabetes, but their Spanish language ability and awareness of Latino culture are unknown. We surveyed 512 Midwestern health center providers and staff who managed Latino patients with diabetes. Few respondents had high Spanish language (13%) or cultural awareness scores (22%). Of respondents who self-reported 76-100% of their patients were Latino, 48% had moderate/low Spanish language and 49% had moderate/low cultural competency scores. Among these respondents, 3% lacked access to interpreters and 27% had neither received cultural competency training nor had access to training. Among all respondents, Spanish skills and Latino cultural awareness were low. Respondents who saw a significant number of Latinos had good access to interpretation services but not cultural competency training. Improved Spanish-language skills and increased access to cultural competency training and Latino cultural knowledge are needed to provide linguistically and culturally tailored care to Latino patients.


Fragment spanning the SV40 replication origin is the only DNA sequence required in cis for viral excision.
A 311-base pair fragment containing the SV40 origin of replication was linked to the chicken thymidine kinase gene on a recombinant plasmid. This molecule was transfected into human 143 thymidine kinase-deficient (TK-) cells, and colonies positive for thymidine kinase were selected. When cell lines derived from these colonies were fused to permissive simian cells that produce SV40 T antigen, the recombinant plasmid excised itself from the human cellular genome and replicated with a high copy number per cell. These results show that this segment of the viral genome is the only sequence required in cis to mediate SV40 excision and replication upon fusion to permissive cells. In addition, we have shown that excised plasmids apparently identical to the input DNA can be efficiently rescued in Escherichia coli. SV40 excision and replication may therefore be useful for the recovery of cloned genes from eukaryotic cells.


Advancing health information technology roadmaps in long term care.
Our purpose is to provide evidence that health information technology should be a mainstay of all future health and social support services for older people globally, both within and across community and residential care services. This work was conducted in two phases. In phase I, the authors conducted a focused exploration by selecting a convenience sample of four long term care health information technology roadmaps, developed by members of four different long term care health information technology collaboratives in United States, Australia, United Kingdom, and New Zealand. During Phase II the research team carried out an extensive systematic review of existing literature sources (2000-2018) to support roadmap assumptions. Using converging domains and content, we offer recommendations among five aged care roadmap domains: Strategy/Vision, Continuing Care Community, Services and Support Provided, External Clinical Support, and Administrative. Within these domains we provide recommendations in five content areas: Innovation, Policy, Evaluation, Delivery Systems and Human Resources. We recommend future strategies for LTC HIT roadmaps that include 61 emphasis areas in aged care in these content areas and domains. The roadmap provides a navigation tool for LTC leaders to take a strategic and comprehensive approach as they harness the potential of health information technologies to address the challenges and opportunities of LTC in the future.


Identical tricuspid ring sizing in simultaneous functional tricuspid and mitral valve repair: A simple and effective strategy.
Mitral valve repair for functional mitral regurgitation is common. Concomitant tricuspid valve repair for associated functional tricuspid regurgitation has gained favor. Controversy exists regarding annuloplasty sizing for tricuspid valve repair. Patients with heart failure having functional mitral regurgitation at the University of Michigan and undergoing mitral valve repair and tricuspid valve repair using identical sized annuloplasty rings between April 2007 and January 2012 were identified. Demographic and clinical records were retrospectively reviewed. Institutional review board approval was obtained for this study. Fifty-three patients met inclusion criteria. Mean age was 65 ± 1.7 years. Preoperative New York Heart Association class was III or IV in 81% (43) and mean left ventricular ejection fraction was 33% ± 2.2%. All patients had moderate or greater mitral regurgitation preoperatively and moderate or severe tricuspid regurgitation or a preoperative tricuspid annulus diameter greater than 40 mm. There was no 30-day mortality. Mean immediate postoperative tricuspid valve gradient was 1.75 ± 0.12 mm Hg and was 2.3 ± 0.19 mm Hg at 4 weeks. Four weeks postoperatively 88% (42/48) of patients had tricuspid regurgitation considered to be mild or less. There was no significant decline in right ventricular function by echocardiography over this time period. Functional tricuspid regurgitation can be repaired using an undersized rigid annuloplasty ring. Our data suggest that an identical sizing strategy can be used for tricuspid valve repair, as was used for mitral valve repair, without development of tricuspid stenosis or negative effect on right ventricular function. This method seems to prevent recurrence of significant tricuspid regurgitation. The technique we describe provides effective and reproducible results.


The outcome of patients with surgically treated meningioma in England: 1999-2013. A cancer registry data analysis.
Purpose: Meningiomas are the commonest predominantly non-malignant brain tumour in adults. The use of surgery appears to be increasing, and outcomes are thought to be good, but whole nation data for England is scarce. The aim of this report is to examine the epidemiology of patients operated for cranial and spinal meningioma in England, and to assess associations between outcomes and gender, age, meningioma site (cranial or spinal), and grade.Material and methods: A search strategy encompassing all patients coded with cranial and spinal meningioma treated between January 1999 and December 2013 was obtained from data linkage between the National Cancer Registration and Analysis Service and Hospital Episode Statistics for England.Results: 25,694 patients were diagnosed with meningioma in England between 1999 and 2013, in whom 24,302 were cranial and 1392 spinal. Of these patients, 14,229 (60%) cranial and 1188 (85%) spinal meningioma received surgery. Of those operated on 70.1% were women, and, where the tumour grade was recorded, 79.5% were WHO grade I, 18.4% grade II, and 2.1% grade III. Five and ten year net survival rates for surgically treated cranial meningiomas were respectively 90% and 81% for those with WHO grade I, 80% and 63% for grade II, and 30% and 15% for WHO grade III tumours. Overall survival after surgery is better in women, younger adults, and people with spinal or lower grade meningiomas. Outcomes have improved over the time period examined.Conclusion: The outcome for patients with meningioma is good and is improving. However, there remains a significant mortality related to the disease process.


The evolution of a successful telemedicine mental health service.
Development of telemedicine mental health services in Alberta evolved via a pilot project, the delivery of routine services to a small group of centres and subsequent expansion to a province-wide programme. Success of the service was linked to support for telehealth by the provincial government and consultation between the Alberta Mental Health Board (AMHB) and local stakeholders. Assessments by the AMHB have shown that telepsychiatry is acceptable and sustainable at a realistic cost. However, there are few measures of clinical effectiveness available and none of cost-effectiveness. A detailed economic evaluation of the telemedicine mental health network would now be a major task. The expansion of telemedicine mental health services has increased the expectations of health-care decision makers. In addition, the complexity of the network has increased and new initiatives, such as the use of telepsychology, have been introduced. Management of this successful telehealth programme continues to be time consuming and challenging.


Calculation of the electrostatic potential of lipid bilayers from molecular dynamics simulations: methodological issues.
The electrostatic properties of lipid membranes are of profound importance as they are directly associated with membrane potential and, consequently, with numerous membrane-mediated biological phenomena. Here we address a number of methodological issues related to the computation of the electrostatic potential from atomic-scale molecular dynamics simulations of lipid bilayers. We discuss two slightly different forms of Poisson equation that are normally used to calculate the membrane potential: (i) a classical form when the potential and the electric field are chosen to be zero on one of the sides of a simulation box and (ii) an alternative form, when the potential is set to be the same on the opposite sides of a simulation box. Both forms differ by a position-dependent correction term, which has been shown to be proportional to the overall dipole moment of a bilayer system (for neutral systems). For symmetric bilayers we demonstrate that both approaches give essentially the same potential profiles, provided that simulations are long enough (a production run of at least 100 ns is required) and that fluctuations of the center of mass of a bilayer are properly accounted for. In contrast, for asymmetric lipid bilayers, the second approach is no longer appropriate due to a nonzero net dipole moment across a simulation box with a single asymmetric bilayer. We demonstrate that in this case the electrostatic potential can adequately be described by the classical form of Poisson equation, provided that it is employed in conjunction with tin-foil boundary conditions, which exactly balance a nonzero surface charge of a periodically replicated multibilayer system. Furthermore, we show that vacuum boundary conditions give qualitatively similar potential profiles for asymmetric lipid bilayers as compared to the conventional periodic boundaries, but accurate determination of the transmembrane potential difference is then hindered due to detachment of some water dipoles from bulk aqueous solution to vacuum.


[Ulcer therapy without acid inhibition].
The mechanism of action of ulcer drugs without acid inhibition appears to involve improvement of defensive factors of the gastroduodenal mucosa. The concept of ulcer healing without acid inhibition is attractive for theoretical reasons, because doubts have arisen about the safety of elevation of intragastric pH, especially in long-term treatment of peptic ulcer disease. Ulcer drugs that do not affect gastric acidity may therefore be preferred, provided they compare favorably to the best acid inhibitors available in terms of efficacy, adverse effects and other requirements. Among these drugs, sucralfate fulfills these criteria to a large extent.


Developmental potential of the earliest precursor cells from the adult mouse thymus.
A new, numerically minute population of cells representing the earliest T precursor cells in the adult mouse thymus has recently been isolated. This population has been shown to be similar to bone marrow hemopoietic stem cells in surface antigenic phenotype and to express moderate levels of CD4. We now show, by fluorescence-activated cell sorting and intrathymic transfer to irradiated mice, that this apparently homogeneous population differs from multipotent stem cells in expressing the surface stem cell antigen 2 (Sca-2), that it differs from most early B lineage cells in lacking B220 and class II major histocompatibility complex expression, and that it binds rhodamine 123 like an activated rather than a quiescent cell. Irradiated recipient mice differing at the Ly 5 locus were used to compare the developmental potential of these early intrathymic precursors with bone marrow stem cells. Only T lineage product cells were detected when the intrathymic precursor population was transferred back into an irradiated thymus. However, when the intrathymic precursor population was transferred intravenously, it displayed the capacity to develop into both B and T lymphoid cells in recipient bone marrow, spleen, and lymph nodes, but no donor-derived myeloid cells were detected. The absence of myeloid and erythroid precursor activity was confirmed by showing that the intrathymic precursor population was unable to develop into myeloid or erythroid spleen colonies on intravenous transfer or to form colonies in an agar culture. These findings indicate that this earliest intrathymic precursor population has become restricted (or strongly biased) to lymphoid lineage development, but not exclusively to T lymphocytes.


The Mycoplasma pneumoniae MPN229 gene encodes a protein that selectively binds single-stranded DNA and stimulates Recombinase A-mediated DNA strand exchange.
Mycoplasma pneumoniae has previously been characterized as a micro-organism that is genetically highly stable. In spite of this genetic stability, homologous DNA recombination has been hypothesized to lie at the basis of antigenic variation of the major surface protein, P1, of M. pneumoniae. In order to identify the proteins that may be involved in homologous DNA recombination in M. pneumoniae, we set out to characterize the MPN229 open reading frame (ORF), which bears sequence similarity to the gene encoding the single-stranded DNA-binding (SSB) protein of other micro-organisms. The MPN229 ORF has the capacity to encode a 166-amino acid protein with a calculated molecular mass of 18.4 kDa. The amino acid sequence of this protein (Mpn SSB) is most closely related to that of the protein predicted to be encoded by the MG091 gene from Mycoplasma genitalium (61% identity). The MPN229 ORF was cloned, and different versions of Mpn SSB were expressed in E. coli and purified to > 95% homogeneity. The purified protein was found to exist primarily as a homo-tetramer in solution, and to strongly and selectively bind single-stranded DNA (ssDNA) in a divalent cation- and DNA substrate sequence-independent manner. Mpn SSB was found to bind with a higher affinity to ssDNA substrates larger than 20 nucleotides than to smaller substrates. In addition, the protein strongly stimulated E. coli Recombinase A (RecA)-promoted DNA strand exchange, which indicated that Mpn SSB may play an important role in DNA recombination processes in M. pneumoniae. The M. pneumoniae MPN229 gene encodes a protein, Mpn SSB, which selectively and efficiently binds ssDNA, and stimulates E. coli RecA-promoted homologous DNA recombination. Consequently, the Mpn SSB protein may play a crucial role in DNA recombinatorial pathways in M. pneumoniae. The results from this study will pave the way for unraveling these pathways and assess their role in antigenic variation of M. pneumoniae.


Short-Infusion Trabectedin in Heavily Pretreated Ovarian Cancer Patients: A Single-Institution Experience.
The aim of this study was to assess the efficacy and tolerability of trabectedin given every 10 days as a single agent in recurrent ovarian cancer after 3 prior regimens. Trabectedin 0.6 mg/m2 was administered as a 3-h infusion every 10 days on a 21-day cycle. The study population was compared to patients treated with weekly paclitaxel 80 mg/m2 intravenously on days 1, 8, 15, and 22 every 4 weeks. We identified 34 patients previously submitted to at least 3 lines of chemotherapy who received single-agent trabectedin between 2010 and 2015. They were matched with a historical series of 34 patients who received weekly paclitaxel. No significant differences in response rate were found. Median progression-free survival was 4 months; 5 months in the trabectedin group and 4 months in the paclitaxel group. Overall survival (OS) was 13 months for the trabectedin group and 7 months for the paclitaxel group (p = 0.015). Patients who received platinum after trabectedin had a significant OS increase compared to those who received platinum after paclitaxel (18 vs. 9 months, respectively; p = 0.009). The most frequent drug-related grade 3/4 toxicities were reversible hepatic toxicity, neutropenia, anemia, thrombocytopenia, and gastrointestinal toxicity. Single-agent trabectedin every 10 days is an active treatment with a manageable toxicity profile in heavily pretreated advanced relapsed ovarian cancer patients.


Molecular characterization of the plant virus genus Ourmiavirus and evidence of inter-kingdom reassortment of viral genome segments as its possible route of origin.
Ourmia melon virus (OuMV), Epirus cherry virus (EpCV) and Cassava virus C (CsVC) are three species placed in the genus Ourmiavirus. We cloned and sequenced their RNA genomes. The sizes of the three genomic RNAs of OuMV, the type member of the genus, were 2814, 1064 and 974 nt and each had one open reading frame. RNA1 potentially encoded a 97.5 kDa protein carrying the GDD motif typical of RNA-dependent RNA polymerases (RdRps). The putative RdRps of ourmiaviruses are distantly related to known viral RdRps, with the closest similarity and phylogenetic affinity observed with fungal viruses of the genus Narnaviridae. RNA2 encoded a 31.6 kDa protein which, expressed in bacteria as a His-tag fusion protein and in plants through agroinfiltration, reacted specifically with antibodies made against tubular structures found in the cytoplasm. The ORF2 product is significantly similar to movement proteins of the genus Tombusviridae, and phylogenetic analysis supported this evolutionary relationship. The product of OuMV ORF3 is a 23.8 kDa protein. This protein was also expressed in bacteria and plants, and reacted specifically with antisera against the OuMV coat protein. The sequence of the ORF3 protein showed limited but significant similarity to capsid proteins of several plant and animal viruses, although phylogenetic analysis failed to reveal its most likely origin. Taken together, these results indicate that ourmiaviruses comprise a unique group of plant viruses that might have evolved by reassortment of genomic segments of RNA viruses infecting hosts belonging to different eukaryotic kingdoms, in particular, fungi and plants.


Forest structure and carbon dynamics in Amazonian tropical rain forests.
Living trees constitute one of the major stocks of carbon in tropical forests. A better understanding of variations in the dynamics and structure of tropical forests is necessary for predicting the potential for these ecosystems to lose or store carbon, and for understanding how they recover from disturbance. Amazonian tropical forests occur over a vast area that encompasses differences in topography, climate, and geologic substrate. We observed large differences in forest structure, biomass, and tree growth rates in permanent plots situated in the eastern (near Santarém, Pará), central (near Manaus, Amazonas) and southwestern (near Rio Branco, Acre) Amazon, which differed in dry season length, as well as other factors. Forests at the two sites experiencing longer dry seasons, near Rio Branco and Santarém, had lower stem frequencies (460 and 466 ha(-1) respectively), less biodiversity (Shannon-Wiener diversity index), and smaller aboveground C stocks (140.6 and 122.1 Mg C ha(-1)) than the Manaus site (626 trees ha(-1), 180.1 Mg C ha(-1)), which had less seasonal variation in rainfall. The forests experiencing longer dry seasons also stored a greater proportion of the total biomass in trees with >50 cm diameter (41-45 vs 30% in Manaus). Rates of annual addition of C to living trees calculated from monthly dendrometer band measurements were 1.9 (Manaus), 2.8 (Santarém), and 2.6 (Rio Branco) Mg C ha(-1) year(-1). At all sites, trees in the 10-30 cm diameter class accounted for the highest proportion of annual growth (38, 55 and 56% in Manaus, Rio Branco and Santarém, respectively). Growth showed marked seasonality, with largest stem diameter increment in the wet season and smallest in the dry season, though this may be confounded by seasonal variation in wood water content. Year-to-year variations in C allocated to stem growth ranged from nearly zero in Rio Branco, to 0.8 Mg C ha(-1) year(-1) in Manaus (40% of annual mean) and 0.9 Mg C ha(-1) year(-1) (33% of annual mean) in Santarém, though this variability showed no significant relation with precipitation among years. Initial estimates of the C balance of live wood including recruitment and mortality as well as growth suggests that live wood biomass is at near steady-state in Manaus, but accumulating at about 1.5 Mg C ha(-1) at the other two sites. The causes of C imbalance in living wood pools in Santarém and Rio Branco sites are unknown, but may be related to previous disturbance at these sites. Based on size distribution and growth rate differences in the three sites, we predict that trees in the Manaus forest have greater mean age (approximately 240 years) than those of the other two forests (approximately 140 years).


Opposite social gradient for alcohol use and misuse among French adolescents.
This study investigates the association of the family occupational category (F-OC) with adolescent alcohol use and its potential variation according to the frequency of use. A national survey representative of adolescents aged 17 living in continental France conducted in 2005 (n = 29,393). Three outcomes were considered: overall use describes the drinking status (lifetime abstinence, use before the month prior the survey, use in the month prior the survey) without considering the frequency of use; last month use and binge drinking detail the frequency of use (1-5 uses, 6-9, 10-19 and 20+ uses) and of binge drinking (0, 1-2, 3-5, 6+ episodes of 5+ glasses in a single occasion) of the previous month users. F-OC was described in 7 categories based on the highest occupational category of the parents (from managers/professionals to unemployed). Analysis used generalised logistic regressions, controlling for gender, F-OC, parental separation, autonomy, other substance use, being out of school and sociability. There was a double gradient: adolescents from high F-OC families were more often experimenters and drinkers during the previous month whereas those of low F-OC families were more often binge drinkers. Adolescents from farmers' families were the most at risk for frequent use and binge drinking in the last month. Interactions tests show that the effect of F-OC was not significantly related to gender. Except for gender, adolescents' patterns of use reflect those observed in the adult population. Mechanisms that favour and hinder progression in alcohol use should be studied in various socioeconomic groups.


A novel invasive Streptococcus pyogenes variant sublineage derived through recombinational replacement of the emm12 genomic region.
Group A streptococcal strains potentially acquire new M protein gene types through genetic recombination (emm switching). To detect such variants, we screened 12,596 invasive GAS genomes for strains of differing emm types that shared the same multilocus sequence type (ST). Through this screening we detected a variant consisting of 16 serum opacity factor (SOF)-positive, emm pattern E, emm82 isolates that were ST36, previously only associated with SOF-negative, emm pattern A, emm12. The 16 emm82/ST36 isolates were closely interrelated (pairwise SNP distance of 0-43), and shared the same emm82-containing recombinational fragment. emm82/ST36 isolates carried the sof12 structural gene, however the sof12 indel characteristic of emm12 strains was corrected to confer the SOF-positive phenotype. Five independent emm82/ST36 invasive case isolates comprised two sets of genetically indistinguishable strains. The emm82/ST36 isolates were primarily macrolide resistant (12/16 isolates), displayed at least 4 different core genomic arrangements, and carried 11 different combinations of virulence and resistance determinants. Phylogenetic analysis revealed that emm82/ST36 was within a minor (non-clade 1) portion of ST36 that featured almost all ST36 antibiotic resistance. This work documents emergence of a rapidly diversifying variant that is the first confirmed example of an emm pattern A strain switched to a pattern E strain.


Plasma exchange plus glucocorticoids in the treatment of immune checkpoint inhibitor-induced myocarditis: A case series and review.
Immune checkpoint inhibitors (ICIs), including antiprogrammed cell-death (PD)-1/anti-PD-ligand (PDL-1) monoclonal antibodies, are effective at improving the prognosis of patients with cancer. Among immune-related adverse events, myocarditis associated with anti-PD-1/anti-PD-L1 antibodies is rare but lacks effective treatment and mortality is very high. In this study, the authors extracted data from the previous 8 years from electronic medical records housed in the hospital information system to identify patients hospitalized with myocarditis putatively caused by anti-PD-1/anti-PD-L1 tumor therapy. Clinical data from these patients are reported. Four patients who developed myocarditis after undergoing treatment with anti-PD-1/anti-PD-L1 antibodies for malignant tumors, all of whom responded favorably to therapy consisting of plasma exchange and glucocorticoids for myocarditis, and all patients improved and were discharged from hospital. Plasma exchange plus systemic glucocorticoids may be effective for treating anti-PD-1/anti-PD-L1 antibody-induced myocarditis in patients with cancer.


Urinary biomarkers for sensitive and specific detection of acute kidney injury in humans.
Acute kidney injury (AKI) is associated with high morbidity and mortality. The lack of sensitive and specific injury biomarkers has greatly impeded the development of therapeutic strategies to improve outcomes of AKI.The unique objective of this study was to evaluate the diagnostic performance of nine urinary biomarkers of AKI-kidney injury molecule-1 (KIM-1), neutrophil gelatinase associated lipocalin (NGAL), interleukin-18 (IL-18), hepatocyte growth factor (HGF), cystatin C (Cys), N-acetyl-beta-D-glucosaminidase (NAG), vascular endothelial growth factor (VEGF), chemokine interferon-inducible protein 10 (IP-10; CXCL10), and total protein-in a cross-sectional comparison of 204 patients with or without AKI.Median urinary concentrations of each biomarker were significantly higher in patients with AKI than in those without AKI (p < 0.001). The area under the receiver operating characteristics curve (AUC-ROC) for the combination of biomarkers using a logic regression model [risk score of 2.93*(NGAL > 5.72 and HGF > 0.17) + 2.93*(PROTEIN > 0.22) -2*(KIM < 0.58)] was greater (0.94) than individual biomarker AUC-ROCs. Age-adjusted levels of urinary KIM-1, NAG, HGF, VEGF, and total protein were significantly higher in patients who died or required renal replacement therapy (RRT) when compared to those who survived and did not require RRT.Our results demonstrate the comparative value of multiple biomarkers in the diagnosis and prognosis of AKI.


Prevalence of fatigue in Parkinson disease and its clinical correlates.
To assess in a noninterventional setting the prevalence and severity of fatigue in patients with Parkinson disease (PD). This was a cross-sectional study conducted in Italian patients with PD. Objectives included the evaluation of the current prevalence and severity of fatigue in patients with PD measured using the 16-item Parkinson Fatigue Scale (PFS-16), distressing fatigue (defined as a PFS-16 mean score ≥3.3), and assessment of its clinical correlates. A total of 402 patients were enrolled and 394 patients completed the PFS-16 questionnaire with a PFS-16 mean (±SD) score of 2.87 ± 0.99. Of these, 136 patients (33.8%) reported distressing fatigue (PFS-16 mean score ≥3.3). Patients with distressing fatigue were older (p = 0.044) and had a longer duration of PD (p < 0.0001) than those without distressing fatigue. The presence of distressing fatigue was associated with higher total Unified Parkinson's Disease Rating Scale (UPDRS) scores, poorer quality of life (39-item Parkinson's Disease Questionnaire [PDQ-39]), worse social and psychological behaviors, a higher severity of depressive symptoms, and a higher prevalence of sleep disorders (all p < 0.001). Logistic regression analyses revealed that higher total UPDRS scores, female sex, depression, sleep disorders, as well as higher UPDRS activities of daily living scores and PDQ-39 mobility scores increase the likelihood of distressing fatigue in patients with PD. Approximately one-third of patients with PD have distressing fatigue, which is significantly associated with depression and sleep disorders. The fact that the presence of fatigue worsens patient quality of life supports the need to better diagnose and treat this debilitating symptom.


Altered 5-HT2C receptor agonist-induced responses and 5-HT2C receptor RNA editing in the amygdala of serotonin transporter knockout mice.
The serotonin 5-HT2C receptor (5-HT2CR) is expressed in amygdala, a region involved in anxiety and fear responses and implicated in the pathogenesis of several psychiatric disorders such as acute anxiety and post traumatic stress disorder. In humans and in rodent models, there is evidence of both anxiogenic and anxiolytic actions of 5-HT2C ligands. In this study, we determined the responsiveness of 5-HT2CR in serotonin transporter (SERT) knockout (-/-) mice, a model characterized by increased anxiety-like and stress-responsive behaviors. In the three-chamber social interaction test, the 5-HT2B/2C agonist mCPP decreased sociability and sniffing in SERT wildtype (+/+) mice, both indicative of the well-documented anxiogenic effect of mCPP. This 5-HT2C-mediated response was absent in SERT-/- mice. Likewise, in the open field test, the selective 5-HT2C agonist RO 60-0175 induced an anxiogenic response in SERT+/+ mice, but not in SERT-/- mice. Since 5-HT2CR pre-mRNA is adenosine-to-inosine (A-to-I) edited, we also evaluated the 5-HT2CR RNA editing profiles of SERT+/+ and SERT-/- mice in amygdala. Compared to SERT+/+ mice, SERT-/- mice showed a decrease in less edited, highly functional 5-HT2C isoforms, and an increase in more edited isoforms with reduced signaling efficiency. These results indicate that the 5-HT2CR in the amygdala of SERT-/- mice has increased RNA editing, which could explain, at least in part, the decreased behavioral responses to 5-HT2C agonists in SERT-/- mice. These alterations in 5-HT2CR in amygdala may be relevant to humans with SERT polymorphisms that alter SERT expression, function, and emotional behaviors.


Social organization, grouping, and domestication in fish.
The zebrafish (Danio rerio) is now established as one of the pre-eminent model vertebrate study animals in biology, providing an excellent opportunity to integrate the fields of genetics and behavioral ecology. Considerable attention has been paid to the social organization of animals and the study of zebrafish in this context allows behavioral geneticists to gain an insight into this fundamentally important field. This paper reviews the literature on the social organization of fish, with special reference to the zebrafish. The mechanisms and functions of social behavior in fish and the current understanding of the behavioral genetics of these are discussed. Finally, the impact of domestication on the expression of wild-type behavior patterns in laboratory fish is considered.


Copper and zinc concentrations in uterine fluid and blood serum during the estrous cycle and pre-pubertal phase in water buffaloes.
To investigate uterine fluid and serum copper (Cu) and zinc (Zn) variations during the estrous cycle in water buffaloes, 71 genital tracts and blood samples were collected from the abattoir in Urmia, Iran. The phase of the estrous cycle was determined by examining ovarian structures; 18, 15, 16 and 22 were pro-estrous, estrous, met-estrous and diestrous, respectively. The uterine fluid was collected by gentle scraping of the uterine mucosa with a curette. Blood serum and uterine fluid samples of 71 pre-pubertal buffalo calves were also collected and treated in similar manners. The mean (± SEM) total serum (77.10 ± 1.50 µg dL(-1)) and uterine fluid (296.40 ± 9.40 μg dL(-1)) Cu in cyclic cows was higher than the values of 54.00 ± 1.10 μg dL(-1) and 133.40 ± 5.70 μg dL(-1) in pre-pubertal calves, respectively. Blood serum (114.60 ± 3.20 μg dL(-1)) and the uterine fluid (349.90 ± 8.90 μg dL(-1)) Zn content in cyclic cows were also higher than those (98.80 ± 1.50 μg dL(-1) and 246.6 ± 4.50 μg dL(-1) respectively) in pre-pubertal calves. Serum Cu in pro-estrus and estrus were lower than those in other stages and also lower than those in the uterine fluid. The lowest serum Zn content was recorded in pro- and met-estrus, while in the uterine fluid it was observed in estrus. In all stages of estrous cycle the uterine fluid Zn content was significantly higher than those of the serum. These results suggested that during the estrous cycle in the buffalo cows, Cu and Zn were actively secreted in uterine lumen and were not dependent on blood serum. The values also increased after puberty.


Morphologic features resembling transplant rejection in core biopsies of native livers from patients with Hepatitis C.
Morphologic differentiation of recurrent Hepatitis C from transplant rejection is a major problem in posttransplant liver biopsies. Although biopsies of the native livers from patients with Hepatitis C are known to display bile duct damage, other morphologic features similar to those seen in rejection, such as endotheliitis, portal eosinophils, and pericentral fibrosis, are not generally acknowledged. To determine the frequency with which features morphologically similar to rejection might be present, we examined 50 cases of core-needle biopsy from the native livers of patients with Hepatitis C for the presence of the following: bile duct damage, portal eosinophils, portal or central vein endotheliitis, ductopenia, vascular obliteration, pericentral fibrosis, and pericentral mononuclear cell infiltrate. Biopsy specimens with other concurrent disease processes were excluded. The frequency of each morphologic feature was as follows: bile duct damage (30%), portal eosinophils (42%), portal endotheliitis (20%), central vein endotheliitis (0%), pericentral mononuclear cell infiltrate (14%), ductopenia (2%), atrophic-looking bile ducts (2%), vascular obliteration (0%), and pericentral fibrosis (10%). Bile duct damage and portal endotheliitis were both more common with higher grade hepatitis (Fisher exact test, P = .001). None of the morphologic parameters correlated with biopsy stage, viral genotype, or liver function tests. We conclude that features similar to those found in acute rejection are common in Hepatitis C, whereas features resembling chronic rejection are less frequent. This study provides quantitative data that supports the need to interpret these features with great caution in posttransplant liver biopsies from patients with recurrent Hepatitis C who are suspected of rejection.


Myocardial expression of endothelin-2 is altered reciprocally to that of endothelin-1 during ischemia of cardiomyocytes in vitro and during heart failure in vivo.
We and other groups have reported that endothelin (ET)-1 expression in the heart is altered in the setting of heart diseases. We have also reported that myocardial ET-1 is involved in the progression of heart failure, and that an ET receptor antagonist improves long-term survival in heart failure (Nature 384: 353-355, 1996). However, the role of myocardial ET-2 in disease states are not known. To characterize the role of ET-2, we used a) the failing hearts of rats with heart failure caused by myocardial infarction, and b) primary cultured cardiomyocytes subjected to hypoxia. In the failing heart in vivo, ET-1 mRNA increased by 390% compared with that in the non-failing heart, while ET-2 mRNA drastically decreased by 88%. Thus, gene expression of ET-1 and ET-2 was reciprocally altered in the failing heart in vivo. In in vitro studies, reciprocal alterations in ET-1 and ET-2 gene expression were also observed in isolated primary cultured cardiomyocytes, subjected to hypoxia. Specifically, acute hypoxic stress induced a significant increase (360% of the basal level) in ET-2 mRNA expression compared with that in normoxic cells, whereas it decreased ET-1 mRNA expression by 62% in primary cultured cardiomyocytes. Although these two crucial conditions, i.e., heart failure in vivo and acute hypoxic stress in vitro, are pathophysiologically distinct from each other, reciprocal alteration of ET-1 and ET-2 gene expression was observed in both cases. To further investigate the regulatory mechanism of the altered gene expression, luciferase analysis was performed using primary cultured cardiomyocytes. ET-2 promoter, which is the 5'-flanking region of preproET-2 gene (5'ET-2), showed a marked increase in luciferase activity during acute hypoxia. In contrast, the luciferase activity of 5'ET-1 (ET-1 promoter) did not change in response to hypoxic stress. The present study suggests that there are transcriptionally distinct regulatory mechanisms for ET-1 and ET-2 expression in cardiomyocytes, and therefore this study may provide a new aspect of cardiac ET system that not only ET-1 but also ET-2 can be participated in the pathophysiological conditions.


The association between state housing policy and lead poisoning in children.
This study examined the effect of an active program of household lead paint hazard abatement, applied over 22 years, on childhood lead poisoning in Massachusetts. A small areas analysis was used to compare screening blood lead levels of children in Worcester County, Mass (n = 27,590), with those in Providence County, RI (n = 19,071). Data were collapsed according to census tract. The percentage of children with lead poisoning (blood lead level > or = 20 micrograms/dL [Pe20]) was, on average, 3 times higher in Providence County census tracts (3.2% vs 0.9% in Worcester County census tracts, P < .0001), despite similar percentages of pre-1950s housing in both counties. The ratio of Pe20 in Providence vs Worcester County census tracts was 2.2 (95% confidence interval = 1.8, 2.7), after adjustment for differences in housing, sociodemographic, and screening characteristics. This estimate was robust to alternative regression methods and sensitivity analyses. Massachusetts policy, which requires lead paint abatement of children's homes and places liability for lead paint poisoning on property owners, may have substantially reduced childhood lead poisoning in that state.


Non-quaternary oximes detoxify nerve agents and reactivate nerve agent-inhibited human butyrylcholinesterase.
Government-sanctioned use of nerve agents (NA) has escalated dramatically in recent years. Oxime reactivators of organophosphate (OP)-inhibited acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) serve as antidotes toward poisoning by OPNAs. The oximes used as therapeutics are quaternary compounds that cannot penetrate the blood-brain barrier (BBB). There remains an urgent need for the development of next generation OPNA therapeutics. We have developed two high-throughput screening (HTS) assays using a fluorogenic NA surrogate, O-ethyl methylphosphonyl O-4-methyl-3-cyano-coumarin (EMP-MeCyC). EMP-MeCyC detoxification and EMP-BChE reactivation screening campaigns of ~155,000 small molecules resulted in the identification of 33 nucleophile candidates, including non-quaternary oximes. Four of the oximes were reactivators of both Sarin- and VX-inhibited BChE and directly detoxified Sarin. One oxime also detoxified VX. The novel reactivators included a non-quaternary pyridine amidoxime, benzamidoxime, benzaldoxime and a piperidyl-ketoxime. The VX-inhibited BChE reactivation reaction rates by these novel molecules were similar to those observed with known bis-quaternary reactivators and faster than mono-quaternary pyridinium oximes. Notably, we discovered the first ketoxime reactivator of OP-ChEs and detoxifier of OPNAs. Preliminary toxicological studies demonstrated that the newly discovered non-quaternary oximes were relatively non-toxic in mice. The discovery of unique non-quaternary oximes opens the door to the design of novel therapeutics and decontamination agents following OPNA exposure.


Surgical hand antisepsis to reduce surgical site infection.
Surgical hand antisepsis, to destroy transient micro-organisms and inhibit the growth of resident micro-organisms, is routinely carried out before undertaking invasive procedures. Antisepsis may reduce the risk of surgical site infections in patients. To determine the effects of surgical hand antisepsis on the number of surgical site infections (SSIs) in patients. The secondary objective is to determine the effects of surgical hand antisepsis on the numbers of colony forming units (CFUs) of bacteria on the hands of the surgical team. We searched the Cochrane Wounds Group Specialised Register (June 2007), the Cochrane Central Register of Controlled Trials (Issue 2, 2007), MEDLINE (Week 5, 2007), CINAHL (June 2007), EMBASE (Week 23, 2007) and ZETOC (2005). Randomised controlled trials comparing surgical hand antisepsis of varying duration, methods and antiseptic solutions. Three authors independently assessed studies for selection, trial quality and extracted data. Ten trials were included in this review. Only one trial reported the primary outcome, rates of SSIs, and nine trials measured numbers of CFUs. One trial involving 4387 patients found alcohol rubs with additional active ingredients were as effective as aqueous scrubs in reducing SSIs. Four trials compared different alcohol rubs containing additional active ingredients with aqueous scrubs for numbers of CFUs on hands. One trial found N-duopropenide more effective than chlorhexidine and povidone iodine aqueous scrubs. One trial found 45% propanol-2, 30% propanol-1 with 0.2% ethylhexadecyldimethyl ammonium ethylsulfate more effective than chlorhexidine scrubs. One trial found no difference between 1% chlorhexidine gluconate in 61% ethyl alcohol or zinc pyrithione in 70% ethyl alcohol against aqueous povidone iodine. A fourth trial found 4% chlorhexidine gluconate scrubs more effective than chlorhexidine in 70% alcohol rubs. Four trials compared the relative effects of different aqueous scrubs in reducing CFUs on hands. Three trials found chlorhexidine gluconate scrubs were significantly more effective than povidone iodine scrubs. One trial found no difference between chlorhexidine gluconate scrubs and povidone iodine plus triclosan scrubs. Two trials found no evidence of a difference between alternative alcohol rubs in terms of the number of CFUs. Four trials compared the effect of different durations of scrubs and rubs on the numbers of CFUs on hands. One trial found no difference after the initial scrub but found subsequent three minute scrubs using chlorhexidine significantly more effective than subsequent scrubs lasting 30 seconds. One trial found that following a one minute hand wash, a three minute rub appears to be more effective than the five minute rub using alcohol disinfectant. The other comparisons demonstrated no difference. Alcohol rubs used in preparation for surgery by the scrub team are as effective as aqueous scrubbing in preventing SSIs however this evidence comes from only one, equivalence, cluster trial which did not appear to adjust for clustering. Four comparisons suggest that alcohol rubs are at least as, if not more, effective than aqueous scrubs though the quality of these is mixed and each study presents a different comparison, precluding meta analysis. There is no evidence to suggest that any particular alcohol rub is better than another. Evidence from 4 studies suggests that chlorhexidine gluconate based aqueous scrubs are more effective than povidone iodine based aqueous scrubs in terms of the numbers of CFUs on the hands. There is limited evidence regarding the effects on CFUs numbers of different scrub durations. There is no evidence regarding the effect of equipment such as brushes and sponges.


Excited state dipole moments and lifetimes of 2-cyanoindole from rotationally resolved electronic Stark spectroscopy.
The permanent dipole moments of 2-cyanoindole (cyanoindole = CNI) in its ground and lowest excited singlet states have been determined from rotationally resolved electronic Stark spectroscopy under jet-cooled conditions. From the orientation of the transition dipole moment and the geometry changes upon electronic excitation the lowest excited singlet state could be shown to be of Lb-symmetry. The general statement, that the La-state has the larger permanent dipole moment of the two lowest excited singlet states, will be challenged in this contribution. On the basis of the different electronic nature of the first excited singlet state the behavior of 2-, 3-, 4- and 5-CNI is discussed. The excited state lifetime of isolated 2-CNI in the gas phase has been determined to be 9.4 ns. This value is compared to the excited state lifetime in ethyl acetate solution of 2.6 ns, which was quantified with a Strickler-Berg analysis. Using water as solvent shortens the 2-CNI lifetime to <40 ps. The reason for this drastic shortening is discussed in detail. Additionally, the rotationally resolved electronic spectrum of 2-CNI(1-d1) has been measured and analyzed.


Environmental variability and child growth in Nepal.
Data from the 2011 Nepal Demographic Health Survey are combined with satellite remotely sensed Normalized Difference Vegetation Index (NDVI) data to evaluate whether interannual variability in weather is associated with child health. For stunting, we focus on children older than 24 months of age. NDVI anomaly averages during cropping months are evaluated during the year before birth, the year of birth, and the second year after birth. For wasting, we assess children under 59 months of age and relate growth to NDVI averages for the current and most recent growing periods. Correlations between short-run indicators of child growth and intensity of green vegetation are generally positive. Regressions that control for a range of child-, mother- and household-specific characteristics produce mixed evidence regarding the role of NDVI anomalies during critical periods in a child's early life and the subsequent probability of stunting and wasting. Overall findings suggest that the relationship between environmental conditions and child growth are heterogeneous across the landscape in Nepal and, in many cases, highly non-linear and sensitive to departures from normality.


14-3-3 proteins in neurological disorders.
14-3-3 proteins were originally discovered as a family of proteins that are highly expressed in the brain. Through interactions with a multitude of binding partners, 14-3-3 proteins impact many aspects of brain function including neural signaling, neuronal development and neuroprotection. Although much remains to be learned and understood, 14-3-3 proteins have been implicated in a variety of neurological disorders based on evidence from both clinical and laboratory studies. Here we will review previous and more recent research that has helped us understand the roles of 14-3-3 proteins in both neurodegenerative and neuropsychiatric diseases.


Nocardia caviae: a report of 13 new isolations with clinical correlation.
Thirteen isolates of Nocardia caviae from 12 different clinical sources were received and identified over a 5(1/2)-year period by the Mycology Division of the Center for Disease Control. The results of morphological, biochemical, and physiological studies on these isolates were compared with those obtained with four reference cultures of N. caviae received from the Institute of Microbiology, Rutgers University. Comparison showed that N. caviae isolates form a homogeneous group that is usually easily distinguished from N. asteroides, N. brasiliensis, and other pathogenic aerobic actinomycetes. The clinical sources included nine human and two animal infections and one human isolate apparently not associated with disease. Previous reports of N. caviae infections in man have been limited to rare cases of actinomycotic mycetoma. Among the human infections reported in this series are one case of mycetoma, one case of "mycotic" keratitis, one case of skin abscess, two cases of osteomyelitis, and four cases of serious pulmonary infection caused by N. caviae.


Impact of target-to-background ratio, target size, emission scan duration, and activity on physical figures of merit for a 3D LSO-based whole body PET/CT scanner.
The aim of our work is to describe the way in which physical figures of merit such as contrast-to-noise ratio (CNR) behave when varying acquisition parameters such as emission scan duration (ESD) or activity at the start of acquisition (A(acq)) that in clinical practice can be selected by the user, or object properties such as target dimensions or target-to-background (T/B) ratio, which depend uniquely on the intrinsic characteristics of the object being imaged. Figures of merit, used to characterize image quality and quantitative accuracy for a 3D-LSO based PET/CT scanner, were studied as a function of ESD and A(acq) for different target sizes and T/B ratios using a multivariate approach in a wide range of conditions approaching the ones that can be encountered in clinical practice. An annular ring of water bags of 3 cm thickness was fitted over an IEC phantom in order to obtain counting rates similar to those found in average patients. The average scatter fraction (SF) of the modified IEC phantom was similar to the mean SF measured on patients with a similar scanner. A supplemental set of micro-hollow spheres was positioned inside the phantom. The NEMA NU 2-2001 scatter phantom was positioned at the end of the IEC phantom to approximate the clinical situation of having activity that extends beyond the scanner. The phantoms were filled with a solution of water and 18F (12 kBq/mL) and the spheres with various T/B ratios of 22.5, 10.3, and 3.6. Sequential imaging was performed to acquire PET images with varying background activity concentrations of about 12, 9, 6.4, 5.3, and 3.1 kBq/mL, positioned on the linear portion of the phantom's NECR curve, well below peak NECR of 61.2 kcps that is reached at 31.8 kBq/mL. The ESD was set to 1, 2, 3, and 4 min/bed. With T/B ratios of 3.6, 10.3, and 22.5, the 13.0, 8.1, and 6.5 mm spheres were detectable for the whole ranges of background activity concentration and ESD, respectively. The ESD resulted as the most significant predictor of CNR variance, followed by T/B ratio and the cross sectional area of the given sphere. Only last comes A(acq) with a weight more than halved with respect to ESD. Thus, raising ESD seems to be much more effective than raising A(acq) in order to obtain higher CNR, which is the physical figure of merit closely related with target detectability, at least in the simple task of the signal known exactly background known exactly model.


Antibody anti-p16(INK4a) in cervical cytology.
To evaluate sensitivity, specificity and positive and negative predictive values (PPV, NPV) of anti-p16(INK4a) in cervical cytology. A case-control study was conducted in a reference center for cervical pathology. Cytology slides were collected in a standard way with Ayre spatula and Cytobrush. The slides were interpreted by 2 independent pathologists (P1, P2). The cases (n = 61) represented all cervical examinations that had resulted in a biopsy with the diagnosis of CIN 1, 2 or 3 or squamous cell carcinoma. Controls (n = 87) included all examinations with negative cytology (Papanicolaou) and negative colposcopy. The sensitivity for the histologic diagnosis of CIN 2, 3 (n = 23) was 100% and 95.7% (P1, P2), respectively. The NPV for CIN 2 or worse was 100% (P1) and 98.9% (P2). The sensitivity for the diagnosis of CIN 1 was 77.8% (P1) and 58.3% (P2). The NPV for CIN 1 or worse was 90.6% (P1) and 82% (P2). The K index between the 2 pathologists was 0.74. Our results suggest that the antibody anti-p16(INK4a) could contribute as an adjuvant tool in the follow-up of cervical intraepithelial lesions when the cytology sample is collected in the standard way.


Dynamic changes of serum trace elements following cardiac surgery: A systematic review and meta-analysis.
Cardiac surgeries are known to induce an inflammatory response. Besides, dietary factors such as trace elements contribute to promoting cardiovascular health by maintaining oxidative balance. Here we systematically review the literature about alterations in serum concentrations of zinc (Zn), copper (Cu), and selenium (Se) in response to cardiac surgeries. A systematic search was performed on databases until the end of December 2022. Studies assessing the changes of mentioned elements in adult patients undergoing cardiac surgery were included. Changes in the means and standard deviations of the elements before and after the cardiac surgery were utilized as desired effect sizes. Among 1252 records found in the primary search, 23 and 21 articles were included in the systematic review and meta-analysis respectively. Seventeen studies evaluated the changes in serum Zn and Cu levels, and fifteen studies assessed Se levels. According to the results of quantitative analysis, Zn, Cu, and Se concentrations, one day after the surgery were significantly lower than preoperative values (WMD for Zn: 4.64 µmol/L [3.57-5.72], WMD for Cu: 1.62 µmol/L [0.52-2.72], and WMD for Se: 0.1 µmol/L [0.03-0.16]). The concentration of trace elements recovered gradually during the first-week post-operation and reached preoperative levels or even higher. Serum trace elements dropped significantly soon after the cardiac surgery, but they reached their baseline levels mostly during the first week after the surgery. Future studies are warranted to elucidate the impact of alterations in serum concentration of trace elements on the outcomes and complications of open-heart surgeries.


A novel Thr56Met mutation of the autosomal recessive hypercholesterolemia gene associated with hypercholesterolemia.
The autosomal recessive hypercholesterolemia (ARH) gene is located on chromosome 1p35 and encodes a 308-amino acid protein containing a phosphotyrosine-binding domain. Several researchers have identified mutations of ARH that cause autosomal recessive hypercholesterolemia; however, it remains unknown whether this gene is involved in common hypercholesterolemia. We searched for polymorphisms of the ARH gene by denaturing high-performance liquid chromatography and direct sequencing. We identified 18 single nucleotide polymorphisms of the gene, including 9 novel polymorphisms, and determined 2 haplotype blocks. No association was observed between common hypercholesterolemia and any polymorphisms or haplotypes of the ARH gene; however, we newly identified a rare Thr56Met missense mutation located in the phosphotyrosine-binding domain, which is the functional domain responsible for cholesterol metabolism. Among 1,800 Japanese individuals enrolled in the Suita study, only 4 were heterozygous for Thr56Met and all had hypercholesterolemia. The total cholesterol level and low-density lipoprotein cholesterol level of diabetic patients with the Thr56Met missense mutation was 276.3+/-13.8 mg/dL and 185.3+/-7.37 mg/dL, respectively. Because the Thr56Met missense mutation occurs in an orthologously conserved functional domain and all subjects with the mutation had hypercholesterolemia resembling familiar hypercholesterolemia, it may be a cause of familial hypercholesterolemia.


Point-of-care diagnostic tools to detect circulating microRNAS as biomarkers of disease.
MicroRNAs or miRNAs are a form of small non-coding RNAs (ncRNAs) of 19-22 nucleotides in length in their mature form. miRNAs are transcribed in the nucleus of all cells from large precursors, many of which have several kilobases in length. Originally identified as intracellular modulators of protein synthesis via posttranscriptional gene silencing, more recently it has been found that miRNAs can travel in extracellular human fluids inside specialized vesicles known as exosomes. We will be referring to this miRNAs as circulating microRNAs. More interestingly, the miRNA content inside exosomes changes during pathological events. In the present review we analyze the literature about circulating miRNAs and their possible use as biomarkers. Furthermore, we explore their future in point-of-care (POC) diagnostics and provide an example of a portable POC apparatus useful in the detection of circulating miRNAs.


The influence of 1,25-dihydroxyvitamin D3 and 1,24-dihydroxyvitamin D3 on alphavbeta3 integrin expression in cancer cell lines.
Integrins are cell-surface receptors engaged in important cancer invasion processes, such as adhesion, migration, proliferation and differentiation. The aim of this study was to evaluate the effect of 1,25-dihydroxyvitamin D3 (calcitriol) and its metabolite 1,24-dihydroxyvitamin D3 (PRI-2191) on alphavbeta3 integrin expression in various cancer cell lines. The expression levels of the beta3 and alphav integrins were reduced only in the WEHI-3 and LLC cell lines by the two compounds. Calcitriol or PRI-2191 treatment caused differentiation of WEHI-3 mouse leukemia cells, but apoptosis of LLC cells. WEHI-3 and LLC cells exposed to calcitriol or PRI-2191 lost their migratory and adhesive potentials. The inhibition of migratory potential was higher in the LLC cells than in the WEHI-3 cells and appeared to correlate with the increased down-regulation of alphavbeta3 integrin by calcitriol or PRI-2191. The observed in vivo effects (antitumor and antimetastatic) in mice bearing subcutaneously transplanted LLC cancer are possibly associated with inhibited migratory potential as a consequence of the lowered integrin expression caused by calcitriol or PRI-2191.


Multiplex ligation-dependent probe amplification identification of whole exon and single nucleotide deletions in the CFTR gene of Hispanic individuals with cystic fibrosis.
A disparity between Caucasian and Hispanic mutation detection for cystic fibrosis continues to exist, although the carrier frequency is only moderately lower in Hispanics. We aimed to identify exonic rearrangements that remained undetected by conventional methods. In seven of 32 cystic fibrosis-affected self-identified Hispanics for whom only one or no mutations were identified by extensive molecular testing, exon deletions appeared to be present with a multiplex ligation-dependent probe amplification (MLPA) assay. Two recurrent deletions (of exons 2-3 and exons 22-23) were identified in one and three patients, respectively (12.5%, 11.1% of unidentified alleles). Two apparently novel deletions (exons 6b and 20) were identified in three additional patients. Subsequent sequencing to characterize deletion breakpoints, however, identified single nucleotide deletions at the probe binding sites close to the ligation point. All resulted in false positive MLPA deletion signals. Interestingly, these mutations were not common in Caucasians, and one (935delA) was common in U.S. Hispanics. On examination of all probe binding sites, we identified a total of 76 reported mutations and five silent variants that immediately surrounded the MLPA ligation sites, with 22 occurring in non-Caucasians. These mutations are not all rare. Thus, apparent exon deletions by MLPA may indicate the presence of both large deletions and point mutations, with important implications for pan-ethnic MLPA testing in cystic fibrosis and other genetic conditions.


Pregnancy-associated esterase in sera of baboons.
Baboon serum samples were resolved by starch gel electrophoresis and polyacrylamide gradient gel electrophoresis and stained with naphthol substrates for esterase activity. An esterase that hydrolyzed alpha-naphthyl butyrate in preference to alpha-naphthyl acetate was found in very high activities in some individuals but not others. It migrated just cathodal of the albumin band in starch gels. In polyacrylamide gradient gels, it co-migrated with albumin and had an apparent molecular weight of approximately 65,000 daltons. Electrophoretic analysis by gel electrophoresis of random serum samples from male and female baboons indicated that this esterase was present only in the sera of pregnant baboons. Further investigation of serial samples collected from carefully monitored baboons confirmed that the amount of activity of this esterase was correlated with stage of pregnancy. Therefore, it was named pregnancy esterase (PE). PE was detectable by gel electrophoresis and chromogenic staining techniques as early as day 30 of pregnancy; its activity gradually increased with progressive pregnancy and reached maximum activity near full term (182 days). Soon after parturition, the activity of PE decreased rapidly and was not detected in maternal sera by day 14 postpartum. No evidence of PE was detected in sera of pregnant humans.


Toggling a conformational switch in Wnt/β-catenin signaling: regulation of Axin phosphorylation. The phosphorylation state of Axin controls its scaffold function in two Wnt pathway protein complexes.
The precise orchestration of two opposing protein complexes - one in the cytoplasm (β-catenin destruction complex) and the other at the plasma membrane (LRP6 signaling complex) - is critical for controlling levels of the transcriptional co-factor β-catenin, and subsequent activation of the Wnt/β-catenin signal transduction pathway. The Wnt pathway component Axin acts as an essential scaffold for the assembly of both complexes. How the β-catenin destruction and LRP6 signaling complexes are modulated following Wnt stimulation remains controversial. A recent study in Science by He and coworkers reveals an underlying logic for Wnt pathway control in which Axin phosphorylation toggles a switch between the active and inactive states. This mini-review focuses on this and two other recent studies that provide insight into the initial signaling events triggered by Wnt exposure. We emphasize regulation of the β-catenin destruction and LRP6 signaling complexes and propose a framework for future work in this area.


Principal axis-based correspondence between multiple cameras for people tracking.
Visual surveillance using multiple cameras has attracted increasing interest in recent years. Correspondence between multiple cameras is one of the most important and basic problems which visual surveillance using multiple cameras brings. In this paper, we propose a simple and robust method, based on principal axes of people, to match people across multiple cameras. The correspondence likelihood reflecting the similarity of pairs of principal axes of people is constructed according to the relationship between "ground-points" of people detected in each camera view and the intersections of principal axes detected in different camera views and transformed to the same view. Our method has the following desirable properties: 1) Camera calibration is not needed. 2) Accurate motion detection and segmentation are less critical due to the robustness of the principal axis-based feature to noise. 3) Based on the fused data derived from correspondence results, positions of people in each camera view can be accurately located even when the people are partially occluded in all views. The experimental results on several real video sequences from outdoor environments have demonstrated the effectiveness, efficiency, and robustness of our method.


Mixed-valent dicobalt and iron-cobalt complexes with high-spin configurations and short metal-metal bonds.
Cobalt-cobalt and iron-cobalt bonds are investigated in coordination complexes with formally mixed-valent [M2](3+) cores. The trigonal dicobalt tris(diphenylformamidinate) compound, Co2(DPhF)3, which was previously reported by Cotton, Murillo, and co-workers (Inorg. Chim. Acta 1996, 249, 9), is shown to have an energetically isolated, high-spin sextet ground-state by magnetic susceptibility and electron paramagnetic resonance (EPR) spectroscopy. A new tris(amidinato)amine ligand platform is introduced. By tethering three amidinate donors to an apical amine, this platform offers two distinct metal-binding sites. Using the phenyl-substituted variant (abbreviated as L(Ph)), the isolation of a dicobalt homobimetallic and an iron-cobalt heterobimetallic are demonstrated. The new [Co2](3+) and [FeCo](3+) cores have high-spin sextet and septet ground states, respectively. Their solid-state structures reveal short metal-metal bond distances of 2.29 Å for Co-Co and 2.18 Å for Fe-Co; the latter is the shortest distance for an iron-cobalt bond to date. To assign the positions of iron and cobalt atoms as well as to determine if Fe/Co mixing is occurring, X-ray anomalous scattering experiments were performed, spanning the Fe and Co absorption energies. These studies show only a minor amount of metal-site mixing in this complex, and that FeCoL(Ph) is more precisely described as (Fe0.94(1)Co0.06(1))(Co0.95(1)Fe0.05(1))L(Ph). The iron-cobalt heterobimetallic has been further characterized by Mössbauer spectroscopy. Its isomer shift of 0.65 mm/s and quadrupole splitting of 0.64 mm/s are comparable to the related diiron complex, Fe2(DPhF)3. On the basis of spectroscopic data and theoretical calculations, it is proposed that the formal [M2](3+) cores are fully delocalized.


Longitudinal variations in the gastrointestinal microbiome of the white shrimp, Litopenaeus vannamei.
The shrimp gut is a long digestive structure that includes the Foregut (stomach), Midgut (hepatopancreas) and Hindgut (intestine). Each component has different structural, immunity and digestion roles. Given these three gut digestive tract components' significance, we examined the bacterial compositions of the Foregut, Hindgut, and Midgut digestive fractions. Those bacterial communities' structures were evaluated by sequencing the V3 hypervariable region of the 16S rRNA gene, while the functions were predicted by PICRUSt2 bioinformatics workflow. Also, to avoid contamination with environmental bacteria, shrimp were maintained under strictly controlled conditions. The pairwise differential abundance analysis revealed differences among digestive tract fractions. The families Rhodobacteraceae and Rubritalaceae registered higher abundances in the Foregut fraction, while in the Midgut, the families with a higher proportion were Aeromonadaceae, Beijerinckiaceae and Propionibacteriaceae. Finally, the Cellulomonadaceae family resulted in a higher proportion in the Hindgut. Regarding the predicted functions, amino acid and carbohydrate metabolism pathways were the primary functions registered for Foregut microbiota; conversely, pathways associated with the metabolism of lipids, terpenoids and polyketides, were detected in the Midgut fraction. In the Hindgut, pathways like the metabolism of cofactors and vitamins along with energy metabolism were enriched. Structural changes were followed by significant alterations in functional capabilities, suggesting that each fraction's bacteria communities may carry out specific metabolic functions. Results indicate that white shrimp's gut microbiota is widely related to the fraction analyzed across the digestive tract. Overall, our results suggest a role for the dominant bacteria in each digestive tract fraction, contributing with a novel insight into the bacterial community.


TGF-beta signal transduction in oro-facial health and non-malignant disease (part I).
The transforming growth factor-beta (TGF-beta) family of cytokines consists of multi-functional polypeptides that regulate a variety of cell processes, including proliferation, differentiation, apoptosis, extracellular matrix elaboration, angiogenesis, and immune suppression, among others. In so doing, TGF-beta plays a key role in the control of cell behavior in both health and disease. In this report, we review what is known about the mechanisms of activation of the peptide, together with details of TGF-beta signal transduction pathways. This review summarizes the evidence implicating TGF-beta in normal physiological processes of the craniofacial complex-such as palatogenesis, tooth formation, wound healing, and scarring-and then evaluates its role in non-malignant disease processes such as scleroderma, submucous fibrosis, periodontal disease, and lichen planus.


The biosynthesis in vitro of chondroitin sulphate in neonatal rat epiphysial cartilage.
1. A system is described, which was used to incubate neonatal rat epiphysial cartilage in vitro with [U-(14)C]glucose and [(35)S]sulphate. 2. The acid glycosaminoglycans of neonatal rat epiphyses were extracted and fractionated on cetylpyridinium chloride-cellulose columns. The major components were chondroitin 4-sulphate (65%), chondroitin 6-sulphate (15%), hyaluronic acid (4%) and keratan sulphate (2%). 3. The acid-soluble nucleotides and intermediates of glycosaminoglycan synthesis were separated on a Dowex 1 (formate) system. The tissue contents and cellular concentrations of these metabolites were determined. 4. The rates of synthesis of UDP-glucuronic acid and UDP-N-acetyl-hexosamine from [U-(14)C]glucose were found to be 0.79+/-0.16 and 3.2+/-0.08nmol/min per g wet wt. respectively. 5. The incorporation of [U-(14)C]glucose into the uronic acid and hexosamine moieties of the polymers was also measured and the turnover rates of the glycosaminoglycans were calculated. It was found that chondroitin sulphate was turning over in about 70h and hyaluronic acid in about 120h. 6. The relative rates of synthesis of the sulphated glycosaminoglycans were calculated from [(35)S]sulphate incorporation and were found to be in good agreement with those obtained from [U-(14)C]glucose labelling.


Going the distance--experiences of women with gynaecological cancer residing in rural remote north Queensland.
Women who are diagnosed with gynaecological cancer face a difficult journey. For women residing in areas geographically removed from major health providers the journey can be much more difficult. While they 'make do' and 'struggle on', their lived experiences can provide valuable insight into the complex issues surrounding a cancer diagnosis in rural areas. This study aimed to understand their experiences through the women's stories and sought to identify the major themes impacting on these stories. This qualitative phenomenological study undertook interviews with seven women with gynaecological cancer who reside in rural and remote north Queensland. Analysis of the data collected revealed three themes: seeking answers at a distance; sharing information within a small community; and experiences of navigating the health system. The results show the inherent difficulties in accessing support in rural areas and the difficulties associated with travelling considerable distances to undergo treatment.


Gender and retention patterns among U.S. faculty.
Women remain underrepresented among faculty in nearly all academic fields. Using a census of 245,270 tenure-track and tenured professors at United States-based PhD-granting departments, we show that women leave academia overall at higher rates than men at every career age, in large part because of strongly gendered attrition at lower-prestige institutions, in non-STEM fields, and among tenured faculty. A large-scale survey of the same faculty indicates that the reasons faculty leave are gendered, even for institutions, fields, and career ages in which retention rates are not. Women are more likely than men to feel pushed from their jobs and less likely to feel pulled toward better opportunities, and women leave or consider leaving because of workplace climate more often than work-life balance. These results quantify the systemic nature of gendered faculty retention; contextualize its relationship with career age, institutional prestige, and field; and highlight the importance of understanding the gendered reasons for attrition rather than focusing on rates alone.


Micro-organisms in the midgut of tsetse fly larvae.
Two types of micro-organisms were found in the midgut of Glossina morsitans larvae, a large Gram-negative bacterial rod and a small Gram-negative rickettsia-like micro-organism, although the occurrence of the rickettsial type is restricted. The location of these micro-organisms in a small area of the proventriculus of all three larval instars is discussed. The large micro-organisms resemble milk-gland bacteria, and further evidence is presented in support of a milk transmission hypothesis for these micro-organisms.


Global quantitative phosphoproteome analysis of human tumor xenografts treated with a CD44 antagonist.
The cell surface glycoprotein CD44 plays an important role in the development and progression of various tumor types. RG7356 is a humanized antibody targeting the constant region of CD44 that shows antitumor efficacy in mice implanted with CD44-expressing tumors such as MDA-MB-231 breast cancer cells. CD44 receptor seems to function as the main receptor for hyaluronic acid and osteopontin, serving as coreceptor for growth factor pathways like cMet, EGFR, HER-2, and VEGFR and by cytoskeletal modulation via ERM and Rho kinase signaling. To assess the direct impact of RG7356 binding to the CD44 receptor, a global mass spectrometry-based phosphoproteomics approach was applied to freshly isolated MDA-MB-231 tumor xenografts. Results from a global phosphoproteomics screen were further corroborated by Western blot and ELISA analyses of tumor lysates from CD44-expressing tumors. Short-term treatment of tumor-bearing mice with RG7356 resulted in modifications of the MAPK pathway in the responsive model, although no effects on downstream phosphorylation were observed in a nonresponsive xenograft model. Taken together, our approach augments the value of other high throughput techniques to identify biomarkers for clinical development of targeted agents.


Baby on board: olfactory cues indicate pregnancy and fetal sex in a non-human primate.
Olfactory cues play an integral, albeit underappreciated, role in mediating vertebrate social and reproductive behaviour. These cues fluctuate with the signaller's hormonal condition, coincident with and informative about relevant aspects of its reproductive state, such as pubertal onset, change in season and, in females, timing of ovulation. Although pregnancy dramatically alters a female's endocrine profiles, which can be further influenced by fetal sex, the relationship between gestation and olfactory cues is poorly understood. We therefore examined the effects of pregnancy and fetal sex on volatile genital secretions in the ring-tailed lemur (Lemur catta), a strepsirrhine primate possessing complex olfactory mechanisms of reproductive signalling. While pregnant, dams altered and dampened their expression of volatile chemicals, with compound richness being particularly reduced in dams bearing sons. These changes were comparable in magnitude with other, published chemical differences among lemurs that are salient to conspecifics. Such olfactory 'signatures' of pregnancy may help guide social interactions, potentially promoting mother-infant recognition, reducing intragroup conflict or counteracting behavioural mechanisms of paternity confusion; cues that also advertise fetal sex may additionally facilitate differential sex allocation.


Temporal mapping of transcripts in human herpesvirus-7.
Transcription of human herpesvirus-7 (HHV-7) in cultures of productively infected T-cells was studied. Transcription of HHV-7 was regulated by the typical herpesvirus cascade in which alpha, beta and gamma genes are sequentially transcribed. Transcripts of U10, U14, U18, U31, U39, U41, U42, U53, U73 and U89/90 were detected 3 h after infection and were not inhibited by the absence of protein synthesis and therefore were alpha functions. U19 and U18/20 were beta genes; their transcription was inhibited by cycloheximide but not by phosphonoacetate, an inhibitor of DNA synthesis. U60/66 and U98/100 were gamma genes since their spliced transcripts were not detected in cells treated with phosphonoacetate. HHV-7 transcription was regulated by complex mechanisms, which involve the temporal coordinated activation of specific viral promoters and post-transcriptional processing. Splice mechanisms were also temporally regulated. Transcription of U89/90 pre-mRNA and splice took place simultaneously in the immediate-early phase. On the other hand, U16/17 pre-mRNA was synthesized with typical alpha kinetics, but the spliced product was regulated as a beta function. Likewise, the primary transcripts of U60/66 and U98/100 were alpha and beta, respectively, but both spliced products were synthesized in the late phase of virus replication. Finally, HHV-7 supported a bona fide latent infection in the adult population, since viral transcripts were not detected in peripheral blood mononuclear cells of healthy donors infected with HHV-7.


PEG-b-PPA/DNA micelles improve transgene expression in rat liver through intrabiliary infusion.
We have developed a new block copolymer gene carrier that comprises of a polyethylene glycol segment and a degradable cationic polyphosphoramidate (PPA) segment. This PEG-b-PPA copolymer carrier formed micelles upon condensation with plasmid DNA in aqueous solution. PEG-b-PPA/DNA micelles exhibited uniform and reduced particle size ranging from 80 to 100 nm and lowered surface charge, compared with complexes of DNA with the corresponding cationic PPA carrier. PEG-b-PPA/DNA micelles maintained similar transfection efficiency as PPA/DNA complexes, which was comparable to that of PEI/DNA complexes in HepG2 cells, but yielded about 16-fold lower transgene expression in primary rat hepatocytes than PPA/DNA complexes. Following bile duct infusion in Wistar rats, PEG-b-PPA/DNA micelles mediated 4-fold higher and more uniform gene expression in the liver than PPA/DNA complexes. Liver function tests and histopathological examination indicated that PEG-b-PPA/DNA micelles showed low toxicity and good biocompatibility in the liver. This study demonstrated the potential of PEG-b-PPA/DNA micelles as an efficient carrier for liver-targeted gene delivery.


DNA Methylation and Potential for Epigenetic Regulation in Pygospio elegans.
Transitions in developmental mode are common evolutionarily, but how and why they occur is not understood. Developmental mode describes larval phenotypes, including morphology, ecology and behavior of larvae, which typically are generalized across different species. The polychaete worm Pygospio elegans is one of few species polymorphic in developmental mode, with multiple larval phenotypes, providing a possibility to examine the potential mechanisms allowing transitions in developmental mode. We investigated the presence of DNA methylation in P. elegans, and, since maternal provisioning is a key factor determining eventual larval phenotype, we compared patterns of DNA methylation in females during oogenesis in this species. We demonstrate that intragenic CpG site DNA methylation and many relevant genes necessary for DNA methylation occur in P. elegans. Methylation-sensitive AFLP analysis showed that gravid females with offspring differing in larval developmental mode have significantly different methylation profiles and that the females with benthic larvae and non-reproductive females from the same location also differ in their epigenetic profiles. Analysis of CpG sites in transcriptome data supported our findings of DNA methylation in this species and showed that CpG observed/expected ratios differ among females gravid with embryos destined to different developmental modes. The differences in CpG site DNA methylation patterns seen among the samples suggest a potential for epigenetic regulation of gene expression (through DNA methylation) in this species.


Dynamics of memory T cell proliferation under conditions of heterologous immunity and bystander stimulation.
By examining adoptively transferred CSFE-labeled lymphocytic choriomeningitis virus (LCMV)-immune donor T cells in Thy-1 congenic hosts inoculated with viruses or with the cytokine inducer poly(I:C), strikingly different responses of bona fide memory T cells were found in response to different stimuli. Poly(I:C) (cytokine) stimulation caused a limited synchronized division of memory CD8 T cells specific to each of five LCMV epitopes, with no increase and sometimes a loss in number, and no change in their epitope hierarchy. Homologous LCMV infection caused more than seven divisions of T cells specific for each epitope, with dramatic increases in number and minor changes in hierarchy. Infections with the heterologous viruses Pichinde and vaccinia (VV) caused more than seven divisions and increases in number of T cells specific to some putatively cross-reactive but not other epitopes and resulted in substantial changes in the hierarchy of the LCMV-specific T cells. Hence, there can be memory T cell division without proliferation (i.e., increase in cell number) in the absence of Ag and division with proliferation in the presence of Ag from homologous or heterologous viruses. Heterologous protective immunity between viruses is not necessarily reciprocal, given that LCMV protects against VV but VV does not protect against LCMV. VV elicited proliferation of LCMV-induced CD8 and CD4 T cells, whereas LCMV did not elicit proliferation of VV-induced T cells. Thus, depending on the pathogen and the sequence of infection, a heterologous agent may selectively stimulate the memory pool in patterns consistent with heterologous immunity.


Gene expression profiling of bovine endometrium during the oestrous cycle: detection of molecular pathways involved in functional changes.
The endometrium plays a central role among the reproductive tissues in the context of early embryo-maternal communication and pregnancy. It undergoes typical changes during the sexual/oestrous cycle, which are regulated by the ovarian hormones progesterone and oestrogen. To identify the underlying molecular mechanisms we have performed the first holistic screen of transcriptome changes in bovine intercaruncular endometrium at two stages of the cycle--end of day 0 (late oestrus, low progesterone) and day 12 (dioestrus, high progesterone). A combination of subtracted cDNA libraries and cDNA array hybridisation revealed 133 genes showing at least a 2-fold change of their mRNA abundance, 65 with higher levels at oestrus and 68 at dioestrus. Interestingly, genes were identified which showed differential expression between different uterine sections as well. The most prominent example was the UTMP (uterine milk protein) mRNA, which was markedly upregulated in the cranial part of the ipsilateral uterine horn at oestrus. A Gene Ontology classification of the genes with known function characterised the oestrus time by elevated expression of genes, for example related to cell adhesion, cell motility and extracellular matrix and the dioestrus time by higher expression of mRNAs encoding for a variety of enzymes and transport proteins, in particular ion channels. Searching in pathway databases and literature data-mining revealed physiological processes and signalling cascades, e.g. the transforming growth factor-beta signalling pathway and retinoic acid signalling, which are potentially involved in the regulation of changes of the endometrium during the oestrous cycle.


Evaluating the public health impacts of legalizing recreational cannabis use in the United States.
Since 2012 four US states have legalized the retail sale of cannabis for recreational use by adults, and more are likely to follow. This report aimed to (1) briefly describe the regulatory regimes so far implemented; (2) outline their plausible effects on cannabis use and cannabis-related harm; and (3) suggest what research is needed to evaluate the public health impact of these policy changes. We reviewed the drug policy literature to identify: (1) plausible effects of legalizing adult recreational use on cannabis price and availability; (2) factors that may increase or limit these effects; (3) pointers from studies of the effects of legalizing medical cannabis use; and (4) indicators of cannabis use and cannabis-related harm that can be monitored to assess the effects of these policy changes. Legalization of recreational use will probably increase use in the long term, but the magnitude and timing of any increase is uncertain. It will be critical to monitor: cannabis use in household and high school surveys; cannabis sales; the number of cannabis plants legally produced; and the tetrahydrocannabinol (THC) content of cannabis. Indicators of cannabis-related harms that should be monitored include: car crash fatalities and injuries; emergency department presentations; presentations to addiction treatment services; and the prevalence of regular cannabis use among young people in mental health services and the criminal justice system. Plausible effects of legalizing recreational cannabis use in the United States include substantially reducing the price of cannabis and increasing heavy use and some types of cannabis-related harm among existing users. In the longer term it may also increase the number of new users.


Mode of action of medical methods of abortion.
Several pharmacologic agents capable of inducing abortion have become available in the last 20 years. Prostaglandins cause powerful contractions of the uterus that lead eventually to expulsion of the fetal or embryonic tissue, but their effects on smooth muscle elsewhere in the body lead to such troublesome side effects as vomiting and diarrhea. Antimetabolites such as methotrexate inhibit DNA synthesis in rapidly dividing cells such as the trophoblast, resulting in release of prostaglandins and cytokines, extravasation of blood into the decidua, uterine contractions, and expulsion of embryonic or fetal tissue. Drugs that inhibit the synthesis of progesterone (epostane) or block its receptor (mifepristone) reverse the dominant influence of progesterone during pregnancy. As a result, a cascade of events is initiated, including influx of leukocytes and red blood cells into the decidua, release of prostaglandins and cytokines, and uterine contractions. Addition of uterotonic agents such as prostaglandins results in powerful uterine contractions, which supplement those induced by the withdrawal of progesterone. Because these methods reproduce many of the same physiological changes, clinical management of medical abortion is similar to that of spontaneous abortion. These methods provide a useful alternative to surgical abortion in early pregnancy.


MERS-CoV in Upper Respiratory Tract and Lungs of Dromedary Camels, Saudi Arabia, 2013-2014.
To assess the temporal dynamics of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in dromedary camels, specimens were collected at 1-2 month intervals from 2 independent groups of animals during April 2013-May 2014 in Al-Ahsa Province, Saudi Arabia, and tested for MERS-CoV RNA by reverse transcription PCR. Of 96 live camels, 28 (29.2%) nasal swab samples were positive; of 91 camel carcasses, 56 (61.5%) lung tissue samples were positive. Positive samples were more commonly found among young animals (<4 years of age) than adults (>4 years of age). The proportions of positive samples varied by month for both groups; detection peaked during November 2013 and January 2014 and declined in March and May 2014. These findings further our understanding of MERS-CoV infection in dromedary camels and may help inform intervention strategies to reduce zoonotic infections.


An economic evaluation of vasoactive agents used to treat acute bleeding oesophageal varices in Belgium.
Increasingly, cost influences all areas of healthcare, including the management of life threatening events, such as bleeding oesophageal varices (BOV). In light of the need to control costs, an economic evaluation of vasoactive agents used to treat cirrhotic patients with BOV within the emergency setting in Belgium has been assessed. A previously reported economic evaluation of vasoactive agents used to treat BOV was identified and adapted to the Belgium hospital setting. The economic evaluation was based on double-blind randomised controlled trials of vasoactive agents previously reported as Cochrane meta-analyses. Belgian cost data was obtained from local published sources and hospital databases. We assessed average disaggregated and aggregated treatment costs, average and incremental cost per quality adjusted life years (QALYs) and life-years gained (LYG). Total treatment costs at 1 year were: terlipressin Euro 2,734; somatostatine Euro 2,972; octreotide Euro 2,801; and placebo Euro 2,874. The average costs per QALY were: terlipressin Euro 4,672; somatostatine Euro 5,878; octreotide Euro 5,540; and placebo Euro 5,687. In the cost per LYG analysis terlipressin achieved the lowest cost per life-year. Results from the incremental cost per QALY and LYG analysis indicated that terlipressin was the most cost-effective agent. One year simulations indicate somatostatine is the most expensive treatment option and terlipressin the least costly. Amongst the vasoactive products, the incremental analysis indicated terlipressin was dominant when compared with octreotide and somatostatine because of improved survival and cost-saving potential that is likely attributed to avoiding additional and more costly interventions.


Acute Kidney Injury After Pediatric Liver Transplantation.
The aim of the present study is to assess acute kidney injury (AKI) incidence according to the pRIFLE and AKIN criteria and to evaluate the risk factors for early developing AKI in postoperative intensive care unit after pediatric liver transplantation (LT). After exclusion of retransplantations, 7 cadaveric and 44 living donors, totaling 51 pediatric LT patients that were performed between 2005 and 2017, were reviewed retrospectively. AKI was defined according to both pediatric RIFLE (Risk for renal dysfunction, Injury to the kidney, Failure of kidney function, Loss of kidney function, and End-stage renal disease) and Acute Kidney Injury Network (AKIN) criteria. Documented data were compared between AKI and non-AKI patients. AKI incidences were 17.6% by AKIN and 37.8% by pRIFLE criteria. AKIN-defined AKI group had statistically lower serum albumin level, higher serum sodium level, higher furosemide dose, and higher rate of red blood cell (RBC) transfusion than the non-AKI group (P = .02, P = .02, P = .01 and P = .04, respectively). AKI patients had significantly prolonged mechanical ventilation (P = .01) and hospital LOS (P = .02). The pRIFLE-defined AKI group had significantly lower serum albumin level, higher blood urea nitrogen (BUN) level, and higher ascites drained and also showed higher requirement for RBC and 20% human albumin transfusions than the non-AKI group (P = .02, P = .04, P: =.007, P = .02 and P = .05, respectively). We evaluated that hypoalbuminemia, high requirement for RBC and 20% human albumin transfusions, high serum sodium, high furosemide use, and high flow of ascites are risk factors for AKI and high BUN levels can be predictive for AKI in pediatric LT patients. The effect of AKI on outcome variables were prolonged mechanical ventilation and hospital LOS.


Transcriptional profiling of ectoderm specification to keratinocyte fate in human embryonic stem cells.
In recent years, several studies have shed light into the processes that regulate epidermal specification and homeostasis. We previously showed that a broad-spectrum γ-secretase inhibitor DAPT promoted early keratinocyte specification in human embryonic stem cells triggered to undergo ectoderm specification. Here, we show that DAPT accelerates human embryonic stem cell differentiation and induces expression of the ectoderm protein AP2. Furthermore, we utilize RNA sequencing to identify several candidate regulators of ectoderm specification including those involved in epithelial and epidermal development in human embryonic stem cells. Genes associated with transcriptional regulation and growth factor activity are significantly enriched upon DAPT treatment during specification of human embryonic stem cells to the ectoderm lineage. The human ectoderm cell signature identified in this study contains several genes expressed in ectodermal and epithelial tissues. Importantly, these genes are also associated with skin disorders and ectodermal defects, providing a platform for understanding the biology of human epidermal keratinocyte development under diseased and homeostatic conditions.


Behaviors and characteristics of African American and European American females that impact weight management.
This report explores the extent to which sociodemographic and psychosocial factors could explain differences in obesity or dietary and exercise behaviors between middle-aged African American (AA) and European American (EA) women seen in primary care. We focus on "race × predictor" interactions that could explain how AA and EA women differ in ways that affect the prevalence of obesity. This comparative exploratory study uses data from the baseline examination of the Reasonable Eating and Activity to Change Health (REACH) trial, which included 173 AA women and 278 EA women. Inclusion criteria were membership in one of the study family medicine practices, an elevated body mass index (greater than 27 kg/m(2) ), age 40 to 69 years, and no contraindications to increased activity and dietary change. Secondary data analyses were employed. There was evidence of race differences in the level of multiple variables related to weight management but there were only three significant "race × predictor" interactions out of 48 comparisons: (a) race × physical health, with BMI as the dependent variable; (b) race × the percentage of dietary fat, with total dietary kilocalories as the dependent variable; and (c) race × median income, with exercise minutes per week as the dependent variable. The results support the proposition that the weight management experience of AA and EA primary care women is similar after different exposure levels are taken into account. The results contribute to the body of literature that addresses obesity management for AA and EA women in primary care settings. Findings illustrate the need for obesity prevention and management efforts from both multidisciplinary primary care providers and community-wide public health interventions. AA and EA women have different resources, but the same factors generally influence weight management, whether one is AA or EA. This suggests that clinical interventions and public health interventions for AA and EA women can be designed around the same principles while paying attention to relevant cultural issues.


Newborn transition.
The transition from intrauterine to extrauterine life is a complex adaptation. Although, in a sense, the entire time in utero is in preparation for this transition, there are many specific anatomic and physiologic changes that take place in the weeks and days leading up to labor that facilitate a healthy transition. Some, including increasing pulmonary vasculature and blood flow, are part of an ongoing process of maturation. Others, such as a reversal in the lung from secreting fluid to absorbing fluid and the secretion of pulmonary surfactant, are associated with the hormonal milieu that occurs when spontaneous labor is impending. Interventions such as elective cesarean birth or induction of labor may interfere with this preparation for birth. Postnatal interventions such as immediate clamping of the umbilical cord and oropharyngeal suction may also compromise the normal process of newborn transition. This article reviews the physiology of the fetal to newborn transition and explores interventions that may facilitate or hinder the optimal process.


Absolute and real time experimental radiative loss measurements of spherical expanding free flames: FAIRS (Fast Absolute InfraRed Sensor)-An innovative technique.
An innovative technique was developed for the direct measurement of the absolute radiant flux emitted from transient flames. The design of the experimental device, called FAIRS (Fast Absolute Infra-Red Sensor), is detailed in this work. The main concept of FAIRS is based on the combination of a carbon nano-tube-based black body as a sensitive element, coupled to a fast IR HgCdTe detector via an achromatic optical setup. A specific calibration protocol based on a laboratory blackbody (ambient to 850 °C) allows the qualification of the FAIRS for absolute radiative heat-flux measurements, with a response time less than 1 µs that was checked, thanks to pulsed laser irradiation. It is thus demonstrated that FAIRS is a good candidate for transient measurements, with a simplified calibration procedure. FAIRS was coupled with ultra-fast schlieren imaging on spherical expanding CH4/air and C3H8/air flames. In this condition, it is possible to correlate the real time flame diameter to its absolute radiative heat losses.


Smad6 suppresses the growth and self-renewal of hepatic progenitor cells.
Activation of hepatic progenitor cells (HPCs) is commonly observed in chronic liver disease and Wnt/β-catenin signaling plays a crucial role in the expansion of HPCs. However, the molecular mechanisms that regulate the activation of Wnt/β-catenin signaling in the liver, especially in HPCs, remain largely elusive. Here, we reported that ectopic expression of Smad6 suppressed the proliferation and self-renewal of WB-F344 cells, a HPC cell line. Mechanistically, we found that Smad6 inhibited Wnt/β-catenin signaling through promoting the interaction of C-terminal binding protein (CtBP) with β-catenin/T-cell factor (TCF) complex to inhibit β-catenin mediated transcriptional activation in WB-F344 cells. We used siRNA targeting β-catenin to demonstrate that Wnt/β-catenin signaling was required for the proliferation and self-renewal of HPCs. Taken together, these results suggest that Smad6 is a regulatory molecule which regulates the proliferation, self-renewal and Wnt/β-catenin signaling in HPCs.