The Effect of Gene Flow on Coalescent-based Species-Tree Inference.
Most current methods for inferring species-level phylogenies under the coalescent model assume that no gene flow occurs following speciation. Several studies have examined the impact of gene flow (e.g., Eckert and Carstens 2008; Chung and Ané 2011; Leaché et al. 2014; Solís-Lemus et al. 2016) and of ancestral population structure (DeGeorgio and Rosenberg 2016) on the performance of species-level phylogenetic inference, and analytic results have been proven for network models of gene flow (e.g., Solís-Lemus et al. 2016; Zhu et al. 2016). However, there are few analytic results for a continuous model of gene flow following speciation, despite the development of mathematical tools that could facilitate such study (e.g., Hobolth et al. 2011; Andersen et al. 2014; Tian and Kubatko 2016). In this article, we consider a three-taxon isolation-with-migration model that allows gene flow between sister taxa for a brief period following speciation, as well as variation in the effective population sizes across the species tree. We derive the probabilities of each of the three gene tree topologies under this model, and show that for certain choices of the gene flow and effective population size parameters, anomalous gene trees (i.e., gene trees that are discordant with the species tree but that have higher probability than the gene tree concordant with the species tree) exist. We characterize the region of parameter space producing anomalous trees and show that the probability of the gene tree that is concordant with the species tree can be arbitrarily small. We then show that there is theoretical support for using SVDQuartets with an outgroup to infer the rooted three-taxon species tree in a model of gene flow between sister taxa. We study the performance of SVDQuartets on simulated data and compare it to three other commonly-used methods for species tree inference, ASTRAL, MP-EST, and concatenation. The simulations show that ASTRAL, MP-EST, and concatenation can be statistically inconsistent when gene flow is present, while SVDQuartets performs well, though large sample sizes may be required for certain parameter choices.


[Chordal cutting for the treatment of ischemic mitral regurgitation: two case reports].
The surgical treatment for ischemic mitral regurgitation remains controversal. Ring annuloplasty results in recurrent mitral regurgitation in some cases. Strut chordal cutting is a new surgical procedure in addition to ring annuloplasty for ischemic mitral regurgitation. Two patients (63-year-old woman, 53-year-old man) with severe ischemic mitral regurgitation were treated with this procedure. The patients had congestive heart failure due to mitral regurgitation, associated with inferior myocardial infarction. Regurgitant fraction of mitral regurgitation was 70% and 52% before surgery. Mitral leaflet tethering caused by apical displacement of the papillary muscle was observed. Mitral valve repair was performed by ring annuloplasty and chordal cutting. Intraoperative echocardiography showed that chordal cutting improved the configuration of the anterior leaflet, resulting in good mitral valve coaptation without regurgitation.


A glimpse into the black box of celiac disease complications: a case report with a rare presentation.
The purpose of this article is to report a case of celiac disease in a child with uncommon presentation and severe complications, and briefly review recent literature regarding celiac disease complications in children. We describe a case report of celiac disease in a child (to our knowledge, this is the first to be reported in its unique presentation in the Russian Federation) and precisely review its presenting complications with the exiting works of literature. Many cases of celiac disease in children who are not diagnosed and treated properly suffer from a plethora of complications due to malabsorption and concurrent autoimmune reactions that affect mainly but are not limited to the endocrine system. Complications of celiac disease in children should always be suspected, and evidence-based follow-up recommendations should be introduced as soon as possible because the burden of celiac disease complications in children is remarkable.


Polybrominated Diphenylethers (PBDEs) in ambient air samples at the electronic waste (e-waste) reclamation site.
Polybrominated Diphenylethers (PBDEs) were used as flame-retardants in various building materials, plastic and other polymers, airplanes, electronics etc. All or some of their congeners have been already banned in many countries, due to their persistency and adverse health effects. In this study, we are focusing on the e-wastes as a source of emission of PBDEs in ambient air during reclamation processes. The ambient air particulate matter (PM) samples were collected at and near e-waste reclamation site in Bangkok, Thailand. Results showed the presence of various homologues viz: tri, tetra, penta, hexa, and hepta-PBDEs on both PM2.5 and Total Suspended Particle (TSP) samples. The comparison of samples as a function of distance from reclamation site indicated elevated levels of PBDEs in the close proximity to e-waste site. Interestingly, a shift in the congener pattern was observed with lower brominated PBDEs being more prevalent on nearby off-site samples as compared to the PM collected at the e-waste site. The total penta-PBDEs concentration is about double on e-waste site PM2.5 compared to control site samples. For TSP, tetra, penta, and hepta-PBDEs congeners are at higher concentrations at e-waste sites and its vicinity compared to reference sites. Overall, a clear trend can be observed indicating a debromination of PBDEs to more toxic tri and tetra congeners during reclamation process and PBDEs are being translocated from treated materials to ambient air PM. BDE 30 congener is identified as a specific marker of thermal reclamation processes of e-wastes as a most stable degradation product. This work indicates potential hazards related to the reclamation of e-wastes and remediation of sites containing PBDEs. In particular, thermal treatment methods can lead to congener transformation and increased emissions of more toxic lower-brominated congeners.


[Nuclear families in Turkey].
This study examines the household or family types in Turkey in 1983, especially nuclear families. Nuclear families constitute 61.6% of all households in Turkey, and the majority of them are in the West and the Central regions. The highest % of nuclear families was found in the Mediterranean regions, and the lowest in the Black Sea region. Among all nuclear families, 87% of them consist of husband, wife and children, whereas 13% of them have only husband and wife. Nuclear families without children are common in urban areas and in the West while nuclear families with children are mostly found in rural areas and in the East and the Black Sea regions. Nuclear families with 3 or more children constitute 32% of all nuclear households in the West. On the other hand, the corresponding % is 73 for the Eastern region. As a result, it is concluded that nuclear families have significant regional and residential differentiations and households with the same formation in a developed and a less developed region should have different social, economic, and cultural characteristics.


2D gene expression parameters of wing imaginal disc of Drosophila for developmental analysis.
By using high resolution two-dimensional (2D) gel electrophoresis coupled with computer-analysis we have established a quantitative Drosophila wing imaginal disc protein database of third instar larvae as a reference to be used for comparative purposes in genetic studies. A general catalogue integrated by 1,184 (35)S-methionine-labelled polypeptides from wing imaginal disc has been obtained. The level of expression for all the proteins has been quantitatively determined. The quantitative reproducibility of the analysis system has been estimated and all the controls studied as database reference to interpret the results of experiments with mutant discs. One example, corresponding to iro (1) mutation, has been used to show how some of the changes observed with mutant discs clearly extend out of the limits defined by the controls. This enables us to generate comparative parameters for the study of proliferation, morphogenesis and differentiation of Drosophila and opens the possibility of rapidly defining the nature and quantity of changes in patterns of gene expression in developmental genetic studies.


Bilateral acute acquired toxoplasmic retinochoroiditis after steroid therapy for hantavirus pulmonary syndrome: case report.
Description of a case of acute acquired ocular toxoplasmosis following hantavirus pulmonary syndrome. A 41-year-old man presenting hantavirus pulmonary syndrome, confirmed in the laboratory by detection of IgM antibodies to the virus, was submitted to high doses of intravenous corticosteroids for two months. After clinical improvement of hantavirus pulmonary syndrome the patient presented visual loss in both eyes that was secondary to a toxoplasmosis retinitis. The retinitis resolved with anti-toxoplasma therapy. Acquired toxoplasmic retinochoroiditis can occur following steroid therapy for hantavirus pulmonary syndrome.


Appetite is associated with the time of recovery after the dialytic session in patients on chronic hemodialysis.
The aim of this cross-sectional study was to assess the correlation between self-reported appetite and the time of recovery after the hemodialysis session (TIRD). All patients on chronic hemodialysis at the Hemodialysis Service of the Catholic University of Rome underwent assessment of appetite through the first three questions of the Hemodialysis Study Appetite questionnaire, TIRD (through the question 'How long does it take you to recover from a dialysis session?'), number and severity of comorbidities according to the Charlson Comorbidity Index (CCI), and daily activities through the ADL (activities of daily living) and the IADL (instrumental activities of daily living). We studied 106 patients. According to the appetite questionnaire, in 45 patients appetite was very good or good (group 1), in 33 fair (group 2) and in 28 poor or very poor (group 3). Age, CCI, TIRD and serum parathyroid hormone levels were significantly higher in group 3 than in groups 1 and 2, while the IADL was significantly lower. Age, CCI, TIRD, IADL and serum parathyroid hormone were significantly correlated with appetite. At multiple regression analysis, TIRD and CCI only were independently correlated with appetite. Poor appetite is independently associated with the time of recovery after the hemodialysis session.


Cost effectiveness in new technology in cervix cancer screening.
The new techniques in cervix cancer screening are reviewed. Literature relevant to the performance and cost effectiveness of these technologies is reviewed. Literature relevant to cost effectiveness of other techniques used for cervix cancer screening is reviewed. Prospective trials of competing technology are proposed to resolve the question utilizing contemporaneous methods of assessing cost effectiveness.


Endogenous soluble receptor for advanced glycation endproducts is increased in preeclampsia.
Preeclampsia is a serious complication in pregnancy with an increased future cardiovascular risk for both mother and newborn. Recently, low levels of endogenous soluble receptor for advanced glycation endproducts (esRAGE) have been associated with increased cardiovascular risk. In the current study, we investigated esRAGE serum levels in patients with preeclampsia as compared to healthy gestational age-matched controls. esRAGE was quantified by enzyme-linked immunosorbent assay in controls and patients with preeclampsia during pregnancy (control: n = 20, preeclampsia: n = 16) and 6 months after delivery (control: n = 19, preeclampsia: n = 15). Furthermore, esRAGE was correlated to clinical and biochemical measures of renal function, glucose and lipid metabolism, as well as inflammation. During pregnancy, median maternal serum esRAGE concentrations were more than three-fold higher in patients with preeclampsia (200 ng/l) than in controls (63 ng/l) (P < 0.01). Furthermore, esRAGE levels positively correlated with age, blood pressure, creatinine, adiponectin, and C-reactive protein, whereas a negative correlation existed with fasting insulin and the homeostasis model assessment of insulin resistance index. In multivariate analyses, homeostasis model assessment of insulin resistance and C-reactive protein independently predicted esRAGE serum levels and explained 44% of the variation in esRAGE concentrations. Surprisingly, median esRAGE concentrations 6 months after delivery were significantly lower in former patients with preeclampsia (270 ng/l) than in controls (342 ng/l) in contrast to the results obtained during pregnancy. We showed that maternal esRAGE concentrations are significantly increased in patients with preeclampsia during pregnancy. Here, insulin sensitivity and inflammatory status independently predict serum esRAGE levels.


Use of melatonin in the treatment of phase shift and sleep disorders.
When administered to humans the pineal hormone melatonin can phase shift a number of circadian rhythms. This property has prompted the investigation of exogenous melatonin in sleep disorders known to have an underlying chronophysiological basis (i.e. circadian rhythm sleep disorders). Both in field and simulated studies of jet lag and shift work suitably timed melatonin improved sleep and, in some cases, hastened readaptation of the circadian rhythms following the phase shift. Melatonin treatment has also been evaluated in the circadian sleep disorders: delayed sleep phase syndrome (DSPS) and non-24-hour sleep wake disorder. Compared with placebo, melatonin advanced the sleep period in subjects with DSPS. Melatonin also improved a number of sleep parameters in blind subjects suffering from non-24-hour sleep wake disorder.


Generalized theory of steady-state voltammetry without a supporting electrolyte. Effect of product and substrate diffusion coefficient diversity.
A generalized theory of the steady-state voltammetric response of a microelectrode in the absence of supporting electrolyte and for any values of diffusion coefficients of the substrate and the product of an electrode process is presented. The treatment applies to any reasonable combination of the charge numbers of the substrate, its counterion, and the product. A way to incorporate the activation polarization into the model is also demonstrated. It has been shown that the height, position, and shape of the migrational voltammogram are affected by the ratio of the product to substrate diffusivity (theta). In particular, for the electrode processes with sign retention, unequal diffusivities of electroactive species influence both characteristic points of the voltammogram (the limiting current and the half-wave potential). For charge neutralization processes (uncharged product), the changes in theta parameter are accompanied only by a shift in the half-wave potential. The most dramatic changes in the I-E relation can be observed for the charge reversal processes. In this case, a consecutive increase in theta results in the transition of the voltammogram shape from rapid exponential growth (theta < 1), through ramp shape (theta = 1), to common wave shape (theta > 1). On the basis of the expressions derived for the limiting current (exact and linearized), a possibility of the determination of the diffusion coefficient of the electrode reaction product is demonstrated. In addition, the ranges of theta where the assumption of equal diffusivities of the substrate and the product is obeyed within an insignificant error have been determined quantitatively. The theory has been experimentally verified using voltammetric oxidation of hexacyanoferrate(II).


Integrin activation by R-ras.
Expression of a constitutively active R-ras converted two cell lines that grow in suspension into highly adherent cells. There was little change in cell surface expression of integrins, but attachment to surfaces coated with the integrin ligands was greatly enhanced. Cells transfected with activated R-ras bound integrin ligands from solution with higher affinities and assembled severalfold more fibronectin matrix than control transfectants. Introduction of a dominant negative R-ras into adherent cells reduced the adhesiveness of the cells, indicating that endogenous R-ras can control the ligand-binding activity of integrins. These results provide a mechanism for the modulation of integrin ligand-binding activity as well as novel function for R-ras.


Intravenous fluorescein for detection of perilymphatic fistulas.
It has been reported, in animal models and recently in human beings, that intravenous fluorescein is taken up in perilymph and may be useful as a tracer for the detection of perilymphatic fistulas. We attempted to reproduce the results of these animal experiments. Twenty-one middle ears of eight cats and four dogs were exposed. Fluorescein was given intravenously. Fluorescence was initially noted in transudates pooling in the oval and round window niches. Fistulas created with a straight pick produced a bright fluorescence in the leaking fluids, possibly from a ruptured small membrane vessel. Fistulas created with the carbon dioxide laser and with complete hemostasis demonstrated no fluorescence. We concluded that intravenously administered fluorescein causes dramatic fluorescence of vessels and transudates that may be interpreted falsely as fluorescence of perilymph. Fluorescence was not evident in perilymph when complete hemostasis was obtained.


P2X receptors in peripheral neurons.
P2X receptors are a family of ligand-gated ion channels, activated by extracellular ATP. The seven subunits cloned (P2X1-7) can assemble to form homomeric and heteromeric receptors. Peripheral neurons of neural crest origin (e.g. those in dorsal root, trigeminal, sympathetic and enteric ganglia) and placodal origin (e.g. those in nodose and petrosal ganglia) express mRNAs for multiple P2X subunits. In this review, we summarize the molecular biological, electrophysiological and immunohistochemical evidence for P2X receptor subunits in sensory, sympathetic, parasympathetic, pelvic and myenteric neurons and adrenomedullary chromaffin cells. We consider the pharmacological properties of these native P2X receptors and their physiological roles. The responses of peripheral neurons to ATP show considerable heterogeneity between cells in the same ganglia, between ganglia and between species. Nevertheless, these responses can all be accounted for by the presence of P2X2 and P2X3 subunits, giving rise to varying proportions of homomeric and heteromeric receptors. While dorsal root ganglion neurons express predominantly P2X3 and rat sympathetic neurons express mainly P2X2 receptors, nodose and guinea-pig sympathetic neurons express mixed populations of P2X2 and heteromeric P2X2/3 receptors. P2X receptors are important for synaptic transmission in enteric ganglia, although their roles in sympathetic and parasympathetic ganglia are less clear. Their presence on sensory neurons is essential for some processes including detection of filling of the urinary bladder. The regulation of P2X receptor expression in development and in pathological conditions, along with the interactions between purinergic and other signalling systems, may reveal further physiological roles for P2X receptors in autonomic and sensory ganglia.


Blood transfusion is associated with donor leukocyte microchimerism in trauma patients.
Blood transfusion can result in survival of donor leukocyte subpopulations in the recipient. Persistence of donor leukocytes in the transfusion recipient is termed microchimerism. Microchimerism likely reflects engraftment of the recipient with donor hematopoietic stem cells and is very uncommon with transfusion for elective surgery, sickle cell anemia, thalassemia, and HIV. We have found, however, that microchimerism may be more common in trauma patients. To determine how frequently transfusion after trauma is associated with microchimerism. We prospectively enrolled 45 trauma patients who were transfused > or =2 units of PRBCs. We sampled blood before hospital discharge and determined microchimerism by polymerase chain reaction (PCR) analysis of specimens using quantitative allele-specific HLA DR assays to detect non-recipient alleles. Data are expressed as median with interquartile range. Patients had a median age of 38 (interquartile range 25, 58) years, ISS of 19 (13, 29), and mortality of 7%. Seventy-eight percent were men, and 84% had blunt trauma. Patients received a median of 6 (4, 16) (range 2, 87) units of PRBCs. Of the 45 patients, 24 (53%) had evidence of microchimerism. Compared with patients without evidence of microchimerism, these patients had no difference in mean age, gender, ISS, units of PRBCs transfused, time from transfusion to blood sampling, or proportion that underwent splenectomy. Twenty-one of the 24 patients with microchimerism had only 1 or 2 non-recipient DR alleles identified by PCR. Transfusion after trauma is associated with over half of recipients having evidence of microchimerism. Age, sex, ISS, and splenectomy of the recipient and the number of transfused units did not correlate with microchimerism. Because the median time from transfusion to sampling for PCR analysis was not longer in the group without microchimerism, it is unlikely microchimerism is due merely to failure of the recipient to clear transfused donor leukocytes.


Intraguild indirect effects through trophic cascades between stream-dwelling fishes.
1. To examine the strength and role of indirect effects through trophic cascades by omnivorous fish on algal biomass in streams, we introduced one of four fish species (ayu Plecoglossus altivelis altivelis, pike gudgeon Pseudogobio esocinus esocinus, Japanese dace Tribolodon hakonensis and pale chub Zacco platypus) in experimental pools. We also investigated the indirect effects of gudgeon, dace and chub on the growth of ayu. 2. We chose the four fish species across a continuum of omnivory. Ayu fed mainly on benthic algae, and gudgeon predominantly on invertebrates. Dace and chub fed on both algae and invertebrates, but dace preyed on invertebrates more than chub. 3. The presence of gudgeon, dace and chub reduced the number of algal-feeding invertebrates and increased the algal biomass through trophic cascades. Consequently, ayu growth rate over the experimental period in pools with one of the three fish species was 25.9-44.1 times greater than the growth rate in pools with only ayu. 4. The positive indirect effect on ayu growth was large for gudgeon and dace and small for chub, whereas the addition of ayu reduced ayu growth considerably due to intraspecific competition. 5. The relative intensity of indirect effects on ayu growth through trophic cascades was predictable from the food overlap between ayu and the other fishes. However, the similar strength of indirect effects by gudgeon and dace that fed differently on algae and invertebrates suggests that feeding behaviour, prey preference and trait-mediated indirect interactions were also important in the prediction.


HLA complex-linked heat shock protein genes and childhood acute lymphoblastic leukemia susceptibility.
Three heat shock protein 70 (HSP70) genes, HSPA1L, HSPA1A, and HSPA1B, are located within the human leukocyte antigen (HLA) class III region. HSPs act as stress signals and regulate natural killer cell response to cancer. HSP70 gene polymorphisms show disease associations partly due to their linkage disequilibrium with HLA alleles. To systematically evaluate their associations with childhood acute lymphoblastic leukemia (ALL), we examined the three functional single nucleotide polymorphisms (SNPs) rs2227956 (T493M) in HSPA1L, rs1043618 in HSPA1A 5'UTR, and rs1061581 (Q351Q) in HSPA1B by TaqMan assays or polymerase chain reaction-restriction fragment length polymorphism in 114 ALL cases and 414 controls from Wales (UK), in 100 Mexican Mestizo ALL cases and 253 controls belonging to the same ethnic group, and in a panel of 82 HLA-typed reference cell line samples. Homozygosity for HSPA1B rs1061581 minor allele G was associated with protection (odds ratio (OR) = 0.37, 95% confidence interval (CI) = 0.16-0.78; P = 0.007) with gene-dosage effect (additive model) reaching significance (P = 0.0001) in the Welsh case-control group. This association was replicated in the second case-control group from Mexico (OR (recessive model) = 0.49, 95% CI = 0.24-0.96; P = 0.03), and the pooled analysis yielded a strong association (Mantel-Haenszel OR = 0.43, 95% CI = 0.27-0.69, P = 0.0004). The association was stronger in males in each group and in the pooled analysis. A three-SNP haplotype including the major allele A of rs1061581 showed a highly significant increase in Welsh cases compared with respective controls (6.7% vs 1.8%; P = 0.0003) due to the difference between male cases and controls. The protective allele of rs1061581 occurred more frequently on the HLA-DRB3 haplotypes (especially DRB1*03) in the cell line panel, but the HSPA1B association was independent from the HLA-DRB4 association previously detected in the same case-control group from Wales (adjusted P = 0.001). Given the cancer promoting roles played by HSPs intracellularly as well as roles in immune surveillance when expressed on the cell surface and the known correlations between expression levels and the HSP polymorphisms, these results are likely to indicate a primary association and warrant detailed assessment in childhood ALL development.


Thermochemical valorization and characterization of household biowaste.
Valorization of municipal solid waste (MSW), by means of energy and material recovery, is considered to be a crucial step for sustainable waste management. A significant fraction of MSW is comprised from food waste, the treatment of which is still a challenge. Therefore, the conventional disposal of food waste in landfills is being gradually replaced by recycling aerobic treatment, anaerobic digestion and waste-to-energy. In principle, thermal processes like combustion and gasification are preferred for the recovery of energy due to the higher electrical efficiency and the significantly less time required for the process to be completed when compared to biological process, i.e. composting, anaerobic digestion and transesterification. Nonetheless, the high water content and the molecular structure of biowaste are constraining factors in regard to the application of thermal conversion pathways. Investigating alternative solutions for the pre-treatment and more energy efficient handling of this waste fraction may provide pathways for the optimization of the whole process. In this study, by means of utilizing drying/milling as an intermediate step, thermal treatment of household biowaste has become possible. Household biowaste has been thermally processed in a bench scale reactor by means of torrefaction, carbonization and high temperature pyrolysis. According to the operational conditions, fluctuating fractions of biochar, bio-oil (tar) and syngas were recovered. The thermochemical properties of the feedstock and products were analyzed by means of Simultaneous Thermal Analysis (STA), Ultimate and Proximate analysis and Attenuated Total Reflectance (ATR). The analysis of the products shows that torrefaction of dried household biowaste produces an energy dense fuel and high temperature pyrolysis produces a graphite-like material with relatively high yield.


Quantification of P450scc, P450(17) alpha, and iron sulfur protein reductase in Leydig cells and adrenals of inbred strains of mice.
The relationship of maximal testosterone production to the amounts of cholesterol side-chain cleavage (P450scc), 17 alpha-hydroxylase/C17-20 lyase (P450(17) alpha), and iron sulfur protein (ISP) reductase was determined in Leydig cells from four inbred strains of mice (RF/J, SWR/J, C3H/He, and DBA/2). The amounts of P450scc, P450(17) alpha, and ISP reductase were also determined in adrenal glands of the same mice. cAMP-stimulated testosterone production and P450scc protein were high in RF/J and SWR/J compared to C3H/He and DBA/2 Leydig cells. A significant correlation between the amount of this enzyme and the capacity for testosterone production was found (r = 0.89; P less than 0.0005). ISP reductase was highest in RF/J, SWR/J, and C3H/He Leydig cells, which are significantly different from DBA/2. No significant differences in the amount of P450(17) alpha in Leydig cells from the four strains could be detected, and neither ISP reductase nor P450(17) alpha correlated with testosterone production. To ascertain if tissue-specific factors affect the expression of these enzymes, P450scc, ISP reductase, and P450(17) alpha were quantitated in adrenals from the same mice. P450scc and ISP reductase were expressed differently in adrenals compared to Leydig cells; levels of both proteins were high in C3H/He and RF/J adrenals compared to SWR/J and DBA/2. P450scc and ISP reductase were coordinately expressed in the adrenal, unlike in Leydig cells. P450(17) alpha was not detected in mouse adrenal glands. The results of this study suggest that strain-related differences in the capacity of Leydig cells for testosterone production may be determined by the amount of P450scc per Leydig cell. The expression of P450scc and ISP reductase in Leydig cells and adrenal glands appears to be influenced by both genetic and tissue-specific factors.


Alcohol Inhibits Odontogenic Differentiation of Human Dental Pulp Cells by Activating mTOR Signaling.
Long-term heavy alcohol consumption could result in a range of health, social, and behavioral problems. People who abuse alcohol are at high risks of seriously having osteopenia, periodontal disease, and compromised oral health. However, the role of ethanol (EtOH) in the biological functions of human dental pulp cells (DPCs) is unknown. Whether EtOH affects the odontoblastic differentiation of DPCs through the mechanistic target of rapamycin (mTOR) remains unexplored. The objective of this study was to investigate the effects of EtOH on DPC differentiation and mineralization. DPCs were isolated and purified from human dental pulps. The proliferation and odontoblastic differentiation of DPCs treated with EtOH were subsequently investigated. Different doses of EtOH were shown to be cytocompatible with DPCs. EtOH significantly activated the mTOR pathway in a dose-dependent manner. In addition, EtOH downregulated the alkaline phosphatase activity, attenuated the mineralized nodule formation, and suppressed the expression of odontoblastic markers including ALP, DSPP, DMP-1, Runx2, and OCN. Moreover, the pretreatment with rapamycin, a specific mTOR inhibitor, markedly reversed the EtOH-induced odontoblastic differentiation and cell mineralization. Our findings show for the first time that EtOH can suppress DPC differentiation and mineralization in a mTOR-dependent manner, indicating that EtOH may be involved in negatively regulating the dental pulp repair.


Cytotoxic Potential of the Novel Horseshoe Crab Peptide Polyphemusin III.
Biological activity of the new antimicrobial peptide polyphemusin III from the horseshoe crab Limulus polyphemus was examined against bacterial strains and human cancer, transformed, and normal cell cultures. Polyphemusin III has the amino acid sequence RRGCFRVCYRGFCFQRCR and is homologous to other β-hairpin peptides from the horseshoe crab. Antimicrobial activity of the peptide was evaluated and MIC (minimal inhibitory concentration) values were determined. IC50 (half-maximal inhibitory concentration) values measured toward human cells revealed that polyphemusin III showed a potent cytotoxic activity at concentrations of <10 μM. Polyphemusin III caused fast permeabilization of the cytoplasmic membrane of human leukemia cells HL-60, which was measured with trypan blue exclusion assay and lactate dehydrogenase-release assay. Flow cytometry experiments for annexin V-FITC/ propidium iodide double staining revealed that the caspase inhibitor, Z-VAD-FMK, did not abrogate disruption of the plasma membrane by polyphemusin III. Our data suggest that polyphemusin III disrupts the plasma membrane integrity and induces cell death that is apparently not related to apoptosis. In comparison to known polyphemusins and tachyplesins, polyphemusin III demonstrates a similar or lower antimicrobial effect, but significantly higher cytotoxicity against human cancer and transformed cells in vitro.


Chromosome Microdissection on Semi-Archived Material.
Glass needle-based chromosome microdissection (midi) is a standard approach developed in the 1980s and remains more frequently applied in testing than the comparable technique using laser-based platforms. As the amount of DNA extracted by this technique is minimal and often in the range of picograms, the isolated DNA must be further amplified prior to use; the isolated amplified product can be readily utilized in multiple molecular research and diagnostic investigation. DNA libraries created by midi are either chromosome- or chromosome-region-specific. However, a critical component to this process is the need for timely chromosome preparation via the air-drying method not to exceed a ~2-3 h before midi is performed. Failure of this time-sensitive step often results in the chromosomes drying out after dropping, and upon initiation of the midi technique, the dissected material can jump away while touching by the needle, and collection of a suitable sample is inhibited. Herein, we demonstrate with a simple adaptation of the standard procedure, midi can be performed on semi-archived material stored for longer periods at -20°C. Thus, the critical step to obtain well-spread chromosome preparations can be completed under established conditions, for example, in the primary laboratory, stored at -20°C, and sent directly to specialized reference laboratories offering midi. In our study, we were able to obtain high-quality DNA libraries, as verified by gel electrophoreses and reverse fluorescence in situ hybridization, via midi extracted chromosome spreads derived from human, fish, snake, lampbrush, and insect stored for up to 6 months. © 2019 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.


Treating osteoporosis with bisphosphonates and addressing adherence: a review of oral ibandronate.
Osteoporosis is a common, chronic condition, affecting approximately half of all postmenopausal Caucasian women in the US. Vertebral fractures occur as a result of osteoporosis and lead to increased hospitalisation and mortality, and adversely affect patient quality of life. The burden of osteoporosis on healthcare systems is expected to rise as the elderly population continues to grow. Yet there are many medications for preventing and treating osteoporosis. Oral bisphosphonates are first-line treatment for osteoporosis, with demonstrated efficacy in increasing bone mineral density and reducing bone turnover, which reduces the incidence of fractures. However, adherence to medication is suboptimal, with approximately 40% of patients discontinuing treatment within 6 months. Recent reports have suggested simplifying the dosage regimen as a strategy to help address this issue. Ibandronate is a potent, nitrogen-containing bisphosphonate which is administered once-monthly. Preclinical studies initially revealed the feasibility of extending the between-dose interval. Subsequent clinical studies have provided further evidence of the positive effects of extended-interval ibandronate administration in reducing the risk of vertebral fractures through increasing bone mineral density and reducing bone turnover without compromising bone quality. These studies have also demonstrated that ibandronate has a safety profile similar to placebo. Ibandronate has recently been approved for use in the US to treat postmenopausal osteoporosis. This review summarises the efficacy and safety of once-monthly oral ibandronate and discusses the implications of such a treatment in primary care in the US.


Are chirps better than clicks and tonebursts for evoking middle latency responses?
The middle latency response (MLR) is considered a valid clinical tool for assessing the integrity of cortical and subcortical structures. Several investigators have demonstrated that a rising frequency chirp stimulus is capable of eliciting not only larger wave V amplitudes but larger MLR components as well. However, the chirp has never been specifically examined in a hemispheric electrode montage setup that is typical for neurodiagnostic application and site-of-lesion testing. The purpose of this study was to examine the effect of chirp, click, and toneburst stimuli on MLR waveform peak latency and peak-to-peak amplitude in a hemispheric electrode montage setup. This study used a repeated-measures design. A total of 10 young adult participants (3 males, 7 females) with normal hearing were recruited and had negative histories of audiologic, otologic, and neurologic involvement, and no reported language or learning difficulties. MLR latencies (Na, Pa, Nb, and Pb) and peak-to-peak amplitudes (Na-Pa, Pa-Nb, and Nb-Pb) were measured for all conditions and were statistically evaluated for left hemisphere-right ear (C3-A2) and right hemisphere-left ear (C4-A1) recordings. Statistical analyses revealed no significant difference between C3-A2 and C4-A1 peak-to-peak amplitudes; therefore, data were collapsed. Stimulus comparisons revealed that Na evoked by tonebursts were statistically prolonged compared with both chirp and click, and that both Na-Pa and Pa-Nb peak-to-peak amplitudes were statistically larger for chirps compared with both clicks and tonebursts, and for clicks compared with tonebursts. The results of this study support the hypothesis that a chirp would offer a clinical advantage to the click and toneburst in overall peak-to-peak amplitude. As expected, normal-hearing participants did not exhibit hemispheric differences when comparing C3-A2 and C4-A1 peak-to-peak amplitudes demonstrating symmetric auditory brain function. However, chirp-evoked MLRs will require further study to determine its usefulness in clinical practice.


erythro-5-[1-Hydroxy-2-(isopropylamino)butyl]-7-hydroxycarbostyril, a terbutaline-type derivative of the bronchodilator procaterol.
erythro-5-[1-Hydroxy-2-(isopropylamino)butyl]-7-hydroxycarbostyril (4), which is a terbutaline-type derivative of the bronchodilator procaterol, was synthesized by transfer of the 8-hydroxyl group of procaterol to the 7 position. Compound 4 showed less potent beta-adrenoceptor stimulant activities than procaterol or terbutaline in an in vitro test using guinea pig tracheal muscle and right atrium. In an in vivo assay on anesthetized dogs, compound 4 showed 42 times less bronchodilator activity and 87 times less effect on the heart rate than l-isoproterenol.


Root-type ferredoxin-NADP+ oxidoreductase isoforms in Arabidopsis thaliana: Expression patterns, location and stress responses.
In Arabidopsis, two leaf-type ferredoxin-NADP+ oxidoreductase (LFNR) isoforms function in photosynthetic electron flow in reduction of NADP+ , while two root-type FNR (RFNR) isoforms catalyse reduction of ferredoxin in non-photosynthetic plastids. As the key to understanding, the function of RFNRs might lie in their spatial and temporal distribution in different plant tissues and cell types, we examined expression of RFNR1 and RFNR2 genes using β-glucuronidase (GUS) reporter lines and investigated accumulation of distinct RFNR isoforms using a GFP approach and Western blotting upon various stresses. We show that while RFNR1 promoter is active in leaf veins, root tips and in the stele of roots, RFNR2 promoter activity is present in leaf tips and root stele, epidermis and cortex. RFNR1 protein accumulates as a soluble protein within the plastids of root stele cells, while RFNR2 is mainly present in the outer root layers. Ozone treatment of plants enhanced accumulation of RFNR1, whereas low temperature treatment specifically affected RFNR2 accumulation in roots. We further discuss the physiological roles of RFNR1 and RFNR2 based on characterization of rfnr1 and rfnr2 knock-out plants and show that although the function of these proteins is partly redundant, the RFNR proteins are essential for plant development and survival.


A modification of the Health Assessment Questionnaire for the spondyloarthropathies.
A functional status measure was developed by adding 5 items to the Health Assessment Questionnaire (HAQ-S), and compared to anthropometric measures of spinal mobility. Forty-four patients with spondylitis were evaluated by the HAQ-S and measures of spine flexibility (finger-to-floor, Smythe test, neck rotation, and chest expansion). Modification of the HAQ raised the mean difficulty score by 29% from 0.38 (SD = 0.49) to 0.49 (SD = 0.51), indicating increased ability to capture functional limitations. Neck rotation correlated most strongly with the HAQ-S score (r = -0.57), which suggests an important role for this measure in clinical management and followup of spondylitis.


Primary intrathoracic liposarcomas: A clinicopathologic and molecular study of 43 cases in one of the largest medical centers of China.
Primary intrathoracic liposarcoma is extremely rare, and most published series lack genetic analyses. The aim of our study is to better understand the clinicopathologic and genetic features of these rare lesions. Forty-three primary intrathoracic liposarcomas were identified and most cases were analyzed by systematic genetic studies, including fluorescence in situ hybridization (FISH), whole-exome sequencing (WES), and Sanger sequencing. This series included 27 males and 16 females (ratios, 1.68:1) aged 24-73 years (median, 53 years). Tumors mainly occurred in the mediastinum (n=23, 53.5%), followed by pleural cavity (n=16, 37.2%) and lung (n=4, 9.3%). The study included 21 well-differentiated liposarcomas (WDLs), 19 dedifferentiated liposarcomas (DDLs), 2 myxoid pleomorphic liposarcomas (MPLs) and 1 pleomorphic liposarcoma (PL), without identification of myxoid liposarcoma. FISH analysis identified MDM2 amplification in 17 of 18 WDLs (94.4%) and all DDLs (16/16, 100.0%). The MDM2-nonamplified WDL was CDK4-nonamplified but FRS2-amplified. WES and Sanger sequencing found somatic TP53 mutation in the 2 MPLs. Follow-up information was available for 33 of 38 cases (86.8%). Thirteen patients (39.4%) showed no evidence of disease, 10 patients (30.3%) were alive with disease, and 8 patients (24.2%) died of disease. Fourteen cases developed recurrence and 1 with metastasis. WDL/DDL was the overwhelming subtype in this location, followed by MPL and PL. Analysis of the FRS2 gene, in combination with MDM2 and other genes of 12q13-15, may more precisely characterize WDL/DDLs. MPL is the most fatal subtype of this site. Further studies are needed to explore the role of TP53 in the pathogenesis of MPL.


Application of microcatheter shaping based on computational fluid dynamics simulation of cerebral blood flow in the intervention of posterior communicating aneurysm of the internal carotid artery.
The present study aimed to investigate the application of the aneurysm embolization microcatheter plasticity method based on computational fluid dynamics (CFD) to simulate cerebral blood flow in the interventional treatment of posterior communicating aneurysms in the internal carotid artery and to evaluate its practicality and safety. A total of 20 patients with posterior internal carotid artery communicating aneurysms who used CFD to simulate cerebral flow lines from January 2020 to December 2022 in our hospital were analyzed. Microcatheter shaping and interventional embolization were performed according to the main cerebral flow lines, and the success rate, stability, and effect of the microcatheter being in place were analyzed. Among the 20 patients, the microcatheters were all smoothly placed and the catheters were stable during the in vitro model test. In addition, the microcatheters were all smoothly placed during the operation, with a success rate of 100%. The catheter tips were stable and well-supported intraoperatively, and no catheter prolapse was registered. The aneurysm was completely embolized in 19 cases immediately after surgery, and a small amount of the aneurysm neck remained in one case. There were no intraoperative complications related to the embolization catheter operation. Microcatheter shaping based on CFD simulation of cerebral blood flow, with precise catheter shaping, leads to a high success rate in catheter placing, stability, and good support, and greatly reduces the difficulty of catheter shaping. This catheter-shaping method is worthy of further study and exploration.


Radon exposure in the thermal spas of Lesvos Island--Greece.
The aim of this work is to study the exposure due to radon to bathers and personnel in the spas of Lesvos Island under a specific use pattern. 222Rn concentrations in the supplying water were measured during a long time period. Variations in indoor 222Rn, attached and unattached progenies, and influence of the ambient atmosphere were thoroughly analysed during bath treatment for the purpose of investigating a consequent probable short-term health impact. Concentration peaks both for 222Rn and PAEC were found to appear during bathtubs filling. These peaks considered imposing an additional short-term radiation burden for spa users. The additional doses delivered to bathers during bath treatment were found to be very low and for personnel did not exceed the value of 5 mSv per year.


UVA and endogenous photosensitizers--the detection of singlet oxygen by its luminescence.
UVA irradiation (320-400 nm) comprises about 95 percent of incident midday solar ultraviolet irradiation. It penetrates skin much deeper than UVB irradiation. The absorption of UVA irradiation in endogenous chromophores frequently leads to the generation of reactive oxygen species such as singlet oxygen ((1)O(2)). (1)O(2) is an important biochemical intermediate in multiple biological processes. Beside other procedures, the direct detection of (1)O(2) by its luminescence is a powerful tool that helps to understand the generation of (1)O(2) during UVA exposure in solution, in vitro and in vivo. This article describes the endogenous photosensitizers, their ability to generate (1)O(2) under UVA irradiation, and the detection technology to visualize the action of (1)O(2).


Pulmonary toxicity of systemic terbium chloride in mice.
Terbium (Tb) is a rare earth metal that finds use in several emerging technologies. However, little is known about the biological effects of Tb. Thus, in this study the pulmonary toxicity of systemic Tb in mice was investigated. Mice were treated intravenously with a single dose of 20 or 200 mumol Tb/kg, as TbCly and killed at 3, 6, 12, 24, 48, or 72 h later. Administration of Tb at a dose of 200 mumol/kg increased pulmonary weight, lipid peroxidation, and protein content but decreased pulmonary glutathione content. Pulmonary gamma-glutamyl transpeptidase (gamma-GTP) activity was increased after Tb administration at a dose of 200 mumol/kg. Pulmonary alkaline phosphatase (ALP) activity was also increased after Tb administration at a dose of 200 mumol/kg. Investigation of the defense system against oxidative damage in the lung showed that superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were all decreased after Tb administration at the higher dose. The concentrations of Tb, Ca, and P in lung was increased by the dose of 200 mumol/kg. These results suggest that pulmonary lipid peroxidation may be an early and sensitive consequence of Tb exposure and that SOD, CAT, and GSH-Px might be considered as potential modulators of Tb-induced lipid peroxidation. The mechanisms involved in Tb-induced pulmonary lipid peroxidation deserve further study.


Hypoglycemia after accidental pediatric sulfonylurea ingestions.
Because the prevalence of type 2 diabetes increases annually, there has been an increase in pediatric exposures to sulfonylureas. These medications are associated with delayed and often prolonged hypoglycemia. As such, most authorities but not all recommend admission for all pediatric patients with an accidental sulfonylurea ingestion. This study is a retrospective chart review of all pediatric patients with sulfonylurea exposures admitted for 9 years at an urban, pediatric teaching hospital. The incidence and characteristics of the hypoglycemia were recorded and analyzed. During this time span, 93 patients with accidental sulfonylurea exposures were admitted, with a median age of 1.83 years. Glyburide and glipizide accounted for most sulfonylureas. Hypoglycemia (blood glucose level <50 mg/dL) developed in 25 (58.1%) of 43 patients who ingested glipizide, compared with 10 (25.6%) of 39 patients who ingested glyburide. The overall incidence of hypoglycemia was 44%. Hypoglycemia was more likely to occur with glipizide ingestion than glyburide (odds ratio, 3.89 [95% confidence interval, 1.51-9.98]). No patient with a known time of ingestion developed hypoglycemia after 13 hours. Hypoglycemia is common after accidental sulfonylurea exposures. The results of this study support mandatory admission to a monitored setting for at least 16 hours, with frequent glucose determinations.


Improvement in phosphorescence efficiency through tuning of coordination geometry of tridentate cyclometalated platinum(II) complexes.
A series of tridentate cyclometalated platinum(II) complexes (C(∧)N*N)PtL (L = Cl or acetylide) featuring a fused five-six-membered metallacycle were synthesized. The structure of the complexes was confirmed by X-ray crystallography. In contrast to the C(∧)N(∧)N platinum complexes with a fused five-five-membered metallacycle, the platinum coordination in C(∧)N*N complexes is much closer to a square planar geometry. The photophysical properties of the complexes were studied. The geometrical change from C(∧)N(∧)N to C(∧)N*N led to a substantial improvement in phosphorescence efficiency of the complexes with an acetylide ligand in solution at room temperature. For example, the quantum yield of (C(∧)N*N)PtCCPh was measured to be 56%, demonstrating a big jump from 4% reported for (C(∧)N(∧)N)PtCCPh.


Changes in and stability of cardiovascular responses to behavioral stress: results from a four-year longitudinal study of children.
This study examined the changes in and stability of cardiovascular responses to behavioral stress among 132 children in a 4-year longitudinal study. Children's heart rate and blood pressure were measured at rest and while performing 3 tasks: serial subtraction, mirror image tracing, and isometric exercise. This procedure was followed at study entry when children were in grades 2-12 (ages 6-18 years) and at follow-up when children were in grades 6 through post-high school (ages 11-21 years). Results showed that blood pressure and heart rate responses during the tasks were reliable across time for all measures except heart rate responses during isometric exercise. Systolic blood pressure responses to all tasks increased with age for boys, but not for girls. These results support the notion that cardiovascular responses to behavioral stress are a stable individual difference variable.


Spontaneous Malignant T-cell Lymphoma in a Young Adult Crl:CD (SD) Rat.
We investigated a case of spontaneous malignant T-cell lymphoma observed in a 19-week-old male Crl:CD (SD) rat. The rat showed paralysis beginning 1 week before euthanasia. Hematological examination revealed marked lymphocytosis without distinct atypia. Macroscopically, hepatosplenomegaly and partial atrophy of the thoracic spinal cord were observed. Microscopically, neoplastic cells infiltrated into the liver, splenic red pulp, bone marrow and epidural space of the thoracic spinal cord, while no neoplastic cells were observed in the thymus and lymph nodes. Moreover, the spinal cord showed focal degeneration due to compression by marked infiltration of neoplastic cells in the subdural space. The neoplastic cells were generally small-sized round cells that had a round nucleus with/without a single nucleolus and scanty cytoplasm. Immunohistochemically, the neoplastic cells were positive for CD3 and CD8 and negative for CD79α. Judging from these results, the present tumor in this young adult rat was diagnosed as malignant T-cell lymphoma.


Genetic polymorphisms of debrisoquine and S-mephenytoin oxidation metabolism in Chinese populations: a meta-analysis.
Chinese data on the polymorphic metabolism of debrisoquine, metoprolol, codeine and mephenytoin were collected and re-analysed using a meta-analysis method. There were no significant differences in the incidences of poor metabolizer (PM) between the separate series of debrisoquine, metoprolol and codeine, which are the three probe drugs reflecting the same enzyme polymorphism. PMs were detected at low frequencies for debrisoquine (1.20%; 95% confidence interval, CI: 0.67-1.98%), metoprolol (0.72%; CI: 0.29-1.49%) and codeine (0.48%, CI: 0.01-2.68%). The overall estimate of PM was 0.95% (CI: 0.60-1.42%) based on the 2427 determinations of all three probe drugs. The overall mean of PM of mephenytoin was 14.32% (12.26-16.38%) in the 1117 subjects. In summary, the present meta-analysis determined the accurate incidences of the genetic deficiency of S-mephenytoin 4'-hydroxylase (cytochrome P450 2C19) and debrisoquine hydroxylase (cytochrome P450 2D6) in Chinese populations.


Structure, function, and inhibitor targeting of HIV-1 Nef-effector kinase complexes.
Antiretroviral therapy has revolutionized the treatment of AIDS, turning a deadly disease into a manageable chronic condition. Life-long treatment is required because existing drugs do not eradicate HIV-infected cells. The emergence of drug-resistant viral strains and uncertain vaccine prospects highlight the pressing need for new therapeutic approaches with the potential to clear the virus. The HIV-1 accessory protein Nef is essential for viral pathogenesis, making it a promising target for antiretroviral drug discovery. Nef enhances viral replication and promotes immune escape of HIV-infected cells but lacks intrinsic enzymatic activity. Instead, Nef works through diverse interactions with host cell proteins primarily related to kinase signaling pathways and endosomal trafficking. This review emphasizes the structure, function, and biological relevance of Nef interactions with host cell protein-tyrosine kinases in the broader context of Nef functions related to enhancement of the viral life cycle and immune escape. Drug discovery targeting Nef-mediated kinase activation has allowed identification of promising inhibitors of multiple Nef functions. Pharmacological inhibitors of Nef-induced MHC-I down-regulation restore the adaptive immune response to HIV-infected cells in vitro and have the potential to enhance immune recognition of latent viral reservoirs as part of a strategy for HIV clearance.


[Successful treatment with splenic irradiation for idiopathic thrombocytopenic purpura associated with primary immunodeficiency syndrome].
A 50-year-old man was admitted to our hospital because of intracranial hemorrhage and thrombocytopenia (platelet count: 3,000/microliter). Low levels of IgG (76 mg/dl) and IgA (30 mg/dl) and a normal pattern of peripheral blood T and B cell subsets yielded a diagnosis of common variable immunodeficiency (CVID). The number of megakaryocytes in bone marrow was within normal limits (64/microliter), and a diagnosis of idiopathic thrombocytopenic purpura was made. Both high-dose intravenous gamma-globulin and prednisolone were ineffective. Because of the coexistence of CVID, splenic irradiation (total 15 Gy) was performed instead of splenectomy. The platelet number began to increase 5 days after the initiation of irradiation, had increased to 8.7 x 10(4)/microliter at the end of irradiation, and was 22.9 x 10(4)/microliter 2 weeks later.


Cyst of accessory lacrimal gland.
When a patient is presented with a subconjunctival cyst, it is not only hard to reveal its true nature clinically but also easy to rupture during excision. We experienced cases with cysts of the accessory lacrimal gland in two patients with subconjunctival cysts. They had lid swelling at initial presentation and underwent surgical excision of subconjunctival cysts located in superior portion of the upper tarsal plate. The lining of these cysts composed of ductal epithelia. Biochemical analyses for serum and cystic fluid were performed in one case, in which was found high Ig A titer in the cystic fluid. These cysts seemed to originate from the duct of Wolfring's accessory lacrimal gland, considering their anatomic locations and pathologic findings. Complete removal of the cyst is important, because recurrences have been reported in cases of incomplete removal or simple aspiration.


Menopause across cultures: clinical considerations.
Although many clinicians are aware of cross-cultural variation in the frequency of hot flash reports at midlife, they may underestimate the extent to which the meaning of menopause, as well as attitudes toward treatment, varies across populations. Likewise, variations in symptom frequency may influence help-seeking behavior. This Practice Pearl offers guidance regarding the issues pertinent to the midlife care of patients from diverse cultures and ethnicities.


[Raman micro spectroscopic analysis of relationship between DNA degradation in tissue cells and postmortem interval].
The present work is to study the relationship between DNA degradation in tissue cells and estimation of postmortem interval, and to provide a new way for the estimation of postmortem interval (PMI). The tissue cells of kidney and liver in vitro obtained at different time points were kept in a controlled environment. The kidney tissue and liver tissue were taken out every 4 h, during 48-72 h after death at 25 degrees C. The DNA content in different tissue cells was examined by means of confocal Raman micro spectroscopy with an excitation wavelength of 532 nm. Results show that the relative peak intensities (I1 094/I2 923) of confocal Raman microscopy for the tissue cells decreased gradually with the prolongation of postmortem interval from 48 to 72 h after death, while the peak intensity at 1 094 cm(-1) was reduced obviously; and the peak intensity at 1 454 and 2 923 cm(-1) did not change significantly. It is concluded that the DNA content in tissue cells decreased gradually with the prolongation of postmortem interval from 48 to 72 h after death. There is a linear relationship between the degradation rate of DNA in the tissue cells and postmortem interval. This investigation shows that Raman micro spectroscopy is useful to the estimation of postmortem interval (PMI).


Change in Crown-to-Implant Ratio of Implants Placed in Grafted and Nongrafted Posterior Maxillary Sites: A 5-year Prospective Randomized Study.
The aim of this study was to evaluate the performance of implants placed for 5 years in grafted vs nongrafted sinuses in relation to crown-to-implant ratio. The measurements of crown and implant lengths took into account changes in both endo-sinus and crestal bone levels over 5 years. Enrolled patients required one or two implants in at least one sinus and presented a residual bone height of posterior maxilla ≤ 4 mm. Individual sinuses were randomly allocated either to be grafted or not before surgery. Implants of 8 mm in length were placed using osteotome sinus floor elevation (OSFE). After 10 weeks of healing, they were loaded functionally using definitive single crowns. Radiographic measurements were made on periapical radiographs taken at surgery, prosthetic steps, and 5 years. The implant length was measured between the most apical and coronal contact of bone and implant, and the crown length was measured between the most occlusal point of the crown and the crestal bone. Data were analyzed using mixed linear models. Twenty implants were placed in grafted sinuses and 17 in native bone (12 patients). One of the 35 restored implants failed. Immediately after surgery, the mean lengths of the implants placed in grafted and nongrafted sites were 2.4 ± 0.8 and 2.7 ± 0.9 mm, respectively (P = .351). At loading, the mean crown-to-implant ratios were 3.8 ± 0.8 and 4.6 ± 2.0 (P = .033), respectively, whereas at 5 years, they were 2.0 ± 0.8 and 2.1 ± 0.4, respectively (P = .341). The use of grafting material is not necessary to restore posterior maxilla ≤ 4 mm with OSFE and simultaneous implant placement. Over 5 years, all restored implants but one were functional. Despite unfavorable conditions in terms of initial bone anchorage and height of single crown restoration, a high initial crown-to-implant ratio did not compromise the long-term survival of implants placed in grafted or nongrafted sinuses.


Cross-species virus transmission and its pandemic potential.
The majority of pandemics are known to be a result of either bacteria or viruses out of which viruses seem to be an entity of growing concern due to the sheer number of yet unidentified and potentially threatening viruses, their ability to quickly evolve and transform, their ability to transfer and change from one host organism to another and the difficulty in creating safe vaccines on time. The present review attempts to bring forth the potential risks, prevention and its impact on the global society in terms of sociological and economic parameters. Taking hindsight from previously as well as ongoing current viral epidemics, this article aims to draw a concrete correlation between these viruses in terms of their origin, spread and attempts to compare how much they can affect the population. The study also assesses the worst-case scenarios and the amount of preparedness, required to fight against such pandemics and compares the required amount of preparedness to the current precautions and measures by different governments all across the world. Learning from the current pandemic, we can implement certain measures to prevent the adverse effects of pandemics in the future and through severe preparedness can combat the challenges brought about by the pandemic.


[Examination of function and structure of respiratory cilia of adult patients suffering from chronic obstructive pulmonary disease (COPD)--comparison of nasal and bronchial mucosa (pilot of CILIARY STUDY)].
Borderline between upper and lower respiratory tract pathology is probably artificial (bronchial asthma). Also inflammation of bronchial mucosa during chronic obstructive pulmonary disease (COPD) is likely combined with inflammatory involvement of nasal mucosa. Ciliary edge of respiratory epithelium is very important part of mucosa layer. To investigate and compare nasal and bronchial ciliary beat frequency (CBF), degree of nasal and bronchial ciliary dyskinesia, presence of ciliary akinesia and incidence of spinocellular metaplasia in the both mucosa localities among of stable COPD patients (pts). Nasal and bronchial mucosa were obtained in the course of bronchoscopy examination of COPD pts in general intravenous anesthesia. Native samples of mucosa tissue were assessed by digital high-speed video microscopy (1,000x magnification). Paired t-test was used to evaluate differences in average frequencies. Significance level was alpha = 0.05. Mode was used to describe "index of dyskinesia", as a measure of association was used K coefficient. Seventeen COPD pts (6 weeks free of exacerbation) at the age 47-80 (average 64.2 years +/- 9.7) were examined (13 male), average FEV1 61% predic. value (21-81, +/- 15). All patients were active smokers (average 42 pack years +/- 22.8) and all suffered from bronchitic (daily sputum production) phenotype of COPD. We did not find any difference in average ciliary beat frequencies between nose (6.0 Hz +/- 1.3) and bronchus (5.9 +/- 1.3) locality (p = 0.427). We find weak association between nose and bronchus in "ciliary akinesia" (kappa = 0.282) but medium association in "metaplasia" (kappa = 0.485), in index of dyskinesia (kappa = 0.733). We did not find in our data any difference in nasal and bronchial ciliary beat frequencies and we found medium association between nasal and bronchial spinocellular metaplasia and index of ciliary dyskinesia. Possible generalization of these results would require further investigation and analysis.


[Hospitalization of patients with eating disorders: an eight years review].
Eating disorders (Eds) are pathologies with a multifactorial etiopathogenesis. Their treatment requires an interdisciplinary team. The aim of this paper is to discuss in patient treatment (n=80) of patients with eating disorders during eight years. This treatment was in charge of the Eating Disorders Team of the Hospital Italiano of Buenos Aires. The approach to critical stages of eating disorders envolves the clinical or psychiatric admission of the patients as the principal means to ward off patients from death or the appearance of cronifications. 77,5% of the patients were admitted to the psychiatric ward, 5% to a clinical ward and 17,5% to a clinical followed by a psychiatric ward. The average B.M.I. in admission was 16,83. The average time in psychiatry was 35 days. During inpatient treatment 21,25% required a nasogastric tube and 82% received psychopharmacological treatment. The mortality rate was 1,25%. During the ambulatory treatment that followed hospitalizations, 32,5% were readmitted to the psychiatric ward and there were 10% of dropouts. Hospitalization of these patients looks after the achievement of healthier eating habits and the establishment of a therapeutic alliance which allows the follow up of an ambulatory treatment.


Hypertension and orthostatic hypotension with venlafaxine treatment in depressed older adults.
Venlafaxine, a serotonin-norepinephrine reuptake inhibitor, is often used as first- or second-line therapy for depression in older adults. It can be associated with adverse blood pressure (BP) effects. Adults ⩾60 years of age in a current major depressive episode were treated in a protocolized manner with venlafaxine XR; 429 participants were treated for 8-16 weeks with a daily dose up to 300 mg to achieve remission from depression. Cardiac measures included sitting and standing BP and heart rate. Of participants who were normotensive at baseline, 6.5% were found to have elevated BP during the study (1.9% <225 mg/day; 9.8% ⩾225 mg/day). There was no significant change in mean BP in the overall sample, or in the subgroup treated with doses ⩾225 mg/day. Additionally, 20.1% of the participants who did not have orthostatic hypotension at baseline were found to have orthostatic hypotension (16.8% <225 mg/day; 22.4% ⩾225 mg/day). Participants with new-onset orthostatic hypotension were significantly more likely to fall than the other participants. A large proportion of older adults treated with venlafaxine experience orthostatic hypotension, putting them at risk for falls. A smaller proportion experience elevated BP. Older patients prescribed venlafaxine, particularly at high doses, should be advised and counseled about these adverse effects.


Role(s) of formyl-peptide receptors expressed in nasal epithelial cells.
Chronic rhinosinusitis is one of the most frequent chronic diseases in humans. Little is known about stimuli initiating tissue remodeling process that determines the morphological expression of the disease. N-formyl peptide receptors (FPRs) are innate immunity receptors important in tissue remodeling of gastric and intestinal epithelium. The expression and functions of FPRs in nasal epithelial cells were examined to evaluate whether they could be important in the remodeling of nasal mucosa. The aim of this study is to examine FPR expression in a nasal epithelial cell line (RPMI-2650) at mRNA and protein levels. To determine whether FPRs were functional, chemotaxis experiments were carried out. In addition the effects of FPRs agonists on the expression (PCR and ELISA) of VEGF-A and TGF-beta, two key mediators of tissue remodelling, were examined. Here we demonstrate that RPMI-2650 express FPR and FPRL2, but not FPRL1. fMLP, a bacterial product active on FPR, and uPAR(84-95), an inflammatory mediator agonist for FPRL2, stimulated migration of nasal epithelial cells. fMLP and uPAR(84-95) induce expression and secretion of VEGF-A and TGF-beta. Our results suggest a possible mechanisms initiating tissue remodeling observed during chronic rhinosinusitis. This study provides further evidence that FPRs play a more complex role in human pathophysiology than bacterial recognition.


Facilitating scholarship among clinical faculty.
This article describes an evolving model of clinical scholarship for clinical-track faculty. Contemporary literature regarding scholarship emphasizes broader definitions of scholarship among university faculty, usually with an implicit focus on university faculty with doctoral degrees. Discussions of clinical scholarship focus on scholarship projects with clear application to improved patient care. Clinical-track faculty in university settings serve as exemplars of professional nurse clinicians for their students and for community-based colleagues, and also participate in university life as full faculty. Furthermore, scholarship for clinical faculty is consistent with their participation as academic scholars and as clinical scholars. An important strategy for fostering scholarship among clinical faculty in one school was the creation of a position, Director of Clinical Scholarship, with responsibilities for strengthening organizational support for scholarship activities among clinical-track faculty. Examples of activities and resources designed to foster scholarship are presented, along with preliminary evaluation of scholarship activities of clinical-track faculty. J Prof Nurs 17:141-146, 2001.


Palladium-catalyzed enantioselective C-3 allylation of 3-substituted-1H-indoles using trialkylboranes.
We have developed a new enantioselective C-3 allylation of 3-substituted indoles using allyl alcohol and trialkylboranes. Asymmetric syntheses of 3,3-disubstituted indolines and indolenines in enantiomeric excesses up to 90% have been achieved using the bulky borane 9-BBN-C6H13 as the promoter of the reaction. The dependence of the selectivity on the nature of the borane suggests that the boron reagent has a role beyond promoting ionization of the allyl alcohol. A protocol for oxidation of indolenines to oxindoles has also been developed and led to a formal synthesis of (-)-phenserine.


Worry, beliefs about worry and problem solving in young children.
Childhood worry is common, and yet little is known about why some children develop pathological worry and others do not. Two theories of adult worry that are particularly relevant to children are Davey's problem-solving model in which perseverative worry occurs as a result of thwarted problem-solving attempts, and Wells' metacognitive model, in which positive and negative beliefs about worry interact to produce pathological worry. The present study aimed to test hypotheses that levels of worry in young children are associated with poor or avoidant solution generation for social problems, and poor problem-solving confidence. It also aimed to explore beliefs about worry in this age group, and to examine their relationships with worry, anxiety and age. Fifty-seven young children (6-10 years) responded to open ended questions about social problem-solving situations and beliefs about worry, and completed measures of worry, anxiety and problem-solving confidence. Children with higher levels of worry and anxiety reported using more avoidant solutions in social problem situations and children's low confidence in problem solving was associated with high levels of worry. Children as young as 6 years old reported both positive and negative beliefs about worry, but neither were associated with age, gender, or level of anxiety or worry. RESULTS indicate similarities between adults and children in the relationships between problem-solving variables and worry, but not in relationships between beliefs about worry and worry. This may be due to developmental factors, or may be the result of measurement issues.


Characteristics of Sprint Fidelis lead failure.
Background. The Medtronic Sprint Fidelis ICD lead is prone to failure and the rate of failure seems to be increasing. The aim of this study was to investigate the rate of Sprint Fidelis lead failure, the characteristics, the mode of presentation and possible predictors of lead failure.Methods and Results. The rate, characteristics and presentation of Sprint Fidelis lead failure was assessed in this single-centre survey. 619 Sprint Fidelis ICD leads were implanted at our centre between December 2004 and August 2007. The mean follow-up was 32+/-10 (range 22-60) months; 35 patients (5.7%) required a lead re-implantation because of failure of the pace-sense conductor. Mean duration of lead survival was 23+/-12 (2-46) months and the rate of failure did not stabilise during follow-up. The mode of presentation was inappropriate shocks in 16 patients (45.7%), alarm alert in 12 patients (34.3%), and detection at routine follow-up in seven patients (20%). In 31 patients (89%), interrogation data revealed a sudden rise in impedance and/or frequent short VV intervals prior to lead failure and in five patients an isolated decrease of R wave (<2.5 mV). The interrogation data were not different from patients with shocks compared with patients without shocks. The interrogation data at routine follow-up in the first three months after implant were normal and stable.Conclusion. The rate of Sprint Fidelis lead failure reaches 5.7% at a mean follow-up duration of 32 months. The rate of failure does not seem to stabilise. Routine follow-up can not predict lead failure or prevent inappropriate shocks. (Neth Heart J 2010;18:12-7.).


Cholecalciferol-PEG Conjugate Based Nanomicelles of Doxorubicin for Treatment of Triple-Negative Breast Cancer.
Triple-negative breast cancer (TNBC) is the leading cancer in women. Chemotherapeutic agents used for TNBC are mainly associated with dose-dependent toxicities and development of resistance. Hence, novel strategies to overcome resistance and to offer dose reduction are warranted. In this study, we designed a novel dual-functioning agent, conjugate of cholecalciferol with PEG2000 (PEGCCF) which can self-assemble into micelles to encapsulate doxorubicin (DOX) and act as a chemosensitizer to improve the therapeutic potential of DOX. DOX-loaded PEGCCF (PEGCCF-DOX) micelles have particle size, polydispersity index (PDI), and zeta potential of 40 ± 8.7 nm, 0.180 ± 0.051, and 2.39 ± 0.157 mV, respectively. Cellular accumulation studies confirmed that PEGCCF was able to concentration-dependently enhance the cellular accumulation of DOX and rhodamine 123 in MDA-MB-231 cells through its P-glycoprotein (P-gp) inhibition activity. PEGCCF-DOX exhibited 1.8-, 1.5-, and 2.9-fold enhancement in cytotoxicity of DOX in MDA-MB-231, MDA-MB-468, and MDA-MB-231DR (DOX-resistant) cell lines, respectively. Western blot analyses showed that PEGCCF-DOX caused significant reduction in tumor markers including mTOR, c-Myc, and antiapoptotic marker Bcl-xl along with upregulation of preapoptotic marker Bax. Further, reduction in mTOR activity by PEGCCF-DOX indicates reduced P-gp activity due to P-gp downregulation as well and, hence, PEGCCF causes enhanced chemosensitization and induces apoptosis. Substantially enhanced apoptotic activity of DOX (10-fold) in MDA-MB-231(DR) cells confirmed apoptotic potential of PEGCCF. Conclusively, PEGCCF nanomicelles are promising delivery systems for improving anticancer activity of DOX in TNBC, thereby reducing its side effects and may act as a potential carrier for other chemotherapeutic agents.


Microwave-assisted synthesis of organometallic complexes of ⁹⁹mTc(CO)₃ and Re(CO)₃: its application to radiopharmaceuticals.
(99m)Tc-tricarbonyl [(99m)Tc(CO)(3)] complexes have been conventionally synthesized by heating [(99m)Tc(CO)(3)(H(2)O)(3)](+) and a tridentate chelating ligand under atmospheric pressure; however, this method is poor in terms of chemical yield and reproducibility. Moreover, since the half-life of (99m)Tc is very short (6 h), the development of facile and rapid methods of synthesizing (99m)Tc-labeled compounds, which could be used as radioactive tracers for single photon emission computed tomography (SPECT), is required. Thus, we initiated a study on the application of a microwave reaction to the synthesis of (99m)Tc(CO)(3)-2-picolylamine monoacetic acid (PAMA) [(99m)Tc(CO)(3)-PAMA] complexes on the basis of the fact that synthesis of metal complexes proceeds rapidly by microwave irradiation owing to an efficient exothermic phenomenon and heat conduction effect. Formation of by-products could be markedly suppressed by comparison with that in conventional methods. In the present study, rhenium (Re), an element belonging to the same group in the periodic table as technetium (Tc), and which also forms bipyramidal complexes, was first used to investigate the synthetic reaction because no stable isotopes exist for Tc. As a result, when water was used as the solvent under the irradiation of microwaves within 1 min, the Re(CO)(3)-PAMA complex could be directly synthesized from ethyl ester of PAMA (PAMAEE) and [Re(CO)(3)(H(2)O)(3)]Br in one step and with a high yield (94%). Finally, the (99m)Tc(CO)(3)-PAMA complex was successfully synthesized at a high radiochemical yield (>99%) within 1 min of reaction using (99m)Tc instead of Re under the same conditions.


Delirium after cardiac surgery: incidence and risk factors.
Delirium after cardiac surgery is a problem with consequences for patients and healthcare. Preventive strategies from known risk factors may reduce the incidence and severity of delirium. The present aim was to explore risk factors behind delirium in older patients undergoing cardiac surgery with cardiopulmonary bypass. Patients (≥70 years) scheduled for routine cardiac surgery were included (n = 142). The patients were assessed and monitored pre-/postoperatively, and delirium was diagnosed from repeated assessments with the Mini-Mental State Examination and the Organic Brain Syndrome Scale, using the DSM-IV-TR criteria. Variables were analysed by uni-/multivariable logistic regression, including both preoperative variables (predisposing) and those extracted during surgery and in the early postoperative period (precipitating). Delirium was diagnosed in 78 patients (54.9%). Delirium was independently associated with both predisposing and precipitating factors (P-value, odds ratio, upper/lower confidence interval): age (0.036, 1.1, 1.0/1.2), diabetes (0.032, 3.5, 1.1/11.0), gastritis/ulcer problems (0.050, 4.0, 1.0/16.1), volume load during operation (0.001, 2.8, 1.5/5.1), ventilator time in ICU (0.042, 1.2, 1.0/1.4), highest temperature recorded in ICU (0.044, 2.2, 1.0/4.8) and sodium concentration in ICU (0.038, 1.2, 1.0/1.4). Delirium was common among older patients undergoing cardiac surgery. Both predisposing and precipitating factors contributed to delirium. When combined, the predictive strength of the model improved. Preventive strategies may be considered, in particular among the precipitating factors. Of interest, delirium was strongly associated with an increased volume load during surgery.


Adaptive neural control of nonlinear time-delay systems with unknown virtual control coefficients.
In this paper, adaptive neural control is presented for a class of strict-feedback nonlinear systems with unknown time delays. The proposed design method does not require a priori knowledge of the signs of the unknown virtual control coefficients. The unknown time delays are compensated for using appropriate Lyapunov-Krasovskii functionals in the design. It is proved that the proposed backstepping design method is able to guarantee semiglobal uniformly ultimately boundedness of all the signals in the closed-loop. In addition, the output of the system is proven to converge to a small neighborhood of the origin. Simulation results are provided to show the effectiveness of the proposed approach.


Phosphorylation of nuclear proteins in myelinating oligodendrocytes and its control by cyclic AMP.
Oligodendroglial nuclei isolated from rat brains at different stages of myelinogenesis (10, 18, and 30 days of age) were incubated with [gamma-32P]ATP and extracted with 0.75 M perchloric acid to yield a fraction of nonacidic chromatin proteins. The protein extracts were then analyzed by polyacrylamide gel electrophoresis. The phosphorylation pattern of these proteins was found to be different for different age groups. In 10-day-old rat oligodendrocytes the most extensive phosphorylation occurred in low molecular mass species (less than 30 kDa), in contrast to fractions obtained from 18- and 30-day-old rat oligodendrocytes which showed a significantly higher labeling of the proteins with molecular masses greater than 30 kDa. The phosphorylation of the latter species was greatly stimulated by the presence of cyclic AMP in the incubation media. The results suggest that the phosphorylation of specific nuclear proteins, which may play a regulatory role at different stages of oligodendroglial maturation and myelinogenesis, may be at least partially modulated by intracellular cyclic AMP.


Hippocratic fingers in Behçet's disease.
Digital clubbing has been a well recognised feature of several distinct clinical conditions, including respiratory, cardiac, and gastrointestinal diseases since the Hippocratic era. However, clubbing associated with Behçet's disease has not been reported before. We describe a case of clubbing in a young man with Behçet's disease, in the absence of any other apparent aetiology and propose that clubbing might be an accompanying feature of Behçet's disease.


Interaction between glucose-6-phosphate dehydrogenase deficiency and sickle cell gene in Saudi Arabia.
Sickle cell haemoglobin (Hb S) and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency occur at a variable prevalence in different regions of Saudi Arabia. The interaction between the two genes was investigated in 1859 Saudi males in different regions where the two genes were known to exist at both a high and a low frequency. The frequency of G-6-PD deficiency was the highest in the sickle cell anaemia (SS) cases. Furthermore, in all areas except Tehamat-Aseer (on the Red Sea), the frequency of G-6-PD deficiency was greater in the sickle cell heterozygotes (AS) than in the normal (AA) individuals. The interaction between G-6-PD deficiency and sickle cell gene in the homozygotes and heterozygotes may provide additional benefit against environmental and genetical factors, and may play a role in the amelioration of sickle cell disease in Saudis.


The Impaired Anesthesia Provider: Strategies to Prevent, Recognize, and Treat Substance Use Disorder within the Workplace.
The development of a substance use disorder within an anesthesia provider is complex and multifactorial. Substance use disorder is considered the number one occupational hazard for anesthesia professionals, and it is estimated that 10%-15% of anesthesia providers will experience a substance use disorder. High stress levels within the workplace environment contribute to the risk of an anesthesia professional developing a substance use disorder. This article will discuss strategies to prevent, recognize, and treat substance use disorder within the workplace.


Role of a T-type calcium current in supporting a depolarizing potential, damped oscillations, and phasic firing in vasopressinergic guinea pig supraoptic neurons.
Guinea pig magnocellular neurosecretory cells (MNCs) of the supraoptic nucleus (SON) were studied using the in vitro slice preparation. Intracellular recordings were made with biocytin-filled electrodes, permitting immunocytochemical identification of the recorded cells as arginine vasopressin- (AVP) versus oxytocin- (OT) containing. Only AVP cells displaying a depolarizing potential (DP) fired phasically. The DP was associated with a transient inward current measured in voltage clamp, which exhibited a number of properties of the T-type calcium current: activation threshold of -64 mV, time course of up to 250 ms, blockade by nickel and augmentation by barium chloride. This current has not been reported previously in SON neurons. The T-type current (IT) was always associated with a damped oscillation of the membrane following the offset from hyperpolarizing steps. In all cells tested, an apamin-sensitive afterhyperpolarization (AHP) was observed, similar to the calcium-dependent potassium current (IK, Ca) described in rat SON and other CNS regions. Therefore, as with other CNS regions displaying damped oscillations, guinea pig SON cells possess both an IT and an IK, Ca. We have previously described an Ih activating at hyperpolarized potentials in these cells, which depolarizes the membrane to a range in which the IT and IK, Ca can interactively support oscillations. In summary, the IT and associated depolarizing potential appears to be a requisite feature for phasic firing in AVP cells of guinea pig SON.


Sisters Together: Move More, Eat Better: a community-based health awareness program for African-American women.
Statistics indicate that African-American women have the highest rate of obesity among all racial groups. In response, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) developed "Sisters Together: Move More, Eat Better," a national program that encourages African-American women to maintain a healthy weight by becoming more physically active and by eating healthier foods. "Sisters Together" programs are run locally by individuals or community groups in locations such as churches and health departments. The NIDDK offers culturally relevant materials and technical assistance to program leaders, including a recently updated program guide. The guide walks leaders through program planning, promotion, implementation, and evaluation. It is based on obesity, nutrition, and physical activity research; evidence-based programs for African-American women; and proven health communication strategies. The guide is consumer friendly, using clear language and real-life examples. "Sisters Together" programs encourage African-American women and their families to improve their eating habits and their physical activity habits.


[Relationship between community composition and water infiltration of biological soil crusts in the hilly Loess Plateau, China].
Biological soil crusts (biocrusts) are the mixed community composed of different ratios of cyanobacteria, mosses, and lichens at the slope scale in the Hilly Loess Plateau region. Biocrusts significantly affect water infiltration in this area. The relationship between infiltration rate and community structure of mixed biocrusts is unknown, which would hinder the assessment of soil permeability of biocrusts at the slope scale. We measured the stable infiltration rate of cyanobacteria, moss, and mixed biocrusts with different proportions of cyanobacteria and moss including moss coverage of <15%, 15%-30%, 30%-45%, 45%-60% and >60%, respectively. The principal component analysis and path analysis were used to understand the influencing factors of stable infiltration rate of mixed biocrusts, and to clarify the relationship between the stable infiltration rate and the community structure of mixed biocrusts. The results showed that the saturated hydraulic conductivity of cyanobacteria and moss crusts was 0.66 mm·min-1 and 2.40 mm·min-1, respectively. The stable infiltration rates of mixed biocrusts with moss coverage <15% to >60% were 0.80-2.30 mm·min-1. The stable infiltration rate of mixed biocrusts at the slope scale depended on moss coverage and its improvement on soil pore structure, with the correlation coefficients being 0.636 (P=0.011) and 0.835 (P=0.000) respectively. Herein, the saturated hydraulic conductivity and coverage of cyanobacteria and moss confirmed the weighted prediction of water infiltration volume (y) i.e., a significant correlation (r=0.945) with the measured water infiltration volume (x) of mixed biocrusts. The linear fitting of measured and predicted water infiltration volume of mixed biocrusts was y=0.85x (R2=0.98, P<0.05). This study clarified the relationship between water infiltration of mixed biocrust community composition and individual biocrust composition, which provided a scientific basis for accurately evaluating the hydrological process of biocrusts in this area.


Does a brief work-stress intervention prevent sick-leave during the following 24 months? A randomized controlled trial in Swedish primary care.
Work-related stress (WRS) presents a risk for sick leave. However, effective methods to identify people at risk for sick leave due to WRS at an early stage are lacking in primary health care. To evaluate whether a systematic early identification of WRS can prevent sick leave over 24 months after the intervention. Study participants (n = 132 intervention; n = 139 control) were employed, non-sick-listed persons seeking care at primary health care centres. The intervention included early identification of WRS by a validated instrument, general practitioner (GP) awareness supported by a brief training session, patients' self-reflection by instrument completion, GP giving the patient feedback at consultation and GP identifying preventive measures. The control group received treatment as usual. Outcome data were retrieved from the Swedish Social Insurance Agency. The intervention group had less registered median sick leave days (n = 56) than the control group (n = 65) but the difference was not statistically significant. The brief intervention was not proven effective in preventing sick leave in the following 24 months compared to treatment as usual. Further research on how to identify, advice and treat those at high risk for sick leave in primary health care is needed.


Cancer stem cells: understanding tumor hierarchy and heterogeneity.
Heterogeneity within and between tumors is a well-known phenomenon that greatly complicates the diagnosis and treatment of cancer. A large body of research indicates that heterogeneity develops through time as tumor-initiating stem cells, also known as cancer stem cells (CSCs), evolve genetic or epigenetic alterations that allow them to differentiate into multiple tumor cell types. Similar to normal stem cells, CSCs can self-renew and possess long-term repopulation potential. However, unlike normal stem cells, CSCs are not subject to the usual controls that limit growth. Different models have been postulated to explain the heterogeneity of tumors, but it is widely agreed that interactions between tumor cells and their microenvironment create niches that promote CSC properties and enable their survival. Within the microenvironment, CSC self-renewal, replication, and differentiation are postulated to produce a hierarchy of cells constituting the tumor mass. Increased understanding of the factors that create and contribute to tumor heterogeneity may support the design of therapies that affect CSC function and their microenvironments.


Inbreeding effect on morbidity: III. A review of the world literature.
A review of the international literature on the inbreeding effect on morbidity is presented. For anomalies in general, the estimates of B vary from 0.2 to 5.8, of A from 0.01 to 0.23, and of B/A from 3 to 77. The respective modal estimates are roughly around 0.5, 0.03, and 20. A review of the estimates for specific anomalies also shows a wide range of values; from B = 0.0008, A = 68 X 10(-8), and B/A = 1,176 (for acheiropodia) to B = 2.9, A = 0.24, and B/A = 12 (for "incapacity for military service"). Some estimates of B/A lower than 12 have been obtained for congenital malformations in some countries. An overall analysis of the whole body of data suggests that most of the anomalies are either entirely or predominantly mutational in origin.


Assessment of Breast Cancer Management in Sub-Saharan Africa.
To document progress and bottlenecks in breast cancer management in sub-Saharan Africa, subsequent to a 2013 pilot survey conducted through the African Organization for Research and Treatment in Cancer (AORTIC) network. An anonymous survey of breast cancer management was conducted in 2018 among AORTIC members. Results concerning respondent specialty, access to tumor boards, treatment accessibility, diagnostic services, and factors influencing treatment outcomes were compared with the 2013 findings. Thirty-seven respondents from 30 facilities in 21 sub-Saharan Africa countries responded. The majority (92%) were clinical oncologists. Radiotherapy facilities were available in 70% of facilities. Seventy-eight percent of these had linear accelerators, and 42% had cobalt60 machines. Eighty percent of facilities had multidisciplinary tumor boards. Immunohistochemistry was routinely performed in 74% of facilities, computed tomography scan in 90%, bone scan in 16%, and positron emission tomography scans in 5%. Anthracyclines, taxanes, tamoxifen, letrozole, anastrozole, and zoledronic acid were available in the majority; trastuzumab, fertility, and genetic counseling were available in 66%, 58%, and 16%, respectively. There were a 50% increase in oncologist respondents over 2013 and a > 50% increase in radiotherapy facilities, particularly linear accelerators. Availability of trastuzumab, aromatase inhibitors, and taxanes increased. Immunohistochemistry capacity remained the same, whereas facilities harvesting at least 10 axillary lymph nodes increased. Bone scan facilities decreased. Responses suggested improved diagnostic services, systemic therapies, and radiotherapy. Sociocultural and economic barriers, system delays, and advanced stage at presentation remain. Clinicians in sub-Saharan Africa have basic tools to improve breast cancer outcomes, recording positive strides in domains such as radiotherapy and systemic therapy. Socioeconomic and cultural barriers and system delays persist. Workforce expansion must be prioritized to improve quality of care to improve outcomes.


Applications of positron emission tomography in the newborn nursery.
Positron emission tomography (PET) is a relatively noninvasive imaging test that is able to detect abnormalities in different organs based on derangements in the chemical functions and/or receptor expression at the cellular level. PET imaging of the brain has been shown to be a powerful diagnostic tool for detecting neurochemical abnormalities associated with various neurologic disorders as well as to study normal brain development. Although its use in detecting neurological abnormalities has been well described in adults and pediatrics, its application in the newborn nursery has not been explored adequately. Early detection of brain injury secondary to intrauterine and perinatal insults using PET imaging can provide new insight in prognosis and in instituting early therapy. In this review, the authors describe applications of PET imaging in the newborn nursery specifically related to the detection of metabolic changes seen in hypoxic ischemic encephalopathy, neonatal seizures, and neuroinflammation in the neonatal period.


Molecular modeling of cytochrome P450 1A1: enzyme-substrate interactions and substrate binding affinities.
Human cytochrome P450 1A1, which is present in lungs, plays an important role in the metabolic activation of chemical carcinogens, and in particular, is thought to be linked to lung cancer. The mechanism of carcinogenesis is related to the enzyme's ability to oxidize highly toxic compounds, such as polycyclic aromatic hydrocarbons (PAHs), to their carcinogenic derivatives. In order to better understand P450 1A1 function, a homology model of this enzyme has been constructed. The model has been based on the structure of P450 2C5, the first mammalian P450 to be crystallized. The coordinates of the model have been calculated using a consensus strategy, and the resulting structure has been evaluated with the ProStat and Profiles-3D programs. P450 1A1 substrates, such as benzo[a]pyrene, ethoxyresorufin and methoxyresorufin, were then docked into the active site of the model, and key amino acid residues able to interact with the substrate, have been identified. The analysis of enzyme-substrate interactions indicated that hydrophobic interactions are mainly responsible for binding of these substrates in the active site. Moreover, the non-bond enzyme-substrate interaction energy for ethoxyresorufin was lower than that for methoxyresorufin, which is consistent with higher activity of 1A1 towards the former substrate. Key residue Val-382 may play an important role in these interactions. Additionally, we performed binding free energy calculations for the three substrates. The obtained values were similar to those observed experimentally, which suggests that this approach might be useful for prediction of binding constants.


[Motivational interviewing and cognitive behavior therapy for smoking cessation].
The combination therapy of counseling and medication is very important in smoking cessation treatment. Motivational interviewing (MI) and cognitive behavior therapy (CBT) are interventions recommended in two well-recognized guidelines for smoking cessation in the United States. MI is effective for those who do not want to quit smoking; CBT for those who cannot but want to quit smoking, those who repeatedly quit and re-smoke, those who are depressed, and women who are concerned about their weight. However, neither MI nor CBT for smoking cessation is widely practiced in Japan. We describe the nature of, evidence for, and practice of MI and CBT in smoking cessation treatment, hopeful that clinicians and other healthcare staff learn and apply these techniques.


Vowel acoustics in adults with apraxia of speech.
To investigate the hypothesis that vowel production is more variable in adults with acquired apraxia of speech (AOS) relative to healthy individuals with unimpaired speech. Vowel formant frequency measures were selected as the specific target of focus. Seven adults with AOS and aphasia produced 15 repetitions of 6 American English vowels in /hVC/ context (hid, head, hat, hot, hub, hoot). Vowel formant frequency measures (F1, F2) were Bark transformed and compared with data from archival sources. Measures of vowel acoustics in speakers with AOS did not differ from those of unimpaired speakers, including absolute Bark formant values, vowel space area, intervowel distance, and individual trial-to-trial formant variability. Comparison with normative acoustic measures suggested that vowel production at the word level is unimpaired in the current speakers with AOS, supporting previous studies that have shown vowel production is relatively intact in AOS.