Cardiovascular disease and air pollutants: evaluating and improving epidemiological data implicating traffic exposure.
Evidence suggests that traffic-related pollutants play a role in the observed associations between air pollution and adverse cardiovascular health effects. The contribution of traffic to individual exposures is difficult to quantify in traditional epidemiological studies, however, and researchers have employed various approaches in attempt to isolate its effects. Many investigators have employed ambient measurements such as nitrogen oxides, carbon monoxide, or black carbon as surrogates for traffic in studying associations with health outcomes. Source-apportionment techniques also have been used in a few studies to identify associations with the mixture of pollutants from specific origins, including traffic. In other studies, estimates of traffic near a person's home have predicted cardiovascular endpoints, and local traffic levels have modified the effect of regional air pollution. More recently, studies have linked changes in cardiovascular health to time spent in traffic. In this article, we review the epidemiological evidence regarding the impact of traffic-related pollution on cardiovascular diseases and examine the different techniques used to examine this important research question. We conclude with a discussion of the future directions being used in ongoing epidemiological studies to identify the cardiovascular health impacts of traffic.


Kidney injury molecule 1 (KIM-1): a potential biomarker of acute kidney injury and tubulointerstitial injury in patients with ANCA-glomerulonephritis.
Kidney injury molecule 1 (KIM-1) is a transmembrane glycoprotein expressed by proximal tubular cells, recognized as an early, sensitive and specific urinary biomarker for kidney injury. Blood KIM-1 was recently associated with the severity of acute and chronic kidney damage but its value in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis with glomerulonephritis (ANCA-GN) has not been studied. Thus, we analyzed its expression at ANCA-GN diagnosis and its relationship with clinical presentation, kidney histopathology and early outcomes. We assessed KIM-1 levels and other pro-inflammatory molecules (C-reactive protein, interleukin-6, tumor necrosis factor α, monocyte chemoattractant protein-1 and pentraxin 3) at ANCA-GN diagnosis and after 6 months in patients included in the Maine-Anjou registry, which gathers data patients from four French Nephrology Centers diagnosed since January 2000. Blood KIM-1 levels were assessed in 54 patients. Levels were elevated at diagnosis and decreased after induction remission therapy. KIM-1 was associated with the severity of renal injury at diagnosis and the need for kidney replacement therapy. In opposition to other pro-inflammatory molecules, KIM-1 correlated with the amount of acute tubular necrosis and interstitial fibrosis/tubular atrophy (IF/TA) on kidney biopsy, but not with interstitial infiltrate or with glomerular involvement. In multivariable analysis, elevated KIM-1 predicted initial estimated glomerular filtration rate (β = -19, 95% CI -31, -7.6, P = .002). KIM-1 appears as a potential biomarker for acute kidney injury and for tubulointerstitial injury in ANCA-GN. Whether KIM-1 is only a surrogate marker or is a key immune player in ANCA-GN pathogenesis remain to be determined.


Bio-Electron-Fenton (BEF) process driven by microbial fuel cells for triphenyltin chloride (TPTC) degradation.
The intensive use of triphenyltin chloride (TPTC) has caused serious environmental pollution. In this study, an effective method for TPTC degradation was proposed based on the Bio-Electron-Fenton process in microbial fuel cells (MFCs). The maximum voltage of the MFC with graphite felt as electrode was 278.47% higher than that of carbon cloth. The electricity generated by MFC can be used for in situ generation of H2O2 to a maximum of 135.96μmolL-1 at the Fe@Fe2O3(*)/graphite felt composite cathode, which further reacted with leached Fe2+ to produce hydroxyl radicals. While 100μmolL-1 TPTC was added to the cathodic chamber, the degradation efficiency of TPTC reached 78.32±2.07%, with a rate of 0.775±0.021μmolL-1h-1. This Bio-Electron-Fenton driving TPTC degradation might involve in SnC bonds breaking and the main process is probably a stepwise dephenylation until the formation of inorganic tin and CO2. This study provides an energy saving and efficient approach for TPTC degradation.


Cellular senescence as a stress response.
This review discusses cellular senescence, the state in which normal cells do not respond to growth stimuli, and shows characteristic alterations in their cytologic and biochemical properties and their gene expression profiles. Cellular senescence is elicited by various stresses. It was recently shown that the stress-induced mitogen-activated protein kinase p38 has a pivotal role in inducing cellular senescence. This finding provided biochemical evidence to support the notion that cellular senescence is a kind of stress response. Stress responses are typically found in cells and organisms surviving unfavorable environmental conditions. It can be argued that cellular senescence is an adaptive process that maintains the cell's viability by reducing the energy consumed for reproduction (ie, cell division) and differentiation-related activities.


An assessment of aetiology-based guidelines for the management of nausea and vomiting in patients with advanced cancer.
The aim of this study was to assess the effectiveness of aetiology-based guidelines for the management of nausea and vomiting (N&V) in patients with advanced cancer. This was a prospective study of 121 patients admitted to a hospice. Patients with N&V underwent assessments at presentation, 48 h and 1 week, to determine the aetiology of N&V and the response to treatment. Antiemetics were prescribed according to aetiology-based guidelines. Sixty-one patients (50%) had N&V during their admission: 21 (17%) had isolated nausea, 2 (2%) had isolated vomiting and 38 (31%) had combined N&V. During the assessment period, physicians altered their opinion about the primary cause of N&V in 26% of cases and finally expressed confidence about the aetiology in 75% of patients. The most common cause of N&V was impaired gastric emptying (contributing in 44% of patients), followed by chemical causes (33%) and bowel obstruction (19%). At 1 week, nausea was controlled in 56% of patients, and vomiting in 89% of patients, and residual symptoms were generally mild. An approach using aetiology-based guidelines in the management of N&V is moderately effective, although there are some patients with N&V refractory to standard antiemetic regimens.


The Under- and Over-Identification of Autism: Factors Associated With Diagnostic Referral.
As reported prevalence and public awareness of Autism Spectrum Disorder (ASD) have grown in recent years, clinicians will likely see increased referrals for suspected ASD. The current study sought to elucidate factors associated with referral for possible ASD, as well as diagnostic outcome among youth referred for suspected ASD. Youth referred for psychological evaluations at an outpatient clinic (N = 69, 6-18 years, 48 male) were categorized into four groups: referred for suspected ASD and diagnosed as such, referred for ASD and not diagnosed as such, not referred for ASD but diagnosed as such, and neither referred for nor diagnosed with ASD. Approximately half of cases referred for suspected ASD did not meet diagnostic criteria. A significant effect of group was found for cognitive ability and anxiety. Youth receiving ASD diagnoses, regardless of whether they were referred for suspected ASD, demonstrated lower cognitive ability than children not receiving ASD diagnoses. Youth neither referred for nor diagnosed with ASD demonstrated lower anxiety than those who were referred and diagnosed. Maternal education significantly differed among the four groups. Although group differences are seen for youth cognitive ability, anxiety, and maternal education, we found no clear indicators differentiating referrals that were "accurate" (i.e., those diagnosed with ASD) and those that were not (i.e., those who did not receive ASD diagnosis). Comorbidity was high in all groups, including those referred primarily for ASD assessment, underscoring the importance of comprehensive assessment regardless of specificity of the referral.


Hierarchical micro/nano-structured cobalt sulfide spindles as low-cost counter electrodes for dye-sensitized solar cells.
Hierarchical micro/nano-structured cobalt sulfide spindles are synthesized via a hydrothermal method and investigated as counter electrodes for dye-sensitized solar cells (DSCs). It is demonstrated that DSCs with hierarchical cobalt sulfide spindle electrodes show an excellent photovoltaic performance competing with that of a device with a Pt counter electrode.


[Effect of daunorubicin and cytarabine on cell line NB4].
To explore whether daunorubicin (DNR) combined with cytosine arabinoside (Ara-C) and DNR alone have similar effect on acute promyelocytic leukemia (APL) cell line NB4 and acute myeloblastic leukemia cell line HL-60 in vitro. Cell morphology, cells viability, and cell apoptosis (Annexin-V by flow cytometry assay) were analysed. After incubation with DNR plus Ara-C for 24 hours,NB4 cell viability [(36.75 +/- 3.82)%] (n = 6) and cell apoptosis rate [(21.24 +/- 5.82)%] (n = 3) did not change significantly compared to that treated with DNR alone for 24 hours [(35.73 + 6.28 )%, (22.55 +/- 3.26)%, respectively] (P > 0.05). However, HL-60 cell viability [(67.17 +/- 2.07)%] and cell apoptosis rate [(48.05 +/- 0.92)%] changed significantly in DNR plus Ara-C group compared with DNR alone [(63.31 +/- 1.80)% ,(41.51 +/- 0.89)%, respectively] (P < 0.01 and < 0.05, respectively). DNR plus Ara-C and DNR alone have similar effect on NB4 cells, but have different effect on HL-60 cells.


Epidermal growth factor receptor mutated oligometastatic adeno-squamous lung cancer transformation to small cell lung cancer.
A 66-year-old non-smoker was diagnosed with stage IIIB, epidermal growth factor receptor (EGFR) mutated, squamous cell lung carcinoma. Treatment included chemotherapy, 35 fractions of radiotherapy and later Gefitinib for 3.5 years. On progression he developed a solitary brain and liver lesion. The brain lesion was excised and histology revealed adenocarcinoma of a lung primary. Afatanib was commenced for 1 further year. At the second time of progression re-biopsy identified small cell carcinoma. He completed four cycles of Carboplatin and Etoposide however deteriorated on completion of chemotherapy. EGFR directed treatment is associated with improved patient outcomes. It has been suggested that EGFR mutated squamous cell carcinoma more likely represent mixed morphology or poorly differentiated adenocarcinoma. Patients with oligometastatic progression can be treated beyond progression however the addition of a local therapy may be required. Small cell transformation is described as a rare mechanism of resistance to EGFR treatment as in our case.


Xanthogranulomatous pyelonephritis.
Xanthogranulomatous pyelonephritis is a stage in the progress of chronic pyelonephritis characterized by a combination of clinical and radiologic findings which suggest the diagnosis. Pathologically there are xanthogranulomatous deposits and large lipid-filled foam cells. These clinical-radiologic-pathologic features are demonstrated by means of a case report.


Robot-assisted heminephrectomy for chromophobe renal cell carcinoma in L-shaped fused crossed ectopia: Surgical challenge.
Renal cell carcinoma associated with fused ectopic kidneys has rarely been reported in the literature. Here we report the first case of robot-assisted heminephrectomy for chromophobe renal cell carcinoma in an L-shaped fused ectopic kidney. The present case report highlights the importance of three-dimensional vision and enhanced maneuverability with the EndoWrist technology of the robotic surgical system for precise dissection. This report also highlights the importance of preoperative contrast-enhanced computed tomography with three-dimensional arterial reconstruction for surgical planning.


Fcp1-dependent dephosphorylation is required for M-phase-promoting factor inactivation at mitosis exit.
Correct execution of mitosis in eukaryotes relies on timely activation and inactivation of cyclin B-dependent kinase 1 (cdk1), the M-phase-promoting factor (MPF). Once activated, MPF is sustained until mitotic spindle assembly by phosphorylation-dependent feedback loops that prevent inhibitory phosphorylation of cdk1 and ubiquitin-dependent degradation of cyclin B. Whether subsequent MPF inactivation and anaphase onset require a specific phosphatase(s) to reverse these feedback loops is not known. Here we show through biochemical and genetic evidence that timely MPF inactivation requires activity of the essential RNA polymerase II-carboxy-terminal domain phosphatase Fcp1, in a transcription-independent manner. We identify Cdc20, a coactivator of the ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C) required for cyclin degradation and anaphase onset, USP44, a deubiquitinating peptidase that opposes APC/C action, and Wee1, a cdk1 inhibitory kinase, as relevant Fcp1 targets. We propose that Fcp1 has a crucial role in the liaison between dephosphorylation and ubiquitination that drives mitosis exit.


Distinct parafacial regions in control of breathing in adult rats.
Recently, based on functional differences, we subdivided neurons juxtaposed to the facial nucleus into two distinct populations, the parafacial ventral and lateral regions, i.e., pFV and pFL. Little is known about the composition of these regions, i.e., are they homogenous or heterogeneous populations? Here, we manipulated their excitability in spontaneously breathing vagotomized urethane anesthetized adult rats to further characterize their role in breathing. In the pFL, disinhibition or excitation decreased breathing frequency (f) with a concomitant increase of tidal volume (VT), and induced active expiration; in contrast, reducing excitation had no effect. This result is congruent with pFL neurons constituting a conditional expiratory oscillator comprised of a functionally homogeneous set of excitatory neurons that are tonically suppressed at rest. In the pFV, disinhibition increased f with a presumptive reflexive decrease in VT; excitation increased f, VT and sigh rate; reducing excitation decreased VT with a presumptive reflexive increase in f. Therefore, the pFV, has multiple functional roles that require further parcellation. Interestingly, while hyperpolarization of the pFV reduces ongoing expiratory activity, no perturbation of pFV excitability induced active expiration. Thus, while the pFV can affect ongoing expiratory activity, presumably generated by the pFL, it does not appear capable of directly inducing active expiration. We conclude that the pFL contains neurons that can initiate, modulate, and sustain active expiration, whereas the pFV contains subpopulations of neurons that differentially affect various aspects of breathing pattern, including but not limited to modulation of ongoing expiratory activity.


The effect of fluoride on apatite structure and growth.
Fluoride participates in many aspects of calcium phosphate formation in vivo and has enormous effects on the process and on the nature and properties of formed mineral. The most well-documented effect of fluoride is that this ion substitutes for a column hydroxyl in the apatite structure, giving rise to a reduction of crystal volume and a concomitant increase in structural stability. In the process of enamel mineralization during amelogenesis (a unique model for the cell-mediated formation of well-crystallized carbonatoapatite), free fluoride ions in the fluid phase are supposed to accelerate the hydrolysis of acidic precursor(s) and increase the driving force for the growth of apatitic mineral. Once fluoride is incorporated into the enamel mineral, the ion likely affects the subsequent mineralization process by reducing the solubility of the mineral and thereby modulating the ionic composition in the fluid surrounding the mineral, and enhancing the matrix protein-mineral interaction. But excess fluoride leads to anomalous enamel formation by retarding tissue maturation. It is worth noting that enameloid/enamel minerals found in vertebrate teeth have a wide range of CO3 and fluoride substitutions. In the evolutionary process from elasmobranch through enameloid to mammalian enamel, the biosystems appear to develop regulatory functions for limiting the fluoridation of the formed mineral, but this development is accompanied by an increase of carbonate substitution or defects in the mineral. In research on the cariostatic effect of fluoride, considerable emphasis is placed on the roles of free fluoride ions (i.e., preventing the dissolution and accelerating the kinetics of remineralization) in the oral fluid bathing tooth mineral. Fluoride also has been used for the treatment of osteoporosis, but much still remains to be learned about maximizing the benefit and minimizing the risk of fluoride when used as a public health measure.


Vapor-liquid equilibrium of hexadecapolar fluids from a perturbation-based equation of state.
In this work a numerically tractable expression for the interaction potential between two point hexadecapoles with octahedral symmetry and a molecular-based equation of state derived by perturbation theory for hexadecapolar fluids are presented. The polar system is modeled by square-well particles with a point hexadecapole with octahedral symmetry at their centers. This equation of state is analytical in the state variables and in the potential parameters and allows us to study the effects of the hexadecapolar moment strength on the thermodynamic properties and liquid-vapor phase diagram. The equation presented here is applied to the thermodynamics of sulfur hexafluoride and gives very good predictions for the saturation pressures and the vapor-liquid phase diagram.


[Liver regeneration].
The liver is one of the most complex organs in the body, containing at least seven different cell types and carrying out over 5000 functions. The liver transplantation became a known and effective method for treating its end-stage insufficiency. In response to hepatocellular damage (viral, chemical or surgical injury) the liver mounts inflammatory, regenerative and repair processes with the aim of restoring the functional liver tissue mass. Restoration or liver regeneration after a partial hepatectomy has been scientifically observed since the late nineteenth century. By definition, liver regeneration is an orchestrated response induced by specific external stimuli, involving sequential changes in gene expression, growth factor production, and morphologic structure. During this process, the liver undergoes compensatory hyperplasia in order to reestablish the optimal mass set in relationship to its body size. Many growth factors and cytokines, most notably HGF, EGF, TGF-alpha, IL-6, TNF-alpha, insulin and norepinephrine, seem to play important roles in this process.


Incidental finding - the discovery of a bronchopulmonary foregut malformation through investigations for Crohn's disease.
Pulmonary sequestration (PMS) is a rare bronchopulmonary malformation. It has an incidence of between 0.15% to 1.7%. Likewise, cystic adenomatoid malformation (CCAM) is another relatively rare category of a bronchopulmonary malformation with a reported incidence of between 1 in 25,000 to 1 in 35,000. Moreover, a bronchopulmonary malformation with features allied to both of these forms is considered an even rarer entity. In general, bronchopulmonary malformations present with a range of non-specific symptoms. Radiological features can be non-specific yet distinctive when related to clinical features. Ultimately, definitive diagnosis depends upon histological assessment of lung tissue. We present an adult female with radiological features of both pulmonary sequestration and cystic adenomatoid malformation. This was an incidental finding unrelated to the patients presenting complaint. This case highlights the importance of using a structured and systematic approach when interpreting medical imagery.


Avoiding UV light.
The larvae of an annelid worm use nitric oxide signalling to activate the neural pathways needed to swim away from the harmful ultraviolet light of the sun.


A Winogradsky-based culture system shows an association between microbial fermentation and cystic fibrosis exacerbation.
There is a poor understanding of how the physiology of polymicrobial communities in cystic fibrosis (CF) lungs contributes to pulmonary exacerbations and lung function decline. In this study, a microbial culture system based on the principles of the Winogradsky column (WinCF system) was developed to study the physiology of CF microbes. The system used glass capillary tubes filled with artificial sputum medium to mimic a clogged airway bronchiole. Chemical indicators were added to observe microbial physiology within the tubes. Characterization of sputum samples from seven patients showed variation in pH, respiration, biofilm formation and gas production, indicating that the physiology of CF microbial communities varied among patients. Incubation of homogenized tissues from an explant CF lung mirrored responses of a Pseudomonas aeruginosa pure culture, supporting evidence that end-stage lungs are dominated by this pathogen. Longitudinal sputum samples taken through two exacerbation events in a single patient showed that a two-unit drop in pH and a 30% increase in gas production occurred in the tubes prior to exacerbation, which was reversed with antibiotic treatment. Microbial community profiles obtained through amplification and sequencing of the 16S rRNA gene showed that fermentative anaerobes became more abundant during exacerbation and were then reduced during treatment where P. aeruginosa became the dominant bacterium. Results from the WinCF experiments support the model where two functionally different CF microbial communities exist, the persistent Climax Community and the acute Attack Community. Fermentative anaerobes are hypothesized to be the core members of the Attack Community and production of acidic and gaseous products from fermentation may drive developing exacerbations. Treatment targeting the Attack Community may better resolve exacerbations and resulting lung damage.


[Effect of annexin A2 on EGFR/NF-κB signal transduction and mucin expression in human airway epithelial cells treated with Mycoplasma pneumoniae].
To investigate the effect of annexin A2 (AnxA2) on epithelial growth factor receptor (EGFR)/nuclear factor-κB (NF-κB) signal transduction and mucin expression in human airway epithelial H292 cells treated with Mycoplasma pneumoniae (MP). H292 cells were divided into control group, MP group, NC-siRNA+MP group, and AnxA2 siRNA+MP group. The cells in the MP group were incubated with 5 μg/mL MP antigen for 2 hours. The cells in the NC-siRNA+MP and AnxA2 siRNA+MP groups were transfected with NC-siRNA and AnxA2 siRNA for 24 hours, followed by MP antigen stimulation for 2 hours. The MTT method was used to measure cell viability; quantitative real-time PCR was used to measure the mRNA expression of AnxA2; Western blot was used to measure the protein expression of AnxA2, phosphorylated EGFR (p-EGFR), and phosphorylated p65 NF-κB (p-p65 NF-κB); ELISA was used to measure the secretion of mucin 5AC (MUC5AC) and mucin 5B (MUC5B). The MP and NC-siRNA+MP groups had lower cell viability than the control group (P<0.05). The AnxA2 siRNA+MP group had higher cell viability than the MP and NC-siRNA+MP groups and lower cell viability than the control group (P<0.05). The MP and NC-siRNA+MP groups had significantly higher mRNA and protein expression of AnxA2 than the AnxA2 siRNA+MP group (P<0.05). Compared with the control group, the MP and NC-siRNA+MP groups had significant increases in the protein expression of p-EGFR, p-p65 NF-κB, MUC5AC, and MUC5B (P<0.05); the AnxA2 siRNA+MP group had lower protein expression than the MP and NC-siRNA+MP groups, but higher protein expression than the control group (P<0.05). AnxA2 is involved in the airway lesion induced by MP antigen via mediating EGFR/NF-κB signaling activation and mucin expression in human airway epithelial cells.


Assembly of Iron Oxide Nanocubes for Enhanced Cancer Hyperthermia and Magnetic Resonance Imaging.
Multiple formulations of iron oxide nanoparticles (IONPs) have been proposed for enhancing contrast in magnetic resonance imaging (MRI) and for increasing efficacy in thermal ablation therapies. However, insufficient accumulation at the disease site and low magnetic performance hamper the clinical application of IONPs. Here, 20 nm iron oxide nanocubes were assembled into larger nanoconstructs externally stabilized by a serum albumin coating. The resulting assemblies of nanocubes (ANCs) had an average diameter of 100 nm and exhibited transverse relaxivity (r₂ = 678.9 ± 29.0 mM‒1·s‒1 at 1.41 T) and heating efficiency (specific absorption rate of 109.8 ± 12.8 W·g‒1 at 512 kHz and 10 kA·m‒1). In mice bearing glioblastoma multiforme tumors, Cy5.5-labeled ANCs allowed visualization of malignant masses via both near infrared fluorescent and magnetic resonance imaging. Also, upon systemic administration of ANCs (5 mgFe·kg‒1), 30 min of daily exposure to alternating magnetic fields for three consecutive days was sufficient to halt tumor progression. This study demonstrates that intravascular administration of ANCs can effectively visualize and treat neoplastic masses.


5-HMF Attenuates Liver Fibrosis in CCl4-Plus-Alcohol-Induced Mice by Suppression of Oxidative Stress.
The aim of this study was to investigate the effects of 5-hydroxymethyl-2-furfural (5-HMF) on liver fibrosis induced by carbon tetrachloride (CCl4) and alcohol. Male ICR mice were treated with CCl4 dissolved in olive oil (10% v/v, 2.5 μg/L) intraperitoneally (i.p.), and given at a dose of 2.5×10-5 mg/kg B.W. twice a week for 7 wk. Concurrently, mice received drinking water with or without alcohol. The mice in treatment groups and positive control group were gavaged with 5-HMF (7.5, 15, and 30 mg/kg B.W.) or Huganpian (350 mg/kg B.W.) daily starting in the fourth week and lasting for 4 wk. The blood samples were analyzed for biochemical markers of hepatic injury and tissue samples were subjected for estimation of liver antioxidants and histopathological studies. The concentrations of HA (hyaluronic acid), LN (laminin), CIV (collagen type IV), and MDA (malondialdehyde), as well as the serum levels of ALT (alanine aminotransferase) and AST (aspartate aminotransferase) were markedly reduced by 5-HMF. On the other hand, enzymatic antioxidants SOD (superoxide dismutase), CAT (catalase) and GSH-Px (glutathione peroxidase) were markedly elevated in liver tissue treated with 5-HMF. Histopathological examination revealed that 5-HMF treatment noticeably prevented hepatocyte apoptosis, fatty degeneration and inflammatory cell infiltration on liver fibrosis induced by CCl4 and alcohol. Hoechst 33258 staining also revealed hepatocyte apoptosis. 5-HMF could exert protective effects against liver injury and reduce liver fibrosis induced by CCl4 and alcohol in mice.


Use of the ketogenic diet in neonates and infants.
The ketogenic diet (KD) is still viewed as virtually last-line therapy in childhood epilepsies, and specifically as unsafe and difficult to initiate and maintain in neonates and infants. Information is presented to show that the KD is safe and efficacious in this population, and should be carefully studied to determine its real usefulness as first-line or early therapy (one or fewer anticonvulsants) in the catastrophic epilepsies of infancy.


Alcohol use disorders and cognitive abilities in young adulthood: a prospective study.
The effect of alcohol use disorder (AUD) on cognitive and neuropsychological abilities was investigated in a prospective study of 68 freshmen who met past-year criteria for AUD on 2 or more occasions during their college years and 66 matched controls. At baseline, participants were administered a total of 14 subtests from the Wechsler Adult Intelligence Scale-Revised, Wechsler Memory Scale, and Halstead-Reitan Neuropsychological Battery. At 7-year follow-up, most measures were readministered, along with the Reflective Judgment Interview, Watson-Glaser Critical Thinking Appraisal, and Plant Test. Analyses revealed few differences between AUD and control groups. However, visuospatial deficits may be present among AUD participants with poor baseline visuospatial performance. Alcohol exposure measures yielded similar patterns to those shown with AUD.


Wnt signaling through inhibition of β-catenin degradation in an intact Axin1 complex.
Degradation of cytosolic β-catenin by the APC/Axin1 destruction complex represents the key regulated step of the Wnt pathway. It is incompletely understood how the Axin1 complex exerts its Wnt-regulated function. Here, we examine the mechanism of Wnt signaling under endogenous levels of the Axin1 complex. Our results demonstrate that β-catenin is not only phosphorylated inside the Axin1 complex, but also ubiquinated and degraded via the proteasome, all within an intact Axin1 complex. In disagreement with current views, we find neither a disassembly of the complex nor an inhibition of phosphorylation of Axin1-bound β-catenin upon Wnt signaling. Similar observations are made in primary intestinal epithelium and in colorectal cancer cell lines carrying activating Wnt pathway mutations. Wnt signaling suppresses β-catenin ubiquitination normally occurring within the complex, leading to complex saturation by accumulated phospho-β-catenin. Subsequently, newly synthesized β-catenin can accumulate in a free cytosolic form and engage nuclear TCF transcription factors.


Acute airway compromise and coagulopathy: a rare presentation of acquired haemophilia A.
Acquired haemophilia A is a rare but important diagnosis, carrying a mortality rate of 22%. Life-threatening sequalae of this diagnosis includes airway compromise, which can rapidly lead to demise of the patient if left untreated. Our case examines an 80-year-old man presenting with a supraglottic haematoma resulting from acquired haemophilia A causing airway compromise and necessitating definitive airway control. A review of current understanding and management of the disease is also ddiscussed.


Microstructural Characterization and Prior Particle Boundary (PPB) of PM Nickel-Based Superalloys by Spark Plasma Sintering (SPS).
This research investigates the microstructure and defects of powder metallurgy (PM) nickel-based superalloys prepared by spark plasma sintering (SPS). The densification, microstructural evolution, and precipitate phase evolution processes of FGH96 superalloy after powder heat treatment (PHT) and sintering via SPS are specifically analyzed. Experimental results demonstrate that SPS technology, when applied to sinter at the sub-solidus temperature of the γ' phase, effectively mitigates the formation of a prior particle boundary (PPB). Based on experimental and computational findings, it has been determined that the presence of elemental segregation and Al2O3 oxides on the surface of pre-alloyed powders leads to the preferential precipitation of MC-type carbides and Al2O3 and ZrO2 oxides in the sintering necks during the hot consolidation process, resulting in the formation of PPB. This study contributes to the understanding of microstructural modifications achieved through SPS technology, providing crucial information for optimizing sintering conditions and reducing the widespread occurrence of PPB, ultimately enhancing the material performance of PM nickel-based superalloys.


Language structure in the n -object naming game.
We examine a naming game with two agents trying to establish a common vocabulary for n objects. Such efforts lead to the emergence of language that allows for an efficient communication and exhibits some degree of homonymy and synonymy. Although homonymy reduces the communication efficiency, it seems to be a dynamical trap that persists for a long, and perhaps indefinite, time. On the other hand, synonymy does not reduce the efficiency of communication but appears to be only a transient feature of the language. Thus, in our model the role of synonymy decreases and in the long-time limit it becomes negligible. A similar rareness of synonymy is observed in present natural languages. The role of noise, that distorts the communicated words, is also examined. Although, in general, the noise reduces the communication efficiency, it also regroups the words so that they are more evenly distributed within the available "verbal" space.


Evaluation of prothrombin induced by vitamin K absence, macrophage migration inhibitory factor and Golgi protein-73 versus alpha fetoprotein for hepatocellular carcinoma diagnosis and surveillance.
Hepatocellular carcinoma (HCC) represents a challenging malignancy of worldwide importance. It is the third most common cause of cancer-related death globally as most patients present with unresectable disease. Alpha-fetoprotein (AFP) is the widely and solely used biomarker for HCC diagnosis; yet, its usefulness is hampered by low sensitivity and specificity. We aimed to identify more sensitive biomarkers for HCC diagnosis and a surveillance algorithm that may facilitate early detection of HCC. A total of 305 Egyptian and Saudi participants grouped as healthy controls, cancer controls, benign hepatic lesions, chronic viral hepatitis and HCC were included. Serum AFP, prothrombin induced by vitamin K absence-II (PIVKA-II), macrophage migration inhibitory factor (MIF) and Golgi protein-73 (GP-73) levels were quantitated by enzyme immunoassay. Significantly higher levels of GP-73 and PIVKA-II were detected in the HCC group than in all other groups, while MIF showed a highly significant increase in HCC from all groups except the cancer control group. The HCC group showed no significant difference between the studied biomarkers and the type of chronic viral hepatitis. On the basis of multiple ROC curve analyses, GP-73 and PIVKA-II showed the highest sensitivity and specificity for surveillance and diagnosis. In conclusion, PIVKA-II and GP-73 offer an effective approach for early HCC diagnosis and surveillance of high-risk groups with a higher accuracy than AFP. MIF may serve as a promising screening tumor marker for the detection of gastrointestinal tract (GIT) malignancy.


Ultrastructural Features of Neurovascular Units in a Rat Model of Chronic Compressive Spinal Cord Injury.
Chronic spinal cord compression is the most common cause of spinal cord impairment worldwide. Objective of this study is to assess the ultrastructural features of the neurovascular unit (NVU) in a rat model of chronic compressive spinal cord injury, 24 SD rats were divided into two groups: the control group (n = 12), and the compression group (n = 12). A C6 semi-laminectomy was performed in the control group, whereas a water-absorbent polyurethane polymer was implanted into the C6 epidural space in the compression group. The Basso Beattie Bresnahan (BBB) scores and the somatosensory evoked potentials (SEP) were used to evaluate neurological functions. Transmission Electron Microscopy (TEM) was performed to investigate the change of NVU at the 28th day after modeling. Compared with the control group, the compression group shows a significant reduction (P < 0.05) of BBB score and a significant severity (P < 0.05) of abnormal SEP. TEM results of the compression group showed a striking increase in endothelial caveolae and vacuoles; a number of small spaces in tight junctions; a significant increase in pericyte processing area and vessel coverage; an expansion of the basement membrane region; swollen astrocyte endfeet and mitochondria; and the degeneration of neurons and axons. Our study revealed that damage to NVU components occurred followed by chronic compressive spinal cord injury. Several compensatory changes characterized by thicker endothelium, expansive BM, increased pericyte processing area and vessel coverage were also observed.


Osteopathy in the French-speaking part of Switzerland: Practitioners' profile and scope of back pain management.
Osteopathy is commonly used for spinal pain, but knowledge about back pain management by osteopaths is scarce. The aim of this study was to survey osteopaths across the French-speaking part of Switzerland about the scope of their practice and their management of patients with back pain. This cross-sectional observational study was based on an online survey conducted from March to June 2017. Setting and participants: All registered osteopaths of the French-speaking part of Switzerland were asked to complete the survey. Outcome measures: In addition to descriptive statistics (practice characteristics, patients' profiles, scope of treatment modalities, health promotion, research, and osteopathic practice), we explored variables associated with osteopaths' practice, such as age and gender. A total of 241 osteopaths completed the questionnaire (response rate: 28.8%). Almost two thirds of osteopaths were female. Ages ranged from 25 to 72 years with an overall mean of 42.0 (SD 10.7) years. Male osteopaths reported more weekly working hours than female osteopaths did (38.2 [SD 11.0] vs 31.6 [SD 8.9], respectively, p<0.001). Almost a third (27.8%,) of osteopaths could arrange an appointment for acute conditions on the same day and 62.0% within a week. Acute or subacute spinal conditions, mainly low back and neck pain, were the most frequent conditions seen by our respondents. For 94.4% of osteopaths, one to three consultations were required for the management of such conditions. Osteopaths play a role in the management of spinal conditions, especially for acute problems. These findings, combined with short waiting times for consultations for acute conditions, as well as prompt management capabilities for acute low back and acute neck pain, support the view that the osteopathic profession constitutes an added value to primary care.


Primary malignant chest wall tumours.
Neoplasms of the chest wall are not uncommon. Majority of the tumours occurring in the chest wall are benign. The tumours may arise from the soft tissues,connective tissues or bone. Metastatic tumours can arise as a result of direct infiltration or haematogenous spread. The management of these tumours is challenging. Resection of the chest wall with or without the excision of ribs, require reconstruction not only for aesthetic reasons but also for providing the stability to the chest wall which is of prime importance in maintaining the respiratory functions. In this article, 46 cases of the primary malignant chest wall tumours seen over a period of 5 years are reviewed.


[Nanomaterials in cosmetics--present situation and future].
Cosmetics are consumer products intended to contribute to increasing quality of life and designed for long-term daily use. Due to such features of cosmetics, they are required to ensure quality and safety at a high level, as well as to perform well, in response to consumers' demands. Recently, the technology associated with nanomaterials has progressed rapidly and has been applied to various products, including cosmetics. For example, nano-sized titanium dioxide has been formulated in sunscreen products in pursuit of improving its performance. As some researchers and media have expressed concerns about the safety of nanomaterials, a vague feeling of anxiety has been raised in society. In response to this concern, the Japan Cosmetic Industry Association (JCIA) has begun original research related to the safety assurance of nanomaterials formulated in cosmetics, to allow consumers to use cosmetics without such concerns. This paper describes the activities of the JCIA regarding safety research on nanomaterials, including a survey of the actual usage of nanomaterials in cosmetics, analysis of the existence of nanomaterials on the skin, and assessment of skin carcinogenicity of nano-sized titanium dioxide. It also describes the international status of safety assurance and regulation regarding nanomaterials in cosmetics.


Thermally-assisted ultrasonic separation of giant vesicles.
We report on a newly-developed membrane stiffness-based separation of vesicles using a thermally-assisted acoustophoretic approach. By tuning the temperature, we achieved the separation of vesicles of the same size, shape, and charge but with different stiffness values. It was observed that at a specific transition point, the acoustic contrast factor of vesicles changed sign from positive to negative. This change was mainly due to the change in the acoustic compressibility of the vesicles, which is inversely proportional to stiffness. The acoustic contrast temperature, corresponding to the temperature at which the acoustic contrast factor switches sign, was determined to be unique to the composition of the vesicles. This unique temperature signature allowed us to develop a separation method of vesicles with distinct membrane stiffness with target outlet purities exceeding 95%. Our studies suggest that this method may be applied for the separation of cells affected by diseases that affect the cellular stiffness.


Short- and long-term exposure to air pollution increases the risk of stroke.
Many epidemiological studies have observed the association of air pollutant exposure with the onset, progression, and mortality of stroke. The aim of this study was to investigate the associations of air pollutants, including SO2, NO2, O3, CO, and PM10, with stroke according to exposure duration. Data from the Korean National Health Insurance Service-Health Screening Cohort from 2002 to 2015 were obtained. The 21,240 patients who were admitted for or died due to stroke were 1:4 matched for age, sex, income, and region of residence with 84,960 control participants. The meteorological factors of mean, highest, and lowest temperatures; relative humidity; ambient atmospheric pressure; and air pollutant concentrations (SO2, NO2, O3, CO, and PM10) were analyzed to determine their associations with stroke. The odds ratios for stroke after exposure to each meteorological factor and air pollutant at 7 and 30 days were calculated in the stroke and control groups. Subgroup analyses were conducted according to age, sex, income, and region of residence. The odds ratio associated with seven days of exposure to CO was 1.16 (95% CI = 1.04-1.31) in stroke patients. For 30 days of exposure, the odds ratio associated with CO was 1.16 (95% CI = 1.02-1.32) in stroke patients. Seven and 30 days of NO2 exposure were inversely associated with stroke. The odds ratio associated with seven days of exposure to O3 was 1.16 (95% CI = 1.01-1.32) in ischemic stroke patients. Both ischemic and hemorrhagic stroke had negative associations with 7 and 30 days of NO2 exposure. Both short- and long-term exposure to CO were related to stroke.


Luminescence line shapes of band to deep centre and donor-acceptor transitions in AlN.
Energy structure and electron coupling with local lattice vibrations have been investigated for deep centres in AlN using hybrid functional density functional theory. Local phonon energies and Huang-Rhys parameters have been calculated for defects and defect complexes containing most common unintentional impurities of carbon, oxygen and silicon, and for intrinsic vacancies, nitrogen split-interstitial defect, and complexes of Al and N vacancies in AlN. Luminescence line shapes of band to deep centre transitions in AlN have been calculated in dependence on temperature for most abundant defects in AlN. Donor-acceptor luminescence line shapes for shallow donor to deep acceptor and deep donor to deep acceptor transitions have been considered theoretically. Configuration diagrams of oxygen and silicon DX centres have been calculated by density functional theory with hybrid functional, and peak energies of optical transitions of an electron from the DX-centres to deep acceptors have been estimated. Possible assignments of the experimental luminescence bands in AlN based on the calculations have been discussed.


Histamine-release effectors from Angelica dahurica var. dahurica root.
Six compounds isolated from the EtOAc fraction of the dried roots of Angelica dahurica var. dahurica inhibited compound 48/80-induced histamine levels in mouse peritoneal cavity (in vivo). Bergapten, oxypeucedanin hydrate, and byakangelicin inhibited compound 48/80-induced histamine elevation at a dose of 25 mg/kg. Conversely, sec-O-acetylbyakangelicin [8-(2-acetoxy-3-hydroxy-3-methylbutoxy)-5-methoxypsoralenI enhanced compound 48/80-induced histamine elevation at a dose of 25 mg/kg, while phellopterin and oxypeucedanin had no effect.


Cryptococcal meningoencephalitis relapse after an eight-year delay: an interplay of infection and immune reconstitution.
We report a case of a symptomatic relapse of HIV-related cryptococcal meningoencephalitis eight years after the first diagnosis on the background of immune reconstitution. The findings as well as the clinical course suggests a combination of smouldering localised infection and enhanced inflammatory reaction related to immune restoration due to antiretroviral therapy. A combination of antifungal and anti-inflammatory therapy resulted in clinical and radiological improvement. Our case challenges the concept that immune reconstitution inflammatory syndrome and microbiological relapse are dichotomous entities.


Nationwide population-based study of trends and regional variation in breast-conserving treatment for breast cancer.
Landmark trials have shown breast-conserving surgery (BCS) combined with radiotherapy to be as safe as mastectomy in breast cancer treatment. This population-based study aimed to evaluate trends in BCS from 1989 to 2015 in nine geographical regions in the Netherlands. All women diagnosed between 1989 and 2015 with primary T1-2 N0-1 breast cancer, treated with BCS or mastectomy, were identified from the Netherlands Cancer Registry. Crude and case mix-adjusted rates of BCS were evaluated and compared between nine Dutch regions for two time intervals: 1989-2002 and 2003-2015. The annual percentage change in BCS per region over time was assessed by means of Joinpoint regression analyses. Explanatory variables associated with the choice of initial surgery were evaluated using multivariable logistic regression. A total of 202 934 patients were included, 82 200 treated in 1989-2002 and 120 734 in 2003-2015. During 1989-2002, the mean rate of BCS was 50·6 per cent, varying significantly from 39·0 to 71·7 per cent between the nine regions. For most regions, a marked rise in BCS was observed between 2002 and 2003. During 2003-2015, the mean rate of BCS increased to 67·4 per cent, but still varied significantly between regions from 58·5 to 75·5 per cent. A significant variation remained after case-mix correction. This large nationwide study showed that the use of BCS increased from 1989 to 2015 in the Netherlands. After adjustment for explanatory variables, a large variation still existed between the nine regions. This regional variation underlines the need for implementation of a uniform treatment and decision-making strategy.


Distribution of bifidobacteria in the gastrointestinal tract of calves.
Development of gastrointestinal microflora of calves with special reference to bifidobacteria was investigated; fecal bacteria were enumerated in calves aged 3 days to 7 weeks. Bacteria were detected by using selective media, bifidobacteria using modified TPY agar with an addition of mupirocin and acetic acid and by fluorescence in situ hybridization (FISH). Bifidobacteria were dominant group of fecal flora of calves after 7 d of life, constituting 10 % of total bacterial counts. The highest bacterial concentrations were observed in rumen, cecum, and colon, the lowest in abomasum and duodenum. Bifidobacteria and lactobacilli exhibited the highest survival ability during stomach passage and dominated in all parts of the digestive tract. Bifidobacteria counts determined by FISH were significantly higher than those provided by cultivation. Modified TPY agar was highly selective and suitable for bifidobacteria isolation but FISH was shown to be a more precise method for their enumeration. Our results show that gastrointestinal microflora of calves in the milk-feeding period is similar to breast-fed infants with respect to the occurrence of bifidobacteria as a dominant bacterial group. The use of Bifidobacterium strains offers a promising way for providing beneficial effectors for calves in the milk-feeding period.


Electrically deactivating nearest-neighbor donor-pair defects in Si.
Based on first-principles density-functional calculations, we propose a class of nearest-neighbor donor pairs that are energetically favorable in highly n-type Si. These donor pairs comprise dopant atoms either fourfold coordinated at the nearest-neighbor distance or threefold coordinated through bond-breaking relaxations. For P and As dopants, the two defect states are very close in energy, less than 0.1 eV, while the threefold coordinated state is more stable by 0.24 eV for Sb dopants. The former state has a very deep donor level close to the valence band maximum, while the defect level lies deep inside the valence band for the latter. Thus, both the donor pairs are electrically inactive at very high doping levels, and they are suggested to be responsible for the observed saturation of carriers.


Infectious complications in patients with cardiac implantable electronic devices: risk factors, prevention, and prognosis.
INTRODUCTION Cardiac implantable electronic device (CIED) infections still constitute a significant challenge. The knowledge of risk factors for CIED infections is crucial for preventing infections and reducing mortality rates. OBJECTIVES The aim of this study was to assess the risk factors and long-term survival of patients with CIED infections. PATIENTS AND METHODS We analyzed the clinical data of 1837 patients (including 750 [40.9%] patients with CIED infections), who underwent transvenous lead extraction at a single institution between 2006 and 2015. We compared the clinical and procedure-related factors for all types of CIED infections: isolated pocket infection (IPI), isolated lead-related infective endocarditis (ILRIE), and lead-related infective endocarditis with coexisting pocket infection (LRIE + PI). We also analyzed long-term survival rates. RESULTS The development of IPI and LRIE + PI depended mainly on age, male sex, number of leads, presence of implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy defibrillator (CRT-‑D), and the number of previous procedures. The factors that determined ILRIE included chronic kidney disease (CKD), ICD/CRT-D, lead loops, and intracardiac lead abrasion. Chronic anticoagulation and antiplatelet treatment protected against the development of infection. Long-term survival was significantly related to age, heart failure, diabetes mellitus, CKD, malignancy, and chronic atrial fibrillation. CONCLUSIONS The development of all types of CIED infection was associated mainly with procedure-related factors, while long-‑term mortality was dependent on clinical factors. The dissimilarity of factors affecting the development of IPI and ILRIE confirms that there are 2 variants of CIED infection. The protective effects of chronic anticoagulation and antiplatelet treatment should prompt us to consider such therapy in the prevention of CIED infection.


The role of insulin-like growth factor binding protein-3 in the growth inhibitory actions of androgens in LNCaP human prostate cancer cells.
Insulin-like growth factor binding protein-3 (IGFBP-3), an antiproliferative and proapoptotic protein, has been shown to be upregulated by growth inhibitory concentrations of androgens in LNCaP human prostate cancer (PCa) cells, but the mechanism of regulation and the role of IGFBP-3 in the modulation of PCa cell proliferation are unknown. In this study, we have examined the effects of a range of concentrations of the synthetic androgen R1881 on IGFBP-3 expression and cell growth in LNCaP cells. We have also investigated the role of androgen-stimulated IGFBP-3 in androgen-induced growth inhibition. We show that low doses of R1881 stimulate LNCaP cell proliferation, but do not induce IGFBP-3 expression, whereas high doses of R1881 that inhibit cell growth, significantly increase expression of IGFBP-3. Importantly, we demonstrate that the combination of calcitriol and androgens not only synergistically upregulates IGFBP-3 expression but also inhibits cell growth better than either hormone alone. siRNA knockdown of IGFBP-3 expression partially reverses the growth inhibition by calcitriol and by androgens. Furthermore, we find that the growth inhibitory dose of R1881 leads to increases in the cyclin dependent kinase inhibitors (CDKIs), p21 and p27 as well as to G1 arrest. These changes can be blocked or partially reversed by IGFBP-3 siRNA, indicating that the induction of CDKIs is downstream of IGFBP-3. Our data suggest, for the first time, that IGFBP-3 is involved in the antiproliferative action of high doses of androgens partly through p21 and p27 pathways and that IGFBP-3 may contribute significantly to androgen-induced changes in LNCaP cell growth.


A Prospective Evaluation of Duplex Ultrasound for Thoracic Outlet Syndrome in High-Performance Musicians Playing Bowed String Instruments
Thoracic outlet syndrome (TOS) is a neurovascular condition involving the upper extremity, which is known to occur in individuals who perform chronic repetitive upper extremity activities. We prospectively evaluate the incidence of TOS in high-performance musicians who played bowed string musicians. Sixty-four high-performance string instrument musicians from orchestras and professional musical bands were included in the study. Fifty-two healthy volunteers formed an age-matched control group. Bilateral upper extremity duplex scanning for subclavian vessel compression was performed in all subjects. Provocative maneuvers including Elevated Arm Stress Test (EAST) and Upper Limb Tension Test (ULTT) were performed. Abnormal ultrasound finding is defined by greater than 50% subclavian vessel compression with arm abduction, diminished venous waveforms, or arterial photoplethysmography (PPG) tracing with arm abduction. Bowed string instruments performed by musicians in our study included violin (41%), viola (33%), and cello (27%). Positive EAST or ULTT test in the musician group and control group were 44%, and 3%, respectively (p = 0.03). Abnormal ultrasound scan with vascular compression was detected in 69% of musicians, in contrast to 15% of control subjects (p = 0.03). TOS is a common phenomenon among high-performance bowed string instrumentalists. Musicians who perform bowed string instruments should be aware of this condition and its associated musculoskeletal symptoms.


Preliminary study of total flavonoids from Litsea coreana Levl. on experimental adjuvant-induced arthritis in rats.
Litsea coreana Levl., a traditional Chinese medicine, has long been used for its diverse benefits such as detoxification and detumescence. Total flavonoids from Litsea coreana Levl. (TFLC) are the effective fraction of L. coreana. This study was designed to investigate the anti-inflammatory effects and mechanisms of TFLC against Feund's complete adjuvant (FCA)-induced arthritis in rats. Arthritis was evaluated by secondary paw swelling, polyarthritis index, body weight and histopathologic analysis. Con A- or LPS-stimulated splenocyte proliferation and cytokine (IL-1 and IL-2) production were assessed by MTT assay and activated mouse cell proliferation assay, respectively. The results indicate that therapeutic administration of TFLC (50, 100, 200 mg/kg, ig x 12 days) could significantly suppress secondary arthritis in rats with adjuvant-induced arthritis (AA). In vivo, TFLC (50, 100, 200 mg/kg, ig x 12 days) augmented splenocyte proliferation and increased IL-2 production in splenocytes, while reduced IL-1 activity in peritoneal macrophages (PM(Phi)) of AA rats. In vitro, TFLC at concentrations from 0.005 to 50 microg/ml exerted the same immunoregulatory effects on AA rats as those in vivo. In addition, an attractive feature of TFLC lies in its apparent lack of toxicity. These results suggest that TFLC without toxicity has a significant anti-arthritic effect on AA rats which could be associated with its anti-inflammatory and immunomodulatory properties.


Text mining for improved exposure assessment.
Chemical exposure assessments are based on information collected via different methods, such as biomonitoring, personal monitoring, environmental monitoring and questionnaires. The vast amount of chemical-specific exposure information available from web-based databases, such as PubMed, is undoubtedly a great asset to the scientific community. However, manual retrieval of relevant published information is an extremely time consuming task and overviewing the data is nearly impossible. Here, we present the development of an automatic classifier for chemical exposure information. First, nearly 3700 abstracts were manually annotated by an expert in exposure sciences according to a taxonomy exclusively created for exposure information. Natural Language Processing (NLP) techniques were used to extract semantic and syntactic features relevant to chemical exposure text. Using these features, we trained a supervised machine learning algorithm to automatically classify PubMed abstracts according to the exposure taxonomy. The resulting classifier demonstrates good performance in the intrinsic evaluation. We also show that the classifier improves information retrieval of chemical exposure data compared to keyword-based PubMed searches. Case studies demonstrate that the classifier can be used to assist researchers by facilitating information retrieval and classification, enabling data gap recognition and overviewing available scientific literature using chemical-specific publication profiles. Finally, we identify challenges to be addressed in future development of the system.


The transcription factor T-bet is essential for the development of NKp46+ innate lymphocytes via the Notch pathway.
NKp46+ innate lymphoid cells (ILCs) serve important roles in regulating the intestinal microbiota and defense against pathogens. Whether NKp46+ ILCs arise directly from lymphoid tissue-inducer (LTi) cells or represent a separate lineage remains controversial. We report here that the transcription factor T-bet (encoded by Tbx21) was essential for the development of NKp46+ ILCs but not of LTi cells or nuocytes. Deficiency in interleukin 22 (IL-22)-producing NKp46+ ILCs resulted in greater susceptibility of Tbx21-/- mice to intestinal infection. Haploinsufficient T-bet expression resulted in lower expression of the signaling molecule Notch, and Notch signaling was necessary for the transition of LTi cells into NKp46+ ILCs. Furthermore, NKp46+ ILCs differentiated solely from the CD4- LTi population, not the CD4+ LTi population. Our results pinpoint the regulation of Notch signaling by T-bet as a distinct molecular pathway that guides the development of NKp46+ ILCs.


Efficacy of cytokine-induced killer cells targeting CD40 and GITR.
Since the publication of a novel protocol in 1991, cytokine-induced killer (CIK) cells have shown promising results in the treatment against neoplastic diseases. Despite ongoing preclinical and clinical studies, CIK cell treatment in the context of human monoclonal antibodies targeting tumor-necrosis factor receptors remains overlooked. The present study investigated whether a combination of CIK cells with human monoclonal antibody anti-CD40 and anti-Glucocorticoid-induced TNF-related protein (GITR) would lead to further cytotoxicity against tumor cells expressing CD40 and GITR ligand (L). Therefore, in vitro experiments with human lymphoma cell lines SU-DHL-4 and Daudi (both CD40 positive) and human breast adenocarcinoma MCF-7 (GITRL positive) were performed and the secretion of interferon (IFN)-γ was measured. Three interesting results emerged: i) a combination of CIK cells and anti-CD40 mAb is more effective than CIK cell treatment alone; ii) the use of anti-GITR mAb and CIK cells significantly enhanced the cytotoxicity of CIK cells against MCF-7 compared with single CIK cell treatment and iii) the combination of both antibodies and CIK cells abrogates the anti tumoral effect of CIK cells on all three cell lines. By performing an ELISA for IFN-γ measurement, a lower secretion was observed when anti-CD40 or anti-GITR mAb was added. This outcome indicates that further studies in vitro and in vivo may aid in understanding the synergistic molecular mechanisms of CIK cells, and anti-CD40 and anti-GITR mAb.


Reportable infections following colon surgery in a large public healthcare system in New York City: The consequences of being a level 1 trauma center.
To examine differences in risk factors and outcomes of patients undergoing colon surgery in level 1 trauma centers versus other hospitals and to investigate the potential financial impact of these reportable infections. Retrospective cohort study between 2015 and 2022. Large public healthcare system in New York City. All patients undergoing colon surgery; comparisons were made between (1) all patients undergoing colon surgery at the level 1 trauma centers versus patients at the other hospitals and (2) the nontrauma and trauma patients at the level 1 trauma centers versus the nontrauma patients at other hospitals. Of 5,217 colon surgeries reported, 3,531 were at level 1 trauma centers and 1686 at other hospitals. Patients at level 1 trauma centers had significantly increased American Society of Anesthesiology (ASA) scores, durations of surgery, rates of delayed wound closure, and rates of class 4 wounds, resulting in higher SIRs (1.1 ± 0.15 vs 0.75 ± 0.18; P = .0007) compared to the other hospitals. Compared to the nontrauma patients at the other hospitals, both the nontrauma and trauma patients at the level 1 trauma centers had higher ASA scores, rates of delayed wound closure, and of class 4 wounds. The SIRs of the nontrauma patients (1.16 ± 1.29; P = .008) and trauma patients (1.26 ± 2.69; P = .066) at the level 1 trauma center were higher than the SIRs of nontrauma patients in the other hospitals (0.65 ± 1.18). Patients undergoing colon surgery at level 1 trauma centers had increased complexity of surgery compared to the patients in other hospitals. Until there is appropriate adjustment for these risk factors, the use of infections following colon surgery as a reportable quality measure should be re-evaluated.


Radical-mediated damage to parasites and erythrocytes in Plasmodium vinckei infected mice after injection of t-butyl hydroperoxide.
Intravenous injection of t-butyl hydroperoxide rapidly killed Plasmodium vinckei in mice, and caused haemolysis. The same dose seemed harmless to unparasitized mice. Many parasites disintegrated inside circulating erythrocytes, so parasite death was not simply a passive consequence of haemolysis. Injection of desferrioxamine, which removes the traces of free iron that promote the dissociation of t-butyl hydroperoxide into radical species, prevented both parasite death and haemolysis. Lipid peroxidation, as measured by accumulation of malonyldialdehyde over 2 h in vitro, occurred in erythrocytes exposed to t-butyl hydroperoxide, and was particularly marked in erythrocytes from parasitized mice. These erythrocytes accumulated appreciable malonyldialdehyde even without exposure to t-butyl hydroperoxide. Desferrioxamine inhibited the accumulation of malonyldialdehyde, but did not prevent depletion of reduced glutathione by t-butyl hydroperoxide. This suggests that t-butyl hydroperoxide damaged parasites and erythrocytes by dissociating into radical species, rather than by decreasing intraerythrocyte anti-oxidant capacity. In earlier experiments we suggested that intraerythrocytic parasite death and haemolysis caused by alloxan were mediated by radical species, and these experiments with t-butyl hydroperoxide add weight to this interpretation. We regard both of these systems as models for macrophage-induced parasite death and host pathology in acute malaria.


Hydrating effects of a corticoid oil formulation and its vehicle on human skin.
Factors in the treatment of atopic dermatitis include restoring skin moisture and reducing inflammation. This study evaluated a corticoid oil formulation and its components with respect to their skin hydration potential. Ten healthy Caucasians were enrolled. Five test sites on the left and right forearm of each subject were tested: one site served as a normal skin control (without treatment), whereas four were wetted by spraying distilled water (approximately 0.1 ml) over a 3-cm2 skin surface area, and spraying was repeated every 5 min for a total of three applications. Five minutes after the final application, 0.2 ml of the corticoid oil formulation, moisturizing vehicle, and plain peanut oil were applied to each pre-designated site (3 cm2); one site was kept as a blank control (water saturation only). Thirty minutes later, test sites were gently wiped with paper tissues, and visual scoring, transepidermal water loss (TEWL), and capacitance were recorded and repeated at 2 and 3 h. The corticoid oil formulation, plain peanut oil, and moisturizing vehicle significantly increased skin hydration 30 min after each single application, with no statistically significant difference among the treatments at any point. The corticoid oil formulation and plain peanut oil slightly but not significantly elevated TEWL 30 min after application. The results support intuitive dermatologic judgment of advising patients to apply moisturizing medicaments after bathing.


Enhancement of radiation response in human cervical cancer cells in vitro and in vivo by arsenic trioxide (As2O3).
Arsenic trioxide (As2O3) inhibits cell growth and induces apoptosis in certain types of cancer cells including acute promyelocytic leukemia, prostate and ovarian carcinomas, but its effect on response of tumor cells to ionizing radiation has never been explored before. Here we demonstrate that As2O3 can sensitize human cervical cancer cells to ionizing radiation both in vitro and in vivo. As2O3 in combination with ionizing radiation have a synergistic effect in decreasing clonogenic survival and in the regression of established human cervical tumor xenografts. Pretreatment of the cells with As2O3 also synergistically enhanced radiation-induced apoptosis. Apoptosis of the cells by combined treatment of As2O3 and radiation was associated with reactive oxygen species generation and loss of mitochondrial membrane potential, resulting in the activation of caspase-9 and caspase-3. The combined treatment also resulted in an increased G2/M cell cycle distribution at the concentration of As2O3 which did not alter cell cycle when applied alone. These results indicate that As2O3 can synergistically enhance radiosensitivity of human cervix carcinoma cells in vitro and in vivo, suggesting a potential clinical applicability of combination treatment of As2O3 and ionizing radiation in cancer therapies.


Earliest steps in primary tumor formation and micrometastasis resolved with histochemical markers of gene-tagged tumor cells.
To facilitate detection of tumor cells at the highest resolution in any organ in athymic nude mouse model systems, a histochemical marker gene [bacterial lacZ or human placental alkaline phosphatase (ALP)] was transfected into specified transformed/tumor cells (fibrosarcoma or neuroblastoma). The fates of tumor cells were followed qualitatively and quantitatively by histochemical staining of whole organs or organ sections. Primary tumors developed initially via formation of "curly-haired" complexes of cells in the subcutis or dermis, followed by division of a large fraction of cells. When two tumor classes were mixed before injection, outgrowth occurred in regional concentrations of the primary tumor. Blood microvessels were detectable within 72 hr of injection, growing into tumor regions. iv injection routinely yielded multicellular foci in the lungs within minutes as precursors of experimental metastases. Micrometastasis was further resolved with cells "inactivated" by different treatments and by co-injection of two different tagged cell types. These approaches using different histochemical marker genes to "tag" different tumor cell classes, along with more advanced molecular biological approaches, permit us to characterize gene expression and its reversibility during the earliest stages of primary tumor formation and micrometastasis to virtually any organ in the recipient animal.


Type II Secretion in Escherichia coli.
The type II secretion system (T2SS) is used by Escherichia coli and other gram-negative bacteria to translocate many proteins, including toxins and proteases, across the outer membrane of the cell and into the extracellular space. Depending on the bacterial species, between 12 and 15 genes have been identified that make up a T2SS operon. T2SSs are widespread among gram-negative bacteria, and most E. coli appear to possess one or two complete T2SS operons. Once expressed, the multiple protein components that form the T2S system are localized in both the inner and outer membranes, where they assemble into an apparatus that spans the cell envelope. This apparatus supports the secretion of numerous virulence factors; and therefore secretion via this pathway is regarded in many organisms as a major virulence mechanism. Here, we review several of the known E. coli T2S substrates that have proven to be critical for the survival and pathogenicity of these bacteria. Recent structural and biochemical information is also reviewed that has improved our current understanding of how the T2S apparatus functions; also reviewed is the role that individual proteins play in this complex system.


Cholestatic fibrosing hepatitis and hepatitis B after bone marrow transplantation.
In the setting of transplantation and chronic hepatitis B viral infection there is a unique histological feature termed cholestatic fibrosing hepatitis. The use of nucleoside analogues in the treatment of this condition has been successful. We describe a case of cholestatic fibrosing hepatitis, which occurred after intense immunosuppression for graft versus host disease in a patient with bone marrow transplantations. She was commenced on lamivudine therapy and showed good clinical, biochemical and virological response. However she succumbed due to sepsis.


Obesity-induced CerS6-dependent C16:0 ceramide production promotes weight gain and glucose intolerance.
Ceramides increase during obesity and promote insulin resistance. Ceramides vary in acyl-chain lengths from C14:0 to C30:0 and are synthesized by six ceramide synthase enzymes (CerS1-6). It remains unresolved whether obesity-associated alterations of specific CerSs and their defined acyl-chain length ceramides contribute to the manifestation of metabolic diseases. Here we reveal that CERS6 mRNA expression and C16:0 ceramides are elevated in adipose tissue of obese humans, and increased CERS6 expression correlates with insulin resistance. Conversely, CerS6-deficient (CerS6(Δ/Δ)) mice exhibit reduced C16:0 ceramides and are protected from high-fat-diet-induced obesity and glucose intolerance. CerS6 deletion increases energy expenditure and improves glucose tolerance, not only in CerS6(Δ/Δ) mice, but also in brown adipose tissue- (CerS6(ΔBAT)) and liver-specific (CerS6(ΔLIVER)) CerS6 knockout mice. CerS6 deficiency increases lipid utilization in BAT and liver. These experiments highlight CerS6 inhibition as a specific approach for the treatment of obesity and type 2 diabetes mellitus, circumventing the side effects of global ceramide synthesis inhibition.


Isolation, molecular characterization, and in vitro differentiation of bovine Wharton jelly-derived multipotent mesenchymal cells.
Extrafetal tissues are a noncontroversial and inexhaustible source of mesenchymal stem cells that can be harvested noninvasively at low cost. In the veterinary field, as in man, stem cells derived from extrafetal tissues express plasticity, reduced immunogenicity, and have high anti-inflammatory potential making them promising candidates for treatment of many diseases. Umbilical cord mesenchymal cells have been isolated and characterized in different species and have recently been investigated as potential candidates in regenerative medicine. In this study, cells derived from bovine Wharton jelly (WJ) were isolated for the first time by enzymatic methods, frozen/thawed, cultivated for at least 10 passages, and characterized. Wharton jelly-derived cells readily attached to plastic culture dishes displaying typical fibroblast-like morphology and, although their proliferative capacity decreased to the seventh passage, these cells showed a mean doubling time of 34.55 ± 6.33 hours and a mean frequency of one colony-forming unit fibroblast like for every 221.68 plated cells. The results of molecular biology studies and flow cytometry analyses revealed that WJ-derived cells showed the typical antigen profile of mesenchymal stem cells and were positive for CD29, CD44, CD105, CD166, Oct-4, and c-Myc. They were negative for CD34 and CD14. Remarkably, WJ-derived cells showed differentiation ability. After culture in induced media, WJ-derived cells were able to differentiate into osteogenic, adipogenic, chondrogenic, and neurogenic lines as shown by positive staining and expression of specific markers. On polymerase chain reaction analysis, these cells were negative for MHC-II and positive for MHC-I, thus reinforcing the role of extrafetal tissue as an allogenic source for bovine cell-based therapies. These results provide evidence that bovine WJ-derived cells may have the potential to differentiate to repair damaged tissues and reinforce the importance of extrafetal tissues as stem cell sources in veterinary regenerative medicine. A more detailed evaluation of their immunologic properties is necessary to better understand their potential role in cellular therapy.


Skin expansion to eliminate large scalp defects.
In three children aged 3 to 8 years with large scalp defects temporary expanders of silicone elastomer were inserted under the scalp above the pericranium and under the galea through an incision at the junction of the defect and the normal scalp. Over the following six to eight weeks, the expanders were inflated weekly or semiweekly with injections of saline. During expansion, hair growth continued. When the scalp flap expansion was completed, the scalp margin was advanced. Two of the 3 patients required additional expansion, so a deflated expander was left under the scalp. The entire defect was covered in each case. This technique has wide application for a variety of reconstructive problems.


Distinct aetiopathogenesis in subgroups of functional dyspepsia according to the Rome III criteria.
Whether there is distinct pathogenesis in subgroups of functional dyspepsia (FD), the postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS) remains controversial. We aimed to identify the risk factors of FD and its subgroups in the Chinese population. Patients with dyspepsia and healthy subjects who underwent gastric cancer screening were enrolled in this multicentre study from 2010 to 2012. All patients were evaluated by questionnaire, oesophagoduodenoscopy, histological examination and Helicobacter pylori tests. Subgroups of FD were classified according to the Rome III criteria. Psychiatric stress was assessed by the short form Brief Symptom Rating Scale. CagA and VacA genotypes were determined by PCR. Of 2378 patients screened for eligibility, 771 and 491 fulfilled the diagnostic criteria of uninvestigated dyspepsia and FD, respectively. 298 (60.7%) and 353 (71.9%) individuals were diagnosed with EPS and PDS, respectively, whereas 169 (34.4%) had the overlap syndrome. As compared with 1031 healthy controls, PDS and EPS shared some common risk factors, including younger age (OR 0.95; 99.5% CI 0.93 to 0.98), non-steroidal anti-inflammatory drugs (OR 6.60; 99.5% CI 3.13 to 13.90), anxiety (OR 3.41; 99.5% CI 2.01 to 5.77) and concomitant IBS (OR 6.89; 99.5% CI 3.41 to 13.94). By contrast, H. pylori (OR 1.86; 99.5% CI 1.01 to 3.45), unmarried status (OR 4.22; 99.5% CI 2.02 to 8.81), sleep disturbance (OR 2.56; 99.5% CI 1.29 to 5.07) and depression (OR 2.34; 99.5% CI 1.04 to 5.36) were associated with PDS. Moderate to severe antral atrophy and CagA positive strains were also more prevalent in PDS. Different risk factors exist among FD subgroups based on the Rome III criteria, indicating distinct aetiopathogenesis of the subdivisions that may necessitate different therapeutic strategies.


Do You See What I See? The Effect of Gaze Tracking on Task Space Remote Collaboration.
We present results from research exploring the effect of sharing virtual gaze and pointing cues in a wearable interface for remote collaboration. A local worker wears a Head-mounted Camera, Eye-tracking camera and a Head-Mounted Display and shares video and virtual gaze information with a remote helper. The remote helper can provide feedback using a virtual pointer on the live video view. The prototype system was evaluated with a formal user study. Comparing four conditions, (1) NONE (no cue), (2) POINTER, (3) EYE-TRACKER and (4) BOTH (both pointer and eye-tracker cues), we observed that the task completion performance was best in the BOTH condition with a significant difference of POINTER and EYETRACKER individually. The use of eye-tracking and a pointer also significantly improved the co-presence felt between the users. We discuss the implications of this research and the limitations of the developed system that could be improved in further work.


Prognostic significance of positive lymph node number in early cervical cancer.
The aim of the present study was to investigate whether the number of metastatic lymph nodes (LNs) is an independent prognostic factor for early cervical cancer. The medical records of 163 stage IB-IIA cervical cancer patients, treated with radical hysterectomy with accompanying pelvic and/or para-aortic lymphadenectomy between 1999 and 2007, were retrospectively reviewed. All prognostic factors identified as being significant in the univariate analysis were included in the multivariate analysis using the Cox proportional hazards model. Of the 156 patients included in our analysis, 27 had LN metastasis, of whom 14 patients had 1 positive node and 13 patients had ≥2 positive nodes. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 92.9 and 87.2%, respectively. In terms of OS, tumour stage (P=0.002) and the number of positive LNs (P=0.021) were identified as significant prognostic factors. In terms of PFS, tumour stage (P=0.049) was identified as a significant prognostic factor. In conclusion, the number of LN metastases is an independent risk factor for poorer survival outcomes in patients with cervical cancer.


[A Prediction Model for Human Immunodeficiency Virus Infection and Mother-to-Child Transmission Based on the Expression Levels of Selenoprotein Genes].
Objective To study the expression of selenoprotein genes in human immunodeficiency virus(HIV)infection and its mother-to-child transmission,so as to provide a theoretical basis for the prevention,diagnosis,and treatment of acquired immunodeficiency syndrome.Methods The dataset GSE4124 was downloaded from the Gene Expression Omnibus(GEO).Two groups of HIV-positive mothers(n=25)and HIV-negative mothers(n=20)were designed.HIV-positive mothers included a subset of transmitter(TR)mothers(n=11)and non-transmitter(NTR)mothers(n=14).Then,t-test was carried out to compare the expression levels of selenoprotein genes between the four groups(HIV-positive vs. HIV-negative,NTR vs. HIV-negative,TR vs. HIV-negative,TR vs. NTR).Univariate and multivariate Logistic regression were adopted to analyze the effects of differentially expressed genes on HIV infection and mother-to-child transmission.R software was used to establish a nomogram prediction model and evaluate the model performance.Results Compared with the HIV-negative group,HIV-positive,NTR,and TR groups had 8,5 and 8 down-regulated selenoprotein genes,respectively.Compared with the NTR group,the TR group had 4 down-regulated selenoprotein genes.Univariate Logistic regression analysis showed that abnormally high expression of GPX1,GPX3,GPX4,TXNRD1,TXNRD3,and SEPHS2 affected HIV infection and had no effect on mother-to-child transmission.The multivariate Logistic regression analysis showed that the abnormally high expression of TXNRD3(OR=0.032,95%CI=0.002-0.607,P=0.022)was positively correlated with HIV infection.As for the nomogram prediction model,the area under the receiver-operating characteristic curve for 1-year survival of HIV-infected patients was 0.840(95%CI=0.690-1.000),and that for 3-year survival of HIV-infected patients was 0.870(95%CI=0.730-1.000).Conclusions Multiple selenoprotein genes with down-regulated expression levels were involved in the regulation of HIV infection and mother-to-child transmission.The abnormal high expression of TXNRD3 was positively correlated with HIV infection.The findings provide new ideas for the prevention,diagnosis,and treatment of acquired immunodeficiency syndrome.


Fractures in children in south eastern Nigeria.
To evaluate the pattern of fractures in children in the south eastern region of Nigeria, seeking to highlight the planning and designs of buildings, roads and playgrounds to prevent paediatric fractures. Retrospective review of paediatric patients with fractures who presented at the only tertiary referral centre in the region. A university teaching hospital situated in the south eastern corner of Nigeria. 102 paediatric patients treated for fractures between January 1993 and December 1995. Causes of fractures and their anatomical distribution. 71 boys and 31 girls were treated for fractures. The commonest cause of fractures was road traffic accidents accounting for 50% of the patients, followed by falls and collapsing mud walls. Most of the fractures seen (58 patients) were of the green stick type. The femur was the commonly fractured bone (25 patients) followed by the radius (22 patients) and humerus (20 patients). Road traffic accident victims presented earlier at the hospital than victims of other causes. Also lower limb fracture patients presented earlier than patients with upper limb fractures. Paediatric fractures are amenable to conventional conservative therapy and open reduction became necessary in long neglected cases with associated malunion. Since the causes of fractures are largely preventable, public enlightenment campaigns, provision of pedestrian pathways, care on the part of school authorities and proper structural construction of the traditional houses may help reduce the number of cases of fracture in our environment.


Admissions to a provincial psychiatric hospital: the effects of opening a second in-patient facility.
Until 1955, the Saskatchewan Hospital, North Battleford, was the only facility designated for in-patient psychiatric treatment of the northern half of Saskatchewan's population. In that year the University Hospital's 39-bed psychiatric unit was opened in Saskatoon, but the number of Saskatoon patients referred to North Battleford have continued to increase.A statistical study of changes in the annual admission rates (patients/1000 population) to the Saskatchewan Hospital shows that the opening of the University Hospital unit has reduced the rate of intake of Saskatoon residents to the Saskatchewan Hospital. This decrease is related to specific diagnostic groups. There have also been changes in methods of referral.


Improving Performance of Devanagari Script Input-Based P300 Speller Using Deep Learning.
The performance of an existing Devanagari script (DS) input-based P300 speller with conventional machine learning techniques suffers from low information transfer rate (ITR). This occurs due to its required large size of display, i.e., 8 × 8 row-column (RC) paradigm which exhibits issues like crowding effect, adjacency, fatigue, task difficulty, and required large number of trials for character recognition. For P300 detection, deep learning algorithms have shown the state of art performance compared to the conventional machine learning algorithms in the recent past. Therefore, authors have been motivated to develop a deep learning architecture for DS-based P300 speller which can detect the target characters more accurately and in less number of trials. For this, two proven deep learning algorithms, stacked autoencoder (SAE) and deep convolution neural network (DCNN) have been adopted. For further bettering their performances, batch normalization and innovative double batch training is included here to achieve accelerated training and alleviate the problem of overfitting. Additionally, a leaky ReLU activation function has also been used in DCNN to overcome dying ReLU problem. The experiments have been performed on self-generated dataset of 20 Devanagari words with 79 characters acquired from 10 subjects using 16 channel actiCAP Xpress EEG recorder. The experimental results illustrated that the proposed DCNN is able to detect 88.22% correct targets in just three trials. Moreover, it also provides ITR of 20.58 bits per minutes, which is significantly higher than existing techniques.


Management of precipitated opiate withdrawal syndrome induced by nalmefene mistakenly prescribed in opiate-dependent patients: a review for clinicians.
Nalmefene, a long-acting µ-opioid antagonist approved to treat alcohol use disorder, is occasionally mistakenly prescribed to opiate-dependent or opioid-treated patients. We review recent literature on drug-drug interactions between nalmefene and opioids that lead to precipitated opioid withdrawal, and focus on its management and planning for care at discharge. Areas covered: This article provides a brief and comprehensive review of management of precipitated opioid withdrawal syndrome when nalmefene is associated with an opioid, whether misused or legally prescribed. Expert opinion: When treating an opiate-dependent patient with co-occurring alcohol use disorder, both conditions need to be a focus of clinical attention. New drugs for alcohol use disorder have been approved, but must be given cautiously and with a full understanding of their potential drug-drug interactions with opioid medications. Opiate-dependent patients should be intensively monitored for risk factors of alcohol use disorder and should be continuously motivated for treatment maintenance. When nalmefene is administered to opiate-dependent patients, acute opioid withdrawal syndrome may occur. Management of precipitated acute opioid withdrawal may include short or long-acting µ-opioid agonists during hospitalization, in addition to supportive treatment. The best management of polydrug abusers is based on a multidisciplinary approach, which should be pursued and improved through continuing medical education.


Rare Root Canal Configuration of Mandibular Second Premolar Using Cone-beam Computed Tomographic Scanning.
The aim of this case report was to demonstrate how the use of cone-beam computed tomographic (CBCT) imagery is beneficial when treating a tooth with an unusual anatomic variation. A 43-year-old female patient presented to our private practice after a referral from her general dentist. Endodontic therapy was previously initiated and unable to be completed because of suspicious anatomic anatomy. CBCT imagery confirmed the presence of a C-shaped root configuration and 3 canals within the tooth. Root canal treatment was completed successfully without complications. The use of CBCT imaging was valuable in determining the root morphology and rare canal anatomy to enhance treatment and success.


Urethral 'recurrence' found 14 years after radical cystectomy.
We report a case of transitional cell urethral cancer diagnosed 14 years after radical cystectomy. Traditionally, in the postcystectomy setting, these cancers have been referred to as 'recurrences'. We review the biological models for the oncogenesis of these cancers and propose that they are typically a result of a field cancerization effect, rather than being derived from the same clone responsible for the original urothelial tumor.


Polybrominated dibenzo-p-dioxins and related compounds: quantitative in vivo and in vitro structure-activity relationships.
The effects of structure on the in vitro receptor binding affinities, aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase (EROD) induction potencies in rat hepatoma cells were determined for the following compounds: 2-bromo-, 2,7/2,8-dibromo-, 2,3,7-tribromo-, 2,4,6,8/1,3,7,9-tetrabromo-, 2,3,7,8-tetrabromo-, 1,3,7,8-tetrabromo-, 1,2,3,7,8-pentabromo-, 1,2,4,7,8-pentabromo-, 2,3-dibromo-7,8-dichloro-, 2,8-dibromo-3,7-dichloro- and 2-bromo-3,7,8-trichlorodibenzo-p-dioxin. The structure-activity relationships (SARs) for the polybrominated dibenzo-p-dioxins (PBDDs) were comparable for both in vitro responses: the most active compounds were substituted only in the lateral 2,3,7 and 8 position and the addition of non-lateral or removal of lateral halogen substituents reduced the activity of the resultant compound. The biologic and toxic effects of 2,3,7,8-tetrabromo-, 1,3,7,8-tetrabromo-, 1,2,4,7,8-pentabromo-1,2,3,7,8-pentabromo-, 2-bromo-3,7,8-trichloro- and 2,3-dibromo-7,8-dichlorodibenzo-p-dioxin on several receptor-mediated responses (thymic atrophy, body weight loss, hepatic microsomal AHH and EROD induction) were determined in a dose-response fashion in immature male Wistar rats. A comparison of the ED50 values for the in vivo responses demonstrated that the SARs for the PBDDs and brominated polychlorinated dibenzo-p-dioxins were comparable to those observed for in vitro receptor binding and AHH induction. Moreover, there was an excellent linear correlation between the -log EC50 (in vitro AHH induction) vs. the in vivo -log ED50 (thymic atrophy) and -log ED50 (body wt loss) correlation coefficient, r = 0.97 for all 2 correlations).


Coronary artery endothelial dysfunction is present in HIV-positive individuals without significant coronary artery disease.
HIV-positive (HIV+) individuals experience an increased burden of coronary artery disease (CAD) not adequately accounted for by traditional CAD risk factors. Coronary endothelial function (CEF), a barometer of vascular health, is depressed early in atherosclerosis and predict future events but has not been studied in HIV+ individuals. We tested whether CEF is impaired in HIV+ patients without CAD as compared with an HIV-negative (HIV-) population matched for cardiac risk factors. In this observational study, CEF was measured noninvasively by quantifying isometric handgrip exercise-induced changes in coronary vasoreactivity with MRI in 18 participants with HIV but no CAD (HIV+CAD-, based on prior imaging), 36 age-matched and cardiac risk factor-matched healthy participants with neither HIV nor CAD (HIV-CAD-), 41 patients with no HIV but with known CAD (HIV-CAD+), and 17 patients with both HIV and CAD (HIV+CAD+). CEF was significantly depressed in HIV+CAD- patients as compared with that of risk-factor-matched HIV-CAD- patients (P < 0.0001) and was depressed to the level of that in HIV- participants with established CAD. Mean IL-6 levels were higher in HIV+ participants (P < 0.0001) and inversely related to CEF in the HIV+ patients (P = 0.007). Marked coronary endothelial dysfunction is present in HIV+ patients without significant CAD and is as severe as that in clinical CAD patients. Furthermore, endothelial dysfunction appears inversely related to the degree of inflammation in HIV+ patients as measured by IL-6. CEF testing in HIV+ patients may be useful for assessing cardiovascular risk and testing new CAD treatment strategies, including those targeting inflammation.


On possible trypsin-induced biases in peptides analysis with aerolysin nanopore.
Nanopore-based single-molecule analysis technique is a promising approach in the field of proteomics. In this Technical Brief, the interaction between the biological nanopore of Aerolysin (AeL) and peptides is investigated, focusing on potential biases depending on the AeL activation protocol. Our results reveal that residual trypsin, which may be unintentionally introduced in analyte solution when using a classical AeL activation protocol, can induce a significant formation of shorter peptides by enzymatic degradation of longer ones, which may lead to unwanted effects and/or misinterpretations. AeL free-trypsin activation protocol eliminates this bias and appears more appropriate for peptide/proteins analysis, specifically in the perspective of nanopore-based molecular fingerprinting or of low-abundance species characterization.


The single-stranded-DNA-binding proteins (SSB) of Proteus mirabilis and Serratia marcescens.
The single-stranded-DNA-binding (SSB) proteins from Proteus mirabilis and Serratia marcescens were purified from overproducing Escherichia coli strains, which were devoid of their own ssb gene. The strains harboured an endA insertion mutation and a xonA mutation resulting in the absence of endonuclease I and exonuclease I activities from the preparations. The amino acid sequences of the SSB of all three species are nearly identical in the N-terminal parts of the proteins that contain the DNA-binding domain, but differ in the C-terminal parts. Both proteins have an apparent binding-site size of 65 and 35 nucleotides at high and low salt concentrations, respectively. The association-rate constant for binding to poly(dT) is 3.2 x 10(8) M-1 s-1 for P. mirabilis SSB (PmiSSB) and 3.4 x 10(8) M-1 s-1 for S. marcescens SSB (SmaSSB). These binding parameters are very similar to those of E. coli SSB (EcoSSB). The structural similarity of the proteins is also documented by the finding that they can exchange subunits among each other to form mixed tetramers. The transcriptional regulation of the ssb and uvrA genes from P. mirabilis and S. marcescens in SOS-induced E. coli cells was studied using lacZ fusions. While the uvrA genes were inducible, there was no induction of the ssb genes transcribed divergently from the uvrA genes. Apparently, regions with nucleotide sequence similarity to the E. coli SOS-box preceding the ssb genes of P. mirabilis and S. marcescens had no gross effect on the transcription. Studies on growth of the cells and recovery from ultraviolet damage indicate that the heterologous SSB proteins support DNA replication and recombinational DNA repair of E. coli with the same efficiency as the E. coli SSB protein. Interactions with other E. coli proteins involved in these processes either do not occur, or are not impeded.


Evaluating the vaccine potential of an influenza A viral hemagglutinin and matrix double insertion DNA plasmid.
A DNA plasmid expressing both the influenza viral matrix protein (M1) and hemagglutinin (HA) (pHA/M1) as a potential vaccine candidate was investigated. Vaccination with pHA/M1 double insertion plasmids not only induced HA-specific protective antibodies, but also elicited HA and M1-specific CD8 T cell responses. Mice immunized with pHA/M1 dual expressing plasmid showed enhanced HA inhibition titer and increased CD69(+) CD8alpha(+) T cell response compared to groups that received either the vector or a mixture of both pHA and pM1 (pHA+pM1). Furthermore, pHA/M1 immunization resulted in improved protection against both homologous and heterologous challenges.


Ring-expansion protocol: preparation of synthetically versatile dihydrotropones.
A ring-expansion protocol that consisted of the 1,2-addition of various enolate nucleophiles to 6-trimethylsiloxy-2-cyclohexene-1-one (1) and the NaIO(4)-promoted oxidative ring opening of the resulting diols 2, followed by an intramolecular Knoevenagel condensation, furnished versatile dihydrotropones 6. Maintaining Z-configuration in the oxidative ring-opening products 3 is crucial for the success of the ring-expansion strategy. Dihydrotropones 6 are ripe for further elaborations such as oxidation to tropones 8 and Diels-Alder reaction with the Danishefsky's diene 10 to afford polycyclic compounds 12.


Multidisciplinary management of rectal cancer: the OSTRICH.
Disparity exists in outcomes for rectal cancer patients in the US. Similar problems in several European countries have been addressed by the creation of national networks of rectal cancer centers of excellence (CoEs) that follow evidence-based care pathways and specified protocols of care and process and are certified by regular external validation. This paper reviews the current status of rectal cancer care in the U.S. and examines the evidence for multidisciplinary rectal cancer management. A U.S. rectal cancer CoE system based on the existing U.K. model is proposed. A literature search was performed for publications related to US rectal cancer outcomes, multidisciplinary management of rectal cancer, and European rectal cancer programs. U.S. rectal cancer outcomes are highly variable. The majority of US rectal cancer patients are treated by generalists in low-volume hospitals. Current evidence supports five main principles of rectal cancer care that have been incorporated into European rectal cancer CoE programs. These programs have dramatically improved rectal cancer outcomes in Scandanavian countries and the U.K. A similar CoE program should be established in the U.S. to improve the outcomes of rectal cancer patients.