Single cell and bulk transcriptome analysis identified oxidative stress response-related features of Hepatocellular Carcinoma.
Background: Hepatocellular Carcinoma (HCC) is a common lethal digestive system tumor. The oxidative stress mechanism is crucial in the HCC genesis and progression. Methods: Our study analyzed single-cell and bulk sequencing data to compare the microenvironment of non-tumor liver tissues and HCC tissues. Through these analyses, we aimed to investigate the effect of oxidative stress on cells in the HCC microenvironment and identify critical oxidative stress response-related genes that impact the survival of HCC patients. Results: Our results showed increased oxidative stress in HCC tissue compared to non-tumor tissue. Immune cells in the HCC microenvironment exhibited higher oxidative detoxification capacity, and oxidative stress-induced cell death of dendritic cells was attenuated. HCC cells demonstrated enhanced communication with immune cells through the MIF pathway in a highly oxidative hepatoma microenvironment. Meanwhile, using machine learning and Cox regression screening, we identified PRDX1 as a predictor of early occurrence and prognosis in patients with HCC. The expression level of PRDX1 in HCC was related to dysregulated ribosome biogenesis and positively correlated with the expression of immunological checkpoints (PDCD1LG2, CTLA4, TIGIT, LAIR1). High PRDX1 expression in HCC patients correlated with better sensitivity to immunotherapy agents such as sorafenib, IGF-1R inhibitor, and JAK inhibitor. Conclusion: In conclusion, our study unveiled variations in oxidative stress levels between non-tumor liver and HCC tissues. And we identified oxidative stress gene markers associated with hepatocarcinogenesis development, offering novel insights into the oxidative stress response mechanism in HCC.


Asymptomatic primary hyperparathyroidism in the elderly--a review.
The use of routine calcium estimations has led to a marked increase in the number of cases of hyperparathyroidism diagnosed, especially in the elderly. The results of surgery in the elderly are reviewed, as are some studies on the natural history of untreated hyperparathyroidism, and on this basis it is recommended that in the asymptomatic elderly patient observation is the appropriate management.


Pharmacoangiographic manipulation of renal collateral blood flow.
Vasodilatory or vasoconstrictive renal pharmacoangiography was applied in investigating the significance of 50 renal artery stenoses. The technique involves comparison of selective magnification renal arteriograms before and after intra-arterial injection of epinephrine or acetylcholine, seeking changes in direction of flow in potential collateral routes. The drug injected depended upon the hemodynamic conditions during control arteriography. Final determination of significance depended on response to surgery in most patients, and renin levels in a few. Vasoconstrictive angiography was determinate in 18/26 (69%) of significant stenoses and correctly identified hemodynamic significance in each. Other angiographic signs of collateral circulation were present in seven of the other eight significant stenoses studied with the vasoconstrictive method. Vasodilatory pharmacoangiography was determinate in 20 arteries, and correctly evaluated each of nine significant and 11 insignificant lesions. Pharmacoangiography is a moderately sensitive and completely specific angiographic method for evaluating the hemodynamic significance of renal artery stenoses.


[Optical coherence tomography in neuro-ophthalmology].
Optical coherence tomography (OCT) is a potential tool for diagnosis and follow-up in diseases of the anterior visual pathway in that it provides a reproducible and reliable quantification of retinal nerve fiber layer (RNFL) thickness. A review of the literature was conducted to define the utility of OCT in neuro-ophthalmology. The clinical applications of RNFL thickness measurement by OCT time domain were analyzed. The PubMed search engine enabled us to select the relevant publications, using the following keywords: "optic neuropathy", "retinal nerve fiber layer thickness", and "optical coherence tomography". Publications concerning glaucoma were excluded from this review. The course of RNFL thickness depends on the underlying disease: (I) progressive reduction toward atrophy (e.g., optic neuritis, chiasmal compression) or (II) initial increase in RNFL thickness followed by a reduction toward (IIa) normalization (papilledema) or (IIb) atrophy (anterior ischemic optic neuropathy, Leber hereditary optic neuropathy). Depending on the type of anterior visual pathway impairment, OCT provides RNFL data relevant for diagnosis, follow-up, and prognosis. As in macular disease, OCT has become an important clinical tool for routine disease assessment in neuro-ophthalmology.


NOX2 and NOX4 mediate proliferative response in endothelial cells.
Increased levels of reactive oxygen species (ROS) contribute to many cardiovascular diseases. In neutrophils, ROS are generated by a NADPH oxidase containing p22phox and NOX2. NADPH oxidases are also major sources of vascular ROS. Whereas an active NOX2-containing enzyme has been described in endothelial cells, the contribution of recently identified NOX homologues to endothelial ROS production and proliferation has been controversial. The authors, therefore, compared the role of NOX2 with NOX4 and NOX1 in endothelial EaHy926 and human microvascular endothelial cells. NOX2 and NOX4 were abundantly expressed, whereas NOX1 expression was less prominent. NOX2, NOX4, and NOX1 were simultaneously present in a single cell in a perinuclear compartment. NOX2 and NOX4 co-localized with the endoplasmic reticulum (ER) marker calreticulin. Additionally, NOX2 co-localized with F-actin at the plasma membrane. NOX2 and NOX4, which interacted with p22phox, as was shown by bimolecular fluorescent complementation, contributed equally to endothelial ROS production and proliferation, whereas NOX1 depletion did not alter ROS levels under basal conditions. These data show that endothelial cells simultaneously express NOX2, NOX4, and NOX1. NOX2 and NOX4, but not NOX1, equally contributed to ROS generation and proliferation under basal conditions, indicating that a complex relation between NOX homologues controls endothelial function.


Endobronchial ultrasound diagnosis of pulmonary embolism.
A 68-year-old woman presented for mediastinal lymph node sampling while undergoing work up for a solitary pulmonary nodule. During endobronchial ultrasound examination of the airways, an echogenic abnormality was noted within the right pulmonary artery. The patient underwent computed tomography angiography of the chest, and diagnosis of pulmonary embolism was confirmed. We describe endobronchial ultrasound evaluation of a pulmonary embolus.


A serologic survey of wild felids from central west Saudi Arabia.
Forty-five wildcats (Felis silvestris), 17 sand cats (Felis margarita), and 17 feral domestic cats were captured in central west Saudi Arabia, between May 1998 and April 2000, with the aim to assess their exposure to feline immunodeficiency virus/puma lentivirus (FIV/PLV), feline leukaemia virus (FeLV), feline herpesvirus (FHV-1), feline calicivirus (FCV), feline coronavirus (FCoV), and feline panleukopenia virus (FPLV). Serologic prevalence in wildcats, sand cats, and feral domestic cats were respectively: 6%, 0%, 8% for FIV/PLV; 3%, 8%, 0% for FeLV; 5%, 0%, 15% for FHV-1; 25%, 0%, 39% for FCV; 10%, 0%, 0% for FCoV; and 5%, 0%, 8% for FPLV. We recorded the first case of FeLV antigenemia in a wild sand cat. Positive results to FIV/PLV in wildcats and feral cats confirmed the occurrence of a feline lentivirus in the sampled population.


Risk of haemolytic uraemic syndrome caused by shiga-toxin-producing Escherichia coli infection in adult women in Japan.
Shiga-toxin-producing Escherichia coli (STEC) infections usually cause haemolytic uraemic syndrome (HUS) equally in male and female children. This study investigated the localization of globotriaosylceramide (Gb3) in human brain and kidney tissues removed from forensic autopsy cases in Japan. A fatal case was used as a positive control in an outbreak of diarrhoeal disease caused by STEC O157:H7 in a kindergarten in Urawa in 1990. Positive immunodetection of Gb3 was significantly more frequent in female than in male distal and collecting renal tubules. To correlate this finding with a clinical outcome, a retrospective analysis of the predictors of renal failure in the 162 patients of two outbreaks in Japan was performed: one in Tochigi in 2002 and the other in Kagawa Prefecture in 2005. This study concludes renal failure, including HUS, was significantly associated with female sex, and the odds ratio was 4·06 compared to male patients in the two outbreaks. From 2006 to 2009 in Japan, the risk factor of HUS associated with STEC infection was analysed. The number of males and females and the proportion of females who developed HUS were calculated by age and year from 2006 to 2009. In 2006, 2007 and 2009 in adults aged >20 years, adult women were significantly more at risk of developing HUS in Japan.


Changes in responses of neurons in spinal and medullary subnucleus reticularis dorsalis to acupoint stimulation in rats with visceral hyperalgesia.
The purpose of this study was to explore the mechanism of acupoints sensitization phenomenon at the spinal and medulla levels. Experiments were performed on adult male Sprague-Dawley rats and visceral noxious stimuli was generated by colorectal distension (CRD). The activities of wide dynamic range (WDR) and subnucleus reticularis dorsalis (SRD) neurons were recorded. The changes of the reactions of WDR and SRD neurons to electroacupuncture (EA) on acupoints of "Zusanli-Shangjuxu" before and after CRD stimulation were observed. The results showed that visceral nociception could facilitate the response of neurons to acupoints stimulation. In spinal dorsal horn, EA-induced activation of WDR neurons further increased to 106.84 ± 17.33% (1.5 mA) (P < 0.001) and 42.27 ± 13.10% (6 mA) (P < 0.01) compared to the neuronal responses before CRD. In medulla oblongata, EA-induced activation of SRD neurons further increased to 63.28 ± 15.96% (1.5 mA) (P < 0.001) and 25.02 ± 7.47% (6 mA) (P < 0.01) compared to that before CRD. Taken together, these data suggest that the viscerosomatic convergence-facilitation effect of WDR and SRD neurons may underlie the mechanism of acupoints sensitization. But the sensitizing effect of visceral nociception on WDR neurons is stronger than that on SRD neurons.


Salt concentration determines 1,25-dihydroxyvitamin D3 dependency of vitamin D receptor-retinoid X receptor--vitamin D-responsive element complex formation.
The electrophoretic mobility shift assay was used to determine in vitro formation of the vitamin D receptor-retinoid X receptor beta (VDR-RXR beta) heterodimer complex on vitamin D-response elements (VDREs) from rat osteocalcin, mouse osteopontin, rat 25-hydroxyvitamin D3 24-hydroxylase, and human parathyroid hormone (PTH) genes. Baculovirus-expressed rat VDR was used as VDR and the binding reactions were performed at salt concentrations ranging from 50 to 170 mM KCI. Without ligand, optimum complex formation was observed at 50 mM KCI and markedly decreased with increasing KCI for all VDREs. In the presence of 1,25-dihydroxyvitamin D3, optimum complex formation occurred between 110 and 130 mM KCI for positive (enhancer) VDREs. At low salt concentrations (50-70 mM KCI), 1,25-dihydroxyvitamin D3 did not increase complex formation and actually caused a slight decrease. However, above 90 mM KCI, 1,25-dihydroxy-vitamin D3 markedly increased complex formation and at 150-170 mM KCI, a concentration that presumably mimics physiologic nuclear levels, 1,25-dihydroxy-vitamin D3 appeared to be required for complex formation. With the suppressive cis-acting sequence, i.e., PTH-VDRE, optimum detection of VDR complexes in the presence of 1,25-dihydroxyvitamin D3 occurred at a lower salt concentration (90-110 mM KCI). Moreover, no specific complexes were formed at high salt concentrations, even when 1,25-dihydroxyvitamin D3 was added. Thus, when analyzing an effect of ligand on VDR-RXR-VDRE complex formation, it is essential that the reaction be carried out with a range of salt concentrations. Further, 1,25-dihydroxyvitamin D3 appears to be required for formation of the VDR-RXR beta-VDRE complex at salt concentrations approaching physiological.


Ovine and Bovine Congenital Abnormalities Associated With Intrauterine Infection With Schmallenberg Virus.
In December 2011, a previously unknown congenital syndrome of arthrogryposis and hydranencephaly in sheep and cattle appeared in the Netherlands as an emerging epizootic due to Schmallenberg virus (SBV). Gross lesions in 102 lambs and 204 calves included porencephaly, hydranencephaly, cerebellar dysplasia and dysplasia of the brainstem and spinal cord, a flattened skull with brachygnathia inferior, arthrogryposis, and vertebral column malformations. Microscopic lesions in the central nervous system showed rarefaction and cavitation in the white matter, as well as degeneration, necrosis, and loss of neurons in the gray matter. Brain and spinal cord lesions were more severe in lambs than in calves. Ovine and bovine cases examined early in the outbreak showed encephalomyelitis. SBV infection was confirmed by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) in brain samples in 46 of 102 lambs (45%) and in 32 of 204 calves (16%). Immunohistochemistry, performed on tissue samples from 18 RT-qPCR-positive lambs, confirmed the presence of bunyaviral antigen in neurons of the brain in 16 cases. SBV antibodies were detected by enzyme-linked immunosorbent assay in fetal blood in 56 of 61 sampled ovine cases (92%). In a virus neutralization test, all tested dams of affected newborns, 46 ewes and 190 cows, were seropositive. Compared with other teratogenic viral infections, the pathogenesis and lesions of SBV in sheep and cattle fetuses are similar to those of other ruminant orthobunyaviruses. However, the loss of spinal ventral motor neurons and their tracts, resulting in micromyelia, distinguishes SBV infection from other viral central nervous system lesions in newborn ruminants.


Developmental regulation of calcineurin isoforms in the rodent kidney: association with COX-2.
Calcineurin (Cn)-Aalpha-deficient mice develop abnormalities of postnatal kidney development, similar to that of cyclooxygenase (COX)-2-deficient mice. The present study was undertaken to examine expression and regulation of Cn isoforms in the developing kidney during the postnatal period and further characterize the relationship between Cn and COX-2. The protein expressions of all three Cn isoforms, including Cn-Aalpha, -Abeta, and -B, as determined by immunoblotting, increased in parallel in the first postnatal week and declined gradually with age. Renal Cn-Aalpha and -Abeta mRNA expressions were both developmentally regulated in the same fashion as their protein expressions, whereas renal Cn-B1 mRNA was not obviously induced in the first postnatal week. Immunohistochemistry demonstrated colocalization of Cn-Aalpha, Cn-Abeta, and COX-2 in the same cells of thick ascending limb and macula densa. Administration with cyclosporine A (2.5 mg.kg(-1).day(-1)) during the postnatal period remarkably suppressed renal COX-2 expression as assessed by both immunoblotting and immunohistochemistry. Deletion of Cn-Aalpha but not Cn-Abeta in mice significantly reduced renal COX-2 expression at the postnatal period. Together, these data suggest that renal Cn isoforms are subject to normal developmental regulation and they may play a role in postnatal kidney development via interaction with COX-2.


Morphological and biometric revision of the cleithra, opercular and pharyngeal bones of Iberian teleosts belonging to the genus Barbus (Pisces, Cyprinidae).
Species of the genus Barbus present in the Iberian Peninsula are an interesting study group, due to its diversity and complex taxonomic position. In this work, 299 specimens of eight species were studied. All of them are endemic to the Iberian Peninsula, except for Barbus meridionalis. Cleithra, opercular and pharyngeal bones were extracted from each specimen. These bones were morphologically compared and measured, obtaining biometric indices. From these indices, the biometric differences of each bone were analysed with a principal component analysis. Later, a principal component analysis and a discriminant analysis were performed considering the three bones together. The morphological differences and similarities are congruous with the biometric results. In addition, this osteological comparison partially agrees with the present taxonomic position of these species, being a contribution to the systematics and phylogeny of genus.


Performance Enhancement of Learning Tracking Systems Over Fading Channels With Multiplicative and Additive Randomness.
This paper applies learning control to repetitive systems over fading channels at both output and input sides to improve tracking performance without applying restrictive fading conditions. Both multiplicative and additive randomness of the fading channel are addressed, and the effects of fading communication on the data are carefully analyzed. A decreasing gain sequence and a moving-average operator are introduced to modify the generic learning control algorithm to reduce the fading effect and improve control system performance. Results reveal that the tracking error converges to zero in the mean-square sense as the iteration number increases. Illustrative simulations are presented to verify the theoretical results.


Isolated lichen planus of lip: Diagnosis and treatment monitoring using dermoscopy.
Lichen planus (LP) of lip has chances of malignant transformation as it may be exposed to external trauma, smoking, and ultraviolet light. This case highlights the use of dermoscope as a quick noninvasive tool for the diagnosis of LP of lip and monitoring the response to treatment.


Diversity in the enteric viruses detected in outbreaks of gastroenteritis from Mumbai, Western India.
Faecal specimens collected from two outbreaks of acute gastroenteritis that occurred in southern Mumbai, India in March and October, 2006 were tested for seven different enteric viruses. Among the 218 specimens tested, 95 (43.6%) were positive, 73 (76.8%) for a single virus and 22 (23.2%) for multiple viruses. Single viral infections in both, March and October showed predominance of enterovirus (EV, 33.3% and 40%) and rotavirus A (RVA, 33.3% and 25%). The other viruses detected in these months were norovirus (NoV, 12.1% and 10%), rotavirus B (RVB, 12.1% and 10%), enteric adenovirus (AdV, 6.1% and 7.5%), Aichivirus (AiV, 3% and 7.5%) and human astrovirus (HAstV, 3% and 0%). Mixed viral infections were largely represented by two viruses (84.6% and 88.9%), a small proportion showed presence of three (7.7% and 11%) and four (7.7% and 0%) viruses in the two outbreaks. Genotyping of the viruses revealed predominance of RVA G2P[4], RVB G2 (Indian Bangladeshi lineage), NoV GII.4, AdV-40, HAstV-8 and AiV B types. VP1/2A junction region based genotyping showed presence of 11 different serotypes of EVs. Although no virus was detected in the tested water samples, examination of both water and sewage pipelines in gastroenteritis affected localities indicated leakages and possibility of contamination of drinking water with sewage water. Coexistence of multiple enteric viruses during the two outbreaks of gastroenteritis emphasizes the need to expand such investigations to other parts of India.


Postnatal refinement of auditory nerve projections to the cochlear nucleus in cats.
Studies of visual system development have suggested that competition driven by activity is essential for refinement of initial topographically diffuse neuronal projections into their precise adult patterns. This has led to the assertion that this process may shape development of topographic connections throughout the nervous system. Because the cat auditory system is very immature at birth, with auditory nerve neurons initially exhibiting very low or no spontaneous activity, we hypothesized that the auditory nerve fibers might initially form topographically broad projections within the cochlear nuclei (CN), which later would become topographically precise at the time when adult-like frequency selectivity develops. In this study, we made restricted injections of Neurobiotin, which labeled small sectors (300-500 microm) of the cochlear spiral ganglion, to study the projections of auditory nerve fibers representing a narrow band of frequencies. Results showed that projections from the basal cochlea to the CN are tonotopically organized in neonates, many days before the onset of functional hearing and even prior to the development of spontaneous activity in the auditory nerve. However, results also demonstrated that significant refinement of the topographic specificity of the primary afferent axons of the auditory nerve occurs in late gestation or early postnatal development. Projections to all three subdivisions of the CN exhibit clear tonotopic organization at or before birth, but the topographic restriction of fibers into frequency band laminae is significantly less precise in perinatal kittens than in adult cats. Two injections spaced > or = 2 mm apart in the cochlea resulted in labeled bands of projecting axons in the anteroventral CN that were 53% broader than would be expected if they were proportional to those in adults, and the two projections were incompletely segregated in the youngest animals studied. Posteroventral CN (PVCN) projections (normalized for CN size) were 36% broader in neonates than in adults, and projections from double injections in the youngest subjects were nearly fused in the PVCN. Projections to the dorsal division of the CN were 32% broader in neonates than in adults when normalized, but the dorsal CN projections were always discrete, even at the earliest ages studied.


Innovations in injury prevention education.
Innovations in Injury Prevention Education describes four programs presented at the Annual Injury Free Coalition for Kids National Meeting in December 2006. The programs were developed by Injury Free sites in Providence, RI; Detroit, MI; Hartford, CT; and Peoria, IL. Each demonstrates how education continues to be an essential aspect of injury prevention interventions, either as a means of disseminating knowledge among children or as a way to assess baseline knowledge to develop more appropriate interventions. For each program, summaries of methods are provided, along with the results of basic statistical analyses. The need for continued research on education's role in injury prevention is emphasized.


Changing patterns in presentation and management of the Zollinger-Ellison syndrome in Northern Ireland, 1970-1988.
The clinical features, diagnostic methods, management and survival in 16 cases of Zollinger-Ellison syndrome encountered in Northern Ireland between the years 1970 and 1988 are described. While the majority of patients in the first decade of the study period had surgical treatment, those presenting in the latter period have been managed with medical therapy in the form of H2-receptor antagonists or omeprazole. The increasing use of these agents seems to be altering the severe clinical features of this condition, reducing the indications for surgery and maintaining patients, with or without evidence of metastatic disease, in clinical remission.


A new species of the genus Mesambria Stål, 1878 with notes on the tribe Mesambriini (Orthoptera: Acrididae, Catantopinae).
The new species Mesambria intermedia Storozhenko, sp. nov. is described from Indonesia. Male genitalia of the type species of the genera Mesambria Stål, 1878 and Traulia Stål, 1873 are described and illustrated for the first time. The diagnosis of the tribe Mesambriini is given and the position of this tribe in the modern classification of grasshoppers is discussed. New synonymy is proposed: Mesambriini Brunner von Wattenwyl, 1893 = Trauliini Bolivar, 1917, syn. nov., = Ranacridinae Xia, 2006, syn. nov.


Self-reported smoking status and exhaled carbon monoxide: results from two population-based epidemiologic studies in the North of England.
To investigate the validity of self-reported responses to questions on current smoking in two cohorts based in Northern England. A cross-sectional population-based study (the Newcastle Heart Project [NHP]) and a follow-up of the Newcastle Thousand Families birth cohort established in 1947. Participants included 1,189 members of the NHP and 410 members of the Newcastle Thousand Families cohort who completed a health and lifestyle questionnaire, including questions on current smoking, and attended a clinical examination, including testing for exhaled carbon monoxide between April 1993 and December 1998. The number of self-reporting smokers for whom very low (ie, < 6 ppm) exhaled carbon monoxide levels were recorded varied between 9% in the Newcastle Thousand Families Study and 26% among the members of the NHP who were of South Asian origin. Using a cutoff of 8 ppm, 80% of self-reported smokers were identified in both the Newcastle Thousand Families study and in the NHP European population, but only 60% were identified in the NHP South Asian population. In each population, < 7% of nonsmokers had exhaled carbon monoxide measurements of > 6 ppm, with nonsmoking men more likely to have higher levels than nonsmoking women. Among the nonsmokers, the levels of exhaled carbon monoxide did not vary with respect to the smoking status of a partner or socioeconomic status. Using a cutoff value of 6 ppm would potentially miss a large number of smokers, although this may vary with ethnicity. Epidemiologic studies should continue to use biochemical markers to validate responses to smoking surveys. However, the use of exhaled carbon monoxide measurements as a method of assessing the validity of self-reported smoking status may require additional analyses of whether the cutoff level should vary for different populations.


Giardia duodenalis and Cryptosporidium occurrence in Australian sea lions (Neophoca cinerea) exposed to varied levels of human interaction.
Giardia and Cryptosporidium are amongst the most common protozoan parasites identified as causing enteric disease in pinnipeds. A number of Giardia assemblages and Cryptosporidium species and genotypes are common in humans and terrestrial mammals and have also been identified in marine mammals. To investigate the occurrence of these parasites in an endangered marine mammal, the Australian sea lion (Neophoca cinerea), genomic DNA was extracted from faecal samples collected from wild populations (n = 271) in Southern and Western Australia and three Australian captive populations (n = 19). These were screened using PCR targeting the 18S rRNA of Giardia and Cryptosporidium. Giardia duodenalis was detected in 28 wild sea lions and in seven captive individuals. Successful sequencing of the 18S rRNA gene assigned 27 Giardia isolates to assemblage B and one to assemblage A, both assemblages commonly found in humans. Subsequent screening at the gdh and β-giardin loci resulted in amplification of only one of the 35 18S rRNA positive samples at the β-giardin locus. Sequencing at the β-giardin locus assigned the assemblage B 18S rRNA confirmed isolate to assemblage AI. The geographic distribution of sea lion populations sampled in relation to human settlements indicated that Giardia presence in sea lions was highest in populations less than 25 km from humans. Cryptosporidium was not detected by PCR screening in either wild colonies or captive sea lion populations. These data suggest that the presence of G. duodenalis in the endangered Australian sea lion is likely the result of dispersal from human sources. Multilocus molecular analyses are essential for the determination of G. duodenalis assemblages and subsequent inferences on transmission routes to endangered marine mammal populations.


Thermodynamic studies and loading of 7-ethyl-10-hydroxycamptothecin into mesoporous silica particles MCM-41 in strongly acidic solutions.
A major limitation of the clinical efficacy of the 7-ethyl-10-hydroxycamptothecin (SN38) therapy is its facile conversion of the active lactone form into a less active carboxylate species at physiological pH and limited aqueous solubility. The present manuscript embodies a detailed description of several physicochemical properties of SN38 and further details the thermodynamic basis for its poor aqueous solubility. The ionization and increased solubility of the drug in highly acidic media were subsequently employed to efficiently load the positively charged drug in its biologically active lactone form into mesoporous silica material of type MCM-41, achieving a maximum loading of 250 mg of SN38 per gram of silicate. It was also found that the equilibrium association constant K(A) varies with the extent of drug adsorption. At low and high drug load, corresponding to one SN38 molecule bound for every 70 and 13 -SiO(2)-, K(A) was determined to be 1253.5 and 127.39 M(-1), respectively.


Ebola Virus Disease in Health Care Workers--Guinea, 2014.
An outbreak of Ebola virus disease (Ebola) began in Guinea in December 2013 and has continued through September 2015. Health care workers (HCWs) in West Africa are at high risk for Ebola infection owing to lack of appropriate triage procedures, insufficient equipment, and inadequate infection control practices. To characterize recent epidemiology of Ebola infections among HCWs in Guinea, national Viral Hemorrhagic Fever (VHF) surveillance data were analyzed for HCW cases reported during January 1–December 31, 2014. During 2014, a total of 162 (7.9%) of 2,210 laboratory-confirmed or probable Ebola cases among Guinean adults aged ≥15 years occurred among HCWs, resulting in an incidence of Ebola infection among HCWs 42.2 times higher than among non-HCWs. The disproportionate burden of Ebola infection among HCWs taxes an already stressed health infrastructure, underscoring the need for increased understanding of transmission among HCWs and improved infection prevention and control measures to prevent Ebola infection among HCWs.


Antenatal nephromegaly and propionic acidemia: a case report.
Propionic acidemia (PA) is a rare but severe recessive autosomal disease, presenting with non specific signs in the first years of life. Prenatal diagnosis is invasive (amniocentesis) and limited to suspect cases. No screening test has been described, in particular no correlations between prenatal sonography and PA have been documented so far. We report the case of a boy with fetal bilateral nephromegaly and hyperechogenic kidneys, along with neonatal acute kidney injury; no etiology could be found in the first months of life. At 3 months of life, he presented with tachypnea and altered mental status, which lead to the diagnosis of PA. The renal ultrasound at 8 months of life, after a symptomatic treatment of PA had been initiated, showed a regression of the renal abnormalities. This case describes PA as a novel cause of large and hyperechogenic kidneys in the antenatal period. It suggests that, when confronted to fetal nephromegaly, hyperechogenic kidneys and risk factors of metabolic disease such as consanguineous parents, PA should be considered, and a prenatal test should be proposed.


Modulation instability in waveguides with an arbitrary frequency-dependent nonlinear coefficient.
In this Letter, we present, for the first time, to the best of our knowledge, the modulation instability (MI) gain spectrum of waveguides with an arbitrary frequency-dependent nonlinear coefficient ensuring strict energy and photon-number conservation of the parametric process. This is achieved by starting from a linear stability analysis of the recently introduced photon-conserving nonlinear Schrödinger equation. The derived MI gain is shown to predict some unique features, such as a nonzero gain extending beyond a zero-nonlinearity wavelength and a complex structure of the MI gain spectrum. Analytical results are shown to be in excellent agreement with numerical simulations.


Tolerance-inducing strategies in islet transplantation.
Allogeneic islet transplantation is a promising approach for restoring normoglycemia in type 1 diabetic patients. Current use of immunosuppressive therapies for management of islet transplant recipients can be counterintuitive to islet function and can lead to complications in the long term. The induction of donor-specific tolerance eliminates the dependency on immunosuppression and allows recipients to retain responses to foreign antigens. The mechanisms by which tolerance is achieved involve the deletion of donor-reactive T cells, induction of T-cell anergy, immune deviation, and generation of regulatory T cells. This review will outline the various methods used for inducing donor-specific tolerance in islet transplantation and will highlight the previously unforeseen potential of tissue stromal cells in promoting islet engraftment.


Epidemiology of physician-diagnosed neuropathic pain in Brazil.
Estimate the prevalence of neuropathic pain (NeP) among chronic pain patients attending Brazilian hospitals and pain clinics in São Paulo, Ceara, and Bahia and explore clinical characteristics by subtypes: painful diabetic peripheral neuropathy (pDPN), central neuropathic pain (CNP), chronic low back pain with a neuropathic component (CLBP-NeP), postherpetic neuralgia (PHN), post-traumatic neuropathic pain (PTN), and post-surgical neuropathic pain (PSN). Physicians screened patients reporting chronic pain for ≥3 months (n=2,118) for probable NeP, using the Douleur Neuropathique 4 questionnaire and physician assessment, and reported their NeP subtype(s), symptoms, and medications. Identified NeP patients completed a questionnaire including treatment experiences, quality of life EuroQol 5 Dimensions [EQ-5D]), pain severity and interference (Brief Pain Inventory [BPI]), and Work Productivity and Activity Impairment scales. Descriptive analyses were performed by NeP subtype. The prevalence of probable NeP was 14.5% (n=307). NeP patients were mostly female (80.5%), middle-aged (mean [M]=52.5, SD=13.9), and Pardo (44.3%). Of those diagnosed with an NeP subtype (n=209), the largest proportions were CLBP-NeP (36.8%), followed by pDPN (18.7%), CNP (17.7%), PTN (17.2%), PSN (13.4%), and PHN (3.3%). Across subtypes, the most widely reported symptoms were numbness (range: 62.2%-89.7%) and hyperalgesia (range: 32.1%-76.9%) and the most commonly prescribed pain analgesics were NSAID (range: 18.2%-57.1%), opioids (range: 0.0%-39.3%), and antiepileptics (range: 18.2%-57.1%). PTN and PSN patients reported the least favorable EQ-5D index scores (M=0.42, SD=0.19) and BPI-Pain Severity scores (M=7.0, SD=1.9), respectively. Those diagnosed with CNP had the least favorable BPI-Pain Interference scores (M=6.0, SD=2.7). Patients with PHN reported the least impairment based on EQ-5D index scores (M=0.60, SD=0.04). Those with pDPN had the most favorable BPI scores (BPI-Pain Severity: M=4.6, SD=2.3; BPI-Pain Interference: M=4.7, SD=2.7). Evaluation of chronic pain patients in Brazil yielded a 14.5% probable NeP prevalence. NSAIDs and opioids were commonly used, and there was a high incidence of NeP-related symptoms with varying levels of dysfunction across subtypes.


Lipid segregation from human erythrocyte tethers.
Fluid shear force may deform point-attached erythrocytes to become droplike shaped and anchored by a single long or 2-4 short tethers. By addition of glutaraldehyde to the medium the cells were fixed such as to stabilize this deformation for ensuing SEM, freeze-fracture, fine structural, and ultrahistochemical studies. Freeze-fracture specimens revealed identical numbers and distribution patterns of membrane particles in both the membrane of tethers and of the droplike portions of red cells. Segregated vesicles most often were located adjacent to the attachment site of the tether. All of the vesicles were devoid of membrane particles. Irrespective of their length, the tethers were about 0.1 micrometer in diameter. Cross-sections of the tether membrane and the plasmalemma of the major part of the cell appeared identical. Ultrahistochemical studies revealed the same intensity of iron binding capacity and affinity to ferritin labelled anti AHP at either area of the deformed erythrocyte membrane. Segregating vesicles were also stained by colloidal iron and by fer-anti AHP. By means of the DAB-reaction no haemoglobin was demonstrated within the vesicles. All of these findings corroborate the notion, that lipid molecules were segregated from the membrane whose curvature increased considerably during the formation of the tether.


A diagnostic screening tool for identifying safe drivers among dialysis patients.
Studies have shown that adverse effects of dialysis are associated with increased risk of driving impairment. While recommendations have been made that physicians should place an increased focus on detecting risks for driving impairment among patients on dialysis, there are currently no diagnostic tools designed to help physicians assess driving impairment among this patient population. In addition to driver self-assessment tools provided by AAA (American Automobile Association), one of the only tools specifically designed to help physicians assess driver safety is the "Am I a Safe Driver?" checklist, originally designed to assess for driving impairment among geriatric patients. This study aimed to determine the utility of this checklist in detecting dialysis patients at risk for driving impairment. The checklist was administered to dialysis patients who were predetermined to either be at risk or not at risk for driving impairment. The checklist was used to identify patients who test positive for driving impairment. ROC (receiver operationg characteristic) analysis was done to identify the best cut off to consider as a positive test. The study found that the checklist is very good in detecting risk for driving impairment among dialysis patients. ROC analysis determined that answering "yes" to at least two statements in the "Am I a Safe Driver?" checklist gives the highest sensitivity and specificity combination (Youden's index = 0.42). Higher sensitivity and lower specificity of the "Am I Safe Driver" checklist implies that it is effective only as a preliminary screening test for ruling out risk of driving impairment among dialysis patients.


Nitrogen regulation of acid phosphatase in Neurospora crassa.
Neurospora crassa possesses a repressible acid phosphatase with phosphodiesterase activity which appears to permit it to utilize ribonucleic acid as a phosphorus and as a nitrogen source. This acid phosphatase, which is specified by the pho-3 locus, is derepressed approximately eightfold during nitrogen limitation and to an even greater extent during phosphorus limitation, but is unaffected by sulfur limitation. Derepression of the enzyme did not occur when adenosine 5'-monophosphate was the sole phosphorus or nitrogen source. Synthesis of the acid phosphatase is not under the control of the nit-2 locus, which regulates the expression of a large number of other nitrogen catabolic enzymes. The structural gene of the acid phosphatase appears to be a member of both the phosphorus and nitrogen regulatory circuits.


DNA Fingerprinting of in vitro Micropropagated Pomegranate Genotypes.
Pomegranate is grown for its rich flavour in numerous tropical and subtropical areas, like Egypt and the Kingdom of Saudi Arabia (KSA). Assessing the genetic background of the pomegranate is the key to its expansion through the Middle East, where tissue culture reproduction strategies could be used to solve environmental and economic problems. This study aimed at studying the genetic stability of 2 pomegranate genotypes in vitro micro-propagated in the Kingdom of Saudi Arabia by using the random amplified polymorphic DNA (RAPD) polymerase chain reaction (PCR) and inter simple sequence repeats (ISSR) tools. The two above mentioned molecular tools were used to evaluate the DNA fingerprints of Taify and Yemeni pomegranate genotypes 12 weeks post in vitro propagation in Taif, Kingdom of Saudi Arabia compared to the mother plant. Shoot tip explants of 4-5 cm long were grown on Murashige and Skoog (MS) medium supplemented by 1.0 mg L-1 NAA, 2.00 mg L-1 IBA and 2 g L-1 activated carbon for 4 weeks for rooting. On 12 weeks DNA extracts were prepared from the acquired plantlets obtained and used as templates for each of RAPD-PCR and ISSR tools. The RAPD-PCR and ISSR assays generated a total of 79-94 and 57-72 DNA fragments, respectively. In case of RAPD-PCR 80 and 90% of the primers used and developed monomorphic fragments of the Yemeni and Taify genotypes, respectively, particularly OPG08 primer for Taify genotype and OPA04 and OPD07 primers for the Yemeni genotype. Regarding ISSR, no DNA polymorphic for the micropropagated clones were recorded compared to the mother plant. The ISSR assay's findings indicated the genetic homogeneity between the in vitro micropropagated clones of both pomegranate genotypes and the mother plants.


Hyperuricosuria, an often overlooked cause of recurrent oliguria in children.
The association of oliguria with hyperuricosuria is often overlooked. Herein, we report an infant who since the age of five months had recurrent oliguria secondary to hyperuricosuria documented several times in the hospital. The decreased urine output coincided with the presence of increased excretion of uric acid, which fluctuated within 24 hours as well as every few weeks. The child responded to treatment with increase in the fluid fluid intake along with the xanthine oxidase inhibitor, allopurinol. Being alert for hyperuricosuria in cases of oliguria, especially if there is history of gout or stones, may avoid performing many unnecessary investigations.


Developing effective institutional managers in the 1980s--part 2: some new directions.
In the earlier paper (published in the March 1980 issue of the Journal of Advanced Nursing) two dominant themes were developed. One was that the organizational behaviour of nurse managers could be traced to the social defence system learned during early nursing, the other was that many of the assumptions which underpin much of the current thinking on nurse management training can do little either to help them unlearn these early behaviours or to prepare them to take more innovative action in their respective roles. Part 2 analyses some implications of this. The initial discussion examines the purpose of management training and what it is intended to achieve, which embraces the issues of the transfer of course learning back to the workplace and the greater involvement of line managers in the development of their staff. By redefining nursing in terms of open-system boundary management, some new directions are suggested which management trainers may find useful in clarifying and redefining their own task, as well as enabling nurse managers to be more innovative and effective within the constraints of their organizational situations. The implications go beyond just nursing and nurse management training. They are concerned with the wider range of institutions whose task is the throughput of people, and which tend to be managed by groups of professionals.


[Preliminary Investigation of the Amount, the Molecular Weight and the Activity of Polysaccharides from Chaenomeles Speciosa Fruits in Ethanol Fractional Precipitation].
Chaenomeles speciosa fruits were extracted using water. The extracts were precipitated with 20%~95% (φ) ethanol, respectively. The amount of total polysaccharide was measured with phenol-sulfuric acid method. A method using high-performance size-exclusion chromatography (HPSEC) equipped with multiangle laser-light-scattering photometry (MALLS) and differential refractometry (RI) was presented for determining the molecular weight and molecular weigh distribution. RAW264.7 macrophage were cultured and stimulated with the polysaccharides in vitro and the production of nitric oxide in the cells was determined by the Griess assay. The aim of the study is to determine the amount and the molecular weight of the polysaccharides from Chaenomeles speciosa fruits, and preliminary investigate the immunomodulatory activity, The study provided the basis datas for the further research of Chaenomeles speciosa fruits. , and provided a simple and system method for the research of natural polysaccharide. The ethanol fractional precipitation showed that the order of total polysaccharide content was 95%>80%>40% ≥60%>20%. The results indicated that most polysaccharide from Chaenomeles speciosa fruits might be precipitated when ethanol concentration was up to 95% (T) and the crude polysaccharide purity had risen from 35. 1% to 45. 0% when the concentration of ethanol increased from 20% to 95%. HPSEC-MALLS-RI system showed that all the polysaccharide samples had the similar compositions. They appeared three chromatographic peaks and the retention time were not apparently different. The Mw were 6. 570 X 10(4) g . mol-1 and 1. 393 X 10(4) g . mol-1 respectively, and one less than 10 000 which was failure to obtain accurate values. The molecular weight of the first two polysaccharide distribution index(Mw/Mn)were 1. 336 and 1. 639 respectively. The polysaccharide samples had not exhibited immunomodulatory activity assessed on the basis of nitric oxide production by RAW264. 7 macrophage cells in the experiment.


Captopril versus hydralazine in primary pulmonary hypertension.
Captopril was tested as the treatment for a patient with primary pulmonary hypertension (PPH) and its effects were compared with those of hydralazine. Captopril induced a rise in pulmonary pressures and in intrapulmonary shunt; hydralazine lowered pulmonary resistances and increased paO2 and blood O2 transport. Prospective studies in PPH treated with captopril are recommended and evaluation of all drugs not only by hemodynamic but also respiratory and O2 transport measurements.


[Superior sagittal sinus thrombosis suffered as a complication of ulcerative colitis: case report].
A case of superior sagittal sinus thrombosis which was complicated with ulcerative colitis is reported. A 16-year-old male patient had a 2-year history of ulcerative colitis. He was admitted to our hospital complaining of abdominal pain, bloody bowel discharge and appetite loss, and was then treated conservatively. Two days after admission, he demonstrated generalized convulsions which were followed by right hemiplegia. MRI showed a low intensity lesion on T1 and an irregular high intensity in the subcortical area of the left frontal lobe on T2 and T2 FLAIR-weighted images. The MRI findings resembled either invasive brain tumor or local inflammation. Cerebral angiography appeared to demonstrate complete obstruction of the superior sagittal sinus with congestion of venous flow in the cortical veins. Ulcerative colitis has been reported to show hypercoagulation, leading to deep vein thrombosis within the body which sometimes causes pulmonary infarction; however, occurrence of venous thrombosis in the intracranial veins and sinus is rare. This report underscores the fact that cerebral venous thrombosis should be suspected in the case of patients with ulceritive colitis who suffer sudden onset of neurological deficits.


Myocardial perfusion by myocardial contrast echocardiography and endothelial dysfunction in obstructive sleep apnea.
Obstructive sleep apnea is associated with increased cardiovascular morbidity and mortality. We investigated myocardial perfusion using real-time quantitative myocardial contrast echocardiography with concurrent assessment of macrovascular and microvascular endothelial dysfunction in normotensive subjects with moderate-to-severe obstructive sleep apnea, who were compared with hypertensive and healthy subjects, as well as the impact of continuous positive airway pressure treatment on obstructive sleep apnea subjects. We measured flow (hyperemia)-mediated dilation and response to glyceryl trinitrate of brachial artery (ultrasound), cutaneous perfusion responses to acetylcholine and sodium nitroprusside (laser Doppler), pulse wave velocity, and circulating endothelial and endothelial progenitor cells in a total of 108 subjects (n=36 each of matched obstructive sleep apnea, hypertension, and healthy cohorts). Subjects with obstructive sleep apnea and hypertension demonstrated abnormal myocardial perfusion (P<0.001 for both comparisons), attenuated brachial artery reactivity (P<0.001), and cutaneous perfusion responses (P<0.001) compared with healthy individuals. Both hypertensive and obstructive sleep apnea patients showed significant improvements in myocardial perfusion (P<0.01), brachial artery reactivity (P<0.001), and cutaneous perfusion responses (P<0.001) after 26 weeks of continuous positive airway pressure therapy. There were no significant differences in pulse wave velocity and endothelial cells across the 3 groups. Concomitant endothelial dysfunction and impaired myocardial perfusion are present in otherwise normal subjects with moderate-to-severe obstructive sleep apnea, and effective continuous positive airway pressure treatment reverses many of these macrovascular/microvascular abnormalities.


Chelating Surfaces for Native State Proteins Patterning: The Human Serum Albumin Case.
The paper reports a new "soft" surface functionalization strategy, based on a highly selective ion metal chelation process. The proposed stepwise methodology implies at first the construction of a monolayer of terpyridine-based thiol (Tpy), whose highly packed structuring has been followed in situ by using quartz crystal microbalance (QCM-D) measurements, showing that the monolayers consist of about 2.7 × 10(14) Tpy/cm(2). Then, the tridentate sites of the each Tpy moiety are employed to partially chelate divalent metal ions, providing an effective platform to anchoring proteins by completing the metal ion coordination with an available site on the protein of interest. We report the case study of the application of the process to the HSA immobilization onto various surfaces, including Tpy-Fe(II) and Tpy-Cu(II) complexes, as well as hydrophilic bare gold substrates and hydrophobic self-assembled Tpy-based monolayers. It is shown that the chelation interaction between Tpy-Cu(II) complexes and HSA produces the highest and most robust HSA immobilization, with an adsorbed mass at the steady state of ∼800 ng/cm(2), with respect to an average adsorption of ∼350 ng/cm(2) for the other surfaces. Furthermore, Cu(II)-chelated surfaces seem to promote a sort of protein "soft" landing, preventing the ubiquitous surface-induced major unfolding and transmitting an orientation information to the protein, owing to the highly specific symmetry coordination of the Tpy-Cu(II)-protein complex. Indeed, the interaction with a specific monoclonal antiboby (anti-HSA) indicated the lack of a significant protein denaturation, while a massive reorientation/denaturation process was found for all the remaining surfaces, including the Tpy-Fe(II) complex. Finally, the metal-ion-dependent HSA immobilization selectivity has been exploited to obtain micropatterned surfaces, based on the strikingly different strength of interaction and stability observed for Fe(II) and Cu(II) complexes.


The effects of a face-name mnemonic in young, middle-aged, and elderly adults.
A mnemonic for learning name-to-face associations was taught to young, middle-aged, and elderly adults. Recall of names was assessed initially, before participants were introduced to the mnemonic, and after it had been learned. The youngest group recalled the most names overall whereas the oldest group recalled the least; middle-aged participants performed at intermediate levels. Despite this decline in performance with age, all three groups showed significant gains in recall after learning the mnemonic, and the amount of improvement was comparable across groups.


[Nocardia pellegrini: III. An attempt of phage typing(author's transl)].
The typing of Nocardia pellegrini with different Nocardia-phages was studied. The investigation included 25 Nocardia pellegrini strains, 19 strains of different Nocardia species and also strains of different species of mycobacteria. It could be stated that phages typical for Nocardia pellegrini were also active against other fast fragmentating Nocardia species, such as Nocardia corallina or Nocardia rubra. However, they did not attack Nocardia asteroides or strains of mycobacteria. Phages typical for mycobacteria or for Nocardia asteroides did not lysate the fast fragmentating nocardia (Table 1 and 2). Mutants of one Nocardia pellegrini phage could be isolated which showed a broader host range than the parent phage (Table 1 and 2). Some lysogenic strains of Nocardia pellegrini with a changed phage sensitivity could be isolated after action of the phages (Table 3). The taxonomical position of Nocardia pellegrini and Nocardia rubra is discussed.


Molecular epidemiology of Aspergillus fumigatus isolates harboring the TR34/L98H azole resistance mechanism.
A rapid emergence of azole resistance has been observed in Aspergillus fumigatus in The Netherlands over the past decade. The dominant resistance mechanism appears to be of environmental origin and involves the TR(34)/L98H mutations in cyp51A. This resistance mechanism is now also increasingly being found in other countries. Therefore, genetic markers were used to gain more insights into the origin and spread of this genotype. Studies of 142 European isolates revealed that those with the TR(34)/L98H resistance mechanism showed less genetic variation than azole-susceptible isolates or those with a different genetic basis of resistance and were assigned to only four CSP (putative cell surface protein) types. Sexual crossing experiments demonstrated that TR(34)/L98H isolates could outcross with azole-susceptible isolates of different genetic backgrounds, suggesting that TR(34)/L98H isolates can undergo the sexual cycle in nature. Overall, our findings suggest a common ancestor of the TR(34)/L98H mechanism and subsequent migration of isolates harboring TR(34)/L98H across Europe.


Developing molar occlusion.
This article has focused on developmental changes in molar occlusion. Its purpose is to alert the reader to changes in these relationships, which can occur naturally from birth to the period of developed dentition. The practitioner should be cognizant of these changes and the importance of preserving and promoting good molar relationships, which are the foundation of occlusions.


Magnetic resonance imaging of the optic nerves and chiasm.
Magnetic resonance imaging (MR) of the optic nerves and chiasm was compared with computed tomography (CT) in 4 healthy volunteers, 4 patients without orbital or chiasmal abnormalities, and 4 patients with tumor (anterior clinoid meningioma in 2, optic nerve glioma in 1, and optic nerve sheath meningioma in 1). MR was found to be effective in demonstrating the optic nerves and related structures, particularly the intracanalicular portion of the nerve which is difficult to see with CT. Best results were achieved with partial saturation recovery (SR) images; inversion recovery (IR) and spin echo (SE) techniques were less successful because of decreased spatial resolution (in the case of SE) as well as difficulty in seeing the anterior clinoid processes. As axial views cannot always distinguish the ethmoid sinus tissue from the optic nerve, it may be necessary to employ both axial and coronal images.


Multifunctional Nanofibers for Specific Purification and Release of CTCs.
Recovering pure and viable circulating tumor cells (CTCs) from blood has been a challenging task for molecular characterization and functional analysis, which has attracted wide attention these days. Herein, we fabricate a thermoresponsive chitosan nanofiber substrate to effectively capture, purify, and release the target cancer cells, assisted by PNIPAAm brushes and DNA hybridization. The PNIPAAm brushes are designed to enable WBCs to detach from aptamer-PNIPAAm-chitosan-nanofiber (aptamer-P-CNFs) surfaces during the conformational transition. Meanwhile these specific captured CTCs are retained at a high purity. Moreover, effective and intact release of CTCs from the substrates without any foreign agents is realized by complementary sequences efficiently hybridizing with aptamers, and the specific cell release makes CTCs further purified. The present work provides a new strategy in the design of biointerface for recovering target CTCs from whole blood samples with high purity.


α-smooth muscle actin-positive fibroblasts correlate with poor survival in hepatocellular carcinoma.
The current case-control study was conducted to assess the value of activated fibroblasts with high α-smooth muscle actin (α-SMA) expression as an indicator of survival in hepatocellular carcinoma (HCC) patients. In total, 47 patients diagnosed with HCC who underwent a liver biopsy at the Veterans Affairs Medical Center (Memphis, TN, USA) between January 2000 and December 2009, and 10 age- and gender-matched controls with normal liver biopsy samples were included in the study. The immunohistochemical staining for α-SMA was performed and classified qualitatively and quantitatively within tumor stroma and perisinusoidal spaces. HCC patients with high qualitative and quantitative expression of α-SMA revealed a statistically significant negative correlation with 3-year [odds ratio (OR), 0.021 and 0.111; P=0.001 and 0.0302, respectively] and 1.5-year (OR, 0.040 and 0.051; P=0.0330 and 0.0492, respectively) survival rates in comparison with low expression. The results of the present study demonstrated a predictive role of high qualitative and quantitative expression in activated fibroblasts for poor survival in patients with HCC.


Structure of an HIF-1alpha -pVHL complex: hydroxyproline recognition in signaling.
The ubiquitination of the hypoxia-inducible factor (HIF) by the von Hippel-Lindau tumor suppressor (pVHL) plays a central role in the cellular response to changes in oxygen availability. pVHL binds to HIF only when a conserved proline in HIF is hydroxylated, a modification that is oxygen-dependent. The 1.85 angstrom structure of a 20-residue HIF-1alpha peptide-pVHL-ElonginB-ElonginC complex shows that HIF-1alpha binds to pVHL in an extended beta strand-like conformation. The hydroxyproline inserts into a gap in the pVHL hydrophobic core, at a site that is a hotspot for tumorigenic mutations, with its 4-hydroxyl group recognized by buried serine and histidine residues. Although the beta sheet-like interactions contribute to the stability of the complex, the hydroxyproline contacts are central to the strict specificity characteristic of signaling.


Estimating population salt intake in India using spot urine samples.
To compare estimates of mean population salt intake in North and South India derived from spot urine samples versus 24-h urine collections. In a cross-sectional survey, participants were sampled from slum, urban and rural communities in North and in South India. Participants provided 24-h urine collections, and random morning spot urine samples. Salt intake was estimated from the spot urine samples using a series of established estimating equations. Salt intake data from the 24-h urine collections and spot urine equations were weighted to provide estimates of salt intake for Delhi and Haryana, and Andhra Pradesh. A total of 957 individuals provided a complete 24-h urine collection and a spot urine sample. Weighted mean salt intake based on the 24-h urine collection, was 8.59 (95% confidence interval 7.73-9.45) and 9.46 g/day (8.95-9.96) in Delhi and Haryana, and Andhra Pradesh, respectively. Corresponding estimates based on the Tanaka equation [9.04 (8.63-9.45) and 9.79 g/day (9.62-9.96) for Delhi and Haryana, and Andhra Pradesh, respectively], the Mage equation [8.80 (7.67-9.94) and 10.19 g/day (95% CI 9.59-10.79)], the INTERSALT equation [7.99 (7.61-8.37) and 8.64 g/day (8.04-9.23)] and the INTERSALT equation with potassium [8.13 (7.74-8.52) and 8.81 g/day (8.16-9.46)] were all within 1 g/day of the estimate based upon 24-h collections. For the Toft equation, estimates were 1-2 g/day higher [9.94 (9.24-10.64) and 10.69 g/day (9.44-11.93)] and for the Kawasaki equation they were 3-4 g/day higher [12.14 (11.30-12.97) and 13.64 g/day (13.15-14.12)]. In urban and rural areas in North and South India, most spot urine-based equations provided reasonable estimates of mean population salt intake. Equations that did not provide good estimates may have failed because specimen collection was not aligned with the original method.


Effects of polygalacturonase overexpression on pectin distribution in the elongation zones of roots under aluminium stress.
The roots of many plant species contain large amounts of pectin and it contributes to the formation of the rhizosphere. In the present study, the relationship between the root-tip pectin content and aluminium (Al) tolerance in wild-type (WT) and demethylesterified pectin degradation enzyme gene overexpressor (OsPG2-FOX) rice lines was compared. OsPG2-FOX rice showed reduced pectin content in roots, even under control conditions; Al treatment reduced root elongation and the pectin content in the root elongation zone. Wild-type rice showed more pectin accumulation in the root elongation zone after Al treatment. Relative to WT rice, OsPG2-FOX rice showed more Al accumulation in the root elongation zone. These results indicate that the amount of pectin influences Al tolerance and that the distribution of pectin in the root elongation zone inhibits Al accumulation in rice roots. Pectin accumulation in cell walls in the root elongation zone may play a role in protecting rice plants from the Al-induced inhibition of root elongation by regulating pectin distribution.


Signaling through the LFA-1 leucocyte integrin actively regulates intercellular adhesion and tumor necrosis factor-alpha production in natural killer cells.
The LFA-1 leucocyte integrin is known to participate in natural killer (NK) cytolytic activity, mediating effector target interactions. The possibility that LFA-1 may also play an active regulatory role in NK cells has been explored. To this end, we have employed a monoclonal antibody (HP1N) raised against recombinant interleukin-2 (rIL-2)-activated NK cells, which recognizes the alpha chain of the LFA-1 heterodimer (CD11a). In contrast to other anti-CD11a mAb the HP1N and its F(ab')2 fragment did not affect NK cell-mediated cytotoxicity and triggered a strong homotypic adhesion of NK cells and other LFA-1+ cells. Cellular aggregation was inhibited by anti-CD18 mAb, anti-ICAM-1 mAb, and other anti-CD11a mAb. Remarkably, the HP1N mAb was also shown to induce tumor necrosis factor-alpha (TNF-alpha) production from NK cells upon costimulation with anti-CD16 mAb. Such an effect appeared to be independent from homotypic adhesion since it took place in Mg(2+)-free medium, where NK cell aggregation was inhibited. Moreover, incubation with the HP1N mAb triggered a Ca2+ influx into the cytosol; this effect was clearly observed upon cross-linking of cell bound HP1N and was also substantiated with other anti LFA-1 (CD11a and CD18) mAb. Taken together these results indicate that the LFA-1 molecule is capable of transducing signals in NK cells, which regulate the intercellular interaction with its ligand, and enhance the activation via Fc gamma receptor type III.


ClC-3 deficiency prevents apoptosis induced by angiotensin II in endothelial progenitor cells via inhibition of NADPH oxidase.
Endothelial progenitor cells (EPCs) play an important role in postnatal neovascularization and re-endothelialization in response to tissue ischemia and endothelial injury. It is reported that the circulating EPCs number is decreased during hypertension. However, the detailed mechanism is still unclear. Our previous studies have shown that ClC-3 chloride channel is up-regulated with the development of hypertension. This study aims to test whether ClC-3 participates in EPC apoptosis under the condition of increased oxidative stress in angiotensin II (Ang II)-induced hypertension. The results showed that stimulation with 10(-6)mol/L Ang II significantly up-regulated the endogenous ClC-3 expression and increased intracellular reactive oxygen species (ROS) generation in EPCs of wild type mice, accompanied by an enhanced NADPH oxidase activity and the expression of gp91(phox) (NOX-2), a key catalytic subunit of NADPH oxidase. However, these effects of Ang II were significantly reduced in EPCs of ClC-3(-/-) mice. Compared with control, treatment with Ang II induced EPCs apoptosis in wild type mice, concomitantly with declined Bcl-2/Bax ratio, depressed mitochondrial membrane potential and activation of poly(ADP-ribose) polymerase, which was remarkably prevented by both ClC-3 knockout and NADPH oxidase inhibitor apocynin. In addition, the role of ClC-3 deficiency in protecting EPCs against Ang II-induced oxidative stress and apoptosis was further confirmed in Ang II-infused hypertensive mice in vivo. In conclusion, ClC-3 deficiency inhibited Ang II-induced EPC apoptosis via suppressing ROS generation derived from NADPH oxidase.


Object-oriented modeling and terminologies for drug contraindications.
There is no available standardized representation of contraindications that can be used in drug knowledge bases. In this paper, an object-oriented representation of contraindications is proposed that would allow computerized checking of drug prescription safety. It distinguishes four types of contraindications: pathological state, physiological state, findings of investigation procedures, and diagnostic or therapeutic procedures. The vocabulary usable for expressing the contraindications appropriate for automated prescription checking was also investigated. ICD10 (International Classification of Diseases, tenth revision), SNOMED III (Systematized Nomenclature of Medicine), ICPC (International Classification of Primary Care), and ATC (Anatomic Therapeutic and Chemical Classification) were studied as potential sources of standardized vocabulary. A system to support entering data on contraindications into a drug knowledge base, compatible with the proposed structure and using the identified vocabulary sources, is also presented.


Micro-tensile bond strength of sound and caries-affected primary tooth dentin measured with original designed jig.
To measure the micro-tensile bond strength (MTBS) on sound and caries-affected primary tooth dentin using an original designed jig that was developed for making symmetric and uniformly-sized specimens for the micro-tensile strength testing. The MTBS of dumbbell-shaped specimens and matchstick-shaped specimens were measured. Dumbbell-shaped specimens: The occlusal surfaces of 15 sound primary molars were ground with a water-cooled air turbine using a diamond bur. The adhesive systems and resin-based composites were Clearfil SE Bond and Clearfil AP-X (SE group) and Single Bond and Z250 (SB group). Matchstick-shaped specimens: Sixteen primary molars (5 sound and 11 carious) were used. The occlusal surfaces of sound teeth were ground with a water-cooled air turbine using a diamond bur. Infected dentin was determined by a caries detecting dye solution and removed with a round-shaped steel bur under water-cooling and with a hand instrument. SE was applied. Data was statistically analyzed using ANOVA and Fisher's PLSD at p < 0.05. The MTBSs (MPa) for the dumbbell-shaped specimens were 8.9 +/- 7.0 in the SE group and 10.3 +/- 5.8 in the SB group and that for the matchstick-shaped specimens were 9.0 +/- 6.3 in the sound-SE group and 9.2 +/- 5.8 in the carious-SE group. No significant difference was observed among them.


[The treatment of Wilm's tumor, improvements and new trends. A study of 724 cases treated at the Gustave-Roussy Institute. 1952-1980 (author's transl)].
Study of 724 cases of Wilm's tumor treated between 1952 and 1980 at the Gustave-Roussy Institute, according to 5 successive therapeutic protocols with or without chemotherapy (Actinomycin alone or Actinomycin and Vincristine). Recovery rates change from 44 to over 90% during this period. Improvement of survival was first obtained by the efficient treatment of metastases, then by preventing their development with systematic chemotherapy with Actinomycin and Vincristine. Rate of survival without relapse changed from 38 to 71 and 86%. Thus, the decrease in the number of patent metastases subjected to heavy treatments responsible for severe respiratory and orthopedic sequelae improved the quality of survival of these children.


[Health and healthcare of homeless persons].
Homelessness is a complex issue linked to poverty and structural conditions. It is increasing in Western countries with younger people and multiple generations being affected. Hard and unstable living conditions and inappropriate access to care predispose people to increase morbidity with poor health outcomes. This article reviews recent evidence about homeless health and strategies to improve health outcomes while harnessing societal benefits.


The role of complement inhibitors beyond controlling inflammation.
The complement system is an arm of innate immunity that aids in the removal of pathogens and dying cells. Due to its harmful, pro-inflammatory potential, complement is controlled by several soluble and membrane-bound inhibitors. This family of complement regulators has been recently extended by the discovery of several new members, and it is becoming apparent that these proteins harbour additional functions. In this review, the current state of knowledge of the physiological functions of four complement regulators will be described: cartilage oligomeric matrix protein (COMP), CUB and sushi multiple domains 1 (CSMD1), sushi domain-containing protein 4 (SUSD4) and CD59. Complement activation is involved in both the development of and defence against cancer. COMP expression is pro-oncogenic, whereas CSMD1 and SUSD4 act as tumour suppressors. These effects may be related in part to the complex influence of complement on cancer but also depend on unrelated functions such as the protection of cells from endoplasmic reticulum stress conveyed by intracellular COMP. CD59 is the main inhibitor of the membrane attack complex, and its deficiency leads to complement attack on erythrocytes and severe haemolytic anaemia, which is now amenable to treatment with an inhibitor of C5 cleavage. Unexpectedly, the intracellular pool of CD59 is crucial for insulin secretion from pancreatic β-cells. This finding is one of several relating to the intracellular functions of complement proteins, which until recently were only considered to be present in the extracellular space. Understanding the alternative functions of complement inhibitors may unravel unexpected links between complement and other physiological systems, but is also important for better design of therapeutic complement inhibition.


Prevalence of dementia among older age people and variation across different sociodemographic characteristics: a cross-sectional study in Bangladesh.
Dementia is a significant global health issue, particularly for low-income and middle-income countries which majorly contribute to the dementia cases reported globally (67%). We estimated the prevalence of dementia among older people in Bangladesh and compared the estimate across different sociodemographic characteristics and divisions. A cross-sectional study was conducted in 2019 among individuals aged 60 years or older in seven administrative divisions in Bangladesh. Equal numbers of male and female participants were recruited from each division through a multi-stage random sampling technique. Recruitment was proportionally distributed in urban and rural areas in each division. Following consent, the Mini Mental State Examination (MMSE) was performed on all participants. Dementia was defined as an MMSE score of <24 out of 30. Data on age, sex, education, marital status, occupation, socioeconomic status, and type of community (urban or rural) were obtained using a structured questionnaire to compare the prevalence of dementia across different sociodemographic characteristics. Between January and December 2019, 2795 individuals were recruited including ∼400 from each of the seven administrative divisions. The mean age was 67 years (SD: 7), 68% were from rural areas and 51% were female. The prevalence of dementia was 8.0% (95% CI: 7.0-8.9%) with variations across age, sex, education, marital status, occupation, and division. No variations in prevalence were observed across urban/rural locations or socioeconomic status. After adjusting for age, sex, education, occupation and marital status, the odds of dementia was two times higher in females than males (OR: 2.15, 95% CI: 1.43-3.28); nine times higher in people aged ≥90 years than people aged 60-69 years (OR: 9.62, 95% CI: 4.79-19.13), and three times higher in people with no education compared to those who had completed primary school (OR: 3.10, 95% CI: 1.95-5.17). The prevalence of dementia is high in Bangladesh and varies across sociodemographic characteristics with a higher prevalence among females, older people, and people with no education. There is an urgent need to identify the key risk factors for dementia in developing countries, such as Bangladesh, to inform the development of context-relevant risk reduction and prevention strategies. None.


Expression of surface markers and myogenic potential of rat bone marrow- and adipose-derived stem cells: a comparative study.
In recent years, examination and comparison of the biological characteristics of bone marrow- and adipose-derived mesenchymal stem cells (MSCs) from various perspectives have come into the focus of stem cell research, as these cells should be well characterized in order to utilize them in future cellular therapies. Therefore, in the present study, surface protein markers and the skeletal myogenic differentiation potential of rat bone marrow- and adipose-derived MSCs were examined. The expression of CD44, CD45, CD73, and CD90 on bone marrow- and adipose-derived MSCs was characterized using flow cytometry. Subsequently, the stem cells were differentiated into myogenic lineages, and the expression of the skeletal myogenic markers MyoD1, Myog, and Myh2 was studied in cells using real time polymerase chain reaction and immunofluorescence. Our results reveal that the pattern of CD marker expression differs between these 2 types of MSCs to some extent, whereas no significant difference was observed with respect to their myogenic differentiation potential. Therefore, we concluded that despite the differences observed in the biological features of these 2 types of MSCs, their myogenic potential appears to be similar, and that adipose-derived stem cells may be useful in skeletal muscle tissue engineering, due to their easy isolation and capacity for rapid expansion in a short time span.


Blockade of ACK1/TNK2 To Squelch the Survival of Prostate Cancer Stem-like Cells.
Prostate cancer stem-like cells (PCSCs) are not only enriched in the CD44+PSA-/lo subpopulation but also employ androgen-independent signaling mechanisms for survival. CD44+ PCSCs defy androgen deprivation, resist chemo- and radiotherapy and are highly tumorigenic. Human prostate tissue microarray (TMA) staining revealed an increased membranous staining of CD44 in the luminal compartment in higher grade G7-G9 tumors versus staining of the basal layer in benign hyperplasia. To uncover tyrosine kinase/s critical for the survival of the CD44+PSA-/lo subpopulation, we performed an unbiased screen targeting 87 tyrosine kinases with gene specific siRNAs. Among a subset of tyrosine kinases crucial for PCSC survival, was a non-receptor tyrosine kinase, ACK1/TNK2, a critical regulator of castration resistant prostate cancer (CRPC) growth. Consistently, activated ACK1 as measured by phosphorylation at Tyr284 was significant in the CD44+PSA-/lo population. Conversely, pharmacological inhibition by ACK1 inhibitor, (R)-9bMS mitigated CD44+PSA-/lo sphere formation, overcame resistance to radiation-induced cell death, induced significant apoptosis in PCSCs and inhibited CD44+PSA-/lo xenograft tumor growth in castrated mice suggesting dependency of PCSCs on ACK1 for survival. Thus, blockade of ACK1/TNK2 could be a new therapeutic modality to target recalcitrant PCSCs.


Association of Maternal Gestational Weight Gain With the Infant Fecal Microbiota.
Pregnancy characteristics may influence the infant fecal microbiota during early life. We aimed to examine associations of maternal gestational weight gain with infant fecal microbiota composition, bacterial community richness, and Shannon diversity index. We analyzed data from a prospective cohort study of healthy infants. We collected prenatal data, including report of mother's gestational weight gain, and infant fecal samples from 84 infant-mother dyads. By applying 16S rRNA gene sequencing and an unbiased clustering by partitioning around medoids using Bray-Curtis distances, we identified 4 fecal microbiota profiles, and examined the associations of maternal gestational weight gain with the 4 fecal microbiota profiles, bacterial community richness, and Shannon diversity index. Overall, the median age of infants was 4.0 months and 43% were girls. The mothers of the 84 infants gained a mean of 14.2 kg (standard deviation, 5.4 kg) during pregnancy. We identified 4 distinct microbiota profiles: Bifidobacterium-dominant (42%), Enterobacter/Veillonella-dominant (23%), Bacteroides-dominant (19%), and Escherichia-dominant (17%). Infants whose mothers had higher gestational weight gain were less likely to have a Bacteroides-dominant profile, corresponding to a relative risk ratio of 0.83 (95% confidence interval, 0.71-0.96; P = 0.01) per 1 kg increase in weight. In addition, higher gestational weight gain was also associated with lower bacterial community richness and Shannon diversity index (P < 0.05). In this prospective cohort study of healthy infants, maternal gestational weight gain was associated with the infant fecal microbiota profiles, bacterial community richness, and Shannon diversity index.


Inflammatory response and neuronal necrosis in rats with cerebral ischemia.
In the middle cerebral artery occlusion model of ischemic injury, inflammation primarily occurs in the infarct and peripheral zones. In the ischemic zone, neurons undergo necrosis and apoptosis, and a large number of reactive microglia are present. In the present study, we investigated the pathological changes in a rat model of middle cerebral artery occlusion. Neuronal necrosis appeared 12 hours after middle cerebral artery occlusion, and the peak of neuronal apoptosis appeared 4 to 6 days after middle cerebral artery occlusion. Inflammatory cytokines and microglia play a role in damage and repair after middle cerebral artery occlusion. Serum intercellular cell adhesion molecule-1 levels were positively correlated with the permeability of the blood-brain barrier. These findings indicate that intercellular cell adhesion molecule-1 may be involved in blood-brain barrier injury, microglial activation, and neuronal apoptosis. Inhibiting blood-brain barrier leakage may alleviate neuronal injury following ischemia.


[Risk factors for Toxoplasma gondii infection in pregnant women in Armenia, Colombia].
To determine the risk factors associated with acute toxoplasmosis during pregnancy in Armenia. Case-control study; 14 cases and 34 controls (mean ages 23 +/- 5.5 and 23 +/- 5.1 respectively; p = 0.93). Cases were pregnant women with serological criteria for acute toxoplasmosis and controls were seronegative pregnant women for Toxoplasma IgG. The risk factors more strongly predictive of acute toxoplasmosis in pregnant women were: eating undercooked meat (OR: 13.2; 95% CI: 1.3-132; p = 0.01), drinking beverages prepared with un-boiled water (OR: 4.5; 95% CI: 1.1-17; p = 0.01), and contact with cats aged less than 6 months (OR: undefined, p = 0.01). Drinking of bottled water was a protective factor (OR: 0.24; 95% CI: 0.06-0.95; p = 0.02). 42% of Toxoplasma gondii infections in pregnant women Armenia were associated to contact with young cats and to consumption of undercooked meat. Drinking of bottled water to prevent toxoplasma infection during pregnancy is also recommended.


Cinnamic Acid Inhibited Growth of Faba Bean and Promoted the Incidence of Fusarium Wilt.
To ascertain the role and mechanism of cinnamic acid in the process of soil-borne Fusarium wilt infection with fava bean, we studied the effect of cinnamic acid on the faba bean and Fusarium oxysporum f. fabae (FOF). Our results showed that cinnamic acid treatment affected the physiological resistance of faba bean to FOF after inoculation with the pathogen and enhanced the pathogenicity of the pathogen, which may have led to aggravation of infection by the pathogen and increases in the incidence rates of Fusarium wilt and disease.


False security or greater social inclusion? Exploring perceptions of CCTV use in public and private spaces accessed by the homeless.
It has been well documented that owing to the vulnerability inherent in their situation and status, the homeless experience high rates of harassment and criminal victimization. And yet, the question of whether CCTV surveillance of public and private spaces - so frequently viewed by the middle classes as a positive source of potential security - might also be viewed by the homeless in similar ways. Within the present paper, I address this issue by considering the possibility that CCTV might be seen by some homeless men and women as offering: a) a measure of enhanced security for those living in the streets and in shelters, and; b) to the extent that security is conceived of as a social good, the receipt of which marks one as a citizen of the state, a means by which they can be reconstituted as something more than 'lesser citizens'. To test these ideas, I rely on data from interviews conducted with homeless service users, service providers for the homeless, and police personnel in three cities. What is revealed is a mixed set of beliefs as to the relative security and meaning of CCTV.


Effects of source and particle size on the biological availability of calcium in calcium supplements for growing pigs.
Five experiments were conducted to determine the biological availability of the Ca in high-Ca (calcitic) limestone, dolomitic limestone, oyster shell flour, gypsum, marble dust and aragonite for the growing pig, and to determine the influence of particle size of the Ca source on the bioavailability of Ca. A low-Ca, fortified, corn soybean meal basal diet calculated to contain .2% Ca and .6% P was used. This diet was supplemented with 0 or .3% Ca from either CaCO3 precipitate (the standard) or the test source of Ca. Diets were fed on an ad libitum basis to three to eight replicate pens of pigs (one or two/pen) for 35 to 42 d. Average initial weight of the pigs was 15 kg. At the end of each experiment the pigs were killed, the third and fourth metacarpals and metatarsals and the femurs were removed, and breaking strength and ash were determined. The increase in bone strength from feeding the test source of Ca relative to the increase in bone strength from feeding the CaCO3 standard was used to calculate the relative availability of Ca in the supplements. The bioavailability of Ca in calcitic limestone (two sources), oyster shell flour, gypsum, marble dust and aragonite was similar, ranging from 93 to 102%. However, the Ca in two sources of dolomitic limestone was less available (51 and 78%) than in the other sources. Particle size of the Ca sources (geometric mean diameter of .10 to .54 mm) did not influence the availability of Ca.


Self-Assembly-Driven Bi2S3 Nanobelts Integrated a Silk-Fibroin-Based 3D-Printed Aerogel-Based Scaffold with a Dual-Network Structure for Photothermal Bone Cancer Therapy.
Multifunctional all-in-one biomaterial combining the therapeutic and regeneration functionalities for successive tumor therapy and tissue regeneration is in high demand in interdisciplinary research. In this study, a three-dimensional (3D) aerogel-based composite scaffold with a dual-network structure generated through self-assembly and photo-cross-linking with combined properties of photothermally triggered controlled anticancer drug release and photothermal cancer cell ablation was successfully fabricated. The fabrication of composites consists of self-assembly of a silk fibroin methacrylate (SF-MA) biopolymer incorporated with hydrothermally driven bismuth sulfide (Bi2S3) methacrylate nanobelts, followed by a photo-cross-linking-assisted 3D-printing process. The developed scaffolds presented hierarchically organized porosity and excellent photothermal conversion thanks to the strong near-infrared (NIR) photon absorption of incorporated Bi2S3 nanobelts inside the scaffold matrix. The heat generated in the scaffold mediated by laser irradiation has not only triggered controlled and prolonged release of the anticancer drug but also significantly ablated the bone cancer cells adhered on the scaffold. In addition, the developed 3D composite scaffolds have demonstrated excellent biodegradability for organic and inorganic network constituents at different media, enabling them as potential implants to be replaced by de novo tissue. In combination of chemotherapy and photothermal therapy, the multifunctional 3D-printed composite aerogel scaffold is expected to be an excellent implantable material in bone tissue engineering (BTE) for successive cancer therapy and tissue regeneration.


The Experience of Advanced Practice Nurses in US Emergency Care Settings.
Little information has been published regarding the actual practice, training, and validation of basic skills and competencies needed by the advanced practice registered nurse (APRN) in the emergency care setting. The purpose of this study was to (1) identify skills being performed by APRNs practicing in emergency care settings (2); explore types of training; and (3) describe competency validation. Additionally, we explored frequency of skill use and facilitators and barriers to performing a skill to the full extent of training and education. An exploratory mixed-methods study was performed incorporating a self-report survey and focus group interviews. The educational path to advanced practice nursing in emergency care settings is not standardized. Few programs incorporate or address the need for APRNs to receive acute care training across the life span, which is the hallmark of emergency nursing practice. Similarly, training is reported as fragmented, and validation of skills for both nurse practitioners and clinical nurse specialists can vary. APRN practice autonomy is affected by the presence of other providers (specifically physicians), institutional culture, and state boards of nursing that regulate practice. Integrated educational and orientation programs are needed that address high-acuity patients across the life span. Additionally, a more nuanced approach to assessing APRN capabilities as a combination of hard (clinical emergency) and soft (communication and organizational) skills may be an appropriate framework within which to examine the advanced practice role. Future research should continue to evaluate training, competency assessment, and outcomes for APRNs in the emergency care setting.


[New possibilities of monotherapy of symptomatic and cryptogenic partial epilepsy].
This literature review is devoted to the use of the antiepileptic drug zonisamide in the initial monotherapy of symptomatic and cryptogenic partial epilepsy. The review is based on the results of the trials, level of evidence A, that demonstrate the efficacy and tolerability of zonisamide comparable to those of carbamazepine. The possible advantages of zonisamide in different clinical situations and characteristics of its use related to molecule structure, pharmacokinetics, mechanisms of drug action are discussed.


Sutureless nerve repair with laser-activated chitosan adhesive: a pilot in vivo study.
The anastomosis of peripheral nerves is a demanding procedure that has potential complications due to foreign body reactions elicited by sutures. In this study, the sutureless in vivo anastomosis of rat tibial nerves was successfully performed, using for the first time a chitosan-based laser-activated adhesive. The nerve thermal damage caused by the laser irradiation was quantitatively assessed. A novel adhesive composed of chitosan, indocyanine green, acetic acid, and water, was fabricated in thin sheets. Its adhesive strength was tested in vitro by bonding strips (surface area approximately 20 mm2, thickness approximately 20 microm) onto rat sciatic nerves and sheep intestine by laser activation with low fluence ( approximately 50 J/cm2), using a fiber-coupled diode laser (n = 13). The tensile strength of the adhesive/tissue bonds was measured after tissue repair. The chitosan adhesive was then used to perform sutureless anastomosis of tibial nerves in vivo (n = 6). Adhesive strips were also bonded in vivo onto intact rat sciatic nerves (n = 6) in order to quantitatively assess, by counting myelinated axons, the thermal damage induced by the laser. The adhesive bonded well to tissue with a tensile strength of 12.5 +/- 2.6 KPa (mean +/- SD; n = 13). The in vivo anastomosed nerves were in continuity 3 d after surgery. Axon counting showed the number and morphology of myelinated axons were normal proximally ( approximately 96%) compared with intact nerves (100%). Axon demyelination was observed at the operation site ( approximately 49%) and distally ( approximately 27%), and was attributed to laser-induced thermal damage. Nerve anastomosis, performed by the laser-adhesive procedure, was successful 3 d postoperatively. Proximal myelinated axons were not significantly damaged by the low laser fluence.


The application of constitutively solvent-tolerant P. taiwanensis VLB120ΔCΔttgV for stereospecific epoxidation of toxic styrene alleviates carrier solvent use.
For whole-cell biotransformations involving toxic organic compounds, two-liquid phase setups are typically applied employing an apolar extractive phase. Bis(2-ethylhexyl)phthalate (BEHP) has proven to be an ideal solvent for stereospecific styrene epoxidation with recombinant E. coli, providing excellent extractive properties and a high biocompatibility. In eco-efficiency evaluations, BEHP, however, has been identified as a critical factor regarding costs and environmental impact. In this study, the constitutive solvent tolerance of Pseudomonas taiwanensis VLB120ΔCΔttgV is shown to enable high specific activities (up to 180 U gCDW-1 ) and extensive reduction of the BEHP amount in two-liquid phase setups and thus to constitute an excellent tool to improve the environmental and economic efficiency of such processes. At a 90% reduction of carrier solvent use and accordingly increased aqueous styrene concentrations, this strain still showed reasonably high specific styrene epoxidation activities (100 U gCDW-1 ), while the solvent-adaptable wildtype strain immediately was toxified. A moderate 55% reduction of BEHP enabled a specific activity of 150 U gCDW-1 and thus represents a good trade-off between volumetric productivity maximization and environmental impact minimization. These results for the first time show a clear benefit of a solvent-tolerant compared to solvent-sensitive host strains and how such a benefit can be achieved.


HOI-02 induces apoptosis and G2-M arrest in esophageal cancer mediated by ROS.
Reactive oxygen species (ROS) are chemically reactive molecules that perform essential functions in living organisms. Accumulating evidence suggests that many types of cancer cells exhibit elevated levels of ROS. Conversely, generation of ROS has become an effective method to kill cancer cells. (E)-3-hydroxy-3-(4-(4-nitrophenyl)-2-oxobut-3-en-1-yl) indolin-2-one, which is an NO2 group-containing compound designated herein as HOI-02, generated ROS and, in a dose-dependent manner, decreased esophageal cancer cell viability and inhibited anchorage-independent growth, followed by apoptosis and G2-M arrest. Moreover, results of an in vivo study using a patient-derived xenograft mouse model showed that HOI-02 treatment suppressed the growth of esophageal tumors, without affecting the body weight of mice. The expression of Ki-67 was significantly decreased with HOI-02 treatment. In addition, the phosphorylation of c-Jun, and expression of p21, cleaved caspase 3, and DCFH-DA were increased in the HOI-02-treated group compared with the untreated control group. In contrast, treatment of cells with (E)-3-(4-(4-aminophenyl)-2-oxobut-3-en-1-yl)-3-hydroxyindolin-2-one, which is an NH2 group-containing compound designated herein as HOI-11, had no effect. Overall, we identified HOI-02 as an effective NO2 group-containing compound that was an effective therapeutic or preventive agent against esophageal cancer cell growth.


Fast Nanoliter-Scale Cell Assays Using Droplet Microarray-Mass Spectrometry Imaging.
In pharmaceutical research and development, cell-based assays are primarily used with readout that rely on fluorescence-based and other label-dependent techniques for analysis of different cellular processes. Superhydrophobic-hydrophilic droplet microarrays (DMA) and matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) have recently emerged as key technologies for miniaturized high-throughput cell assays and for label-free molecular high-content drug profiling, respectively. Here, nanoliter-scale cell assays are integrated on DMAs with MALDI-MS imaging (MALDI-MSI) approaches to a droplet microarray-mass spectrometry imaging (DMA-MSI) platform. Using A549 lung cancer cells, concentration-response profiling of a pharmaceutical compound, the fatty acid synthase inhibitor GSK2194069, are demonstrated. Direct cell culture on DMAs enables combination of microscopy and high speed, high molecular content analysis using MALDI-MSI. Miniaturization of array spots down to 0.5 mm confining 40 nL droplets allows for MALDI imaging analysis of as few as ten cells per spot. Partial automation ensures a fast sample preparation workflow. Taken together, the integrated DMA-MSI platform that combines MALDI-MSI, as a label-free analytical readout, with the miniaturized droplet microarray platform is a valuable complement to high throughput cell-based assays technologies.


Bacillary angiomatosis in an immunosuppressed dog.
A dog being treated with immunosuppressive doses of prednisone and azathioprine for pancytopenia of unknown origin, developed, over a 2-week period, multiple erythematous nodular lesions in the skin including footpads. Skin samples revealed lesions identical to those of human bacillary angiomatosis (BA). The nodules were composed of multifocal proliferations of capillaries, each lined by protuberant endothelial cells. The capillary clusters were separated by an oedematous connective tissue, lightly infiltrated with degenerate inflammatory cells, including neutrophils and macrophages. Tissue sections stained with Warthin-Starry silver stain revealed large numbers of positively stained bacilli in the stromal tissue, most heavily concentrated around the proliferating capillaries. Lesions of vascular degeneration and inflammation were evident. Bartonella vinsonii subsp. berkhoffii genotype 1 was independently amplified and sequenced from the blood and the skin tissue. The pathognomonic nature of the histological lesions, demonstration of compatible silver-stained bacilli in the tissue, and identification of B. vinsonii subsp. berkhoffii in the blood and tissue indicates that this is most likely the aetiologic agent responsible for the lesions. Antibiotic therapy was successful in resolving the nodules. It would appear that B. vinsonii subsp berkhoffii, like Bartonella henselae and Bartonella quintana, has the rare ability to induce angioproliferative lesions, most likely in association with immunosuppression. The demonstration of lesions identical to those of human BA in this dog is further evidence that the full range of clinical manifestations of human Bartonella infection occurs also in canines.


[Medullar cancer of the thyroid associated with dermal mucinosis].
Dermal mucinosis can be associated with numerous pathologies, in particular involving the thyroid, but has never been described in the case of a medullar cancer of the thyroid (MCT). A 69-year-old man consulted for a facial erythrosis, which had been developing for a few weeks without any identified triggering factor. The skin biopsy showed dermal mucinosis and tests revealed a sporadic medullar cancer of the thyroid with secondary bone, ganglion and medullar localizations. The association between medullar cancer of the thyroid and dermal mucinosis has never been described. Several hypotheses may explain this: the thyroid pathology itself, whatever its nature, the capacity of the MCT to synthesize mucin and the medullar metastatic overgrowth.