Renin measurement in blood collected from the efferent arteriole of the kidney of the rat.
Plasma renin could be detected in 16 nl of rat plasma by incubating at 50 degrees C, pH 6.2 with 20 mul of a rat renin substrate. In 60 nl samples it could be estimated and differences in concentration of 20% could be detected. Plasma renin concentration was measured in blood from the superficial efferent arterioles of a rat's kidney. The concentration of renin in different efferent arterioles of the same rat were similar. The renin concentration of efferent arteriolar blood was 361 plus or (-1)89 (S.D.) ng Al ml minus 1 (blood) hour (-1) which was not different from the renin concentration of simultaneously taken femoral artery blood (340 +/- 217). Plasma concentration can be measured in efferent arteriolar blood and will allow the control of renin secretion to be studied.


Interaction of bradykinin and angiotensin-(1-7) in the central modulation of the baroreflex control of the heart rate.
Previous studies have shown that angiotensin-(1-7) potentiates the vascular actions of bradykinin. In the present study, we evaluated the interaction of bradykinin and angiotensin-(1-7) in the central modulation of baroreflex control of the heart rate. Blood pressure and reflex bradycardia, elicited by intravenous injection of phenylephrine, were evaluated in conscious male Wistar rats before and at the end of 1 h of an intracerebroventricular infusion of angiotensin-(1-7) at 0.5 or 1.0 microg/h combined with bradykinin at 2.5 microg/h; or angiotensin-(1-7) at 2.0 microg/h combined with bradykinin at 4.0 microg/h; or angiotensin-(1-7) alone at 2.0 or 4.0 microg/h; or bradykinin alone at 4.0 or 8.0 microg/h; or saline at 8 microl/h. In addition, baroreflex bradycardia was evaluated before and at the end of 1 and 2 h of intracerebroventricular infusion of angiotensin-(1-7) at 4 microg/h for 2 h; or saline at 8 microl/h in the first hour followed by HOE 140 at 90 ng/h in the second hour; or angiotensin-(1-7) at 4 microg/h in the first hour followed by angiotensin-(1-7) at 4 microg combined with HOE 140 at 90 ng/h in the second hour; or HOE 140 at 90 ng/h in the first hour followed by HOE 140 at 90th ng/h combined with angiotensin-(1-7) at 4 microg/h in the second hour; or saline at 8 microl/h for 2 h. The intracerebroventricular infusion of angiotensin-(1-7) or bradykinin alone required a dose of 4.0 and 8.0 microg/h, respectively, to facilitate baroreflex control of the heart. However, a simultaneous infusion of these peptides at subeffective rates was able to produce a significant increase in baroreflex sensitivity. In addition, the facilitation of the baroreflex control of the heart rate induced by angiotensin-(1-7) at 4.0 microg/h was inhibited by HOE 140. These results suggest that centrally, bradykinin and angiotensin-(1-7) can interact in order to modulate baroreflex control of the heart rate. In addition, our data indicate that the central modulatory effect of angiotensin-(1-7) on the baroreflex is mediated, at least in part, by the release of kinins.


Carbamylcholine stimulation of protein secretion in pancreatic acinar carcinoma of rat.
Pancreatic acinar carcinoma fragments, pulse-chase labeled with [3H]-leucine, responded to carbamylcholine chloride by increased secretion of [3H]leucine-labeled protein into external buffer medium. Secretion of labeled protein by the carcinoma fragments increased in concentration-dependent fashion between 10(-8) -10(-5) M carbamylcholine, was completely inhibited at 4 degrees C, and was accompanied by an equivalent increase in the secretion of preformed amylase. A maximally effective carbamylcholine concentration of 10(-5) M was observed for both carcinoma fragments and normal pancreas lobules. However, the maximal rate of protein secretion by the carcinoma fragments was only approximately one-fifth the rate determined for the normal pancreas lobules. This modest secretory response indicates a population of partially differentiated cells in the pancreatic acinar carcinoma which secrete less enzyme than fully differentiated adult pancreatic acinar cells. Secretory responsiveness can be utilized as a quantitative acinar cell response in studies on differentiation in pancreatic carcinoma.


Propylimidazole Functionalized Coumarin Derivative as Dual Responsive Fluorescent Chemoprobe for Picric Acid and Fe3+ Recognition: DFT and Natural Spring Water Applications.
A propylimidazole functionalized coumarin derivative (IPC) was fabricated for the first time and applied as a dual responsive fluorescent chemoprobe for sensitive and selective recognition of picric acid (PA) and Fe3+. Strong fluorescence quenching phenomena of the IPC were observed in H2O/ACN (5/95, v/v) medium (λem=408 nm) upon the additions of Fe3+or PA. The fabricated dual responsive IPC offered good selectivity and sensitivity with the low limit of detection values (0.92 µM for PA and 0.22 µM for Fe3+) lower than the acceptable amounts of Fe3+ and PA by the international official authorities. The validation study for the chemoprobe IPC for PA and Fe3+ was also performed. The interaction phenomena of IPC with PA and Fe3+ based on the findings of a range of experiments were considered and DFT computations were done to verify their recognition mechanisms. The sensing phenomena of IPC towards PA (1:1) and Fe3+ (3:1) were confirmed by the MALDI TOF-MS, FT-IR, 1H-NMR titration and Job's methods. Furthermore, the compound IPC was effectively applied as a fluorescent sensor for Fe3+ and PA detection in real natural spring water samples.


COVID-19 and Private Health: Market and Governance Failure.
The COVID-19 pandemic has produced mass market failure in global private health, particularly in tertiary care. Low-and-middle income countries (LMICs) dependent on private providers as a consequence of neglect of national health systems or imposed conditionalities under neoliberal governance were particularly effected. When beds were most needed for the treatment of acute COVID-19 cases, private providers suffered a liquidity crisis, itself propelled by the primary effects of lockdowns, government regulations and patient deferrals, and the secondary economic impacts of the pandemic. This led to a private sector response-involving, variously, hospital closures, furloughing of staff, refusals of treatment, and attempts to profit by gouging patients. A crisis in state and government relations has multiplied across LMICs. Amid widespread national governance failures-either crisis bound or historic-with regards to poorly resourced public health services and burgeoning private health-governments have responded with increasing legal and financial interventions into national health markets. In contrast, multilateral governance has been path dependent with regard to ongoing commitments to privately provided health. Indeed, the global financial institutions appear to be using the COVID crisis as a means to recommit to the roll out of markets in global health, this involving the further scaling back of the state.


Feasibility of 2,4,6-trichlorophenol and malonic acid as metabolic uncoupler for sludge reduction in the sequence batch reactor for treating organic wastewater.
The activated sludge process generates a large amount of excess sludge as a byproduct, which is one of the most serious challenges in biological wastewater treatment. In the present study, the feasibility of 2,4,6-trichlorophenol (TCP) and malonic acid (MA) as metabolic uncouplers to reduce sludge generation in the sequence batch reactor (SBR) for treating organic wastewater for a long period was studied. The results showed that 2 mg/L TCP could reduce sludge generation by about 47%, while chemical oxygen demand (COD) removal efficiency and sludge settlability were not obviously influenced. Although 10 mg/L MA could also reduce excess sludge production by about 30% while slightly affecting COD removal, it seriously deteriorated sludge settlability. Accordingly, TCP is a better uncoupler for sludge reduction for a longer period in the SBR for treating organic wastewater, and MA can only be used as a short-term or transitional uncoupler. Microscopic and 16S ribosomal deoxyribonucleic acid analyses showed that the microbial population of sludge varied when uncouplers were fed to the activated sludge system. Occurrence of large amounts of filament and the disappearance of protozoa may be the main reason for the aggravation of sludge settlability under uncoupled metabolic conditions caused by MA.


Demonstration of enhanced temperature elevation due to nonlinear propagation of focussed ultrasound in dog's thigh in vivo.
The results of an experimental study quantifying the temperature elevation gains produced by nonlinear propagation of focussed ultrasound fields in dogs' thighs in vivo are presented. Also, the intensity dependence of power absorption from a focussed ultrasound field was studied. The absorbed power appeared to elevate above intensities of 150-250 W cm-2 at 1 MHz in vivo. Enhanced temperature elevations were demonstrated at the same intensity levels, with the size of the elevation increasing with intensity. This phenomenon was large enough to be useful during focussed ultrasound hyperthermia since the maximum temperature gain was about 2 degrees C when a 5 degrees C temperature elevation was induced in the tissue. Using multiple overlapping beams, this effect was further increased.


Regulation of hexose transport in BALB/c 3T3 preadipose cells: effects of glucose concentration and 12-O-tetradecanoylphorbol-13-acetate.
Like many cell types in culture, both undifferentiated and differentiated BALB/c 3T3 preadipose cells respond to glucose deprivation with an increased uptake of 2-deoxy-D-glucose (deoxyglucose) and 3-O-methyl-D-glucose (methylglucose). Glucose readdition to glucose-deprived cultures resulted in a prompt fall in uptake activity; in undifferentiated cells, a half-maximally effective concentration of glucose was approximately 0.5 mM, while 0.1 mM was ineffective. Several hexoses differed in their efficacy of "deactivating" methylglucose transport in glucose-deprived cells; it appeared that a particular hexose must be metabolized beyond the 6-phosphate form to deactivate the transport system. Previous studies have shown that the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) stimulates hexose transport in undifferentiated and differentiated BALB/c 3T3 cells. In this study, it was found that TPA (and insulin in differentiated cells) prevented the glucose-induced deactivation of transport activity. Glucose-induced deactivation of transport activity was also prevented by cycloheximide or actinomycin D addition concomitantly with glucose. In glucose-starved cells, agents such as TPA and insulin appear to override a cellular control mechanism sensitive to the external concentration of glucose, so that elevated levels of transport activity are maintained under environmental conditions (i.e., a return to physiological glucose concentrations) that normally induce a fall in transport activity.


The acceleration of cosmic-ray protons in the supernova remnant RX J1713.7-3946.
Protons with energies up to approximately 10(15) eV are the main component of cosmic rays, but evidence for the specific locations where they could have been accelerated to these energies has been lacking. Electrons are known to be accelerated to cosmic-ray energies in supernova remnants, and the shock waves associated with such remnants, when they hit the surrounding interstellar medium, could also provide the energy to accelerate protons. The signature of such a process would be the decay of pions (pi(0)), which are generated when the protons collide with atoms and molecules in an interstellar cloud: pion decay results in gamma-rays with a particular spectral-energy distribution. Here we report the observation of cascade showers of optical photons resulting from gamma-rays at energies of approximately 10(12) eV hitting Earth's upper atmosphere, in the direction of the supernova remnant RX J1713.7-3946. The spectrum is a good match to that predicted by pion decay, and cannot be explained by other mechanisms.


Erv1 mediates the Mia40-dependent protein import pathway and provides a functional link to the respiratory chain by shuttling electrons to cytochrome c.
Unlike matrix-targeted or inner membrane proteins, those that are targeted to the mitochondrial intermembrane space (IMS) do not require ATP or the inner membrane electrochemical potential. Their import is mediated primarily by the essential IMS protein Mia40/Tim40. Here, we show that the mitochondrial flavin adenine dinucleotide (FAD)-linked sulfhydryl oxidase Erv1 (essential for respiration and vegetative growth 1) plays a central role in the biogenesis of small, cysteine proteins of the IMS that are import substrates for Mia40. In a temperature-sensitive strain of Erv1, steady-state levels of small translocases of the inner membrane (Tims) are specifically affected when cells are grown at the non-permissive temperature. Furthermore, mitochondria isolated from the erv1-ts show a specific import and assembly defect for the small Tims but not in any other protein import pathway. Erv1 does not directly oxidise the small Tims, as thiol trapping assays show that the small Tims can still be oxidised in erv1-ts cells grown at the non-permissive temperature and in isolated mitochondria from this strain. Moreover, addition of pure Erv1 into erv1-ts mitochondria lacking the endogenous protein restores import and assembly of the small Tims only to an extent, arguing for a cascade of interactions with Erv1 rather than for a direct interaction of Erv1 with the small Tims. Cytochrome c (cyt c) is the in vivo oxidase for Erv1, as yeast cells mutated in cyt c cannot grow under anaerobic conditions. Therefore, Erv1 functionally links the Mia40-dependent import pathway to the Mia40-independent cyt c import pathway transferring electrons from the incoming precursors to cyt c as an acceptor. In this context, the protein import process is linked to the respiratory chain via the communication of Erv1 with cyt c.


Linking psychophysiological adaptation, emotion regulation, and subjective stress to the occurrence of paranoia in daily life.
As stress is relevant to the formation of paranoia, maladaptive behavioral and physiological stress regulation is discussed as a crucial indicator of vulnerability. This is supported by research linking psychosis to the tendency to make less use of functional and more use of dysfunctional emotion regulation strategies (ER) and with a lower vagally-mediated heart rate variability (HRV). However, it remains unclear whether ER serves as a mediator between resting-state HRV on the one hand and subjective stress levels and paranoia on the other and whether this is specific to paranoia as compared to depression. We used an experience sampling method during seven days to repeatedly assess the experience of stress, usage of ER strategies, paranoia und depression (9/day) in a sample with subclinical positive symptoms (N = 32). Resting-state HRV was measured during a 5min interval in the laboratory. Data was analyzed by multi-level models. Higher resting-state HRV was predictive of lower stress-levels and of using more functional ER strategies (reappraisal, acceptance) in daily life, but did not predict the use of dysfunctional strategies (rumination, suppression) or paranoia. The association between resting-state HRV and stress was mediated by the usage of functional ER. Less functional and more dysfunctional ER were linked to higher levels of stress, paranoia and depression. Our study highlights that deficits in ER represent a link between psychophysiological and phenomenological aspects of paranoia but also of depression. This encourages to further investigate transdiagnostic prevention and therapy programs aiming to improve ER and to increase HRV.


Discovering neuropeptides in Caenorhabditis elegans by two dimensional liquid chromatography and mass spectrometry.
Completion of the Caenorhabditis elegans genome sequencing project in 1998 has provided more insight into the complexity of nematode neuropeptide signaling. Several C. elegans neuropeptide precursor genes, coding for approximately 250 peptides, have been predicted from the genomic database. One can, however, not deduce whether all these peptides are actually expressed, nor is it possible to predict all post-translational modifications. Using two dimensional nanoscale liquid chromatography combined with tandem mass spectrometry and database mining, we analyzed a mixed stage C. elegans extract. This peptidomic setup yielded 21 peptides derived from formerly predicted neuropeptide-like protein (NLP) precursors and 28 predicted FMRFamide-related peptides. In addition, we were able to sequence 11 entirely novel peptides derived from nine peptide precursors that were not predicted or identified in any way previously. Some of the identified peptides display profound sequence similarities with neuropeptides from other invertebrates, indicating that these peptides have a long evolutionary history.


Differential diagnosis of infarct-like intracranial ectopic germinomas and subacute lacunar infarct on susceptibility-weighted imaging.
To determine the efficacy of susceptibility-weighted imaging (SWI) in the differential diagnosis between basal ganglia (BG) infarct-like early stage intracranial ectopic germinomas (IEGs) and subacute lacunar infarct (SLI). Six children with early stage BG IEGs displaying an infarct-like episode proven by pathology and eight children with BG SLI proven by clinic and vascular imaging were investigated retrospectively. On SWI, the contrast-to-noise ratio (CNR) in abnormal signal intensity regions was calculated and compared between the two groups. For both IEGs and SLI the BG lesions were invisible or showed slight hyperintensity/hypointensity on T1-weighted images and diffusion-weighted images, patchy slight hyperintensity on T2-weighted images without mass effect, and variable enhancement on postcontrast magnetic resonance imaging (MRI). On SWI, obvious hypointensity in BG lesions and pineal gland (PG) was found in IEG patients but unremarkable in SLI patients. The CNRs of BG lesions and PG were significantly higher in IEG patients compared with those in SLI patients (P < 0.01). SWI is useful in differentiating IEGs from SLI when clinical symptoms and conventional MRI manifestations overlap in these two conditions. PG may be involved with tumor, although it is normal on conventional MRI in patients with IEGs.


Effects of intracerebroventricular administration of neurotensin, substance P and calcitonin on gastrointestinal motility in normal and vagotomized rats.
The effects of intracerebroventricular (ICV) vs. intravenous (IV) injection of neurotensin, substance P and calcitonin on intestinal myoelectrical activity were examined in fed rats. ICV administered neurotensin and calcitonin restored the 'fasted' pattern of intestinal activity, i.e. the migrating myoelectric complex (MMC) at a dose as low as 12 and 0.2 pmol, respectively, whereas substance P only reduced significantly (P less than 0.01) the duration of the postprandial pattern when injected ICV (48 pmol). Administered systemically at doses 100 times higher than the smallest active doses by the ICV route, calcitonin induced a fasted pattern, while neurotensin and substance P did not modify the fed pattern. The effects of ICV administration of neurotensin and calcitonin were abolished after vagotomy but the shortening effect of substance P on the duration of the postprandial pattern was still present. It is concluded that these three neuropeptides act centrally to control the pattern of intestinal motility in fed rats by shortening the 'fed' pattern for substance P and by restoring the MMC pattern for calcitonin and neurotensin, this last effect being mediated by the vagus.


Structure of human cholecystokinin gene and its chromosomal location.
We have determined the entire structure of human cholecystokinin (CCK) gene, which is 7 kb in size and separated into three exons. S1 endonuclease analysis has shown two putative transcription initiation sites that are preceded by 'TATA' equivalent sequences located 39 bp and 35 bp upstream from these sites. The promoter region contains five 'G-C box'-like sequences, which are believed to be sp 1-binding sites. By chromosome sorting in combination with velocity sedimentation and Southern hybridization, the human cck gene was mapped on the short arm of human chromosome 3.


Identification of O-diglycosyl flavanones in Fructus aurantii by liquid chromatography with electrospray ionization and collision-induced dissociation mass spectrometry.
This study reported the application of LC-ESI/MS method to characterize O-diglycosyl flavanones of traditional Chinese medicine Fructus aurantii(Zhiqiao) and UPLC retention parameters method to expatiate the structure-retention relationship of these O-diglycosyl flavanones. The extract of F. aurantii was found containing neoeriocitrin, isonaringin, naringin, hesperidin, neohesperidin and neoponcirin. Tandem mass spectrometric method has been utilized to elucidate structure and differentiate the interglycosidic linkage of isomeric O-diglycosyl flavanones. Based on the relative abundance of fragments formed by fragmentation at glycosidic bonds in positive ion mode and CID MS spectra of deprotonated molecule [M-H](-) in negative ion mode, the interglycosidic linkage of O-diglycosyl flavanones (flavonoid O-neohesperidosides and O-rutinosides, 1,2- and 1,6-) can be unambiguously differentiated. UPLC and a CSASS software were performed to obtain the retention parameters a, c and k values of these compounds. The Deltaa, Deltac and alpha values within compound pair naringin to neoriocitrin, neoponcirin to neohesperidin, naringin to isonaringin, neohesperidin to hesperidin, hesperidin to isonaringin, neohesperidin to naringin were calculated. We found there were some relationship between structure and retention parameters.


Clofazimine in Nontuberculous Mycobacterial Infections: A Growing Niche.
Infection secondary to rapidly growing mycobacteria (RGM) is associated with significant morbidity and mortality, especially in individuals with underlying structural lung disease or immune compromise. Such infections, particularly those caused by the Mycobacterium abscessus group, are challenging to treat due to high virulence, antibiotic resistance, and the lack of effective and tolerable therapies. Although novel antimycobacterials are under development, clofazimine-a drug historically administered as part of multidrug therapy regimens for Mycobacterium leprae-holds promise as a chemotherapeutic for the treatment of RGM. The history, pharmacologic properties of clofazimine, as well as in vitro and in vivo studies against RGM are described here and highlight a potential new niche for an old drug.


X-ray-sensitive mutants of Chinese hamster ovary cell line. Isolation and cross-sensitivity to other DNA-damaging agents.
A standard technique of microbial genetics, which involves the transfer of cells from single colonies by means of sterile toothpicks, has been adapted to somatic cell genetics. Its use has been demonstrated in the isolation of X-ray-sensitive mutants of CHO cells. 9000 colonies have been tested and 6 appreciably X-ray-sensitive mutants were isolated. (D10 values 5-10-fold of wild-type D10 value.) A further 6 mutants were obtained which showed a slight level of sensitivity (D10 values less than 2-fold of wild-type D10 value). The 6 more sensitive mutants were also sensitive to bleomycin, a chemotherapeutic agent inducing X-ray-like damage. Cross-sensitivity to UV-irradiation and treatment with the alkylating agents, MMS, EMS and MNNG, was investigated for these mutants. Some sensitivity to these other agents was observed, but in all cases it was less severe than the level of sensitivity to X-irradiation. Each mutant showed a different overall response to the spectrum of agents examined and these appear to represent new mutant phenotypes derived from cultured mammalian cell lines. One mutant strain, xrs-7, was cross-sensitive to all the DNA-damaging agents, but was proficient in the repair of single-strand breaks.


Microsomal warfarin binding and vitamin K 2,3-epoxide reductase.
Rat liver microsomal 4-hydroxycoumarin binding was studied by assaying specific [14C]warfarin binding. Microsomes of warfarin-sensitive rats contained about 40 pmole of specific binding sites per mg of microsomal protein. There was no difference for R- or S-[14C]warfarin. Neither was there any difference between the enantiomers of acenocoumarol and phenprocoumon to prevent the in vitro racemic [14C]warfarin binding. Pretreatment of the microsomes with dithiothreitol, the in vitro reductor for microsomal vitamin K epoxide reductase activity, reduced the warfarin binding. Vitamin K epoxide nor vitamin K affected the warfarin binding. Microsomes of the Welsh warfarin resistant genotype showed weak warfarin binding properties. The Scottish resistant variant, on the other hand, did not differ from sensitive microsomes. Warfarin binding was reduced in microsomes of rats to which S-warfarin was administered. The reduction in warfarin binding was linear with the inhibition of microsomal vitamin K epoxide reductase activity and was linear with the amount of S-warfarin present in the microsomes. The results show the microsomal 4-hydroxycoumarin binding to be related to the target enzyme vitamin K epoxide reductase.


[A comparison of laparoscopic versus open repair for the surgical treatment of perforated peptic ulcers].
To analyse the outcomes of laparoscopic versus open repair for perforated peptic ulcers (PPU). All patients undergoing PPU repair between January 2002 and March 2012 were included in the study. Demographic characteristics, operation time, complications, and length of hospital stay were evaluated. Two hundred and twelve patients (median age, 49 years) were included, 60 in the laparoscopic group and 52 in the open group. Patients operated laparoscopically were significantly younger and had a higher consumption of tobacco, alcohol and cannabis. Median acute symptoms time was shorter in the laparoscopic group (6h) compared to the open group (12h; P=.025) Symptoms time was shorter in the laparoscopic group. Median operating time was significantly longer in the laparoscopic group (104.5min vs. 76min, P=.025). The percentage of conversion to open repair was 25%. There was no difference in morbidity between 2 groups, but there were 3 deaths in the open group. Median hospital stay was significantly shorter in patients treated laparoscopically when compared with the open group (6 days vs. 8 days; P=.041). Laparoscopic and open repair are equally safe in the management of PPU. A shorter hospital stay can be achieved in the laparoscopic group.


Impact of deranged B cell subsets distribution in the development of HCV-related cirrhosis and HCC in type two diabetes mellitus.
Type II diabetes (T2D) may worsen the course of hepatitis C virus infection with a greater risk of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). In chronic viral infections, the deranged B cell subset signifies uncontrolled disease. The study aimed to verify the relation between B cell subsets' distribution and liver disease progression in chronic hepatitis C (CHC) patients with T2D. A total of 67 CHC patients were divided into two groups; 33 non-diabetic and 34 with T2D. Each group was subdivided into CHC-without LC or HCC (N-CHC), CHC-with LC (CHC-LC), and CHC-with HCC (CHC-HCC). Twenty-seven healthy individuals also participated as controls. Flow cytometry was used to analyze CD19+ B cell subsets based on the expression of CD24 and CD38. CD19+CD24hiCD38hi Immature/transitional B cells elevated in diabetic than non-diabetic patients. In diabetic patients, while CD19+CD24+CD38- primarily memory B cells were higher in CHC-N and CHC-HCC groups than LC with a good predictive accuracy of LC, the opposite was observed for CD19+CD24-CD38- new memory B cells. Only in diabetic patients, the CD19+CD24intCD38int naïve mature B cells were high in CHC-HCC patients with good prognostic accuracy of HCC. Merely in diabetic patients, several correlations were observed between B cell subsets and liver function. Immature/transitional B cells increase remarkably in diabetic CHCpatients and might have a role in liver disease progression. Memory and Naïve B cells are good potential predictors of LC and HCCin diabetic CHCpatients, respectively. Further studies are needed to investigate the role of the CD19+CD24-CD38- new memory B cells in disease progression in CHC patients.


Diesel exhaust but not ozone increases fraction of exhaled nitric oxide in a randomized controlled experimental exposure study of healthy human subjects.
Fraction of exhaled nitric oxide (FENO) is a promising non-invasive index of airway inflammation that may be used to assess respiratory effects of air pollution. We evaluated FENO as a measure of airway inflammation after controlled exposure to diesel exhaust or ozone. Healthy volunteers were exposed to either diesel exhaust (particle concentration 300 μg/m3) and filtered air for one hour, or ozone (300 ppb) and filtered air for 75 minutes. FENO was measured in duplicate at expiratory flow rates of 10, 50, 100 and 270 mL/s before, 6 and 24 hours after each exposure. Exposure to diesel exhaust increased FENO at 6 hours compared with air at expiratory flow rates of 10 mL/s (p = 0.01) and at 50 mL/s (p = 0.011), but FENO did not differ significantly at higher flow rates. Increases in FENO following diesel exhaust were attenuated at 24 hours. Ozone did not affect FENO at any flow rate or time point. Exposure to diesel exhaust, but not ozone, increased FENO concentrations in healthy subjects. Differences in the induction of airway inflammation may explain divergent responses to diesel exhaust and ozone, with implications for the use of FENO as an index of exposure to air pollution.


Structure of the fibronectin type 1 module.
The rapid accumulation of sequence data has provided insight into the evolution of proteins and led to the identification of 'mosaic proteins'. These proteins have evolved by duplication, insertion and deletion of a common pool of structural units or modules, yet their biological functions are diverse. They are involved in cell adhesion and migration, embryogenesis and the pathways of blood clotting, fibrinolysis and complement. The modular units are defined by 'consensus sequences' which often include conserved disulphide bonds. Despite the available sequence information, little is known of the tertiary structure of mosaic proteins. If, however, the 'consensus structure' of the modules were known, valuable structural information could be inferred about a wide variety of proteins and biological systems. An important mosaic protein is fibronectin, an extracellular matrix protein that consists of three types of module (see refs 3, 7 for reviews). Here we describe the structure of the fibronectin type 1 module which appears twelve times in fibronectin and is also found in factor XII and tissue plasminogen activator. The module was produced using a yeast expression system and the structure was determined in solution using 1H NMR. This methodology promises to be extremely powerful in the investigation of modules from a wide range of mosaic proteins.


Associations with duration of compensation following whiplash sustained in a motor vehicle crash.
Continued exposure to compensation systems has been reported as deleterious to the health of participants. Understanding the associations with time to claim closure could allow for targeted interventions aimed at minimising the time participants are exposed to the compensation system. To identify the associations of extended time receiving compensation benefits with the aim of developing a prognostic model that predicts time to claim closure. Prospective cohort study in people with whiplash associated disorder. Time to claim closure, in a privately underwritten fault based third party traffic crash insurance scheme in New South Wales, Australia. Cox proportional hazard regression modelling. Of the 246 participants, 25% remained in the compensation system longer than 24 months with 15% remaining longer than three years. Higher initial disability (Functional Rating Index≥25 at baseline) (HRR: 95% CI, 1.916: 1.324-2.774, p<0.001); and lower initial mental health as measured by SF-36 Mental Component Score (HRR: 95% CI, 0.973: 0.960-0.987, p<0.001) were significantly and independently associated with an increased time-to-claim closure. Shorter time to claim closure was associated with having no legal involvement (HRR: 95% CI, 1.911: 1.169-3.123, p=0.009); and, not having a prior claim for compensation (HRR: 95% CI, 1.523: 1.062-2.198, p=0.022). Health and insurance related factors are independently associated with time to claim closure. Both factors need to be considered by insurers in their assessment of complexity of claims. Interventions aimed at minimising the impact of these factors could reduce claimants' exposure to the compensation system. In turn insurers can potentially reduce claims duration and cost, while improving the health outcomes of claimants.


Diagnostic Value of Endorectal Ultrasound in Preoperative Assessment of Lymph Node Involvement in Colorectal Cancer: a Meta-analysis.
Nodal invasion by colorectal cancer is a critical determinant in estimating patient survival and in choosing appropriate preoperative treatment. The present meta-analysis was designed to evaluate the diagnostic value of endorectal ultrasound (EUS) in preoperative assessment of lymph node involvement in colorectal cancer. We systematically searched PubMed, Web of Science, Embase, and China National Knowledge Infrastructure (CNKI) databases for relevant studies published on or before December 10th, 2014. The sensitivity, specificity, likelihood ratios, diagnostic odds ratio (DOR) and area under the summary receiver operating characteristics curve (AUC) were assessed to estimate the diagnostic value of EUS. Subgroup analysis and meta-regression were performed to explore heterogeneity across studies. Thirty-three studies covering 3,016 subjects were included. The pooled sensitivity and specificity were 0.69 (95%CI: 0.63-0.75) and 0.77 (95%CI: 0.73-0.82), respectively. The positive and negative likelihood ratios were 3.09 (95%CI: 2.52-3.78) and 0.39 (95%CI: 0.32-0.48), respectively. The DOR was 7.84 (95%CI: 5.56-11.08), and AUC was 0.80 (95%CI: 0.77-0.84). This meta-analysis indicated that EUS has moderate diagnostic value in preoperative assessment of lymph node involvement in colorectal cancer. Further refinements in technology and diagnostic criteria are necessary to improve the diagnostic accuracy of EUS.


Combined 0.01% atropine with orthokeratology in childhood myopia control (AOK) study: A 2-year randomized clinical trial.
To investigate whether combining 0.01% atropine with orthokeratology (AOK) has a better effect in retarding axial elongation, compared with orthokeratology alone (OK) over two years. A total of 96 Chinese children aged six to < 11 years with myopia (1.00 - 4.00 D, inclusive) were randomized into either the AOK or OK group in a 1:1 ratio. Axial length (the primary outcome), and secondary outcomes (e.g. pupil size and choroidal thickness) were measured at 1-month and at 6-monthly intervals after commencement of treatment. Both intention-to-treat and per-protocol analyses showed significantly slower axial elongation in the AOK group than OK group over two years (P = 0.008, P < 0.001, respectively). AOK subjects had statistically slower axial elongation (adjusted mean [standard error], 0.17 [0.03] mm vs 0.34 [0.03] mm, P < 0.001), larger increase in mesopic (0.70 [0.09] mm vs 0.31 [0.09] mm, P = 0.003) and photopic pupil size (0.78 [0.07] mm vs 0.23 [0.07] mm, P < 0.001), and greater thickening of the choroid (22.6 [3.5] µm vs -9.0 [3.5] µm, P < 0.001) than OK subjects over two years. Except for a higher incidence of photophobia in the AOK group (P = 0.006), there were no differences in the incidence of any other symptom or adverse events between the two groups. Slower axial elongation was associated with a larger increase in the photopic pupil size and a greater thickening in the choroid in the AOK group. Slower axial elongation following 2-year AOK treatment may result from increased pupil dilation and a thickening in the choroid observed in the AOK group.


Composition of a polysaccharide from mycoplasma (F-38) recognised by antibodies from goats with contagious pleuropneumonia.
A polysaccharide was extracted by warm aqueous phenol from the F-38 strain of mycoplasma which causes contagious caprine pleuropneumonia (CCPP). After acid hydrolysis, the polysaccharide was found to be composed of the neutral sugars glucose, galactose, mannose and fucose and the amino sugars galactosamine and glucosamine. All the sugars were present in approximately equal quantities. Unmodified goat erythrocytes bound the polysaccharide readily and the sensitised cells reacted with antibodies in sera from goats with experimental or natural CCPP. The unique composition of the F-38 polysaccharide and the specific reactivity of polysaccharide-sensitised red cells with antibodies from CCPP infected animals suggests that the polysaccharide should be useful for identification of F-38 organisms and diagnosis of the disease.


Effect of Fe doping concentration on optical and magnetic properties of ZnO nanorods.
Herein, a facile low temperature, aqueous solution-based chemical method has been demonstrated for large-scale fabrication of Fe doped ZnO nanorods (ZnO:Fe) with a series percentage of Fe dopant. Interestingly, the SEM results reveal a uniform well dispersed synthesis of ZnO:Fe nanorods throughout the substrate. The x-ray diffraction result suggests that Fe substitutes Zn in the ZnO matrix and rules out the formation of any secondary phase. Selected area electron diffraction investigation verifies the single crystal, hexagonal wurtzite structure of the ZnO:Fe nanorods. Energy dispersive spectroscopy data confirm Fe doping of the ZnO nanorods with a concentration ranging from 0.9 to 2.2 at.%. The photoluminescence spectrum reveals a continuous suppression of defect related broad-band emission (I(D)/I(UV) = 1-0.11) by increasing the concentration of the dopant ion, which produces the quenching of surface defects present in the nanostructures. An enhancement in ferromagnetism (M = 0.15 × 10⁻²-0.24 × 10⁻¹ emu g⁻¹ at 2000 Oe) is found in doped ZnO nanorods.


Potential Criteria for Frameworks to Support the Evaluation of Innovative Medicines in Upper Middle-Income Countries-A Systematic Literature Review on Value Frameworks and Multi-Criteria Decision Analyses.
Multicriteria Decision Analysis (MCDA), a formal decision support framework, has been growing in popularity recently in the field of health care. MCDA can support pricing and reimbursement decisions on the macro level, which is of great importance especially in countries with more limited resources. The aim of this systematic review was to facilitate the development of future MCDA frameworks, by proposing a set of criteria focusing on the purchasing decisions of single-source innovative pharmaceuticals in upper middle-income countries. A systematic literature review was conducted on the decision criteria included in value frameworks (VFs) or MCDA tools. Scopus, Medline, databases of universities, websites of Health Technology Assessment Agencies, and other relevant organizations were included in the search. Double title-abstract screening and double full-text review were conducted, and all extracted data were double-checked. A team of researchers performed the merging and selection process of the extracted criteria. A total of 1,878 articles entered the title and abstract screening. From these, 341 were eligible to the full-text review, and 36 were included in the final data extraction phase. From these articles 394 criteria were extracted in total. After deduplication and clustering, 26 different criteria were identified. After the merging and selection process, a set of 16 general criteria was proposed. Based on the results of the systematic literature review, a pool of 16 criteria was selected. This can serve as a starting point for constructing MCDA frameworks in upper middle-income countries after careful adaptation to the local context.


Mitochondrial DNA haplogroups and incidence of lipodystrophy in HIV-infected patients on long-term antiretroviral therapy.
We investigated the rates of lipodystrophy events, according to mitochondrial DNA haplogroup, in 187 patients starting combination antiretroviral therapy and following it. Incidence rates of lipoatrophy and fat accumulation were 8.2 and 4.8 per 100 person-years of follow-up, respectively. In multivariable models, patients with haplogroup K were at higher risk of any lipodystrophy [adjusted relative risk (aRR) 4.02, P = 0.0009], lipoatrophy (competing-risk aRR 2.42, P = 0.09; cause-specific aRR 2.99, P = 0.031), and fat accumulation (competing-risk aRR, 2.63, P = 0.11; cause-specific aRR 5.27, P = 0.019) than those with haplogroup H. Mitochondrial haplogroups may explain part of the genetic predisposition to lipodystrophy during combination antiretroviral therapy.


Reduction of hemorrhagic transformation by PJ34, a poly(ADP-ribose)polymerase inhibitor, after permanent focal cerebral ischemia in mice.
Hemorrhagic transformation is an aggravating event that occurs in 15 to 43% of patients suffering from ischemic stroke. This phenomenon due to blood-brain barrier breakdown appears to be mediated in part by matrix metalloproteinases (MMPs) among which MMP-2 and MMP-9 could be particularly involved. Recent experimental studies demonstrated that post-ischemic MMP-9 overexpression is regulated by poly(ADP-ribose)polymerase (PARP). In this context, our study aimed to evaluate the effect of PJ34 (N-(6-oxo-5,6-dihydrophenanthridin-2-yl)-2-(N,N-dimethylamino)acetamide), a potent PARP inhibitor, on MMP-2 and MMP-9 levels and on hemorrhagic transformations in a model of permanent focal cerebral ischemia in mice. PJ34 (6.25-12.5 mg/kg, i.p.) was given at the time of ischemia onset and 4 h later. Hemorrhagic transformations, divided into microscopic and macroscopic hemorrhages, were counted 48 h after ischemia on 12 coronal brain slices. Microscopic and macroscopic hemorrhages were respectively reduced by 38% and 69% with 6.25 mg/kg PJ34. The anti-hemorrhagic effect of PJ34 was associated with a 57% decrease in MMP-9 overexpression assessed by gelatin zymography. No increase in MMP-2 activity was observed after ischemia in our model. The vascular protection achieved by PJ34 was associated with a reduction in the motor deficit (P<0.05) and in infarct volume (-31%, P<0.01). In conclusion, our study demonstrates for the first time that PJ34 reduces hemorrhagic transformations after cerebral ischemia. Thus this PARP inhibitor exhibits both anti-hemorrhagic and neuroprotective effects that may be of valuable interest for the treatment of stroke.


Stereotactic body radiotherapy for spine metastases: a review of 24 Gy in 2 daily fractions.
Stereotactic body radiotherapy (SBRT) has proven to be a highly effective treatment for selected patients with spinal metastases. Randomized evidence shows improvements in complete pain response rates and local control with lower retreatment rates favoring SBRT, compared to conventional external beam radiotherapy (cEBRT). While there are several reported dose-fractionation schemes for spine SBRT, 24 Gy in 2 fractions has emerged with Level 1 evidence providing an excellent balance between minimizing treatment toxicity while respecting patient convenience and financial strain. We provide an overview of the 24 Gy in 2 SBRT fraction regimen for spine metastases, which was developed at the University of Toronto and tested in an international Phase 2/3 randomized controlled trial. The literature summarizing global experience with 24 Gy in 2 SBRT fractions suggests 1-year local control rates ranging from 83-93.9%, and 1-year rates of vertebral compression fracture ranging from 5.4-22%. Reirradiation of spine metastases that failed prior cEBRT is also feasible with 24 Gy in 2 fractions, and 1-year local control rates range from 72-86%. Post-operative spine SBRT data are limited but do support the use of 24 Gy in 2 fractions with reported 1-year local control rates ranging from 70-84%. Typically, the rates of plexopathy, radiculopathy and myositis are under 5% in those series reporting mature follow up, with no cases of radiation myelopathy (RM) reported in the de novo setting when the spinal cord avoidance structure is limited to 17 Gy in 2 fractions. However, re-irradiation RM has been observed following 2 fraction SBRT. More recently, 2-fraction dose escalation with 28 Gy, with a higher dose constraint to the critical neural tissues, has been reported suggesting improved rates of local control. This regimen may be important in those patients with radioresistant histologies, high grade epidural disease, and/or paraspinal disease. The dose-fractionation of 24 Gy in 2 fractions is well-supported by published literature and is an ideal starting point for centers looking to establish a spine SBRT program.


Healing of ExcisionAl wounds on Lower legs by Secondary intention (HEALS) cohort study. Part 1: a multicentre prospective observational cohort study in patients without planned compression.
There is no agreed treatment pathway following excision of keratinocyte cancer (KC). Compression therapy is considered beneficial for secondary intention healing on the lower leg; however, there is a lack of supportive evidence. To plan a randomized controlled trial (RCT), suitable data are needed. We report a multicentre prospective observational cohort study in this patient population with the intention of informing a future trial design. To estimate the time to healing in wounds healing by secondary intention without planned postoperative compression, following excision of KC on the lower leg; to characterize the patient population, including factors affecting healing; and to assess the incidence of complications. This was a multicentre prospective observational cohort study. Inclusion criteria were age ≥ 18 years with planned excision of KC on the lower leg and healing by secondary intention, an ankle-brachial pressure index (ABPI) of ≥ 0.8; and written informed consent. Exclusion criteria included planned excision with primary closure, skin graft or flap; compression therapy for another indication; planned compression; inability of patient to receive, comply with or tolerate high compression; or a suspected diagnosis other than KC. This study recruited 58 patients from 9 secondary care dermatology clinics. In the analysis population (n = 53), mean age was 81 years (range 25-97 years), median time to healing was 81 days (95% CI 73-92) and 45 patients (84.9%) had healing of the wound at the 6-month follow-up. The healing prognostic factors were wound parameters and ABPI. Wound infections occurred in 16 participants (30.2%). Four patients (7.5%) were admitted to hospital; three because of an infection and one because of a fall. The collected data have informed the RCT preparation. A relatively high proportion (7.5-15%) of unhealed wounds, infection and hospital admissions demonstrate the need for clearly establishing potentially effective treatments to improve outcomes for this population.


Prevention and treatment of adverse effects of corticosteroids in systemic lupus erythematosus.
Corticosteroid therapy has had a major impact on improvement in disease activity and long-term survival in patients with systemic lupus erythematosus (SLE). Unfortunately, the therapeutic advantages are accompanied by many manifestations of toxicity, some of which are short term and potentially reversible, while others cause chronic irreversible damage. Many of these features of toxicity have similar presentations to manifestations of SLE disease activity, and must be distinguished in the individual patient. The features of corticosteroid toxicity are reviewed in this chapter, and means of prevention and/or treatment are discussed.


Integrated treatment of perennial ryegrass: Structural characterization of hemicelluloses and improvement of enzymatic hydrolysis of cellulose.
An integrated treatment coupling ultrasonic and hydrothermal pretreatments with sequential alkali post-extractions was performed to isolate and characterize hemicelluloses from perennial ryegrass and improve the enzymatic hydrolysis efficiency of cellulose. The yield, chemical composition, and structure of water-soluble and alkali-soluble hemicelluloses obtained from the hydrothermal supernatant and hydrothermally pretreated ryegrass as well as the enzymatic hydrolysis efficiency of cellulose were comprehensively investigated by gel permeation chromatograph, high-performance anion exchange chromatography, Fourier transform infrared spectroscopy, and nuclear magnetic resonance spectra. Results showed that more than 90 % of the original hemicelluloses in ryegrass were released during the integrated treatment and all hemicellulosic fractions obtained were mainly composed of ʟ-arabino-(4-O-methyl-ᴅ-glucurono)-ᴅ-xylans, galactoanrabinoxylans and β-glucans. In addition, the effective removal of amorphous hemicelluloses and lignin significantly increased the cellulose enzymatic hydrolysis rate of ryegrass from 43.8 to 91.1 %. These results provided new insights into the collaborative utilization of hemicelluloses and cellulose in ryegrass.


Nipple aspirate fluids in adult nonlactating women--lactose content, cationic Na+, K+, Na+/K+ ratio, and coloration.
The presence of lactose in nipple secretions is considered biochemical evidence of breast secretory activity, and has been reported to occur more frequently in white compared to brownish or green colored breast fluid. We studied lactose, Na+, and K+ concentrations, the Na+/K+ ratio, and the coloration of nipple aspirate fluid (NAF) from 49 nonpregnant women. A significant relationship was found between the concentrations of lactose, Na+, and K+, and age and the coloration of NAF. Lactose was present in 22/49 (44.8%) of the NAF samples and declined with age from 100% positivity in women less than or equal to 29 years to 29% in those less than or equal to 35 years. In NAF of deep yellow, brown and green colorations, only traces of lactose were found. Na+ and K+ increased with age and with darker colorations compared to white, pale yellow, or colorless NAF. Lactose was present in NAF samples from both parous and nulliparous younger women, indicating that the breasts of many nonpregnant women respond to prolactin stimulation; hence, lactose may provide a simple marker indicating active physiologic secretory activity of the breast. As reported previously, NAF of darker coloration, containing elevated levels of cholesterol, cholesterol oxidation products, and other substances, suggests retention and impaired reabsorption of these and other products of secretion. Because of the secretion and temporary retention by the breast glands of chemical substances of exogenous and endogenous origin, including mutagens and carcinogens, lactose concentration and coloration of NAF may be useful as markers of secretion and reabsorption in future physiologically based clinical and epidemiologic studies of the pathogenesis of breast disease.


Preliminary clinical studies with PDT by topical TPPS administration in neoplastic skin lesions.
Cutaneous photosensitization by topical administration of a porphyrin derivative has been previously reported from experimental studies. Preliminary clinical trials performed at the National Cancer Institute of Milan in the last six months have confirmed the feasibility of treating skin lesions by topical application of photosensitizers. Fourteen cases of basal cell carcinoma were treated by local administration of tetraphenylporphinesulphonate (TPPS), vehicled by azone. Later, the tumor was exposed to a wavelength of 630 nm from a dye laser. We noted complete remission, as documented by biopsies, in all tumors, with clinical thickness less than 2 mm, whereas partial remission was obtained in tumors with clinical thickness more than 2 mm. Our experience suggests the possibility of a routine treatment by this method for flat basal cell carcinoma and pre-malignant lesions, with remarkable advantages to conventional therapies. Our results have to be confirmed by increasing the number of cases and length of follow up; our short follow up does not allow us to make definitive claims regarding this therapy.


Localization of c-fos, c-jun, and hsp70 mRNA expression in brain after neonatal hypoxia-ischemia.
The sites of expression of early response mRNAs were determined in the brains of 7-day-old rat pups exposed to unilateral carotid artery ligation followed by 3 h of hypoxia. Pups were sacrificed after recovery periods ranging from 10 min to 24 h. In agreement with our previous northern blot analysis, in situ hybridization of coronal brain sections to probes for c-fos, c-jun, and heat-inducible hsp70 revealed a marked induction and subsequent disappearance of all three mRNAs during this time period. We observed co-localization of the 2 immediate early gene (IEG) mRNAs, c-fos and c-jun, which encode proteins that act in combination to regulate subsequent gene expression. These mRNAs were expressed in all regions known to be vulnerable to permanent injury in this model, such as the cortex, hippocampus, and striatum, as well as in other regions that are spared from permanent damage, such as contralateral cortex and lateral ventricular neuroepithelium. The temporal and regional co-localization of c-fos and c-jun suggests that the transcriptional regulatory activity of their protein products could play a role in plasticity associated with death or recovery from injury in the immature brain. Hsp70 mRNA expression was induced in nearly all of the animals that were positive for IEG mRNAs. Although the most frequent site of expression for all three mRNAs was the ipsilateral cerebral cortex, hsp70 expression was restricted to the ipsilateral hemisphere and absent from a number of structures that were positive for c-fos and c-jun. In addition, the patterns of expression of hsp70 within specific structures frequently differed from those of the IEGs, implying that although both cellular early response systems are activated in this model, their specific functions are carried out within different microenvironments.


A pathway of coagulation on endothelial cells.
Although the endothelial cell is considered antithrombogenic, endothelium has recently been shown to participate in procoagulant reactions. Factor IX bound to specific endothelial cell sites can be activated by the intrinsic and extrinsic pathways of coagulation. Perturbation of endothelium results in induction of tissue factor which promotes factor VIIa-mediated activation of factors IX and X, thus initiating procoagulant events on the endothelial surface. Cell bound factor IXa, in the presence of factor VIII, promotes activation of factor X. The factor Xa formed can interact with endothelial cell factor V/Va, resulting in prothrombin activation. Thrombin then cleaves fibrinogen and a fibrin clot closely associated with the endothelial cell forms. The perturbed endothelial cell thus provides a focus of localized procoagulant events. This model suggests a simple endothelial-cell-dependent mechanism for initiation of coagulation at the site of an injured or pathological vessel.


A new RNase-based immunoconjugate selectively cytotoxic for ErbB2-overexpressing cells.
We report a new tumor-directed immunoRNase, a chimeric protein made up of an antibody fragment (single-chain Fv fragment) directed to ErbB2, a cell surface receptor, and a non-toxic, human ribonuclease, which upon cell internalization becomes cytotoxic. The immunoRNase is active as a ribonuclease, specifically binds and selectively kills ErbB2-positive cells. ErbB2 is one of the most specific tumor-associated antigens identified so far, overexpressed on tumor cells of different origin. Its choice as target antigen and that of a non-toxic, human RNase as the killer moiety makes this immunoRNase a new, potentially attractive anticancer agent.


Synthesis of MnCoO/CNT nanoflakes for the photocatalytic degradation of methyl orange dye and the evaluation of their activity against Culex pipiens larvae in the purification of fresh water.
Researchers worldwide have been looking forward to using novel ways to purify fresh water containing pollutants and disease vectors. In the current work, nanoparticles were introduced as a promising technique for cleaning water and saving human health and living organisms. The nanocomposites, MnCoO and MnCoO/CNTs, were fabricated by a cost-effective co-precipitation method. Phase and molecular structures were investigated by XRD and Raman spectroscopy. The samples exhibited polycrystalline nature of binary phase and weak crystallinity. The elemental composition was recorded by EDX spectra, revealing the purity of the nanoparticles. The surface morphology and particle distribution were described using SEM and TEM micrographs, indicating that MnCoO/CNTs are nanoflakes with a large surface area. The optical parameters include α, E g, n, k, which were identified from T% and R% measurements, suggesting that MnCoO has a direct band gap that reduced with the CNT support. The photocatalytic activity of MnCoO/CNTs was examined for the degradation of methyl orange dye with an efficiency of ∼90.97% over 0.6 g L-1 within 50 min under UV irradiation. In the larvicidal activity, the micrograph images revealed the impact of the nanoflake particles on the 4th instar larvae, where the enzymatic activity of esterases acetylcholinesterase, α- and β-carboxylesterase, and transaminases drastically decreased with the MnCoO/CNT ratio.


Potential for the Australian and New Zealand paediatric intensive care registry to enhance acute flaccid paralysis surveillance in Australia: a data-linkage study.
Australia uses acute flaccid paralysis (AFP) surveillance to monitor its polio-free status. The World Health Organization criterion for a sensitive AFP surveillance system is the annual detection of at least one non-polio AFP case per 100,000 children aged less than 15 years, a target Australia has not consistently achieved. Children exhibiting AFP are likely to be hospitalised and may be admitted to an intensive care unit. This provides a potential opportunity for active AFP surveillance. A data-linkage study for the period from 1 January 2005 to 31 December 2008 compared 165 non-polio AFP cases classified by the Polio Expert Panel with 880 acute neurological presentations potentially compatible with AFP documented in the Australian and New Zealand Paediatric Intensive Care (ANZPIC) Registry. Forty-two (25%) AFP cases classified by the Polio Expert Panel were matched to case records in the ANZPIC Registry. Of these, nineteen (45%) cases were classified as Guillain-Barré syndrome on both registries. Ten additional Guillain-Barré syndrome cases recorded in the ANZPIC Registry were not notified to the national AFP surveillance system. The identification of a further ten AFP cases supports inclusion of intensive care units in national AFP surveillance, particularly specialist paediatric intensive care units, to identify AFP cases that may not otherwise be reported to the national surveillance system.


Feeding the anorectic client: comfort foods and happy hour.
The anorectic patient presents a dilemma to the health care provider. As the patient refuses oral intake, quality of life diminishes, and health care costs increase. This article describes two approaches that have demonstrated effectiveness: comfort food and happy hour. "Comfort foods" describe foods associated with bygone years, intended to trigger recollections of pleasant childhood experiences and feelings of caring and healing. A second alternative described is the offering of a "happy hour" beverage, presented in a social milieu. These treatments are reproducible in a variety of clinical care settings and stimulate oral intake in the failure-to-thrive patient.


Causative agents of acute diarrhoea in the first 3 years of life: hospital-based study.
During the 2 years of the study, 402 patients and an equal number of age- and sex-matched controls were investigated for the presence of diarrhoeal pathogens. Pathogenic organisms were recovered from 277 (68.9%) patients and 97 (24.1%) controls. In the patient group, possible bacterial pathogens were found in 210 (52.2%) cases. Enteropathogenic Escherichia coli (EPEC) was the most frequently found potential pathogen, being recovered in 132 cases (32.8%) with serotypes 026, 086, 0111 and 0124 being the most frequently identified. Other bacterial pathogens identified were enterotoxigenic E. coli (ETEC) 57 (14.2%), Shigella 13 (3.2%) and Salmonella eight (2%). Rotavirus was identified in 33 (8.2%) cases. Mixed bacterial and viral infections were also seen in 26 (6.5%) cases. In the control group, enteric pathogens were recovered from 97 (24.1%) specimens. The most common bacterial pathogen found in this group was again EPEC (40, 9.9%), with serogroups 018, 044, 0111 and 0126 being the most frequent. Giardia lamblia and Entamoeba histolytica were found in 31 (7.7%) and 10 (2.5%) controls, respectively. Rotavirus was found in 16 (4%) controls. The results of both centres where the study was performed (Karachi and Rawalpindi) were compared.


Left ventricular volume determination using single-photon emission computed tomography.
A new method for measuring left ventricular (LV) volume based on gated single-photon emission computed tomography (SPECT) is described. Preliminary phantom studies showed an excellent correlation between SPECT and observed volumes (r = 0.99, standard error of the estimate [SEE] = 4.9 ml). SPECT was performed 24 hours after biplane contrast LV angiography in 36 patients. Transaxial blood pool tomograms were reconstructed by filtered back projection and reoriented to views orthogonal to the cardiac axes. Volume was calculated from serial short-axis tomograms by determining the base, apex and lateral borders of the LV blood pool, ascertaining the number of pixels in this volume and multiplying by the known volume of a pixel. Gated SPECT volumes were compared with contrast angiographic volumes. At end-systole, r = 0.96 and SEE = 12 ml; at end-diastole, r = 0.81 and SEE = 27 ml. For ejection fraction, r = 0.85 and SEE = 0.06. To test interobserver variation in processing, count data from 5 patients were processed twice (r = 0.98, SEE = 8.3 ml). There is an excellent correlation between SPECT and contrast angiographic volumes at end-systole; at end-diastole the relation is good. SPECT requires no arbitrary background correction, allows systematic isolation of the left ventricle from other overlapping cardiac chambers and requires no geometric assumptions for volume determination. It has promise as a direct method for measuring LV volume in a minimally invasive manner.


[Mucous graft in acute spastic ectropion (author's transl)].
Acute spactic ectropion often occurs with concomitant inflammatory and degenerative conditions of the conjunctiva. This is the cause of failures in the classic ectropion's surgery. Authors suggest to replace the altered conjunctiva with transplant of oral mucous membrane.


Selection and validation of novel stable reference genes for qPCR analysis in EMT and MET.
Quantitative real-time polymerase chain reaction is a powerful tool for quantifying gene expression. The relative quantification relies on normalizing the data to reference genes or internal controls not modulated by the experimental conditions. The most widely used internal controls occasionally show changed expression patterns in different experimental settings, such as the mesenchymal to epithelial transition. Thus, identifying appropriate internal controls is of utmost importance. We analyzed multiple RNA-Seq datasets using a combination of statistical approaches such as percent relative range and coefficient of variance to define a list of candidate internal control genes, which was then validated experimentally and by using in silico analyses as well. We identified a group of genes as strong internal control candidates with high stability compared to the classical ones. We also presented evidence for the superiority of the percent relative range method for calculating expression stability in data sets with larger sample sizes. We used multiple methods to analyze data collected from several RNA-Seq datasets; we identified Rbm17 and Katna1 as the most stable reference genes in EMT/MET studies. The percent relative range approach surpasses other methods when analyzing datasets of larger sample sizes.


Gastro-esophageal reflux in severely retarded children.
Eight severely mentally retarded children with histories of recurrent vomiting, anemia and chest disease are reported. It is suggested that appropriate medical management improves the quality of life for such children and may also reduce the number of hospital admissions for the treatment of this cluster of symptoms. Symptoms of vomiting, anemia and recurrent pneumonia in retarded children should suggest gastro-esophageal reflux. Investigations should include the upper gastrointestinal tract, with specific attention being paid to esophageal reflux.


Ocular toxoplasmosis in human immunodeficiency virus-infected patients.
The files of 45 human immunodeficiency virus-infected patients with ocular toxoplasmosis were reviewed, with a median follow-up of eight months. The condition was unilateral in 37 of the 45 patients (82%) and was bilateral in eight (18%). Inflammation of the anterior chamber and the vitreous was present in 32 of 53 eyes (60%) and 38 of 53 eyes (72%), respectively. Cytomegalovirus retinitis developed during the follow-up period in nine patients (20%). Cerebral toxoplasmosis was concurrently diagnosed with the ocular toxoplasmosis in 13 patients (29%). The efficacy of the combination of pyrimethamine and sulfadiazine or clindamycin was assessed in 42 patients for the induction therapy and in 38 patients for the maintenance therapy. Induction therapy was always effective within a median period of six weeks. During maintenance treatment, the 24-month relapse rates were 0.20 and 0.18 for the 50-mg/day and 25-mg/day dosage of pyrimethamine, respectively. The overall 12-month survival rate was 0.72. Our results suggested that ocular toxoplasmosis has a better ocular prognosis than cytomegalovirus retinitis, but that it requires appropriate treatment because life-threatening cerebral involvement is often associated.


[Value of positron emission tomography in urological neoplasms: more form than substance?].
Positron emission tomography/computed tomography (PET/CT) is widely used for imaging urological neoplasms. This overview should help the urologist actively involved in oncology to assess the value of PET or PET/CT in each tumor entity. Besides prostate, testicular, renal, and bladder cancer less common urological malignancies like penile carcinoma and retroperitoneal masses are discussed. Differences in using PET/CT for primary diagnosis, staging, or restaging are outlined separately. Appropriate indications for the use in clinical practice are cited.


A Dynamic Modeling Approach to Estimate Nitrogen Loading in Coastal Bays on Cape Cod, Massachusetts, USA.
Solving estuarine water quality problems on Cape Cod, Massachusetts, or elsewhere, is difficult. Nitrogen from septic systems takes years to decades to travel by groundwater to estuaries, depending on local hydrogeology, meaning that nitrogen loading in future years may exceed current conditions. We created a dynamic nitrogen model of Cape Cod's 54 estuaries to better understand 1. how past and present conditions, including legacy nitrogen in groundwater, influence future nitrogen loading, and 2. how different development and nitrogen abatement scenarios could have additional effects. We find that 43 of 54 estuaries are not in equilibrium with current watershed nitrogen loading levels; this increases to 52 of 54 under a buildout scenario. Watersheds contain up to 1000 tons of legacy nitrogen in groundwater; yet, we find that a rapid investment in source control successfully reduces nitrogen loading, revealing a wide range of potential outcomes that depend ultimately on the resources and attention invested in the problem.


Do Hypertensive Disorders of Pregnancy and Abnormal Placentation Mediate the Association between Advanced Maternal Age and Adverse Perinatal Outcomes?
A tertiary-hospital-based retrospective study (2011-2019) was conducted to determine the mediating role of hypertensive disorders of pregnancy and abnormal placentations between advanced maternal age and adverse neonatal outcomes. Data from a tertiary-hospital-based retrospective study (n= 23051) was used and conducted regression-based mediation analysis to assess the mediating role of hypertensive disorders of pregnancy and abnormal placentation between the advanced maternal age and adverse neonatal outcomes. After adjusting for confounding factors, the indirect effect of advanced maternal age on preterm births, perinatal mortality, and low birth weight mediated by hypertensive disorders of pregnancy was [aOR 4.95 (95% CI: 4.05, 5.85)], [aOR 2.82 (95% CI: 1.78, 3.86)], and [aOR 5.90 (95% CI: 4.93, 6.87)], respectively. The indirect effect of advanced maternal age on preterm births and low birth weight mediated by abnormal placentation was [aOR 6.83 (95% CI: 5.70, 7.97)] and [aOR 4.18 (95% CI: 3.26, 5.11)]. About, 23%, 37%, and 17% of the effect of advanced maternal age on preterm births, perinatal mortality, and low birth weight was mediated by hypertensive disorders of pregnancy, respectively. Furthermore, abnormal placentation mediates the association between advanced maternal age and preterm births by 18% and low birth weight by 23%. Hypertensive disorders of pregnancy and abnormal placentation partially mediate the association between advanced maternal age and adverse neonatal outcomes.


Visualisation of RNA by electron microscopic in situ hybridisation.
Visualisation of RNA at an ultrastructural level represents a major approach to study organisation and function of the cell nucleus. In addition to methods allowing one to visualise a general distribution of RNA-containing structural constituents, in situ hybridisation (ISH) is a powerful tool for revealing specific RNA sequences or species. In this chapter we describe a method for detecting RNA by electron microscopic in situ hybridisation (EMISH) using anti-sense RNAs as probes. We first present the protocol for preparation of anti-sense RNA probes labeled with different markers, and then describe how such probes are applied to ultrathin sections by a method of ultrastructural ISH. The great advantage of this method is that it does not require denaturing either the specimen or the probe, thus allowing nuclear fine structure to be well preserved. The presence of the marker in the probe can be detected by immunoelectron microscopy using colloidal gold-conjugated antibodies, offering the possibility to evaluate the signal quantitatively. The method can also be combined with cytochemical techniques such as EDTA staining for preferential visualisation of ribonucleoprotein-containing nuclear structural components.


Protein kinase C-regulated production of prostacyclin by rat endothelium is increased in the presence of lipoxin A4.
Prostacyclin is generated by cultured rat endothelial cells. Compound blocking activity of protein kinase C and cyclic nucleotide-dependent protein kinases (H7) and compound blocking interaction between Ca2+ and calmodulin (W7) diminish generation of prostacyclin in rat endothelial cells. These compounds give a synergistic effect when they are introduced to the endothelial cell cultures simultaneously. Compound HA1004, an inhibitor of cAMP- and cGMP-dependent protein kinases has no effect on prostacyclin generation. Lipoxin A4, a potent direct stimulator of protein kinase C, rapidly induces prostacyclin generation in rat endothelium in a dose- and time-dependent fashion. Lipoxin A4-induced generation of prostacyclin can be inhibited by H7 and W7 but not by HA1004. Lipoxin B4 has no significant effect on prostacyclin generation in rat endothelium. In conclusion, our results demonstrate that generation of prostacyclin by rat endothelial cells is regulated via a pathway involving protein kinase C and Ca2+.


Does preterm birth increase a child's risk for language impairment?
Although premature birth is associated with lags in language acquisition, it is unclear whether preterms exhibit an elevated risk for language impairment (LI). This study determined whether preterms, without frank cerebral damage, at 2;6 and 3;6 exhibited a higher rate of risk for LI as compared to full-terms, and also sought to identify predictors of risk. Sixty-four Italian very immature preterms were assessed longitudinally at 2;6 and 3;6; age-matched full-terms served as controls at 2;6 (n=22) and 3;6 (n=40). Each completed individualized assessments of cognition and language ability. At each time point, using cut-offs specific to each of the language measures, children were differentiated into two groups (at risk for LI, not at risk). The percentage of full-terms at risk for LI at 2;6 (9.1% to 13.6%) and 3;6 (7.5%) was consistent with prior estimates of LI at these ages. The percentage of preterms at risk for LI at 2;6 (16.1% to 24.1%) and 3;6 (34.4%) was higher at both ages and statistically significant at 3;6 (difference=26.8%, 95% CI=12.3% to 41.4%). The best model predicting risk status at 3;6 was preterms' mean length of utterance (MLU) at 2;6, (sensitivity 72.73%, specificity 85%) when adjusting for maternal education. Preterms exhibit a heightened risk for LI in the preschool years, since about one in four preterms at 2;6 and one in three preterms at 3;6 experiences significant lags in language acquisition. Findings argue the importance of early identification of language difficulties among preterms coupled with implementation of systematic language-focused interventions for these youngsters.


Comparative efficacy of selective serotonin reuptake inhibitors (SSRI) in treating major depressive disorder: a protocol for network meta-analysis of randomised controlled trials.
There have been inconsistent findings from randomised controlled trials (RCTs) and systematic reviews on the efficacies of selective serotonin reuptake inhibitors (SSRIs) as the first-line treatment of major depressive disorder (MDD). Besides inconsistencies among randomised controlled trials (RCTs), their risks of bias and evidence grading have seldom been evaluated in meta-analysis. This study aims to compare the efficacy of SSRIs by conducting a Bayesian network meta-analysis, which will be the most comprehensive evaluation of evidence to resolve the inconsistency among previous studies. SSRIs including citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline and vilazodone have been selected. Systematic database searching and screening will be conducted for the RCTs on drug treatment of patients with MDD according to pre-specified search strategies and selection criteria. PubMed, the Cochrane Library, EMBASE, ScienceDirect, the US Food and Drug Administration Website, ClinicalTrial.gov and WHO Clinical Trials will be searched. Outcome data including Hamilton Depression Rating Scale (HDRS), Montgomery-Åsberg Depression Rating Scale (MADRS) and Clinical Global Impression (CGI) from eligible RCTs will be extracted. The outcomes will be analysed as ORs and mean differences under a random-effects model. A Bayesian network meta-analysis will be conducted with WinBUGS software, to compare the efficacies of SSRIs. Subgroup and sensitivity analysis will be performed to explain the study heterogeneity and evaluate the robustness of the results. Meta-regression analysis will be conducted to determine the possible factors affecting the efficacy outcomes. The Cochrane risk of bias assessment tool will be used to assess the RCT quality, and the Grading of Recommendation, Assessment, Development and Evaluation will be used to assess the strength of evidence from the meta-analysis. No ethical approval is required because this study includes neither confidential personal patient data nor interventions with patients. CRD42015024879.


Halogen Bonding in Perovskite Solar Cells: A New Tool for Improving Solar Energy Conversion.
Hybrid organic-inorganic halide perovskites (HOIHPs) have recently emerged as a flourishing area of research. Their easy and low-cost production and their unique optoelectronic properties make them promising materials for many applications. In particular, HOIHPs hold great potential for next-generation solar cells. However, their practical implementation is still hindered by their poor stability in air and moisture, which is responsible for their short lifetime. Optimizing the chemical composition of materials and exploiting non-covalent interactions for interfacial and defects engineering, as well as defect passivation, are efficient routes towards enhancing the overall efficiency and stability of perovskite solar cells (PSCs). Due to the rich halogen chemistry of HOIHPs, exploiting halogen bonding, in particular, may pave the way towards the development of highly stable PSCs. Improved crystallization and stability, reduction of the surface trap states, and the possibility of forming ordered structures have already been preliminarily demonstrated.


The human factor in development cooperation: An effective way to deal with unintended effects.
Development policy and implementation are a human endeavor. Too often, however, the human factor is relegated to an input or an externality in a quasi-technical process for transforming public funds into measurable results. Within the Weberian rational-legal order, policies and bureaucracies are impersonal and objective. Policy objectives tend to get depersonalized and the human stories get filtered out of impact evaluations. This article, on the basis of case descriptions, argues that following the human stories in development policy and implementation can offer surprising insights into why at times policies may work or not work. The article explores how the idiosyncrasies of individuals' agency impact on achievement of policy outcomes and what the unintended effects are. It describes how the human factor can give rise to beneficial unplannable, unforeseeable, and thus unintended policy outcomes. This article argues that, instead of negating this, policy makers ought to embrace the human factor of development cooperation.


Seroprevalence of hepatitis C virus among blood donors in Rivers State, Nigeria.
Anti-HCV pre-transfusion testing among blood donors has not been introduced as a mandatory test in Rivers State, hence the risk of transfusion-transmitted HCV cannot be fully ascertained. One thousand (1000) apparently healthy blood donors were screened using a rapid second - generation test, the HEP C SPOT HCV assay. An overall prevalence of 2.9% was observed in this study. The highest prevalence (8.1%) was found among adults aged between 26 and 33 years and commercial donors.


Purification and characterization of Cop, a protein involved in the copy number control of plasmid pE194.
Cop protein has been overexpressed in Escherichia coli using a T7 RNA polymerase system. Purification to apparent homogeneity was achieved by the sequential chromatography on ion exchange, affinity chromatography, and reverse phase high performance liquid chromatography system. The molecular weight of the purified Cop was estimated as 6.1 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). But the molecular mass of the native state Cop was shown to be 19 kDa by an analytical high performance size exclusion chromatography, suggesting a trimer-like structure in 50 mM Tris-HCl buffer (pH 7.5) containing 100 mM NaCl. Cop protein was calculated to contain 39.1% alpha-helix, 16.8% beta-sheet, 17.4% turn, and 26.8% random structure. The DNA binding property of Cop protein expressed in E. coli was preserved during the expression and purification process. The isoelectric point of Cop was determined to be 9.0. The results of amino acid composition analysis and N-terminal amino acid sequencing of Cop showed that it has the same amino acid composition and N-terminal amino acid sequence as those deduced from its DNA sequence analysis, except for the partial removal of N-terminal methionine residue by methionyl-aminopeptidase in E. coli.


Awareness under anaesthesia due to a defective gas-loaded regulator.
Awareness under anaesthesia occurred in two patients due to a defect in an anaesthesic machine, which caused an inadequate supply of nitrous oxide. A defective fail-safe gas-loaded regulator was found to have caused communication between the pipelines for oxygen and nitrous oxide. This resulted in oxygen flow through the nitrous oxide flowmeter. A simple test to detect this type of defect is suggested.


Revision of Ascra with proposition of the bifida species group and description of two new species (Hemiptera: Pentatomidae: Edessinae).
Edessa is comprised of six subgenera, Aceratodes, Ascra, Dorypleura, Edessa, Hypoxys and Pygoda. Ascra is here elevated to genus status based on characteristics of the male and female genitalia and the gibbous pronotum. This genus is comprised of eight species previously placed in Edessa-E. bifida, E. cordifera, E. petersii, E. abdita, E. championi, E. privata, E. conspersa and E. morbosa, as well as six new species. The genus Ascra was further divided into two groups of species bifida and privata separated by a different pattern of punctuation on body and pygophore. Here we present only the bifida species group formed by A. bifida, A. cordifera, A. petersii, A. abdita, and A. championi, as well as two new species-A. vluteum and A. flavoscutellata. Lectotypes of Aceratodes sigillatus, Edessa abdita, E. championi, E. cornuta, E. densata and E. petersii are designated. Aceratodes sigillatus, Edessa cornuta, E. densata, E. picata, and E. florida are considered junior synonyms of A. bifida. Interestingly, some species of this genus are considered edible in Mexico.


Assessment of Intratumoral and Peritumoral Computed Tomography Radiomics for Predicting Pathological Complete Response to Neoadjuvant Chemoradiation in Patients With Esophageal Squamous Cell Carcinoma.
For patients with locally advanced esophageal squamous cell carcinoma, neoadjuvant chemoradiation has been shown to improve long-term outcomes, but the treatment response varies among patients. Accurate pretreatment prediction of response remains an urgent need. To determine whether peritumoral radiomics features derived from baseline computed tomography images could provide valuable information about neoadjuvant chemoradiation response and enhance the ability of intratumoral radiomics to estimate pathological complete response. A total of 231 patients with esophageal squamous cell carcinoma, who underwent baseline contrast-enhanced computed tomography and received neoadjuvant chemoradiation followed by surgery at 2 institutions in China, were consecutively included. This diagnostic study used single-institution data between April 2007 and December 2018 to extract radiomics features from intratumoral and peritumoral regions and established intratumoral, peritumoral, and combined radiomics models using different classifiers. External validation was conducted using independent data collected from another hospital during the same period. Radiogenomics analysis using gene expression profile was done in a subgroup of the training set for pathophysiological explanation. Data were analyzed from June to December 2019. Computed tomography-based radiomics. The discriminative performances of radiomics models were measured by area under the receiver operating characteristic curve. Among the 231 patients included (192 men [83.1%]; mean [SD] age, 59.8 [8.7] years), the optimal intratumoral and peritumoral radiomics models yielded similar areas under the receiver operating characteristic curve of 0.730 (95% CI, 0.609-0.850) and 0.734 (0.613-0.854), respectively. The combined model was composed of 7 intratumoral and 6 peritumoral features and achieved better discriminative performance, with an area under the receiver operating characteristic curve of 0.852 (95% CI, 0.753-0.951), accuracy of 84.3%, sensitivity of 90.3%, and specificity of 79.5% in the test set. Gene sets associated with the combined model mainly involved lymphocyte-mediated immunity. The association of peritumoral area with response identification might be partially attributed to type I interferon-related biological process. A combination of peritumoral radiomics features appears to improve the predictive performance of intratumoral radiomics to estimate pathological complete response after neoadjuvant chemoradiation in patients with esophageal squamous cell carcinoma. This study underlines the significant application of peritumoral radiomics to assess treatment response in clinical practice.


Stress-activated protein kinase inhibition to ameliorate lung ischemia reperfusion injury.
Inhibition of cytokines offers modest protection from injury in animal models of lung ischemia-reperfusion. Improved strategies would selectively inhibit the transcriptional activation response to oxidative stress. Mitogen-activated protein kinases (p38, c-jun N-terminal kinase, extracellular signal-regulated kinase) have been shown to be activated after oxidative stress and in animal models of acute inflammatory lung injury. We hypothesized that mitogen-activated protein kinase inhibition would block downstream transcriptional activation, providing robust protection from lung ischemia-reperfusion injury. Experimental rats received inhibitors of p38, c-jun kinase, or extracellular signal-regulated kinase before in situ left lung ischemia-reperfusion. Immunohistochemistry localized cellular sites of mitogen-activated protein kinase activation. Several markers of lung injury were assessed. Enzyme-linked immunosorbent assay measured soluble cytokine and chemokine contents. Western blotting assessed mitogen-activated protein kinase phosphorylation. Electromobility shift assays measured transcription factor nuclear translocation. Immunohistochemistry localized p38 and c-jun kinase activations in positive controls to alveolar macrophages. Extracellular signal-regulated kinase was activated in endothelial and epithelial cells. Animals treated with p38 or c-jun kinase inhibitor demonstrated significant reductions in transcription factor activation and markers of lung injury. Extracellular signal-regulated kinase inhibition was not protective. Western blotting confirmed inhibitor specificity. Inhibition of p38 and c-jun kinase provided significant protection from injury. The alveolar macrophage appears to be the key coordinator of injury in response to oxidative stress. Therapeutically targeting specific cell population (macrophage) responses to oxidative stress has the potential benefit of reducing lung reperfusion injury severity while leaving host immune responses intact.


The prosthodontic management of endodontically treated teeth: a literature review. Part II. Maintaining the apical seal.
Part II of the three-part literature review series addresses factors related to prosthodontic treatment that can affect the apical seal and endodontic success.


Presence of thyroxine in eggs and changes in its content during early development of chum salmon, Oncorhynchus keta.
In order to examine the role of thyroid hormones during salmonid development, techniques were developed for quantitative extraction of thyroxine from eggs, whole embryos, and alevins of chum salmon (Oncorhynchus keta) at various stages of development. Frozen eggs, embryos, alevins, or fry were homogenized in ice-cold methanol. The homogenate was centrifuged, and the supernatant was washed with a mixture of chloroform and 0.05% CaCl2. The aqueous layer was lyophilized, and the residue was redissolved in barbital buffer for thyroxine radioimmunoassay (RIA). Serial dilutions of the egg or tissue extracts gave inhibition slopes that were parallel to that of the thyroxine standard in the RIA. Immunoreactivity of the extracts coeluted with thyroxine standard in reverse-phase HPLC on an ODS column. Recovery of thyroxine from egg and tissue extracts was estimated from the recovery of 125I-labeled thyroxine added to the initial homogenates. Thyroxine content of eggs just after fertilization was 4-5 ng/egg, and this level was maintained until hatching. A decrease in thyroxine content was seen during yolk absorption. Total thyroxine increased to about 10 ng/fish, a level higher than that in the unfertilized egg, at the time of complete yolk absorption, and decreased within 10 days to a low level of 1 ng/fish. These findings are discussed in relation to the role of maternal thyroid hormones during early development and also to the onset of larval thyroid function.


Myelin antigen load influences antigen presentation and severity of central nervous system autoimmunity.
This study was designed to understand the impact of self-antigen load on manifestation of organ specific autoimmunity. Using a transgenic mouse model characterized by CNS hypermyelination, we show that larger myelin content results in greater severity of experimental autoimmune encephalomyelitis attributable to an increased number of microglia within the hypermyelinated brain. We conclude that a larger self-antigen load affects an increase in number of tissue resident antigen presenting cells (APCs) most likely due to compensatory antigen clearance mechanisms thereby enhancing the probability of productive T cell-APC interactions in an antigen abundant environment and results in enhanced severity of autoimmune disease.


Zernike aberration coefficients transformed to and from Fourier series coefficients for wavefront representation.
The set of Fourier series is discussed following some discussion of Zernike polynomials. Fourier transforms of Zernike polynomials are derived that allow for relating Fourier series expansion coefficients to Zernike polynomial expansion coefficients. With iterative Fourier reconstruction, Zernike representations of wavefront aberrations can easily be obtained from wavefront derivative measurements.


Spatial relationship between neuronal activity and BOLD functional MRI.
Despite the ubiquitous use of functional magnetic resonance imaging (fMRI), the extent to which the magnitude and spatial scale of the fMRI signal correlates with neuronal activity is poorly understood. In this study, we directly compared single and multiunit neuronal activity with blood oxygenation level-dependent (BOLD) fMRI responses across a large area of the cat area 18. Our data suggest that at the scale of several millimeters, the BOLD contrast correlates linearly with the underlying neuronal activity. At the level of individual electrode recording sites, however, the correlation between the two signals varied substantially. We conclude from our study that T(2)*-based positive BOLD signals are a robust predictor for neuronal activity only at supra-millimeter spatial scales.


A Novel VACTERL Assessment Tool to Facilitate Counseling for Expectant Families.
VACTERL is defined as 3 or more of the following congenital defects: vertebral, anorectal, cardiac, tracheoesophageal (TE), renal, and limb. The purpose of this study was to create an easy-to-use assessment tool to help providers counsel expecting families regarding the likelihood of additional anomalies and postnatal outcomes. Employing the Kids' Inpatient Database from 2003-2016, neonates (<29 days old) with VACTERL were identified using ICD-9-CM and ICD-10-CM codes. For each unique combination of VACTERL, multivariable logistic regression was used to estimate inpatient mortality, and Poisson regression was used to estimate length-of-stay during the initial hospitalization. The assessment tool used in this study is available at <ext-link ext-link-type="uri" xlink:href="https://choc-trauma.shinyapps.io/VACTERL" xmlns:xlink="http://www.w3.org/1999/xlink">https://choc-trauma.shinyapps.io/VACTERL</ext-link>. 1,886 of 11,813,782 (0.016%) neonates presented with VACTERL. 32% weighed <1,750 g, and 239 (12.7%) died prior to discharge. Associated with mortality were limb anomaly (1.8 [1.01-3.22], p < 0.05), prematurity (1.99 [1.14-3.47], p < 0.02), and weight <1,750 g (2.19 [1.25-3.82], p < 0.01). Median length-of-stay was 14 days (IQR: 7-32). Associated with increased length-of-stay were cardiac defect (1.47 [1.37-1.56], p < 0.001), vertebral anomaly (1.1 [1.05-1.14], p < 0.001), TE fistula (1.73 [1.66-1.81], p < 0.001), anorectal malformation (1.12 [1.07-1.16], p < 0.001), and weight <1,750 g (1.65 [1.57-1.73], p < 0.001). This novel assessment tool may help providers counsel families confronting a VACTERL diagnosis.


An in vitro study on the involvement of LINGO-1 and Rho GTPases in Nogo-A regulated differentiation of oligodendrocyte precursor cells.
Nogo-A has been considered as one of the most important myelin-associated axonal regeneration inhibitors in the central nervous system. Recent studies have demonstrated various additional physiological roles of Nogo family members. To understand the possible effect of Nogo-A on the differentiation of oligodendrocytes, antibodies against distinct extracellular domains of Nogo-A were applied in cell cultures. Oligodendrocyte precursor cells from P2 rat cortex were grown in the presence of monoclonal antibody against the N-terminal inhibitory domain of Nogo-A or the C-terminal 66 amino acid loop of Nogo-A for 3 days, and the antibody treatment resulted in stunted process extension and inhibited differentiation of oligodendrocytes. Concomitant with morphology changes, Rho GTPases activity was greatly increased upon the antibody treatment and the expression level of LINGO-1, which was recently shown to be a negative regulator for the oligodendrocyte maturation, was upregulated in the process of antibody treatment. These results indicate that endogenous Nogo-A expressed in oligodendrocyte may act though Rho GTPase and LINGO-1 to influence the morphological differentiation of oligodendrocytes and will help us to understand the physiology role of Nogo-A in oligodendrocyte biology.


Anterior subdiaphragmatic vagotomy decreases the IgA antibody response in the small intestines of BALB/c mice.
To assess the impact of vagotomy on the IgA-response, male BALB/c mice underwent anterior vagotomy or a sham procedure were sacrificed on day 14 post-operation and the proximal and distal small-gut segments were dissected. In intestinal lavages IgA/IgM antibodies were analysed by ELISA; in Peyer's-patches and lamina-propria cell suspensions the intracellular IgA-associated interleukins (ILs) and pro-inflammatory cytokines in CD4+ T cells were analysed by cytofluorometry. Vagotomy reduced the IgA or increased the IgM antibody concentration in both segments and reduced or increased the lamina- propria CD4+ T cell pro-inflammatory cytokine responses in the distal or proximal segments, respectively. Data show the role of the vagus nerve on the IgA response.


N-ethyl-tauroursodeoxycholic acid, a novel deconjugation-resistant bile salt analogue: effects of acute feeding in the rat.
The purpose of this study was to investigate the physicochemical/biological properties and the effects of acute administration of N-ethyl-tauroursodeoxycholic acid in bile-fistula rats. In vitro determination of high-performance liquid chromatography mobility, octanol/ water partitioning, cholesterol solubilizing capacity, and sensitivity to enzyme deconjugation by bacteria and cholylglycine-hydroxylase were performed. In vivo determination of the following was also performed: (1) maximum secretory rate (SRmax) and choleretic/secretory properties during intravenous (IV) administration; (2) site/ extent of absorption, effects on bile flow, lipid secretion, and biotransformations after intraduodenal infusion. N-ethyl-tauroursodeoxycholate has a lipophilicity slightly higher than tauroursodeoxycholate, close to taurocholate, and similar cholesterol solubilizing capacity. Deconjugation of N-ethyl-tauroursodeoxycholate was 3.4 +/- 2.1% after 72 hours, that of tauroursodeoxycholate was 100% after 24 hours. During IV infusion of 300 nmol/min/ 100g, biliary secretion of N-ethyl-tauroursodeoxycholic and tauroursodeoxycholic acids averaged 185 +/- 76 (standard deviation) nmol/min/100 g and 221 +/- 77 nmol/min/ 100 g (not significant). Increasing infusion rates caused progressive enhancement of bile flow and bile salt secretion until the SRmax was reached (1,305 +/- 240 nmol/min/ 100 g for N-ethyl-tauroursodeoxycholic acid and 3,240 nmol/min/100 g for tauroursodeoxycholate). The two bile salts were similarly choleretic. IV feeding of N-ethyl-tauroursodeoxycholic promoted a greater lipid secretion than tauroursodeoxycholate. After intraduodenal feeding of 800 mumol, 38.8 +/- 14.0% and 43.4 +/- 12.4% of the two bile salts were recovered in bile. No unconjugated bile salts nor unusual metabolites were detected.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of nicotine 6 mg gum on urges to smoke, a randomized clinical trial.
Ability to manage urges to smoke is fundamental to maximizing the chances of success in smoking cessation. Previous studies have linked a higher dose of nicotine in nicotine replacement therapy to a higher success rate for smoking cessation. Thus, this study was performed to compare relief of urges to smoke, up until 5 h following treatment with a new 6 mg nicotine gum versus currently marketed 4 mg nicotine gum. This was a randomized crossover clinical study. Following 12 h of abstinence from smoking, either one 6 mg or one 4 mg nicotine gum was given to 240 healthy adult smokers. Thereafter, urges to smoke were scored on a 100 mm Visual Analogue Scale repeatedly over 5 h. The reductions in urges to smoke over the first 1 and 3 h after administration were statistically significantly greater with 6 mg than 4 mg gum, (p < 0.005). A 50% reduction in perceived urges to smoke was reached in 9.4 min with 6 mg gum compared to 16.2 min with 4 mg gum (median values). The median duration of a 50% or more reduction in VAS urges to smoke score was 111 min with the 6 mg gum, versus 74 min for the 4 mg gum. This study provides evidence that the 6 mg nicotine gum provided a greater reduction, faster and longer relief of urges to smoke than the 4 mg nicotine gum. EudraCT Number: 2010-023268-42. Study was first entered in EudraCT 2011-02-23.