Reactivity of thiols towards derivatives of 2- and 6-methyl-1,4-naphthoquinone bioreductive alkylating agents.
The stoichiometry and kinetics of the anaerobic reactions between some thiols and derivatives of 2- and 6-methyl-1,4-naphthoquinones in water were measured using stopped flow spectrophotometry. The stoichiometry of the reaction with representative compounds was 1:2 thiol:quinone, a finding consistent with the formation of a hydroquinone as well as a thioether in the reaction. The first-order dependence of rate on thiol concentration, and the pH-dependent rate constants indicated that the thiolate anion was involved in the rate-limiting step, with rate constants at pH 7.6 generally increasing in the order glutathione (GSH) less than cysteamine less than dithiothreitol (DTT) less than cysteine. Despite the lower reactivity of GSH, the half-lives of the uncatalyzed conjugation reaction of these quinones at typical biological concentrations of GSH (e.g. 2 mM) ranged from about 2.0 to 20 s at pH 7.6 and 25 degrees C. The implications of these reactions in the use of naphthoquinones as potential bioreductive alkylating agents and as hypoxic cell radiosensitizers are discussed.


Ureteropelvic junction obstruction unmasked after correction of vesicoureteral reflux using endoscopic treatment with Deflux.
A case of intermittent ureteropelvic junction obstruction unmasked after correction of vesicoureteral reflux using endoscopic treatment with Deflux is presented. The difficulty in diagnosis and making treatment decisions for patients with coexisting ureteropelvic junction obstruction and vesicoureteral reflux is discussed.


Protein adsorption to (3-acrylamido propyl) trimethyl ammonium chloride-grafted Sepharose gel: Charge density reduction via copolymerizing with electroneutral monomer drastically increases uptake rate.
Polymer-grafting to porous materials is an effective way to create protein ion-exchangers of high capacity and uptake rate because the 3D architecture of the polymeric ion exchange groups provides high binding space and facilitated transport of the bound protein. Herein, a new anion exchanger was fabricated by grafting (3-acrylamide propyl) trimethyl ammonium chloride (APTAC) onto Sepharose FF gel for protein adsorption and chromatography. The ion exchanger, denoted as FF-pAPTAC, presented high capacity but limited uptake rate in bovine serum albumin (BSA) adsorption due to the high charge density of the cationic polymer chains. To solve the problem, we proposed to copolymerize APTAC with an electroneutral monomer, acrylamide (AM), onto Sepharose FF to modulate the charge density of the grafted polymer chains. By decreasing the feeding molar ratio of APTAC to AM, the ionic capacity (IC) of the copolymerized resins, FF-p(AM-APTAC)n (n denotes IC in mmol/L), decreased, but the chain length could be remained almost unchanged due to the similar reactivity ratios of the two monomers. With decreasing IC, the static adsorption capacity (qm) of FF-p(AM-APTAC)n decreased gradually because of the decline of protein binding sites. The uptake rate, however, represented by the ratio of effective pore diffusivity to the free solution diffusivity (De/D0), exhibited a strong uptrend with decreasing IC, reaching ~2.5-fold of the maximum observed with FF-pAPTACn. It is considered that the decrease of charge density weakened protein binding strength to the chains and increased the chain flexibility, which consequently facilitated the transport of bound proteins on the chains. Moreover, at the same IC, each FF-p(AM-APTAC)n displayed similar adsorption capacity but high uptake rate as compared with its FF-pAPTACn counterpart mainly due to the longer chain length of the copolymer. Particularly, ~6.5-fold enhancement of De/D0 was observed at IC = 50 ± 2 mmol/L. Both high adsorption capacity and uptake rate made FF-p(AM-APTAC)n exhibit superior dynamic binding performance. The findings proved that reducing chain charge density by copolymerizing an electroneutral monomer was promising for fabrication of high-performance protein ion exchangers.


Angiotensin Receptor Blockers Associated with Improved Breast Cancer Survival-A Nationwide Cohort Study from Finland.
Breast cancer incidence has been associated with hypertension, which might worsen disease prognosis, but few nationwide studies have investigated the association between antihypertensive drug use and breast cancer prognosis. A cohort of 73,170 women diagnosed with breast cancer during 1995-2013 identified from the Finnish Cancer Registry was combined with information on antihypertensive drug use during the same time period from a national prescription database. Antihypertensive drugs were analyzed in groups categorized by mechanism of action. Usage of antihypertensive drugs, statins, antidiabetic, and anticoagulative drugs was analyzed as time-dependent exposure to model for simultaneous use of multiple drug groups. Influence of protopathic bias was evaluated in lag-time analyses. In prediagnostic use, only angiotensin receptor (ATR)-blockers were associated with decreased risk of breast cancer death as compared with nonusers (HR: 0.76, 95% confidence interval, CI: 0.69-0.82), and there was an inverse association with cumulative dose of use. Postdiagnostic use of ATR-blockers, angiotensin-converting enzyme (ACE)-inhibitors, beta-blockers, and calcium-channel blockers was dose dependently associated with better breast cancer survival compared with nonusers. The risk decrease was strongest for ATR-blockers (HR: 0.69, 95% CI: 0.63-0.75) and remained for exposures occurring up to 3 years earlier. Only ATR-blockers were associated with improved breast cancer survival in both prediagnostic and postdiagnostic use. The association was dose dependent and supported by a biological rationale as a causal explanation. In postdiagnostic use, similar reduction was found also for other antihypertensives, supporting a prognostic role of hypertension control. Inhibition of angiotensin receptor subtype 1 (AT1) could be a promising novel way to affect breast cancer progression.


Ionic liquid pretreatment of biomass for sugars production: Driving factors with a plausible mechanism for higher enzymatic digestibility.
In this study, five ionic liquids (ILs) have been explored for biomass pretreatment for the production of fermentable sugar. We also investigated the driving factors responsible for improved enzymatic digestibility of various ILs treated biomass along with postulating the plausible mechanism thereof. Post pretreatment, mainly two factors impacted the enzymatic digestibility (i) structural deformation (cellulose I to II) along with xylan/lignin removal and (ii) properties of ILs; wherein, K-T parameters, viscosity and surface tension had a direct influence on pretreatment. A systematic investigation of these parameters and their impact on enzymatic digestibility is drawn. [C2mim][OAc] with β-value 1.32 resulted 97.7% of glucose yield using 10 FPU/g of biomass. A closer insight into the cellulose structural transformation has prompted a plausible mechanism explaining the better digestibility. The impact of these parameters on the digestibility can pave the way to customize the process to make biomass vulnerable to enzymatic attack.


Toward a Harmonized WHO Family of International Classifications Content Model.
An overarching WHO-FIC Content Model will allow uniform modeling of classifications in the WHO Family of International Classifications (WHO-FIC) and promote their joint use. We provide an initial conceptualization of such a model.


Chromium levels in insulin-sensitive tissues and the thigh bone are modulated by prednisolone and high-fat diets in mice.
Glucocorticoids (GCs) are often prescribed in clinics but many adverse effects are also attributed to GCs. It is important to determine the role of GCs in the development of those adverse effects. Here, we investigated the impact of GCs on trivalent chromium (Cr) distribution in animals. Cr has been proposed to be important for proper insulin sensitivity, and deficits may lead to disruption of metabolism. For comparison, the effect of a high-fat diet on Cr modulation was also evaluated. C57BL/6JNarl mice were fed regular or high-fat diets for 12 weeks and further grouped for treatment with prednisolone or saline. Cr levels in tissues were determined 12 h after the treatments. Interestingly, prednisolone treatment led to significantly reduced Cr levels in fat tissue in mice fed regular diets; compared to the high-fat diet alone, prednisolone plus the high-fat diet led to a further reduction in Cr levels in the liver, muscle, and fat. Notably, a single dose of prednisolone was linked with elevated Cr levels in the thigh bones of mice fed by either regular or high-fat diets. In conclusion, this report has provided evidence that prednisolone in combination with a high-fat diet effects modulation of Cr levels in selected tissues.


Myocardial infarction and risk region relationships: evaluation by direct and noninvasive methods.
Optimal quantitation of myocardial infarction requires resolution of the three-dimensional geometry of the ischemic region at a time that progression of tissue necrosis has been completed and can be sharply delineated from noninfarcted myocardium but before significant remodeling of the ventricular chamber. Although this can be achieved at two to three days after coronary occlusion by histologic techniques, a variety of technologies including two-dimensional echo, CTT, SPECT, PET, and NMR have demonstrated potential for providing noninvasive quantitative measurements of the extent of myocardial infarction. Additional studies are needed to clarify the utility of these technologies for resolving the highly variable transmural distribution of infarction that is present in the clinical setting. Assessment of the region at risk for infarction, the ischemic zone, requires quantitative measurements of the degree of ischemia as well as the size of the ischemic region. Although the above technologies may provide quantitative measurements of the dimensions of the ischemic zone, the utility for resolving the highly variable transmural distribution of regional myocardial blood flow using clinically applicable methodologies has not been convincingly established at present. It is possible that cine CT, new generation PET, and NMR technologies may eventually provide noninvasive quantitative measurements of regional myocardial blood flow.


Unsaturated Lipid Assimilation by Mycobacteria Requires Auxiliary cis-trans Enoyl CoA Isomerase.
Mycobacterium tuberculosis (Mtb) can survive in hypoxic necrotic tissue by assimilating energy from host-derived fatty acids. While the expanded repertoire of β-oxidation auxiliary enzymes is considered crucial for Mtb adaptability, delineating their functional relevance has been challenging. Here, we show that the Mtb fatty acid degradation (FadAB) complex cannot selectively break down cis fatty acyl substrates. We demonstrate that the stereoselective binding of fatty acyl substrates in the Mtb FadB pocket is due to the steric hindrance from Phe287 residue. By developing a functional screen, we classify the family of Mtb Ech proteins as monofunctional or bifunctional enzymes, three of which complement the FadAB complex to degrade cis fatty acids. Crystal structure determination of two cis-trans enoyl coenzyme A (CoA) isomerases reveals distinct placement of active-site residue in Ech enzymes. Our studies thus reveal versatility of Mtb lipid-remodeling enzymes and identify an essential role of stand-alone cis-trans enoyl CoA isomerases in mycobacterial biology.


Comparison of full-iodine conventional CT and half-iodine virtual monochromatic imaging: advantages and disadvantages.
To compare image quality of abdominal arteries between full-iodine-dose conventional CT and half-iodine-dose virtual monochromatic imaging (VMI). We retrospectively evaluated images of 21 patients (10 men, 11 women; mean age, 73.9 years) who underwent both full-iodine (600 mg/kg) conventional CT and half-iodine (300 mg/kg) VMI. For each patient, we measured and compared CT attenuation and the contrast-to-noise ratio (CNR) of the aorta, celiac artery, and superior mesenteric artery (SMA). We also compared CT dose index (CTDI). Two board-certified diagnostic radiologists evaluated visualisation of the main trunks and branches of the celiac artery and SMA in maximum-intensity-projection images. We evaluated spatial resolution of the two scans using an acrylic phantom. The two scans demonstrated no significant difference in CT attenuation of the aorta, celiac artery, and SMA, but CNRs of the aorta and celiac artery were significantly higher in VMI (p = 0.011 and 0.030, respectively). CTDI was significantly higher in VMI (p = 0.024). There was no significant difference in visualisation of the main trunk of the celiac artery and SMA, but visualisation of the gastroduodenal artery, pancreatic arcade, branch of the SMA, marginal arteries, and vasa recta was significantly better in the conventional scan (p < 0.001). The calculated modular transfer function (MTF) suggested decreased spatial resolution of the half-iodine VMI. Large-vessel depiction and CNRs were comparable between full-iodine conventional CT and half-iodine VMI images, but VMI did not permit clear visualisation of small arteries and required a larger radiation dose. ・Reducing the dose of iodine contrast medium is essential for chronic kidney disease patients to prevent contrast-induced nephropathy. ・In virtual monochromatic images at low keV, contrast of relatively large vessels is maintained even with reduced iodine load, but visibility of small vessels is impaired with decreased spatial resolution. ・We should be aware about the advantages and disadvantages associated with virtual monochromatic imaging with reduced iodine dose.


A new species of oak gall wasp (Hymenoptera: Cynipidae, Cynipini) from Turkey.
A new species of the genus Andricus Hartig, 1840 (Cynipidae: Cynipini) is described from Burdur province in Turkey: Andricus arslani Azmaz Katlm sp. n. sexual generation. The new species induce galls on Quercus cerris L. belonging to section Cerris. SEM images, photos of the host galls, and data on the diagnosis, distribution, and biology of the new species are provided.


Natural history and treatment of low and high risk superficial bladder tumors.
Since 1979 a prospective randomized trial was done to examine the efficacy of intravesical doxorubicin as prophylaxis against recurrence. After complete transurethral resection of the tumor, patients were divided into 3 groups at random: group 1-no further treatment after transurethral resection, group 2-doxorubicin twice weekly for 6 weeks and group 3-doxorubicin for 1 year. A total of 268 patients entered the study. Neither frequency of recurrences, tumor progression nor survival rate was improved significantly by the adjuvant treatment, so that only a limited number of patients will profit by instillation therapy. Analysis of previously reported data suggests that patients with superficial bladder tumors can be stratified into groups with appreciable differences in risk of progression. With regard to these results a differentiated use of a "wait and see" adjuvant intravesical therapy and more aggressive treatment after transurethral resection of superficial bladder tumors seems to be indicated rather than a general practice of chemoprophylaxis.


Performance of the Disc Diffusion Method, MTS Gradient Tests and Two Commercially Available Microdilution Tests for the Determination of Cefiderocol Susceptibility in Acinetobacter spp.
Cefiderocol is a siderophore-conjugated cephalosporin with potent activity against multidrug-resistant Gram-negative pathogens including Acinetobacter baumannii. The aim of this study was to evaluate cefiderocol testing methods on a relevant collection of 97 Acinetobacter spp. isolates. Commercialized broth microdilution methods (ComASP®, Liofilchem and UMIC®, Bruker), MIC test strips (Liofilchem) and disc diffusion using discs of three different brands (Mast Diagnostic, Liofilchem and Oxoid-Thermo Fisher Scientific) were compared with the broth microdilution reference method. None of the methods tested fulfilled acceptable criteria (essential agreement [EA] ≥ 90%; bias = ±30%) but both BMD methods achieved acceptable categorical agreement rates (CA = 95.9% [93/97, 95% CI 89.9-98.4] and CA = 93.8% [91/97, 95% CI 87.2-97.1] for ComASP® and UMIC®, respectively) and bias < 30% (-7.2% and -25.2% for ComASP® and UMIC®, respectively). The use of MIC gradient testing is strongly discouraged due to misclassification of 55% (n = 23/42) of resistant strains. Finally, the disc diffusion method could be used to rapidly screen for susceptible strains by setting a critical diameter of 22 mm.


Nuclear import of Ran is mediated by the transport factor NTF2.
A concentration gradient of the GTP-bound form of the GTPase Ran across nuclear pores is essential for the transport of many proteins and nucleic acids between the nuclear and cytoplasmic compartments of eukaryotic cells [1] [2] [3] [4]. The mechanisms responsible for the dynamics and maintenance of this Ran gradient have been unclear. We now show that Ran shuttles between the nucleosol and cytosol, and that cytosolic Ran accumulates rapidly in the nucleus in a saturable manner that is dependent on temperature and on the guanine-nucleotide exchange factor RCC1. Nuclear import in digitonin-permeabilized cells in the absence of added factors was minimal. The addition of energy and nuclear transport factor 2 (NTF2) [5] was sufficient for the accumulation of Ran in the nucleus. An NTF2 mutant that cannot bind Ran [6] was unable to facilitate Ran import. A GTP-bound form of a Ran mutant that cannot bind NTF2 was not a substrate for import. A dominant-negative importin-beta mutant inhibited nuclear import of Ran, whereas addition of transportin, which accumulates in the nucleus, enhanced NTF2-dependent Ran import. We conclude that NTF2 functions as a transport receptor for Ran, permitting rapid entry into the nucleus where GTP-GDP exchange mediated by RCC1 [7] converts Ran into its GTP-bound state. The Ran-GTP can associate with nuclear Ran-binding proteins, thereby creating a Ran gradient across nuclear pores.


Research paper: The three-dimensional mechanical response of orthodontic archwires and brackets in vitro during simulated orthodontic torque.
Orthodontic archwire rotation around its long axis, known as third-order torque, is utilised to correct tooth rotational misalignments moving the tooth root closer to or away from the cheek through engagement with an orthodontic bracket. Studying the behaviour of archwire and brackets during an applied rotation can aid in better understanding and appreciating the mechanics of third-order torque, potentially allowing for more effective orthodontic treatment protocols. Mechanically characterising archwire behaviour during third-order torque application is a complex task due to their physical scale and geometries. An advanced measurement technique was needed to address these constraints. A three-dimensional (3D) non-contact optical method using a digital image correlation (DIC) system was developed. An orthodontic torque simulator (OTS) was used to apply and measure third-order torque with 0.483 × 0.635 mm (0.019″ x 0.025″) rectangular archwires in tandem with a 3D DIC system, whereby surface deformations and strains could be computed using correlation algorithms. The 3D DIC system was implemented to enable third-order torque experimentation with the OTS while imaging the archwire and bracket surfaces. The 3D DIC system's ability to measure 3D archwire deformations and strains was verified using a finite element model, where comparisons between 3D DIC measurements and calculated results from the model were made to ensure the measurement capabilities of 3D DIC in the context of third-order torque. The 3D DIC system was then used to compare archwire behaviour between stainless steel (SS) and titanium molybdenum alloy (TMA) archwires to study potential clinical differences in archwire behaviour, in which the archwires were rotated with a custom SS rigid dowel (RD) as well as commercial Damon Q orthodontic brackets. The quantification of third-order torque and archwire deformations and strains led to the conclusion that SS archwires led to larger torque magnitudes compared to TMA archwires. The RD resulted in larger archwire strains compared to Damon Q brackets. The 3D DIC system provides a non-contact measurement technique that can further be used with third-order torque experimentation with the OTS.


Harnessing the potential of LPMO-containing cellulase cocktails poses new demands on processing conditions.
The emerging bioeconomy depends on improved methods for processing of lignocellulosic biomass to fuels and chemicals. Saccharification of lignocellulose to fermentable sugars is a key step in this regard where enzymatic catalysis plays an important role and is a major cost driver. Traditionally, enzyme cocktails for the conversion of cellulose to fermentable sugars mainly consisted of hydrolytic cellulases. However, the recent discovery of lytic polysaccharide monooxygenases (LPMOs), which cleave cellulose using molecular oxygen and an electron donor, has provided new tools for biomass saccharification. Current commercial enzyme cocktails contain LPMOs, which, considering the unique properties of these enzymes, may change optimal processing conditions. Here, we show that such modern cellulase cocktails release up to 60 % more glucose from a pretreated lignocellulosic substrate under aerobic conditions compared to anaerobic conditions. This higher yield correlates with the accumulation of oxidized products, which is a signature of LPMO activity. Spiking traditional cellulase cocktails with LPMOs led to increased saccharification yields, but only under aerobic conditions. LPMO activity on pure cellulose depended on the addition of an external electron donor, whereas this was not required for LPMO activity on lignocellulose. In this study, we demonstrate a direct correlation between saccharification yield and LPMO activity of commercial enzyme cocktails. Importantly, we show that the LPMO contribution to overall efficiency may be large if process conditions are adapted to the key determinants of LPMO activity, namely the presence of electron donors and molecular oxygen. Thus, the advent of LPMOs has a great potential, but requires rethinking of industrial bioprocessing procedures.


Resistance of group B streptococcus to selected antibiotics, including erythromycin and clindamycin.
Resistance of group B streptococcus (GBS) to antibiotics, particularly erythromycin and clindamycin, was studied. Erythromycin resistance was present in 22% of GBS isolates, and these isolates were constitutively resistant, inducibly resistant, or sensitive to clindamycin. Erythromycin and clindamycin MICs were related to the presence of ermA, ermB, or mefA genes.


Extracellular matrix components and amyloid in neuritic plaques of Alzheimer's disease.
1. There has been an enormous amount of information relating to the molecular components involved in Alzheimer's disease. 2. Recently some attention has been focused on the extracellular matrix (ECM) components present in the brain amyloid deposits. 3. Here we discuss, the direct involvement of ECM constituents such as laminin, collagen type IV, fibronectin, proteoglycans (PGs) and basic fibroblast growth factor in the formation of neuritic plaques. 4. We suggest that PGs act as nucleating agents in the formation of the diffuse amyloid deposits that precede the formation of the neuritic plaque in the brain of patients affected with Alzheimer's disease.


Temperature response of methane production in liquid manures and co-digestates.
Intensification of livestock production makes correct estimation of methanogenesis in liquid manure increasingly important for inventories of CH4 emissions. Such inventories currently rely on fixed methane conversion factors as knowledge gaps remain with respect to detailed temperature responses of CH4 emissions from liquid manure. Here, we describe the temperature response of CH4 production in liquid cattle slurry, pig slurry, and fresh and stored co-digested slurry from a thermophilic biogas plant. Subsamples of slurry were anoxically incubated at 20 temperatures from 5-52°C in a temperature gradient incubator and CH4 production was measured by gas chromatographic analysis of headspace gas after a 17-h incubation period. Methane production potentials at 5-37°C were described by the Arrhenius equation (modelling efficiencies, 79.2-98.1%), and the four materials showed a consistent activation energy (Ea) which averaged 81.0kJmol(-1) (95% confidence interval, 74.9-87.1kJmol(-1)) corresponding to a temperature sensitivity (Q10) of 3.4. In contrast, the frequency factor (A) differed among the slurry materials (30.1<ln A<33.3; mean, 31.3) reflecting that origin, age and composition of the manure affect this parameter. The Ea estimate, based on individual slurry materials, was intermediate when compared to published values of 63 and 112.7kJmol(-1) derived from composite data, but was similar to Ea estimated for CH4 production at microbial community level across aquatic ecosystems, wetlands and rice paddies (89.3kJmol(-1)). This supports that the derived temperature sensitivity parameters may be applicable to dynamic modelling of CH4 emissions from livestock manure.


Calcium.
This chapter describes the chemical and biological value of the calcium ion. In calcium chemistry, our main interest is in equilibria within static, nonflowing systems. Hence, we examined the way calcium formed precipitates and complex ions in solution. We observed thereafter its uses by humankind in a vast number of materials such as minerals, e.g., marble, concrete, mortars, which parallel the biological use in shells and bones. In complex formation, we noted that many combinations were of anion interaction with calcium for example in the uses of detergents and medicines. The rates of exchange of calcium from bound states were noted but they had little application. Calcium ions do not act as catalysts of organic reactions. In biological systems, interest is in the above chemistry, but extends to the fact that Ca2+ ions can carry information by flowing in one solution or from one solution to another through membranes. Hence, we became interested in the details of rates of calcium exchange. The fast exchange of this divalent ion from most organic binding sites has allowed it to develop as the dominant second messenger. Now the flow can be examined in vitro as calcium binds particular isolated proteins, which it activates as seen in physical mechanical changes or chemical changes and this piece-by-piece study of cells is common. Here, however, we have chosen to stress the whole circuit of Ca2+ action indicating that the cell is organized both at a basal and an activated state kinetic level by the steady state flow of the ion (see Fig. 11). Different time constants of exchange utilizing very similar binding constants lead to: 1) fast responses as in the muscle of an animal; or 2) slower change as in differentiation of an egg or seed. Many other changes of state may relate to Ca2+ steady-state levels of flow in the circuitry and here we point to two: 1) dormancy in reptiles and animals; and 2) sporulation in both bacteria and lower plants. In the other chapters of this volume many components of the overall circuitry will be described. The reader should try to marry these into the overall activity of the cell for on top of molecular biology there is the cooperative system molecular biology of cells. To give an analogy, whereas much can be understood from the analysis of the properties of single-isolated water molecules, even examining their interaction in ice, this study alone cannot lead to an appreciation of the melting or boiling points of bulk water.


Nitrothiadiazolo[3,2-a]pyrimidines as promising antiglycating agents.
Managing the advanced glycation end-products (AGEs) concentration is a reliable approach to achieve control over the pathogenesis of diabetic vascular complications. Inhibition of dipeptidyl peptidase-4 (DPP-4) is also an attractive way to tackle type 2 diabetes mellitus (T2DM). We showed previously that azoloazine heterocycles have the potential to prevent the formation of AGEs and in this work, we conducted docking studies with DPP-4 of 5-alkylamino-6-nitro-1,3,4-thiadiazolo[3,2-a]pyrimidines. Consequently, we have developed a synthetic approach to these structures by chlorodeoxygenation and amination reactions. Antidiabetic properties of obtained compounds were studied by evaluating DPP-4 (ex vivo/in vitro) and AGEs formation inhibition (in vitro). It was shown that the nitrothiadiazolopyrimidines exhibit a higher antiglycation activity than reference compound aminoguanidine, but only moderate inhibition of DPP-4. The most active DPP-4 inhibitor 1l had IC50 of 55.87 μM and showed the ability to inhibit serum DPP-4 activity in rats after 10 mg/kg oral administration but with the less and shorter effect than vildagliptin. At the same time, 1l was the most active antiglycating compound in the series (IC50 134.4 μM). Copper chelation properties of synthesized compounds were also investigated since the formation of AGEs is catalyzed by the transition metal cations. A noticeable correlation between antiglycation activity and metal chelation was revealed. Both activities (antiglycation and copper chelation) correlated with quantum-chemical properties (calculated with ab initio) of the tested compounds. These findings will allow us to predict both activities in the future, without the need to model multiple steps of glycation reaction.


Treatment Strategy for Distant Synchronous Metastatic Head and Neck Squamous Cell Carcinoma.
Management of metastatic head and neck squamous cell cancers (HNSCC) can be challenging. This review gives an insight of current treatment options for patients with synchronous metastatic HNSCC and suggests a therapeutic algorithm. With the rise of novel therapeutic techniques and medications, many treatment options for both locoregional and distant metastatic disease have become available. The evolving paradigm of metastatic disease now integrates the concept of oligometastatic disease. On top of systemic treatments, patients with low metastatic burden can benefit from curative approaches such as local therapies (surgery, radiotherapy) directed to either primary tumour and distant metastasis. However, data integrating these considerations in the management of metastatic HNSCC is still lacking. Based on this algorithm, we can provide a tailored treatment to each patient with synchronous metastatic HNSCC, according to their age, general condition and metastatic burden.


Thickness and roughness of transparent gold-palladium anodes have no impact on growth kinetics and yield coefficients of early-stage Geobacter sulfurreducens biofilms.
Geobacter sulfurreducens is the model organism for electroactive microorganisms performing direct extracellular electron transfer and forming thick mature biofilm electrodes. Although numerous physiological properties of mature biofilm electrodes are deciphered, there is an extensive gap of knowledge on the early-stage biofilm formation. We have shown recently that transparent gold-palladium (AuPd) electrodes allow for analysis of early-stage biofilm formation using confocal laser scanning microscopy. Here we analysed the influence of thickness (ranging from 12.5 to 200 nm) and roughness of AuPd electrodes on physiological parameters of G. sulfurreducens early-stage biofilms. We show that when grown potentiostatically at -200 mV vs. Ag/ AgCl sat. KCl neither maximum current density (jmax of ∼ 80-150 µA cm-2) nor lag time (lag t of ∼ 0.2-0.4 days) or single cell yield coefficients (YNe of 1.43 × 1012 cells mole--1) of the biofilms are influenced by the electrode preparation. This confirms the robustness of the experimental approach, which is an inevitable prerequisite for obtaining reliable results in follow-up experiments.


Duchenne muscular dystrophy--Meryon's disease.
In a communication to the Royal Medical and Chirurgical Society of London in December 1851, which was published in the Transactions of the Society the following year, Edward Meryon, an English physician, described, in considerable detail, eight boys in three families with a disease later referred to as Duchenne muscular dystrophy. He was particularly impressed by the predilection for males and its familial nature, and that the progressive muscle wasting and weakness was essentially due to a disease of muscle and not the nervous system. His detailed histological studies revealed no abnormality of the spinal cord or nerves but in muscle tissue he noted extensive "granular degeneration" and in particular that the sarcolemma was broken down and destroyed. He appears to have been the first physician to make a detailed clinical, genetic, and pathological study of the disorder several years before Duchenne.


New approach to sulfonated diphosphine complexes: synthesis and amphoteric behaviour of zwitterionic [Mn+(CO4{(PPh2)2C(H)SO3-}].
Oxidation of the thioketone residue in the complex [Mn(CO)4{(PPh2)2C=S}]+ (2) with hydrogen peroxide affords the sulfonate derivative [Mn(CO)4{(PPh2)2C(H)SO3}] (3), which shows amphoteric behaviour in reversible acid-base processes, and is easily chlorinated to give [Mn(CO)4{(PPh2)2C(Cl)SO3}] (8).


Influence of head or trunk oscillations on visually induced self-motion perception in humans.
The influence of concurrent head or trunk movements on optokinetically induced self-motion perception has been investigated by measuring circularvection (CV) latencies. Active head as well as passive trunk oscillation cause an increase in circularvection latency of about 50% as compared to latencies with the head and trunk stationary during full field optokinetic stimulation. The results point towards an intersensory inhibition of self-motion perception.


An in vivo study on the synchronizing effect of hydroxyurea.
The effect of hydroxyurea (HU; 0.5 mg/g body wt) on L 1210 ascites tumor cells has been studied using various cell kinetic methods. In contrast to the general assumption that HU blocks cells at the G1/S boundary [J. Brachet (1985) Molecular Cytology, Vol. I, p. 266, Academic Press, New York], the present results show that the cells are not held at G1/S but enter S at about the normal rate and are accumulated in early S phase due to a dose-dependent inhibiting effect of HU on DNA synthesis. Partial synchronization of the cells demonstrated by a distinct mitotic peak 10 h after HU application is not due to a G1/S block of the cells and their subsequent synchronous passage through the cycle after release from the block but is due to rather complex mechanisms of action of HU: a differential cytocidal effect and an effect on the passage of the cells through the cycle, both depending on the position of the cells throughout the cycle. HU kills S-phase cells, mainly cells in early S phase; i.e., a great portion of the cells "accumulated" in early S phase is killed by the drug, while G1-phase cells are almost not affected by the lethal effect of HU. These G1-phase cells pass through the cycle more rapidly after cessation of the HU effect. The same is true for the surviving cells accumulated in early S phase, while part of the cells in the remaining S phase are delayed in their passage through the cycle. This causes partial synchronization, since a great portion of all cells that survive HU treatment reach mitosis at the same time.


The electrochemically-tuneable interactions between flavin-functionalised C60 derivatives and 2,6-diethylamidopyridine.
We report the electrochemically-tuneable interactions between flavin-functionalised C60 derivatives and a diamidopyridine derivative.


Possible involvement of oxidative stress in hypoxia-induced adrenomedullin secretion in cultured rat cardiomyocytes.
Although hypoxia induces adrenomedullin gene expression in cultured rat cardiac myocytes, it is still unknown whether oxidative stress is involved in the hypoxia-induced adrenomedullin production. We investigated whether oxidative stress might participate in hypoxia-induced adrenomedullin secretion and whether adrenomedullin might have a protective effect on damaged myocytes. Hypoxia increased adrenomedullin secretion and its gene expression in cardiac myocytes, but not in nonmyocytes. Furthermore, oxidative stress (hydrogen peroxide) also increased adrenomedullin secretion from myocytes. N-acetyl-L-cysteine, a free radical scavenger, completely inhibited the stimulation of adrenomedullin secretion by hydrogen peroxide, and this agent reduced the stimulation of adrenomedullin secretion by hypoxia. Lactate dehydrogenase leakage, a marker of cell injury, was significantly increased with the exposure to hydrogen peroxide and adrenomedullin significantly reduced this leakage. These findings suggest that an oxidative stress may be involved, in part, in the increased adrenomedullin secretion from cardiac myocytes under hypoxic condition. Adrenomedullin secreted from myocytes may play a cell protective role in an autocrine manner.


Effects of microscale particles in red mud amended artificial soils on bioaccumulation of elements in E. fetida.
Red mud (RM) contains large quantities of microscale particles < 1 μm and high concentrations of potentially toxic elements. In this research, we have used two types of RM of similar chemical properties but containing different quantities of micro-particles, to test whether their size plays a role in the uptake of chemical elements by earthworm Eisenia fetida. Earthworms were exposed for seven days to artificial soils (prepared in the laboratory following a protocol) amended with increasing quantities of RM. Mortality of 86 % occurred when earthworms were exposed to amended soil containing 46 % of particles below 1 μm. Surprisingly, tissue analyses have shown decreased concentrations of metals instead of the expected toxic effect. SEM analysis revealed that micro-particles strongly adhere to the earthworm epidermis putting them under the large stress. Micro-particles in RM clog their minute dermal pores of 90 nm-735 nm in diameter, which size depends on whether the earthworm's body is contracted or stretched. Strong adhesion of micro-particles to earthworms' epidermis and blockage of their microsize pores prevented normal dermal respiration and absorption of chemical elements through their epithelium resulting in a decrease of most measured metals, especially essential elements potassium, calcium and iron, followed by the lethal outcomes.


Risk of cardiovascular disease in lean patients with nonalcoholic fatty liver disease.
Patients with nonalcoholic fatty liver disease (NAFLD) are highly at risk for cardiovascular disease (CVD). However, the risk of developing CVD in patients with lean NAFLD is not yet fully understood. Therefore, this study aimed to compare the CVD incidence in Japanese patients with lean NAFLD and those with non-lean NAFLD. A total of 581 patients with NAFLD (219 with lean and 362 with non-lean NAFLD) were recruited. All patients underwent annual health checkups for at least 3 years, and CVD incidence was investigated during follow-up. The primary end-point was CVD incidence at 3 years. The 3-year new CVD incidence rates in patients with lean and non-lean NAFLD were 2.3% and 3.9%, respectively, and there was no significant difference between two groups (p = 0.3). Multivariable analysis adjusted for age, sex, hypertension, diabetes, and lean NAFLD/non-lean NAFLD revealed that age (every 10 years) as an independent factor associated with CVD incidence with an odds ratio (OR) of 2.0 (95% confidence interval [CI]: 1.3-3.4), whereas lean NAFLD was not associated with CVD incidence (OR: 0.6; 95% CI: 0.2-1.9). CVD incidence was comparable between patients with lean NAFLD and those with non-lean NAFLD. Therefore, CVD prevention is needed even in patients with lean NAFLD.


Electrical and mechanical activity in the ex vivo perfused total canine colon.
Electrical and mechanical activity were studied in the ex vivo total canine colon, supported in a perfusion chamber by a supporting dog. Regular electrical activity could be recognized visually in 50--70% of the records. The frequency of this activity was in the range of 7--10/min. Fourier analysis also revealed dominant frequencies in this range. Two types of mechanical activity were observed. The first consisted of small amplitude repetitive contractions, which appeared both during quiescent periods and during vigorous contractions. The frequency of this rippling, when periodic, usually approximated that of the electrical activity. The second type consisted of large amplitude prolonged (30--135 sec) contractions. Without stimulation, the large amplitude contractions were asynchronous and not propagated. Following neostigmine, however, the large amplitude contractions were always propagated aborally and were usually associated with evacuation of the colon. The rippling contractions had a frequency similar to the regular electrical activity and are probably under their control. The large amplitude, prolonged duration contractions are unlikely, however, to be solely under myogenic control.


Rh(III)- and Zn(II)-Catalyzed Synthesis of Quinazoline N-Oxides via C-H Amidation-Cyclization of Oximes.
Quinazoline N-oxides have been prepared from simple ketoximes and 1,4,2-dioxazol-5-ones via Rh(III)-catalyzed C-H activation-amidation of the ketoximes and subsequent Zn(II)-catalyzed cyclization. The substrate scope and functional group compatibility were examined. The reaction features relay catalysis by Rh(III) and Zn(II).


Renal transplantation with donors older than 70 years: does age matter?
The need for organs for renal transplantation has encouraged the use of grafts from increasingly older donors. Studies of transplantation results with donors older than 70 years are sparse. The main purpose of this study is to compare the results of transplantation with donors older and younger than 70 years old. This retrospective study included 1233 consecutive deceased-donor renal transplantations performed between January 1, 2001, and December 31, 2011. We compared outcomes of grafts from donors older than 70 years (group ≥ 70; n = 82) versus donors younger than 70 years (group < 70; n = 1151). Univariate analysis of pretransplantation data showed statistically significant differences (P < .05) among the following variables for the group < 70 and group ≥ 70, respectively: recipient age (46 ± 13 versus 61 ± 5 years), donor age (44 ± 16 versus 73 ± 3 years), donor male gender (69.4% versus 47.6%), use of antibody induction immunosuppression (51.7% versus 70.7%), and HLA compatibilities (2.4 versus 2). The group ≥ 70 showed increased postoperative minor complications: bleeding (8.5% versus 3.4%; P = .017), lymphocele formation (3.7% versus 0.5%; P = .011), and incisional hernia (2.4% versus 0.2%; P < .001). Regarding transplantation results, we observed that mean serum creatinine was significantly lower among group < 70, at 1, 3, 6, 12, 24, and 60 months after transplantation (P < .05). Cumulative graft survival at 1, 3, and 4 years was 90%, 85%, and 83% in the group < 70 versus 87%, 79%, and 72% in the group ≥ 70. In the subgroup of recipients younger than 60 years, we did not verify statistically significant differences in allograft survival between group ≥ 70 and group < 70. Using Cox regression for survival analysis, we verified that donor age was not an independent risk factor for graft failure. The group of patients who received kidneys from donors younger than 70 years achieved better transplantation outcomes. Nevertheless, kidneys from older donors represent an excellent alternative for older recipients.


Cloning and biochemical characterization of APIT, a new l-amino acid oxidase from Aplysia punctata.
The purple ink of the sea hare Aplysia punctata contains a 60 kDa protein with tumoricidal activity. This A. punctata ink toxin (APIT) kills tumor cells within 6--8h in an apoptosis independent manner by the production of high amounts of hydrogen peroxide which induce a necrotic form of oxidative stress. Here, we describe the biochemical features of APIT associated with its anti-tumor activity. APIT is a weakly glycosylated FAD-binding L-amino acid oxidase that catalyzes the oxidative deamination of L-lysine and L-arginine and thereby produces hydrogen peroxide (H(2)O(2)), ammonia (NH(4)(+)) and the corresponding alpha-keto acids. The tumoricidal effect is completely abrogated in the absence of the amino acids L-lysine and L-arginine. The enzyme is stable at temperatures from 0 to 50 degrees C. Similar to other FAD-binding enzymes, it is resistant against tryptic digest. Even digest with proteinase K fails to degrade the enzyme. Cloning of the APIT gene and subsequent sequencing revealed a FAD-binding domain followed by a so-called GG-motif, which is typical for L-amino acid oxidases. Strongest homology exists to escapin, aplysianin A precursor, the cyplasins L and S and achacin.


Inhibition of cholesterol side chain cleavage by active site directed antibody to corpus luteum cytochrome P-450.
Goat antibody IgG produced against bovine corpus luteum mitochondrial cytochrome P-450 (P-450scc) associated with cholesterol side chain cleavage (CSCC) was used to compare immunological characteristics of mitochondrial cytochrome P-450s from the bovine adrenal cortex (BAM), bovine corpus luteum (BCLM), and human placenta (HPM). In Ouchterlony double diffusion, anti-P450scc produced a single band with BAM and BCLM P-450scc, but not with HPM P-450scc or BAM P-450 11 beta. Appropriate concentrations of this anti-P-450scc IgG inhibited the conversion of cholesterol to pregnenolone in BCLM and BAM preparations equivalently, but inhibition of placental P-450scc was considerably less. The addition of BCLM iron sulfur protein and iron sulfur protein reductase to HPM P-450scc increased CSCC approximately 5-fold. Under these conditions, anti-P-450scc inhibited CSCC in HPM. Solubilized and sonicated BCLM preparations were inhibited equivalently but more than whole mitochondria. Addition of anti-P-450scc IgG to BAM increased 11 beta-hydroxylation activity in concentration-dependent fashion. It appears that the cytochrome P-450sccs from BAM and BCLM are very similar if not identical, but immunologically different from HPM P-450scc. The BAM P-450 11 beta is immunochemically distinct from BCLM P-450scc. The CSCC and 11 beta-hydroxylation systems of the adrenal are intimately linked because inhibition of P-450scc markedly stimulated 11 beta-hydroxylation. Finally, the inhibition of CSCC activity of BAM, BCLM, and HPM P-450 indicates that the antigenic effect is directed toward the active site.


More effective assessment of adverse effects and comorbidities in epilepsy: results of a Phase II communication study.
Research was conducted to evaluate conversations about epilepsy between community-based neurologists and patients. Adverse effects of antiepileptic drugs and mood/behavioral issues were infrequently discussed, and neurologists and patients disagreed about these issues postvisit. Follow-up research was conducted to assess the impact of a previsit assessment tool on discussions of epilepsy. Twenty neurologists reviewed a tool incorporating questions from validated instruments (Adverse Events Profile [AEP] and Neurological Disorders Depression Inventory for Epilepsy [NDDI-E]). Naturally occurring interactions between neurologists and 60 patients were recorded. Neurologists and patients were interviewed separately. All components were transcribed and analyzed using sociolinguistics. Using the previsit assessment tool increased the number of discussions about adverse effects and mood/behavioral issues and increased neurologist-patient agreement about issues postvisit. Visit length did not increase significantly when the tool was used. Ten months after follow-up research, 50% of neurologists reported continuing to use the tool in everyday practice with patients with epilepsy.


PAX1 hypomethylation as a prognostic biomarker for radioresistance of cervical cancer.
PAX1 gene methylation plays an important role in the development of cervical cancer. However, its prognostic value after radiotherapy for locally advanced cervical cancer is unknown, so this study aimed to investigate the value of PAX1 gene methylation for predicting the sensitivity of radiotherapy for cervical cancer. We selected 125 patients with primary cervical cancer who underwent concurrent chemo-radiotherapy as the study population, quantitative methylation-specific polymerase chain reaction (QMSP) was used for detecting PAX1 methylation status of cervical exfoliated cells. Logistic regression model was used to analyze the risk factors associated with the short-term efficacy and to establish a prediction model of radiotherapy sensitivity based on PAX1 gene methylation. Cell viability after radiation of Hela and SiHa cells transfected with PAX1 or control vector was evaluated by CCK8. Furthermore, RNA-Seq analyses identified different expressed genes (DEGs) in PAX1 overexpressed SiHa cells. Gene Ontology (GO) and pathway enrichment analysis was carried out to determine the biological function of DEGs. PAX1 methylation level was associated with HPV16/18-positive rate. PAX1 hypomethylation was found to be a risk factor for tumor residual after chemo-radiotherapy. A nomogram containing the risk factors for PAX1 methylation status, lymph node metastasis, pathological type and tumor size was further constructed to predict the probability of tumor residual after chemo-radiotherapy (AUC = 0.823, 95% CI 0.736-0.910). High PAX1 protein level was more likely to cause radioresistance in both Hela and SiHa cells. Transcriptomic sequencing of PAX1 overexpressed and control cells identified 615 differentially expressed genes, and GO enrichment analysis suggested that PAX1 may be involved in the regulation of signaling receptor activity and response to viruses. PAX1 hypomethylation status could be used as a promising biomarker to predict radioresistance in cervical cancer. This further provides a new idea for the individualized treatment strategy of simultaneous radiotherapy for cervical cancer.


Umbilical cord mesenchymal stem cell-conditioned media prevent muscle atrophy by suppressing muscle atrophy-related proteins and ROS generation.
The therapeutic potential of mesenchymal stem cell-conditioned medium (MSC-CM) has been reported with various types of disease models. Here, we examine the therapeutic effect of umbilical cord MSC-CM (UCMSC-CM) on muscle-related disease, using a dexamethasone (Dex)-induced muscle atrophy in vitro model. The expressions of muscle atrophy-related proteins (MuRF-1 and MAFbx) and muscle-specific proteins (desmin and myogenin) were evaluated by Western blot analysis. The level of production of reactive oxygen species (ROS) was determined using a 2',7'-dichlorofluorescein diacetate (DCFDA) dye assay. The expression of antioxidant enzymes (copper/zinc-superoxide dismutase (Cu/Zn-SOD), manganese superoxide dismutase (MnSOD), glutathione peroxidase-1 (GPx-1), and catalase (CAT)) was verified by reverse transcription polymerase chain reaction (RT-PCR). When L6 cells were exposed to Dex, the expression of muscle atrophy-related proteins was increased by 50-70%, and the expression of muscle-specific proteins was in turn decreased by 23-40%. Conversely, when the L6 cells were co-treated with UCMSC-CM and Dex, the expression of muscle atrophy-related proteins was reduced in a UCMSC-CM dose-dependent manner and the expression of muscle-specific proteins was restored to near-normal levels. Moreover, ROS generation was effectively suppressed and the expression of antioxidant enzymes was recovered to a normal degree. These data imply that UCMSC-CM clearly has the potential to prevent muscle atrophy. Thus, our present study offers fundamental data on the potential treatment of muscle-related disease using UCMSC-CM.


Laccase activity is proportional to the abundance of bacterial laccase-like genes in soil from subtropical arable land.
Laccase enzymes produced by both soil bacteria and fungi play important roles in refractory organic matter turnover in terrestrial ecosystems. We investigated the abundance and diversity of fungal laccase genes and bacterial laccase-like genes in soil from subtropical arable lands, and identified which microbial group was associated with laccase activity. Compared with fungal laccase genes, the bacterial laccase-like genes had greater abundance, richness and Shannon-Wiener diversity. More importantly, laccase activity can be explained almost exclusively by the bacterial laccase-like genes, and their abundance had significant linear relationship with laccase activity. Thus, bacterial laccase-like gene has great potential to be used as a sensitive indicator of laccase enzyme for refractory organic matter turnover in subtropical arable lands.


Avoiding malalignment in proximal femur fractures treated with newer generation cephalomedullary nails: Some technical tips.
Three techniques to avoid malalignment in proximal femoral fractures managed with cephalomedullary nails, have been described. Issues related to rotational mismatch at fracture site, central placement of lag screw in femoral head neck fragment and limb rotation restoration have been addressed. We believe these simple techniques can help in minimizing malreduction in proximal femur fractures and result in favourable outcomes.


Development of an acellular bioengineered matrix with a dominant vascular pedicle.
This study assessed the feasibility of creating a tissue engineering platform by decellularization of fasciocutaneous tissue. A fasciocutaneous flap based upon the superficial inferior epigastric artery was harvested from the abdominal wall of 8-wk-old male Sprague-Dawley rats. All cellular components were removed by sequential treatment with sodium azide, DNAse, and sodium deoxycholate. The degree of decellularization was qualitatively assessed by histology and quantitatively assessed by spectrophotometry. Persistence of relevant extracellular matrix proteins was shown following staining with orcein and hematoxylin. The duration of circuit patency was determined by continuous perfusion with a peristaltic perfusion pump. Gross and histologic examination demonstrated removal of cellular constituents with preservation of tissue matrix architecture, including macrochannels and microchannels. This was confirmed by the application of spectrophotometry to DNA isolates, which showed that the decellularized flap retained 4.04 ng/μL DNA, compared with the non-processed control, which retained 37.03 ng/μL DNA, and the acellular control, which was read as having 0.65 ng/μL DNA. The extracellular matrix of vessel walls was shown to remain intact. Peristaltic perfusion of the cannulated pedicle inflow channel with phosphate buffered saline at a rate of 200 μL/min confirmed circuit patency for 6 h. Fasciocutaneous flaps harvested with an intact vascular pedicle and associated tissue vascular network can be successfully decellularized and perfused ex vivo. This methodology, which is scalable to human size tissues, provides promise as a technique for the production of customizable engineered tissues.


Aging of red blood cells and impaired erythropoiesis following prolonged administration of dichloromethylene diphosphonate containing liposomes in rats.
To investigate whether macrophage-depleted rats may serve as a model for studying red blood cell (RBC) aging. Rats were macrophage-depleted by 4 weekly injections of dichloromethylene diphosphonate-containing liposomes (Cl2MDP-CL). The macrophage content of spleens and bone marrows (BMs) was investigated by immunohistochemistry and light microscopy and by flow cytometry, respectively, after staining with macrophage-specific monoclonal antibodies. In addition, the ultrastructure of residual BM macrophages and their ability to phagocytose zymosan was studied. BM was also studied for apoptosis (by the TUNEL reaction) and for erythroid progenitor cell content. Furthermore, RBC indices, morphology, life span (by 51Cr labeling) and aging features (MCV, density, 4.1a/4.1b membrane protein ratio, anti-spectrin IgG binding, microvesiculation) were investigated. Serum TNF-alpha, iron, total iron-binding capacity (TIBC) and ferritin were also determined. Prolonged treatment with Cl2MDP-CL caused an almost complete depletion of macrophages in the spleen and a 58% reduction of those in the BM; the residual BM macrophages were activated as judged by their ultrastructure and phagocytic capacity in vitro. These alterations were accompanied by an increase in RBC life span and age-related RBC changes, as well as by mild anemia associated with a reduced reticulocyte count, reduced BM erythroid progenitors, increased numbers of apoptotic cells in the BM, low serum iron, high TIBC and increased serum TNF-alpha levels. Rats subjected to prolonged macrophage depletion showed an increased prevalence of senescent RBC in the circulation due to their impaired clearance by macrophages. Hence, these animals provide a model system in which mechanisms of RBC aging can be delineated. They also showed impaired erythropoiesis, presumably related to a reduction in BM macrophages and increased production of proinflammatory cytokines by residual activated marrow macrophages and other cells.


Anatomical variations of the thyroid gland: possible surgical implications.
The organogenesis of the thyroid gland in humans is often disturbed, leading to a variety of morphological variations of the gland, such as hypoplasia, ectopy, hemiagenesis and agenesis. As the morphological variations are usually diagnosed incidentally during examination for other thyroid gland diseases, the true incidence is therefore uncertain. This study was structured to investigate the gross anatomical features of the thyroid gland in 105 (88 male and 17 female) cadavers from the coastal belt of southern India, an endemic goitre region. The pyramidal lobe was present in 61 (58 percent) male cadavers, and 52 (49.5 percent) cadavers showed the presence of the levator glandulae thyroideae. 33 percent of the specimens studied showed agenesis of the isthmus. However, the accessory thyroid tissue was found in only one cadaver. This study highlights the various developmental anomalies of the thyroid gland, which forms a cornerstone to safe and effective surgery.


Accumulation of pharmaceuticals, Enterococcus, and resistance genes in soils irrigated with wastewater for zero to 100 years in central Mexico.
Irrigation with wastewater releases pharmaceuticals, pathogenic bacteria, and resistance genes, but little is known about the accumulation of these contaminants in the environment when wastewater is applied for decades. We sampled a chronosequence of soils that were variously irrigated with wastewater from zero up to 100 years in the Mezquital Valley, Mexico, and investigated the accumulation of ciprofloxacin, enrofloxacin, sulfamethoxazole, trimethoprim, clarithromycin, carbamazepine, bezafibrate, naproxen, diclofenac, as well as the occurrence of Enterococcus spp., and sul and qnr resistance genes. Total concentrations of ciprofloxacin, sulfamethoxazole, and carbamazepine increased with irrigation duration reaching 95% of their upper limit of 1.4 µg/kg (ciprofloxacin), 4.3 µg/kg (sulfamethoxazole), and 5.4 µg/kg (carbamazepine) in soils irrigated for 19-28 years. Accumulation was soil-type-specific, with largest accumulation rates in Leptosols and no time-trend in Vertisols. Acidic pharmaceuticals (diclofenac, naproxen, bezafibrate) were not retained and thus did not accumulate in soils. We did not detect qnrA genes, but qnrS and qnrB genes were found in two of the irrigated soils. Relative concentrations of sul1 genes in irrigated soils were two orders of magnitude larger (3.15 × 10(-3) ± 0.22 × 10(-3) copies/16S rDNA) than in non-irrigated soils (4.35 × 10(-5)± 1.00 × 10(-5) copies/16S rDNA), while those of sul2 exceeded the ones in non-irrigated soils still by a factor of 22 (6.61 × 10(-4) ± 0.59 × 10(-4) versus 2.99 × 10(-5) ± 0.26 × 10(-5) copies/16S rDNA). Absolute numbers of sul genes continued to increase with prolonging irrigation together with Enterococcus spp. 23S rDNA and total 16S rDNA contents. Increasing total concentrations of antibiotics in soil are not accompanied by increasing relative abundances of resistance genes. Nevertheless, wastewater irrigation enlarges the absolute concentration of resistance genes in soils due to a long-term increase in total microbial biomass.


The dorsal hippocampus' role in context-based timing in rodents.
To act proactively, we must predict when future events will occur. Individuals generate temporal predictions using cues that indicate an event will happen after a certain duration elapses. Neural models of timing focus on how the brain represents these cue-duration associations. However, these models often overlook the fact that situational factors frequently modulate temporal expectations. For example, in realistic environments, the intervals associated with different cues will often covary due to a common underlying cause. According to the 'common cause hypothesis,' observers anticipate this covariance such that, when one cue's interval changes, temporal expectations for other cues shift in the same direction. Furthermore, as conditions will often differ across environments, the same cue can mean different things in different contexts. Therefore, updates to temporal expectations should be context-specific. Behavioral work supports these predictions, yet their underlying neural mechanisms are unclear. Here, we asked whether the dorsal hippocampus mediates context-based timing, given its broad role in context-conditioning. Specifically, we trained rats with either hippocampal or sham lesions that two cues predicted reward after either a short or long duration elapsed (e.g., tone-8 s/light-16 s). Then, we moved rats to a new context and extended the long cue's interval (e.g., light-32 s). This caused rats to respond later to the short cue, despite never being trained to do so. Importantly, when returned to the initial training context, sham rats shifted back toward both cues' original intervals. In contrast, lesion rats continued to respond at the long cue's newer interval. Surprisingly, they still showed contextual modulation for the short cue, responding earlier like shams. These data suggest the hippocampus only mediates context-based timing if a cue is explicitly paired and/or rewarded across distinct contexts. Furthermore, as lesions did not impact timing measures at baseline or acquisition for the long cue's new interval, our data suggests that the hippocampus only modulates timing when context is relevant.


Marijuana: dose effects on pulse rate, subjective estimates of intoxication, free recall and recognition memory.
The effect of marijuana on memory as measured by free recall and recognition, pulse rate and self ratings of intoxication was evaluated in 16 male volunteers. Marijuana containing 0, 5, 10 or 15 mg delta9-THC was administered to all subjects by smoking in 4 sessions separated by a 1 week interval. Free recall was reduced in a dose related manner by the drug, but recognition memory was unaffected. A 2 sec word presentation rate produced inferior recall in comparison to a 4 sec rate, but this variable did not interact with drug condition. Intrusion errors increased following intoxication but this effect was not systematically related to dosage of delta9-THC. Both pulse rate and self ratings of intoxication increased with dosage.


Interleukin-10 stimulation of corticotrophin releasing factor median eminence in rats: evidence for dependence upon nitric oxide production.
Following treatment with interleukin-10 (IL-10), basal corticotrophin releasing factor (CRF) levels from rat hypothalamic median eminence (ME) were found to be increased. Our data show: (1) the specificity of stimulation of CRF through the use of recombinant IL-10 and its blockage by monoclonal anti-IL-10 antibody; (2) the requirement of NO in this process through the use of N(omega)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor; (3) the blockage of IL-10 stimulated NO production by anti-IL-10; and, (4) the presence of IL-10 transcripts in hypothalamic poly A+ mRNA. These results provide the first evidence of IL-10 acting in the ME to influence CRF levels and further support our earlier findings of a potential for IL-10 in the hypothalamic-pituitary axis.


Clustering of unhealthy behaviors in a Brazilian population of industrial workers.
To analyze the clustering of four unhealthy behaviors (tobacco use, excessive alcohol consumption, physical inactivity and low consumption of fruits and vegetables) and their association with sociodemographic factors among adult industrial workers in Brazil. Data from 23 Brazilian states and the Federal District were collected via questionnaire from 2006 to 2008. Clustering of risk behaviors was identified using the ratio between the observed and expected percentages of each combination of unhealthy behaviors. Among the 44,477 workers surveyed, 18.0% of men and 11.4% of women accumulated three or four unhealthy behaviors. The most frequent combination was physical inactivity and low consumption of fruits and vegetables. The concurrent presence of all four behaviors was 86% higher in men and 148% higher in women than would be predicted if the frequency of these behaviors were independent. Presence of one or more negative behaviors was more frequent in men, younger individuals and in those with lower levels of education and family income than subjects without these characteristics. There was a strong tendency for unhealthy behaviors to assume combinatorial patterns, mainly in men, people with less education, income, and age, suggesting important disparities.


Conspecific and Human Sociality in the Domestic Cat: Consideration of Proximate Mechanisms, Human Selection and Implications for Cat Welfare.
Sociality can be broadly defined as the ability and tendency of individuals to reside in social groups with either conspecifics and/or other species. More specifically, sociability relates to the ability and tendency of individuals to display affiliative behaviours in such contexts. The domestic cat is one of the most globally popular companion animals and occupies a diverse range of lifestyles. Despite an arguably short period of domestication from an asocial progenitor, the domestic cat demonstrates an impressive capacity for both intra- and interspecific sociality and sociability. At the same time, however, large populations of domestic cats maintain various degrees of behavioural and reproductive autonomy and are capable of occupying solitary lifestyles away from humans and/or conspecifics. Within social groups, individuals can also vary in their tendency to engage in both affiliative and agonistic interactions, and this interindividual variation is present within free-living populations as well as those managed in confined environments by humans. Considerable scientific enquiry has focused on cats' social behaviour towards humans (and conspecifics to a much lesser extent) in this latter context. Ontogeny and human selection, in addition to a range of proximate factors including social and environmental parameters and individual cat and human characteristics, have been highlighted as important moderators of cats' sociability. Such factors may have important consequences regarding individuals' adaptability to the diverse range of lifestyles that they may occupy. Where limitations to individuals' social capacities do not enable sufficient adaption, compromises to their wellbeing may occur. This is most pertinent for cats managed by humans, given that the physical and social parameters of the cats' environment are primarily dictated by people, but that positive human-selection for traits that enhance cats' adaptability to such lifestyles appears to be limited. However, limitations in the availability and quality of evidence and equivocal findings may impede the current understanding of the role of certain factors in relation to cat sociability and associations with cat wellbeing, although such literature gaps also present important opportunities for further study. This review aims to summarise what is currently known about the various factors that may influence domestic cats' sociality and sociability towards both humans and conspecifics, with a predominant focus on cats managed by humans in confined environments. Current limitations, knowledge gaps, and implications for cat wellbeing are also discussed.


Multi-modal Medical Image Fusion Algorithm Based on Spatial Frequency Motivated PA-PCNN in the NSST Domain.
Image fusion has been grown as an effectual method in diseases related diagnosis schemes. In this paper, a new method for combining multimodal medical images using spatial frequency motivated parameter-adaptive PCNN (SF-PAPCNN) is suggested. The multi- modal images are disintegrated into frequency bands by using decomposition NSST. The coefficients of low frequency bands are selected using maximum rule. The coefficients of high frequency bands are combined by SF-PAPCNN. In this paper, a new method for combining multimodal medical images using spatial frequency motivated parameter-adaptive PCNN (SF-PAPCNN) is suggested. The multi-modal images are disintegrated into frequency bands by using decomposition NSST. The coefficients of low frequency bands are selected using maximum rule. The coefficients of high frequency bands are combined by SF-PAPCNN. The fused medical images is obtained by applying INSST to above coefficients. The quality metrics such as entropy ENT, fusion symmetry FS, deviation STD, mutual information QMI and edge strength QAB/F are used to validate the efficacy of suggested scheme.


Performance evaluation of eigendecomposition-based adaptive clutter filter for color flow imaging.
In this paper, a newly developed eigendecomposition-based adaptive filter is applied in flow velocity estimation and its performance is evaluated and compared with the static polynomial regression filter. Results demonstrate that the eigendecomposition-based filter is the fully-adaptive and can not only suppress the clutter signals with minimal loss of low-flow signal, but also give less influence on the flow velocity estimation especially under the circumstance of high clutter velocity.


Evidence that myosin light chain phosphorylation regulates contraction in the body wall muscles of the sea cucumber.
The Ca2+ activation mechanism of the longitudinal body wall muscles of Parastichopus californicus (sea cucumber) was studied using skinned muscle fiber bundles. Reversible phosphorylation of the myosin light chains correlated with Ca2+-activated tension and relaxation. Pretreatment of the skinned fibers with AT-P gamma S and high Ca2+ (10(-5)M) resulted in irreversible thiophosphorylation of the myosin light chains and activation of a Ca2+ insensitive tension. In contrast, pretreatment with low Ca2+ (10(-8)M) and ATP gamma S results in no thiophosphorylation of the myosin light chains or irreversible activation of tension. These results are consistent with a Ca2+-sensitive myosin light chain kinase/phosphatase system being responsible for the activation of the muscle. Other agents known to have an effect upon the Ca2+-activated tension in skinned vertebrate smooth muscle fibers (trifluoperazine, catalytic subunit of the cyclic AMP-dependent protein kinase, and calmodulin) did not have an effect on myosin light chain phosphorylation or Ca2+-activated tension. These results suggest a different type of myosin light chain kinase than is found in vertebrate smooth muscle is responsible for the activation of parastichopus longitudinal body wall muscle.


Lung ultrasound to detect and monitor pulmonary congestion in patients with acute kidney injury in nephrology wards: a pilot study.
Lung congestion and frank pulmonary edema are established complications of acute kidney injury (AKI) and early detection and monitoring of lung congestion may be useful for the clinical management of AKI patients. We compared standardized clinical criteria (including lung crackles and peripheral edema grading) and simultaneous chest ultrasound (US) to detect lung congestion in a series of 39 inpatients with AKI. At baseline, twelve patients (31%) were clinically euvolemic and twelve presented clear-cur cardiovascular congestion (31%) by clinical criteria. Fifteen patients (38%) were hypovolemic. The median number of US-B lines in patients with cardiovascular congestion was much higher (50, inter-quartile range 27-99) than in euvolemic (14, IQR 11-37) and hypovolemic patients (7, IQR 3-16, P < 0.001). Remarkably, a substantial proportion of asymptomatic euvolemic (66%) and hypovolemic (46%) patients had lung congestion of moderate to severe degree (> 15 US-B lines) by lung US. Crackles severity and the number of US-B lines over time were inter-related (Spearman's ρ = 0.38, P < 0.01) but the agreement (Cohen k statistics) between the two metrics was unsatisfactory. Forty-eight percent of patients had lung congestion of moderate to severe degree by lung US and this estimate by far exceeded that by clinical criteria (32%). This pilot study shows that chest US has potential for the detection of lung congestion at a pre-clinical stage in AKI. The results of this pilot study form the basis for a clinical trial testing the usefulness of this technique for guiding lung congestion treatment in patients with AKI.


Diagnostic value of serum cystatin C for diabetic nephropathy: a meta-analysis.
Although dozens of studies have investigated the relationship between the content of serum cystatin C (Cys-C) and diabetic nephropathy (DN), the results are still controversial. Hence, This study aims to explore the accuracy of serum Cys-C for diagnosing DN by meta-analysis. The studies about serum Cys-C diagnosing DN were searched from six online databases from inception to September 22, 2020. The data were processed by Stata 15.0 statistic software. The corresponding diagnostic effect sizes, such as sensitivity and specificity, were obtained. We drew a summary receiver operating characteristic (SROC) curve. We assess the risk of literature bias was following the QUADAS-2 guidelines. Twenty-six published studies were identified. The results showed a pooled sensitivity of 0.86 (95% confidence interval (CI): 0.82-0.90), specificity of 0.89 (95%CI: 0.85-0.92), positive likelihood ratio of 7.59 (95%CI: 5.66-10.19), negative likelihood ratio of 0.16 (95%CI: 0.12-0.21), and diagnostic odds ratio of 48.03 (95%CI: 30.64-75.29). The area under the SROC curve was given a value of 0.94 (95%CI: 0.91-0.96). Serum cystatin C has an excellent diagnostic value with good sensitivity and specificity for diabetic nephropathy.


Effect of aortic valve movements on gastrointestinal bleeding that occured in continuous flow left ventricular assist device patients.
Gastrointestinal (GI) bleeding is one of the recently reported complications with continuous flow left ventricular assist devices (LVAD). The pathophysiology and etiology are unclear. We sought to describe the relationship between aortic valve movements and GI bleeding among patients with a new generation of LVAD. We evaluated the data of 30 patients who underwent LVAD (HeartWare VAD) implantation from December 2010 to September 2012. The most common etiologic diagnosis was dilated cardiomyopathy. Patients were considered to show GI bleeding if they had hematemesis, melena, or hematochezia. Among 3 patients, 2 displayed upper GI bleeding and 1 had lower GI bleeding based on endoscopic and colononoscopic examinations. Pathological reports showed arteriovenous malformations in patients diagnosed with upper GI bleeding. The absence of aortic valve movements and a history of previous GI bleeding were significant risk factors (P = .021 and P = .007, respectively). In addition to aortic valve movements, we believe that a GI bleeding history was an equally important factor predisposing to this complication.


A study of H+ production using metal hydride and other compounds by means of laser ion source.
A laser ion source can provide wide variety of ion beams from solid target materials, however, it has been difficult to create proton beam efficiently. We examined capability of proton production using beeswax, polyethylene, and metal hydrides (MgH(2) and ZrH(2)) as target materials. The results showed that beeswax and polyethylene could not be used to produce protons because these targets are transparent to the laser wavelength of 1064 nm. On the other hand, the metal hydrides could supply protons. Although the obtained particle numbers of protons were less than those of the metal ions, the metal hydrides could be used as a target for proton laser ion source.


Trends in nasopharyngeal carriage of Streptococcus pneumoniae among children attending daycare centers in southeastern France from 1999 to 2006.
Pneumococcal nasopharyngeal carriage, serotype distribution, and penicillin-susceptibility were monitored among children attending daycare centers in France from 1999 to 2006 to assess the impact of pneumococcal conjugate vaccine and antibiotic-reducing policies. Pneumococcal carriage remained stable. Immunization rates reached 68% in 2006. Serotype distribution shifted significantly from vaccine serotypes to vaccine-related and nonvaccine serotypes. Antibiotic treatments fell by 50%.


The functional architecture for face-processing expertise: FMRI evidence of the developmental trajectory of the core and the extended face systems.
Expertise in processing faces is a cornerstone of human social interaction. However, the developmental course of many key brain regions supporting face preferential processing in the human brain remains undefined. Here, we present findings from an FMRI study using a simple viewing paradigm of faces and objects in a continuous age sample covering the age range from 6 years through adulthood. These findings are the first to use such a sample paired with whole-brain FMRI analyses to investigate development within the core and extended face networks across the developmental spectrum from middle childhood to adulthood. We found evidence, albeit modest, for a developmental trend in the volume of the right fusiform face area (rFFA) but no developmental change in the intensity of activation. From a spatial perspective, the middle portion of the right fusiform gyrus most commonly found in adult studies of face processing was increasingly likely to be included in the FFA as age increased to adulthood. Outside of the FFA, the most striking finding was that children hyperactivated nearly every aspect of the extended face system relative to adults, including the amygdala, anterior temporal pole, insula, inferior frontal gyrus, anterior cingulate gyrus, and parietal cortex. Overall, the findings suggest that development is best characterized by increasing modulation of face-sensitive regions throughout the brain to engage only those systems necessary for task requirements.


Vascular leakage, neovascularization, and vitreous hemorrhage in senile bullous retinoschisis.
Retinal detachment is the primary complication of bullous retinoschisis, a benign abnormality of the peripheral retina. We examined three patients (all women, 43, 55, and 56 years old) with typical bullous retinoschisis who had vitreous hemorrhage. In each case, there were sclerotic retinal vessels over the surface of the schisis cavity along with neovascularization above the central portion of the cyst. In one case there was also neovascularization of the peripheral retina in an area distant from the schisis. These findings were confirmed by fluorescein angiography in one case; the other two cases demonstrated similar changes by fluorescein angioscopy. Fluorescein angiography, also demonstrated intraretinal dye leakage from vessels along the posterior extent of the schisis, as well as from an adjacent area of white without pressure.


Biopsy in indeterminate intraocular tumors.
To describe an intraocular biopsy technique that allows accurate histopathologic diagnosis in cases of clinically unclassifiable uveal tumors. Retrospective noncomparative consecutive interventional case series. Intraocular biopsies were performed by a vitreous cutter either by a two-port clear cornea approach in 11 patients with unclassifiable iris tumors or by a three-port pars plana vitrectomy in 23 patients with unclassifiable choroidal tumors. Specimens were formalin fixed and paraffin processed. Hematoxylin-eosin and periodic acid-Schiff stains were performed in all cases, with additional immunohistochemical stains using the alkaline phosphatase, antialkaline phosphatase method in cases that could not be conventionally classified. Clinical observation and histopathologic examination of intraocular biopsies. In 97% of cases (n = 33) a definite diagnosis could be established by the biopsy specimen. A melanoma could be diagnosed in 73% of cases (n = 8) of iris tumors and in 57% of cases (n = 13) of posterior intraocular tumors. Other diagnoses included nevus, metastasis, vasoproliferative tumor, hemorrhage, gliosis, and scleritis. Complications were encountered in four cases: a vitreous hemorrhage occurred twice, an inconclusive biopsy result, and an intraocular tumor spread occurred once, respectively. No increased tumor-related mortality was observed after a mean follow-up of 44 months. Intraocular biopsy by a vitreous cutter allows the histopathologic examination of formalin-fixed paraffin-embedded tumor tissue. This increases the diagnostic accuracy, avoiding the risk of extraocular tumor spread seen with transscleral biopsy techniques.


A new index to monitor central visual field progression in glaucoma.
The visual field index (VFI) summarizes global visual field (VF) data and was developed to monitor glaucoma progression using 24-2 and 30-2 strategies. We applied similar principles and statistical procedures to develop a new parameter, the central field index (CFI), to monitor 10-2 VF progression. Retrospective cohort. Glaucoma patients with paracentral defects seen on 24-2 perimetry and followed up with at least 5 10-2 VF tests. The CFI was developed by calculating age-corrected defect depth at test points obtained during 10-2 examinations. The sensitivities at these points were scored as percentages similar to the method described for the VFI: 100-[(|total deviation|/age-corrected normal threshold) × 100]. A weighting procedure was applied based on published estimates of the occipital cortical spatial magnification. For validation, we performed mixed linear model testing for the association between CFI rates of change (%/year) and known risk factors for glaucoma progression in a population with established glaucoma and at least 5 10-2 VF tests. To determine whether the CFI was affected by cataract, as is known to occur with mean deviation (MD), we conducted a pilot evaluation comparing rates of CFI change in 3 groups: (1) eyes with cataract, (2) pseudophakic eyes, and (3) eyes in which cataract surgery was performed in the middle of the series. Rates of CFI and MD change. Central field index values were calculated for 176 eyes of 142 patients. The mean rate of CFI change of the entire sample was -1.10%/year (95% confidence interval, -1.03 to -1.16%/year). Elevated intraocular pressure (P<0.001) was associated significantly with faster CFI change, whereas lens status did not influence CFI rates of change (P>0.100) CONCLUSIONS: We developed and validated a new index to monitor central field progression that is minimally affected by the presence or removal of cataract and that correlates significantly with an important risk factor for glaucoma progression. This new index may become useful for glaucoma management, especially when combined with conventional static perimetry strategies.


Application of the microwave acid digestion technique to the pyrophosphoric acid method for quantitative analysis of free silica in dust.
An accurate and simple procedure for determining the quantity of free silica in respirable dust samples by the pyrophosphoric acid method was achieved by employing a closed vessel dissolution technique using microwave heating. Dissolution conditions were optimized by using quartz particles less than 10 microns in diameter as representative respirable-size free silica and potassium feldspar (K-feldspar) of the same size as the matrix. The technique enabled dissolution of 100 mg of K-feldspar by pyrophosphoric acid in 3 min. Quartz recovery was 97% under these conditions. The technique was also tested on mixtures of quartz and K-feldspar in various ratios with reproducible and accurate results. These data satisfy the requirements for analysis of small amounts of respirable dust samples in work environments.


Extubation Failure in a Burn Intensive Care Unit: Examination of Contributing Factors.
Extubation failure is associated with negative outcomes making the identification of risk factors for failure paramount. Burn patients experience a high incidence of respiratory failure requiring mechanical ventilation. There is no consensus on the acceptable rate of extubation failure and many conventional indices do not accurately predict extubation outcomes in burn patients. The purpose of this study was to examine the rate of extubation failure in the burned population and to examine the impact of factors on extubation outcomes. Burn patients from a single center over 9 years were examined and included if they were intubated prior to arrival or within 48 hours of admission and underwent a planned extubation. From this cohort, a matched case-control analysis based on age, TBSA, and sex was performed of patients who succeeded after extubation, defined as not requiring reintubation within 72 hours, to those who failed. Characteristics and clinical parameters were compared to determine whether any factors could predict extubation failure. There was a 12.3% incidence of extubation failure. In the matched case-control analysis, the presence of inhalation injury was associated with extubation success. Higher heart rate and lower serum pH were associated with extubation failure. ANCOVA analysis demonstrated that a sodium trending higher before extubation was associated with more successes, possibly indicative of a lower volume status. Classic extubation criteria do not accurately predict extubation outcomes in burn patients; analysis of other parameters may be able to provide better predictions. A constellation of these parameters needs to be studied prospectively.


Opposing effects of ecdysone signaling regulate neuroblast proliferation to ensure coordination of brain and organism development.
Growth regulation must be robust to ensure correct final size, but also adaptative to adjust to less favorable environmental conditions. Developmental coordination between whole-organism and the brain is particularly important, as the brain is a critical organ with little adaptability. Brain growth mainly depends on neural stem cell (NSC) proliferation to generate differentiated neural cells, it is however unclear how organism developmental progression is coordinated with NSCs. Here we demonstrate that the steroid hormone ecdysone plays a multi-step, stage specific role in regulating Drosophila NSCs, the neuroblasts. We used animals that are unable to synthesize ecdysone, to show that the developmental milestone called "critical weight peak", the peak that informs the body has reached minimum viable weight to survive metamorphosis, acts a checkpoint necessary to set neuroblast cell cycle pace during larval neurogenesis. The peaks of ecdysone that occur post-critical weight are no longer required to maintain neuroblast division rate. We additionally show that in a second stage, at the onset of pupariation, ecdysone is instead required to trigger neuroblast's proliferation exit and consequently the end of neurogenesis. We demonstrate that, without this signal from ecdysone, neuroblasts lose their ability to exit proliferation. Interestingly, although these neuroblasts proliferate for a longer period, the number of differentiated neurons is smaller compared to wild-type brains, suggesting a role for ecdysone in neuron maintenance. Our study provides insights into how neural stem cells coordinate their division rate with the pace of body growth, identifying a novel coordination mechanism between animal development and NSC proliferation.


Microgap and bacterial microleakage during the osseointegration period: An in vitro assessment of the cover screw and healing abutment in a platform-switched implant system.
Microgap and bacterial microleakage at the implant-prosthetic abutment interface are recognized concerns for implant-supported restorations, leading to inflammation of the peri-implant tissues, with deleterious consequences for crestal bone levels. However, little is known regarding the interface established between the implant and the healing abutment or cover screw placed for the osseointegration phase. The purpose of this in vitro study was to characterize the implant-cover screw and implant-healing abutment interfaces of a platform-switched implant system to determine the microgap and bacterial microleakage of the system and evaluate the biological response and functionality of an interface sealing agent. The interfacial microgaps of the implant-healing abutment and implant-cover screw interfaces were characterized by scanning electron microscopy (n=10), and bacterial microleakage was evaluated after colonization with Enterococcus faecalis in a 30-day follow-up (n=10). The sealing efficacy and irritation potential of a silicone-based sealer were determined by using the hen's egg test on chorioallantoic membrane assay. The 2-sample t test was performed to compare means between groups, and data presented with the Kaplan-Meier method were compared statistically by using the log-rank test (α=.05). The interfacial microgap was less than 2.5 μm for both systems. Bacterial microleakage was noted in approximately 50% of the specimens, particularly at early time points, at both the healing abutment and cover screw interfaces. The silicone-based sealer prevented bacterial leakage in the experimental setting. The implant-healing abutment and implant-cover screw interfaces of the tested system, despite the low microgap, allowed for bacterial microleakage after internal colonization. The use of a nonirritating silicone-based sealing agent effectively sealed the system.


Learning through teaching: empowering students and culturally diverse patients at a community-based nursing care center.
This article addresses the effect of a nursing care center on student learning. Associate degree nursing students spend clinical days at a nursing care center that was created in collaboration with an inner-city clinic serving individuals who are uninsured and underinsured. The nursing students learn cultural sensitivity, teaching strategies, and interdisciplinary skills. The service-learning experience benefits the nursing students, the nursing department of the college, the patients who visit the nursing care center, the clinic, and the community. This article describes the development of the nursing care center, examples of teaching-learning opportunities, and evidence of student learning. This successful collaboration between a community college and an inner-city clinic can be Associareplicated by other nursing programs.


[Hb 1.1 g/dl: successful treatment of a polytraumatized patient in hemorrhagic shock].
We report on the successful treatment of a seriously traumatized patient (injury severity score=59) who presented with exsanguinating hemorrhage in the emergency room. Preclinical and emergency room management included "small volume" hypertonic resuscitation as well as massive transfusion, C-clamp stabilization of a pelvic ring instability, and attachment of external fixators to multiple bone fractures. During the intensive care period,we started enteral immunonutrition immediately after an abdominal compartment syndrome was removed by laparotomy and a jejunal catheter had been inserted. Multiple fractures were stabilized rapidly and the soft tissue wounds were covered by split skin grafts. Additionally, we provided sufficient analgesia with few side effects using an epidural catheter for continuous application of local anesthetics. In summary, an effective synthesis of up-to-date strategies for preclinical, emergency room, and intensive care management prevented multiple organ failure and achieved survival with good quality of life after a "fatal" multiple trauma.


Survey of chemotherapy of metastatic renal cancer.
A critical survey is made of cytotoxic chemotherapy of metastatic renal cancer. On the basis of representative summaries, only a few substances such as vinblastine, CCNU, hydroxyurea, and ifosfamide seem to act with some degree of success, but no specific antirenal cancer agent has as yet become available. This outline should provide a more realistic view of the therapeutic possibilities and of the limits of cytostatic chemotherapy in the metastatic phase of renal cancer. It is postulated that chemotherapy should feature more prominently in future therapeutic strategies. Newer cytostatic substances, i.e., second-generation alkylating agents and anthracyclines as well as platinum analogues, may present an advance with regard to side effects and tolerance but are discouraging with regard to their therapeutic efficiency in metastatic renal cancer.


Degenerative cartilage lesions of the hip--magnetic resonance evaluation.
The capability of magnetic resonance imaging (MRI) to visualize early degenerative arthritis of the hip was investigated. The study was performed on 8 healthy students and 45 elderly volunteers. Images were obtained by using an electronically variable Helmholtz coil (switched-array coil, SAC). In order to diagnose degenerative lesions of the joint cartilage, FISP sequences with a flip angle of 70 degrees were found preferable to compared sequences. MRI-detectable signs of degenerative arthritis of the hip were narrowed joint space due to partially thinned cartilage layers, focal areas of either increased or decreased signal intensity in the hyaline cartilage, complete loss of cartilage, and signal variation in the bone marrow. MRI of the hip may be appropriate to detect early degenerative changes in the hips of young high-risk patients to facilitate therapy planning.


The use of corticosteroid as treatment in SARS was associated with adverse outcomes: a retrospective cohort study.
To study the effect of corticosteroids in the treatment of severe acute respiratory syndrome (SARS). A retrospective cohort of 78 consecutive adult SARS patients admitted to a regional hospital in Hong Kong between March and May 2003 was analysed to study the effectiveness of corticosteroid. They were categorized according to whether or not corticosteroid therapy was given, and compared in terms of demographic characteristics, comorbidities, peak lactate dehydrogenase (LDH) levels and clinical outcomes. Established adverse prognostic factors including old age, comorbidities and high LDH levels were used as covariates in multiple logistic regressions to adjust for their confounding effect on adverse outcomes. Among 78 patients, 66 patients (84.6%) received corticosteroid. The LDH level was similar in both groups. The corticosteroid group had more adverse outcomes (37.9% vs. 16.7%) despite younger age and less comorbidity. In multivariate analysis, corticosteroid treatment was associated with a 20.7-fold increase in risk of either ICU admission or mortality, independent of age and disease severity. Despite more favourable baseline characteristics and similar peak LDH levels, SARS patients given corticosteroid had more adverse outcomes.


Evaluation of WO2013076170: the use of a dihydroorotate dehydrogenase inhibitor for the treatment of psoriasis.
Inhibition of dihydroorotate dehydrogenase (DHODH) modulates pyrimidine biosynthesis. Effective inhibitors are immunomodulatory drugs clinically useful in the treatment of diseases such as rheumatoid arthritis, psoriatic arthritis and multiple sclerosis. There is limited evidence of their potential utility in treating psoriasis. This patent application claims topical formulations of the non-hepatotoxic DHODH inhibitor 2-[(3,5-difluoro-3'-methoxy-1,1'-biphenyl-4-yl)amino]nicotinic acid for use in the treatment of psoriasis. This inhibitor had previously been claimed to be useful in treating various autoimmune disease.