A face a mother could love: depression-related maternal neural responses to infant emotion faces.
Depressed mothers show negatively biased responses to their infants' emotional bids, perhaps due to faulty processing of infant cues. This study is the first to examine depression-related differences in mothers' neural response to their own infant's emotion faces, considering both effects of perinatal depression history and current depressive symptoms. Primiparous mothers (n = 22), half of whom had a history of major depressive episodes (with one episode occurring during pregnancy and/or postpartum), were exposed to images of their own and unfamiliar infants' joy and distress faces during functional neuroimaging. Group differences (depression vs. no-depression) and continuous effects of current depressive symptoms were tested in relation to neural response to own infant emotion faces. Compared to mothers with no psychiatric diagnoses, those with depression showed blunted responses to their own infant's distress faces in the dorsal anterior cingulate cortex. Mothers with higher levels of current symptomatology showed reduced responses to their own infant's joy faces in the orbitofrontal cortex and insula. Current symptomatology also predicted lower responses to own infant joy-distress in left-sided prefrontal and insula/striatal regions. These deficits in self-regulatory and motivational response circuits may help explain parenting difficulties in depressed mothers.


NADPH-induced oxidative damage of rat liver microsomes: protective role of chlorpromazine and trifluoperazine.
Two widely used antipsychotic drugs, chlorpromazine (CPZ) and trifluoperazine (TFZ) inhibit NADPH-induced microsomal lipid peroxidation (LPO). Study of microsomal membrane fluidity revealed considerable disorganization in its architecture in the presence of NADPH, which can be restored back in the presence of CPZ and TFZ. NADPH-dependent microsomal LPO is catalyzed by NADPH: cytochrome P450 reductase. These drugs also inhibit the activity of this enzyme. TFZ always shows stronger inhibitory effect than CPZ. TFZ contains a trifluromethyl group (CF3) in its second position that gives rise to stronger electron abstraction tendency by which LPO and NADPH: cytochrome P450 reductase activity is inhibited more potently than by CPZ which contains a chlorine ligand in the same position. Due to the stronger antioxidant property of TFZ, it can be prescribed as a better therapeutic agent, which plays a protective role for the cellular system.


Penicillamine-protected Ag20 nanoclusters and fluorescence chemosensing for trace detection of copper ions.
We report the synthesis of penicillamine-protected Ag20 nanoclusters (NCs), with properties of high monodispersity, red fluorescence and water solubility. Full characterization of the Ag20 NCs is addressed, along with first-principles optimization calculations, revealing the chemical composition and structure of the as-prepared Ag NCs within a molecular formula [Ag20(DPA)18-H]-. Moreover, natural bond orbital (NBO) analysis demonstrates the charge-transfer interactions between the ligand and Ag atoms, and helps in understanding the origins of fluorescence of Ag20 NCs related to the ligand-to-metal charge transfer (LMCT) mechanism. Further, fluorescence chemosensing of the Ag20 NCs is demonstrated for tracing copper ions with high sensitivity and selectivity in aqueous solution.


Collagen XVII is expressed in malignant but not in benign melanocytic tumors and it can mediate antibody induced melanoma apoptosis.
The 180 kDa transmembrane collagen XVII is known to anchor undifferentiated keratinocytes to the basement membrane in hemidesmosomes while constitutively shedding a 120 kDa ectodomain. Inherited mutations or auto-antibodies targeting collagen XVII cause blistering skin disease. Collagen XVII is down-regulated in mature keratinocytes but re-expressed in skin cancer. By recently detecting collagen XVII in melanocyte hyperplasia, here we tested its expression in benign and malignant melanocytic tumors using endodomain and ectodomain selective antibodies. We found the full-length collagen XVII protein in proliferating tissue melanocytes, basal keratinocytes and squamous cell carcinoma whereas resting melanocytes were negative. Furthermore, the cell-residual 60 kDa endodomain was exclusively detected in 62/79 primary and 15/18 metastatic melanomas, 8/9 melanoma cell lines, HT199 metastatic melanoma xenografts and atypical nests in 8/63 dysplastic nevi. The rest of 19 nevi including common, blue and Spitz subtypes were also negative. In line with the defective ectodomain, sequencing of COL17A1 gene revealed aberrations in the ectodomain coding region including point mutations. Collagen XVII immunoreaction-stained spindle cell melanomas, showed partly overlapping profiles with those of S100B, Melan A and HMB45. It was concentrated at vertical melanoma fronts and statistically associated with invasive phenotype. Antibody targeting the extracellular aa507-529 terminus of collagen XVII endodomain promoted apoptosis and cell adhesion, while inhibiting proliferation in HT199 cells. These results suggest that the accumulation of collagen XVII endodomain in melanocytic tumors is associated with malignant transformation to be a potential marker of malignancy and a target for antibody-induced melanoma apoptosis.


Nanoconfined surfactant templated electrodeposition to porous hierarchical nanowires and nanotubes.
Porous metal (Pd and Co) and semiconductor (ZnO) nanowires, porous metal (Pt and Ni) nanotubes, and unique multiple Pt nanowires are prepared from a novel nanoconfined surfactant templated electrodeposition approach. More specifically, the overall diameter of nanowires or nanotubes is defined by the pore channels of membranes. Surfactant assembled structure nanoconfined within the pores of membranes is used to generate the porosity and to control the texture of the nanowires or nanotubes. As compared to solid nanowires and nanotubes, the porous nanowires and nanotubes exhibit unique properties. For example, porous cobalt nanowires show higher coercivity.


Beta-adrenoceptor responsiveness in intact leukocytes from adults and newborn infants; effect of phosphodiesterase inhibitors.
Intact mononuclear and polymorphonuclear leukocytes from adults and newborn infants were used to estimate the beta 2-adrenoceptor responsiveness in vitro. The accumulation of cAMP in response to receptor stimulation by isoprenaline was used as a measure of the receptor responsiveness. The relevance of the method is dependent on the activity of the cAMP phosphodiesterase inside the cells. The xanthine derivatives, theophylline (4 mmol l-1) and 3-isobutyl-l-methyl-xanthine (0.1-2.5 mmol l-1), were used to inhibit the cAMP phosphodiesterase activity. It appears that 3-isobutyl-l-methyl-xanthine at 2.5 mmol l-1 inhibits the phosphodiesterase activity almost completely. By use of this concentration no age-dependent changes in the isoprenaline-stimulated cAMP accumulation in mononuclear and polymorphonuclear leukocytes from adults and newborn infants could be demonstrated.


Cross-linking induces homodimer formation and inhibits enzymatic activity of chicken stomach ecto-apyrase.
We have investigated the effect of cross-linking on the enzymatic activity and oligomer formation of the chicken stomach ecto-apyrase. Cross-linking with the hydrophobic, lysine-specific dithiobis(succinimidylpropionate) (DSP) caused equal inhibition of ATPase and ADPase activity in both the membrane-bound and detergent-solubilized ecto-apyrase. The inhibitory effect of cross-linking was reversed upon the addition of the reductant dithiothreitol. Western blots of aliquots of the cross-linked samples show decreased amounts of the monomeric 80 kDa ecto-apyrase and the appearance of a 160 kDa dimer under conditions inducing enzyme inhibition. Therefore, the chicken stomach ecto-apyrase, like the chicken gizzard ecto-ATPase, is likely a homodimer in vivo. Unlike the related gizzard ecto-ATPase, however, the native stomach ecto-apyrase is not stimulated, but rather inhibited by cross-linking, presumably due to different quaternary structural stability of the two enzymes.


Effects of amino acid infusions on liver regeneration after partial hepatectomy in the rat.
Administration of solutions high in branched-chain amino acids (BCAA) has been advocated in patients with severe liver failure; however, the effect of this treatment on the process of liver regeneration is still unclear. In the present study using rats we investigated the influence on liver regeneration of infusing solutions differing in amino acid content. After 75% hepatectomy, rats were infused via jugular vein with one of the following solutions: Sol A) 10% dextrose, Sol B) 10% dextrose + 3% amino acids (22% BCAA), Sol C) 10% dextrose + 3% amino acids (35% BCAA). Liver regeneration was estimated by measuring the incorporation of 3H-thymidine into DNA at five different time points after the operation. Peak regeneration occurred earlier in rats infused with the BCAA-enriched solution compared to animals infused with the standard amino acid solution or with dextrose alone. The increased incorporation of 3H-thymidine into DNA at 24 hr in rats infused with the BCAA-enriched solution was associated with elevated plasma levels of BCAA and decreased concentrations of tyrosine, phenylalanine, and methionine in comparison with the other two treatment groups. These results suggest that liver regeneration in rats can be accelerated by administering a parenteral nutrition solution tailored to normalize the deranged pattern of plasma amino acids associated with compromised liver function.


Cryodiluents optimization of Glossogobius giuris (hamilton-buchanan) spermatozoa.
Biodiversity conservation by germplasm maintenance by cryobanks is an accepted way of saving species. The edible fish Glossogobius giuris is reported to be threatened in India and needs rehabilitation measures to improve their numbers in natural waters. To investigate the standardization of cryoprotectants for the preservation of male gametes of this species. Four different cryoprotectants were used: DMSO, glycerol, ethylene glycol and methanol. Different combinations of diluents and milt were processed inside a cold handling unit at -5 degree C and stored for the short-term. Prior to exposure to cryoprotectants, the motility of fresh sperm was 98.3 ± 2.5%. After 10 min equilibration at room temperature in 7.5 % glycerol, sperm motility was 95.6 1.5%, and 93 , 3.2% after 180 min at -5 degree C in this cryoprotectant. In contrast, motility was 65C3% after equilibration in 12.5 % methanol, and survivability fell to 30.7 0.9% after 180 min storage at -5 degree C. Analysis by Bonferroni and Holm Multiple Comparison showed highly significant variations between the effect of methanol and the other cryoprotectants. There was a statistically significant fall in motility when using methanol compared to glycerol. Glycerol provides greater protection to spermatozoa during cold storage at -5 degree C, possibly as a result of its membrane stabilizing power.


Gill Transcriptome Analysis Revealed the Difference in Gene Expression Between Freshwater and Seawater Acclimated Guppy (Poecilia reticulata).
Guppy (Poecilia reticulata) can adapt to a wide range of salinity changes. To investigate the gene expression changes in the guppy exposed to seawater, we characterized its gill transcriptome using RNA sequencing. Experimental fish were exposed to salinity increase from 0 to 30‰ within 4 days, while control fish were cultured in freshwater (0‰ salinity). Seven days after salinity exposure, the gills were sampled and the mortality within 2 weeks was recorded. No significant difference in the cumulative mortality at the second week was found between the two groups. Transcriptomic analysis identified 3477 differentially expressed genes (DEGs), including 1067 upregulated and 2410 downregulated genes. These DEGs were enriched in several biological processes, including ion transport, ion homeostasis, ATP biosynthetic process, metabolic process, and immune system process. Oxidative phosphorylation was the most activated pathway. DEGs involved in the pathway "endoplasmic reticulum (ER)-mediated phagocytosis," "starch and sucrose metabolism," and "steroid biosynthesis" were mainly downregulated; chemokines and interleukins involved in "cytokine-cytokine receptor interaction" were differentially expressed. The present results suggested that oxidative phosphorylation had essential roles in osmoregulation in the gills of seawater acclimated guppy, during which the decline in the expression of genes encoding V-ATPases and calreticulin had a negative effect on the phagocytosis and immune response. Besides, several metabolic processes including "starch and sucrose metabolism" and "steroid biosynthesis" were affected. This study elucidates transcriptomic changes in osmotic regulation, metabolism, and immunity in seawater acclimated guppy.


Protection by borneol on cortical neurons against oxygen-glucose deprivation/reperfusion: involvement of anti-oxidation and anti-inflammation through nuclear transcription factor κappaB signaling pathway.
Borneol, a terpene and bicyclic organic compound found in several species, can easily penetrate the blood-brain barrier (BBB) and helps the absorption of many agents through BBB in the brain, but there has been no study about its direct action on neurons in the CNS. In the present study, we used an in vitro ischemic model of oxygen-glucose deprivation followed by reperfusion (OGD/R) to investigate the neuroprotective effects of borneol and the related mechanisms. We demonstrated that borneol reversed OGD/R-induced neuronal injury, nuclear condensation, intracellular reactive oxygen species (ROS) generation, and mitochondrial membrane potential dissipation. The elevation of nitric oxide (NO), the increase of inducible nitric oxide synthase (iNOS) enzymatic activity and the upregulation of iNOS expression were also attenuated by borneol. The inhibition of caspase-related apoptotic signaling pathway was consistently involved in the neuroprotection afforded by borneol. Meanwhile, borneol inhibited proinflammatory factor release and IκBα degradation, and blocked nuclear transcription factor κappaB (NF-κB) p65 nuclear translocation induced by OGD/R. On the other hand, borneol did not show obvious effect on the inhibition of phospho-IKKα activation. Furthermore, it failed to affect the OGD/R-induced enhanced level of phospho-SAPK/JNK. In conclusion, our study indicated that borneol protects against cerebral ischemia/reperfusion injury through multifunctional cytoprotective pathways. The mechanisms of this reversal from OGD/R may be involved in the alleviation of intracellular ROS and iNOS/NO pathway, inhibition of inflammatory factor release and depression of caspase-related apoptosis. Among these effects, the inhibition of IκBα-NF-κB and translocation signaling pathway might play a significant role in the neuroprotection of borneol.


[Emotional alterations in attention deficit hyperactivity disorder: existing data and open questions].
Research on attention deficit hyperactivity disorder (ADHD) has focused mainly on cognitive aspects, leaving in the background the study of the affective deficiencies accompanying the disorder. To review the research on emotional competence of children, teenagers and adults with ADHD (recognition, regulation, and expression of emotions), and identify which issues have been scarcely studied yet and require further attention. Convergent data from different behavioral studies indicate that children as well as adults with ADHD show a primary dysfunction in the recognition of emotional stimuli (facial expression and affective prosody), and an important disability to modulate their emotions, specially the negative ones. Nevertheless, the existing knowledge concerning the emotional dysfunctions in ADHD is limited, and several open questions, most of them concerning the neural basis underlying these dysfunctions, still remain. The present review highlights the need to develop new research in the study of emotional dysfunctions in ADHD using not only behavioral measures, but also cerebral activity measures, and to assess and treat emotional problems in the clinical practice.


[Comparison of functional outcome in implantation of Natural Knee knee prostheses with and without patellar resurfacing].
Despite the great progress in knee arthroplasty made within the previous decade the problem of patellar resurfacing is still unsolved. In a retrospective matched-pairs study in 62 patients with Natural Knee endoprostheses including one group with and another without patella resurfacing were compared. Results were assessed according to the American Knee Society Score and the patients subjective assessments. At an average follow-up time 2 years there were no differences in the clinical findings and the patients subjective opinions between both patient groups. However, patients with rheumatoid arthritis and patella resurfacing showed significantly better results in both categories than those rheumatoid patients without patella resurfacing. Summing our results up we cannot give a general advise towards the use of patella resurfacing in knee replacements. In patients with severe arthrosis of the femoro-patellar joint and in patients with rheumatoid arthritis, however, the patella replacement is considered to be the therapy of choice at our department.


Genomic Analysis of Antibiotic-Resistant Staphylococcus epidermidis Isolates From Clinical Sources in the Kwazulu-Natal Province, South Africa.
Staphylococcus epidermidis has become an important nosocomial pathogen. Multidrug resistance makes S. epidermidis infections difficult to treat. The study aims to describe the genomic characteristics of methicillin-resistant S. epidermidis (MRSE) isolated from clinical sources, to comprehend the genetic basis of antibiotic resistance, virulence, and potential pathogenicity. Sixteen MRSE underwent whole-genome sequencing, and bioinformatics analyses were carried out to ascertain their resistome, virulome, mobilome, clonality, and phylogenomic relationships. In all, 75% of isolates displayed multidrug resistance and were associated with the carriage of multiple resistance genes including mecA, blaZ, tet(K), erm(A), erm(B), erm(C), dfrG, aac(6')-aph(2''), and cat(pC221) conferring resistance to β-lactams, tetracyclines, macrolide-lincosamide-streptogramin B, aminoglycosides, and phenicols, which were located on both plasmids and chromosomes. Their virulence profiles were evidenced by the presence of genes involved in adherence/biofilm formation (icaA, icaB, icaC, atl, ebh, and ebp), immune evasion (adsA, capC, and manA), and antiphagocytosis (rmlC, cdsA, and A). The community-acquired SCCmec type IV was the most common SCCmec type. The CoNS belonged to seven multilocus sequence types (MLSTs) and carried a diversity of mobile genetic elements such as phages, insertion sequences, and plasmids. The bacterial anti-phage defense systems clustered regularly interspaced short palindromic repeats/CRISPR-associated (CRISPR-Cas) immunity phage system and restriction-modification system (R-M system) and the arginine catabolic mobile element (ACME) involved in immune evasion and transport of virulence genes were also found. The insertion sequence, IS256, linked with virulence, was found in 56.3% of isolates. Generally, the isolates clustered according to STs, with some similarity but also considerable variability within isolates. Whole-genome sequencing and bioinformatics analysis provide insights into the likely pathogenicity and antibiotic resistance of S. epidermidis, necessitating surveillance of this emerging pathogen.


Groundwater Chemistry and Blood Pressure: A Cross-Sectional Study in Bangladesh.
Background: We assessed the association of groundwater chemicals with systolic blood pressure (SBP) and diastolic blood pressure (DBP). Methods: Blood pressure data for ≥35-year-olds were from the Bangladesh Demographic and Health Survey in 2011. Groundwater chemicals in 3534 well water samples from Bangladesh were measured by the British Geological Survey (BGS) in 1998-1999. Participants who reported groundwater as their primary source of drinking water were assigned chemical measures from the nearest BGS well. Survey-adjusted linear regression methods were used to assess the association of each groundwater chemical with the log-transformed blood pressure of the participants. Models were adjusted for age, sex, body mass index, smoking status, geographical region, household wealth, rural or urban residence, and educational attainment, and further adjusted for all other groundwater chemicals. Results: One standard deviation (SD) increase in groundwater magnesium was associated with a 0.992 (95% confidence interval (CI): 0.986, 0.998) geometric mean ratio (GMR) of SBP and a 0.991 (95% CI: 0.985, 0.996) GMR of DBP when adjusted for covariates except groundwater chemicals. When additionally adjusted for groundwater chemicals, one SD increase in groundwater magnesium was associated with a 0.984 (95% CI: 0.972, 0.997) GMR of SBP and a 0.990 (95% CI: 0.979, 1.000) GMR of DBP. However, associations were attenuated following Bonferroni-correction for multiple chemical comparisons in the full-adjusted model. Groundwater concentrations of calcium, potassium, silicon, sulfate, barium, zinc, manganese, and iron were not associated with SBP or DBP in the full-adjusted models. Conclusions: Groundwater magnesium had a weak association with lower SBP and DBP of the participants.


Brain metastasis in lung cancer. Comparison of cerebral MRI and 18F-FDG-PET/CT for diagnosis in the initial staging.
FDG-PET/CT is increasingly used in staging of lung cancer as single "one stop shop" method. AIM, PATIENTS, METHODS: We prospectively included 104 neurological asymptomatic patients (65 years, 26% women) with primary diagnosis of lung cancer. In all patients PET/CT including cerebral imaging and cerebral MRI were performed. Diagnosis of brain metastases (BM) was made by PET/CT in 8 patients only (7.7%), by MRI in 22 (21.2%). In 80 patients both PET/CT and MRI showed no BM. In 6 patients (5.8%) BM were detectable on PET/CT as well as on MRI. Exclusive diagnosis of BM by MRI with negative finding on PET/CT was present in 16 patients (15.4%). 2 patients (1.9%) had findings typical for BM on PET/CT but were negative on MRI. With MRI overall 100 BM were detected, with PET/CT only 17 BM (p < 0.01). For the diagnosis of BM PET/CT showed a sensitivity of 27.3%, specificity of 97.6%, positive predictive value of 75% and negative predictive value of 83.3%. BM diameter on PET/CT and MRI were consistent in 43%, in 57% BM were measured larger on MRI. Compared to the gold standard of MRI for cerebral staging a considerable number of patients are falsely diagnosed as free from BM by PET/CT. MRI is more accurate than PET/CT for detecting multiple and smaller BM. In patients with a curative option MRI should be performed additionally to PET/CT for definitive exclusion of brain metastases.


A platform for x-ray absorption fine structure study of dynamically compressed materials above 1 Mbar.
A platform consisting of a multi-shock drive and an implosion backlighter has been developed for x-ray absorption fine structure (XAFS) measurements on materials compressed to multi-Mbar pressures. The experimental setup, target design, and backlighter characteristics are presented. Extended XAFS (EXAFS) measurements for various materials have been demonstrated. A quintuple-crystal design is described to enhance the efficiency of the x-ray spectrometer, enabling observation of very weak EXAFS signals in a single shot.


Genotoxicity assessment of Rokanol B2 and Rokamid R1.
Two surface-active compounds, Rokanol B2 and Rokamid R1, were examined with three types of screening tests: 1. standard Ames test in vitro using S. typhimurium TA97a, TA98, TA100 and TA102 strains; 2. micronucleus test in vivo; 3. sister chromatid exchange (SCE) on bone marrow cells of Balb C mice. Negative results of the testing, in terms of the effects of activity of both the technical preparations on S. typhimurium cells and bone marrow of Balb C mice, were found for both tested chemicals.


Resistance to CD4+CD25+ regulatory T cells and TGF-beta in Cbl-b-/- mice.
Cbl-b(-/-) mice have signaling defects that result in CD28-independent T cell activation, increased IL-2 production, hyper-reactive T cells, and increased autoimmunity. Although the increased autoimmunity in these mice is believed to result from the hyper-reactive T cells, the mechanisms leading from T cell hyper-reactivity to autoimmunity remain unclear. Specifically, the function and interaction of CD4(+)CD25(+) regulatory T cells (T(reg)) and CD4(+)CD25(-) effector T cells (T(eff)) in Cbl-b(-/-) mice have not been examined. We now report that Cbl-b(-/-) CD4(+)CD25(+) T(reg) exhibit normal regulatory function in vitro. In contrast, the in vitro response of Cbl-b(-/-) CD4(+)CD25(-) T(eff) is abnormal, in that it is not inhibited by either Cbl-b(-/-) or wild-type T(reg). This resistance of Cbl-b(-/-) T(eff) to in vitro regulation is seen at the levels of both DNA synthesis and cell division. In addition to this resistance to CD4(+)CD25(+) T(reg), Cbl-b(-/-) T(eff) demonstrate in vitro resistance to inhibition by TGF-beta. This second form of resistance in Cbl-b(-/-) T(eff) is seen despite the expression of normal levels of type II TGF-beta receptors and normal levels of phosphorylated Smad3 after TGF-beta stimulation. Coupled with recent reports of resistance to T(reg) in T(eff) exposed to LPS-treated dendritic cells, our present findings suggest that resistance to regulation may be a relevant mechanism in both normal immune function and autoimmunity.


[A new star in the heavens of epidermal proteins: loricrin--what is it?].
A cDNA clone, encoding for a major component of the cornified cell envelope now termed loricrin, was isolated by cross-hybridization with the end domains of keratin 1 and 10. Loricrin is expressed very late in terminal epidermal differentiation in the upper stratum granulosum and is identical to the sulfur-rich component of the single type keratohyaline granule. Moreover, loricrin appears later to become cross-linked by the formation of glutamyl-lysyl-isopeptide bonds and thereby incorporated as a major component into the cornified cell envelope. In vivo, loricrin is expressed in all mammalian stratified epithelia tested so far. However, the highest levels of expression are found in humid tissues such as newborn epidermis, the epithelia of oral and anal mucosa, esophagus, foreskin, vagina and the epidermal parts of sweat ducts.


Hepatoma-derived growth factor promotes growth and metastasis of hepatocellular carcinoma cells.
We aimed to elucidate the effects of hepatoma-derived growth factor (HDGF) on growth and metastasis of hepatocellular carcinoma (HCC) cells. Tissue microarrays with 236 HCC specimens and 18 extrahepatic metastases were utilized to detect the HDGF expression by immunohistochemistry. Meanwhile, HDGF expressions in HCC cell lines with different metastatic potentials were examined using immunofluorescence staining, real-time PCR and western blotting. After HDGF silencing, the growth and metastatic potentials of HCC cells were evaluated by soft agar assay, invasion assay, together with tumorigenicity assay in nude mice. The gelatin zymography was performed by detecting MMP-2 and MMP-9 levels. Additionally, western blotting was conducted to determine the levels of total and phosphorylated ERK1/2, JNK, p38 and Akt. The results showed that HDGF was overexpressed in HCC metastasis tumour, and the expression increased with the differentiation degree of tumours (Grade I 44.0%, Grade II 48.4% and Grade III 65.6%). Consistently, HDGF levels were positively associated with the metastatic capability of HCC cells (MHCC97L < MHCC97H < HCCLM3). The growth and metastasis were suppressed by HDGF-siRNA. Gelatinolytic activities were enhanced in the three metastatic HCC cell lines, but had no significant difference among them. The tumourigenicity and metastatic capability of HCCLM3 cells in nude mice were inhibited after silencing HDGF. Meanwhile, HDGF-siRNA specifically suppressed the total and phosphorylated protein levels of ERK1/2, while not JNK, p38 and Akt. In conclusion, HDGF was overexpressed in HCC patients and cells, and HDGF might be closely correlated with HCC metastasis via regulating ERK signalling pathway. Copyright © 2016 John Wiley & Sons, Ltd.


Is the velocity-curvature relationship disrupted in apraxic patients?
Velocity and curvature of human movements are linked by a proportionality relationship (power-law) whose origin has been attributed either to functional properties of cortical areas or to peripheral constraints. 3D movements made by apraxic patients show a time-shift between velocity and curvature which has been considered as a disruption of the power-law, supporting the central hypothesis. We analysed the power-law in 2D drawing-like movements in healthy subjects and apraxic patients (correlation and cross-correlation analyses). The power-law remained preserved in apraxic patients, suggesting that the velocity-curvature relationship is not globally disrupted and thus that the power-law cannot be only attributed to central planning mechanisms in those associative brain areas injured in apraxic patients.


Rhabdomyolysis associated with bacteremic pneumonia due to Staphylococcus aureus.
A case of rhabdomyolysis associated with bacteremic pneumonia due to Staphylococcus aureus is reported. A 58-year-old man was admitted because of severe left lobar pneumonia, and presented myoglobinuria on admission. The serum creatine phosphokinase level was transiently elevated and myoglobinuria were disclosed. Sputum and venous blood cultures grew Staphylococcus aureus. Rhabdomyolysis has rarely been reported in cases of bacterial infection, especially those due to Staphylococcus aureus. This case might be an extremely rare case of rhabdomyolysis complicating Staphylococcus aureus bacteremia following severe left upper lobar pneumonia.


Drug evaluation: apilimod, an oral IL-12/IL-23 inhibitor for the treatment of autoimmune diseases and common variable immunodeficiency.
Apilimod is a small molecule that inhibits IL-12 and IL-23 production - cytokines that are involved in autoimmune diseases - through the prevention of nuclear translocation of c-Rel. Synta Pharmaceuticals Corp is developing apilimod for the potential treatment of Crohn's disease (CD) and other autoimmune diseases. Preclinical studies demonstrated the successful inhibition of IL-12 and IL-23 production by the drug. In the clinical setting, apilimod has been generally well tolerated, with mild-to-moderate side effects reported, including headaches and nausea. Patients with CD responded within 14 days of treatment with apilimod and, after 28 days, the drug significantly reduced the Crohn's disease activity index (CDAI). Apilimod is currently in phase II clinical trials for rheumatoid arthritis, common variable immunodeficiency and CD. From the data available to date, apilimod appears to be a promising treatment for CD, and the oral formulation of this compound provides an advantage for apilimod over injectable therapies.


Mortality Among Hardmetal Production Workers: Occupational Exposures.
To generate quantitative exposure estimates for use in retrospective occupational cohort mortality studies of the hardmetal industry. Job-exposure matrices (JEMs) were constructed for cobalt, tungsten, and nickel over the time period 1952 to 2014. The JEMs consisted of job class categories, based on job titles and processes performed, and exposure estimates calculated from available company industrial hygiene measurements. Exposure intervals of one-half order magnitude were established for all three agents. Eight job classes had significantly decreasing time trends for cobalt exposure; no significant time trends were detected for tungsten or nickel exposures. The levels of exposures determined for this study were similar to or lower than those previously reported for the hardmetal industry during the 1952 to 2014 study period.


Distribution of glycosaminoglycans in the aqueous outflow system of the cat.
Although glycosaminoglycans (GAGs) have been postulated to play a role in the regulation of intraocular pressure, structural localization of specific varieties of GAGs in the outflow system is necessary before their precise role can be determined. In this study, the outflow system of the cat was stained with ruthenium red to identify GAGs with the electron microscope. The composition of the ruthenium red-stainable material was determined by predigestion of tissues with testicular hyaluronidase, neuraminidase, or papain. Testicular hyaluronidase-sensitive GAGs were located on the surfaces of the endothelial cells in the trabecular meshwork and aqueous plexus, within their basal laminae, and in the amorphous tissue of the trabecular beams and tissue adjacent to the aqueous plexus. Collagen and elastic fibers throughout the outflow system were also associated with ruthenium red-stainable material that was resistant to testicular hyaluronidase. Connective tissue GAGs, but not endothelial cell-associated GAGs, were demonstrated to be complexed to protein, since they were disrupted by papain treatment. Neuraminidase-sensitive material (sialoglycoprotein) was identified only on the lumenal surface of the endothelial cells of the aqueous plexus. The complex distribution of GAGs and order polyanions in the outflow system of the cat suggests that the these macromolecules may serve more than one function.


IL-1 in gingival crevicular fluid following closed root planing and papillary flap debridement.
Interleukin (IL)-1 alpha and beta are cytokines which can mediate inflammatory, bone resorbing, and reparative effects in the periodontium, but few longitudinal data exist exploring their role following periodontal therapy. This study examined gingival crevicular fluid (GCF) concentrations of IL-1 alpha and IL-1 beta at sites with shallow sulci (SS) or inflamed moderate/advanced pockets (M/AP) before and 6 months after treatment with closed scaling/root planing (SC/RP) or papillary flap debridement (PFD), all in the same subject (n = 14 patients). No significant differences were noted in IL-1 alpha or beta concentrations (determined with two-site enzyme-linked immunosorbent assays) between SS and M/AP sites at baseline. While both therapies improved clinical parameters of periodontal disease, IL-1 alpha concentration increased significantly (p < 0.05) in M/AP-PFD sites 6 months after treatment, but were unchanged in other groups. IL-1 beta concentrations were numerically lower after therapy, except for a significant increase (p < 0.05) in M/AP-PFD sites. These data suggest that surgical wound healing in an inflamed, plaque-infected site (M/AP-PFD) results in prolonged production of IL-1, which may be a reflection of the extent of tissue trauma and delayed wound healing. In spite of increased IL-1 levels, these sites demonstrated significant short-term improvement in clinical attachment level (+ 1.8 mm, p < or = 0.001) postoperatively.


Asthma in the managed care setting.
The quality improvement techniques of managed care are dramatically upgrading the delivery of asthma education and therapy, yielding cost-effective outcomes through a variety of approaches. Guidelines have been available in national and international references, but successful implementation outside of managed care has been poor. The complex components known to produce success in asthma care have not been properly reimbursed in the fee-for-service tradition. Even within managed care settings, attention to cost-effectiveness varies widely, and creative new approaches promise better returns than early asthma programs. Tools that managed care can offer for improved asthma outcomes and cost-effective options are presented.


Metal artifact reduction using common dental materials.
To determine the effect of different dental lab materials on cone beam computed tomography (CBCT) metal artifact at different resolutions. A total of seven common dental lab materials were molded to a dental sextant of four extracted, restored teeth. In addition to base alone (control), each material was scanned using the Carestream 9600 CBCT unit at three resolutions - 0.3 mm, 0.15 mm, and 0.075 mm - at manufacturer established exposure parameters. A single, representative axial view of each trial was evaluated for metal artifact both quantitatively by histogram analysis and qualitatively by profile plot analysis in ImageJ. No statistically significant differences between the control and the dental materials were found; however, post-hoc tests showed significance between Blu-mousse® and polyvinyl siloxane with dental materials and control, predominantly in lower resolutions. The current study provides initial evidence on the influence of dental materials have on CBCT metal artifact as described by beam hardening, photon starvation, scatter, and noise, especially at lower resolutions. Blu-Mousse® and polyvinyl siloxane reduced the perceived beam hardening and photon starvation artifact the greatest, relative to other materials, at all three resolutions and lower resolutions, respectively.


Experimental thresholds of magnetically induced currents via a figure-of-eight coil up to 25 kHz.
Magnetic particle imaging, uses magnetic fields of frequencies in the kilo-hertz range. Little research has been carried out upon effects on excitable tissue caused by time-varying magnetic fields in that frequency range. To learn about magnetic stimulation thresholds, a system that is capable of generating a very focused magnetic field strong enough to induce a muscular reaction was built. Stimulation thresholds at 7.38, 12.04, 16.5, and 25.27 kHz have been recorded in 31 trial participants. It has been proved that magnetic stimulation is possible up to even 25 kHz, and respective thresholds have been determined. This article presents the trial setup, procedure, and evaluation of field quantities.


Current Validated Clinical and Patient Reported Disease Outcome Measures in Juvenile Idiopathic Arthritis.
Juvenile idiopathic arthritis (JIA) is a common chronic illness in childhood and comprises seven categories based on the International League of Associations for Rheumatology (ILAR) criteria. Accurate assessment and measurement of the clinical, functional, and quality of life outcomes of patients with JIA are paramount for understanding the disease course and formulating effective treatment strategies. Interest in the development and use of outcome measurements specifically focused on rheumatologic conditions has greatly expanded over the last two decades, adding to and improving upon the established disease measures. Furthermore, many of these measures have been validated using the widely accepted Outcome Measures in Rheumatology (OMERACT) core principles of instrument validation, allowing researchers and clinicians to gain confidence in these tools. This review summarizes the current validated disease outcome measures in JIA, including clinical, imaging, patient-reported, and functional outcome measurement tools, and highlights ongoing work that continues to refine and improve upon the available tools. The clinical disease outcome measures discussed in this review include physician global assessment (PhGA), American College of Rheumatology (ACR, Wallace) criteria for clinical inactive disease and clinical remission, juvenile arthritis disease activity scores (JADAS), juvenile spondyloarthritis disease activity index (JSPaDA), juvenile arthritis damage index (JADAI), and the ACR pediatric response scores. The imaging outcome measures discussed include the Dijkstra composite scores, childhood arthritis radiographic score of the hip (CARSH), and Poznanski Score. The patient-reported disease outcome measures discussed include patient global assessment (PtGA), patient-reported outcome measurement information system for JIA (PROMIS), juvenile arthritis parent/child centered disease assessment index (JAPAI, JACAI), juvenile arthritis multidimensional assessment report (JAMAR), and the Pediatric quality of life inventory rheumatology module (PedsQL). The functional outcome tools discussed include the Childhood Health Assessment Questionnaire (CHAQ), juvenile arthritis functionality scale and index (JAFS and JASI), and Juvenile Arthritis Functional Assessment Report and Scale (JAFAS and JAFAR).


Physiological Tau Interactome in Brain and Its Link to Tauopathies.
Alzheimer's disease (AD) and most of the other tauopathies are incurable neurodegenerative diseases with unpleasant symptoms and consequences. The common hallmark of all of these diseases is tau pathology, but its connection with disease progress has not been completely understood so far. Therefore, uncovering novel tau-interacting partners and pathology affected molecular pathways can reveal the causes of diseases as well as potential targets for the development of AD treatment. Despite the large number of known tau-interacting partners, a limited number of studies focused on in vivo tau interactions in disease or healthy conditions are available. Here, we applied an in vivo cross-linking approach, capable of capturing weak and transient protein-protein interactions, to a unique transgenic rat model of progressive tau pathology similar to human AD. We have identified 175 potential novel and known tau-interacting proteins by MALDI-TOF mass spectrometry. Several of the most promising candidates for possible drug development were selected for validation by coimmunoprecipitation and colocalization experiments in animal and cellular models. Three proteins, Baiap2, Gpr37l1, and Nptx1, were confirmed as novel tau-interacting partners, and on the basis of their known functions and implications in neurodegenerative or psychiatric disorders, we proposed their potential role in tau pathology.


Bronchoconstrictor effects of leukotriene E4 in normal and asthmatic subjects.
The bronchoconstrictor activity of an aerosol of leukotriene E4(LTE4) was compared with that of histamine in 5 normal and in 6 asthmatic subjects to define the relative potency of LTE4 between the groups using 3 indices of airway response. The FEV1 and the flow rate measured at 30% of vital capacity from partial and maximal expiratory maneuvers (V30-P and V30-M) were measured. The geometric mean (GSEM) concentration of LTE4 required to reduce the V30-P by 30% was 0.30 (1.46) mM in the normal subjects, and 0.058 (1.63) in the asthmatic subjects; LTE4 was 39-fold more potent than histamine in the former and 14-fold in the latter group. Further, we observed that when normal and asthmatic subjects were compared at a degree of bronchoconstriction resulting in a 30% decrement in the V30-P after inhaling LTE4, there was a greater response in the asthmatic group than in the normal group of the accompanying change in the FEV1. The decrements in the FEV1 were not significantly different between the 2 groups after inhaling histamine. This study demonstrates that LTE4 is a potent bronchoconstrictor agonist in humans and suggests that airway responsiveness to this agonist differs substantially with the index of bronchoconstriction used for assessment of airway response.


[Psychiatric disorders during adolescence (author's transl)].
The psychopathology of adolescence shows three areas of dysfunction: 1. maturity deficits with an attitude of protest, loss of motivations, conversion symptomatology, 2. hypochondriac symptoms, obsessive-compulsive features, dysphorias, intellectual-physical handicaps, 3. antisocial behaviour, delinquency, neglect, addiction. 3. different courses can be distinguished longitudinally: 1. a double peak course with a disorder during childhood and adolescence with antisocial behavior, personality disorders and neurotic developments, 2. disorders during childhood which improve later (enuresis, encopresis, tics), 3. psychosis, maturity crisis, depressive reactions, obsessive compulsive syndromes.


The combination of hawthorn extract and camphor significantly increases blood pressure: A meta-analysis and systematic review.
A fixed combination of hawthorn and camphor (Korodin Herz-Kreislauf-Tropfen®) has been used in the therapy of hypotension for decades. Although its efficacy was evaluated in clinical trials, these studies have not been critically assessed in meta-analyses. To systematically evaluate the efficacy of a fix combination of camphor and hawthorn extract (Korodin®) on blood pressure and cognition compared to placebo, in a meta-analysis based on randomized controlled trials (RCTs). The meta-analysis was carried out following the PRISMA guidelines, using the PICO format, and it was registered in the PROSPERO register. The Cochrane Central Register of Controlled Trials, PubMed, Embase, and Web of Science databases were searched for relevant studies. Placebo-controlled clinical studies involving adult patients receiving a fix combination of hawthorn extract and camphor were included. No language or publication year restrictions were applied. Four randomized trials including a total of 221 patients were pooled for statistical analysis. According to the present meta-analysis, the fixed combination of hawthorn and camphor significantly increases systolic and diastolic blood pressure compared to placebo (p-values: 0.017 and 0.049, respectively) and had a beneficial, but not statistically significant effect on the cognitive performance in the connect-the-numbers test (p-value: 0.071). Korodin® is an effective and presumably safe complementary therapy for the treatment of hypotension. Its blood pressure increasing effect is confirmed; however, the evidence supporting its use is very limited. The optimum dose and duration of treatment is still unclear. The comprehensive evaluation of efficacy and safety is required in further, high-quality clinical studies, involving larger patient populations and comparable endpoints.


Magnetic resonance imaging abnormalities associated with vigabatrin in patients with epilepsy.
Vigabatrin used to treat infantile spasms (IS) has been associated with transient magnetic resonance imaging (MRI) abnormalities. We carried out a retrospective review to better characterize the frequency of those abnormalities in IS and in children and adults treated with vigabatrin for refractory complex partial seizures (CPS). Medical records and 332 cranial MRIs from 205 infants (aged <or=24 months) with IS treated at 10 sites in the United States and Canada were collected. Similarly, 2,074 images from 668 children (aged 2-16 years) and adults (aged >16 years) with CPS were re-reviewed. Prespecified MRI abnormalities were defined as any hyperintensity on T(2)-weighted or fluid-attenuated inversion-recovery (FLAIR) sequences with or without diffusion restriction not readily explained by a radiographically well-characterized pathology. MRIs were read by two neuroradiologists blinded to treatment group. The incidence and prevalence of MRI abnormalities associated with vigabatrin were estimated. Among infants with IS, the prevalence of prespecified MRI abnormalities was significantly higher among vigabatrin-treated versus vigabatrin-naive subjects (22% vs. 4%; p < 0.001). Of nine subjects in the prevalence population with at least one subsequent determinate MRI, resolution of MRI abnormalities occurred in six (66.7%)-vigabatrin was discontinued in four. Among adults and children treated with vigabatrin for CPS, there was no statistically significant difference in the incidence or prevalence of prespecified MRI abnormalities between vigabatrin-exposed and vigabatrin-naive subjects. Vigabatrin is associated with transient, asymptomatic MRI abnormalities in infants treated for IS. The majority of these MRI abnormalities resolved, even in subjects who remained on vigabatrin therapy.


Enhancing Hydrogen Evolution Reaction Activities of 2H-Phase VS2 Layers with Palladium Nanoparticles.
Effective hydrogen (H2) production with surface engineering of less active catalysts by an innovative approach is followed here. In this work, a non-noble 2H phase of VS2 layers, which showed poor activity for hydrogen evolution reaction (HER) in 0.5 M H2SO4, was made highly active by decorating palladium (Pd) nanoparticles (NPs) over VS2 layers. A density functional theory (DFT) study confirmed the successful binding of Pd with VS2, and the bond length in a Pd4 tetrahedron was measured to be 2.60 Å. In VS2-Pd, Pd as a Pd4 tetrahedron is pointed toward the VS2 layer, and the calculated Pd-S bond distance is 2.42 Å with some expansion of three Pd-Pd bonds (2.85 Å). From the density of states, it was confirmed that the band gap was too high for VS2 (0.2 eV; 2H phase) and was reduced to nearly zero in VS2-Pd (0.05 eV). In the electrocatalytic HER part, the obtained ΔGH values from DFT were 0.05, -0.45, and 0.22 eV for VS2/Pd4, Pd4, and VS2, respectively, which imply that VS2-Pd4 had improved HER activity compared to pristine VS2 and Pd4. A concentration-dependent study was carried out with molar ratios of Pd at 0.01, 0.05, and 0.1 M with VS2 layers. From the HER polarization study, VS2-Pd (0.05 M) showed an overpotential of 157 mV at 20 mA cm-2, which is 373 mV less than only VS2 with a Tafel slope of 75 mV dec-1 with overwhelming stability. These highly promising results will be interesting to make less active stable phases by incorporating metal NPs for efficient and stable H2 production.


Thiosemicarbazones and hydrazones of alpha-methylchalkone as potential chemotherapeutic agents.
The effectiveness of chalkones and derivatives as antibacterial and antifungal agents stimulated our interest in the possibility of coupling this type of compound with certain hydrazines and thiosemicarbazides to determine the potential chemotherapeutic activity of these combinations as anticancer and antimalarial agents. Accordingly, 18 hydrazine and thiosemicarbazide derivatives of alpha-methylchalkone (dypnone) have been synthesized for study as potential antitumor agents in animal tumor systems against Walker 256 carcinosarcoma (intramuscular) and leukemia L-1210 and for antimalarial activity against Plasmodium berghei in experimentally infected mice. Of the series of chalkone derivatives, significant inhibition in preliminary tests against the Walker 256 carcinosarcoma (intramuscular) rat tumor system was exhibited by alpha-methylchalkone-1,4-phthalazinediyldihydrazone and showed activity in the leukemia 1210 mouse tumor system. The guanylhydrazone of alpha-methylchalkone showed good inhibition with confirmed activity against Plasmodium berghei in experimentally infected mice.


A ccpp-6 deletion mutation does not impair gross cilia integrity in C. elegans.
Tubulin glutamylation is a reversible modification that regulates microtubule function in cilia. The removal of glutamylation from microtubules is carried out by a family of cytosolic carboxypeptidase (CCP) enzymes. C. elegans has two deglutamylating enzymes, CCPP-1 and CCPP-6, homologs of mammalian CCP1 and CCP5 respectively. CCPP-1 is required for ciliary stability and function. To determine whether CCPP-6 is similarly required for cilia integrity in C. elegans we analyzed the ccpp-6(ok382) deletion mutant. We find that both dye-filling and male mating are normal, suggesting that CCPP-6 is not required for ciliary integrity in C. elegans.


Preparatory neural activity predicts performance on a conflict task.
Advance preparation has been shown to improve the efficiency of conflict resolution. Yet, with little empirical work directly linking preparatory neural activity to the performance benefits of advance cueing, it is not clear whether this relationship results from preparatory activation of task-specific networks, or from activity associated with general alerting processes. Here, fMRI data were acquired during a spatial Stroop task in which advance cues either informed subjects of the upcoming relevant feature of conflict stimuli (spatial or semantic) or were neutral. Informative cues decreased reaction time (RT) relative to neutral cues, and cues indicating that spatial information would be task-relevant elicited greater activity than neutral cues in multiple areas, including right anterior prefrontal and bilateral parietal cortex. Additionally, preparatory activation in bilateral parietal cortex and right dorsolateral prefrontal cortex predicted faster RT when subjects responded to spatial location. No regions were found to be specific to semantic cues at conventional thresholds, and lowering the threshold further revealed little overlap between activity associated with spatial and semantic cueing effects, thereby demonstrating a single dissociation between activations related to preparing a spatial versus semantic task-set. This relationship between preparatory activation of spatial processing networks and efficient conflict resolution suggests that advance information can benefit performance by leading to domain-specific biasing of task-relevant information.


Birth of Four Chimeric Plastid Gene Clusters in Japanese Umbrella Pine.
Many genes in the plastid genomes (plastomes) of plants are organized as gene clusters, in which genes are co-transcribed, resembling bacterial operons. These plastid operons are highly conserved, even among conifers, whose plastomes are highly rearranged relative to other seed plants. We have determined the complete plastome sequence of Sciadopitys verticillata (Japanese umbrella pine), the sole member of Sciadopityaceae. The Sciadopitys plastome is characterized by extensive inversions, pseudogenization of four tRNA genes after tandem duplications, and a unique pair of 370-bp inverted repeats involved in the formation of isomeric plastomes. We showed that plastomic inversions in Sciadopitys have led to shuffling of the remote conserved operons, resulting in the birth of four chimeric gene clusters. Our data also demonstrated that the relocated genes can be co-transcribed in these chimeric gene clusters. The plastome of Sciadopitys advances our current understanding of how the conifer plastomes have evolved toward increased diversity and complexity.


Analysis of obsidian from moho cay, belize: new evidence on classic maya trade routes.
Trace element analysis of obsidian artifacts from Moho Cay, Belize, reveals that the obsidian derives primarily from the El Chayal outcrop in highland Guatemala and not from the Ixtepeque source. This is contrary to the widely accepted obsidian trade route model for Classic Maya civilization and suggests that Classic Maya obsidian trade was a more complex economic phenomenon than has been recognized.


Anti-gastric parietal cell antibodies for autoimmune gastritis screening in juvenile autoimmune thyroid disease.
Patients with autoimmune thyroid disease (ATD) have a higher prevalence of autoimmune gastritis (AIG) compared with the general population. The association between ATD and AIG is poorly characterized in the pediatric age. We reviewed the prevalence of anti-gastric parietal cell antibodies (PCA) in young patients with ATD to evaluate its usefulness as a marker for AIG screening. We evaluated 220 children and adolescents (11.28 ± 6.37 years) with ATD (186 with autoimmune thyroiditis (AT) and 34 with Graves' disease (GD). At ATD diagnosis and annually thereafter, blood counts and PCA levels were measured. In patients positive for PCA, plasma gastrin, chromogranin A, vitamin B12, iron and ferritin levels and H. pylori antigen were measured. PCA-positive patients > 18 years were invited to undergo a gastroscopic exam. PCA positivity was detected in ten (4.5%) subjects (5F/5M; 12.6 ± 3.4 years). The prevalence of PCA positivity was not significantly different in the comparison of GD and AT patients (p = 0.9). PCA positivity was detected after 2.7 ± 2.7 years of follow-up in AT and 4.4 ± 4.0 years in GD (p = 0.4). Autoantibody positivity was more prevalent in female patients, in both AT and GD (p = 0.02 and p = 0.03, respectively). At detection of PCA positivity, five out of ten PCA-positive patients had iron deficiency, four vitamin B12 deficiency, two anemia, three hypergastrinemia and two elevated chromogranin values. Two patients had H. pylori infection. Gastroscopy was performed in the five ATD patients and in all patients, AIG was confirmed. In the juvenile population, ATD and AIG may also be associated. PCA screening is useful to detect subjects at risk for this condition. Due to the longer life expectancy of the pediatric population and considering the relatively high risk of malignant transformation, early surveillance monitoring is mandatory for children and adolescents with ATD.


Adaptation of a real-time PCR method for the detection and quantification of pathogenic leptospires in environmental water.
Leptospirosis is a major zoonotic disease that affects humans and animals in all continents, in both rural and urban areas. In Europe, metropolitan France is the most affected country, with about 300 human cases declared per year. In France, although leptospirosis is now mostly considered as a recreational disease related to freshwater areas, isolation of pathogenic leptospires from environmental water samples still remains difficult. It thus seemed important to set up an efficient method to detect and quantify these bacteria in this environment. We determined a DNA extraction method suitable for freshwater samples and adapted a real-time quantitative PCR based on the detection of the LipL32 gene using the SYBR green chemistry. The method developed is specific for pathogenic Leptospira. It permits the detection of all the pathogenic strains tested and none of the saprophytic strains. Quantification is possible between 10 and 10(7) bacteria/mL, and therefore, the method represents a tool that could be integrated into future public health surveillance programs for recreational freshwater areas.


[Mechanical ventilation in pediatrics (III). Weaning, complications and other types of ventilation. Noninvasive ventilation].
Noninvasive ventilation (NIV), i.e. without tracheal intubation, has been reintroduced for the treatment of respiratory failure to reduce the complications of mechanical ventilation. Nowadays, NIV with positive pressure is the preferred method, applied through a mask held in place by a harness. Several masks can be used (nasal, bucconasal facial) and a variety of means can be used to keep them in place. Many respirators can be selected, ranging from those traditionally used in the intensive care unit(ICU) to specific NV respirators and conventional ICU respirators with specific software for NIV. Many respiratory modalities can be used according to the respirator (biphasic positive airway pressure [BIPAP], proportional assist ventilation, pressure support, synchronized intermittent mandatory ventilation [SIMV], etc.). NIV is mainly indicated in exacerbations of chronic respiratory failure: neuromuscular diseases, pretransplantation cystic fibrosis, and obstructive sleep apnea syndrome. It is also indicated in acute respiratory failure: pneumonia, status asthmaticus, and acute lung edema. The main contraindications are a weakened airway protection reflex(absent cough reflex) and hemodynamic instabiity. The advantages of NIV derive mainly from avoiding the complications associated with invasive ventilation. NIV also presents some disadvantages, especially the greater workload involved to ensure good patient adaptation to the respirator. The most common sequelae of NIV are skin lesions due to pressure on the nasal bridge.


Nonlinear stability analysis of Darcy's flow with viscous heating.
The nonlinear stability of a rectangular porous channel saturated by a fluid is here investigated. The aspect ratio of the channel is assumed to be variable. The channel walls are considered impermeable and adiabatic except for the horizontal top which is assumed to be isothermal. The viscous dissipation is acting inside the channel as internal heat generator. A basic throughflow is imposed, and the nonlinear convective stability is investigated by means of the generalized integral transform technique. The neutral stability curve is compared with the one obtained by the linear stability analysis already present in the literature. The growth rate analysis of different unstable modes is performed. The Nusselt number is investigated for several supercritical configurations in order to better understand how the system behaves when conditions far away from neutral stability are considered. The patterns of the neutrally stable convective cells are also reported. Nonlinear simulations support the results obtained by means of the linear stability analysis, confirming that viscous dissipation alone is indeed capable of inducing mixed convection. Low Gebhart or high Péclet numbers lead to a transient overheating of the originally motionless fluid before it settles in its convective steady state.


[Stability of prolin-containing peptides in biological media].
New data on peptide drugs have been summarized; their high stability is due to both the introduction of Pro-Gly-Pro in various amino acid sequences and the modification of the glyproline fragment itself. Pro-Gly-Pro-Leu, ACTH(6-9)Pro-Gly-Pro, 5-oxo-Pro-Arg-Pro and 5-oxo-Pro-His-Pro-NH2 were used as proline-containing peptides. Tritiated peptides were obtained: Pro-Gly-Pro-Leu with specific radioactivity of 135 Ci/mmol, ACTH(6-9)Pro-Gly-Pro - 26 Ci/mmol, 5-oxo-Pro-Arg-Pro - 60 Ci/mmol and 5-oxo-Pro-His-Pro-NH2 - 75 Ci/mmol. The concentration of Pro-Gly-Pro-Leu, ACTH(6-9)Pro-Gly-Pro, 5-oxo-Pro-Arg-Pro and 5-oxo-Pro-His-Pro-NH2 in the blood was found to be about 200 times more than in the brain for intranasal administration, and in average 600 times more for intravenous administration. The stability of proline-containing peptides in vitro experiments was determined using different commercially available peptidases (leucine aminopeptidases, dipeptidases, carboxypeptidases B and Y), and using nasal mucus, microsomal fraction of the rat brain (IMPC) and rat blood plasma. During peptidase hydrolysis of Pro-Gly-Pro-Leu, the main metabolites were Gly-Pro-Leu, Pro-Gly-Pro, Gly-Pro and Pro-Gly. For ACTH(6-9)Pro-Gly-Pro, the main metabolites were Phe-Arg-Trp-Pro-Gly-Pro and Trp-Pro-Gly-Pro. In peptidase hydrolysis of 5-oxo-Pro-His-Pro-NH2, the major metabolite was 5-oxo-Pro-His-Pro. It was shown that with different methods of peptides administration the composition of the metabolites formed is different. Based on the data obtained, resistance to enzymatic cleavage of peptides and their metabolic pathways were evaluated. Thus, these new data have shown that the above approaches can be used to prolong the action of glyprolines in living objects. In this case, the degradation of proline-containing peptides occurs mainly not due to the action of proteases, but due to other ways of degradation. In general, the data presented in the review indicate the promise of intranasal way of introducing biologically active peptides into the brain of living organisms.


Oral Medication for Agitation of Psychiatric Origin: A Scoping Review of Randomized Controlled Trials.
Understanding more about the efficacy and safety of oral second-generation antipsychotic medications in reducing the symptoms of acute agitation could improve the treatment of psychiatric emergencies. The objective of this scoping review was to examine the evidence base underlying expert consensus panel recommendations for the use of oral second-generation antipsychotics to treat acute agitation in mentally ill patients. The Cochrane Schizophrenia Group's Study-Based Register was searched for randomized controlled trials comparing oral second-generation antipsychotics, benzodiazepines, or first-generation antipsychotics with or without adjunctive benzodiazepines, irrespective of route of administration of the drug being compared. Six articles were included in the final review. Two oral second-generation antipsychotic medications were studied across the six included trials. While the studies had relatively small sample sizes, oral second-generation antipsychotics were similarly effective to intramuscular first-generation antipsychotics in treating symptoms of acute agitation and had similar side-effect profiles. This scoping review identified six randomized trials investigating the use of oral second-generation antipsychotic medications in the reduction of acute agitation among patients experiencing psychiatric emergencies. Further research will be necessary to make clinical recommendations due to the overall dearth of randomized trials, as well as the small sample sizes of the included studies.


Hadamard transform time-of-flight mass spectrometry: a high-speed detector for capillary-format separations.
This work demonstrates that with an intrinsic duty cycle of 50% and spectral storage speeds up to 277 spectra s(-1) Hadamard transform time-of-flight mass spectrometry (HT-TOFMS) is a promising detector for any capillary-format separation that can be coupled to MS by electrospray ionization. Complete resolution of the components of a nine-peptide standard was achieved by coupling pressurized-capillary electrophoresis (pCE) to HT-TOFMS. The addition of pressure to the separation capillary decreased analysis times and stabilized the electrospray ionization source. Pulsed-pressurized injection of reserpine was used to experimentally simulate narrower peaks than those obtained in the pCE. HT-TOFMS was able to sample peaks having widths in the millisecond range.


A Novel Missense Mutation of the MEN1 Gene in a Patient with Multiple Endocrine Neoplasia Type 1 with Glucagonoma and Obesity.
A 35-year-old obese diabetic man presented with recurrent primary hyperparathyroidism during a three-year outpatient follow-up. He was clinically diagnosed with multiple endocrine neoplasia type 1 (MEN1) due to the presence of a pituitary adenoma and multiple glucagonomas. The glucagonomas may have affected his glycemic control. However, he did not demonstrate weight loss, suggesting that the patient's obesity could have obscured the early diagnosis of a glucagonoma. Genetic testing revealed a novel missense mutation at codon 561 in exon 10, resulting in an amino acid substitution from methionine to arginine (M561R) in the MEN1 gene. This mutation appeared to be responsible for the MEN1 pathogenicity.


Prolonged astrocyte-derived erythropoietin expression attenuates neuronal damage under hypothermic conditions.
Hypoxic-ischemic encephalopathy (HIE) has a high morbidity rate and involves severe neurologic deficits, including cerebral palsy. Therapeutic hypothermia (TH) has been shown to decrease the mortality rate and provide neuroprotection in infants with HIE. However, death and disability rates in HIE infants treated with TH remain high. Although the cellular mechanism of the neuroprotective effect of TH remains unclear, astrocytic erythropoietin (EPO) is known to be a key mediator of neuroprotection under hypoxic conditions. In the present study, we investigated the hypothermia effect on EPO expression in astrocytes and determined whether hypothermia attenuates neuronal damage via EPO signaling. Astrocytes derived from rat cerebral cortex were cultured under oxygen/glucose deprivation (OGD). The expression of EPO and hypoxia-inducible factor (HIF), a transcription factor of EPO, was assessed. After OGD, astrocytes were cultured under normothermic (37 °C) or hypothermic (33.5 °C) conditions, and then EPO and HIF expression was assessed. After OGD, rat cortical neurons were cultured in astrocyte-conditioned medium (ACM) derived from the hypothermic group, and neuronal apoptosis was evaluated. OGD induced EPO mRNA and protein expression, although at lower levels than hypoxia alone. HIF-1α and HIF-2α protein expression increased under hypoxia alone and OGD, although OGD increased HIF-2α protein expression less than hypoxia alone. EPO gene and protein expression after OGD was significantly higher under hypothermia. Moreover, expression of HIF-1α and HIF-2α protein was enhanced under hypothermia. In the presence of ACM derived from hypothermic astrocytes following OGD, the number of cleaved caspase 3 and TdT-mediated dUTP nick-end labeling-positive apoptotic neurons was lower than in the presence of ACM from normothermic astrocytes following OGD. Blockade of EPO signaling using anti-EPO neutralization antibody attenuated the anti-apoptotic effect of ACM derived from hypothermic astrocytes following OGD. Hypothermia after OGD stabilized HIF-EPO signaling in astrocytes, and upregulated EPO expression could suppress neuronal apoptosis. Investigating the neuroprotective effect of EPO from astrocytes under hypothermic conditions may contribute to the development of novel neuroprotection-based therapies for HIE.


In Vitro Pharmacodynamics of Human Simulated Exposures of Telavancin against Methicillin-Susceptible and -Resistant Staphylococcus aureus with and without Prior Vancomycin Exposure.
Telavancin is a lipoglycopeptide with potent activity against methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible S. aureus (MSSA). The activity of telavancin against MRSA and MSSA after prior vancomycin exposure was studied in an in vitro pharmacodynamic model. Two clinical MRSA and two MSSA isolates, all with vancomycin MICs of 2 μg/ml, were subjected to humanized free drug exposures of vancomycin at 1 g every 12 h (q12h) for 96 h, telavancin at 750 mg q24h for 96 h, and vancomycin at 1 g q12h for 72 h followed by telavancin at 750 mg q24h for 48 h (120 h total). The microbiological responses were measured by changes from 0 h in log10 CFU/ml at the end of experiments and area under the bacterial killing and regrowth curves over 96 h (AUBC0-96). The control isolates grew to 8.8 ± 0.3 log10 CFU/ml. Initially, all regimens caused -4.5 ± 0.9 reductions in log10 CFU/ml by 48 h followed by slight regrowth over the following 48 to 72 h. After 96 h, vancomycin and telavancin achieved -3.7 ± 0.9 and -3.8 ± 0.8 log10 CFU/ml changes from baseline, respectively (P = 0.74). Sequential exposure to telavancin after vancomycin did not result in additional CFU reductions or increases, with ultimate log10 CFU/ml reductions of -4.3 ± 1.1 at 96 h and -4.2 ± 1.3 at 120 h (P > 0.05 for all comparisons at 96 h). The AUBC0-96 was significantly smaller for the regimen of telavancin for 96 h than for the regimens of vancomycin for 96 h and vancomycin followed by telavancin (P ≤ 0.04). No resistance was observed throughout the experiment. Against these MRSA and MSSA isolates with vancomycin MICs of 2 μg/ml, telavancin was comparable with vancomycin and its activity was unaffected by prior vancomycin exposure.


A Solar-Blind UV Detector Based on Graphene-Microcrystalline Diamond Heterojunctions.
An ultraviolet detector is demonstrated through a whole-wafer, thin diamond film transfer process to realize the heterojunction between graphene and microcrystalline diamond (MCD). Conventional direct transfer processes fail to deposit graphene onto the top surface of the MCD film. However, it is found that the 2 µm thick MCD diamond film can be easily peeled off from the growth silicon substrate to expose its smooth backside for the graphene transfer process for high-quality graphene/MCD heterojunctions. A vertical graphene/MCD/metal structure is constructed as the photodiode device using graphene as the transparent top electrode for solar-blind ultraviolet sensing with high responsivity and gain factor. As such, this material system and device architecture could serve as the platform for next-generation optoelectronic systems.


AutoSolvate: A toolkit for automating quantum chemistry design and discovery of solvated molecules.
The availability of large, high-quality datasets is crucial for artificial intelligence design and discovery in chemistry. Despite the essential roles of solvents in chemistry, the rapid computational dataset generation of solution-phase molecular properties at the quantum mechanical level of theory was previously hampered by the complicated simulation procedure. Software toolkits that can automate the procedure to set up high-throughput explicit-solvent quantum chemistry (QC) calculations for arbitrary solutes and solvents in an open-source framework are still lacking. We developed AutoSolvate, an open-source toolkit, to streamline the workflow for QC calculation of explicitly solvated molecules. It automates the solvated-structure generation, force field fitting, configuration sampling, and the final extraction of microsolvated cluster structures that QC packages can readily use to predict molecular properties of interest. AutoSolvate is available through both a command line interface and a graphical user interface, making it accessible to the broader scientific community. To improve the quality of the initial structures generated by AutoSolvate, we investigated the dependence of solute-solvent closeness on solute/solvent identities and trained a machine learning model to predict the closeness and guide initial structure generation. Finally, we tested the capability of AutoSolvate for rapid dataset curation by calculating the outer-sphere reorganization energy of a large dataset of 166 redox couples, which demonstrated the promise of the AutoSolvate package for chemical discovery efforts.


Autistic disorder in 2 children with mitochondrial disorders.
Autistic disorder is a heterogeneous disorder. The majority of the cases are idiopathic, and only a small number of the autistic children have associated secondary diagnosis. This article reports 2 children with mitochondrial disorders associated with autistic disorder fulfilling the diagnostic criteria of the American Psychiatric Association Manual of Psychiatric Diseases, 4th edition, and briefly reviews the literature on autistic disorder associated with mitochondrial disorders.


Pentraxin 3 production in the adipose tissue and the skeletal muscle in diabetic-obese mice.
: Inflammation has been shown to promote obesity-induced insulin resistance. Although pentraxin (PTX) 3 is known as an anti-inflammatory factor, the effect of PTX3 on insulin sensitivity has not yet been elucidated. The aim of this study is to investigate a part of the role of PTX3 on insulin sensitivity. The authors studied the PTX3 and glucose transport protein expression levels in epididymal adipose tissue and soleus muscles of male diabetic-obese [Tsumura Suzuki obese-diabetic (TSOD)] and lean control mice. The levels of PTX3 in both skeletal muscle and adipose tissue were significantly lower in TSOD mice than in controls, and there was a significant positive correlation between them. They observed a significant positive correlation between PTX3 and glucose transport protein 4 levels in skeletal muscle. This study suggests that PTX3 may play a part of role as promoting insulin sensitivity of skeletal muscle in TSOD mice.


Type B Chloramphenicol Acetyltransferases Are Responsible for Chloramphenicol Resistance in Riemerella anatipestifer, China.
Riemerella anatipestifer causes serositis and septicaemia in domestic ducks, geese, and turkeys. Traditionally, the antibiotics were used to treat this disease. Currently, our understanding of R. anatipestifer susceptibility to chloramphenicol and the underlying resistance mechanism is limited. In this study, the cat gene was identified in 69/192 (36%) R. anatipestifer isolated from different regions in China, including R. anatipestifer CH-2 that has been sequenced in previous study. Sequence analysis suggested that there are two copies of cat gene in this strain. Only both two copies of the cat mutant strain showed a significant decrease in resistance to chloramphenicol, exhibiting 4 μg/ml in the minimum inhibitory concentration for this antibiotic, but not for the single cat gene deletion strains. Functional analysis of the cat gene via expression in Escherichia coli BL21 (DE3) cells and in vitro site-directed mutagenesis indicated that His79 is the main catalytic residue of CAT in R. anatipestifer. These results suggested that chloramphenicol resistance of R. anatipestifer CH-2 is mediated by the cat genes. Finally, homology analysis of types A and B CATs indicate that R. anatipestifer comprises type B3 CATs.


Lineage tracing demonstrates the venous origin of the mammalian lymphatic vasculature.
The origin of the mammalian lymphatic vasculature has been debated for more than 100 years. Whether lymphatic endothelial cells have a single or dual, venous or mesenchymal origin remains controversial. To resolve this debate, we performed Cre/loxP-based lineage-tracing studies using mouse strains expressing Cre recombinase under the control of the Tie2, Runx1, or Prox1 promoter elements. These studies, together with the analysis of Runx1-mutant embryos lacking definitive hematopoiesis, conclusively determined that from venous-derived lymph sacs, lymphatic endothelial cells sprouted, proliferated, and migrated to give rise to the entire lymphatic vasculature, and that hematopoietic cells did not contribute to the developing lymph sacs. We conclude that the mammalian lymphatic system has a solely venous origin.


Adverse effects of nonsteroidal anti-inflammatory drugs on the gastrointestinal system.
Two enzymes, cyclo-oxygenase (COX) and 5-lipoxygenase, act upon arachidonic acids to produce prostaglandins and leukotrienes. Inhibition of COX-2 by non-steroidal anti-inflammatory drugs (NSAIDs) lowers synthesis of proinflammatory prostaglandins and produces analgesia. COX-2 is highly inducible by endotoxin, IL-1, hypoxia, epidermal growth factor (EGF), benzo[a]pyrene, and transforming growth factor beta 1(TGF-beta 1). COX-1 in constitutively expressed. Conventional NSAIDs also inhibit the synthesis of cytoprotective prostaglandins by COX-1 in the gastrointestinal tract. Surplus arachidonic acids accumulate and enhance the generation of leukotrienes via the lipoxygenase pathway inducing neutrophil adhesion to endothelium and vasoconstriction. The NSAIDs harboring a carboxyl group also inhibit oxidative phosphorylation (OXPHOS) lowering adenosine-triphosphate (ATP) generation leading to loss of mucosal cell tight junctions and increased mucosal permeability. Administration of NSAIDs that do not interfere with OXPHOS, and concomitant use of prostaglandin analogues to restore cytoprotection reduces complications of NSAID use. However, no NSAID that lacks potential for serious gastrointestinal toxicity is currently available. Selective inhibitors of COX-2 and 5-lipoxygenase are newer, promising drugs. Surprisingly, COX-2 null mice are able to mount an inflammatory response, suffering however, from kidney dysfunction and a shortened life span. Results of clinical studies on the long-term use of NSAID drugs such as selective inhibitors are still pending.


[Solidarity in the responsibilities of machine manufacturers and shoemakers].
The purpose of this article is to give a general frame of the relationship existing between safety legislation for workplaces and the legislation connected to the CE marking and declaration of conformity for machinery, as provided by the new Directive 2006/42/EC and its Italian implementation (D.L. 17/2010). The main aim is to highlight the issues which, joining their efforts, the manufacturers of work tools and machinery should face in order to avoid disputes, seizures and/or legal procedures. The intersection between the two legal sources can sometimes become complex, although both the law and the controlling institutions intervene to offer possible answers. In such context the necessity for a careful re-examination of the relationship between machine builders and users becomes clear, especially as to the methods of designing and testing, the terms of contract, the conditions of manteinance, installation and updating.


A molecular epidemiological investigation of avian paramyxovirus type 1 viruses isolated from game birds of the order Galliformes.
The partial (370 nucleotides) fusion gene sequences of 55 avian paramyxovirus type 1 (APMV-1) isolates were obtained. Included were 41 published sequences, of which 16 were from strains of APMV-1 of previously determined lineages included as markers for the data analysed and 25 were from APMV-1 viruses isolated from game birds of the order Galliformes. In addition, we sequenced a further 14 game bird isolates obtained from the repository at the Veterinary Laboratories Agency. The game bird isolates had been obtained from 17 countries, and spanned four decades. Earlier studies have shown that class II APMV-1 viruses can be divided into at least 15 lineages and sub-lineages. Phylogenetic analysis revealed that the 39 game bird isolates were distributed across 12 of these sub-lineages. We conclude that no single lineage of Newcastle disease viruses appears to be prevalent in game birds, and the isolates obtained from these hosts reflected the prevailing, both geographically and temporally, viruses in poultry, pigeons or wild birds.


Stethoscopes or Maybe "Bacterioscopes" - Is hand Hygiene Solely Capable of Preventing Hospital-Associated Infections?
The stethoscope remains an indispensable diagnostic tool for medical students. Improper stethoscope hygiene may cause bacterial infections, including hospital-associated infections (HAIs), which challenge the Polish medical system. The study's main objective was to evaluate the hygiene habits declared by medical students. Moreover, microbiological control with the characteristics of potentially pathogenic microorganisms was performed. The study included 66 medical students from the Faculty of Medicine at the Jagiellonian University Medical College in Cracow, Poland. The participants filled in an anonymous questionnaire. Stethoscope contamination was assessed through isolation, identification, testing of antibiotic resistance, and clonality of the isolates bacterial pathogens. The survey showed that only 30.3% of students cleaned their stethoscopes after each patient, and 1.5% never did this. Of the 66 stethoscopes tested, 100% were positive for bacterial growth. Staphylococcus spp. was the most frequently isolated contaminant (50.5%). The questionnaire results demonstrated the necessity of the validated procedures for cleaning the stethoscopes. Stethoscopes used by medical students are contaminated with numerous bacterial species, including multidrug-resistant organisms. The clonal structure of the MRSA and MRSE populations acquired from stethoscopes has been demonstrated. Our results confirm the possibility that these medical devices mediate the spread of hazardous pathogens in the hospital environment. Practical exercises are essential to forming the correct hygiene habits involving stethoscopes, which enable practicing and checking the correctness of the established skills.


Pharmaceutical Industry Perspective on the Non-Clinical Evaluation of Novel Excipients: Results From an Industry Survey Conducted by the IQ Novel Excipient Working Group.
Excipients are essential components within drug products that contribute significantly to their overall quality, effectiveness, and safety. There is a lack of global, harmonized guidance relating to the non-clinical testing of novel excipients which is perceived to create uncertainty and strategic risk, potentially hindering innovation and disincentivizing their use. To test these perceptions, the IQ Novel Excipient Working Group surveyed member companies regarding their main concerns and prior experience regarding the non-clinical evaluation of excipients. Of the 19 respondents, 13 provided, collectively, 33 non-clinical program examples supporting the development of novel excipients. Programs were distributed across a range of therapeutic areas and included a variety of drug modalities and administration routes. Package designs were variable, but where possible, employed the use of existing data, supplemented with new toxicology studies as appropriate. Of the programs which had submitted data to regional health authorities, only three received feedback requesting additional studies or that demonstrated differences in regional opinion. In addition, companies provided recommendations on how the current (or new) guidance related to non-clinical excipient evaluation (and other areas, such as Chemistry, Manufacturing, and Controls and databases) may be improved.


Disseminated Cryptococcosis in an Immunocompetent Child.
Disseminated cryptococcosis in children is a classic affliction associated with human immunodeficiency virus (HIV) infection or primary inherited immunodeficiency disorders (PID) with central nervous system being the most common site of dissemination. We report a rare case of disseminated cryptococcosis in an 11-year-old girl who presented with pulmonary involvement, hepatosplenomegaly, and generalized lymphadenopathy. No known inherited or acquired immune deficiencies were identified after a comprehensive laboratory work-up including genetic sequencing. She responded well to anti-fungal therapy (flucytosine and amphotericin followed by fluconazole) and is on regular follow-up.


Pituitary failure secondary to head trauma. Case report.
A patient presented with hypopituitarism, 2 years after severe head trauma. Deficits of growth-hormone, follicle-stimulating hormone, luteinizing hormone, and borderline thyroid-stimulating hormone (TSH) were demonstrated. Normal TSH-releasing hormone (TRH) response and elevated prolactin indicated viable anterior pituitary tissue with inadequate hypothalamic control. Precautions are suggested for recognition and treatment of this syndrome.


EVALUATION AND MANAGEMENT OF DIFFICULT AIRWAY IN OBESITY A SINGLE CENTER RETROSPECTIVE STUDY.
The primary aim of this single center retrospective study was to evaluate difficult mask ventilation (DMV) and difficult laryngoscopy (DL) in a unique group of obese patients. A total of 427 adult patients with body mass index (BMI) ≥ 25 and surgically treated for endometrial cancer from 2011 to 2014 were assessed. Additional increase in BMI, comorbidities, bedside screening tests for risk factors, and the tools used to manage the patients were noted and their effects on DMV and/or DL investigated. Every escalation in the number of risk factors increased the probability of DMV 2.2-fold, DL 1.8-fold and DMV+DL 3.0-fold. Among bedside tests, limited neck movement (LNM), short neck (SN) and absence of teeth were significant for DMV (p < 0.05), LNM, SN and obstructive sleep apnea for DL (p < 0.05), and LNM and SN for DMV+DL (p < 0.05). However, a 10-point increase of BMI was not an independent risk factor when patients with BMI > 25% were considered. In conclusion, LNM and SN are independent risk factors for developing DMV and/or DL in obese endometrial cancer patients, while BMI increase over 30 was not additionally affecting difficult airway.


Atorvastatin-mediated protection of the retina in a model of diabetes with hyperlipidemia.
Insulin resistance, a key feature of obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM), results in a variety of metabolic and vascular abnormalities. Metabolic disturbances associated with diabetes could contribute to disrupting the structural and (or) functional integrity of the retina. The effects of atorvastatin on retinal cells in hyperlipidemic T2DM rats have not yet been investigated. We used Goto-Kakizaki (GK) rats fed with an atherogenic diet (AD) for 4 months to investigate whether atorvastatin (administered for 1 month) would slow-down or reverse the progression of lesions in the diabetic retina. Fluorogenic substrates were used to measure the proteasome activities in retinal cells. The production of reactive oxygen species was determined by immunofluorescence in frozen retina sections, using dihydroethydium. Nitrotyrosine levels were assessed using immunohistochemistry. Protein levels of ubiquitin conjugates, free ubiquitin, and ubiquitin activating enzyme E1 were determined with Western blotting. Atorvastatin significantly reduced the levels of oxidative stress that were induced by the AD and restored the proteasome activities in the diabetic GK rats. Atorvastatin therapy significantly improved local oxidative stress levels in GK rats fed with AD. Atorvastatin can, at least in part, restore the ubiquitin proteasome system, and may represent a pharmacological approach to prevent some of the complications associated with diabetic retinopathy.


Comparison of long-term survival of patients with BCLC stage B hepatocellular carcinoma after liver resection or transarterial chemoembolization.
Treatment of patients with Barcelona Clinic Liver Cancer Stage B hepatocellular carcinoma (BCLC-B HCC) is controversial. This study compared the long-term survival of patients with BCLC-B HCC who received liver resection (LR) or transarterial chemoembolization (TACE). A total of 257 and 135 BCLC-B HCC patients undergoing LR and TACE, respectively, were retrospectively evaluated. Kaplan-Meier method was used for long-term survival analysis. Independent prognostic predictors were determined by the Cox proportional hazards model. The hospital mortality rate was similar between groups (3.1% vs. 3.7%; P = 0.76). However, the LR group showed a significantly higher postoperative complication rate than the TACE group (28 vs. 18.5%; P = 0.04). At the same time, the LR group showed significantly higher overall survival rates (1 year, 84 vs. 69%; 3 years, 59 vs. 29%; 5 years, 37 vs. 14%; P<0.001). Moreover, similar results were observed in the propensity score model. Three independent prognostic factors were associated with worse overall survival: serum AFP level (≥400 ng/ml), serum ALT level, and TACE. LR appears to be as safe as TACE for patients with BCLC-B HCC, and it provides better long-term overall survival. However, prospective studies are needed to disclose if LR may be regarded as the preferred treatment for these patients as long as liver function is preserved.


Grazoprevir, ruzasvir, and uprifosbuvir for hepatitis C virus after NS5A treatment failure.
People with hepatitis C virus (HCV) infection who have failed treatment with an all-oral regimen represent a challenging treatment population. The present studies evaluated the safety and efficacy of grazoprevir, ruzasvir, and uprifosbuvir, with or without ribavirin, in participants who had failed an NS5A inhibitor-containing regimen. C-SURGE (PN-3682-021) and C-CREST Part C (PN-3682-011 and -012) were open-label, multicenter studies. Participants who had previously relapsed following an NS5A inhibitor-containing all-oral regimen were retreated with grazoprevir 100 mg, ruzasvir 60 mg, and uprifosbuvir 450 mg alone for 24 weeks or with ribavirin for 16 weeks. The primary efficacy endpoint was sustained virologic response (HCV RNA below the limit of quantitation [<15 IU/mL]) 12 weeks after treatment completion (SVR12). In C-SURGE, SVR12 was achieved by 49/49 (100%) and 43/44 (98%) genotype (GT)1 participants in the 24-week no ribavirin arm and the 16-week plus ribavirin arm (lost to follow-up, n = 1), respectively. In C-CREST Part C, SVR12 was achieved by 23/24 (96%) participants treated for 16 weeks with ribavirin (GT1, 2/2 [100%]; GT2, 13/14 [93%]; GT3, 8/8 [100%]). One participant with GT2 infection discontinued study medication after a single dose of grazoprevir, ruzasvir, and uprifosbuvir plus ribavirin due to serious adverse events of vomiting and tachycardia. The presence of baseline resistance-associated substitutions had no impact on SVR12. No participant who completed treatment in either study experienced virologic failure. Grazoprevir, ruzasvir, and uprifosbuvir, with or without ribavirin, for 16 or 24 weeks was safe and highly effective in participants with HCV infection who had previously failed NS5A inhibitor-containing therapy. (Hepatology 2017;66:1794-1804).


Visual and Thermal Image Processing for Facial Specific Landmark Detection to Infer Emotions in a Child-Robot Interaction.
Child-Robot Interaction (CRI) has become increasingly addressed in research and applications. This work proposes a system for emotion recognition in children, recording facial images by both visual (RGB-red, green and blue) and Infrared Thermal Imaging (IRTI) cameras. For this purpose, the Viola-Jones algorithm is used on color images to detect facial regions of interest (ROIs), which are transferred to the thermal camera plane by multiplying a homography matrix obtained through the calibration process of the camera system. As a novelty, we propose to compute the error probability for each ROI located over thermal images, using a reference frame manually marked by a trained expert, in order to choose that ROI better placed according to the expert criteria. Then, this selected ROI is used to relocate the other ROIs, increasing the concordance with respect to the reference manual annotations. Afterwards, other methods for feature extraction, dimensionality reduction through Principal Component Analysis (PCA) and pattern classification by Linear Discriminant Analysis (LDA) are applied to infer emotions. The results show that our approach for ROI locations may track facial landmarks with significant low errors with respect to the traditional Viola-Jones algorithm. These ROIs have shown to be relevant for recognition of five emotions, specifically disgust, fear, happiness, sadness, and surprise, with our recognition system based on PCA and LDA achieving mean accuracy (ACC) and Kappa values of 85.75% and 81.84%, respectively. As a second stage, the proposed recognition system was trained with a dataset of thermal images, collected on 28 typically developing children, in order to infer one of five basic emotions (disgust, fear, happiness, sadness, and surprise) during a child-robot interaction. The results show that our system can be integrated to a social robot to infer child emotions during a child-robot interaction.


CD4(+) CD56(+) lineage-negative malignancies are rare tumors of plasmacytoid dendritic cells.
CD4(+) CD56(+) lineage-negative malignancies are difficult to diagnose and classify. Recent studies have suggested that these malignancies may derive from plasmacytoid dendritic cells (pDC). In this report, we examine 10 cases of CD4+, CD56+ lineage-negative malignancies that presented in various tissue sites. The goal was to identify the morphologic, immunophenotypic, and genotypic findings to devise a diagnostic approach to tissue biopsies of these lesions and to confirm the proposed cell of origin. The mean age was 66 years (range, 45-80 years) with a male predominance (8 males/2 females). Frequent sites of disease included skin (60%) and peripheral blood/bone marrow (70%). Tumor cells were positive for CD45, CD43, CD4, and CD56 (9 of 10). The pDC markers, CD123 (9 of 10) and CD45RA (10 of 10), were detected by immunoperoxidase staining. Also noted was CD2 positivity (1 case), weak CD7 positivity (4 of 8 cases), weak CD33 (4 of 9 cases), TdT (2 cases), and CD68 (2 cases). All cases were otherwise negative for EBV (EBER), B-cell, T-cell, myeloid, and NK cell markers. T-cell receptor-gamma gene rearrangement was negative in all cases. Complex structural chromosomal abnormalities were seen in 3 of 5 cases, a subset of which may be recurrent in pDC malignancy. Overall prognosis was poor despite multiagent chemotherapy and/or radiation. Our study confirms that CD4+/CD56+ lineage-negative tumors are derived from pDC and have characteristic clinical, histopathologic, and immunophenotypic features. Furthermore, these rare neoplasms can be readily diagnosed using recently developed immunoperoxidase techniques.


The influence of a doppler ultrasound in arteriovenous fistula for dialysis failure related to some risk factors.
The increasing prevalence of chronic kidney disease has increased the demand for arteriovenous fistula (AVF) care. The objective of this study was to assess the relationship between some risk factors for AVF failure (advanced age, female sex, diabetes, obesity, central venous catheter, previous fistula, and hospitalization) and having a Doppler ultrasound performed preoperatively. A prospective study was performed with 228 dialysis patients from Imperatriz, Maranhão. Half of the sample was randomly selected to receive preoperative Doppler ultrasound and the other half did not, from the period of October 2016 to September 2018. There were 53 total failures corresponding to 23.2% of our sample, which is almost double that of the patients in the clinical group. Considering the failures and risk factors associated with the overall sample, there was a statistically significant association between a central venous catheter on the same side of the AVF with P = 0.04 (Odds Ratio 1.24) and obesity with P = 0.05 (Odds Ratio 1.36), which was not repeated in the Doppler ultrasound group individually. There was no statistically significant difference between the Doppler group and clinical group with respect to the amount of days of previous AVF hospitalization and failure. We concluded that the reduction of failures with an introduction of the Doppler was statistically significant in the overall sample, but establishing a relationship between specific risk factors and failure was only possible with two of the risk factors in the study - obesity and central venous catheter on the same side of the AVF.


CD4+ T cells and B cells are necessary for the transfer of protective immunity to Plasmodium chabaudi chabaudi.
It is shown here that B cells, in addition to CD4+ T cells, are necessary for the development of protective immunity to Plasmodium chabaudi chabaudi (P. chabaudi) in mice. Reconstitution of severe combined immunodeficient (SCID) mice with immune or normal CD4+ T cells protected the majority of mice against an otherwise lethal challenge but the mice were unable to clear their parasitemias. By contrast, transfer of the same T cell populations into athymic nu/nu mice enabled the recipients to control and clear their infections, immune CD4+ T cells being most effective. Furthermore, SCID mice given CD4+ T cells from immune and normal donors simultaneously with immune B cells also could eliminate their infection. Clearance of parasitemia correlated with the presence of malaria-specific antibodies in the serum. The role of B cells and CD4+ T cells in the protective immune response to P. chabaudi is discussed.