Diversification of the duplicated Rab1a genes in a hypoxia-tolerant fish, common carp (Cyprinus carpio).
Common carp is a widely cultivated fish with longer than 2,000 years domestication history, due to its strong environmental adaptabilities, especially hypoxia tolerance. The common carp genome has experienced a very recent whole genome duplication (WGD) event. Among a large number of highly similar duplicated genes, a pair of Ras-associated binding-GTPase 1a (Rab1a) genes were found fast diverging. Four analogous Rab1a genes were identified in the common carp genome. Comparisons of gene structures and sequences indicated Rab1a-1 and Rab1a-2 was a pair of fast diverging duplicates, while Rab1a-3 and Rab1a-4 was a pair of less diverged duplicates. All putative Rab1a proteins shared conserved GTPase domain, which enabled the proteins serve as molecular switches for vesicular trafficking. Rab1a-1 and Rab1a-2 proteins varied in their C-terminal sequences, which were generally considered to encode the membrane localization signals. Differential expression patterns were observed between Rab1a-1 and Rab1a-2 genes. In blood, muscle, spleen, and heart, the mRNA level of Rab1a-1 was higher than that of Rab1a-2. In liver and intestine, the mRNA level of Rab1a-2 was higher. Expression of Rab1a-1 and Rab1a-2 showed distinct hypoxia responses. Under severe hypoxia, Rab1a-1 expression was down-regulated in blood, while Rab1a-2 expression was up-regulated in liver. Compared with the less diverged Rab1a-3/4 gene pair, common carp Rab1a-1/2 gene pair exhibited strong characteristics of sub-functionalization, which might contribute to a sophisticated and efficient Ras-dependent regulating network for the hypoxia-tolerant fish.


Establishment of porcine transgenic embryonic germ cell lines expressing enhanced green fluorescent protein.
The purpose of this study was to isolate porcine embryonic germ (EG) cells and establish transgenic EG cell lines. Plasmid DNA was the enhanced green fluorescent protein (EGFP) vector. Porcine EG cells in rapid proliferation (4th to 9th passage) were transfected with LipofecTamine 2000 and TransFast reagents. Porcine EG cells transfected with a complex of 1 microg of DNA and 2 microL of LipofecTamine 2000 reagent yielded four EG-EGFP cell lines, which emitted bright green fluorescence. EG-EGFP cells cultured for more than 2 weeks without passage gave rise to various differentiated phenotypes. In addition, to determine the degree to which EG cells become integrated into the inner cell mass of host embryos, 135 embryos were injected with porcine EG-EGFP cells; 110 embryos survived and developed into blastocysts (81.5%). Eighty-four chimeric embryos contained fluorescent cells after culture; 49 blastocysts contained EG-EGFP cells in the inner cell mass. Our results suggested that the chimeric rate would not be improved via using different stages of embryos for injection.


Adolescent Δ-9-tetrahydrocannabinol exposure induces differential acute and long-term neuronal and molecular disturbances in dorsal vs. ventral hippocampal subregions.
Chronic exposure to Δ-9-tetrahydrocannabinol (THC) during adolescence is associated with long-lasting cognitive impairments and enhanced susceptibility to anxiety and mood disorders. Previous evidence has revealed functional and anatomical dissociations between the posterior vs. anterior portions of the hippocampal formation, which are classified as the dorsal and ventral regions in rodents, respectively. Notably, the dorsal hippocampus is critical for cognitive and contextual processing, whereas the ventral region is critical for affective and emotional processing. While adolescent THC exposure can induce significant morphological disturbances and glutamatergic signaling abnormalities in the hippocampus, it is not currently understood how the dorsal vs. ventral hippocampal regions are affected by THC during neurodevelopment. In the present study, we used an integrative combination of behavioral, molecular, and neural assays in a neurodevelopmental rodent model of adolescent THC exposure. We report that adolescent THC exposure induces long-lasting memory deficits and anxiety like-behaviors concomitant with a wide range of differential molecular and neuronal abnormalities in dorsal vs. ventral hippocampal regions. In addition, using matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS), we show for the first time that adolescent THC exposure induces significant and enduring dysregulation of GABA and glutamate levels in dorsal vs. ventral hippocampus. Finally, adolescent THC exposure induced dissociable dysregulations of hippocampal glutamatergic signaling, characterized by differential glutamatergic receptor expression markers, profound alterations in pyramidal neuronal activity and associated oscillatory patterns in dorsal vs. ventral hippocampal subregions.


Ketoconazole therapy of progressive coccidioidomycosis. Comparison of 400- and 800-mg doses and observations at higher doses.
One hundred and twelve patients with progressive pulmonary, skeletal, or soft tissue infections caused by Coccidioides immitis were randomly assigned to treatment with 400 or 800 mg per day dosages of ketoconazole. During therapy, if response was unsatisfactory, the protocol provided for treatment with higher doses. With 400 mg, ketoconazole resulted in 23.2 percent successes, which was similar to 32.1 percent successes with 800-mg treatments (p = 0.29). An additional six of 23 patients in whom initial therapy failed and who later received 1,200 or 1,600 mg per day of ketoconazole also showed improvement. However, among patients completing successful courses of therapy, relapses were more frequent in those requiring higher than 400-mg dosages for their success. From these studies, it is concluded that ketoconazole in doses above those currently recommended offer little or no benefit for most patients with non-meningeal forms of coccidioidomycosis.


Factors affecting the progression of renal dysfunction and the importance of salt restriction in patients with type 2 diabetic kidney disease.
Type 2 diabetic kidney disease (DKD) is the most common cause of end-stage renal failure, and the prevention of its progression has been a topic of discussion. Sixty type 2 DKD patients were retrospectively evaluated for 1 year. Factors independently affecting the annual Ccr decline were examined by multivariable linear regression analysis. Patients were further divided into 2 groups based on their degree of renal function, and between-group differences at study initiation were evaluated. Ccr values were 21.0 ± 11.8 mL/min/1.73 m(2) at study initiation, and 15.7 ± 10.9 mL/min/1.73 m(2) after 1 year of observation. The multivariable linear regression analysis indicated salt intake (standardized coefficient: -0.34, P = 0.010) and urinary protein excretion (standardized coefficient: -0.33, P = 0.011) to be factors independently affecting the annual Ccr decline. Although decliners (-9.8 ± 4.7 mL/min/1.73 m(2)/year) had a significantly higher salt intake than non-decliners (-1.1 ± 3.8 mL/min/1.73 m(2)/year) at study initiation, this difference disappeared at the end of the study as a result of intensive dietary education. In 21 decliners with an additional year of follow-up, the annual Ccr decline significantly improved from -10.1 ± 5.3 to -5.3 ± 7.4 mL/min/1.73 m(2)/year (P = 0.02). Salt intake and urinary protein excretion were associated with annual Ccr decline in type 2 DKD patients. Furthermore, dietary education covering salt intake may have positively affected the change in Ccr.


Sirt3 overexpression alleviates hyperglycemia-induced vascular inflammation through regulating redox balance, cell survival, and AMPK-mediated mitochondrial homeostasis.
Context: Sirtuin-3 (Sirt3), a NAD-dependent deacetylase, has been reported to be involved in many biological processes.Objective: The present study aimed to investigate the effect and mechanism of Sirt3 on diabetic mice and human umbilical vein endothelial cells (HUVECs) under high glucose (HG) condition.Materials and methods: HUVECs were cultured under HG and inflammation pathway was determined via qPCR, western blots, and immunofluorescence.Results: Sirt3 expression was reduced in the progression of diabetic nephropathy. Overexpression of Sirt3 sustains renal function and retard the development of diabetic nephropathy. Mechanistically, Sirt3 overexpression attenuated hyperglycemia-mediated endothelial cells apoptosis in kidney. Besides, Sirt3 overexpression repressed oxidative injury and blocked caspase-9-related apoptosis pathway. Moreover, we found that Sirt3 overexpression was associated with AMPK activation and the latter elevates PGC1α-related mitochondrial protective system, especially mitochondrial autophagy. Loss of opa1 and/or inhibition of AMPK could depress mitochondrial autophagy and exacerbates mitochondrial function, finally contributing to the death of human renal mesangial cells.Conclusions: Our results demonstrated the beneficial effects of Sirt3 in the progression of diabetic nephropathy. Increased Sirt3-activated AMPK pathway, augments PGC1α-related mitochondrial protective system, sustained redox balance and closed caspase-9-involved apoptosis pathway in the setting of diabetic nephropathy.


Epidemiology of cancer of the esophagus in Canada: 1931-1984.
Canadian patterns of morbidity and mortality from malignancies of the esophagus for the periods 1970-1980 and 1931-1984, respectively, were examined. Age-standardized morbidity and mortality rates have increased significantly for men during the two periods studied (p less than 0.01). Analysis of age-specific rates indicates that increases in age-standardized mortality rates for men are mostly attributable to significant increases in age-specific rates for five of the eight age groups studied. In contrast, age-standardized mortality rates for women have declined significantly during the same period (p less than 0.001), with significant declines in age-specific mortality rates noted for four of the eight age groups studied. Age-standardized morbidity rates for men have changed significantly for two age groups (p less than 0.05), with the rate of change of a third group being of borderline significance (p less than 0.10). Age-standardized morbidity rates for women have not changed significantly during the period 1970-1980 (p = 0.97), which was also characteristic of each of the eight age-specific morbidity rates studied (p greater than 0.40).


LodB is required for the recombinant synthesis of the quinoprotein L-lysine-ε-oxidase from Marinomonas mediterranea.
Marinomonas mediterranea is a marine gamma-proteobacterium that synthesizes LodA, a novel L-lysine-ε-oxidase (E.C. 184.108.40.206). This enzyme oxidizes L-lysine generating 2-aminoadipate 6-semialdehyde, ammonium, and hydrogen peroxide. Unlike other L-amino acid oxidases, LodA is not a flavoprotein but contains a quinone cofactor. LodA is encoded by an operon with two genes, lodA and lodB. In the native system, LodB is required for the synthesis of a functional LodA. In this study, we report the recombinant expression of LodA in Escherichia coli using vectors that allow its expression and accumulation in the cytoplasm. To reveal the L-lysine-ε-oxidase activity using the Amplex Red method for hydrogen peroxide detection, it is necessary to first remove the E. coli cytoplasmic catalases. The flavoprotein LodB is the only M. mediterranea protein required in the recombinant system for the generation of the cofactor of LodA. In the absence of LodB, LodA does not contain the quinone cofactor and remains in an inactive form. The results presented indicate that LodB participates in the posttranslational modification of LodA that generates the quinone cofactor.


Photosynthetic and transcriptomic responses of two C4 grass species with different NaCl tolerance.
This report reveals the effects of salt on the photosynthetic electron transport and transcriptome of the glycophyte Setaria viridis (S. viridis) and its salt-tolerant close relative halophyte Spartina alterniflora (S. alterniflora). S. viridis was unable to survive exposed to sodium chloride (NaCl) levels higher than 100 mM, in contrast, S. alterniflora could tolerate NaCl up to 550 mM, with negligible effect on gas exchange related parameters and conductance of electrons transport chain (gETC). Under salt, the prompt fluorescence (OJIP-curves) exhibits an increase in the O- and J-steps in S. viridis and much less for S. alterniflora. Flowing NaCl stress, a dramatic decline in the photosystem II (PSII) primary photochemistry was observed for S. viridis, as reflected by the drastic drop in Fv/Fm, Fv/Fo and ΦPSII; however, no substantial change was recorded for these parameters in S. alterniflora. Interestingly, we found an increase in the primary PSII photochemistry (ΦPSII) for S. alterniflora with increasing either NaCl concentration or NaCl treatment duration. The NPQ magnitude was strongly enhanced for S. viridis even at a low NaCl (50 mM); however, it remains unchangeable or slightly increased for S. alterniflora at NaCl levels above 400 mM. After NaCl treatment, we found an increase in both the proportion of oxidized P700 and the amount of active P700 in S. viridis and almost no change for S. alterniflora. Under salt, the net photosynthetic rate (A) and stomatal conductance (gs) measurements demonstrate that A decreases earlier in S. viridis, even after one week exposure to only 50 mM NaCl; in contrast, in S. alterniflora, the effect of NaCl on A and gs was minor even after exposure for two weeks to high NaCl levels. For S. viridis exposed to 50 mM NaCl for 12 d, carbon dioxide (CO2) at a concentration of 2000 μL L-1 could not fully restore A to the control (Ctrl) level. Conversely, in S. alterniflora, high CO2 can fully restore A for all NaCl treatments except at 550 mM. RNA-seq data shows a major impact of NaCl on metabolic pathways in S. viridis and we found a number of transcription factors potentially related to NaCl responses. For S. alterniflora, no major changes in the transcriptomic levels were recorded under NaCl stress. To confirm our data analysis of RNA-seq, we performed quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis for randomly selected four genes for each species (8 genes in total) and we found that our results (up- and/or down-regulated genes) are fully consistent and match well our RNA-seq data. Overall, this study showed drastically different photosynthetic and transcriptomic responses of a salt-tolerant C4 grass species and one salt-sensitive C4 grass species to NaCl stress, which suggests that S. alterniflora could be used as a promising model species to study salt tolerance in C4 or monocot species.


New frontiers and prospects of metal-organic frameworks for removal, determination, and sensing of pesticides.
Pesticides have been widely used in agriculture to control, reduce, and kill insects. Humans are also being using pesticides to control insidious animals in daily life. By these practices, a huge volume of pesticides is introduced to the environment. Despite broad-spectrum applicability, pesticides also have hazardous effects on both humans and animals at high and low concentrations. Long-term exposure to pesticides can cause different diseases, like leukemia, lymphoma, and cancers of the brain, breasts, prostate, testis, and ovaries. Reproductive disorders from pesticides include birth defects, stillbirth, spontaneous abortion, sterility, and infertility. Therefore, the application of determination and treatment methods for pre-concentration and removal of these toxic materials from the environment appears a vital concern. To date, different materials and approaches have been employed for these purposes. Among these approaches, multifunctional metal-organic frameworks (MOFs)-assisted adsorption and determination processes have always been in the spotlight. These facts are due to exclusive properties of MOFs in terms of the crystallinity, large surface area, high chemical, and physical stability, and controllable structure as well as unique features of adsorption and determination process in terms of simple, easy, cheap, available method and ability to use in large and industrial scales. In the present work, we illustrate the exceptional features of MOFs as well as the possible mechanism for the adsorption of pesticides by MOFs. The use of these fantastic materials for pre-concentration and removal of pesticides are extensively explored. In addition, the performance of MOFs was compared with other adsorbents. Finally, the new frontiers and prospects of MOFs for the determination, sensing, and removal of pesticides are presented.


Survey of the anticoccidial feed additive nicarbazin (as dinitrocarbanilide residues) in poultry and eggs.
A survey was carried out on the occurrence of dinitrocarbanilide (DNC), the marker residue for nicarbazin, in poultry produced in Ireland during 2002-2004. Liver (n = 736) and breast muscle samples (n = 342) were tested. DNC residues were found in 40 and 26% of liver and breast muscle samples at levels greater than 12.5 and 5 microg kg(-1), respectively. DNC residues were found at >200 microg kg(-1) in 12 and 0% of liver and muscle samples, respectively. Samples of breast muscle (n = 217) imported from 11 countries were also tested for DNC residues. A lower incidence of DNC residues (6%) was found in imported breast muscle. Egg samples (n = 546) were tested and DNC residues were found in nine samples, with levels ranging between 14 and 122 microg kg(-1). Analysis of poultry, carried out as part of official food inspection in the period 2004-2006, indicated a reduction in the number of broiler liver samples containing DNC at >200 microg kg(-1), to approximately 7%. Low levels of DNC residues continue to be found in <2% of egg samples.


Detection of placental-type alkaline phosphatase in ovarian cancer.
A monoclonal antibody, H317, has been used for the sensitive and specific detection of placental-type alkaline phosphatase (PLAP) in sera, solubilized tissue extracts and fixed tumour tissue sections from patients representing a variety of ovarian tumours. PLAP was detected in over 30% of these sera and in most solubilized tumour tissue extracts. There was no association between circulating PLAP levels and either tissue extract levels or immunohistological staining of ovarian tumour tissue sections with H317. Nevertheless, immunohistology demonstrated the heterogeneity of cellular localization of PLAP within different tumours, and can often be of value in localizing tumour tissue.


Evaluation of the cancer chemopreventive efficacy of silibinin in genetic mouse models of prostate and intestinal carcinogenesis: relationship with silibinin levels.
Silibinin, a flavonolignan from milk thistle seeds, possesses cancer chemopreventive properties in rodent models of carcinogenesis. We tested the hypotheses that silibinin or silipide, silibinin formulated with phospholipids, delays tumour development in TRAMP or Apc(Min) mice, genetic models of prostate or intestinal malignancies, respectively. Mice received silibinin or silipide with their diet (0.2% silibinin equivalents) from weaning. Intervention with silipide reduced the size of well differentiated TRAMP adenocarcinomas by 31%. Silipide and silibinin decreased the incidence of poorly differentiated carcinomas by 61% compared to mice on control diet. Silipide decreased plasma levels of insulin-like growth factor (IGF)-1 by 36%. Levels of circulating IGF binding protein (IGFBP)-3 in mice on silipide or silibinin were 3.9- or 5.9-fold, respectively, elevated over those in control TRAMP mice. In Apc(Min) mice silibinin, but not silipide, had only a marginal adenoma number-reducing effect. The results cautiously support the advancement of silipide to the stage of clinical investigation in prostate cancer.


Microfilaments and membranes.
Microfilaments are intimately involved in many plasma and internal membrane functions. Recent studies of microfilament-membrane linking proteins and non-filamentous myosins implicate microfilaments in diverse functions, including transmembrane signaling and vesicular transport. Evidence from animal and yeast cells suggests that microfilaments are regulated by protein phosphosphorylation, small GTP-binding proteins and associations involving SH3 domains.


Early repair for infants with cleft lip and nose.
To study the results 10 years after early surgical cleft lip and nose repair. We present the outcome of 123 early cleft lip repairs whose condition was managed in a multidisciplinary team according to a strict protocol. We give the observation results of operations of a single surgeon's neonatal surgery over a 10-year period in term of aesthetic assessments and dental arch relationships. One hundred and twenty-three patients were operated on during the first 4 weeks of life; a subgroup of 40 child had been operated on at a week or less of age. The results show good aesthetic assessments and dental relationships, with facial growth appropriate for the age. We are currently encouraging early cleft lip and nose repair in the full-term baby as the good method of management of newborns with cleft.


A phase II study of stereotactic radiotherapy after FOLFIRINOX for locally advanced pancreatic cancer (LAPC-1 trial): Long-term outcome.
To report the long-term outcome of a multicenter phase II study with FOLFIRINOX followed by stereotactic body radiotherapy (LAPC-1 trial) in patients with locally advanced pancreatic cancer (LAPC). Patients with histological confirmation of LAPC inoperable at diagnosis were enrolled. Induction therapy with 8 cycles of FOLFIRINOX was administered. If no disease progression was found after chemotherapy, patients received stereotactic body radiotherapy (SBRT) at a total dose of 40 Gy in 5 fractions. In LAPC-1 trial, 50 patients were included, but due to disease progression in 11 patients under chemotherapy, 39 patients received stereotactic SBRT after FOLFIRINOX treatment. In whole population, the 1- and 3-year overall survival (OS) were 62% and 10%, respectively. Median follow-up was 13 months. The SBRT group had median OS of 18 months (95% CI 13.2-21.5) versus 5 months (95% CI 4.1-6.7) in non-SBRT group (p<0.001). After chemoradiotherapy, seven patients underwent surgery achieving a radical resection. Patients who underwent surgery had a 3-years OS of 43% compared to 6.5% in the unresected group (p=0.03). Four patients developed grade ≥ 3 adverse events during SBRT. Long-term survival has been found in patients with LAPC underwent FOLFIRINOX followed by SBRT. This approach increased the probability of a radical surgery. The resected patients achieved a significant better survival compared to unresected group.


The Relationship Between HIV Antibody Titer, HIV Viral Load, HIV p24 Antigen, and CD4 T-cell Count Among Iranian HIV-positive Patients.
This study aimed to simultaneously measure and assess the correlation between the available HIV infection parameters including HIV antibody, p24 Antigen, CD4 cell count, and viral load at the different stages of HIV disease among HIV-positive individuals in Iran. Fifty HIV-positive individuals were classified into three stages (1, 2, and 3) according to the HIV disease stages classification, available in Control of Disease and Prevention (CDC) guideline. 10 ml of the venous blood sample was collected to run the tests for HIV antibody and p24 Ag levels, CD4 cell counts, and viral load. Pearson's correlation test was employed to calculate the coefficients for the in-between correlation of different HIV parameters in each stage. Of 50 participants, 17 (34%), 25 (50%), and 8 (16%) patients belonged to stages 1, 2, and 3, respectively. Sexual relationship was the main route of HIV transmission among the patients (36%); however, injecting drug use (20%) was also reported frequently. There was no significant correlation between the parameters of HIV disease in different stages in the present study. The findings showed no correlation between HIV parameters in the present study. Considering the fact that the association of HIV antibodies with HIV disease progression in infected individuals is independent of HIV-1 RNA levels, combined measurement of HIV-1 RNA and CD4 cell counts should be routinely carried out in HIV infected patients follow up.


A constitutional variant in the transcription factor EP300 strongly influences the clinical outcome of patients submitted to allo-SCT.
An adequate response of the innate immune system after allo-SCT is crucial for the clinical outcome of patients submitted to this procedure. EP300 is one of the key genes of the innate immune system (IIS). We evaluated the influence of gene variant A>G rs20551 in EP300 in donor and/or recipient on clinical results after HLA-identical sibling allo-SCT. Patients with AA gene variant had a lower relapse incidence (31 vs 48%, P=0.025; odds ratio (OR)=1.6, P=0.05), attained better disease-free survival (AA: 53% vs AG+GG: 24%, P=0.001; OR=1.8, P=0.01), and better OS (AA: 53% vs AG+GG: 34%, P=0.001; OR=1.9, P=0.007). This beneficial association was more evident when AA gene variant was present in both donor and patient. In healthy individuals, AA gene variant was associated with lower IL2 production after a mitogenic stimuli, higher CD4+ cell response after CMV infection, and higher expression of innate immune genes (IRF-3 and MIF), cell cycle genes (AURKB, CCNA2 and CCNB1), lymphocyte survival genes (NFAT5 and SLC38A2), and with a lower expression of P53 compared with recessive GG gene variant. These findings suggest a beneficial effect of the AA gene variant in rs20551 on clinical outcome after allo-SCT.


Impairment of learning by cueing during postlearning slow-wave sleep in rats.
Rats were trained in a two-way shuttle avoidance task, 20 trials per day for 3 consecutive days. The conditioned stimulus preceding a footshock was an ear shock in expt. 1, it was a tone in expt. 2. In both experiments, experimental animals received non-awakening ear shocks during 6 periods of slow-wave sleep (SWS) following each conditioning session. Control animals received no ear shock during SWS. Results showed that ear shocks delivered during SWS impaired subsequent learning performances only in expt. 1, i.e. when they were relevant to the learning task and could act as a reminder treatment.


Role of intestinal glucose absorption in glucose tolerance.
Intestinal glucose absorption is integral to postprandial glucose homeostasis. Glucose absorption is dependent on a number of factors, including the exposure of carbohydrate to the mucosa of the upper gastrointestinal tract (determined particularly by the rates of gastric emptying and small intestinal transit), the digestion of complex carbohydrate into monosaccharides, and glucose sensing and transport by the intestinal mucosa. The absorption of glucose in the small intestine is not only a determinant of the appearance of exogenous glucose in the peripheral circulation, but is also coupled to the release of gastrointestinal hormones that in turn influence postprandial glucose metabolism through modulating gastrointestinal motor function, insulin and glucagon secretion, and subsequent energy intake. This review describes the physiology and pathophysiology of intestinal glucose absorption in health and type 2 diabetes, including its relevance to glucose tolerance and the management of postprandial hyperglycaemia.


Phorbol ester-induced changes in rat hippocampal glycoprotein fucosylation.
Studies on glycoprotein fucosylation were carried out using hippocampal slices from rat brain. These slices were incubated in the presence of the protein kinase C (PKC) activating phorbol ester, 4 beta-phorbol-12,13-dibutyrate (PDBu), or an inactive isoform, 4 alpha-phorbol-12,13-didecanoate (PDD), respectively, for 7 min followed by a 60 min pulse of [3H]fucose. PDBu caused an increase in [3H]fucose incorporation into glycoproteins by 29% as well as an activation of the fucokinase enzyme reaction by 21%. The PDBu-induced stimulation of [3H]fucose insertion into hippocampal glycoproteins was abolished by the PKC inhibitors, staurosporine and H7. The importance of a PKC-regulated glycoprotein fucosylation in mechanisms underlying changes in neuronal plasticity is discussed.


Active boundary layers in confined active nematics.
The role of boundary layers in conventional liquid crystals is commonly related to the mesogen anchoring on confining walls. In the classical view, anchoring enslaves the orientational field of the passive material under equilibrium conditions. In this work, we show that an active nematic can develop active boundary layers that topologically polarize the confining walls. We find that negatively-charged defects accumulate in the boundary layer, regardless of the wall curvature, and they influence the overall dynamics of the system to the point of fully controlling the behavior of the active nematic in situations of strong confinement. Further, we show that wall defects exhibit behaviors that are essentially different from those of their bulk counterparts, such as high motility or the ability to recombine with another defect of like-sign topological charge. These exotic behaviors result from a change of symmetry induced by the wall in the director field around the defect. Finally, we suggest that the collective dynamics of wall defects might be described in terms of a model equation for one-dimensional spatio-temporal chaos.


Alpha 1-antitrypsin and ilomastat inhibit inflammatory proteases present in human middle ear effusions.
Proteases of both the serine and metalloproteinase families have been shown to play a role in the pathogenesis of otitis media (OM). Inhibitors of proteases from each of these families have been shown to beneficially impact disease progression in a number of related chronic inflammatory conditions, but their use has not been studied in OM. The purpose of this study was to assess the activity of the protease inhibitors recombinant alpha 1-antitrypsin (rAAT) and ilomastat on inflammatory proteases present in human middle ear effusions (MEEs), with a view to their potential utility in the treatment of OM. Prospective and ex vivo. MEEs were collected from 100 patients presenting for middle ear surgery, most commonly tympanostomy tube placement or treatment of acute posttympanostomy otorrhea (APTO). MEEs were analyzed for the presence of matrix metalloproteinases (MMPs) and human neutrophil elastase (HNE) and the inhibitory activity of rAAT and ilomastat on these proteases, respectively. MMP levels were highest in APTO, and HNE was highest in chronic suppurative OM and APTO. High levels of MMP and HNE (>3 mAU/min) were found in 52% and 37% of MEEs, respectively. Ilomastat and rAAT demonstrated significant inhibition of MMP and HNE activity (>30% reduction), respectively, in 80% and 82% of MEEs with high levels of activity. Proteases are commonly found in OM. Ilomastat and rAAT are potent inhibitors of proteases in MEEs across a wide range of OM in humans. Investigation into the potential therapeutic benefits of these protease inhibitors is warranted.


Effects of mycophenolate mofetil on chronic allograft nephropathy by affecting RHO/ROCK signal pathways.
We sought to investigate the effects of mycophenolate mofetil (MMF) on chronic allograft nephropathy (CAN) by affecting Rho and ROCK signal pathways. Male inbred F344 rat renal grafts orthotopically transplanted into Lewis rats were first treated with CsA (10 mg/kg(-1).d(-1) x 10 d) and then divided into 3 groups (each n = 9): (1) orally vehicle, (2) cyclosporine (CsA, 6 mg/kg(-1).d(-1)) and (3) MMF (20 mg/kg(-1).d(-1)). In addition we performed autografts of F344 (n = 10) at 4, 8, and 12 weeks, serum creatinine (SCr) was measured and pathologic changes assessed. Expression of RhoA and ROCK-1 was determined by real-time reverse transcriptase polymerase chain reaction. Expressions of alpha-smooth muscle actin (alpha-SMA) and connective tissue growth factor (CTGF) were observed by immunohistochemistry. SCr and Banff score began to increase at 4 weeks in all 3 allografted groups with obvious deterioration in both the vehicle and CsA groups at 8 and 12 weeks. The differences between vehicle/CsA and autografts were significant (P = .000). SCr and Banff score among the MMF group increased mildly and moderately at 8 and 12 weeks, respectively, but were significantly lower than those in the vehicle/CsA cohort (P < .05). Expressions of RhoA and ROCK-1 mRNAs and proteins were observed in mesangial and tubular cells, increasing gradually along with the progression of chronic allograft nephropathy (CAN). There was a negative correlation between RhoA/ROCK-1 mRNA and Banff score (r = -.637, p = .000; r = -.676, P = .000) or SCr (r = -.705, P = .000; r = -.756, P = .000). MMF downregulated gene and protein expressions of RhoA and ROCK-1. CsA had little effect on these expressions. Expressions of alpha-SMA and CTGF were observed in renal epithelial and tubular cells. Herein we have demonstrated abnormal expression of RhoA and ROCK-1 signal pathways, which may play roles in CAN. MMF may attenuate CAN by downregulating the expression of RhoA/ROCK-1, alpha-SMA, and CTGF.


Urocortin 2 promotes hypertrophy and enhances skeletal muscle function through cAMP and insulin/IGF-1 signaling pathways.
Although it is well established that urocortin 2 (Ucn2), a peptide member of the corticotrophin releasing factor (CRF) family, and its specific corticotrophin-releasing factor 2 receptor (CRF2R) are highly expressed in skeletal muscle, the role of this peptide in the regulation of skeletal muscle mass and protein metabolism remains elusive. To elucidate the mechanisms how Ucn2 directly controls protein metabolism in skeletal muscles of normal mice, we carried out genetic tools, physiological and molecular analyses of muscles in vivo and in vitro. Here, we demonstrated that Ucn2 overexpression activated cAMP signaling and promoted an expressive muscle hypertrophy associated with higher rates of protein synthesis and activation of Akt/mTOR and ERK1/2 signaling pathways. Furthermore, Ucn2 induced a decrease in mRNA levels of atrogin-1 and in autophagic flux inferred by an increase in the protein content of LC3-I, LC3-II and p62. Accordingly, Ucn2 reduced both the transcriptional activity of FoxO in vivo and the overall protein degradation in vitro through an inhibition of lysosomal proteolytic activity. In addition, we demonstrated that Ucn2 induced a fast-to-slow fiber type shift and improved fatigue muscle resistance, an effect that was completely blocked in muscles co-transfected with mitogen-activated protein kinase phosphatase 1 (MKP-1), but not with dominant-negative Akt mutant (Aktmt). These data suggest that Ucn2 triggers an anabolic and anti-catabolic response in skeletal muscle of normal mice probably through the activation of cAMP cascade and participation of Akt and ERK1/2 signaling. These findings open new perspectives in the development of therapeutic strategies to cope with the loss of muscle mass.


An individualized approach to tracking and treating Alzheimer's disease.
There can be substantial variation in the expression of Alzheimer's disease. Patients vary in who is affected (e.g., education, age at onset), in how they are affected (e.g., neuropathological profile, comorbidities), and in when they present (i.e., stage of illness). Even people with similar starting profiles can have dramatically different courses. For these reasons, tracking disease progression in individuals and the effects of treatment on them can be challenging. This variability further complicates the difficulty of dementia's high dimensionality--Alzheimer's disease affects many aspects of cognition, function, and behavior.


Chaperone action of a versatile small heat shock protein from Methanococcoides burtonii, a cold adapted archaeon.
The Methanococcoides burtonii small heat shock protein (Mb-sHsp) is an alphaB-crystallin homolog that delivers protein stabilizing and protective functions to model enzymes, presumably reflecting its role as a molecular chaperone in vivo. Although the gene encoding Mb-shsp was cloned from a cold-adapted microorganism, the Mb-sHsp is an efficient protein chaperone at temperatures far above the optimum growth temperature of M. burtonii. We show that Mb-sHsp can prevent aggregation in E. coli cell free extracts at 60 degrees C for 4 h and can stabilize bovine liver glutamate dehydrogenase for 3 h at 50 degrees C. Surface plasmon resonance was used to determine the binding affinity of Mb-sHsp for denatured proteins. Mb-sHsp bound tightly to denatured lysozyme but not to the native form. When Mb-Cpn and Mg(2+)-ATP were added to the reaction, bound lysozyme was released from Mb-sHsp establishing that Mb-Cpn is able to off-load folding intermediates from Mb-sHsp. In addition, Mb-sHsp and Mb-Cpn also function cooperatively to protect an enzyme substrate. Through characterization of these M. burtonii chaperones, we were able to reconstitute a key heat shock regulated protein folding function of this cold adapted organism in vitro.


[Expression of telomerase activity and its related genes in the marrow hemopoietic stem cells of children with aplastic anemia].
To explore the relationship of telomerase RNA component (hTERC) and the telomerase reverse transcriptase (hTERT) with telomerase activity in the marrow hemopoietic stem cells of children with aplastic anemia (AA). Fifty-two children with chronic AA, 13 children with acute AA and 21 normal controls were enrolled in the study. Telomerase activity and the expression of mRNA of hTERT and hTERC were detected by Telomeric Repeat Amplification Protocol (TRAP) with silver staining and real-time Q-PCR respectively. Levels of telomerase activity in both the chronic and acute AA groups were higher than in the control group (P<0.01). The AA groups had significantly higher expression of hTERT mRNA than the control group (P<0.01). The chronic AA group had higher expression of hTERT mRNA and telomerase activity than the acute AA group (P<0.05). There was no significant difference in the expression of hTERC mRNA among the three groups (P=0.812). There was a significant correlation between the expression of hTERT mRNA and telomerase activity (r=0.660, P<0.01). Expression of telomerase activity may be involved in the pathophysiology and development of AA, and hTERT plays a crucial role in expression of telomerase activity.


Paroxysmal alexia.
This report describes a case of paroxysmal alexia which progressed to a persistent syndrome of alexia without agraphia. The sequence of symptoms beginning with a sensation of eyeball movement followed by blurred vision in the affected eye, alexia and diminished awareness strongly implicates an ictal mechanism. Anatomical, physiological and psychological considerations suggest that the syndrome arose from functional disruption between the visual cortex and the dominant inferior parietal cortex.


A randomized trial of the effects of nebulized albuterol on pulmonary edema in brain-dead organ donors.
Donor lung utilization rates are persistently low primarily due to donor lung dysfunction. We hypothesized that a treatment that enhances the resolution of pulmonary edema by stimulating the rate of alveolar fluid clearance would improve donor oxygenation and increase donor lung utilization. We conducted a randomized, blinded, placebo-controlled trial of aerosolized albuterol (5mg q4h) versus saline placebo during active donor management in 506 organ donors.The primary outcome was change in oxygenation arterial partial pressure of oxygen/fraction of inspired oxygen [PaO2/FiO2] from enrollment to organ procurement.The albuterol (n¼260) and placebo (n¼246)groups were well matched for age, gender, ethnicity,smoking, and cause of brain death. The change in PaO2/FiO2 from enrollment to organ procurement did not differ between treatment groups (p¼0.54) nor did donor lung utilization (albuterol 29% vs. placebo 32%,p¼0.44). Donors in the albuterol versus placebo groups were more likely to have the study drug dose reduced (13% vs. 1%, p<0.001) or stopped (8% vs. 0%,p<0.001) for tachycardia. In summary, treatment with high dose inhaled albuterol during the donor management period did not improve donor oxygenation or increase donor lung utilization but did cause tachycardia.High dose aerosolized albuterol should not be used in donors to enhance the resolution of pulmonary edema.


Bromodeoxyuridine-induced mutations in synchronous Chinese hamster cells: temporal induction of 6-thioguanine and ouabain resistance during DNA replication.
Mutations were induced in synchronous Chinese hamster cells by bromodeoxyuridine (BUdR) incorporated into cells for one-hour periods in the cell cycle. There was a very pronounced temporal dependence during the first half of the DNA synthesis period for the induction of damage leading to 6-thioguanine (6TG) and ouabain resistance. No mutants above background were induced by exposure to BUdR in G1 and G2 cells, and very few mutants were induced in the latter part of the DNA synthesis period. The peak for the induction of 6TG resistance occurs at about two hr in the DNA synthesis period; one hour later there is a peak for the induction of ouabain resistance. Both peaks occur before the time of maximum incorporation of BUdR into DNA. These results suggest that the mutagenesis by BUdR is associated with at least two nuclear genes, which replicate at two hr and three hr in the DNA synthesis period.


Application of Bayer red mud for iron recovery and building material production from alumosilicate residues.
Red mud is a solid waste produced in the process of alumina extraction from bauxite. In this paper, recovery iron from Bayer red mud was studied with direct reduction roasting process followed by magnetic separation, and then building materials were prepared from alumosilicate residues. After analysis of chemical composition and crystalline phase, the effects of different parameters on recovery efficiency of iron were carried out. The optimum reaction parameters were proposed as the following: ratio of carbon powder: red mud at 18:100, ratio of additives: red mud at 6:100, roasting at 1300 degrees C for 110min. With these optimum parameters, total content of iron in concentrated materials was 88.77%, metallization ratio of 97.69% and recovery ratio of 81.40%. Then brick specimens were prepared with alumosilicate residues and hydrated lime. Mean compressive strength of specimens was 24.10MPa. It was indicated that main mineral phase transformed from nepheline (NaAlSiO4) in alumosilicate residues to gehlenite (Ca2Al2SiO7) in brick specimens through X-ray diffraction (XRD) technology. The feasibility of this transformation under the experimental conditions was proved by thermodynamics calculation analysis. Combined the recovery of iron with the reuse of alumosilicate residues, it can realize zero-discharge of red mud from Bayer process.


Quantitative risk assessment for Listeria monocytogenes in smoked or gravad salmon and rainbow trout in Sweden.
The objective of the present work was to develop a quantitative risk assessment model in which the exposure and risk of acquiring listeriosis from consumption of packaged smoked or gravad salmon and rainbow trout were estimated. An Excel spreadsheet model was constructed in which variables were represented by distributions based on surveys of L. monocytogenes in these food products, and on demographic and consumption data. Growth or inactivation was not included in the model. The model was run through Monte Carlo simulations using the @Risk software (Palisade Corporation). The probability of illness per serving was calculated using two dose-response models from the literature. The first was an exponential model in which the species specific constant R, that helps define the dose-response curve, previously has been estimated to be 1.18 x 10(-10) based on German data (GR). In this study, R was estimated to 5.6 x 10(-10) based on Swedish data. The second model was a flexible Weibull-Gamma model (WG), with different coefficients for high- and low-risk groups. The exponential model (GR), although conservative and generally overestimating the risk, still predicted a lower probability of illness than the WG-model. The estimated mean risk per serving was 2.8 x 10(-5) (GR, high-risk group), 2.0 x 10(-3) (WG, low-risk group) and 0.016 (WG, high-risk group), respectively. The average number of reported listeriosis cases in Sweden is 37 per year. In comparison, the mean number of annual cases predicted by the risk assessment model was 168 (range 47 to 2800, GR, high-risk group), and 95 000 (range 34 000 to 1.6 x 10(6), WG high-risk group), respectively. If 1 to 10% (uniform distribution) of strains, instead of all, were considered virulent, the mean number of predicted cases would decrease to nine (GR) and 5200 (WG), respectively. The mean annual cumulative individual risk in the high-risk group based on a monthly exposure was estimated to be 4.0 x 10(-4) (range 8.0 x 10(-8) to 5.4 x 10(-3), GR). This risk increased to 1.5 x 10(-3) (range 1.7 x 10(-5) to 9.2 x 10(-3), GR) based on a weekly exposure. The risk assessment model was most sensitive to the input distribution describing the level of contamination and to a lesser degree on the prevalence of L. monocytogenes, the proportion of virulent strains, and serving sizes. A lack of data on the prevalence and concentration of L. monocytogenes in these products, dose-response data and quantitative information on the proportion of virulent strains were identified.


Discovery of 2-arylamino-4-(1-methyl-3-isopropylsulfonyl-4-pyrazol-amino)pyrimidines as potent anaplastic lymphoma kinase (ALK) inhibitors.
A new series of 2,4-diamino pyrimidine derivatives with a sulfone-substituted pyrazole right side-chain were discovered as potent anaplastic lymphoma kinase inhibitors. Structure-activity relationship of the left side-chain on phenyl substitutions were explored which delivered many potent ALK inhibitors. Among them, 29a showed favorable pharmacokinetic profiles in rats and dogs together with significant antitumor efficacy in EML4-ALK fusion xenograft model.


Studies on digestion and absorption in the intestines of growing pigs. 8. Measurements of the flow of total lipid, acid-detergent fibre and volatile fatty acids.
1. Seventeen pigs fitted with single re-entrant cannulas in either the duodenum (posterior to the point of entry of the bile and pancreatic ducts), the mid-jejunum, or the terminal ileum, and a further twenty-four non-cannulated pigs were used. 2. Three diets were used: these contained barley, fine wheat offal, white fish meal, minerals and vitamins (diet BWF); starch, sucrose, maize oil, cellulose, minerals, vitamins and either groundnut meal (diet SSG) or casein (diet SSC). 3. The quantities of total lipid (TL), acid-detergent fibre (ADF) and volatile fatty acids (VFA) passing through the re-entrant cannulas and excreted in the faeces in 24 h were measured. These were used to determine the net absorption (or synthesis or secretion) in the different regions of the intestine. 4. There was substantial secretion of TL into the proximal small intestine and major absorption from the distal portion for all three diets. In the large intestine there was little or no further net absorption for diets SSG and SSC, but significant synthesis or secretion for diet BWF. 5. Fibre digestion occurred in both the small and large intestines and the apparent absorption of ADF in the different regions studied was influenced by diet. 6. There were detectable amounts of VFA at all sites but only at the ileum and in the faeces could they be accurately measured. Diet did not affect the molar proportions of acetate, propionate and butyrate in ileal digesta, but did have an effect on these VFA in the faeces.


Transcriptomic and clinical heterogeneity of metastatic disease timing within metastatic castration-sensitive prostate cancer.
Metastatic castration-sensitive prostate cancer (mCSPC) is commonly classified into high- and low-volume subgroups which have demonstrated differential biology, prognosis, and response to therapy. Timing of metastasis has similarly demonstrated differences in clinical outcomes; however, less is known about any underlying biologic differences between these disease states. Herein, we aim to compare transcriptomic differences between synchronous and metachronous mCSPC and identify any differential responses to therapy. We performed an international multi-institutional retrospective review of men with mCSPC who completed RNA expression profiling evaluation of their primary tumor. Patients were stratified according to disease timing (synchronous versus metachronous). The primary endpoint was to identify differences in transcriptomic profiles between disease timing. The median transcriptomic scores between groups were compared with the Mann-Whitney U test. Secondary analyses included determining clinical and transcriptomic variables associated with overall survival (OS) from the time of metastasis. Survival analysis was carried out with the Kaplan-Meier method and multivariable Cox regression. A total of 252 patients were included with a median follow-up of 39.6 months. Patients with synchronous disease experienced worse 5-year OS (39% versus 79%; P < 0.01) and demonstrated lower median androgen receptor (AR) activity (11.78 versus 12.64; P < 0.01) and hallmark androgen response (HAR; 3.15 versus 3.32; P < 0.01). Multivariable Cox regression identified only high-volume disease [hazard ratio (HR) = 4.97, 95% confidence interval (CI) 2.71-9.10; P < 0.01] and HAR score (HR = 0.51, 95% CI 0.28-0.88; P = 0.02) significantly associated with OS. Finally, patients with synchronous (HR = 0.47, 95% CI 0.30-0.72; P < 0.01) but not metachronous (HR = 1.37, 95% CI 0.50-3.92; P = 0.56) disease were found to have better OS with AR and non-AR combination therapy as compared with monotherapy (P value for interaction = 0.05). We have demonstrated a potential biologic difference between metastatic timing of mCSPC. Specifically, for patients with low-volume disease, those with metachronous low-volume disease have a more hormone-dependent transcriptional profile and exhibit a better prognosis than synchronous low-volume disease.


Historical process lead to false genetic signal of current connectivity among populations.
Identification of the effects of historical processes on spatial genetic variation is of major importance in landscape genetics, especially in recent systems where the signal of recent isolation is often hardly perceptible. The goal of this study was to assess how differences in colonization patterns could influence spatial genetic variation using two centrarchidae species, the pumpkinseed sunfish (Lepomis gibbosus) and the rock bass (Ambloplites rupestris), from two adjacent drainage systems. The striking difference between the spatial genetic variations of the two species suggests completely opposite patterns of colonization. Rock bass colonized the drainage system from a downstream source, which resulted in a loss of diversity in upstream populations and a strong differentiation between drainage systems. In contrast, the reduction of genetic diversity and increase of differentiation toward downstream populations that were observed among sunfish populations suggest colonization from upstream to downstream. The colonization pattern observed in sunfish, which result in low differentiation between upstream most sites of the two drainages, leads to a false genetic signal of current inter-drainage gene flow. The present study demonstrates through empirical evidence that colonization patterns may impede the capacity to estimate current connectivity.


Feasibility study to assess the delivery of a novel isometric exercise intervention for people with stage 1 hypertension in the NHS: protocol for the IsoFIT-BP study including amendments to mitigate the risk of COVID-19.
Hypertension (HTN) affects approximately 25% of the UK population and is a leading cause of mortality. Associated annual health care costs run into billions. National treatment guidance includes initial lifestyle advice, followed by anti-hypertensive medication if blood pressure (BP) remains high. However, adoption and adherence to recommended exercise guidelines, dietary advice and anti-hypertensive medication is poor. Four short bouts of isometric exercise (IE) performed 3 days per week (d/wk) at home elicits clinically significant reductions in BP in those with normal to high-normal BP. This study will determine the feasibility of delivering personalised IE to patients with stage 1 hypertension for whom lifestyle changes would be recommended before medication within NHS primary care. This is a randomised controlled feasibility study. Participants were 18+ years, with stage 1 hypertension, not on anti-hypertensive medication and without significant medical contraindications. Trial arms will be standard lifestyle advice (control) or isometric wall squat exercise and standard lifestyle advice. Primary outcomes include the feasibility of healthcare professionals to deliver isometric exercise prescriptions in a primary care NHS setting and estimation of the variance of change in systolic BP. Secondary outcomes include accuracy of protocol delivery, execution of and adherence to protocol, recruitment rate, attrition, perception of intervention viability, cost, participant experience and accuracy of home BP. The study will last 18 months. Sample size of 100 participants (50 per arm) allows for 20% attrition and 6.5% incomplete data, based upon 74 (37 each arm) participants (two-sided 95% confidence interval, width of 1.33 and standard deviation of 4) completing 4 weeks. Ethical approval IRAS ID is 274676. Before the efficacy of this novel intervention to treat stage 1 hypertension can be investigated in any large randomised controlled trial, it is necessary to ascertain if it can be delivered and carried out in a NHS primary care setting. Findings could support IE viability as a prophylactic/alternative treatment option. ISRCTN13472393 , registered 18 August 2020.


Trazodone treatment increases plasma prolactin concentrations in depressed patients.
m-Chlorophenylpiperazine (m-CPP), which is a metabolite of trazodone, is a serotonin agonist. To examine for the possibility that m-CPP is involved in biochemical effects during treatment with the parent compound, prolactin response to trazodone treatment (150 mg at bedtime for 3 weeks) was studied in 12 depressed patients. The means +/- S.D. of plasma prolactin concentrations before treatment, 12 h, and 1, 2 and 3 weeks after initiation of treatment were 9.1 +/- 5.6, 14.7 +/- 9.1, 15.3 +/- 8.5, 13.2 +/- 7.0 and 13.0 +/- 7.0 ng/ml, respectively. The mean prolactin concentrations at 12 h (p < 0.01), 1 week (p < 0.001) and 2 weeks (p < 0.05) were significantly higher than that before treatment. The present study thus shows that trazodone treatment increases prolactin concentrations, suggesting that m-CPP is involved in biochemical effects during treatment with the parent compound.


Tubular apocrine adenoma of the eyelid - A case report and literature review.
Tubular apocrine adenoma is a rare benign adnexal neoplasm most commonly identified in the scalp, composed of a dermal proliferation of apocrine tubules in a background of hyalinized stroma. Tubular apocrine adenoma can be a component of various sweat gland tumors and can also morphologically overlap with other sweat gland neoplasms. Isolated tubular apocrine adenoma arising in the glands of Moll is exceedingly rare, with only 4 previously reported cases. We present a 63-year-old male with tubular apocrine adenoma of the left upper eyelid, which recurred following initial incomplete excision. Although the lesion showed focal morphologic similarity to the apocrine variant of pleomorphic adenoma (chondroid syringoma), the diagnosis of tubular apocrine adenoma was supported by fluorescence in situ hybridization studies, which demonstrated absence of PLAG1 and HMGA2 gene rearrangements seen in pleomorphic adenoma. This case illustrates the clinical, microscopic and immunohistochemical features of tubular apocrine adenoma. The recent advances in our understanding of the molecular genetics of tubular apocrine adenoma and related tumors, and how these advances shape the evolving classification of sweat gland tumors are reviewed.


Fatty acid binding protein (FABP) modulates prostaglandin E binding to rat epididymal adipocyte membrane similarly to albumin.
Albumin enhances prostaglandin E2 (PGE2) binding to isolated epididymal adipocyte membrane and also binds PGE2 with low affinity. On the other hand, S-100, ovalbumin and albumin-stearate failed to bind PGE2, as shown by ultrafiltration, and also failed to enhance PGE2 binding to the isolated adipocyte membranes. These results suggested that albumin enhances PGE2 binding possibly by serving as a carrier for the prostaglandin molecules. 3 mM warfarin or 1 mM phenylbutazone inhibited PGE2 binding to albumin by 70% and 95%, respectively, but both drugs failed to affect the enhancement of PGE2 binding to the isolated adipocyte membrane in the presence of albumin. These results exclude the possibility that PGE2 bound to albumin is more accessible to the prostaglandin receptor than free PGE2 in solution. Finally it is shown that fatty acid binding protein (FABP), a cytosolic protein which binds specifically PGE1 but not PGE2, enhances PGE1 and PGE2 binding to isolated adipocyte membranes similarly to albumin. The physiological implications of these findings are discussed.


Dermatophilus dermatitis enzootic in deer in New York State and vicinity.
In a recent 2-year period Dermatophilus congolensis infection, ranging from mild to very severe, was found in 15 white-tailed deer (Odocoileus virginianus) taken in southeastern New York State (12) adjacent New Jersey (2) and central Vermont (1). The host range for Dermatophilus congolensis is given.


Identification of novel cytogenetic markers with prognostic significance in a series of 968 patients with primary myelodysplastic syndromes.
The main prognostic factors in myelodysplastic syndromes (MDS) are chromosomal abnormalities, the proportion of blasts in bone marrow and number and degree of cytopenias. A consensus-defined International Prognostic Scoring System (IPSS) for predicting outcome and planning therapy in MDS has been developed, but its prognostic value in a large and independent series remains unproven. Furthermore, the intermediate-risk cytogenetic subgroup defined by the IPSS includes a miscellaneous number of different single abnormalities of uncertain prognostic significance at present. The main aim of the present study was to identify chromosomal abnormalities with a previously unrecognized good or poor prognosis in order to find new cytogenetic markers with predictive value. We report the cytogenetic findings in a series of 968 patients with primary MDS from the Spanish Cytogenetics Working Group, Grupo Cooperativo Español de Citogenética Hematológica (GCECGH). In this series of 968 MDS patients, we found various cytogenetic aberrations with a new prognostic impact. Complex karyotype, -7/7q- and i(17q) had a poor prognosis; normal karyotype, loss of Y chromosome, deletion 11q, deletion 12p and deletion 20q as single alterations had a good prognosis. Intermediate prognosis aberrations were rearrangements of 3q21q26, trisomy 8, trisomy 9, translocations of 11q and del(17p). Finally, a new group of single or double cytogenetic abnormalities, most of which are considered rare cytogenetic events and are usually included in the intermediate category of the IPSS, showed a trend to poor prognosis. This study suggests that some specific chromosomal abnormalities could be segregated from the IPSS intermediate-risk cytogenetic prognostic subgroup and included in the low risk or in the poor risk groups.


Hereditary atrioventricular conduction defect in a child.
Hereditary atrioventricular conduction defect is an uncommon cause of acquired complete heart block in children. We report a father and son, both of whom presented with seizures as the initial manifestation of acquired complete heart block and required permanent pacemaker implantation. A review of the variations of this entity and the histopathological findings of previously reported cases is presented. Family members of patients with acquired heart block of uncertain etiology should be examined for the presence of conduction abnormalities that may progress to complete heart block.


[Lymph node dissection in papillary and follicular thyroid cancer].
There is still unresolved debate about the optimal surgical management of papillary (PTC) and follicular (FTC) thyroid cancer regarding lymph node dissection. So far the German guidelines recommend the same extent of surgery for both tumors. This study is based on 626 patients with PTC and 191 with FTC from a group of 1062 own patients with thyroid malignancies. The extent of surgery, tumor size, and pN status were analysed. The results were compared with those in the current literature. Tumors < or = 20 mm in size were found significantly more often in PTC than FTC (69.6% vs 28.3%, P<0.05). Positive lymph nodes were found significantly more often in PTC than FTC as well (33.2% vs 5.2%, P<0.05). In PTC up to 10 mm and from 11 mm to 20 mm in size, 16% and 34.4% of patients, respectively, showed positive lymph nodes. In FTC positive lymph nodes occurred only in tumors >25 mm. Due to prevalence and importance of lymph node metastasis differing between PTC and FTC, we recommend treating both tumor entities differently. For PTC a more extended lymph dissection is necessary, even in tumors < or = 20 mm. In small FTC it seems adequate to limit the operation to thyroidectomy without prophylactic lymph dissection.


The Role of Routine Ureteral Stenting Following Uncomplicated Ureteroscopic Treatment for Upper Ureteral and Renal Stones: A Randomized Control Trial.
Purpose: Ureteral stenting following uncomplicated ureteroscopy (URS) is common practice. Several studies have proven the safety of omitting routine stent placement following distal ureteral stone treatment. However, there is a paucity of data regarding the utility of stent placement for proximal URS. We designed a prospective, randomized controlled trial to evaluate the role of ureteral stent placement following URS for proximal ureteral and renal stones. Methods: Seventy-two patients with proximal ureteral or renal stones measuring as much as 1.5 cm were prospectively randomized into stented (37) or unstented (35) groups. The surgeon was blinded to the treatment group until after stone treatment. Patients tracked postoperative pain medications and completed validated pain questionnaires on postoperative days 0, 3, 7, and 28. Stents were removed on postoperative day 7. Postoperative follow-up imaging was obtained at 4 weeks. Results: No statistical differences were observed between the two groups in terms of demographics or stone characteristics. The operative time was longer in the stented group (p < 0.03). Patients in the stented group had more irritative urinary symptoms (p < 0.0001) and pain (p < 0.0001), missed more days of work (p < 0.01), and used more narcotics (p < 0.0005) during the first week, but no differences were observed at 30 days. Emergency room visits and overall complication rates were similar between the two groups. Three nonstented patients required stent placement. Two stented patients required early stent removal. Urinary tract infections developed in three stented patients, but not in unstented patients. Postoperative imaging did not reveal any hydronephrosis in either group, and the total stone-free rate was 94%. Conclusions: For most patients undergoing uncomplicated ureteroscopic treatment for proximal ureteral and kidney stones, it may be safe to omit ureteral stents to potentially decrease urinary symptoms and pain while improving short-term quality of life. Further studies with larger patient cohorts may be warranted to confirm our results.


Basic characterization, antioxidant and immunomodulatory activities of polysaccharides from sea buckthorn leaves.
The polysaccharides from Sea buckthorn leaves (SBLPs) were extracted by hot water and purified by DEAE cellulose, then separated into six polysaccharides (SBLP-S) by DEAE-52 column. Six separated polysaccharides were characterized by Ultraviolet Spectroscopy, Infrared Spectrum, High Performance Liquid Chromatographic and Congo red analysis. The antioxidant activity and immunological activity were investigated in vitro. The results revealed that the monosaccharide composition of SBLP-S-1, SBLP-S-2, SBLP-S-3, SBLP-S-5 and SBLP-S-6 contained Man, GlcN, Rib, Rha, GluA, GalA, Glu, Gal, Xyl, Ara and Fuc, among them, rare glucosamine was found. And SBLP-S-4 contained all above components except GlcN and GluA. FT-IR showed that SBLP-S were sulfated polysaccharide containing uronic acid. Molecular weights of SBLP-S were 338.659, 401.305, 599.849, 393.904, 626.895 and 176.862 kDa. The Congo-red test indicated that SBLP-S-2, SBLP-S-4, SBLP-S-5, and SBLP-S-6 had triple helix conformation. Crude polysaccharides had the strong scavenging activities on DPPH radicals, ABTS radicals and hydroxyl radicals. The six polysaccharides had the activity of immune stimulation on RAW264.7 cell. SBLP-S-2 promoted the phagocytosis best and SBLP-S-6 promoted the NO production best. The results suggested that SBLPs could be used as potential antioxidants and immunomodulatory agents in pharmaceutical and functional food fields.


Feasibility of laparoscopy-assisted gastrectomy for patients with poor physical status: A propensity-score matching study.
Laparoscopically-assisted gastrectomy (LAG) has been established to be a minimally invasive treatment for early gastric cancer. However, few studies have shown the feasibility of LAG in patients with risky comorbidities according to the American Society of Anesthesiologists physical status (ASA-PS) classification. We performed this retrospective cohort study to assess the feasibility of LG in patients with an ASA-PS class of 3 or higher. We retrospectively identified 214 patients with an ASA-PS class of 3 or 4 among 1192 patients who underwent radical gastrectomy with lymph-node dissection between 1999 and 2014 in our hospital. Finally, 106 patients were generated by propensity-score matching between LAG and open gastrectomy (OG). Postoperative complications were compared between LAG and OG. The overall incidence of complications was the same in LAG (30%) and OG (30%). Surgical complications were similar in LAG and OG (19% and 17%, p = 0.80). Medical complications also did not differ significantly between LAG and OG (21% and 15%, p = 0.45). LAG was a feasible procedure for patients with gastric cancer who had an ASA-PS class of 3 or 4 and could undergo general anesthesia. LAG can become an optional treatment for such risky patients.


A modified biodegradable mesh ureteral stent for treating ureteral stricture disease.
Ureteral stricture disease (USD) is a common urologic condition. Patients with ureteral stricture disease may suffer from ipsilateral flank pain, nausea, urinary calculi, infection, and impaired renal function. The treatments of USD include surgery, followed by implantation of the ureteral stent to aid the drainage of the urine. The traditional ureteral stent may sometimes cause urological infection, encrustation, and discomfort. To decrease the complication of the ureteral stent, we modified the structure and material based on the traditional ureteral stent. The traditional nondegradable Double-J shape tubular ureteral stent was turned into the biodegradable mesh ureteral stent. The modified mesh ureteral stent and Double-J ureteral stent were inserted into the ureters of the USD animals, respectively. The results of the gross morphology, serology, urinalysis, histology, microstructure, et al. demonstrated that modified mesh ureteral stent has a favorable ability in supporting the ureter and has no effect on cell proliferation, migration, apoptosis, and cell cycle of the human uroepithelial cells. The mesh ureteral stent could relieve ureter obstruction and can be slowly biodegraded after 3-5 months of implantation without the need for a second surgery to remove the stent. Compared to the Double-J ureteral stent, the modified mesh ureteral stent has a lower rate of urinary tract infection and less encrustation. It is expected to be an alternative treatment approach for USD. However, due to the limited number of animals and clinical data, further study focused on the application value in clinical practice are essential. STATEMENT OF SIGNIFICANCE: This study demonstrates: 1. A modified biodegradable mesh ureteral stent; 2. Without the need for a second surgery to remove the stent; 3. A lower rate of urinary tract infection and less encrustation than a double-J ureteral stent; 4. An alternative treatment approach for USD.


The effect of 5-fluorouracil/leucovorin chemotherapy on CpG methylation, or the confounding role of leukocyte heterogeneity: An illustration.
Blood-based epigenome-wide association studies that aim at comparing CpG methylation between colorectal cancer (CRC) patients and controls can lead to the discovery of diagnostic or prognostic biomarkers. Numerous confounders can lead to spurious associations. We aimed to see if 5-fluorouracil (5-FU)/leucovorin chemotherapy administered to cases prior to the collection of their blood has an effect on methylation. 304 patients who received treatment and 273 who did not were profiled on the HumanMethylation450 array. Association tests were adjusted for confounders, including proxies for leukocyte cell counts. There were substantial methylation differences between these two groups that vanished once the leukocyte heterogeneity was accounted for. We observed a significant decrease of T cells in the treatment group (CD4+: p=10(-6); CD8+: p=0.036) and significant increase of NK cells (p=0.05) and monocytes (p=0.0006). 5-FU/leucovorin has no effect on global and local blood-based methylation profiles, other than through differences in the leukocyte compositions that the treatment induced.


Purely subcortical tumors in eloquent areas: awake surgery and cortical and subcortical electrical stimulation (CSES) ensure safe and effective surgery.
To analyze the efficacy and safety of cortical and subcortical electrical stimulation CSES and awake surgery to approach purely subcortical tumors in highly functional locations, particularly in guiding the choice of the best transcortical path. Prospective analysis of the surgical, neurological, and radiological outcome of patients harboring supratentorial, subcortically located brain tumors or vascular malformations who are operated on through awake surgery and CSES. Functional magnetic resonance (fMRI; either sensory-motor or language, based on the location) was performed in order to confirm the proximity to functional cortical areas. Major white matter tracts were investigated by MRI diffusion tensor fiber tracking (DTI-ft). The Rankin modified score was chosen to express the pre and postoperative functional neurological status. Immediate postoperative MRI was used to evaluate the extent of resection. Seventeen patients were selected. The main distance of the tumors from the cortical surface was 18.2mm (range 9-48 mm). Neuronavigation was used to show the most direct route to the tumor (transsulcal or transgyral), but CSES was fundamental to adapt the surgical corridor to the functional topography both cortically and subcortically. If the transgyral route was chosen, CSES helped to detect a non-eloquent area. When a transsulcal route was preferred, CSES documented the presence or absence of function in the deep sulcus. The transient postoperative morbidity was 76.4%, but at last follow-up (range 4-20 months), all the patients regained preoperative status and 2 improved. Postoperative MRI demonstrated complete resection in all cases. Approaching purely subcortical tumors requires microsurgical skills, but in eloquent areas, functional topography monitoring is mandatory to allow safe surgery. CSES in an awake patient is a method that produces very good results in terms of resection and neurological outcome.


A comparison of halothane and trichloroethylene with isoflurane. A study of drawover air anaesthesia with the Triservice anaesthetic apparatus.
Induction and recovery times were not significantly different between two groups that received halothane with trichloroethylene and isoflurane, respectively. Maintenance of anaesthesia and analgesia was also satisfactory. Isoflurane resulted in a higher heart rate (p less than 0.01), a lower respiratory rate (p less than 0.01) and a higher inspired oxygen concentration (p less than 0.05). Respiration may be more efficient. Other potential advantages of isoflurane for anaesthesia in the field are discussed. Despite the fact that it is 15 times more expensive, the use of isoflurane as sole agent is recommended.


Acute type A dissection of the aorta: surgical management with the sutureless intraluminal prosthesis.
The sutureless intraluminal prosthesis was used in 22 patients with acute dissection of the ascending aorta (type A) between May, 1982, and September, 1985. The patients ranged from 26 to 77 years old (mean, 58 years). Diagnosis was established by aortogram in 18 patients and by two-dimensional echocardiogram in 4 patients. Additional procedures included resuspension of the aortic valve in 7 patients, single coronary artery bypass in 1 patient, and cesarean delivery of a term pregnancy in 1 patient. Nineteen patients survived operation and were discharged from the hospital (86% early survival). Three patients died, 2 of hemorrhage and myocardial failure in the operating room, and 1 of sepsis following a prolonged hospitalization. Early postoperative complications included one instance of renal failure, one perioperative myocardial infarction, and one cerebrovascular accident (CVA). There were no reoperations for bleeding. Follow-up was obtained on 17 patients (90%) and ranged from 10 to 50 months (mean, 30 months). Thirteen of the survivors are well, 11 have returned to work, 2 have had a CVA, and 1 has a descending thoracic aneurysm. We conclude that the intraluminal graft is a good option for repair of acute type A dissections because it reestablishes central aortic flow, obliterates the false channel entry site, minimizes operative blood loss, and permits expeditious repair with minimal trauma to friable tissues.


Single molecule approaches for quantifying transcription and degradation rates in intact mammalian tissues.
A key challenge in mammalian biology is to understand how rates of transcription and mRNA degradation jointly shape cellular gene expression. Powerful techniques have been developed for measuring these rates either genome-wide or at the single-molecule level, however these techniques are not applicable to assessment of cells within their native tissue microenvironment. Here we describe a technique based on single molecule Fluorescence in-situ Hybridization (smFISH) to measure transcription and degradation rates in intact mammalian tissues. The technique is based on dual-color libraries targeting the introns and exons of the genes of interest, enabling visualization and quantification of both nascent and mature mRNA. We present a software, TransQuant, that facilitates quantifying these rates from smFISH images. Our approach enables assessment of both transcription and degradation rates of any gene of interest while controlling for the inherent heterogeneity of intact tissues.


Frameshift mutation in the alpha2-globin gene causing alpha+ -thalassemia: codon 49 (-GC).
We report a new alpha-thalassemia (alpha-thal) point mutation detected in a woman with alpha(+)-thal. Sequence analyses identified a frameshift mutation at codon 49 (-GC) in exon 2 of the alpha2-globin gene.


Predictive classification of pediatric bipolar disorder using atlas-based diffusion weighted imaging and support vector machines.
Previous studies have reported abnormalities of white-matter diffusivity in pediatric bipolar disorder. However, it has not been established whether these abnormalities are able to distinguish individual subjects with pediatric bipolar disorder from healthy controls with a high specificity and sensitivity. Diffusion-weighted imaging scans were acquired from 16 youths diagnosed with DSM-IV bipolar disorder and 16 demographically matched healthy controls. Regional white matter tissue microstructural measurements such as fractional anisotropy, axial diffusivity and radial diffusivity were computed using an atlas-based approach. These measurements were used to 'train' a support vector machine (SVM) algorithm to predict new or 'unseen' subjects' diagnostic labels. The SVM algorithm predicted individual subjects with specificity=87.5%, sensitivity=68.75%, accuracy=78.12%, positive predictive value=84.62%, negative predictive value=73.68%, area under receiver operating characteristic curve (AUROC)=0.7812 and chi-square p-value=0.0012. A pattern of reduced regional white matter fractional anisotropy was observed in pediatric bipolar disorder patients. These results suggest that atlas-based diffusion weighted imaging measurements can distinguish individual pediatric bipolar disorder patients from healthy controls. Notably, from a clinical perspective these findings will contribute to the pathophysiological understanding of pediatric bipolar disorder.


Nitrogen-substitution effect on in vivo mutagenicity of chrysene.
We have previously reported the in vivo mutagenicity of aza-polycyclic aromatic hydrocarbons (azaPAHs), such as quinoline, benzo[f]quinoline, benzo[h]quinoline, 1,7-phenanthroline and 10-azabenzo[a]pyrene. The 1,10-diazachrysene (1,10-DAC) and 4,10-DAC, nitrogen-substituted analogs of chrysene, were shown to exhibit mutagenicity in Salmonella typhimurium TA100 in the presence of rat liver S9 and human liver microsomes in our previous report, although DACs could not be converted to a bay-region diol epoxide, the ultimate active form of chrysene, because of their nitrogen atoms. In the present study, we tested in vivo mutagenicity of DACs compared with chrysene using the lacZ transgenic mouse (Mutatrade markMouse) to evaluate the effect of the nitrogen substitution. DACs- and chrysene-induced mutation in all of the six organs examined (liver, spleen, lung, kidney, bone marrow and colon). The mutant frequencies obtained with chrysene showed only small differences between the organs examined and ranged from 1.5 to 3 times the spontaneous frequency. The 4,10-DAC was more mutagenic than chrysene in all the organs tested. The highest lacZ mutation frequency was observed in the lung of 4,10-DAC-treated mice and it was 19 and 6 times the spontaneous frequency and the frequency induced by chrysene, respectively. The 1,10-DAC induced lacZ mutation in the lung with a frequency 4.3- and 1.5-fold higher than in the control and chrysene-treated mice, respectively, although the mutant frequencies in the other organs of 1,10-DAC-treated mice were almost equivalent to those of chrysene-treated mice. Not only chrysene but also DACs depressed the G:C to A:T transition and increased the G:C to T:A transversion in the liver and lung. These results suggest that the two types of nitrogen substitutions in the chrysene structure may enhance mutagenicity in the mouse lung, although they showed no difference in the target-organ specificity and the mutation spectrum.


No evidence that nest site choice in Pied Flycatchers is mediated by assessing the clutch size of a heterospecific, the Great Tit.
Among species that use similar resources, an individual may benefit by observing and copying the behavioural decision of a heterospecific. We tested the hypothesis of heterospecific social learning in passerine birds, namely that a migrant species, the Pied Flycatcher Ficedula hypoleuca, uses external markings on the nest cavities of a resident species, the Great Tit Parus major, as cues when choosing a nest site. Others have suggested that prospecting flycatchers assess the clutch size of tit "demonstrators" by entering their nest boxes and, assuming that a large clutch indicates a high-quality individual, will copy the nest appearance of tits with large, but not small clutches. During a 4-year period in Norway, we designed a similar study but did not find that flycatchers based their nest choice on the clutch size of tits. Neither were there any relationships between clutch size of the tit and its laying date, incubation behaviour, or the number of eggs visible through nest material during egg-laying so Pied Flycatchers did not use these indirect cues to assess quality of the tutor. Filming of tit nests showed that prospecting flycatchers did not enter tit nest boxes to assess the content. Indeed, incubating female tits only left their nest boxes for short bouts of unpredictable duration so there was little opportunity for flycatchers to inspect the nest contents unnoticed. Our study calls into question the mechanism of using the content of tit nests as public information for choosing traits of nest sites based on external characteristics. We suggest that similar studies of nest site choice in relation to possible social information transfer be replicated more widely.


Evidence based treatment for unstable slipped upper femoral epiphysis: Systematic review and exploratory patient level analysis.
The management of slipped upper femoral epiphysis is controversial and evolving as insight into the condition develops. Loder introduced the concept of slip stability and demonstrated a strong association between poor outcome and instability. Almost half of patients with unstable slip developed femoral head osteonecrosis. This has been influential in surgeons' choice of treatments. Some surgeons have adopted a minimal intervention approach such as pinning in situ or gentle reduction and pinning whereas others advocated an urgent open reduction and stabilisation of slip using various surgical techniques. In this review we analysed the influence of various interventions, timing of surgery and severity of the slip on the outcome of unstable slip.


Proprioception in total, hemi- and reverse shoulder arthroplasty in 3D motion analyses: a prospective study.
The aim of the study was to assess proprioception after shoulder arthroplasty. Twenty-six patients were enrolled who underwent total shoulder arthroplasty (TSA) (n = 13) or hemi-arthroplasty (n = 8) for shoulder osteoarthritis or reversed arthroplasty (n = 5) for cuff tear arthropathy. All patients were examined before the operation and then again six months thereafter in a motion analysis study with an active angle-reproduction (AAR) test. In all groups the AAR deteriorated at 60 degrees flexion (from 5.5 degrees [SD 2.8] to 7.6 degrees [SD 2.7]; p = 0.007) and at 30 degrees external rotation (ER) (from 6.5 degrees [SD 3.6] to 7.3 degrees [SD 4.8 degrees]; p = 0.023) six months after surgery. In the subgroup of TSA, there was deterioration at 30 degrees ER (p = 0.036). Otherwise, there were no significant changes within or among the subgroups. Proprioception, assessed by the AAR test, remained unchanged or deteriorated six months after shoulder arthroplasty. This might be related to the reduced pain or to the relatively short follow-up period.


New concept for the recovery function of short-latency somatosensory evoked cortical potentials following median nerve stimulation.
We investigated the recovery function of the cortical components of somatosensory evoked potentials (SEP) at a very short interstimulus interval (ISI, less than 10 ms) using an integrative computer system in 10 healthy subjects (age, 27-38 years). The SEP and nerve action potentials were recorded at P3 with a reference of Fz in the International 10-20 System and the ipsilateral Erb's point, respectively. Double stimulation of the right median nerve with an ISI from 0.5 to 100 ms was performed to analyze the N20 and P30 components at less than 10 ms. The P30 component was recognized following the second stimulation at an ISI of over 1 ms, while N20 was not identified at an ISI of less than 9 ms. There appeared a sub-component of SEP at 1-12 ms ISI, which was not identified following a single stimulation under control conditions. The results indicated that the recovery function of given SEP components was not simply determined by the number of synapses interposed between the stimulus site and the generator source of the response in the central nervous system, but there might be a structural or functional process of low-cut filtering in the primary sensory cortex. We also considered that the final SEP waveform determined by the excitatory and inhibitory balance of the components, which could be changed with ISI, and that the existence of the sub-component might cause the complexity of the recovery curve and large inter-individual difference of the waveform.


Competitive adsorption-desorption reactions of two hazardous heavy metals in contaminated soils.
Investigating the interactions of heavy metals is imperative for sustaining environment and human health. Among those, Cd is toxic for organisms at any concentration. While Ni acts as a micronutrient at very low concentration but is hazardous toxic above certain threshold value. In this study, the chemical adsorption and desorption reactions of Ni and Cd in contaminated soils were investigated in both single and binary ion systems. Both Ni and Cd experimental data demonstrated Langmuir type adsorption. In the competitive systems, an antagonistic effect was observed, implying that both ions compete for same type of adsorption sites. Adverse effect of Cd on Ni adsorption was slightly stronger than that of opposite system, consistent with adsorption isotherms in single ion systems. Variation in ionic strength indicated that Ca, a much weaker adsorbate, could also compete with Cd and Ni for adsorption on soil particles. Desorption data indicated that Cd and Ni are adsorbed very tightly such that after four successive desorption steps, less than 0.5 % of initially adsorbed ions released into the soil solution. This implies that Ca, at concentration in equilibrium with calcite mineral, cannot adequately compete with and replace adsorbed Ni and Cd ions. This adsorption behavior was led to considerable hysteresis between adsorption and desorption in both single and binary ion systems. In the binary ion systems, desorption of Cd and Ni was increased by increase in both equilibrium concentration of adsorbed ion and concentration of competitor ion. The overall results obtained in this research indicate that Cd and Ni are strongly adsorbed in calcareous soil and Ca, the major dissolved ion, insignificantly influences metal ions adsorption. Consequently, the contaminated soils by Ni and Cd can simultaneously be remediated by environmentally oriented technologies such as phytoremediation.


Structure of tetra-kis-(μ-deca-noato-κ2 O:O')bis-[(4-methyl-pyridine-κN)copper(II)], a dimeric copper(II) complex.
The 4-methyl-pyridine (4-Mepy) based dimeric copper(II) carboxyl-ate complex [Cu2(C10H19O2)4(C6H7N)2] or [Cu2(μ-O2CC9H19)4(4-Mepy)2] crystallizes with triclinic (P ) symmetry. The two CuII ions exhibit a distorted square-pyramidal environment and are connected into a centrosymmetric paddle-wheel dinuclear cluster [Cu⋯Cu = 2.6472 (8) Å] via four bridging carboxyl-ate ligands arranged in the syn-syn coordination mode. The apical positions around the paddle-wheel copper centers are occupied by the N atoms of the 4-methyl-pyridine ligands. The structure exhibits disorder of the terminal alkyl carbon atoms in the deca-noate chains.


Proton affinities of borane-amines: consequences on dihydrogen bonding.
The calculated proton affinities of four borane-amines using Gaussian-2 theory have been found to be comparable to conventional bases such as water, methanol, and ammonia. On the other hand the structure of protonated borane-ammonia, [HBH(3)-NH(3)](+), is found to be drastically different from that of protonated ammonia, [HNH(3)](+), and can appropriately be described as a eta(2)-H(2) complex with [BH(2)-NH(3)](+) molecular cation. Further, the proton affinities of borane-amines are related to the ease of H(2) elimination.


Effect of temperature on food consumption, immune system, antioxidant enzymes, and heat shock protein 70 of Channa punctata (Bloch, 1793).
The impact of water temperature on the physiology of Channa punctata (Bloch, 1793) was evaluated in the present study. Fish were acclimated at 25 ± 1 °C and then exposed at six different temperatures: 10, 15, 20, 25, 30, and 35 °C. C. punctata exposed at 10, 15, and 20 °C showed 30, 21, and 11% reduced food consumption, respectively compared to 25 °C. Significantly higher respiratory burst and myeloperoxidase activities were found in fish exposed at 20 and 25 °C after 12 h of exposure compared to other treatments. Nitric oxide synthase was significantly higher at 25 °C after 12 h and at 25 and 30 °C exposed fish after 7 days compared to others. The reduced glutathione level was significantly higher at 25 °C compared to other treatments after 7 days of exposure. The thiobarbituric acid reactive substances level was minimum at 25 °C. Significantly lower antioxidant enzymes, catalase, glutathione peroxidase, and glutathione S-transferase were found in gills of fish exposed at 25 °C compared to others in both samples. The highest antioxidant enzyme levels were found at 10 °C. Heat shock protein (Hsp) 70 levels were significantly lower in liver and muscle of fish exposed at 25 °C compared to other treatments. The Hsp level was significantly higher at 35 and 30 °C exposed fish compared to others after 12 h, and the level reduced after 7 days in these treatments. Thermal stress affects food consumption rate, immune system, antioxidant enzymes, and enzyme systems in fish. The elevated Hsp70 level serves as a biomarker of stress in C. punctata. Graphical Abstract.


Neural correlates of emotional response inhibition in obsessive-compulsive disorder: A preliminary study.
Failure to inhibit recurrent anxiety-provoking thoughts is a central symptom of obsessive-compulsive disorder (OCD). Neuroimaging studies suggest inhibitory control and disgust processing abnormalities in patients with OCD. However, the emotional modulation of response inhibition deficits in OCD and their neural correlates remain to be elucidated. For this preliminary study we administered an adapted affective response inhibition paradigm, an emotional go/no-go task, during fMRI to characterize the neural systems underlying disgust-related and fear-related inhibition in nine adults with contamination-type OCD compared to ten matched healthy controls. Participants with OCD had significantly greater anterior insula cortex activation when inhibiting responses to both disgusting (bilateral), and fearful (right-sided) images, compared to healthy controls. They also had increased activation in several frontal, temporal, and parietal regions, but there was no evidence of amygdala activation in OCD or healthy participants and no significant between-group differences in performance on the emotion go/no-go task. The anterior insula appears to play a central role in the emotional modulation of response inhibition in contamination-type OCD to both fearful and disgusting images. The insula may serve as a potential treatment target for contamination-type OCD.


High-Resolution Imaging of LA Anatomy Using a Novel Wide-Band Dielectric Mapping System: First Clinical Experience.
This study presents the first report of high-resolution imaging of cardiac anatomy using a novel system. Recently, the wide-band dielectric mapping system Kodex was introduced. This study included 20 consecutive patients with symptomatic atrial fibrillation or left atrial tachycardia who were scheduled for an ablation procedure and who underwent simultaneous left atrial mapping using the Kodex and CARTO 3 systems. Pulmonary vein angiograms served as a reference to compare the craniocaudal dimensions of the pulmonary vein ostia as depicted by either of the 2 mapping systems. Complete left atrial imaging was achieved within a median [first quartile; third quartile] of 9.7 [7.5; 12.8] min. Median procedure time was 97.5 [90; 112.5] min, and median total fluoroscopy time was 8.2 [5.7; 10.6] min, of which a median of 1.4 [1.1; 2.3] min were used during the creation of the left atrial map. High-resolution representations of left atrial anatomy were successfully created in all patients. Both the Kodex and CARTO measurements correlated well with fluoroscopy measurements, as reflected by Pearson's correlation coefficients (r) of 0.91 and 0.95, respectively. Bland-Altman plots revealed that, on average, Kodex measurements underestimated fluoroscopy measurements by 0.04 mm (95% limits of agreement of -5.72 and 5.64 mm), and CARTO measurements underestimated fluoroscopy measurements by 0.02 mm (95% limits of agreement of -3.61 and 3.57 mm). Anatomic mapping of the left atrium using Kodex shows the potential to create computed tomography-like images without the need for additional periprocedural imaging.


Biotechnological advances in the diagnosis, species differentiation and phylogenetic analysis of Schistosoma spp.
Schistosomiasis is a serious parasitic disease caused by blood-dwelling flukes of the genus Schistosoma. Throughout the world, schistosomiasis is associated with high rates of morbidity and mortality, with close to 800 million people at risk of infection. Precise methods for identification of Schistosoma species and diagnosis of schistosomiasis are crucial for an enhanced understanding of parasite epidemiology that informs effective antiparasitic treatment and preventive measures. Traditional approaches for the diagnosis of schistosomiasis include etiological, immunological and imaging techniques. Diagnosis of schistosomiasis has been revolutionized by the advent of new molecular technologies to amplify parasite nucleic acids. Among these, polymerase chain reaction-based methods have been useful in the analysis of genetic variation among Schistosoma spp. Mass spectrometry is now extending the range of biological molecules that can be detected. In this review, we summarize traditional, non-DNA-based diagnostic methods and then describe and discuss the current and developing molecular techniques for the diagnosis, species differentiation and phylogenetic analysis of Schistosoma spp. These exciting techniques provide foundations for further development of more effective and precise approaches to differentiate schistosomes and diagnose schistosomiasis in the clinic, and also have important implication for exploring novel measures to control schistosomiasis in the near future.


Occupational class and risk of hepatitis B and C viral infections: A case-control study-based data from a nationwide hospital group in Japan.
Occupational class, a proxy for socio-economic status, is a known factor for health disparities. However, no study has reported the association between occupational class and the risk of viral hepatitis B and C (HBV/HCV) infections. We investigated the effects of occupational class on the prevalence of HBV/HCV infections. This is an unmatched hospital-based case-control study that included 12,101 patients who were diagnosed with HBV infection (ICD-10, B16.0, B16.1, B16.2, B16.9, B17.0, B18.0, B18.1) or HCV infection (ICD-10, B17.1, B18.2) and 698,168 controls (those with non-HBV/HCV-related diseases) aged ≥ 20 years who were initially hospitalized between 2005 and 2019. Patients were categorized according to occupational class (blue-collar, service, professional, and manager) and industrial sector (blue-collar, service, and white-collar). Managers in the blue-collar industry were set as the reference group, and the odds ratios (ORs) for the risk of HBV and HCV infections were calculated. Occupational class was significantly associated with only HCV infection risk. Professionals in all industrial sectors showed the lowest risk for HCV (OR (95% confidence intervals [CIs]) = 0.69 [0.58-0.82] in the blue-collar industry, 0.52 [0.38-0.73] in the service industry, and 0.60 [0.52-0.70] in the white-collar industry). Further, after adjusting for sex, age, and region of admitting hospital, all occupational classes in the white-collar industry showed lower risks of HCV than those in the other industries (ORs= 0.58 [0.47-0.71] in blue-collar workers, 0.74 [0.64-0.84] in service workers, 0.60 [0.52-0.70] in professionals, and 0.81 [0.64-1.02] in managers in white-collar industry). Occupational class was closely associated with HCV infection risk only. Considering that blue-collar workers in the white-collar industry also showed a low risk, adequate measures should be taken against hepatitis, possibly because of the screening tests and cure implemented in that population.


The Stimulatory Effects of Intracellular α-Synuclein on Synaptic Transmission Are Attenuated by 2-Octahydroisoquinolin-2(1H)-ylethanamine.
α-Synuclein (αSyn) species can be detected in synaptic boutons, where they play a crucial role in the pathogenesis of Parkinson's Disease (PD). However, the effects of intracellular αSyn species on synaptic transmission have not been thoroughly studied. Here, using patch-clamp recordings in hippocampal neurons, we report that αSyn oligomers (αSynO), intracellularly delivered through the patch electrode, produced a fast and potent effect on synaptic transmission, causing a substantial increase in the frequency, amplitude and transferred charge of spontaneous synaptic currents. We also found an increase in the frequency of miniature synaptic currents, suggesting an effect located at the presynaptic site of the synapsis. Furthermore, our in silico approximation using docking analysis and molecular dynamics simulations showed an interaction between a previously described small anti-amyloid beta (Aβ) molecule, termed M30 (2-octahydroisoquinolin-2(1H)-ylethanamine), with a central hydrophobic region of αSyn. In line with this finding, our empirical data aimed to obtain oligomerization states with thioflavin T (ThT) and Western blot (WB) indicated that M30 interfered with αSyn aggregation and decreased the formation of higher-molecular-weight species. Furthermore, the effect of αSynO on synaptic physiology was also antagonized by M30, resulting in a decrease in the frequency, amplitude, and charge transferred of synaptic currents. Overall, the present results show an excitatory effect of intracellular αSyn low molecular-weight species, not previously described, that are able to affect synaptic transmission, and the potential of a small neuroactive molecule to interfere with the aggregation process and the synaptic effect of αSyn, suggesting that M30 could be a potential therapeutic strategy for synucleinopathies.