Novel composites of activated carbon and layered double oxide for the removal of sulfate from synthetic and brackish groundwater.
Sulfate (SO42-) is a major water and environmental concern that causes severe diarrhea, death of invertebrates and plant species, and clogging of industrial pipes. In the current work, treatment of SO42- from synthetic and real groundwater having 3901 mg(SO42-)/L was investigated for the first time using Zn-Al and Mg-Al layered double oxides doped granular activated carbon (GAC/Mg-Al LDO and GAC/Zn-Al LDO). The co-precipitation method was followed to synthesize the GAC/LDO composites using an Mg or Zn to Al molar ratio of 3:1. The GAC/Mg-Al LDO possessed a higher specific surface area (323.9 m2/g) compared to GAC/Zn-Al LDO (195.1 m2/g). The GAC/Mg-Al LDO demonstrated more than 99% removal of SO42- from synthetic water, while it was 50.9% for GAC/Zn-Al LDO and less than 1% for raw GAC at an initial concentration of 50 mg/L. The GAC/Mg-Al LDO was selected for further batch experiments and modeling investigation. The equilibrium data followed the Redlich-Peterson and Langmuir models with determination coefficients of 0.943 and 0.935, respectively. The maximum Langmuir adsorption capacity was 143.5 mg/g. In the real groundwater adsorption study, the screening experiment revealed high selectivity towards SO42- with 62% removal efficiency. The optimum dosage was found to be 50 g/L with an uptake capacity of 61.5 mg/g. The kinetic data of SO42- removal from synthetic and brackish water were in excellent agreement with the pseudo-second order model, and the equilibrium was attained in 5 h. Accordingly, it can be concluded that the GAC/Mg-Al LDO is an efficient material for treating SO42- from real groundwater and can be utilized as a pretreatment unit for high sulfate water resources.


Heap of stones: an unusual cause for biliary colic and elevated liver function tests.
A 40-year old woman presented with symptomatic intrahepatic gallstones in one liver segment only four years after cholecystectomy for cholelithiasis. Multiple small, yellow and round calculi were completely removed from the intrahepatic bile ducts via ERCP. The young age of the patient, recurrence of gallstones after cholecystectomy and intrahepatic gallstones suggested a subtype of the low-phospholipid associated cholelithiasis syndrome, a monogenic form of cholesterol cholelithiasis due to variations of the ABCB4 gene that encodes the canalicular phospholipid transporter MDR3.


Using big data to map the relationship between time perspectives and economic outputs.
Recent studies have shown that population-level time perspectives can be approximated using "big data" on search engine queries, and that these indices, in turn, predict the per-capita Gross Domestic Product of countries. Although these findings seem to support Baumard's suggestion that affluence makes people more future-oriented, they also reveal a more complex relationship between time perspectives and economic outputs.


Is brain a gluconeogenic organ?
Glucagon increased the activities of alanine amino transferase (AAT), fructose-1:6-bisphosphatase (fru-P2ase) and glucose-6-phosphatase (G-6-Pase) in goat brain tissue by about 100%, 150% and 50% respectively. These increase in activities were reversed by beta-antagonists propranolol. Well known alpha-agonist and antagonist like phenylephrine and phenoxybenzamine also increased AAT and G-6-Pase activities and these increased activities were reversed by propranolol. Phenylephrine and phenoxybenzamine however did not increase brain Fru-P2ase activity. However the most interesting finding is that cerebral cortical slices could produce glucose from alanine and this glucose production was enhanced by glucagon, phenylephrine and phenoxybenzamine. Propranolol reversed the effects of these agonists and antagonist to a great extent. From all these experiments we suggest brain to be a gluconeogenic organ although much less efficient than liver.


Investigating the relationship between cancer and orofacial clefts using GWAS significant loci for cancers: A case-control and case-triad study.
Several population-based case-control studies have reported concurrent presentation of cancer and congenital malformations. Many associations have been made between oral clefting and cancers, though some of these results are conflicting. Some studies have reported an increased risk of cancer among 1st-degree relatives of cleft cases and vice versa, and also an excess risk of cancers of the breast, lung, and brain among those with oral clefts. This study aimed to determine if the genetic polymorphisms found in some cancers are also associated with orofacial cleft in an African cohort. The study was a case-control and case-triad study in which cases were 400 individuals clinically diagnosed with non-syndromic cleft lip and/or palate (CL/P), while controls were 450 individuals without CL/P. Samples were obtained from three African countries while DNA extraction, PCR, and genotyping were carried out at the University of Iowa, US. Eleven SNPs in genes coding for SWI/SNF subunits and 13 GWAS significant SNPs for cancers associated with orofacial cleft were selected. Case-control analysis, transmission disequilibrium test (TDT), and DFAM to combine the parent-offspring trio data and unrelated case/control data in a single analysis were carried out using PLINK. For the case-control analyses that included all the clefts and for the CLP subtype, none of the SNPs were statistically significant. Statistically increased risk for the following SNPs rs34775372 (p = 0.02; OR = 1.54, CI:1.07-2.22), rs55658222 (p = 0.009; OR = 2.64, CI:1.28-5.45) and rs72728755 (p = 0.02; OR=2.27, CI:1.17-4.45) was observed with the CL only sub-group. None of these were significant after Bonferoni correction. In the TDT analyses, a significantly reduced risk with rs10941679 (p = 0.003; OR = 0.43, CI:0.24-0.75) was observed and this was significant after Bonferroni correction. The rs10941679 was also significant (p = 0.003) in the DFAM analyses as well even after Bonferroni correction. The results from this study represent an important starting point for understanding the concurrent presentation of some cancers in orofacial clefts, and cancer risks in cleft patients. The associations observed warrant further investigation in a larger cohort and will set the stage for a more mechanistic approach toward understanding the risk for cancers in families with clefts.


Data Science Degree Apprentice.
In September 2019, 27 apprentices enrolled in the Level 6 Applied Data Science Degree Apprenticeship program, the first of its type in Wales. This article details the experiences of an apprentice on the course who works in the Data Science Campus at the Office for National Statistics. It summarizes how they have found the apprenticeship so far, the sort of data science projects they have been involved in, and the experience of studying for the degree at the same time.


Whole genome sequencing of Neisseria meningitidis W isolates from the Czech Republic recovered in 1984-2017.
The study presents the analysis of whole genome sequence (WGS) data for Neisseria meningitidis serogroup W isolates recovered in the Czech Republic in 1984-2017 and their comparison with WGS data from other countries. Thirty-one Czech N. meningitidis W isolates, 22 from invasive meningococcal disease (IMD) and nine from healthy carriers were analysed. The 33-year study period was divided into three periods: 1984-1999, 2000-2009, and 2010-2017. Most study isolates from IMD and healthy carriers were assigned to clonal complex cc22 (n = 10) in all study periods. The second leading clonal complex was cc865 (n = 8) presented by IMD (n = 7) and carriage (n = 1) isolates that emerged in the last study period, 2010-2017. The third clonal complex was cc11 (n = 4) including IMD isolates from the first (1984-1999) and third (2010-2017) study periods. The following clonal complex was cc174 (n = 3) presented by IMD isolates from the first two study periods, i.e. 1984-1999 and 2000-2009. One isolate of each cc41/44 and cc1136 originated from healthy carriers from the second study period, 2000-2009. The comparison of WGS data for N. meningitidis W isolates recovered in the Czech Republic in the study period 1984-2017 and for isolates from other countries recovered in the same period showed that clonal complex cc865, ST-3342 is unique to the Czech Republic since 2010. Moreover, the comparison shows that cc11 in the Czech Republic does not comprise novel hypervirulent lineages reported from both European and non-European countries. All 31 study isolates were assigned to Bexsero® Antigen Sequence Types (BAST), and seven of them were of newly described BASTs. WGS analysis contributed considerably to a more detailed molecular characterization of N. meningitidis W isolates recovered in the Czech Republic over a 33-year period and allowed for a spatial and temporal comparison of these characteristics between isolates from the Czech Republic and other countries. The most interesting finding of this study is that eight of 31 Czech isolates of N. meningitidis W belong to clonal complex cc865, which is uncommon for serogroup W. In addition, the WGS data precised the base for the update of the recommendation for vaccination in the Czech Republic.


5-Aminoimidazole-4-carboxamide ribonucleoside-induced autophagy flux during differentiation of monocytic leukemia cells.
Pharmacological modulators of AMP-dependent kinase (AMPK) have been suggested in treatment of cancer. The biguanide metformin and 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) have been reported to inhibit proliferation of solid tumors and hematological malignancies, but their role in differentiation is less explored. Our previous study demonstrated that AICAR alone induced AMPK-independent expression of differentiation markers in monocytic U937 leukemia cells, and no such effects were observed in response to metformin. The aim of this study was to determine the mechanism of AICAR-mediated effects and to test for the possible role of autophagy in differentiation of leukemia cells. The results showed that AICAR-mediated effects on the expression of differentiation markers were not mimicked by A769662, a more specific direct AMPK activator. Long-term incubation of U937 cells with AICAR and other differentiation agents, all-trans-retinoic acid (ATRA) and phorbol 12-myristate 13-acetate, increased the expression of the autophagy marker LC3B-II, and these effects were not observed in response to metformin. Western blot and immunofluorescence analyses of U937 cells treated with bafilomycin A1 or transfected with mRFP-GFP-LC3 proved that the increase in the expression of LC3B-II was due to an increase in autophagy flux, and not to a decrease in lysosomal degradation. 3-Methyladenine inhibited the expression of differentiation markers in response to all inducers, but had stimulatory effects on autophagy flux at dose that effectively inhibited the production of phosphatidylinositol 3-phosphate. The small inhibitory RNA-mediated down-modulation of Beclin 1 and hVPS34 had no effects on AICAR and ATRA-mediated increase in the expression of differentiation markers. These results show that AICAR and other differentiation agents induce autophagy flux in U937 cells and that the effects of AICAR and ATRA on the expression of differentiation markers do not depend on the normal levels of key proteins of the classical or canonical autophagy pathway.


Publisher Correction: The tuatara genome reveals ancient features of amniote evolution.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Concurrent material and structure optimization of multiphase hierarchical systems within a continuum micromechanics framework.
We present a concurrent material and structure optimization framework for multiphase hierarchical systems that relies on homogenization estimates based on continuum micromechanics to account for material behavior across many different length scales. We show that the analytical nature of these estimates enables material optimization via a series of inexpensive "discretization-free" constraint optimization problems whose computational cost is independent of the number of hierarchical scales involved. To illustrate the strength of this unique property, we define new benchmark tests with several material scales that for the first time become computationally feasible via our framework. We also outline its potential in engineering applications by reproducing self-optimizing mechanisms in the natural hierarchical system of bamboo culm tissue.


Increased adult neurogenesis associated with reactive astrocytosis occurs prior to neuron loss in a mouse model of neurodegenerative disease.
This study was to investigate whether cell proliferation and adult neurogenesis are affected at early neurodegenerative stage when neuron loss has not begun to display. Forebrain-specific nicastrin (NCT) conditional knockout (cKO) mice were generated by crossing NCTf/f with CaMKIIα-Cre Tg mice. BrdU was used as a lineage tracer to label proliferating neural progenitor cells (NPCs). Immunohistochemistry (IHC) on BrdU indicated that the total number of BrdU positive (+) cells was increased in NCT cKO mice. IHC on doublecortin (DCX) showed that the total number of DCX+ cells was also increased in NCT cKO mice. NCT cKO mice displayed significant astrogliosis as well. However, NCT cKO mice at 3 months did not show significant neuronal death or synaptic loss. NCT-dependent γ-secretase activity plays an important role in cell proliferation and immature neuron generation. Enhanced neurogenesis and astrogliosis may be early cellular events prior to the occurrence of neuronal death in neurodegenerative disease.


Multiple-feature discrimination faster than single-feature discrimination within the same object?
In the present study, we investigated whether judging the presence of multiple features within an object would be superior to judging the presence of only one feature. Feature discriminability and the number of features to discriminate within an object were varied. Specific features were judged as present or absent. Results showed that judging the presence of two or three features was faster than judging the presence of the less discriminable of these two or three features alone (multiple-feature benefits). These findings suggest that relevant features within an object activate (prime) a decision or response in a parallel, asynchronous fashion based on discriminability (Miller, 1982a). The ability of a response priming model, a response mapping model, and a template model to account for multiple-feature benefits is discussed.


Does higher gadolinium concentration play a role in the morphologic assessment of brain tumors? Results of a multicenter intraindividual crossover comparison of gadobutrol versus gadobenate dimeglumine (the MERIT Study).
Gadobenate dimeglumine has proved advantageous compared with other gadolinium-based contrast agents for contrast-enhanced brain MR imaging. Gadobutrol is a more highly concentrated agent (1.0 mol/L). This study intraindividually compared 0.1-mmol/kg doses of these agents for qualitative and quantitative evaluation of brain tumors. Adult patients with suspected or known brain tumors underwent 2 identical MR imaging examinations at 1.5T, 1 with gadobenate dimeglumine and the other with gadobutrol, both at a dose of 0.1-mmol/kg body weight. The agents were injected in randomized order separated by 3-14 days. Imaging sequences and acquisition timing were identical for the 2 examinations. Three blinded readers evaluated images qualitatively for diagnostic information (lesion extent, delineation, morphology, enhancement, global preference) and quantitatively for CNR and LBR. One hundred fourteen of 123 enrolled patients successfully underwent both examinations. Final diagnoses were intra-axial tumors, metastases, extra-axial tumors, "other" tumors, and "nontumor" (49, 46, 8, 7, and 4 subjects, respectively). Readers 1, 2, and 3 demonstrated preference for gadobenate dimeglumine in 46 (40.7%), 54 (47.4%), and 49 (43.0%) patients, respectively, compared with 6, 7, and 7 patients for gadobutrol (P < .0001, all readers). Highly significant (P < .0001, all readers) preference for gadobenate dimeglumine was demonstrated for all other qualitative end points. Inter-reader agreement was good for all evaluations (κ = 0.414-0.629). Significantly superior CNR and LBR were determined for gadobenate dimeglumine (P < .019, all readers). Significantly greater morphologic information and lesion enhancement are achieved on brain MR imaging with 0.1-mmol/kg gadobenate dimeglumine compared with gadobutrol at an equivalent dose.


Influence of carrageenan on the rheology and skin permeation of microemulsion formulations.
Three different microemulsions (A-C) and one semisolid preparation D were investigated in terms of viscoelastic properties and skin permeation of the model compound sodium fluorescein. The influence of the polysaccharide carrageenan on these parameters was investigated. Carrageenan is frequently used as food additive and has very interesting properties like good adhesiveness on skin which can be a benefit for topical application. The viscoelastic properties of the preparations (A-D) and of mixtures with carrageenan (A'-D') were characterized by oscillatory measurements. It was possible to adjust the rheologic properties of the formulations and to increase the sodium fluorescein permeation through porcine skin by mixing them with carrageenan gels. Therefore, the presented formulations as well as mixtures with carrageenan might be promising alternative drug carrier systems for topical pharmaceutical as well as cosmetics.


miR-203 inhibits cell proliferation and promotes cisplatin induced cell death in tongue squamous cancer.
Oral squamous cell carcinoma (OSCC) is one of the most common types of the head and neck cancer. Chemo resistance of OSCC has been identified as a substantial therapeutic hurdle. In this study, we analyzed the role of miR-203 in the OSCC and its effects on cisplatin-induced cell death in an OSCC cell line, Tca8113. There was a significant decrease of miR-203 expression in OSCC samples, compared with the adjacent normal, non-cancerous tissue. After 3 days cisplatin treatment, the survived Tca8113 cells had a lower expression of miR-203 than that in the untreated control group. In contrast, PIK3CA showed an inverse expression in cancer and cisplatin survived Tca8113 cells. Transfection of Tca8113 cells with miR-203 mimics greatly reduced PIK3CA expression and Akt activation. Furthermore, miR-203 repressed PIK3CA expression through targeting the 3'UTR. Restoration of miR-203 not only suppressed cell proliferation, but also sensitized cells to cisplatin induced cell apoptosis. This effect was absent in cells that were simultaneously treated with PIK3CA RNAi. In summary, these findings suggest miR-203 plays an important role in cisplatin resistance in OSCC, and furthermore delivery of miR-203 analogs may serve as an adjuvant therapy for OSCC.


Biogenic Synthesis of Carboxymethyl Cashew Gum Modified Gold Nanoparticles and its Sensitive and Selective Calorimetric Detection of Hg2+ Ions and Catalytic Reduction of Methyl Red.
In the present study, we have successfully synthesized and characterized carboxy methyl cashew gum modified gold nanoparticles (CMCG-AuNPs) via a microwave-assisted method and used as a calorimetric probe for selective detection of Hg2+ ions as well as catalytic reduction of methyl red in an aqueous medium. The effect of different parameters including concentration and irradiation time on the formation of CMCG-AuNPs was also investigated. The presence of strong surface plasmon resonance (SPR) peak in the visible region indicated the formation of AuNPs. The characterization techniques were identified the interaction between the CMCG and AuNPs with estimation of size and morphology. The face centred cubic (FCC) crystal structure was identified by using XRD and supporting with SAED pattern. TEM images of CMCG-AuNPs were exhibited as polydispersed with spherical in shape and the average particle size was 12 ± 3 nm. The synthesized CMCG-AuNPs were utilized to sensing Hg2+ ions in an aqueous medium, the presence of Hg2+ ions selectively among other metal ions, the CMCG-AuNPs were aggregated by changing the color from wine red to purple blue accompanied by change in the position of SPR peak and intensity. It was observed as a strong linear relationship based on the change in intensity, the limit of detection was determined to be 0.277 nM. The catalytic activity was also examined for the reduction of methyl red (MR) in the presence of CMCG-AuNPs was completed within 12 min and followed pseudo-first order kinetics with a rate constant of 0.261 min-1. From the obtained results, the synthesized CMCG-AuNPs were useful for detection of heavy metal ions as well as toxic pollutants degradation via a green method, and utilized sensing, environmental, and biomedical application in future.


Methiothepin and a 5-HT pathway to rat substantia nigra.
Methiothepin reduced both median-raphe evoked and exogenous 5-HT depression of single substantia nigra neurones. While this is compatible with a serotonin releasing pathway, additional interactions of methiothepin with exogenous dopamine suggest the need for further pharmacological confirmation.


Cecropia obtusifolia Bertol and its active compound, chlorogenic acid, stimulate 2-NBDglucose uptake in both insulin-sensitive and insulin-resistant 3T3 adipocytes.
Cecropia obtusifolia Bertol (Cecropiaceae) is a plant extensively used for the empirical treatment of type 2 diabetes in México. Although some of its hypoglycemic principles have been described, their mechanisms of action remain unclear. To investigate the anti-diabetic mechanisms of Cecropia obtusifolia aqueous extract (CAE) and its active compound chlorogenic acid (CGA). Non-toxic concentrations of CAE and CGA were assayed on the adipogenesis and 2-NBDglucose uptake in 3T3-F442A murine adipocytes. Added to adipogenic medium, CAE 70 microg/ml induced a modest increment (20%) in 3T3 adipogenesis whereas CGA did not affect adipogenesis at any of the tested concentrations (0.1-100 microM). Both preparations stimulated 2-NBDG uptake in adipocytes by 51% (CAE) and 176% (CGA) in the absence of insulin, and by 174% (CAE) and 404% (CGA) in the presence of the hormone. CAE and CGA also stimulated the 2-NBDG uptake in insulin-resistant 3T3 adipocytes by 35% and 141%, respectively, compared with the incorporation shown by insulin-sensitive adipocytes stimulated by the hormone. The potency of CGA to stimulate 2-NBDG uptake was comparable to the anti-diabetic drug rosiglitazone. Cecropia obtusifolia and CGA exert their anti-diabetic effects stimulating glucose uptake in both insulin-sensitive and insulin-resistant adipocytes without appreciable pro-adipogenic effects.


Exercise testing in the diagnosis of coronary heart disease: a perspective.
The methods of assessing the diagnostic usefulness of exercise testing in detecting coronary obstructive disease are examined. The limitations of long-term clinical follow-up and coronary angiography as standards for the determination of disease are described as are the effects of test methodology, criteria for positivity, prevalence of disease in the study population, reliability of the standard and recognition of false positive and false negative results in determining reliability of such testing. High values were found for sensitivity and specificity for exercise testing of patients with coronary artery disease referred for consultation to medical center cardiology services. Maximal exercise testing and consideration of symptomatic and hemodynamic as well as electrocardiographic criteria for identification of myocardial ischemia are helpful in improving reliability. Diagnostic accuracy is greatly enhanced by recognition of known causes for false positive and false negative results.


A comparison investigation on the solubilization of betulin and betulinic acid in cyclodextrin derivatives.
Betulin (BET) and betulinic acid (BA) are naturally occurring pentacyclic lupane triterpenes, exhibit great promise as bioactive agents for the treatment of many diseases. The poor solubilities of BET and BA in water have limited their applications. In the present work, BET and BA were selected as guest molecules, three hydrophilic gamma-cyclodextrin (CD) thioethers were synthesized and selected as host molecules. beta-, Hydroxypropyl-beta-CD, (HP-beta-CD), gamma-CD and HP-gamma-CD were also investigated as hosts in order to compare the solubilization abilities of these host molecules. The solubilities of BET and BA were estimated from 1H NMR measurements by comparing the relative integral areas of the proton signals between CDs and guests. gamma-CD thioethers 5-7solubilized BET and BA to much higher extends than other host molecules. The obtained maximal solubilities of BET and BA were 5.2 and 4.5 mM, respectively. The topographies of the inclusion compounds were determined by ROESY NMR spectroscopy.


The recent fall in postperinatal mortality in New Zealand and the Safe Sleep programme.
Postneonatal mortality rates changed very little from 2000 until recently. There has been a decrease in mortality in New Zealand from 2009 to 2015. This study describes an infant Safe Sleep programme and postulates it is the cause for the recent decrease in deaths. The Safe Sleep programme involved as follows: a focus on preventing accidental suffocation, a 'blitz' approach to SUDI education, the targeted provision of portable infant Safe Sleep devices (ISSD) and the development of Safe Sleep policy across all district health boards (DHBs). Participation in the education 'blitz' by health professionals exceeded one in 23 live births, distribution of Safe Sleep leaflets exceeded two for every live birth, and over 16 500 ISSDs have been distributed to vulnerable infants. Postperinatal mortality fell 29% from 2009 to 2015 (2.8 to 2.0/1000 live births). The fall has been greatest for Māori and in regions with the most intensive programmes. The recent fall in postperinatal mortality has not happened by chance. It is likely that the components of end-stage prevention strategy, a focus on preventing accidental suffocation, the education 'blitz', the targeted supply of ISSDs and strengthened health policy, have all contributed to varying degrees.


Reduced phosphodiesterase 3 activity and phosphodiesterase 3A level in synthetic vascular smooth muscle cells: implications for use of phosphodiesterase 3 inhibitors in cardiovascular tissues.
Vascular smooth muscle cells (VSMC) in situ function to control contraction and are said to express a contractile phenotype. However, during development or in response to vascular damage, VSMC proliferate and express a more synthetic phenotype. A survey of literature values for contractile and synthetic VSMC phosphodiesterase (PDE) 3 and PDE4 activities identified a marked difference in the PDE3 and PDE4 activities of these cells. In this study, a comparison of PDE3 and PDE4 activities in contractile and synthetic VSMC demonstrates that a reduced PDE3/PDE4 activity ratio in synthetic VSMC correlates with a reduced PDE3 activity and is associated with marked reductions in PDE3A mRNA and protein levels. Because we show that similar reductions in PDE3 activity and PDE3A levels occur upon culture of human aortic VSMC and that this phenomenon associates with the phenotypic switch that occurs to VSMC in response to vascular damage, our findings are presented in the context that PDE3 inhibition might be expected to selectively alter functions of contractile VSMC.


The application of phospholipid removal columns and ultra-high performance liquid chromatography-tandem quadrupole mass spectrometry for quantification of multi-class antibiotics in aquaculture samples.
In this study a robust and sensitive method based on a proposed sample purification procedure, using zirconia-coated Phree™ columns and analysis by ultra-high performance liquid chromatography with triple quadrupole tandem mass spectrometry are presented for the assessment of multi-class antibiotics in farmed fish species. The sample preparation procedure benefited from combined precipitation of proteins and selective removal of phospholipids by Phree™ columns, resulting in a high sensitivity of the method (LOQ 0.3-9mgkg(-1)). The in-house validation results (precision, repeatability, decision limit CCα, detection capability CCβ, etc.) indicate that the elaborated method is fully suitable for the analysis of the main classes of antibiotics in accordance with the European Union (EU) Commission Decision 2002/657/EC. The method was applied to the analysis of antibiotics in trout and sturgeon samples obtained from the local inland aquacultures in Latvia. The results revealed the presence of two antibiotics (enrofloxacin and trimethoprim) in 12 out of the 20 analysed fish samples at concentrations (0.33-12.2μgkg(-1)) below the MRLs, thus causing no acute risks to consumers.


The control of endemic goitre by iodized oil in a community health programme.
A programme of iodized oil injections was carried out in an area of high goitre prevalence (28.5%) in rural Zaire. The iodized oil programme was undertaken as a part of a broader, pre-existing community health programme. No complications were encountered.


Sterile versus nonsterile gloves for repair of uncomplicated lacerations in the emergency department: a randomized controlled trial.
Although sterile technique for laceration management continues to be recommended, studies supporting this practice are lacking. Using clean nonsterile gloves rather than individually packaged sterile gloves for uncomplicated wound repair in the emergency department may result in cost and time savings. This study is designed to determine whether the rate of infection after repair of uncomplicated lacerations in immunocompetent patients is comparable using clean nonsterile gloves versus sterile gloves. A prospective multicenter trial enrolled 816 individuals who were randomized to have their wounds repaired by using sterile or clean nonsterile gloves. The attending physician or resident completed a checklist describing patient, wound, and management characteristics. The patients were provided with a questionnaire to be completed by the physician who removed their sutures at the prescribed time and indicated the presence or absence of infection. When follow-up forms were not returned, a telephone call was made to the patient to determine whether he or she had experienced any wound complications. Follow-up was obtained for 98% of the sterile gloves group and 96.6% of the clean gloves group. There was no statistically significant difference in the incidence of infection between the 2 groups. The infection rate in the sterile gloves group was 6.1% (95% confidence interval [CI] 3.8% to 8.4%) and was 4.4% in the clean gloves group (95% CI 2.4% to 6.4%). The relative risk of infection was 1.37 (95% CI 0.75 to 2.52). This study demonstrated that there is no clinically important difference in infection rates between using clean nonsterile gloves and sterile gloves during the repair of uncomplicated traumatic lacerations.


A simplified determination of total concentrations of Ca, Fe, Mg and Mn in addition to their bioaccessible fraction in popular instant coffee brews.
A direct analysis of instant coffee brews with HR-CS-FAAS spectrometry to determine the total Ca, Fe, Mg and Mn content has been developed and validated. The proposed method is simple and fast; it delivers good analytical performance; its accuracy being within -3% to 3%, its precision--2-3% and detection limits--0.03, 0.04, 0.004 and 0.01 mg l(-1) for Ca, Fe, Mg and Mn, respectively. In addition, Ca, Fe, Mg and Mn bioaccessibility in instant coffee brews was measured by means of the in vitro gastrointestinal digestion with the use of simulated gastric and intestinal juice solutions. Absorption of metals in intestinal villi was simulated by means of ultrafiltration over semi-permeable membrane with a molecular weight cut-off of 5 kDa. Ca, Fe, Mg and Mn concentrations in permeates of instant coffee gastrointestinal incubates were measured with HR-CS-FAA spectrometry.


Cardiovascular safety with linagliptin in patients with type 2 diabetes mellitus: a pre-specified, prospective, and adjudicated meta-analysis of a phase 3 programme.
This study investigated the cardiovascular (CV) safety profile of the dipeptidyl peptidase (DPP)-4 inhibitor linagliptin versus comparator treatments. This was a pre-specified meta-analysis of CV events in linagliptin or comparator-treated patients with type 2 diabetes mellitus (T2DM) from eight Phase 3 studies. All suspected CV events were prospectively adjudicated by a blinded independent expert committee. The primary endpoint was a composite of CV death, stroke, myocardial infarction, and hospitalization for unstable angina. Three secondary composite endpoints derived from the adjudicated CV events were also pre-specified. Risk estimates were calculated using several statistical methods including Cox regression analysis. Of 5239 treated patients (mean ± SD HbA1c 65 ± 10 mmol/mol [8.0 ± 0.9%], age 58 ± 10 years, BMI 29 ± 5 kg/m2), 3319 received linagliptin once daily (5 mg, 3159; 10 mg, 160) and 1920 received comparators (placebo, 977; glimepiride 1-4 mg, 781; voglibose 0.6 mg, 162). Cumulative exposure (patient-years) was 2060 for linagliptin and 1372 for comparators. Primary CV events occurred in 11 (0.3%) patients receiving linagliptin and 23 (1.2%) receiving comparators. The hazard ratio (HR) for the primary endpoint showed significantly lower risk with linagliptin than comparators (HR 0.34 [95% confidence interval (CI) 0.16-0.70]) as did estimates for all secondary endpoints (HR ranging from 0.34 to 0.55 [all upper 95% CIs < 1.0]). These results from a large Phase 3 programme support the hypothesis that linagliptin may have CV benefits in patients with T2DM.


[Prognostic value of PD-1/PD-L1 expression in upper tract urothelial carcinoma].
Current literature supports the efficacy of anti-PD-1 and anti-PD-L1 immune checkpoint inhibitors for the treatment of urothelial carcinomas. While the prognostic value of PD-1 and PD-L1 levels has been comprehensively analyzed for urothelial carcinoma of the bladder, less is known for upper tract urothelial carcinoma. In addition, available data on the prognostic value of PD-1 and/or PD-L1 level in the tumor and/or peritumoral microenvironment are heterogeneous and even sometimes contradictory. In this article, we compared the methodologies of the various available studies in order to highlight the factors that can explain these discordant results.


Comment on "accuracy and precision of four main glucometers used in a sub-Saharan African country: a cross-sectional study" by Choukem et al.
In their article, Choukem et al. report of assessments of the analytical quality of blood glucose monitoring systems. Although there are some commendable aspects regarding the methodology, some major shortcomings could preclude the conclusions drawn by Choukem et al. Nevertheless, independent assessments of the performance of blood glucose monitoring systems are an important issue.


Modification to the Fontan procedure for the prophylaxis of intra-atrial reentrant tachycardia: short-term results of a prospective randomized blinded trial.
We evaluated the feasibility, safety, and short-term efficacy of an interventional atrial incision placed at the time of the Fontan operation to reduce the development of intra-atrial reentrant tachycardia. This prospective randomized blinded trial was conducted in patients with congenital heart disease undergoing an initial lateral tunnel Fontan. Intervention patients underwent a lateral tunnel Fontan with an interventional atrial incision/cryoablation from the atriotomy to the right atrioventricular annulus. Controls underwent a standard lateral tunnel Fontan. Safety of the intervention was monitored. Short-term efficacy was determined by comparisons of conduction block across the incision area and spontaneous or inducible atrial arrhythmias. There were no significant differences between intervention (n = 21, median 2.4 years, range 0.8-3.9) and controls (n = 21, median 2.7 years, range 1.5-13.9) in age, type of heart disease, surgical parameters, or postoperative outcomes. Safety parameters showed no difference between groups in number or severity of adverse events. Short-term efficacy included evidence of conduction block with a longer conduction time across the incision area in intervention patients (median 97 ms, range 35-160) compared with controls (median 40 ms, range 8-77, P =.0001). No intervention patients had spontaneous or inducible intra-atrial reentrant tachycardia versus 2 controls (0/21 versus 2/21, P = NS). An interventional atrial incision to reduce intra-atrial reentrant tachycardia in the Fontan operation was feasible and safe. The intervention changed the atrial substrate as shown by an increase in conduction time. Short-term results showed a low incidence of intra-atrial reentrant tachycardia in all patients. Longer follow-up is necessary to assess clinical efficacy.


Learning, memory and synaptic plasticity in hippocampus in rats exposed to sevoflurane.
Developmental exposure to volatile anesthetics has been associated with cognitive deficits at adulthood. Rodent studies have revealed impairments in performance in learning tasks involving the hippocampus. However, how the duration of anesthesia exposure impact on hippocampal synaptic plasticity, learning, and memory is as yet not fully elucidated. On postnatal day 7(P7), rat pups were divided into 3 groups: control group (n=30), 3% sevoflurane treatment for 1h (Sev 1h group, n=30) and 3% sevoflurane treatment for 6h (Sev 6h group, n=28). Following anesthesia, synaptic vesicle-associated proteins and dendrite spine density and synapse ultrastructure were measured using western blotting, Golgi staining, and transmission electron microscopy (TEM) on P21. In addition, the effects of sevoflurane treatment on long-term potentiation (LTP) and long-term depression (LTD), two molecular correlates of memory, were studied in CA1 subfields of the hippocampus, using electrophysiological recordings of field potentials in hippocampal slices on P35-42. Rats' neurocognitive performance was assessed at 2 months of age, using the Morris water maze and novel-object recognition tasks. Our results showed that neonatal exposure to 3% sevoflurane for 6h results in reduced spine density of apical dendrites along with elevated expression of synaptic vesicle-associated proteins (SNAP-25 and syntaxin), and synaptic ultrastructure damage in the hippocampus. The electrophysiological evidence indicated that hippocampal LTP, but not LTD, was inhibited and that learning and memory performance were impaired in two behavioral tasks in the Sev 6h group. In contrast, lesser structural and functional damage in the hippocampus was observed in the Sev 1h group. Our data showed that 6-h exposure of the developing brain to 3% sevoflurane could result in synaptic plasticity impairment in the hippocampus and spatial and nonspatial hippocampal-dependent learning and memory deficits. In contrast, shorter-duration exposure (1h) results in less damage. These results provide further evidences that duration of anesthesia exposure could have differential effects on neuronal plasticity and neurocognitive performance.


A history of the genetic and molecular identification of genes and their functions controlling insect sex determination.
The genetics of the sex determination regulatory cascade in Drosophila melanogaster has a fascinating history, interlinked with the foundation of the Genetics discipline itself. The discovery that alternative splicing rather than differential transcription is the molecular mechanism underlying the upstream control of sex differences in the Drosophila model system was surprising. This notion is now fully integrated into the scientific canon, appearing in many genetics textbooks and online education resources. In the last three decades, it was a key reference point for starting evolutionary studies in other insect species by using homology-based approaches. This review will introduce a very brief history of Drosophila genetics. It will describe the genetic and molecular approaches applied for the identifying and cloning key genes involved in sex determination in Drosophila and in many other insect species. These comparative analyses led to supporting the idea that sex-determining pathways have evolved mainly by recruiting different upstream signals/genes while maintaining widely conserved intermediate and downstream regulatory genes. The review also provides examples of the link between technological advances and research achievements, to stimulate reflections on how science is produced. It aims to hopefully strengthen the related historical and conceptual knowledge of general readers of other disciplines and of younger geneticists, often focused on the latest technical-molecular approaches.


The tissue expression of cytokines in human acute cutaneous graft-versus-host disease.
Although acute graft-versus-host disease (GVHD) is a common complication after allogeneic bone marrow transplantation (BMT), the specific pathophysiology of tissue damage has not been elucidated. We have previously described an infiltrate of CD2+, CD8+, alpha/beta receptor+ T lymphocytes, and the upregulation of ICAM-1 in tissues with acute GVHD. We hypothesized that these infiltrating lymphocytes may secrete cytokines that could contribute to tissue damage. In the current study, we used reverse transcription (RT) polymerase chain reaction (PCR) to explore the mRNA expression of candidate inflammatory cytokines IL-1 alpha, IL-2, IL-4, IL-6, TNF-alpha, and interferon-gamma (IFN-gamma) in peripheral blood mononuclear cells (PBMC) and skin biopsies of allogeneic BMT patients with GVHD and controls. In post-BMT control PBMC (n = 10); IL-2 RNA was infrequent (20% of samples) but was significantly more frequently detectable (71%; P < 0.05) after development of acute GVHD (n = 7). IL-4 expression was also more common in PBMC from patients with acute GVHD (57% vs. 30%; P < 0.05). Consistent with the PBMC data, IL-2 and IL-4 RNA were also more frequently detectable in skin biopsies with GVHD (n = 10): 70% of samples expressed IL-2 vs. 25% of normal controls (n = 8; P < 0.05); 60% had detectable IL-4 RNA vs. 0% of controls (P < 0.05). IFN-gamma detectability (40% vs. 12%; P < 0.05) was also more frequent in GVH skin. For both PBMC and skin, IL-1 alpha expression was infrequent in GVHD and controls, whereas TNF-alpha and IL-6 were expressed in nearly all samples. These data suggest that upregulated expression of IL-2, IL-4, and IFN-gamma may be part of the inflammatory cascade of human acute GVHD, while IL-1 alpha, TNF-alpha, and IL-6 are not discriminatory for the inflammation observed at the time of initial GVHD diagnosis.


Synthesis of Tetracyclic C2-Symmetric Ketiminium Salts and Evaluation as Catalysts for Epoxidation.
Short synthetic routes to the nonplanar tetracyclic ketiminium salt A and two close analogs are described. These are helical nonplanar structures as shown by X-ray crystallography.


Novel heterozygous variants in the EP300 gene cause Rubinstein-Taybi syndrome 2: Reports from two Chinese children.
Rubinstein-Taybi syndrome (RSTS) is a rare autosomal-dominant genetic disease caused by variants of CREBBP (RSTS1) or EP300 (RSTS2) gene. RSTS2 is much less common, with less than 200 reported cases worldwide to date. More reports are still needed to increase the understanding of its clinical manifestations and genetic characteristics. The clinical data of two children with RSTS2 were analyzed retrospectively, and their clinical manifestations, auxiliary examinations, and mutational spectrum were summarized. Liquid chromatography-tandem mass spectrometer (LC-MS/MS) technology was used to detect the levels of steroid hormones if possible. After analyzing the clinical and genetic characteristics of two boys with RSTS2 (0.7 and 10.4 years old, respectively) admitted in our hospital, we identified two novel heterozygous variants in the EP300 exon 22 (c.3750C > A, p. Cys1250*, pathogenic; c.1889A > G, p. Tyr630Cys, likely pathogenic), which could account for their phenotype. In addition to common clinical manifestations such as special facial features, microcephaly, growth retardation, intellectual disability, speech delay, congenital heart defect, recurrent respiratory infections, and immunodeficiency, we found one of them had a rare feature of adrenal insufficiency, and LC-MS/MS detection showed an overall decrease in steroid hormones. In our study, we identified two novel variants in the EP300 exon 22, and for the first time, we reported a case of RSTS2 associated with adrenal insufficiency, which will enrich the clinical and mutational spectrum of this syndrome.


Enforced CDK4 expression in a hematopoietic cell line confers resistance to the G1 arrest induced by ionizing radiation.
In hematopoietic cells, gamma-irradiation causes a p53-dependent transient G1 phase cell cycle arrest. Various extracellular growth inhibitory signals elicit G1 arrest by targeting CDK4. Here we show that in a myeloid cell line, 32D cl 3, enforced expression of CDK4, but not cyclins D2 nor D3, overrides the gamma-irradiation-induced G1 arrest. CDK4 does not confer resistance to the radiation-induced G2 block observed in parental cells. Ectopic expression of CDK4 overcomes the ionizing radiation-induced inhibition of CDK4 and CDK2 kinase activity. The levels of CDK4 protein do not change after exposure to ionizing radiation in either parental cells or those overexpressing CDK4. Ionizing radiation induces the expression of both p53 and p21, and in cells constitutively synthesizing exogenous CDK4, the return of p53 protein levels to baseline is prolonged. Increased levels of p21 are found associated with CDK4, and not CDK2, in the lines overexpressing CDK4, compared to the parental line, after exposure to ionizing radiation. Enforced expression of CDK4 may therefore overcome a gamma-irradiation-induced G1 arrest through the titration of the CDK inhibitor p21 allowing both CDK4 and CDK2 to remain active.


Both-bone forearm osteotomy for supination contracture: a cadaver model.
To quantify the magnitude of rotational correction possible when comparing a single forearm bone osteotomy and fixation with stepwise osteotomy and fixation of both bones in a cadaver model and to determine if the order in which the stepwise osteotomies are performed influences the amount of correction. Ten fresh-frozen cadaveric forearms were fixed to a frame positioned in the field of view of a motion-capture system. An experimental supination contracture was induced in full supination. Cadaver forearms were assigned randomly to group I (ulna osteotomy, rotation, plating) or group II (radius osteotomy, rotation, plating). Cadavers in group I were used later in group III (ulna + radius) by completing a radial osteotomy, rotation, and fixation in the forearms with the plated ulna. Similarly the specimens assigned to group II were used later in group IV (radius + ulna) by completing an ulna osteotomy, rotation, and fixation in the forearms with the plated radiuses. Measurements of forearm pronation were made after single-bone (groups I, II) and stepwise both-bone (groups III, IV) rotational osteotomies. Stepwise rotational osteotomy and fixation of the ulna followed by the radius produced significantly more corrective pronation (101 degrees) than rotating the radius followed by the ulna (65 degrees). Rotating the radius gave only moderate correction (58 degrees) and minimal correction was produced by ulna osteotomy alone (15 degrees). Rotational osteotomy of both forearm bones can create approximately 100 degrees of correction when performed at the proximal ulna followed by the distal radius. If less rotation is needed then the distal radius osteotomy alone can provide approximately 60 degrees of correction.


Brain and kidney GHS-R1a underexpression is associated with changes in renal function and hemodynamics during neurogenic hypertension.
Ghrelin is a peptide hormone whose effects are mediated by the growth hormone secretagogue receptor subtype 1a (GHS-R1a), mainly expressed in the brain but also in kidneys. The hypothesis herein raised is that GHS-R1a would be player in the renal contribution to the neurogenic hypertension pathophysiology. To investigate GHS-R1a role on renal function and hemodynamics, we used Wistar (WT) and spontaneously hypertensive rats (SHR). First, we assessed the effect of systemically injected vehicle, ghrelin, GHS-R1a antagonist PF04628935, ghrelin plus PF04628935 or GHS-R1a synthetic agonist MK-677 in WT and SHR rats housed in metabolic cages (24 h). Blood and urine samples were also analyzed. Then, we assessed the GHS-R1a contribution to the control of renal vasomotion and hemodynamics in WT and SHR. Finally, we assessed the GHS-R1a levels in brain areas, aorta, renal artery, renal cortex and medulla of WT and SHR rats using western blot. We found that ghrelin and MK-677 changed osmolarity parameters of SHR, in a GHS-R1a-dependent manner. GHS-R1a antagonism reduced the urinary Na+ and K+ and creatinine clearance in WT but not in SHR. Ghrelin reduced arterial pressure and increased renal artery conductance in SHR. GHS-R1a protein levels were decreased in the kidney and brain areas of SHR when compared to WT. Therefore, GHS-R1a role in the control of renal function and hemodynamics during neurogenic hypertension seem to be different, and this may be related to brain and kidney GHS-R1a downregulation.


Influence of environmental factors on social play behavior of juvenile rats.
The effects of light level and familiarity to the testing environment on social behaviors related and unrelated to play were investigated in juvenile rats accustomed to dim light conditions. Pinning, a measure characteristic for social play in rats, was completely suppressed under intense light conditions. Following/chasing and boxing/wrestling, social behaviors related to play, were also decreased under intense light. Of the measures of social behavior not related to play, contact behavior was decreased under intense light whereas social exploration was hardly affected. Levels of social exploration and following/chasing gradually declined during the 15-min test period. Frequency of contact behavior decreased, whereas duration increased with time. Under dim light conditions, unfamiliarity to the test cage suppressed pinning and boxing/wrestling but not the other social behaviors in the first part of the test period. These findings show that social behavior in juvenile rats, as in adult rats, can be influenced by light level and familiarity to the test cage. Social behaviors related and unrelated to play seem to be differentially influenced by environmental stimuli.


The ephemeral stories of our lives.
Johnson et al. make a persuasive case that qualitative, story-like reasoning plays a crucial role in everyday thought and decision-making. This commentary questions the cohesiveness of this type of reasoning and the representations that generate it. Perhaps narratives do not underpin, but are ephemeral products of thought, created when we need to justify our actions to ourselves and others.


Malnutrition in all its forms and socio-economic indicators in Argentina.
To assess the prevalence of five forms of malnutrition (wasting/underweight, overweight, obesity, stunting/short stature and anaemia) by socio-economic wealth (SEW) and educational level (EL) among children, adolescents and women of reproductive age in Argentina. Analysis from a cross-sectional survey. Anthropometric indicators and prevalence of anaemia were estimated. SEW was classified according to the proportion of contributors in the household, employment status, EL and medical coverage. EL was categorized by years of formal education. National Health and Nutrition Survey, 2005. Children (n 27 015) <5 years, adolescent girls (n 1729) 11-19 years, women (n 4401) 20-49 years. In Argentina, 26 % of households lived with unsatisfied basic needs and 23 % received at least one form of food assistance. Any form of malnutrition affected 23 % of children, 36 % of girls and 56 % of women. Children were especially affected by anaemia, overweight/obesity and stunting (15·2, 9·9, 7·4 %, respectively). Girls were affected by overweight/obesity, anaemia and stunting (22·5, 15·2, 6·2 %). Women were strongly affected by overweight/obesity, anaemia and stunting (43·8, 19·8, 10·5 %). Stunting or short stature was higher in low-SEW settings, doubling in prevalence between low and high levels, increasing four times among women in reproductive age (P < 0·05). Excess weight among children was higher in high-SEW settings, in women the tendency was inverse. Anaemia showed different tendency according to SEW. In 2005, Argentina had high rates of excess weight and anaemia, moderate prevalence of stunting and low frequency of wasting/underweight. All forms of malnutrition showed a strong relationship with socio-economic and educational inequality.


MRI compatible small animal monitoring and trigger system for whole body scanners.
Performing magnetic resonance imaging (MRI) experiments with small animals requires continuous monitoring of vital parameters, especially the respiration rate. Clinical whole-body MR scanners represent an attractive option for preclinical imaging as dedicated animal scanners are cost-intensive in both investment and maintenance, thus limiting their availability. Even though impressive image quality is achievable with clinical MR systems in combination with special coils, their built-in physiologic monitoring and triggering units are often not suited for small animal imaging. In this work, we present a simple, MRI compatible low cost solution to monitor the respiration and heart rate of small animals in a clinical whole-body MR scanner. The recording and processing of the biosignals as well as the optimisation of the respiratory trigger generation is decribed. Additionally rat and mouse in-vivo MRI experiments are presented to illustrate the effectiveness of the monitoring and respiratory trigger system in suppressing motion artifacts.


Centromere structure and chromosome number in mitosis of the colourless phytoflagellate Polytoma papillatum (Chlorophyceae, Volvocales, Chlamydomonadaceae).
Centromere structure is described in mitosis of the unicellular biflagellate alga Polytoma papillatum using transmission electron microscopy. The kinetochores are five-layered elements at the poleward surface of the chromosomes. The five layers consist of three dense plates interspersed by two transparent zones. The polemost dense layer serves as the attachment site for kinetochore microtubules and the innermost dense layer is intimately associated with the chromatin. The five-layered organization of the kinetochore in the alga is unusual. In animals, three-layered kinetochores are the rule. This type has also been found in some algae, while higher plants do not possess striated kinetochores. An attempt was made to determine the chromosome number of P. papillatum. Individual chromosomes could not be recognized with confidence, since there were numerous lateral contacts between the chromosomes throughout mitosis. An alternative approach, however, was successful. Counting the kinetochores in serial sections through mitotic metaphase and anaphase plates revealed a number of 15 chromosomes.


Gilbert syndrome, UGT1A1*28 allele, and cardiovascular disease risk: possible protective effects and therapeutic applications of bilirubin.
Serum bilirubin has been shown to be inversely related to cardiovascular disease (CVD) in both retrospective and prospective studies. Meta-analysis of existing studies has also confirmed that serum bilirubin concentrations are inversely related to CVD. Less information is known about the protective effects of slightly elevated serum bilirubin concentrations. In this review, we will focus primarily on the association of serum bilirubin and CVD and the possible protective roles of bilirubin, heme oxygenase (HO), and bilirubin UDP-glucuronosyltransferase (UGT1A1). HO and biliverdin reductase control the formation of bilirubin, whereas UGT1A1 controls bilirubin conjugation and clearance. Because of the health and therapeutic implications of slightly elevated serum bilirubin concentrations, we will discuss the recent prospective studies on cardiovascular risk in individuals with Gilbert syndrome (GS) as well as those with the UGT1A1*28 allele. Such individuals have decreased hepatic bilirubin UDP-glucuronosyltransferase activity, decreased bilirubin clearance, and increased serum bilirubin concentrations. Lastly, we will discuss some of the therapeutic approaches that could be used to increase serum bilirubin concentrations to prevent CVD and other oxidative and inflammatory diseases.


Estrogen in the adult male reproductive tract: a review.
Testosterone and estrogen are no longer considered male only and female only hormones. Both hormones are important in both sexes. It was known as early as the 1930's that developmental exposure to a high dose of estrogen causes malformation of the male reproductive tract, but the early formative years of reproductive biology as a discipline did not recognize the importance of estrogen in regulating the normal function of the adult male reproductive tract. In the adult testis, estrogen is synthesized by Leydig cells and the germ cells, producing a relatively high concentration in rete testis fluid. Estrogen receptors are present in the testis, efferent ductules and epididymis of most species. However, estrogen receptor-alpha is reported absent in the testis of a few species, including man. Estrogen receptors are abundant in the efferent ductule epithelium, where their primary function is to regulate the expression of proteins involved in fluid reabsorption. Disruption of the alpha-receptor, either in the knockout (alphaERKO) or by treatment with a pure antiestrogen, results in dilution of cauda epididymal sperm, disruption of sperm morphology, inhibition of sodium transport and subsequent water reabsorption, increased secretion of Cl-, and eventual decreased fertility. In addition to this primary regulation of luminal fluid and ion transport, estrogen is also responsible for maintaining a differentiated epithelial morphology. Thus, we conclude that estrogen or its alpha-receptor is an absolute necessity for fertility in the male.


Systemic adiponectin levels in colorectal cancer and adenoma: a systematic review and meta-analysis.
Obesity is a well-established risk factor in the development of colorectal cancer; however, the mechanism mediating this relationship is not well understood. The adipokine, adiponectin, has an inverse relationship with obesity. Experimental studies have shown adiponectin to have dichotomous inflammatory and tumorigenic roles. Its role in the development of colorectal cancer, including the potential effect of its increase following bariatric surgery, is not yet clear. There are conflicting results from studies evaluating this relationship. This study sought to provide a systematic review and meta-analysis to examine the association between systemic adiponectin levels in patients with colorectal cancer and adenoma. An electronic literature search was performed using PubMed, EMBASE, Web of Science as well as gray literature. Articles were screened for inclusion criteria and assessed for quality using the Newcastle-Ottawa Scale. Pooled mean differences were calculated using a random effects model. Subgroup and meta-regression analyses were performed to identify potential sources of heterogeneity. Thirty-two observational studies comparing systemic adiponectin in colorectal cancer vs healthy controls were included. Colorectal cancer cases had lower systemic adiponectin levels (overall pooled mean difference = -1.05 μg/ml [95% CI: -1.99; -0.12] p = 0.03); however, significant heterogeneity was present (I2 = 95% p < 0.01). Subgroup and meta- regression analyses results could not identify a source of the significant heterogeneity across the studies. Studies suggest a trend towards lower systemic adiponectin levels in colorectal cancer patients, but the heterogeneity observed showed current evidence is not sufficient to definitively draw any conclusions. These data, however, suggest rising adiponectin is unlikely to account for the reported observation of increased CRC following bariatric surgery. Further studies with prospective age, race, and BMI-matched cohorts, and standardized adiponectin measurements may provide a better understanding of this relationship.


Association of feeding modality with interstage mortality after single-ventricle palliation.
Interstage mortality has been reported in 10% to 25% of hospital survivors after single-ventricle palliation. The purpose of this study was to examine the impact of feeding modality at discharge after single-ventricle palliation on interstage mortality. We conducted a retrospective review of all neonates undergoing single-ventricle palliation from January 2003 to January 2010. A total of 334 patients (90%) survived to hospital discharge, comprising the study group. Preoperative, operative, and postoperative variables were examined, including feeding method at discharge. Multivariate Poisson regression models were constructed to estimate the relative risk of interstage mortality. Of 334 patients, 56 (17%) underwent gastrostomy tube ± Nissen. There was a statistically significant increase in interstage mortality for patients who underwent gastrostomy tube ± Nissen compared with patients who did not (relative risk, 2.38; 95% confidence interval, 1.05-5.40; P = .04]). Of the 278 patients who were not fed via a gastrostomy tube ± Nissen, 190 (68%) were fed with nasogastric feedings and 88 (32%) were fed entirely by mouth. There was no difference in interstage mortality between these 2 groups (relative risk, 0.92; 95% confidence interval, 0.31-2.73; P = .89). Neonates undergoing single-ventricle palliation who require gastrostomy tube ± Nissen are at an increased risk of interstage mortality. The need for gastrostomy tube ± Nissen in this population may be a marker for other unmeasured comorbidities that place them at an increased risk of interstage mortality. Discharge with nasogastric feeds does not increase the risk of interstage mortality.


Effects of mixed application of avermectin, imidacloprid and carbendazim on soil degradation and toxicity toward earthworms.
The application of pesticides in mixtures often exerts multiple pressures on agricultural soils in the short term. Therefore, it is necessary to assess the effects of mixed application on the environmental behavior and ecotoxicity of pesticides in soil. In this study, we assessed the effects of three common pesticides through mixed application on soil degradation and toxicity toward the earthworm Eisenia fetida. Compared with the degradation half-lives (DT50) the single pesticide, the DT50 values of avermectin, imidacloprid and carbendazim in the binary mixtures were similar. However, their DT50 values in the ternary mixtures were approximately 1.5 times longer than those in the individual applications, enhancing their stable in soil after two or three applications. The ternary mixtures of the pesticides showed significantly synergistic toxicity toward E. fetida, while their binary mixtures exhibited a changing interaction throughout the entire effect level range. The ternary mixtures activated higher SOD and CAT activities in E. fetida than the individual treatments, confirming their synergistic effects. By conducting avoidance tests with E. fetida, ternary toxic interactions were effectively assessed within a relatively short testing period. In summary, the three pesticides in ternary mixtures exhibited longer degradation half-lives and synergistic toxicity toward earthworms compared to individual or binary mixtures.


Influence of glucose and inhibitors of glycolysis on release of total proteins and enzymes from human leukocytes.
We studied the influence of substrates and glycolysis inhibitors on the release of proteins and enzymes from human leukocytes. We show the relationship between metabolic level and percentage of enzyme release. Leukocyte kept alive in a nutrient-free bicarbonate medium liberate enzymes even though their metabolic state is satisfactory. The addition of glucose to themedium significantly decreases this phenomenon without affecting the energy level. Addition of glycolysis inhibitors increases it, reduces the energy level, and interferes with other metabolic pathways. The results are discussed and compared to those obtained by other authors using various cell models.


Risk assignment in childhood brain tumors: the emerging role of molecular and biologic classification.
Brain tumors as a group are the most common solid tumors of childhood and currently have the highest mortality rate. A major emphasis has historically been placed on stratifying therapy for these tumors based on histologic and clinical prognostic factors. However, with the increasing application of molecular approaches to refine the categorization of these tumors, it has become apparent that histologically comparable lesions may exhibit diverse patterns of gene expression and genomic alterations, which may correspond with important prognostic distinctions. This paper summarizes these observations and discusses how they are being applied in a preliminary fashion as a foundation for risk-adapted stratification of childhood brain tumor therapy.


Oxidative stress responses and toxin accumulation in the freshwater snail Radix swinhoei (Gastropoda, Pulmonata) exposed to microcystin-LR.
Microcystin-LR (MCLR) is one of the most common toxins in eutrophic freshwater ecosystems. The ecotoxicological effects of MCLR in freshwater ecosystems have been widely documented; however, the physiological effects of MCLR on freshwater snails and the underlying toxicity/detoxification mechanisms have not been well investigated. In this laboratory study, antioxidant system responses in the hepatopancreas and the digestive tract of Radix swinhoei, a typical freshwater snail, exposed to 0.01 mg/L to 2 mg/L MCLR were explored. Antioxidant enzymes, particularly superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD), in the digestive tracts were effectively generated at 0.2 and 2 mg/L MCLR. However, SOD and CAT activities in the hepatopancreas were activated only at 0.2 mg/L MCLR. Glutathione (GSH) concentrations in the digestive tracts significantly increased at 0.01 to 0.2 mg/L MCLR; by comparison, GSH concentrations in the hepatopancreas remained stable. No oxidative damage (lipid peroxidations) occurred in the digestive tracts and the hepatopancreas when the snail was exposed to ≤0.2 mg/L MCLR. MCLR accumulation in different snail tissues was also examined. MCLR accumulated in different tissues and showed the following pattern: hepatopancreas > gonads > digestive tracts > muscles. Bioaccumulated concentrations in these four tissues increased as MCLR exposure concentrations increased; by contrast, bioaccumulation factors decreased as MCLR exposure concentrations increased. Our results indicated that R. swinhoei is sensitively responsive to MCLR by changing antioxidant system status to cope with the toxicity. Snails may be vectors of MCs that transfer MCs in eutrophic lakes via food chains or food web.


Acute subdural hematoma due to minor head trauma in patients with a lumboperitoneal shunt.
The cases of four patients treated with a lumboperitoneal shunt in whom acute subdural hematoma occurred after minor head trauma are presented. Three of the four patients had subdural fluid collection or widening of subarachnoid space observed on computed tomography scan after placement of the lumboperitoneal shunt. We report that patients with a lumboperitoneal shunt have the potential to develop acute subdural hematoma due to minor head trauma, and discuss its mechanism.


Solution structure of barley lipid transfer protein complexed with palmitate. Two different binding modes of palmitate in the homologous maize and barley nonspecific lipid transfer proteins.
The structure of a nonspecific lipid transfer protein from barley (ns-LTPbarley) in complex with palmitate has been determined by NMR spectroscopy. The structure has been compared to the structure of ns-LTPbarley in the absence of palmitate, to the structure of ns-LTPbarley in complex with palmitoyl coenzyme A, to the structure of ns-LTPmaize in its free form, and to the maize protein complexed with palmitate. Binding of palmitate only affects the structure of ns-LTPbarley moderately in contrast to the binding of palmitoyl coenzyme A, which leads to a considerable expansion of the protein. The modes of binding palmitate to the maize and barley protein are different. Although in neither case there are major conformational changes in the protein, the orientation of the palmitate in the two proteins is exactly opposite.


Comment on "Ongoing adaptive evolution of ASPM, a brain size determinant in Homo sapiens" and "Microcephalin, a gene regulating brain size, continues to evolve adaptively in humans".
Mekel-Bobrov et al. and Evans et al. (Reports, 9 Sept. 2005, p. 1720 and p. 1717, respectively) examined sequence data from modern humans within two gene regions associated with brain development, ASPM and microcephalin, and concluded that selection of these genes must be ongoing. We show that models of human history that include both population growth and spatial structure can generate the observed patterns without selection.


Lithogenic risk factors in the urine of black and white subjects.
To identify biochemical and dietary factors which may play a role in the low incidence of stone formation in the black South African population. The study included 31 semiurbanized black and 29 urbanized white subjects. The protocol and modern laboratory techniques used to assess recurrent stone formers were followed. Urinary sodium, potassium, creatinine, calcium, phosphate and urate levels were measured, and urinary citrate, oxalate and cystine assessed. Black subjects ate a diet significantly higher in sodium (P < 0.04); there was no difference in serum levels but urinary sodium was significantly higher (P < 0.001) in black than in white subjects. Urinary potassium, calcium, citrate, phosphate and cystine were all significantly lower in black than in white subjects (P < 0.001 for the first four and P < 0.03 for cystine). Certain intrinsic factors in South African black subjects may account for their lower frequency of stone formation than in white subjects. Of these, the very low urinary calcium, decreased urinary cystine and different interactions between sodium and calcium/cystine are probably important.


OLGA- and OLGIM-based staging of gastritis using narrow-band imaging magnifying endoscopy.
As atrophic gastritis and intestinal metaplasia as a result of Helicobacter pylori are considered risk factors for gastric cancer, it is important to assess their severity. In the West, the operative link for gastritis assessment (OLGA) and operative link for gastric intestinal metaplasia assessment (OLGIM) staging systems based on biopsy have been widely adopted. In Japan, however, narrow-band imaging (NBI)-magnifying endoscopic diagnosis of gastric mucosal inflammation, atrophy, and intestinal metaplasia has been reported to be fairly accurate. Therefore, we investigated the practicality of NBI-magnifying endoscopy (NBI-ME) for gastritis staging. We enrolled 55 patients, in whom NBI-ME was used to score the lesser curvature of the antrum (antrum) and the lesser curvature of the lower body (corpus). The NBI-ME score classification was established from images obtained beforehand, and then biopsy specimens taken from the observed areas were scored according to histological findings. The NBI-ME and histology scores were then compared. Furthermore, we assessed the NBI-ME and histology stages using a combination of scores for the antrum and corpus, and divided the stages into two risk groups: low and high. The degree to which the stage assessed by NBI-ME approximated that assessed by histology was then ascertained. Degree of correspondence between the NBI-ME and histology scores was 69.1% for the antrum and 72.7% for the corpus, and that between the high- and low-risk groups was 89.1%. Staging of gastritis using NBI-ME approximates that based on histology, and would be a practical alternative to the latter.


Influence of azithromycin and other macrolides on the intracellular killing of Staphylococcus aureus by human polymorphonuclear leucocytes of healthy donors and a patient with Chédiak-Higashi syndrome.
A mixture of human blood phagocytes from healthy donors and opsonized staphylococci was incubated in vitro for 30 min. After that time all the bacteria were phagocytosed. The test tubes were further incubated for 2, 4 and 24 h with or without addition of a macrolide (erythromycin, azithromycin, clarithromycin, roxithromycin) and the effect of these drugs on the survival of intracellular staphylococci (Staphylococcus aureus ATCC 25923) was measured. The minimal effective concentration of the antibiotic which killed 80-90% of the bacteria after a 4-hour incubation was 0.1 mg/l for erythromycin, azithromycin and clarithromycin and 1.2 mg/l for roxithromycin. The percentage of surviving bacteria after 2 and 4 h incubation was not significantly different between these macrolides at the minimal effective concentration. Increasing the concentration of each antibiotic above the minimal effective concentration did not alter the killing rate of intracellular staphylococci. The bacterial activity of polymorphonuclear leucocytes (PMNL) from a patient with Chédiak-Higashi syndrome was less in comparison to PMNL from healthy donors, but was improved in vitro by the addition of erythromycin or azithromycin.


[A new therapeutic approach of associated metabolic diseases. 1 000 patients treated with benfluorex (author's transl)].
Multiple metabolic factors of atherosclerosis frequently associated in the same patient proves the interest of a multifactorial treatment of atherosclerosis. In the paper the authors studied the results of the treatment with benfluorex of 1 000 patients suffering one or more metabolic risk factors. After a 3 month treatment, a highly significant and simultaneous reduction of hyperlipidemia, hyperglycemia, hyperuricemia is observed. The treatment is the more efficient that initial values are higher and that the diet is better observed. The results remain significant even in patients who have not lost weight.


Training Future Scientists: Predicting First-year Minority Student Participation in Health Science Research.
Using longitudinal data from the UCLA Cooperative Institutional Research Program (CIRP) and Your First College Year (YFCY) surveys, this study examines predictors of the likelihood that science-oriented students would participate in a health science undergraduate research program during the first year of college. The key predictors of participation in health science research programs are students' reliance on peer networks and whether campuses provide structured opportunities for first-year students even though only 12% of freshmen in the sample engaged in this activity. These experiences are particularly important for Black students. The findings inform efforts to orient students at an early stage, particularly under-represented minorities, toward biomedical and behavioral science research careers.


Expression of soluble human signaling lymphocytic activation molecule in vivo.
Signaling lymphocytic activation molecule (SLAM) is a novel glycoprotein expressed on activated T and B cells. Ligation of cell surface SLAM, either by anti-SLAM mAbs or the recombinant soluble form of SLAM (sSLAM), enhanced the proliferation of T and B cells in vitro. In addition, the engagement of SLAM on T cells preferentially induced IFN-gamma production even by allergen-specific TH2 clones. In this study we investigated the expression of sSLAM in vivo in healthy individuals and in disease conditions that are associated with increased TH1 - or TH2 -cell responses. The expression of mRNA encoding sSLAM in peripheral blood and synovial fluid (SF) lymphocytes was studied by using reverse transcriptase-PCR, and the presence of sSLAM protein in serum and SF samples was investigated by using a specific ELISA. Lymphocytes from patients with rheumatoid arthritis (RA) and healthy individuals consistently expressed mRNA encoding sSLAM. In addition, sSLAM protein was present in 38% of serum and 54% of SF samples from patients with RA and in 47% of serum samples from healthy individuals. The levels of sSLAM in positive serum and SF samples from patients with RA and in positive serum samples from healthy individuals were not significantly different. In contrast, the levels of sSLAM were significantly lower in patients with reactive arthritis or in patients with elevated IgE levels than in patients with RA. Similarly, the frequency of positive SF samples was significantly lower in reactive arthritis (28%) than in RA (54%). These results indicate that sSLAM is present in serum and SF, further suggesting that sSLAM regulates T- and B-cell function in vivo. Moreover, these data suggest an association between low sSLAM production and the occurrence of TH2 responses in vivo.


Effects of bradysole and dibasole on cerebral bloodflow under experimental conditions.
Bradysole (1 mg/kg intravenously) induced a moderate increase in cerebral bloodflow and a minor decrease in systemic blood pressure in narcotized rats. These effects were less pronounced compared to the effects of dibasole (bradysole structural analog) in the same dose.


Incidence and management of chyle leakage after esophagectomy.
Postoperative chyle leakage is a rare but well-recognized complication after esophageal surgery. The aim of this study was to identify its incidence and potentially predisposing factors and to assess the consequences and management. A consecutive series of 536 patients who underwent esophagectomy for malignant disease of the esophagus or gastroesophageal junction was reviewed. There were 20 patients (3.7%) with chyle leakage. After transthoracic esophagectomy the risk for the development of chyle leakage was higher than after transhiatal resection (p = 0.006). Chyle leakage was associated with more positive nodes (p = 0.041). Patients with chyle leakage had significantly more pulmonary complications (p < 0.001) and longer intensive care unit (p = 0.015) and hospital stays (p = 0.001). No patient with chyle leakage died. Conservative management, consisting of no enteral feeding and total parenteral nutrition, was instituted in all patients, but was abandoned in 4 patients (20%) because of persistence of high chyle output through the chest tube. In contrast to patients who were successfully treated with conservative measures, patients who eventually needed a reoperation had a drain output of more than 2 L on the day conservative therapy was started and 1 and 2 days later. Chyle leakage is seen more often in patients who undergo transthoracic esophagectomy and in patients who have more positive nodes. Patients with chyle leakage have more pulmonary complications. Conservative therapy is often successful, but operative therapy should be seriously considered in patients with a persistently high daily output of more than 2 L after 2 days of optimal conservative therapy.


Endothelin-1 and isoprenaline co-stimulation causes contractile failure which is partially reversed by MEK inhibition.
The mitogen-activated kinase kinases (MEK)-extracellular signal-regulated kinases (ERK) signaling pathway is activated by agonists like catecholamines or endothelin-1 (ET-1) and has been implicated in cardiac pathology, such as the progression from cardiac hypertrophy to failure. The purpose of the present study, performed in an in vitro model of contractile failure, was to evaluate whether MEK inhibition prevents functional deterioration. Contractile dysfunction was induced in reconstituted rat heart tissue by concomitant treatment with ET-1 (10 nmol/l) and isoprenaline (ISO, 10 nmol/l) for 5 days. While basal force of contraction was unchanged, contractile responsiveness to beta-adrenoceptor agonists was markedly impaired (active force declined to 51% of controls) and was associated with decreased lusitropy. Moreover, in ET-1+ISO-treated heart tissues, reprogramming of gene expression was observed with an increased ratio of beta-myosin heavy chain (MHC) to alpha-MHC mRNA and increased transcript levels of ANF and skeletal/smooth muscle alpha-actin isoforms. The MEK inhibitor U0126 (10 micromol/l) almost completely prevented the reduction in beta-adrenergic responsiveness and the negative lusitropic effect of ET-1+ISO co-stimulation. In addition, U0126 completely normalized ANF gene expression, but did not affect or only marginally affected expression of MHC and alpha-actin isoforms. These results suggest that interruption of the MEK-ERK signaling pathway with a specific MEK inhibitor prevents, in part, the occurrence of a pathologic phenotype secondary to excessive stimulation with neurohumoral factors. The MEK-ERK pathway seems to be an important but not exclusive regulatory pathway responsible for the development of contractile dysfunction.


Cellular junctions of the midgut in the centipede (Scutigerella pagesi) as revealed by lanthanum tracer and freeze-fracture technique.
In the midgut of a Myriapoda continuous junctions and gap junctions are described for the first time. Continuous junctions form a belt around the upper two-thirds of each cell. In the intercellular space long and smooth septa are clustered in sinuous strands and intramembrane particles appear on the PF. In the gap junctions the intramembrane particles are located on the EF.


Isolated lymphomatoid granulomatosis of the central nervous system: A case report and literature review.
Lymphomatoid granulomatosis (LYG) is an angiocentric and angiodestructive lymphoproliferative disease which can involve multiple organs of the body and is most common in the lungs. Its pathological features are proliferation of large atypical B-cells related to Epstein-Barr virus, T-cell infiltration and tissue necrosis. This disease is rare, and LYG which uniquely involves the central nervous system (CNS) is extremely rare. In this paper, we report a case of isolated lymphomatoid granulomatosis of the CNS (iCNS-LYG) diagnosed by histological biopsy and we review the clinical features of all similar cases reported in the past 46 years. A total of 49 cases of iCNS-LYG have been reported to date. The clinical, imaging and pathological features of iCNS-LYG are discussed in combination with a literature review.


Blepharospasm in a multiplex African-American pedigree.
Isolated blepharospasm (BSP) is a late-onset focal dystonia characterized by involuntary contractions of the orbicularis oculi muscles. Genetic studies of BSP have been limited by the paucity of large multiplex pedigrees. Although sequence variants (SVs) in THAP1 have been reported in rare cases of BSP, the genetic causes of this focal dystonia remain largely unknown. Moreover, in the absence of family history and strong in silico or in vitro evidence of deleteriousness, the pathogenicity of novel SVs in THAP1 and other dystonia-associated genes can be indeterminate. A large African-American pedigree with BSP was phenotypically characterized and screened for mutations in THAP1, TOR1A and GNAL with Sanger sequencing. Whole-exome sequencing of the proband was used to examine other dystonia-associated genes for potentially pathogenic SVs. In silico and co-segregation analyses were performed for a novel THAP1 SV identified in the proband. Seven family members exhibited increased blinking and/or stereotyped bilateral and synchronous orbicularis oculi spasms with age of onset ranging from early childhood to late adult life (7 to 54 years). The proband was found to harbor a novel THAP1 SV (c.314T>C, p.L105S). However, the p.L105S SV did not co-segregate with blepharospasm in the pedigree. Moreover, in silico analyses suggest that p.L105S is benign. No pathogenic or likely pathogenic SVs in other dystonia-associated genes were identified with whole-exome sequencing. Blepharospasm can be familial and may be hereditary in African-Americans. A comprehensive array of in silico tools, and, if possible, co-segregation analysis should be used to classify SVs in dystonia-associated genes.


Dihydromyricetin ameliorated nonalcoholic steatohepatitis in mice by regulating the composition of serous lipids, bile acids and ileal microflora.
Dihydromyricetin (DMY) is a natural flavonoid with anti-nonalcoholic steatohepatitis (NASH) activity. However, the effects of DMY on the composition of lipids and bile acids (BAs) in serum, and gut microbiota (GM) in ileum of mice with NASH are not clear. After male C57BL/6 mice was fed with methionine and choline deficiency (MCD) diet and simultaneously administered with DMY (300 mg/kg/day) by gavage for 8 weeks, the pathological changes of liver tissue were observed by Oil Red O, hematoxylin eosin and Masson staining, the levels of serum alaninea minotransferase, aspartate aminotransferase and liver triglyceride, malonic dialdehyde were detected by the detection kits, the composition and contents of serum lipids and BAs were detected by Liquid Chromatograph-Mass Spectrometry, the mRNA levels of hepatic BAs homeostasis-related genes were detected by RT-qPCR, and microbiological diversity in ileum was analyzed by 16S rDNA sequencing. The results showed that the significant changes including 29 lipids, 4 BAs (23-nor-deoxycholic acid, ursodeoxycholic acid, 7-ketodeoxycholic acid and cholic acid), 2 BA transporters (Mrp2 and Oatp1b2) and 8 GMs between MCD and DMY groups. Among them, DMY treatment significantly down-regulated 21 lipids, 4 BAs mentioned above, the ratio of Firmicutes/Bacteroidota and the abundance of Erysipelotrichaceae, Faecalibacuium, significantly up-regulated 8 lipids and 5 GMs (Verrucomicrobiota, Bacteroidota, Actinobacteria, Akkermansiaceae and Akkermansia). The results suggested that DMY may alleviate MCD diet-induced NASH through decreasing the serum levels of toxic BAs which regulated by liver Oatp1b2 and Mrp2, regulating the metabolism of related lipids, and up-regulating intestinal probiotics (Actinobacteria and Verrucomicrobiota at the phylum level; Akkermansiaceae at the family level; Akkermansiaat at the genus level) and inhibiting intestinal harmful bacteria (Firmicutes at the phylum level; Erysipelotrichaceae at the family level; Faecalibaculum at the genus level).


Synchronous onset of multiple cutaneous neuroendocrine (Merkel cell) carcinomas localized to the scalp.
Merkel cell carcinoma (MCC) is a rare aggressive neoplasm that typically presents as a solitary nodule or plaque on sun-exposed skin of the elderly. Although multiple MCC have been described, they are rare, and metastases must be excluded. We report a case of a 59-year-old white male who presented with abrupt onset of multiple small bluish papules on his frontal scalp. On low power, the tumor had the overall histological silhouette of a nodular basal cell carcinoma. However, because of the lack of an epithelial connection and the cell's cytomorphological features, a MCC was considered and was subsequently confirmed using immunohistochemical stains. The MCC described in this report is unusual in that it presented as multiple cutaneous lesions that arose synchronously, along with micrometastases to sentinel lymph nodes.


Organization of the vimentin system and its spatial relationship to the microtubule complex during the division of mammalian cells growing attached and in suspension.
We have used immunofluorescence staining with antibodies that detect vimentin, tubulin and the centrioles to compare the distributions of these respective antigens during the division of several suspension and attached cultured cells. Our observations demonstrate that 1) from distinct interphase organizations in suspension and attached cells, the vimentin system consistently rearranges with the onset of mitosis into a filamentous cage-like structure enclosing the spindle, 2) during cytokinesis, the polar centrosomes relocalize near the midbody in suspension cells while they remain at the pole opposite to it in attached cells, and 3) the vimentin cage is disintegrated and aggregated on each side of the midbody during cytokinesis in lymphoid cells but may be retained in other suspension cells.


Ambient elemental, reactive gaseous, and particle-bound mercury concentrations in New Jersey, U.S.: measurements and associations with wind direction.
Two and a half years of data of ambient concentrations of elemental mercury (Hg(0)), reactive gaseous mercury (RGM), and particle-bound mercury (Hg(p)) were collected at measurement sites at Elizabeth, New Jersey and New Brunswick, New Jersey with Tekran sampling units. The data were processed, summarized, and analyzed from a variety of perspectives. Data quality control and quality assurance procedures are described. Wind direction and wind speed data for each of the sites were also collected. Significant temporal variations in concentrations of all three species were observed. Some significant directional variations were also seen. The sporadic nature of many of the temporal variations is consistent with and could reflect highly variable emissions patterns from anthropogenic mercury sources. Overall mean concentrations of all species were determined. These were, for Hg(0), Hg(p), and RGM respectively; 2.25 +/- 0.04 nanograms per cubic meter (ng/m(3)), 8.21 +/- 0.39 picograms per cubic meter (pg/m(3)), and 8.93 +/- 0.31 pg/m(3) (arithmetic means and 95% confidence intervals) at Elizabeth, and 2.15 +/- 0.02 ng/m(3), 10.73 +/- 0.45 pg/m(3), and 6.04 +/- 0.30 pg/m(3) at New Brunswick. Mean concentrations were determined for 16 different sectors representing wind directions. The impact of one known large source is suggested by these data. Reasons for some directional variations are not apparent and suggest a need for further investigation.


Fibre loss and distribution in skeletal muscle from patients with severe peripheral arterial insufficiency.
Cross-sections of whole calf muscles (m soleus and m gastrocnemius) were obtained from five previously clinically health individuals who had died accidentally (controls) and from amputated legs of five patients of similar age with severe peripheral arterial insufficiency. In the controls, but not in the patients, a characteristic distribution of different fibre types over the entire cross-sections was found, with a relative increase in number of (slow twitch) type 1 fibres in the central parts of both m soleus and m gastrocnemius. A pronounced neuromuscular pathomorphology was found in the patients, especially in m gastrocnemius. The findings suggested widespread damage to the fibres. There was also a lower total number of fibres in these ischaemic muscles; about 50% of the fibres of m gastrocnemius seemed to have disappeared. The results suggested that the relative inactivity as such may be responsible for some of the structural changes, above all the dedifferentiated distribution of different fibres over the cross-section. However, repeated acute and chronic subacute ischaemia may also cause, in the long term, irreparable damage and loss of many individual fibres. This may explain why muscles of patients with peripheral arterial insufficiency are also weaker, during single contractions. The lack of corresponding muscular atrophy in these patients seems to a large extent to be explained by an increase in connective tissue.


Field emission properties of a three-dimensional network of single-walled carbon nanotubes inside pores of porous silicon.
We report characteristic field emission (FE) properties of single-walled carbon nanotubes (SWCNTs) synthesized inside the pores as well as on the top surface of a porous silicon (PS) substrate. Turn-on fields and emission current densities were measured and compared with those of other types of SWCNTs in similar environments. Investigation of the FE properties of SWCNTs synthesized inside the pores of a PS substrate revealed a low turn-on field of approximately 2.25 V/μm at 10 μA/cm2 and a high field-enhancement factor (6182) compared with other samples. A life-time stability test was performed by monitoring the current density before and after repeated exposure to O2, suggesting that the pore channel can effectively prevent O2(+) ion etching from destroying SWCNTs within the pores of the PS layer.


Exposure of cottonwood plants to ozone alters subsequent leaf decomposition.
Cottonwood saplings were exposed to ozone or charcoal-filtered air in a closed chamber. After leaf abscission, decomposition of individual leaf discs was measured in containers of stream water. Exposure of plants to 200 ppb ozone for 5 h caused early leaf abscission and changes in the chemical composition of leaves at time of abscission. Early-abscised leaves from O3-exposed plants had higher nitrogen, but decomposed more slowly than leaves from control plants. Leaves from O3-exposed plants that abscised at the normal time had lower nitrogen content and lower specific leaf mass than control leaves, but decomposed at the same rate as leaves from control plants. The results imply that O3 exposure can alter fundamental processes important to the functioning of detritus-based aquatic ecosystems.


Electrically elicited blink reflex and early acoustic evoked potentials in circumscribed and diffuse brain stem lesions.
In the present paper, the function of the brain stem in patients with brain stem lesions of various aetiology is investigated with electrophysiological methods. The clinical observations are supplemented by experimental investigations on cats, in which the blink reflex and the early acoustic evoked potentials were registered during the acute elevation of intracranial pressure. The findings in patients with circumscribed space-occupying lesions in the posterior fossa document that the registration of the BR and the BAEP have a functional diagnostic significance above and beyond the neurological and radiological investigation. In the case of the cerebellar space occupations, specific alterations could not be observed. On the contrary, the alterations of BR and BAEP indicate a general disturbance of brain stem function, possibly as a result of a general increase of intracranial pressure. In cerebellopontine angle tumours, both BR and BAEP showed specific alterations which were usually asymmetrical. The BR changes ipsilateral to the tumour are of major topodiagnostic significance, whereas the alterations of the contralateral potential are especially informative in the registration of BAEP. The alterations of BR and BAEP also allow an appraisal of the localization and extent of the lesion in primary space occupations in the brain stem: A pathological R1 indicates a pontine lesion, whereas pathological R2 responses are found in medullary and in oral pontine and mesencephalic lesions. In contrast to cerebellopontine angle tumours, the BAEP tends to show symmetrical alterations in primary brain stem lesions. The prolongations of interpeak latencies correspond to the brain stem segment concerned, and the same also applies to pathological amplitude reduction and deformations of individual potentials. In patients with localized brain stem damage, the reflex pathway of R2 is discussed on the basis of the BR findings. In contrast to the view held up to now that only structures situated caudal of the facial nucleus area are responsible for the genesis of the R2 response, it is assumed on the basis of our own observations that pontomesencephalic structures rostral to the facial nuclei are also important for the genesis of R2. Registration of BR and BAEP in patients with acute diffuse brain stem damage shows that both methods have a high diagnostic and prognostic value. Isolated damage and combined brain stem lesion can be demonstrated and the course can be followed up. Normalization of pathological findings reflects clinical recovery, and conversely a secondary deterioration indicates the presence of complications.(ABSTRACT TRUNCATED AT 400 WORDS)


Bradykinin and muscle stretch alter contralateral cat neck muscle spindle output.
The objective of this study was to investigate the activity of primary and secondary muscle spindle afferents (MSAs) in neck muscles, when the contralateral splenius or trapezius muscles were (1) exposed to i.m. injection of bradykinin (BK) (6-86 microg/ml), (2) stretched, (3) stretched during exposure to BK or (4) stretched after exposure to BK. It was found that injection of BK, muscle stretch and the combination of the two stimuli significantly excited primary and secondary MSAs via reflex effects onto static fusimotor neurones. BK, alone, and in combination with muscle stretch, induced more frequent, potent and long lasting effects as compared to muscle stretch. The effects of muscle stretch was significantly increased after exposure of BK, indicating that stretch-sensitive nerve-endings within neck muscles are sensitised by BK. The results are discussed in relation to the disturbances in motor co-ordination and proprioception found in patients suffering from chronic muscle pain in the cervical region.