Primary hepatocyte cultures as in vitro tools for toxicity testing: quo vadis?
Cultures of primary hepatocytes are versatile tools that can serve many in vitro toxicity testing purposes. However, they cope with dedifferentiation, a process that is already initiated during the hepatocyte isolation procedure and that is manifested as the progressive loss of functionality upon subsequent cultivation. A number of strategies to prevent dedifferentiation have been introduced over the last decades, all which aim at re-establishing the in vivo hepatocyte micro-environment in vitro, but that are of merely limited success. Recent mechanistic insight into the mechanisms that underlie hepatocyte dedifferentiation has opened new avenues for the development of novel approaches that target the actual causes of this deteriorative process and thus for the generation of a long-term hepatic in vitro tool. Such experimental system is urgently needed, especially in the light of the stringent European legislative modifications that are currently encountered by the pharmaceutical, chemical and, particularly, the cosmetic industry.


International students' university choice to study abroad in higher education and influencing factors analysis.
With the development of China's higher education, China has become increasingly popular as an education destination for international students. To explore the rationale and the influencing factors for them to attend Chinese universities, this research adopted a questionnaire survey and interviews with international students from a top university in China. The data were analyzed from four aspects: home countries' push factors, China's pull factors, university attractiveness factors and personal choice factors. The findings show that university attractiveness factors are more significant than the China's pull factors and the home countries push factors; China's pull factors have significant influence on the university attractiveness factors; For students from different regions, the factors of China's pull, home country's push and university attractiveness play significantly different role in affecting their choice of university, with Asian students much more affected than those from other parts of the world. Besides, individual subjective norms and individual value choices also affect students' choices to study abroad.


Percentage of intrinsic and relay cells in a thalamic nucleus projecting to general cortex in reptiles, Caiman crocodilus.
Small injections of horseradish peroxidase (HRP) restricted solely to the general cortex in reptiles, Caiman crocodilus, resulted in retrogradely labeled cells located bilaterally in the nucleus dorsolateralis anterior of the thalamus. Larger cortical injections of HRP labeled greater numbers of nucleus dorsolateralis anterior cells. HRP injections designed to label as much cortex as possible resulted in very few unlabeled ipsilateral neurons in the nucleus dorsolateralis anterior. The percentage of these unlabeled cells was less than 1%. These data indicate that the nucleus dorsolateralis anterior contains few, if any, intrinsic or local circuit neurons.


Secretory immunoglobulin A in preterm infants: determination of normal values in breast milk and stool.
IgA and its secretory form sIgA impact protection from infection and necrotising enterocolitis but little is known about quantities in preterm mums own milk (MOM) or infant stool, onset of endogenous production in the preterm gut, and what affects these. We measured by ELISA in MOM and stool from healthy preterm infants total IgA and sIgA longitudinally and additionally in MOM fresh, refrigerated, frozen, and after traversing feeding systems. In 42 MOM (median gestation 26 weeks), we showed total IgA levels and sIgA were highest in colostrum, fell over 3 weeks, and were not impacted by gestation. Median IgA values matched previous term studies (700 mcg/ml). In MOM recipients stool IgA was detected in the first week, at around 30% of MOM quantities. Formula fed infants did not have detectable stool IgA until the third week. Levels of IgA and sIgA were approximately halved by handling processes. MOM in the 3 weeks after preterm delivery contains the highest concentrations of IgA and sIgA. Endogenous production after preterm birth occurs from the 3 week meaning preterm infants are dependent on MOM for IgA which should be optimised. Routine NICU practices halve the amount available to the infant. (Secretory) Immunoglobulin A (IgA) is present in colostrum of maternal milk from infants as preterm as 23-24 weeks gestational age, falling over the first 3 weeks to steady levels similar to term. Gestation at birth does not impact (secretory) IgA levels in breast milk. IgA is present in very preterm infant stools from maternal milk fed infants from the first week of life, but not in formula milk fed preterm infants until week three, suggesting endogenous production from this point. Refrigeration, freezing, and feeding via plastic tubing approximately halved the amount of IgA available.


Requirement of galactolipids for photosystem I activity in lyophilized spinach chloroplasts.
1. The effect of monogalactosyl diacylglycerol and digalactosyl diacylglycerol on reconstitution of Photosystem I activity in heptane-extracted and galactolipase-treated spinach chloroplasts was investigated. 2. Both galactolipids, in a molar ratio with chlorophyll of 2.5, partially restored Photosystem I activity in heptane-extracted chloroplasts. An addition of saturating amounts of plastocyanin caused complete reactivation of Photosystem I. 3. Similarly, with galactolipase-treated chloroplasts, both galactolipids partially restored Phostosystem I activity and additional amounts of plastocyanin were required for complete reactivation. 4. The action of galactolipids on partial reconstitution of Photosystem I supports the suggestion of their structural role in the restoration of thylakoid membranes.


Effect of green and ripe Carica papaya epicarp extracts on wound healing and during pregnancy.
The traditional use of papaya to treat many diseases, especially skin conditions and its prohibition for consumption during pregnancy has prompted us to determine whether papaya extracts both from green and ripe fruits improve wound healing and also produce foetal toxicity. Aqueous extracts of green papaya epicarp (GPE) and ripe papaya epicarp (RPE) were applied on induced wounds on mice. GPE treatment induced complete healing in shorter periods (13 days) than that required while using RPE (17 days), sterile water (18 days) and Solcoseryl ointment (21 days). Extracts were administered orally (1 mg/g body weight/day) to pregnant mice from day 10 and onwards after conception. 3 (n=7) mice and 1 (n=6) mice given RPE and misoprostol, an abortive drug, respectively experienced embryonic resorption while this effect was observed in none of the mice given GPE (n=5) and water (n=5). The average body weight of live pups delivered by mice given GPE (1.12+/-0.04 g) was significantly lower than those delivered by mice given water (1.38+/-0.02 g). In SDS-PAGE, proteins were distributed in three bands (Mr range approximately 8-29 kDa). Band intensity at Mr approximately 28-29 kDa was higher in GPE than in RPE. In contrast, band intensity at low Mr (approximately 8 kDa) was found to be higher in RPE than in GPE. Notably, the band corresponding to Mr approximately 23-25 kDa was absent in RPE. These differences in composition may have contributed to the different wound healing and abortive effects of green and ripe papaya.


Effectiveness of chlorthalidone/amiloride versus losartan in patients with stage I hypertension: results from the PREVER-treatment randomized trial.
To compare the blood pressure (BP)-lowering efficacy of a chlorthalidone/amiloride combination pill with losartan, during initial management of stage I hypertension. In a randomized, double-blind, controlled trial, 655 participants were followed for 18 months in 21 Brazilian academic centers. Trial participants were adult volunteers aged 30-70 years with stage I hypertension (BP 140-159 or 90-99 mmHg) following 3 months of a lifestyle intervention. Participants were randomized to 12.5/2.5 mg of chlorthalidone/amiloride (N = 333) or 50 mg of losartan (N = 322). If BP remained uncontrolled after 3 months, study medication dose was doubled, and if uncontrolled after 6 months, amlodipine (5 and 10 mg) and propranolol (40 and 80 mg twice daily) were added as open-label drugs in a progressive fashion. At the end of follow-up, 609 (93%) participants were evaluated. The difference in SBP during 18 months of follow-up was 2.3 (95% confidence interval: 1.2 to 3.3) mmHg favoring chlorthalidone/amiloride. Compared with those randomized to diuretic, more participants allocated to losartan had their initial dose doubled and more of them used add-on antihypertensive medication. Levels of blood glucose, glycosilated hemoglobin, and incidence of diabetes were no different between the two treatment groups. Serum potassium was lower and serum cholesterol was higher in the diuretic arm. Microalbuminuria tended to be higher in patients with diabetes allocated to losartan (28.5 ± 40.4 versus 16.2 ± 26.7 mg, P = 0.09). Treatment with a combination of chlorthalidone and amiloride compared with losartan yielded a greater reduction in BP. NCT00971165.


Software coincidence counting.
A system designed for absolute activity measurement is described using a digital method. The system is based on data recording from a coincidence measurement and subsequent software processing of the data records. The data acquisition device collects amplitudes of individual pulses from analogue-to-digital converters and supplies them with time information. Software processing of data records from this system offers many benefits in comparison to conventional coincidence counting, for example it enables to perform time and pulse height analysis and setting of coincidence parameters by using a wide variety of evaluation methods to one data record. The digital system was tested with a 4pi beta-gamma coincidence detectors arrangement consisting of a proportional counter and two NaI(Tl) scintillation detectors. The results obtained with a 60Co source are presented.


Convex plumbings in closed hyperbolic 4-manifolds.
We show that every plumbing of disc bundles over surfaces whose genera satisfy a simple inequality may be embedded as a convex submanifold in some closed hyperbolic four-manifold. In particular its interior has a geometrically finite hyperbolic structure that covers a closed hyperbolic four-manifold.


Intrinsic small polarons (Sn³⁺ ions) in photorefractive Sn₂P₂S₆ crystals.
Unique holelike small polarons are produced at divalent cation sites by optical excitation at low temperature in single crystals of Sn2P2S6, a monoclinic ferroelectric and photorefractive material. Electron paramagnetic resonance (EPR) is used to observe these self-trapped holes. During an illumination near 25 K with either 442 or 633 nm laser light, photoexcited holes become localized at Sn(2+) (5s(2)) ions and form paramagnetic Sn(3+) (5s(1)) ions. The Sn(3+) ions are thermally stable below 50 K. The principal values of the g matrix are 2.0031, 2.0176, and 2.0273 and the principal values of the (119)Sn hyperfine matrix are 12.828, 12.886, and 13.060 GHz. The large interaction with the (119)Sn (and (117)Sn) nucleus results in a highly asymmetric hyperfine pattern in the EPR spectrum. Weaker hyperfine interactions with two neighboring Sn ions are also observed.


Sulfated phenolic acids in plants.
Sulfated phenolic acids are widely occurring metabolites in plants, including fruits, vegetables and crops. The untargeted UHPLC-QTOF-MS metabolomics of more than 50 samples from plant, fungi and algae lead to the discovery of a small group of sulfated metabolites derived from phenolic acids. These compounds were detected in land plants for the first time. In this study, zosteric acid, 4-(sulfooxy)benzoic acid, 4-(sulfoooxy)phenylacetic acid, ferulic acid 4-sulfate and/or vanillic acid 4-sulfate were detected in a number of edible species/products, including oat (Avena sativa L.), wheat (Triticum aestivum L.), barley (Hordeum vulgare L.), tomato (Solanum lycopersicum L.), carrot (Daucus carota subsp. Sativus Hoffm.), broccoli (Brassica oleracea var. Italica Plenck), celery (Apium graveolens L.), cabbage (Brassica oleracea convar. sabauda L.), banana tree (Musa tropicana L.), pineapple fruit (Ananas comosus L.), radish bulb (Raphanus sativus L.) and olive oil (Olea europaea L.). The structural identification of sulfated compounds was performed by comparing retention times and mass spectral data to those of synthesized standards. In addition to above-mentioned compounds, isoferulic acid 3-sulfate and caffeic acid 4-sulfate were putatively identified in celery bulb (Apium graveolens L.) and broccoli floret (Brassica oleracea var. Italica Plenck), respectively. While sulfated phenolic acids were quantified in concentrations ranging from 0.34 to 22.18 µg·g-1 DW, the corresponding non-sulfated acids were mostly undetected or present at lower concentrations. The subsequent analysis of oat symplast and apoplast showed that they are predominantly accumulated in the symplast (> 70%) where they are supposed to be biosynthesized by sulfotransferases.


Increasing maternal age predicts placental protein expression critical for fetal serotonin metabolism: Potential implications for neurodevelopmental research.
High fetal exposure to serotonin and increasing maternal age both contribute to the risk for neurodevelopmental disorders. While identifying covariates for a study of placental protein expression, we found a significant negative correlation between maternal age and the expression of monoamine oxidase A (MAOA), and a significant positive correlation between maternal age and the expression of the serotonin transporter SERT. MAOA and SERT play key roles in placental serotonin metabolism relevant to fetal neurodevelopment. These preliminary findings suggest that the effect of increasing maternal age on neurodevelopmental risk may be mediated in part by changes in placental protein expression relevant to fetal serotonin metabolism.


[Amputation involving the hand: indication and technique (author's transl)].
More than 3% of all work-related hand injuries result in partial or total amputation of fingers or hands (of 14621 patients with hand injuries, 479 patients had 878 amputations). When there is no possibility or indication for microsurgical replantation, the aim of the surgical effort is to rebuild a sensitive, vigorous grasp. The different procedures for plastic surgery of the hand are discussed.


Effect of genotype-nutrition interaction on growth and somatotropic gene expression in the chicken.
The neuroendocrine system integrates genotype with external factors such as nutrition to regulate animal growth. To investigate the role of somatotropic axis in the interaction of genotype and nutrition, two series of experiments were conducted using broiler and layer chickens as a model. In the first experiment, both strains of chickens were raised on their respective standard diets and the mRNA expressions of somatotropic genes were investigated on day 5 (D5), D21, and D42 after hatching as composites of genotype and nutrition. The hypothalamic somatostatin (SS) and pituitary growth hormone (GH) mRNA expression as well as the plasma GH levels were higher in layer chickens while the opposite was true for hepatic GH receptor (GHR) mRNA. Regulation of GHR mRNA expression was found to be tissue-specific. Hepatic GHR mRNA content increased with age whereas in the muscle, the peak levels of expression were observed at D5 with significantly higher abundance ratio in the layer. To evaluate genotype-diet interaction on growth and the patterns of gene expression of both layer and broiler chickens, layers were fed broiler diet and vice versa from D1 to 42 in the second experiment. The D42 body weight of layer chickens increased by 35% when fed with broiler diet, whereas that of broiler chickens decreased by 51% when fed with layer food. The diet exchange completely reversed the patterns of hypothalamic SS and pituitary GH mRNA expression and the strain differences vanished when the comparison was made on the same diet basis. The hepatic GHR mRNA decreased by 46.1% in broilers fed with layer food, but increased by 45.6% in the layer fed with broiler diet. The strain differences were diminished but did not completely disappear on the same diet basis for hepatic GH receptor mRNA. In contrast, however, the muscle GHR mRNA expression was not affected by diet exchange and thus, was more genotype-specific. The results suggest that genes of the somatotropic axis respond to nutrition differently at the level of transcription.


[Efficiency of coadministration of immunomodulators and vaccine in an experiment on tick-borne encephalitis].
Experiments on a tick-borne encephalitis (TBE) model in CBA and BALB/c mice demonstrated that immunomodulators (ridostin, polyribonate, and peptidoglycan-160) and a specific vaccine against TBE were significantly effective in increasing the level of a protective effect and life expectancy in the experimental group as compared to the control group. The findings allow one to recommend the immunomodulator ridostin in combination with the inactivated vaccine for the emergency prophylaxis of TBE in its virus-infected subjects in the foci of infection.


Continuous flow membrane-less air cathode microbial fuel cell with spunbonded olefin diffusion layer.
The power production performance of a membrane-less air-cathode microbial fuel cell was evaluated for 53 days. Anode and cathode electrodes and the micro-fiber cloth separator were configured by sandwiching the separator between two electrodes. In addition, the air-facing side of the cathode was covered with a spunbonded olefin sheet instead of polytetrafluoroethylene (PTFE) coating to control oxygen diffusion and water loss. The configuration resulted in a low resistance of about 4Ω and a maximum power density of 750 mW/m2. However, as a result of a gradual decrease in the cathode potential, maximum power density decreased to 280 mW/m2. The declining power output was attributed to loss of platinum catalyst (8.26%) and biomass growth (38.44%) on the cathode. Coulombic efficiencies over 55% and no water leakage showed that the spunbonded olefin sheet covering the air-facing side of the cathode can be a cost-effective alternative to PTFE coating.


Haplotype-resolved genome assembly of Coriaria nepalensis a non-legume nitrogen-fixing shrub.
Coriaria nepalensis Wall. (Coriariaceae) is a nitrogen-fixing shrub which forms root nodules with the actinomycete Frankia. Oils and extracts of C. nepalensis have been reported to be bacteriostatic and insecticidal, and C. nepalensis bark provides a valuable tannin resource. Here, by combining PacBio HiFi sequencing and Hi-C scaffolding techniques, we generated a haplotype-resolved chromosome-scale genome assembly for C. nepalensis. This genome assembly is approximately 620 Mb in size with a contig N50 of 11 Mb, with 99.9% of the total assembled sequences anchored to 40 pseudochromosomes. We predicted 60,862 protein-coding genes of which 99.5% were annotated from databases. We further identified 939 tRNAs, 7,297 rRNAs, and 982 ncRNAs. The chromosome-scale genome of C. nepalensis is expected to be a significant resource for understanding the genetic basis of root nodulation with Frankia, toxicity, and tannin biosynthesis.


Comparison of Cannabis sativa by random amplification of polymorphic DNA (RAPD) and HPLC of cannabinoids: a preliminary study.
Methods are described for the HPLC and genetic analysis of herbal Cannabis sativa. The latter method was applied to 17 plants grown simultaneously, at the same site. Sixteen of these samples were also compared using HPLC, which resulted in differentiation of the plants into 3 groups. Within two of these groups, the members could not be distinguished. By RAPD analysis, using certain combinations of primers and cladistic analysis, differentiation was possible between all but two of the plants. The use of the RAPD technique enables differentiation between samples that cannot be differentiated by HPLC analysis alone.


Cell-to-cell transfer of SAA1 protein in a cell culture model of systemic AA amyloidosis.
Systemic AA amyloidosis arises from the misfolding of serum amyloid A1 (SAA1) protein and the deposition of AA amyloid fibrils at multiple sites within the body. Previous research already established that mononuclear phagocytes are crucial for the formation of the deposits in vivo and exposure of cultures of such cells to SAA1 protein induces the formation of amyloid deposits within the culture dish. In this study we show that both non-fibrillar and fibrillar SAA1 protein can be readily transferred between cultured J774A.1 cells, a widely used model of mononuclear phagocytes. We find that the exchange is generally faster with non-fibrillar SAA1 protein than with fibrils. Exchange is blocked if cells are separated by a membrane, while increasing the volume of cell culture medium had only small effects on the observed exchange efficiency. Taken together with scanning electron microscopy showing the presence of the respective types of physical interactions between the cultured cells, we conclude that the transfer of SAA1 protein depends on direct cell-to-cell contacts or tunneling nanotubes.


Occurrence and controls on transport and transformation of nitrogen in riparian zones of Dongting Lake, China.
Dongting Lake is the second largest freshwater lake in China. It is suffering from significant eutrophication as a result of excessive nutrients inputs, among which nitrogen (N) is becoming a major contributor. The objective of this study is to document the occurrence and controls on N transport and transformation in riparian zones of Dongting Lake wetland. Field experiments were conducted in the cultivated Li River (LR) and uncultivated Yuan River (YR) regions of the wetlands from June to November, 2014. Groundwater depth, redox potential (Eh), pH, and temperature were measured in situ. Groundwater and surface water samples were collected to determine concentrations of nitrate nitrogen (NO3 (-)-N), nitrite nitrogen (NO2 (-)-N), and ammonia nitrogen (NH4 (+)-N). The results showed that NH4 (+)-N was the dominant N pollutant with maximum average value of 2.7760 mg L(-1). All the groundwater samples were rated to Class V based on NH4 (+)-N content according to the groundwater quality standard, indicating the load of N in riparian zones had exceeded their capacity for assimilation and purification. Internal controls (including Eh and pH, temperature, and groundwater depth) and external controls (including surface water, land use, and rainfall) were analyzed in detail. The results suggested that Eh and pH were more significant in controlling N transport and transformation than temperature and groundwater depth; external controls influenced N fates through imposing an effect on internal controls. This study will provide important insights and a scientific basis for N pollution treatment and better protection of the Dongting Lake wetlands.


Pregnancy nutrition knowledge of antenatal care providers: An evaluation of an online training module.
Nutrition education for clinicians providing pregnancy care has the potential to enhance pregnant women's diet quality, leading to healthier outcomes for mother and baby. Following a study demonstrating nutrition knowledge gaps, an online training module was developed, implemented, and evaluated. Antenatal care providers completed a pregnancy nutrition knowledge questionnaire to assess knowledge levels at baseline (n = 97) and nine months after the introduction of online training (n = 64). Knowledge scores at baseline and post-training implementation were not significantly different. Sub-group post-training knowledge scores between clinicians who completed the training module was higher than for those that did not complete the training module. User experience of the training module was positive and they felt it was useful in enhancing nutrition knowledge. Just under half of clinicians felt more confident in providing nutrition advice as part of their pregnancy care. Clinicians reported that time constraints prevented them from completing the nutrition training and/or providing nutrition education. Despite the positive experience of completing the online training module, a majority of clinicians surveyed indicated they preferred face-to-face training. Further research exploring how nutrition is prioritised in antenatal appointments and how knowledge levels influence nutrition education practices is needed.


Robotic transcranial magnetic stimulation in the treatment of depression: a pilot study.
There has been an increasing demand for robotic coil positioning during repetitive transcranial magnetic stimulation (rTMS) treatment. Accurate coil positioning is crucial because rTMS generally targets specific brain regions for both research and clinical application with other reasons such as safety, consistency and reliability and individual variablity. Some previous studies have employed industrial robots or co-robots and showed they can more precisely stimulate the target cortical regions than traditional manual methods. In this study, we not only developed a custom-TMS robot for better TMS coil placement but also analyzed the therapeutic effects on depression. Treatment effects were evaluated by measuring regional cerebral blood flow (rCBF) using single-photon emission computed tomography and depression severity before and after rTMS for the two positioning methods. The rTMS preparation time with our robotic coil placement was reduced by 53% compared with that of the manual method. The position and orientation errors were also significantly reduced from 11.17 mm and 4.06° to 0.94 mm and 0.11°, respectively, confirming the superiority of robotic positioning. The results from clinical and neuroimaging assessments indicated comparable improvements in depression severity and rCBF in the left dorsolateral prefrontal cortex between the robotic and manual rTMS groups. A questionnaire was used to determine the patients' feelings about the robotic system, including the safety and preparation time. A high safety score indicated good acceptability of robotic rTMS at the clinical site.


Multiple pulse amperometry in low pressure chromatography for parallel determination of oxidizable and reducible compounds. Analysis of a green coffee extract as a case study.
In this paper, the determination of both oxidizable and reducible compounds within a single chromatographic run is exploited for the first time, using a low-pressure chromatographic system and multiple pulse amperometric detection. The case study selected focussed on the analysis of green coffee extracts. The separation of the compounds was carried out using a 1-cm length monolithic column and an eluent prepared by mixing an aqueous solution of an ion-pair reagent, perfluoroheptanoic acid (PFHpA), and acetonitrile. The parallel determination of oxidizable and reducible compounds was performed by application of two consecutive pulses, E1 = +1.6 V and E2 = -1.5 V. At anodic conditions, the chromatographic peaks for 5-caffeoylquinic acid (5-CQA), caffeine and 5-feruloylquinic acid (5-FQA) were detected, while at cathodic conditions, a chromatographic peak was ascribed for trigonelline. In the developed methodology, the use of multiple pulse amperometry provided better sensitivity if compared to previously described amperometric methodologies determining either oxidizable or reducible compounds. Detection limits for the referred compounds of ca. 1 × 10-5 mol L-1, an analysis rate of 12 h-1 and an acetonitrile consumption of 0.07 mL per analysis were achieved. The approach presented demonstrates the possibility of combining low pressure chromatographic systems and multiple pulse amperometry, in the development of new, low-cost and fast methodologies for multi-analyte determinations.


Public health interventions to reduce inequalities: what do we know works?
This commentary focuses on the notion of "what works" to reduce health inequalities. It begins by noting the need for and presence of a wide range of methodologies and approaches internationally. It then argues that it is useful to map out these contributions and those in the present Supplement against a set of principles (Macintyre, 2007) to guide the selection and implementation of public health interventions explicitly aiming to reduce health inequalities. The chosen principles derive largely from efforts to reduce steep and persistent Scottish health inequalities by social class. The commentary summarizes Macintyre's analysis of the main characteristics of public health interventions. It then notes that the present Supplement provides clear examples of population-health interventions and their health impacts that are inequality-reducing. The suggested approach and principles align with calls for the use of structural changes in the environment, early-life interventions, reductions in preventive-care barriers, and a harm-reduction philosophy. The commentary concludes that there remains much to learn and to do in order for public health intervention research to clearly demonstrate how to effectively reduce health inequalities in a lasting manner.


Cytosine-specific type II DNA methyltransferases. A conserved enzyme core with variable target-recognizing domains.
Comparisons of the amino acid sequences of m5C DNA methyltransferases (Mtases) from 11 prokaryotes and one eukaryote reveal a very similar organization. Among all the enzymes one can distinguish highly conserved "core" sequences and "variable" regions. The core sequences apparently mediate steps of the methylation reaction that are common to all the enzymes. The major variable region has been shown in our previous studies on multispecific phage Mtases to contain the target-recognizing domains (TRDs) of these enzymes. Here we have compared the amino acid sequences of various TRDs from phage Mtases. This has revealed the presence of both highly conserved and variable amino acids. We postulate that the conserved residues represent a "consensus" sequence defining a TRD, whereas the specificity of the TRD is determined by the variable residues. We have observed similarity between this consensus sequence and sequences in the variable region of the monospecific Mtases. We predict that the regions thus identified represent part of the TRDs of monospecific Mtases.


Structural and functional determinants of Mucor miehei protease. V. Enthalpy changes upon thermal denaturation in solution of varying pH.
The thermal denaturation of Mucor meihei protease was studied as a function of pH by differential scanning calorimetry. In both citric acid-Na2HPO4 and in acetic acid-sodium acetate buffers, maximum thermal stability was at pH 4.0-4.2. However, the maximum enthalpy changes associated with the denaturation process were buffer-dependent and occurred between pH values of 4.7 and 5.7.


Pathological ultrastructural alterations of myelinated axons in normal appearing white matter in progressive multiple sclerosis.
Multiple sclerosis (MS) pathophysiology includes inflammation, demyelination and neurodegeneration, but the exact mechanisms of disease initiation and progression are unknown. A major feature of lesions is lack of myelin, which increases axonal energy demand and requires adaptation in number and size of mitochondria. Outside lesions, subtle and diffuse alterations are observed in normal appearing white matter (NAWM) and normal appearing grey matter (NAGM), including increased oxidative stress, reduced axon density and changes in myelin composition and morphology. On an ultrastructural level, only limited data is available on alterations in myelinated axons. We generated large scale 2D scanning transmission electron microscopy images ('nanotomy') of non-demyelinated brain tissue of control and progressive MS donors, accessible via an open-access online repository. We observed a reduced density of myelinated axons in NAWM, without a decrease in cross-sectional axon area. Small myelinated axons were less frequently and large myelinated axons were more frequently present in NAWM, while the g-ratio was similar. The correlation between axonal mitochondrial radius and g-ratio was lost in NAWM, but not in NAGM. Myelinated axons in control GM and NAGM had a similar g-ratio and radius distribution. We hypothesize that axonal loss in NAWM is likely compensated by swelling of the remaining myelinated axons and subsequent adjustment of myelin thickness to maintain their g-ratio. Failure of axonal mitochondria to adjust their size and fine-tuning of myelin thickness may render NAWM axons and their myelin more susceptible to injury.


Implantation of fibre encapsulated RIN 1056a cells transfected with NPY cDNA into the lateral ventricle of rats alters body weight.
Neuropeptide Y (NPY) is a hypothalamic neuropeptide thought to play an important role in the regulation of food intake and energy expenditure. Our aim was to over-express bioactive NPY in the lateral ventricle by implanting cells transfected with NPY cDNA. Cells from the RIN 1056a clonal rat islet cell line were transfected with NPY cDNA. Radioimmunoassay, chromatography and receptor binding assays were used to ensure the secreted NPY was bioactive, before and after implantation. NPY cDNA transfected and untransfected control cells were encapsulated in PVDF hollow fibres to prevent tumour formation and implanted into the lateral ventricle of male Wistar rats. The effects on body weight and food intake were measured for 15 days. Animals implanted with NPY cDNA transfected RIN 1056a cells showed a greater rise in body weight than controls. This difference was statistically significant five days after implantation, and remained so until the end of the experiment. Cumulative food intake was also increased in rats implanted with NPY cDNA transfected RIN 1056a cells, but this difference failed to reach statistical significance. We have demonstrated that implantation of NPY over-expressing cells into the lateral hypothalamus of rats increases body weight gain.


Case Report: Not a Mediastinal Mass! a Ruptured Giant Coronary Aneurysm That Occurred in a Young Man.
Coronary artery aneurysm (CAA) is a localized coronary artery dilatation that exceeds 1. 5 times the diameter of a standard adjacent segment or the largest coronary vessel. When the expansion is > 2 cm, it is called a "giant" coronary artery aneurysm. Giant coronary artery aneurysm rupture is extremely rare and fatal. We present a rare case of a 27 years old male with a giant coronary artery aneurysm rupture, but no catastrophic events occurred immediately. He was initially misdiagnosed as having a mediastinal mass with CT (computed tomography). The cardiac ultrasound showed no pericardial effusion. But The cardiac CTA (computed tomography angiography) showed a giant coronary aneurysm rupture with hematoma formation. He eventually underwent surgery and was followed up for 2 months without complications. We report this case of a ruptured giant coronary aneurysm because of its infrequent occurrence in coronary artery disease. It is tough to distinguish this disease from a mediastinal tumor, and chest MRI and cardiac CTA are crucial tests. Finally, surgical resection may be the right choice for coronary aneurysm rupture. More cases need to be reported to facilitate the preoperative diagnosis of this rare coronary aneurysm.


Safety and efficacy of immune checkpoint blockade in patients with advanced nonsmall cell lung cancer and brain metastasis.
The presence of brain metastases (BM) is a negative prognostic factor for patients with advanced nonsmall cell lung cancer (NSCLC). Their incidence seems to be higher in patients with oncogene-driven tumours, especially those with EGFR-mutated or ALK-rearranged tumours. Although targeted treatments demonstrate significant efficacy regarding BM, they only apply to a minority of NSCLC patients. On the other hand, systemic therapies for nononcogenic-driven NSCLC with BM have shown limited clinical benefit. In recent years, immunotherapy alone or combined with chemotherapy has been adopted as a new standard of care in first-line therapy. This approach seems to be beneficial to patients with BM in terms of efficacy and toxicity. Combined immune checkpoint inhibition as well as the combination of immunotherapy and radiation therapy show promising results with significant, but overall acceptable toxicity. A pragmatic approach of allowing enrolment of patients with untreated or symptomatic BM in randomised trials evaluating immune checkpoint inhibitors strategies, possibly coupled with central nervous system-related endpoints may be needed to generate data to refine treatment for this patient population.


Molecular modeling of organic and biomolecular systems using BOSS and MCPRO.
An overview is provided of the capabilities for the current versions of the BOSS and MCPRO programs for molecular modeling of organic and biomolecular systems. Recent applications are noted, particularly for QM/MM studies of organic and enzymatic reactions and for protein-ligand binding.


Characterization of a chronic cough in cerebellar ataxia, neuropathy, vestibular areflexia syndrome.
Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a common cause of late-onset ataxia that often presents with chronic cough. This study is the first to characterize the CANVAS cough both objectively and subjectively. A cross-sectional study of 13 patients was conducted. Medical records and available esophagram, modified barium swallow study, esophageal manometry, and video laryngostroboscopy data were reviewed. Leicester cough questionnaire (LCQ) and Eating Assessment Tool-10 were administered to evaluate quality of life (QoL) impairments and dysphagia symptoms, respectively. CANVAS history questionnaire was developed to characterize the clinical course. 92% of patients endorsed chronic cough that preceded gait instability by a median of 16 years. Cough was dry (67%), disturbed sleep (75%), triggered by various factors, including talking, eating, and dry/spicy foods, did not respond to standard reflux therapy, and inconsistently responded to neuromodulators and superior laryngeal nerve injections. Despite perceived cough severity worsening or remaining constant in most patients, no correlation was found between cough duration and total LCQ scores. Patients reported significantly more negative social QoL impacts compared to physical QoL impacts. Ataxia duration and years of cough before ataxia symptoms were directly and inversely correlated with total LCQ scores, respectively. Imaging data revealed esophageal dysmotility (71%), vestibular penetration (57%), vestibular aspiration (14%), supraglottic compression (63%), vocal fold lesions/atrophy (50%), and arytenoid erythema (38%). Chronic cough is a hallmark presenting symptom in CANVAS with predominantly psychosocial QoL effects and unrecognized laryngeal alterations. In cases of idiopathic, refractory chronic cough, genetic testing for CANVAS should be considered, especially in association with sensory, cerebellar, and/or vestibular involvement. VI.


Possible differential induction of phase 2 enzyme and antioxidant pathways by american ginseng, Panax quinquefolius.
Human immunodeficiency virus (HIV)-infected patients often take herbal medicines, which may interact with antiretrovirals. American ginseng induces phase 2 and antioxidant enzymes in vitro and might increase the clearance of zidovudine and/or enhance antioxidant activity. Ten healthy volunteers received 300 mg of zidovudine orally before and after 2 weeks of treatment with a ginsenoside-enriched American ginseng extract 200 mg twice daily. This ginseng extract induced the phase 2 enzyme quinone reductase with an average concentration of doubling of enzyme activity of 190 microg/mL. Total ginsenoside content was 8.5 +/- 0.5%. Pharmacokinetic profiles of zidovudine and oxidative stress marker concentrations were measured post-zidovudine dose. American ginseng does not significantly affect the formation clearance of zidovudine to its glucuronide (ratio post- to pre-American ginseng = 1.17; 90% confidence interval: 0.95-1.45; P = .21), total clearance (ratio = 0.97; 0.82-1.14; P = .70), or plasma zidovudine AUC0-8 (ratio = 1.03; 0.87-1.21; P = .77). Oxidative stress biomarkers are reduced post-American ginseng (F2-isoprostane ratio = 0.79; 0.72-0.86; P < .001; 8-hydroxy-deoxyguanosine ratio = 0.74; 0.59-0.92; P = .02). Two weeks of American ginseng does not alter zidovudine pharmacokinetics but reduces oxidative stress markers.


Free-Standing Undoped ZnO Microtubes with Rich and Stable Shallow Acceptors.
Fabrication of reliable large-sized p-ZnO is a major challenge to realise ZnO-based electronic device applications. Here we report a novel technique to grow high-quality free-standing undoped acceptor-rich ZnO (A-ZnO) microtubes with dimensions of ~100 μm (in diameter) × 5 mm (in length) by optical vapour supersaturated precipitation. The A-ZnO exhibits long lifetimes (>1 year) against compensation/lattice-relaxation and the stable shallow acceptors with binding energy of ~127 meV are confirmed from Zn vacancies. The A-ZnO provides a possibility for a mimetic p-n homojunction diode with n(+)-ZnO:Sn. The high concentrations of holes in A-ZnO and electrons in n(+)-ZnO make the dual diffusion possible to form a depletion layer. The diode threshold voltage, turn-on voltage, reverse saturated current and reverse breakdown voltage are 0.72 V, 1.90 V, <10 μA and >15 V, respectively. The A-ZnO also demonstrates quenching-free donor-acceptor-pairs (DAP) emission located in 390-414 nm with temperature of 270-470 K. Combining the temperature-dependent DAP violet emission with native green emission, the visible luminescence of A-ZnO microtube can be modulated in a wide region of colour space across white light. The present work opens up new opportunities to achieve ZnO with rich and stable acceptors instead of p-ZnO for a variety of potential applications.


Clinical strategies for ART treatment of infertile women with advanced maternal age.
An ever-increasing number of women in our country with advanced maternal age are choosing to achieve pregnancy. This means effective strategies are needed for infertile patients. Questions arise, however, concerning the need for ovarian stimulation, and, if so, whether intracytoplasmic sperm injection (ICSI) is better than conventional insemination for those women who may have only one mature oocyte. We evaluated our data to answer these questions. Herein, we also introduce our strategy for patients who show unsynchronized follicular growth. Ovarian stimulation in ART treatment for patients with advanced maternal age has resulted in the achievement of higher pregnancy rates, and therefore, this form of stimulation is often selected. Based on our data, ICSI as an insemination procedure has not improved clinical pregnancy rates compared with conventional insemination and has actually decreased the clinical pregnancy rates. In this article, we reviewed and compared the protocols and strategies that are available to increase the number of developed embryos for the patients with advanced maternal age. We hope that this review will be helpful for both patients and clinicians.


Loss of bone stock with cementless hip arthroplasty.
One hundred four porous-coated anatomic cementless hip arthroplasties followed from 2 to 6.5 years (mean, 50 months) were studied. Ninety-four percent had excellent clinical results. Thigh pain occurred in 23% of patients, but was severe in only two. "Cancelization" and rounding off of the calcar were noted in 83% of hips, whereas localized osteolysis occurred in 24 femurs and one acetabulum. Ten of these measured more than 10 mm, and all of those in the femur were located proximally. None of these patients were symptomatic and none have come to revision. Ultrahigh-molecular-weight polyethylene wear and plastic debris were implicated as the cause of osteolysis. Lytic lesions were seen only after 3 years and occurred only in patients with 32-mm femoral heads in whom the outer diameter of the acetabular component was 52 mm or less. Use of excessively thin ultrahigh-molecular-weight polyethylene in these patients may have predisposed them to accelerated wear. Section modulus mismatch resulting in stress protection is considered as an alternate mechanism of proximal bone resorption.


Anticancer, antioxidant, antiviral and antimicrobial activities of Kei Apple (Dovyalis caffra) fruit.
Secondary plant metabolites remain one of the key sources of therapeutic agents despite the development of new approaches for the discovery of medicinal drugs. In the current study, chemical analysis, and biological activities of Kei apple (Dovyalis caffra) methanolic extract were evaluated. Chemical analysis was performed using HPLC and GC-MS. Antiviral and anticancer effect were assessed using the crystal violet technique and activity against human liver cells (HepG2), respectively. Antibacterial activity was tested with the disc diffusion method. The obtained results showed that chlorogenic acid (2107.96 ± 0.07 µg/g), catechin (168 ± 0.58 µg/g), and gallic acid (15.66 ± 0.02 µg/g) were the main bioactive compounds identified by HPLC techniques. While, compounds containing furan moieties, as well as levoglucosenone, isochiapin B, dotriacontane, 7-nonynoic acid and tert-hexadecanethiol, with different biological activities were identified by GC-MS. Additionally, inhibition of 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) scavenging was 79.25% at 2000 µg/mL, indicating its antioxidant activity with IC50 of 728.20 ± 1.04 µg/mL. The tested extract exhibited potential anticancer activity (58.90% toxicity) against HepG2 cells at 1000 µg/mL. Potential bacterial inhibition was observed mainly against Escherichia coli and Proteus vulgaris, followed by Staphylococcus aureus and Bacillus subtilis with a diameter of growth inhibition ranging from 13 to 24 mm. While weak activities were recorded for fungi Candida albicans (10 mm). The extract showed mild antiviral activity against human coronavirus 229E with a selective index (SI) of 10.4, but not against human H3N2 (SI of 0.67). The molecular docking study's energy ratings were in good promise with the experiment documents of antibacterial and antiviral activities. The findings suggest that D. caffra juice extract is a potential candidate for further experiments to assess its use as potential alternative therapeutic agent.


The effect of height on paclitaxel nerve damage.
Dying-back neuropathies result in sensory loss and motor signs in the distal distribution of the longest nerves of the body. It would be expected, therefore, that taller individuals with dying-back neuropathies would tend to have worse nerve damage than shorter individuals. This hypothesis was tested in patients receiving high dose paclitaxel. Nerve conductions and quantitative sensory tests were obtained in 21 breast cancer subjects, prior to and 20-40 days after 725 mg/m(2) paclitaxel administered intravenously over 24 h. Despite the uniform dose of paclitaxel, there was a wide variation in post minus pre-paclitaxel changes. Analysis by linear regression showed that decrease of peroneal nerve compound muscle action potential amplitude was significantly greater in taller subjects (P=0.004), and increase in cold detection threshold was greater in taller subjects (P=0.02). No correlation with height was found for paclitaxel drug clearance, maximum concentration, and area under the curve. Decrease in sural sensory nerve action potential amplitude and increase in vibration detection threshold did not correlate with height. In summary, the wide variation of changes seen in neurophysiological tests suggests that multiple factors are involved in determining the severity of neuropathy. Nerve length is probably one of these factors. To determine whether the effect of height is clinically important would require additional study with a larger number of subjects and longer clinical follow-up.


The efficacy of extracorporeal life support in premature and low birth weight newborns.
Based on data obtained early in the development of neonatal extracorporeal life support (ECLS), contraindications to the use of ECLS have included low estimated gestational age (EGA) and low birth weight (BW). However, multiple improvements in the technical and management aspects of neonatal ECLS have been implemented since those early data were evaluated. The purpose of this study, therefore, is to assess in the "modern era" the efficacy of prolonged extracorporeal support in premature and low birth weight newborns. Examination of the Extracorporeal Life Support Organization (ELSO) Registry showed that between 1988 and 1991 ECLS was utilized in 158 premature (PREM, EGA < or = 34 weeks), 4,128 full-term (FT, EGA > or = 35 weeks), 26 low birth weight (LBW, BW < 2.0 kg), and 4,333 normal birth weight (NBW, BW > or = 2.0 kg) patients with respiratory failure. Data were evaluated for variables thought to be associated with a decrease in survival or an increase in the incidence of intracranial hemorrhage (ICH). A logistic regression model was developed to evaluate the ability of EGA and BW to predict survival. The incidence of survival (SURV) was decreased (63% v 84%) and ICH increased (37% v 14%) significantly in PREM when compared with FT newborns (P < .001). However, respectable survival rates in PREM patients with EGA > 32 weeks were documented. In addition, both survival and ICH in PREM patients have improved substantially when compared with past reports (Past: SURV = 25% and ICH = 100%; current: SURV = 63% and ICH = 37%; ICH P < .001; SURV P = .056). Survival was significantly decreased in LBW when compared to NBW neonates (65% v 83%, P < .05), but there was no significant difference in ICH.(ABSTRACT TRUNCATED AT 250 WORDS)


Sonographic findings in renal parenchymal malacoplakia.
Malacoplakia of the kidney is a rare inflammatory disorder. We describe a case of bilateral renal malacoplakia in which the patient had diffuse involvement of the left kidney and a focal lesion in the right kidney. Sonography showed a diffusely echogenic, enlarged left kidney with loss of corticomedullary differentiation and a single anechoic lesion measuring 1.8 x 1.6 x 1.3 cm in the right kidney. A left nephrectomy was performed, and the right kidney was managed conservatively with sonographic monitoring.


Two are better than one: comparison influences infants' visual recognition memory.
Despite a large literature on infants' memory for visually presented stimuli, the processes underlying visual memory are not well understood. Two studies with 4-month-olds (N=60) examined the effects of providing opportunities for comparison of items on infants' memory for those items. Experiment 1 revealed that 4-month-olds failed to show evidence of memory for an item presented during familiarization in a standard task (i.e., when only one item was presented during familiarization). In Experiment 2, infants showed robust memory for one of two different items presented during familiarization. Thus, infants' memory for the distinctive features of individual items was enhanced when they could compare items.


The benzodiazepine receptor inverse agonist RO 15-3505 reverses recent memory deficits in aged mice.
The benzodiazepine receptor partial inverse agonist RO 15-3505 was tested for its ability to improve impaired recent memory of aged mice. All mice successfully acquired a learning set for accurate identification of the correct arm of a T-maze and could perform with nearly 100% accuracy after 1-min delays. However, performance of the aged mice approached chance levels after 2-h delays. When injected just before testing on a series of 2-h retention tests, RO 15-3505 (from 2.5-3505 (from 2.5-10.0 mg/kg) resulted in a marked improvement of response accuracy. These results confirm the role of benzodiazepine receptor mechanisms in the modulation of memory processes, and suggest that the memory-facilitating effects RO 15-3505 or similar benzodiazepine receptor ligands may be generalized to aged rodents with impaired memory function.


Characterization of a Bacillus subtilis 64-kDa DNA polymerase X potentially involved in DNA repair.
Bacillus subtilis gene yshC encodes a 64-kDa family X DNA polymerase (PolXBs), which contains all the critical residues involved in DNA and nucleotide binding as well as those responsible for catalysis of DNA polymerization, conserved in most family X members. Biochemical analyses of the purified enzyme indicate that PolXBs is a monomeric and strictly template-directed DNA polymerase, preferentially acting on DNA structures containing gaps from one to a few nucleotides and bearing a phosphate group at the 5' end of the downstream DNA. The fact that PolXBs is able to conduct filling of a single-nucleotide gap, allowing further sealing of the resulting nick by a DNA ligase, points to a putative role in base excision repair during the B. subtilis life cycle.


Flexibility Analysis of Bacillus thuringiensis Cry1Aa.
To investigate the flexibility and mobility of the Bacillus thuringiensis toxin Cry1Aa. The graph theory-based program Constraint Network Analysis and normal mode-based program NMsim were used to analyze the global and local flexibility indices as well as the fluctuation of individual residues in detail. The decrease in Cry1Aa network rigidity with the increase of temperature was evident. Two phase transition points in which the Cry1Aa structure lost rigidity during the thermal simulation were identified. Two rigid clusters were found in domains I and II. Weak spots were found in C-terminal domain III. Several flexible regions were found in all three domains; the largest residue fluctuation was present in the apical loop2 of domain II. Although several flexible regions could be found in all the three domains, the most flexible regions were in the apical loops of domain II.


Endoscope-assisted resection of thyroglossal duct cysts via a submaxillary vestibular approach.
Thyroglossal duct cysts (TDCs) are usually resected through an incision over the entire protruding zone. The resulting scar is aesthetically displeasing, so we explored the use of endoscope-assisted excision of TDCs via a submaxillary vestibular approach. The purpose of this study was to demonstrate the feasibility, validity, and safety of this approach and to evaluate the follow-up results. From January 2007 to August 2015, 16 patients with TDCs underwent surgical resection using a submaxillary vestibular approach. All procedures were successfully performed using endoscope-assisted surgery via a submaxillary vestibular approach. There were no postoperative complications and no conversions of the operation. The average follow-up period was 73 months (range 14-117 months) without recurrence. All patients and their families were satisfied with the cosmetic results. Endoscope-assisted excision of TDCs using a submaxillary vestibular approach is feasible and can be applied effectively and safely with good cosmetic results. Therefore, this method should be considered a viable alternative approach for these patients.


Structure-Dependent Thermoelectric Properties of GeSe1-xTex (0 ≤ x ≤ 0.5).
GeSe was theoretically predicted to have thermoelectric (TE) performance as high as SnSe. However, the relatively high TE performance was not achieved experimentally in doped GeSe samples with an original orthorhombic structure but observed in Ag(Sb,Bi)(Se,Te)2 alloyed samples that crystalize in either a rhombohedral or cubic structure. Herein, to clarify the crystal structure-dependent properties, the electrical and thermal transport properties of GeSe1-xTex (0 ≤ x ≤ 0.5), where orthorhombic, hexagonal, and rhombohedral phases are stable at room temperature for different Te content, have been studied, without any intentional manipulation on carrier concentration. It is found that the three phases show intrinsically different hole concentrations: ∼1016 cm-3 for the orthorhombic phase but as high as 1021 cm-3 for the hexagonal and rhombohedral phases. Ge-rich status in the orthorhombic phase and Ge-poor status in hexagonal and rhombohedral phases may be responsible for the huge difference in hole concentrations. The rhombohedral phase shows a much higher Seebeck coefficient than the hexagonal phase with similar hole concentration, indicating that the profile of valance band maximum for the rhombohedral structure is more favorable for high TE performance than the hexagonal phase in GeSe1-xTex. The highest zT of 0.69 has been obtained in GeSe0.55Te0.45 at 778 K, at which temperature the rhombohedral phase has already transformed to a cubic phase; however, a zT value of 1.74 at 628 K is predicted by the quality factor analysis for rhombohedral GeSe0.55Te0.45 if optimum hole concentration can be achieved.


B-cell acute lymphoblastic leukemia and isochromosome 7q.
A 10-year-old girl with cytological and immunological characteristics of B-cell acute lymphoblastic leukemia is reported. Chromosomal analysis revealed the presence of t(8;14) and i(7q).


Growth and structural properties of silicene at multilayer coverage.
At monolayer coverage, silicene on Ag(1 1 1) may present different structural phases depending on the growth conditions. At multilayer coverage, only one structural phase has been reported: the [Formula: see text] phase. However, no link between the structural arrangement of the monolayer and that of the multilayer has been addressed. In this paper, reporting experimental work based on low-energy electron diffraction and scanning tunneling microscopy, we focus on the structural aspects of a multilayer film of silicene. We demonstrate that it exhibits one structural arrangement, namely the [Formula: see text] form, but with different domain orientations resulting from the structural properties of the initial wetting monolayer.


The Potential Therapeutic Effects of Low-Dose Ionizing Radiation in Alzheimer's Disease.
Dementia is an umbrella term used to describe a loss of cognitive function which results in the interference of an individual's daily life and activities. The most common form of dementia is Alzheimer's disease. Alzheimer's is classified as a progressive, debilitating neurodegenerative disease that results in disturbances to a patient's higher executive function, memory, language, and visuospatial orientation. Despite extensive research on Alzheimer's dementia, including both available and potential therapeutic modalities, this neurodegenerative disease is incurable and will continue to pose a major public health concern. Current treatment options for Alzheimer's focus on symptom management and/or delaying the progression of the disease. Therefore, new treatment strategies must be developed to combat such a deadly disease. One field of medicine that has garnered significant interest from researchers to potentially treat Alzheimer's is low-dose ionizing radiation. Various reports suggest that the brain's exposure to low doses of ionizing radiation may serve as a therapeutic modality for combating neurodegenerative diseases, including Alzheimer's dementia. This article serves as a review of the current available treatments for Alzheimer's disease and discusses recent studies that provide evidence for the potential use of low-dose ionizing radiation as a therapeutic in the treatment of Alzheimer's disease.


A comparison of the reliability and vulnerability of 3D sterEOS and 2D EOS when measuring the sagittal spinal alignment of patients with adolescent idiopathic scoliosis.
An essential component of making the diagnosis of adolescent idiopathic scoliosis (AIS) is standing anteroposterior and lateral radiographs. Two-dimensional (2D) radiographs inevitably fail to reflect every plane of the three-dimensional (3D) deformity in scoliosis. We have tested the hypothesis that there is no difference in the assessment of the sagittal plane deformity when measured with either 2D or 3D EOS radiography. A retrospective radiographic analysis was performed on patients diagnosed with AIS, with subdivided into three groups according to the coronal angular deformity (mild group: 45°-69°, moderate group: 70°-89°, and severe group: 90° +). The sagittal parameters were compared between manual measurement with 2D sterEOS and those made using computer-aided 3D reconstruction. Fifty-two patients were included in each group. The inter-study reliability when measuring the thoracic Kyphosis (TK) and lumbar lordosis (LL) between the two study modalities was excellent in mild group (ICC: 0.90, 95% CI 0.82 ~ 0.94 and ICC: 0.84, 95% CI 0.74 ~ 0.91), excellent in TK and fair in LL in moderate group (ICC: 0.76, 95% CI 0.61 ~ 0.85 and ICC: 0.70, 95% CI 0.53 ~ 0.81), and fair in TK and LL in severe group, respectively (ICC: 0.74, 95% CI 0.57 ~ 0.84 and ICC: 0.65, 95% CI 0.46 ~ 0.84). A Bland-Altman plot showed proportional bias in TK measurements in each group and LL in moderate group, which means the measured value is underestimated in 2D method when the angle is small. 3D sterEOS is less vulnerable to the influence of coronal plane than 2D EOS in evaluating the sagittal spinal parameters of patients with a coronal deformity exceeding 70°.


[Effect of nano-hydroxyapatite collagen bone and marrow mesenchymal stem cell on treatment of rabbit osteonecrosis of the femoral head defect].
To evaluate the effect of nano-hydroxyapatite collagen (nHAC) bone and marrow mesenchymal stem cells (MSCs) on the treatment of rabbit osteonecrosis of the femoral head (ONFH) defect. From June to October 2004, animal models of ONFH defect were established in 45 New Zealand rabbits. They were divided into 3 groups randomly: In group A, as the control group, defect was not filled with any implants; In group B with nHAC; In group C with nHAC+MSC. Imaging and histological observation were made 4, 8, 12 weeks after operation. group C had a better osteogenesis ability than group B and group A. group B had a better osteogenesis ability than group A. Obvious new bones and osteogenesis were observed in group C 4 weeks after operation. The defect areas in group C were almost repaired 12 weeks after operation. nHAC has a better effect of osteo-conduction and it is a superior material for repairing bone defect of ONFH and of great value in treating ONFH when compounded with MSCs.


What is the standard regimen for patients with acute promyelocytic leukemia?
Modern guidelines based on a large international consensus indicate that treatment of newly diagnosed acute promyelocytic leukemia (APL) requires distinguishing at presentation low-intermediate (<10 × 10(9)/L WBC) from high-risk (>10 × 10(9)/L WBC) disease. The concomitant use of all-trans retinoic acid (ATRA) and anthracycline based chemotherapy, with inclusion of AraC in consolidation for hyperleucocytic patients, has remained the standard of care for the past two decades. The advent of arsenic trioxide (ATO) and results from a large randomized trial, have recently challenged the standard ATRA-chemotherapy approach suggesting that at least patients in the low-intermediate category may be cured without chemotherapy using the ATRA-ATO combination.


Development and pilot testing of PROACTIVE: A pediatric onco-critical care capacity and quality assessment tool for resource-limited settings.
Nearly 90% children with cancer reside in low- and middle-income countries, which face multiple challenges delivering high-quality pediatric onco-critical care (POCC). We recently identified POCC quality and capacity indicators for PROACTIVE (PediatRic Oncology cApaCity assessment Tool for IntensiVe carE), a tool that evaluates strengths and limitations in POCC services. This study describes pilot testing of PROACTIVE, development of center-specific reports, and identification of common POCC challenges. The original 119 consensus-derived PROACTIVE indicators were converted into 182 questions divided between 2 electronic surveys for intensivists and oncologists managing critically ill pediatric cancer patients. Alpha-testing was conducted to confirm face-validity with four pediatric intensivists. Eleven centers representing diverse geographic regions, income levels, and POCC services conducted beta-testing to evaluate usability, feasibility, and applicability of PROACTIVE. Centers' responses were scored and indicators with mean scores ≤75% in availability/performance were classified as common POCC challenges. Alpha-testing ensured face-validity and beta-testing demonstrated feasibility and usability of PROACTIVE (October 2020-June 2021). Twenty-two surveys (response rate 99.4%) were used to develop center-specific reports. Adjustments to PROACTIVE were made based on focus group feedback and surveys, resulting in 200 questions. Aggregated data across centers identified common POCC challenges: (1) lack of pediatric intensivists, (2) absence of abstinence and withdrawal symptoms monitoring, (3) shortage of supportive care resources, and (4) limited POCC training for physicians and nurses. PROACTIVE is a feasible and contextually appropriate tool to help clinicians and organizations identify challenges in POCC services across a wide range of resource-levels. Widespread use of PROACTIVE can help prioritize and develop tailored interventions to strengthen POCC services and outcomes globally.


T-cell abnormalities in common variable immunodeficiency.
Common variable immunodeficiency (CVI) is a heterogeneous condition marked by a number of different immunologic defects. One group of patients, perhaps 60% of the CVI group as a whole, is characterized by T cells that produce reduced amounts of IL-2 (mRNA and protein product), IL-4, and IL-5 (mRNA) when stimulated with phytohemagglutinin. This defect does not extend to all lymphokines, however, because the cells produce normal amounts of interferon-gamma (mRNA and protein product) when exogenous IL-2 is present. Recently, we have reexamined the T cell lymphokine production defect using a panoply of T-cell activation stimuli and have shown that the defect is a subtle one that depends on activation of the cell via the CD3-T-cell receptor complex. Because T cells proliferate normally when stimulated via this receptor, this finding suggests the presence of a "downstream" defect, perhaps one involving the factors that are necessary for activation of lymphokine genes. A second form of CVI, in this case involving approximately 30% of the CVI group as a whole, is characterized by a reduced CD4/CD8 ratio and elevated numbers of CD8+ T cells bearing the CD57 marker. Although the CD4+ T cells in this patient group elaborate normal amounts of IL-2 under various activation conditions, their CD8+ T cells produce increased amounts of interferon-gamma. Furthermore, the CD8+ T cells in this case act as "suppressor" T cells, which suppress IgG production but not IgM production of purified (normal) SAC+, IL-2-induced B cells.(ABSTRACT TRUNCATED AT 250 WORDS)


Excessive zinc ingestion. A reversible cause of sideroblastic anemia and bone marrow depression.
Two patients with sideroblastic anemia secondary to zinc-induced copper deficiency absorbed excess zinc secondary to oral ingestion. The source of excess zinc was a zinc supplement in one case; in the other, ingested coins. In each case, the sideroblastic anemia was corrected promptly after removal of the source of excess zinc. These two cases emphasize the importance of recognizing this clinical entity, since the myelodysplastic features are completely reversible.


Ultrastructural study of ochratoxicosis in quail (Coturnix coturnix japonica).
Ultrathin sections of liver and kidney from 11-week-old quail fed, from day-old, ochratoxin A (OA) (mixed in the diet at levels of 4 and 8 ppm) were examined in the electron microscope. Pathological changes in the kidneys were limited to the proximal convoluted tubules (PCT) and glomeruli. In the PCTs, abnormal mitochondria and excessive numbers of lipid droplets were the principal findings with glomeruli showing thickened basement membranes. Swollen mitochondria and variable glycogen deposition were the chief features present in the livers. It is suggested that OA is more hepatotoxic in quail than in broilers, as well as being nephrotoxic.


Medical Information Extraction in the Age of Deep Learning.
We survey recent developments in medical Information Extraction (IE) as reported in the literature from the past three years. Our focus is on the fundamental methodological paradigm shift from standard Machine Learning (ML) techniques to Deep Neural Networks (DNNs). We describe applications of this new paradigm concentrating on two basic IE tasks, named entity recognition and relation extraction, for two selected semantic classes-diseases and drugs (or medications)-and relations between them. For the time period from 2017 to early 2020, we searched for relevant publications from three major scientific communities: medicine and medical informatics, natural language processing, as well as neural networks and artificial intelligence. In the past decade, the field of Natural Language Processing (NLP) has undergone a profound methodological shift from symbolic to distributed representations based on the paradigm of Deep Learning (DL). Meanwhile, this trend is, although with some delay, also reflected in the medical NLP community. In the reporting period, overwhelming experimental evidence has been gathered, as illustrated in this survey for medical IE, that DL-based approaches outperform non-DL ones by often large margins. Still, small-sized and access-limited corpora create intrinsic problems for data-greedy DL as do special linguistic phenomena of medical sublanguages that have to be overcome by adaptive learning strategies. The paradigm shift from (feature-engineered) ML to DNNs changes the fundamental methodological rules of the game for medical NLP. This change is by no means restricted to medical IE but should also deeply influence other areas of medical informatics, either NLP- or non-NLP-based.


On the molecular origin of supercapacitance in nanoporous carbon electrodes.
Lightweight, low-cost supercapacitors with the capability of rapidly storing a large amount of electrical energy can contribute to meeting continuous energy demands and effectively levelling the cyclic nature of renewable energy sources. The excellent electrochemical performance of supercapacitors is due to a reversible ion adsorption in porous carbon electrodes. Recently, it was demonstrated that ions from the electrolyte could enter sub nanometre pores, greatly increasing the capacitance. However, the molecular mechanism of this enhancement remains poorly understood. Here we provide the first quantitative picture of the structure of an ionic liquid adsorbed inside realistically modelled microporous carbon electrodes. We show how the separation of the positive and negative ions occurs inside the porous disordered carbons, yielding much higher capacitance values (125 F g(-1)) than with simpler electrode geometries. The proposed mechanism opens the door for the design of materials with improved energy storage capabilities. It also sheds new light on situations where ion adsorption in porous structures or membranes plays a role.


Cystic fibrosis related diabetes: Nutrition and growth considerations.
Nutritional considerations are crucial to the optimal management of cystic fibrosis related diabetes (CFRD). The development of abnormal glucose tolerance and CFRD can have negative effects on CF nutritional status. Treatment of CFRD with insulin replacement is essential; however, medical nutrition therapy is important to maintain nutritional status while normalizing blood glucose levels. CF Foundation Nutritional Guidelines are recommended for the nutritional management of CFRD; specifically, the diet should be high in calories, protein, fat, and salt. Carbohydrate intake is not limited, but carbohydrate counting can be used to guide insulin dosing and maintain consistent blood glucose levels. CFTR modulator therapy shows early promise for the improvement of growth and nutritional parameters in CF.


Development of a Web-based questionnaire to collect exposure and symptom data in children and adolescents with asthma.
Questionnaires are an important component of epidemiologic studies. Maintaining compliance in longitudinal studies is a challenge, particularly from children and adolescents. To implement a Web-based questionnaire for children and adolescents with asthma for daily self-completion, minimizing recall bias and maximizing compliance. We determined symptoms, exposure to asthma triggers, peak expiratory flow rate, and medications taken, including dose and dose time. The Web-based system can be less time-consuming and a source of fewer errors than paper questionnaires and permits review of the data and compliance during the study. The Web programming of the questionnaire included branching, so that questions deemed irrelevant based on a previous response were not presented to participants, minimizing the completion time. Sixty-four students with asthma participated nearly daily for between 2 and 4 months. Financial incentives for the participants were calculated in real time based on completion rates. Monitoring of the subject's completion included an extensive administrative hierarchical alert system, enabling the staff to target individuals who fell behind in entries and needed the most encouragement. Similar compliance and completion rates were obtained using the Web-based questionnaire as reported for smaller paper questionnaires by parents of children. The Web-based system provides a mechanism to obtain daily responses directly from an age group not often accessible by traditional questionnaire approaches.


Periocular granuloma annulare.
A 2-year-old boy presented with a 3-month history of nontender masses involving the right superotemporal orbit and scalp. Over the three-week period before presentation he also developed nodules on his wrist, abdomen, and buttocks. The remainder of the ocular and general physical exam was unremarkable. A biopsy of the right orbital mass demonstrated stellate areas of collagen necrosis surrounded by pallisading epithelioid histiocytes and scattered multinucleated giant cells. Special stains for connective tissue mucin were positive in the areas of necrosis. The diagnosis reached pathologically and clinically were that of pseudorheumatoid nodules and granuloma annulare syndrome respectively. These two diagnostic terms have been used independently in the ophthalmologic and dermatologic literature, despite the identical histologic and clinical behaviors seen by both medical groups. A unified nomenclature system of pseudorheumatoid nodule for the histopathology of an individual lesion and granuloma annulare for the syndrome is suggested.


A workflow for the metabolomic/metabonomic investigation of exhaled breath using thermal desorption GC-MS.
Confounding factors in the analysis of human breath by thermal desorption GC-MS are reviewed, with special emphasis on the high water levels encountered in human breath samples. Multilinear regression optimization of breath sampling factors, along with the selection of ubiquitous sample components used as retention-time standards, enabled data registration based on retention indexing and mass spectral alignment. This was done on a component-by-component basis. The methodology developed reconciled participant safety, artefacts from accelerated hydrolysis of the stationary phase and the destructive nature of thermal desorption. Furthermore, using ubiquitous methylated cyclic-siloxanes in the thermal desorption-GC-MS chromatograms enabled secondary retention indexing for each chromatogram. This methodology enables the creation of a 'breath matrix' that is based on a combination of retention indexing and the mass spectral registration of isolated peaks. This approach facilitated more efficient data modeling and a case study from a 22-participant (10 male, 12 female) stress-intervention experiment. Principal component analysis of data registered by retention indexing did not classify successfully stressed from unstressed states. By contrast, adoption of a breath matrix approach enabled 95% separation.


Use of cork powder and granules for the adsorption of pollutants: a review.
Cork powder and granules are the major subproducts of the cork industry, one of the leading economic activities in Portugal and other Mediterranean countries. Many applications have been envisaged for this product, from cork stoppers passing through the incorporation in agglomerates and briquettes to the use as an adsorbent in the treatment of gaseous emissions, waters and wastewaters. This paper aims at reviewing the state of the art on the properties of cork and cork powder and their application in adsorption technologies. Cork biomass has been used on its original form as biosorbent for heavy metals and oils, and is also a precursor of activated carbons for the removal of emerging organic pollutants in water and VOCs in the gas phase. Through this literature review, different potential lines of research not yet explored can be more easily identified.


Rapid and Semi-automated Extraction of Neuronal Cell Bodies and Nuclei from Electron Microscopy Image Stacks.
Connectomics-the study of how neurons wire together in the brain-is at the forefront of modern neuroscience research. However, many connectomics studies are limited by the time and precision needed to correctly segment large volumes of electron microscopy (EM) image data. We present here a semi-automated segmentation pipeline using freely available software that can significantly decrease segmentation time for extracting both nuclei and cell bodies from EM image volumes.


How to write the recent history of immunology--is the time really ripe for a narrative synthesis?
In June 1992 historians and immunologists met at the International School of Biological Sciences on Ischia, Italy to discuss aspects of the recent history of immunology. This paper takes issue with some of the historiographical recommendations in the report from the meeting by Horace F. Judson and Ian Mackay ('History in the Bay of Naples', Immunology Today, November 1992).


Ileal atresia associated with Hirschsprung disease (total colonic aganglionosis).
One of the most common causes of small bowel obstruction in newborns is ileal atresia, and one of the most common causes of colonic obstruction in neonates is aganglionic megacolon (Hirschsprung disease). However, atresias of the small intestinal tract associated with Hirschsprung disease are extremely rare. We describe an infant born with both ileal atresia and Hirschsprung disease. This is the 19th known report of the case of an infant who had ileal atresia associated with Hirschsprung disease.


Heterogeneity of aspartate aminotransferase (AAT) in bull semen.
Polymorphism of non-genetic character was discovered in aspartate aminotransferase (AAT) of bull semen. A relationship was found between the enzyme heterogeneity and susceptibility of plasmatic membranes of spermatozoa to cryogenic damage. The relation changed with the bull's age.


Characterizing lignin-containing microfibrillated cellulose based on water interactions, fibril properties, and imaging.
Morphological characterization of microfibrillated cellulose (MFC) is critically important to process control in production and product specification for trade and product development yet is extremely difficult. This study evaluated several indirect methods for relative comparison of the morphology of lignin-free and lignin-containing ((L)MFCs). The (L)MFCs studied were produced using a commercial grinder through different passes from a dry lap bleached kraft eucalyptus pulp, a virgin mixed (maple and birch) unbleached kraft hardwood pulp, and two virgin-unbleached kraft softwood (loblolly pine) pulps with one bleachable grade (low lignin content) and one liner grade (high lignin content). The (L)MFCs were indirectly characterized using techniques based on water interactions, i.e., water retention value (WRV) and fibril suspension stability, as well as fibril properties, i.e., cellulose crystallinity and fine content. Optical microscopy and scanning electron microscopy were also applied to directly visualize the (L)MFCs to provide some objective measure of the morphology of the (L)MFCs. The results indicate that most measures such as WRV, cellulose crystallinity, fine content cannot be used to compare (L)MFCs from different pulp fibers. Measures based on water interactions such as (L)MFC WRV and suspension stability appeared can provide some degree of indirect assessment. This study provided the utilities and limits of these indirect methods for relative comparison of the morphologies of (L)MFCs.


Circulatory and mechanical response of skin to loading.
We investigated the tolerance of skin to mechanical loading over the tibia and over the tibialis anterior muscle in 12 normal volunteers. Surface load, subcutaneous tissue pressure, skin deformation under load, and transcutaneous partial pressure of oxygen (TcPO2) were simultaneously monitored. The skin over bone showed a significantly stiffer load deformation relationship than the skin over muscle (p less than 0.001). The displacement required to reduce TcPO2 to 0 over bone, 1.1 +/- 0.3 mm (mean +/- standard deviation), was significantly less than that required over tibialis anterior muscle, 5.4 +/- 1.1 mm (p less than 0.001). The applied pressure required to reduce TcPO2 to 0 was significantly greater for skin over muscle (71 +/- 16 mm Hg) than for skin over bone (42 +/- 8 mm Hg) (p less than 0.001). However, the subcutaneous pressure required to reduce TcPO2 to 0 was not significantly different for skin over muscle (36 +/- 11 mm Hg) than for skin over bone (28 +/- 10 mm Hg) (p greater than 0.05). Our results indicate that skin over muscle tolerates greater locally applied loads and deformations because the pressure is lower within the tissue than when similar loads and deformation are applied to skin over bone. Cutaneous perfusion, as indicated by TcPO2, seems to be linked more closely to the subcutaneous tissue pressure than to the surface load or deformations. These results provide some data for predicting mechanical and physiologic response to locally applied loads such as those that may be encountered in prosthetic wear.


Genetic complementation of human muscle cells via directed stem cell fusion.
Duchenne muscular dystrophy (DMD) is caused by mutations in the X chromosome-linked DMD gene, which encodes the sarcolemma-stabilizing protein-dystrophin. Initial attempts at DMD therapy deployed muscle progenitor cells from healthy donors. The utilization of these cells is, however, hampered by their immunogenicity, while those from DMD patients are scarce and display limited ex vivo replication. Nonmuscle cells with myogenic capacity may offer valuable alternatives especially if, to allow autologous transplantation, they are amenable to genetic intervention. As a paradigm for therapeutic gene transfer by heterotypic cell fusion we are investigating whether human mesenchymal stem cells (hMSCs) can serve as donors of recombinant DMD genes for recipient human muscle cells. Here, we show that forced MyoD expression in hMSCs greatly increases their tendency to participate in human myotube formation turning them into improved DNA delivery vehicles. Efficient loading of hMSCs with recombinant DMD was achieved through a new tropism-modified high-capacity adenoviral (hcAd) vector directing striated muscle-specific synthesis of full-length dystrophin. This study introduces the principle of genetic complementation of gene-defective cells via directed cell fusion and provides an initial framework to test whether transient MyoD synthesis in autologous, gene-corrected hMSCs increases their potential for treating DMD and, possibly, other muscular dystrophies.


Self-expandable metal stents and trans-stent light delivery: are metal stents and photodynamic therapy compatible?
Obstructive non-small cell lung cancer and obstructive esophageal cancer are US FDA approved indications of photodynamic therapy (PDT). The usefulness of PDT for the treatment of cholangiocarcinoma is currently under clinical investigation. Endoscopic stenting for lumen restoration is a common palliative intervention for those indications. It is important to assess whether self-expandable metal stents are compatible with trans-stent PDT light delivery. Direct effects of various components of metal biliary (n = 2), esophageal (n = 2), and bronchial (n = 1) stents on PDT light transmittance and distribution were examined using a point or linear light source (630 or 652 nm diode laser). Resected pig biliary duct and esophageal wall tissues were used to examine the feasibility of PDT light delivery through the fully expanded metal stents. While using a point light source, the metal components (thread and joint) of the stent could cause a significant shadow effect. The liner material (polytetrafluoroethylene or polyurethane) could cause various degrees of light absorption. When the stent was covered with a thin layer of biliary duct and esophageal tissues containing all wall layers, the shadow effect could be mitigated due to tissue scattering. This study clearly demonstrates that it is feasible to combine stenting and PDT for the treatment of luminal lesions. PDT light dose should be adjusted to counteract the reduction of light transmittance caused by the metal and liner materials of stent.


The clinical and biologic significance of serum inhibins in subfertile men.
Inhibin B is a marker of spermatogenesis and Sertoli cell function. The objective of this study was to evaluate the biologic significance of inhibins in subfertile men and the usefulness of inhibin B for the detection of male reproductive dysfunction. Forty-seven subfertile men were evaluated by semen analysis and clinical examination. In addition to semen analysis and hormone determinations, inhibins A and B (Serotec) in all 47 and inhibin A in 25 of these samples using another kit (Biosource) were measured. Higher inhibin B (median, range: 160.3, 81.8-328.5 pg/mL vs. 94.9, 15.6-389.7 pg/mL, P = 0.024) and lower FSH (P = 0.001) were detected in men with sperm concentrations > or =20 million/mL (n = 9), compared to oligozoospermia (sperm concentration <20 million/mL, n = 38). Inhibin B correlated significantly negatively with FSH, LH, and E2, and patient's age and positively with sperm concentration, testicular volume, and TSH. Multiple regression analysis indicated FSH, LH, E2, TSH, and age as the independent variables for inhibin B with a coefficient of determination (R) of 0.53. Simultaneous measurement of both FSH and inhibin B identified more cases with oligozoospermia than either hormone alone. Taking into account the body mass index, the age of the patient, and the indirect mixed antiglobin reaction (MAR) test result in addition to FSH and inhibin B led to the correct semen classification in 45 out of 47 cases. The simultaneous measurement of FSH and inhibin B, taking into account age, body mass index, and the indirect MAR test result appears accurate in identifying subfertility. Inhibin A is detectable in some subfertile men but its significance is not clear.


Ratiometric pH-Responsive 19F Magnetic Resonance Imaging Contrast Agents Based on Hydrazone Switches.
Hydrazone-based molecular switches serve as efficient ratiometric pH-sensitive agents that can be tracked with 19F NMR/MRI and 1H NMR. Structural changes induced between pH 3 and 4 lead to signal appearance and disappearance at 1H and 19F NMR spectra allowing ratiometric pH measurements. The most pronounced are resonances of the CF3 group shifted by 1.8 ppm with 19F NMR and a hydrazone proton shifted by 2 ppm with 1H NMR.


Lead exposure in children: levels in blood, prevalence of intoxication and related factors.
Lead is a highly toxic metal, the main source of which is contamination from combustion of unleaded petrol. The aims of this work were to detect the degree of lead exposure in a large sample of children; determine the relationship between blood lead levels (BPb) and age, sex, habitat and season of the year; and correlate BPb with zinc protoporphyrin (ZPP) values. A cross-sectional study was carried out. Blood from routine extractions drawn at our centre was used. BPb and ZPP were measured by atomic absorption spectrophotometry and haematofluorimetry, respectively. We analysed 1158 blood samples from children. BPb (mean +/- SEM): 0.22 +/- 0.04 mumol l-1. Correlation BPb-age: BPb = 0.19 + 0.086 x age (months), r = 0.129, P < 0.0001. BPb was greater in boys (0.23 +/- 0.007 versus 0.20 +/- 0.006 mumol l-1, P < 0.0002). No differences were observed between habitats (urban versus rural). BPb were higher in the warm months (0.24 +/- 0.013 versus 0.21 +/- 0.007 mumol l-1, P < 0.0001). Prevalence of lead intoxication (BPb > 0.48 mumol l-1) was 4.2%. No differences in prevalence were found among the different groups. The correlation between BPb and ZPP showed r = 0.0969, P = 0.0024. Utility for screening: sensitivity of 53.7% and specificity of 59.3% (cut-off point of 60 mumol ZPP mol-1 haem). We can conclude that lead exposure in children in our sample was in the range reported in similar studies in other areas and countries, and below the toxic limit. None of the factors analysed significantly influenced lead intoxication prevalence. There was no good correlation between ZPP and BPb in our samples and the ZPP cut-off point used did not present good specificity and sensitivity values.


Identification of cancer cell-line origins using fluorescence image-based phenomic screening.
Universal phenotyping techniques that can discriminate among various states of biological systems have great potential. We applied 557 fluorescent library compounds to NCI's 60 human cancer cell-lines (NCI-60) to generate a systematic fluorescence phenotypic profiling data. By the kinetic fluorescence intensity analysis, we successfully discriminated the organ origin of all the 60 cell-lines.


The influence of short-term endurance training on maximum oxygen uptake, submaximum endurance and the ability to perform brief, maximal exercise.
The hypothesis that endurance training impairs sprinting ability was examined. Eight male subjects undertook a 30-s sprint test on a cycle ergometer before and after 6 weeks of cycling training for endurance. Maximum oxygen uptake (VO2 max) and submaximum endurance were determined to evaluate the influence of the training regimen on endurance performance. Endurance was defined as the time to exhaustion at a relative exercise intensity of 85% VO2 max. Maximum oxygen uptake was increased by 18% post-training (3.29 +/- 0.29 1 min-1 versus 3.89 +/- 0.49 1 min-1; P less than 0.01), but endurance at the same absolute work rate as pre-training was increased by more than 200% (32.2 +/- 11.4 min versus 97.8 +/- 27.3 min; P less than 0.01). These improvements were accompanied by changes in the cardiovascular and metabolic responses to standard, submaximum exercise. Despite the improvements in endurance, neither performance during the cycle sprint test nor the increase in blood lactate concentration during the sprint was influenced by endurance training. For short-term cycling training, these findings reinforce the concept of training specificity whilst demonstrating that decrements in sprint performance are not a necessary consequence of improved endurance.


Transplanted interneurons improve memory precision after traumatic brain injury.
Repair of the traumatically injured brain has been envisioned for decades, but regenerating new neurons at the site of brain injury has been challenging. We show GABAergic progenitors, derived from the embryonic medial ganglionic eminence, migrate long distances following transplantation into the hippocampus of adult mice with traumatic brain injury, functionally integrate as mature inhibitory interneurons and restore post-traumatic decreases in synaptic inhibition. Grafted animals had improvements in memory precision that were reversed by chemogenetic silencing of the transplanted neurons and a long-lasting reduction in spontaneous seizures. Our results reveal a striking ability of transplanted interneurons for incorporating into injured brain circuits, and this approach is a powerful therapeutic strategy for correcting post-traumatic memory and seizure disorders.


Trajectories of state anhedonia and recent changes in anhedonia in college students: Associations with other psychiatric syndromes.
Recent works suggest recent changes in anhedonia may be specifically predictive of key elements of psychopathology. The present study aimed to identify the trajectories of state anhedonia and recent changes in anhedonia, and to investigate their associations with other psychiatric syndromes over time. A total of 859 college students were assessed at three time points. State anhedonia was assessed using the Snaith Hamilton Pleasure Scale and recent changes in anhedonia were assessed with a subscale extracted from the Symptom Check-List-90. The Latent Growth Curve Modelling analysis was used to analyze trajectories. Associations with anhedonia were investigated with logistic regression models. Three state anhedonia trajectories and two recent changes in anhedonia trajectories were identified. The decreasing trajectory was the most prevalent class in both two types of anhedonia. Depression and suicidal ideation predicted recent changes in anhedonia whereas other psychiatric syndromes predicted state anhedonia. The current study highlighted the development trajectories of different measures of anhedonia. The results showed that the relationships between anhedonia and psychiatric syndromes were different according to the kind of anhedonia.


Architecture of the Heme-translocating CcmABCD/E complex required for Cytochrome c maturation.
Mono- and multiheme cytochromes c are post-translationally matured by the covalent attachment of heme. For this, Escherichia coli employs the most complex type of maturation machineries, the Ccm-system (for cytochrome c maturation). It consists of two membrane protein complexes, one of which shuttles heme across the membrane to a mobile chaperone that then delivers the cofactor to the second complex, an apoprotein:heme lyase, for covalent attachment. Here we report cryo-electron microscopic structures of the heme translocation complex CcmABCD from E. coli, alone and bound to the heme chaperone CcmE. CcmABCD forms a heterooctameric complex centered around the ABC transporter CcmAB that does not by itself transport heme. Our data suggest that the complex flops a heme group from the inner to the outer leaflet at its CcmBC interfaces, driven by ATP hydrolysis at CcmA. A conserved heme-handling motif (WxWD) at the periplasmic side of CcmC rotates the heme by 90° for covalent attachment to the heme chaperone CcmE that we find interacting exclusively with the CcmB subunit.


SIMULTANEOUS RUPTURE OF THE PATELLAR AND CONTRALATERAL QUADRICEPS TENDONS IN A NEPHROPATHY PATIENT.
Simultaneous rupture of the patellar and contralateral quadriceps tendons in patients with chronic renal failure is an extremely rare condition, with few cases described in the medical literature. Several systemic pathological conditions that lead to a decline in kidney function can predispose individuals to spontaneous tendon rupture, such as rheumatological and endocrine diseases, and even gestational conditions, such as eclampsia. In this case report, we describe the case of a 39-year-old woman with chronic renal failure on dialysis due to a previous history of eclampsia that caused the simultaneous rupture of the patellar and contralateral quadriceps tendons. Data were collected by interviews, direct observation, and medical examinations, and include information about the case history, the patient's characteristics, the former interventions, and the results obtained. The surgery to repair the patellar and contralateral quadriceps tendons was performed by transosseous tunnels and the Krackow technique with nonabsorbable sutures was used. The semitendinosus tendon was removed and used as reinforcement. Patient under follow-up with good functional results in both knees.Level of Evidence V, Expert Opinion.


Psychological aspects of cytogenetic testing of uveal melanoma: preliminary findings and directions for future research.
To determine the proportion of uveal melanoma patients who accept cytogenetic prognostication and to understand the reasons for their decision and the psychological impact of an adverse prognosis. Patients treated by enucleation or local resection for uveal melanoma between 01 January 2003 and 31 December 2006 were identified and the proportion undergoing cytogenetic studies was determined. In-depth interviews of fourteen patients living near our centre were conducted to determine their reasons for accepting cytogenetic testing and their reactions to any results received. In total 97% of 298 eligible patients with uveal melanoma treated by enucleation or local resection accepted an offer of cytogenetic prognostication. None of the patients interviewed in detail expressed any regret about having this test and there was no evidence of any harm. The main benefit perceived by patients was that they would have greater control and that screening for metastatic disease and early treatment might enhance chances of survival. This was despite counselling that prognostication, screening, and treatment are unlikely to prolong life and that the main purpose of cytogenetic studies is to allow for life-planning. Almost all patients with uveal melanoma desire cytogenetic prognostication, although not for the reasons intended by their medical practitioners. Further studies are needed to understand patients' reactions to cytogenetic testing, so that care can be optimised.