Introducing principles of synaptic integration in the optimization of deep neural networks.
Plasticity circuits in the brain are known to be influenced by the distribution of the synaptic weights through the mechanisms of synaptic integration and local regulation of synaptic strength. However, the complex interplay of stimulation-dependent plasticity with local learning signals is disregarded by most of the artificial neural network training algorithms devised so far. Here, we propose a novel biologically inspired optimizer for artificial and spiking neural networks that incorporates key principles of synaptic plasticity observed in cortical dendrites: GRAPES (Group Responsibility for Adjusting the Propagation of Error Signals). GRAPES implements a weight-distribution-dependent modulation of the error signal at each node of the network. We show that this biologically inspired mechanism leads to a substantial improvement of the performance of artificial and spiking networks with feedforward, convolutional, and recurrent architectures, it mitigates catastrophic forgetting, and it is optimally suited for dedicated hardware implementations. Overall, our work indicates that reconciling neurophysiology insights with machine intelligence is key to boosting the performance of neural networks.


Comparative targeting of human colon-carcinoma multicell spheroids using one- and two-step (bispecific antibody) techniques.
In the perspective of radioimmunotherapy (RIT) of micrometastases, we compared, in multicell spheroids (MS), the uptake and retention kinetics of 125I-F(ab)'2 F6 anti-carcinoembryonic antigen (CEA) monoclonal antibody (MAb), and the affinity enhancement system (AES) using an anti-CEA/anti-DTPA-indium bispecific antibody (BsMAb) and a 125I-labeled di-DTPA-In-tyrosine-lysine bivalent hapten. We used MS of colorectal tumor cell lines expressing CEA strongly (LS 174T), weakly (HT-29) or not at all (HRT-18). Uptake and retention kinetics of 125I-F(ab)'2 F6 and 125I-BsMAb used alone gave similar results. The highest uptake values, obtained with LS 174T MS, were slightly lower with AES than with 125I-F(ab)'2 F6. However, effective retention half-lives were longer for AES than for 125I-F(ab)'2 F6 or for 111In-labeled monovalent hapten after pre-incubation of spheroids with BsMAb. Autoradiography showed the same slow and heterogeneous distribution of 125I-F(ab)'2 F6 and 125I-BsMAb. These results indicate that the 2-step technique is more favorable for RIT: uptake values were approximately the same but uptake kinetics were more rapid, and retention half-life was longer than with the one-step technique.


Resistance training improves gait kinematics in persons with multiple sclerosis.
To evaluate the effects of an 8-week lower-body resistance-training program on walking mechanics in persons with multiple sclerosis (MS). Repeated-measures design, evaluating gait kinematics before and after an 8-week progressive resistance-training intervention. Biomechanics laboratory and fitness center (with conventional, commercially available resistance-training equipment). Eight ambulatory subjects with MS (age, 46.0+/-11.5 y) with Expanded Disability Status Scale scores ranging from 2.5 to 5.5. An 8-week progressive resistance-training program. Kinematic gait parameters including knee range of motion, duration of stance, swing, and double-support phases in seconds and as percentages of the stride time, percentage of stride time spent in stance, swing, and double-support phases, step length, foot angle, stride length, velocity, step width, and toe clearance for both the more affected and less affected lower limbs. Isometric strength, 3-minute stepping, fatigue, and self-reported disability were also measured. After 2 months of resistance training, there were significant increases (P<.05) in percentage of stride time in the swing phase, step length, stride length, and foot angle; and significant decreases (P<.05) in percentage of stride time in the stance and double-support phases, duration of the double-support phase, and toe clearance. Isometric leg strength improved (P<.05) in 2 of the 4 muscle groups tested. Fatigue indices decreased (P=.04), whereas self-reported disability tended to decrease (P=.07) following the training program. Three-minute stepping increased by 8.7%. Resistance training may be an effective intervention strategy for improving walking and functional ability in moderately disabled persons with MS.


[Correlation analysis between WNK4 gene and essential hypertension].
To investigate association of mutation in WNK4 gene with essential hypertension and to analyze the expression of WNK4 gene. cSNP in WNK4 gene in a small samples was detected by sequencing, then PCR-RFLP was performed in 98 patients with essential hypertension and 95 control subjects. The expression profile of WNK4 gene was tested by RT-PCR. A cSNP was detected in WNK4 gene exon7 G1662A, and there were significant differences in the distribution of allele frequency of G1662A between essential hypertension group and control group. WNK4 gene were expressed in the tissues of kidney, brain, lung, heart, spleen and intestine of fetus. WNK4 gene is well correlated with essential hypertension.


On the control of visual spatial attention: evidence from human electrophysiology.
We used electrophysiological methods to track the deployment of visual spatial attention while observers were engaged in concurrent central attentional processing, using a variant of the attentional blink paradigm. Two visual targets (T1, T2) were presented at a stimulus onset asynchrony of either 200 ms or 800 ms. T1 was a white digit among white letters presented on a dark background using rapid serial visual presentation at fixation. T2 was another digit that was presented to the left or right of fixation simultaneously with a distractor digit in the opposite visual field, each followed by a pattern mask. In each T2 display, one digit was red and one was green. Half of the subjects reported the red digit and ignored the green one, whereas the other half reported the green digit and ignored the red one. T1 and T2 were reported in one block of trials, and only T2 in another block (order counterbalanced across subjects). Accuracy of report of T2 was lower at short SOA than at long SOA when both T1 and T2 were reported, but was similar across SOA when only T2 was reported. The electrophysiological results focused on the N2pc component, which was used as an index of the locus of spatial attention. N2pc was reduced in amplitude when subjects reported T1, and particularly so at the short SOA. The results suggest that attention to T1 interfered with the deployment of visual spatial attention to T2.


Foetal deterioration following thiopentone-nitrous oxide anaesthesia in the pregnant ewe.
Six pregnant sheep were chronically prepared with indwelling catheters in maternal and foetal vessels and a flow probe around a maternal uterine artery. They were anaesthetized the following day with thiopentone and nitrous oxide (70 per cent)--oxygen (30 per cent) maintenance with tracheal intubation. Maternal uterine blood flow fell about 20 per cent following induction of anaesthesia. This resulted from uterine vasoconstriction which, in turn, probably resulted from maternal catecholamine release during light anaesthesia. The foetus in utero developed a mixed metabolic and respiratory acidosis and a fall in oxygen saturation. The possibility that light maternal anaesthesia increases rather than decreases neonatal depression is discussed.


Protein aggregation in the pathogenesis of familial and sporadic Parkinson's disease.
Parkinson's disease (PD) is a slowly progressive, age-related, neurodegenerative disorder. The cause and mechanism of neuronal death have been elusive. However, recent genetic, postmortem and experimental evidence show that protein accumulation and aggregation are prominent occurrences in both sporadic and familial PD. The relevance of these events to other cellular and biochemical changes, and to the neurodegenerative process, is being unraveled. It is increasingly evident that one or a combination of defects, including mutations, oxidative stress, mitochondrial impairment and dysfunction of the ubiquitin-proteasome system, lead to an excess production and aggregation of abnormal proteins in PD. In this respect, altered protein handling appears to be a central factor in the pathogenic process occurring in the various hereditary and sporadic forms of PD. This suggests that manipulation of proteolytic systems is a rational approach in the development of neuroprotective therapies that could modify the pathological course of PD.


Alterations in the activation of corticotropin-releasing factor neurons in the paraventricular nucleus following a single or multiple days of sleep restriction.
Sleep disturbances are common among disorders associated with hypothalamic pituitary-adrenal (HPA) axis dysfunction, such as depression and anxiety. This comorbidity may partly be the result of the intersection between the role of the HPA axis in mediating the stress response and its involvement in sleep-wake cyclicity. Our previous work has shown that following 20 h of sleep restriction, mice show a blunting of the HPA axis in response to an acute stressor. Furthermore, these responses differ in a sex-dependent manner. This study sought to examine the effect of sleep restriction on corticotropin-releasing factor (CRF)-containing neurons in the paraventricular nucleus (PVN) of the hypothalamus. Male and female Crf-IRES-Cre: Ai14 (Tdtomato) reporter mice were sleep restricted for 20 h daily for either a single or three consecutive days using the modified multiple platform method. These mice allowed the visualization of CRF+ neurons throughout the brain. Animals were subjected to acute restraint stress, and their brains were collected to assess PVN neuronal activation via c-Fos immunohistochemistry. Analyses of cell counts revealed an ablation of the restraint-induced increase in both CRF/c-Fos colocalization and overall c-Fos expression in female mice following both a single day and three days of sleep restriction. Males showed an overall decrease in restraint-induced c-Fos levels following a single day of sleep restriction. However, male mice examined after three days of sleep restriction showed a recovery in PVN-CRF and overall PVN neuronal activation. These data suggest the sex dependent dysregulation in CRF function following sleep restriction.


Biosynthesis and biotransformation of ether lipids.
Some naturally occurring as well as synthetic ether lipids are biologically active. In certain cases, the effects of these substances are enhanced, in others, they are inhibited by compounds that were isolated from natural sources or prepared by chemical synthesis. The biotransformation of natural or "unnatural" ether lipids in microorganisms, plant or animal tissue also can lead to substances that elicit biological effects. The production of such compounds through various biotechnological techniques is a field wide open for future exploration. In addition to animal cell cultures, plant cell cultures may become useful tools in biomedical studies concerned with ether lipids.


T-lymphocyte recognition of a portion of myelin basic protein encoded by an exon expressed during myelination.
The major isoform of myelin basic protein (MBP) in the healthy adult central nervous system is the 18.5-kDa protein which is produced by mRNA derived from exons 1, 3, 4, 5, 6 and 7 of the MBP gene. Since isoforms containing exon 2-encoded protein (X2MBP) are expressed during myelin formation, we examined T cell reactivity specific for X2MBP in a disease characterized by remyelination subsequent to demyelination, multiple sclerosis (MS). T cell lines specific for X2MBP were derived from three MS patients as well as one healthy control. This suggests that candidate autoantigens in demyelinating/remyelinating diseases should include not only the major isoforms of myelin proteins, but also isoforms expressed aberrantly during a disease process since they too may be the target of a T cell-mediated autoimmune process.


Nanoporous silica coatings as a drug delivery system for ciprofloxacin: outcome of variable release rates in the infected middle ear of rabbits.
The present study was performed to examine the impact of the release rate of ciprofloxacin from prostheses coated with nanoporous silica layers on the outcome of an acute bacterial infection of the middle ear of rabbits. Middle ear prostheses are often implanted in an infectious environment because of chronic otitis media and cholesteatoma. Bacterial colonization leads to healing disorders after surgery and may lead to the extrusion of the implants. Nanoporous silica layers appear promising as a drug delivery system for antibiotics placed on implants. Before clinical applications can be envisioned, it is necessary to find an optimal release rate. White New Zealand rabbits were provided unilaterally with either a "slow release" or a "burst release" ciprofloxacin-containing middle ear Bioverit II prosthesis. After implantation, the middle ears were infected with a solution of Pseudomonas aeruginosa. Afterwards, animals were monitored clinically and, after 3 months, sacrificed to perform necropsy and microbiologic examinations. In the "slow release" group, 7 of 12 animals had to be euthanized preterm because of their poor clinical condition compared with 2 of 12 animals of the "burst release" group (p < 0.05). Clinical and microbiologic examination also showed a better outcome for animals of the burst release group. A burst release of ciprofloxacin from middle ear implants is important to combat a perioperative infection with Ps. aeruginosa in the middle ear model of the rabbit.


Late Onset Cerebral Nocardiosis in a Sensitized Renal Transplant Recipient Following Alemtuzumab Induction: A Case Report.
Balancing immunosuppressive regimen to prevent rejection yet avoiding severe infectious complications remains a key challenge following renal transplantation, especially in patients sensitized after exposure to human leukocyte antigens. We herein report a late onset infection with nocardia in a sensitized renal transplant recipient. A 65-year-old male patient, who had received kidney transplantation with alemtuzumab induction due to human leukocyte antigen-sensitization 3 years ago, was admitted with headache and dizziness. A cerebral magnetic resonance imaging scan showed a right parieto-occipital brain abscess. Surgical abscess drainage was performed and microbiology analysis detected Nocardia paucivorans in the abscess fluid. Laboratory results showed persistently reduced lymphocyte and T-cell counts 3 years after transplantation. We started intravenous antibiotic therapy with high dose trimethoprim/sulfamethoxazole and imipenem/cilastatin. Furthermore, immunosuppression was adapted with discontinuation of mycophenolate. After 7 weeks of intravenous antibiotic therapy, the patient was switched to an oral antibiotic regimen with amoxicillin/clavulanic acid and minocycline. In the follow-up magnetic resonance imaging scan, cerebral lesions were substantially reduced, initial symptoms completely disappeared, and allograft function remained stable. Induction therapy with the CD52-antibody alemtuzumab enables transplantation in highly sensitized patients but leads to lymphocyte depletion for several weeks. Our patient presented with prolonged lymphopenia and a significantly reduced T-cell count 3 years after transplantation. To our knowledge, our case is the first to describe a late-onset nocardia infection 3 years after alemtuzumab induction in a renal transplant recipient. It underlines the importance of considering this rare disease in transplant patients, especially after induction therapy with depleting antibodies.


Comparative mitochondrial genome analyses reveal conserved gene arrangement but massive expansion/contraction in two closely related Exserohilum pathogens.
Exserohilum turcicum and E. rostratum, two closely related fungal species, are both economically important pathogens but have quite different target hosts (specific to plants and cross-kingdom infection, respectively). In the present study, complete circular mitochondrial genomes of the two Exserohilum species were sequenced and de novo assembled, which mainly comprised the same set of 13 core protein-coding genes (PCGs), two rRNAs, and a certain number of tRNAs and unidentified open reading frames (ORFs). Comparative analyses indicated that these two fungi had significant mitogenomic collinearity and consistent mitochondrial gene arrangement, yet with vastly different mitogenome sizes, 264,948 bp and 64,620 bp, respectively. By contrast with the 17 introns containing 17 intronic ORFs (one-to-one) in the E. rostratum mitogenome, E. turcicum involved far more introns (70) and intronic ORFs (126), which was considered as the main contributing factors of their mitogenome expansion/contraction. Within the generally intron-rich gene cox1, a total of 18 and 10 intron position classes (Pcls) were identified separately in the two mitogenomes. Moreover, 16.16% and 10.85% ratios of intra-mitogenomic repetitive regions were detected in E. turcicum and E. rostratum, respectively. Based on the combined mitochondrial gene dataset, we established a well-supported topology of phylogeny tree of 98 ascomycetes, implying that mitogenomes may act as an effective molecular marker for fungal phylogenetic reconstruction. Our results served as the first report on mitogenomes in the genus Exserohilum, and would have significant implications in understanding the origin, evolution and pathogenic mechanisms of this fungal lineage.


Metabolic products of microorganisms. 240. Urdamycins, new angucycline antibiotics from Streptomyces fradiae. II. Structural studies of urdamycins B to F.
The structures of the angucycline antibiotics urdamycin B (5), E (2) and F (9) were established by comparing of their spectra with those of urdamycin A (1). The structures of urdamycins C and D, the largest compounds of this series, are still incomplete (10 and 11). The aglycones urdamycinone C, D and E can be liberated by methanolysis of the corresponding urdamycins. The liberation of urdamycinone B (6) requires an alcohol-free medium, to prevent its rearrangement to the naphthacenequinone 7 or 8. The urdamycins differ from other O-glycoside series in their variety of aglycones.


Double T-junction microfluidic and conventional dripping systems for Bacillus subtilis immobilization in calcium alginate microparticles for lipase production.
Bacillus subtilis immobilization in calcium alginate microparticles was investigated using two techniques: droplet microfluidics-based in T-junction geometry composed with a double droplet generation system and conventional dripping system. Alginate microparticles produced by microfluidic technology presented an average size of 68.35 µm with low polydispersity and immobilization efficiency around 86%. The cell response was evaluated in batch cultivation for 24 h, viewing lipase production compared to free cells. In this study, the batch cultivation with immobilized cells in alginate microparticles presented lipase production about 2.4 and 1.7 times higher than cultivation with cells immobilized cells by conventional technique and free cells cultivations. According to the results, this main novelty of the double T junction technique is an innovative contribution as a tool for cell immobilization on a laboratory scale, since the cultivation of immobilized cells in microparticles of small size and low polydispersity favors cell growth and increases the productivity of important metabolites of industrial biotechnology.


Bacterial community structure in treated sewage sludge with mesophilic and thermophilic anaerobic digestion.
Stabilized sewage sludge is applied to agricultural fields and farmland due to its high organic matter content. The aim of this study was to investigate the effects of two types of sludge stabilization, mesophilic anaerobic digestion (MAD) and thermophilic anaerobic digestion (TAD), on bacterial communities in sludge, including the presence of pathogenic microorganisms. Bacterial community structure and phylogenetic diversity were analyzed in four sewage sludge samples from the Czech Republic. Analysis of 16S ribosomal RNA (rRNA) genes showed that investigated sludge samples harbor diverse bacterial populations with only a few taxa present across all samples. Bacterial diversity was higher in sludge samples after MAD versus TAD treatment, and communities in MAD-treated sludge shared the highest genetic similarities. In all samples, the bacterial community was dominated by reads affiliated with Proteobacteria. The sludge after TAD treatment had considerably higher number of reads of thermotolerant/thermophilic taxa, such as the phyla Deinococcus-Thermus and Thermotogae or the genus Coprothermobacter. Only one operational taxonomic unit (OTU), which clustered with Rhodanobacter, was detected in all communities at a relative abundance >1 %. All of the communities were screened for the presence of 16S rRNA gene sequences of pathogenic bacteria using a database of 122 pathogenic species and ≥98 % identity threshold. The abundance of such sequences ranged between 0.23 and 1.57 % of the total community, with lower numbers present after the TAD treatment, indicating its higher hygienization efficiency. Sequences clustering with nontuberculous mycobacteria were present in all samples. Other detected sequences of pathogenic bacteria included Streptomyces somaliensis, Acinetobacter calcoaceticus, Alcaligenes faecalis, Gordonia spp., Legionella anisa, Bordetella bronchiseptica, Enterobacter aerogenes, Brucella melitensis, and Staphylococcus aureus.


Ultrasound-assisted micellar cleanup coupled with large-volume-injection enrichment for the analysis of polar drugs in blood and zebrafish samples.
A novel ultrasound-assisted micellar cleanup strategy (UAMC) coupled with large volume injection (LVI) high performance liquid chromatography (HPLC) method was proposed and successfully applied to the analysis of cefathiamidine in complex biological samples such as whole blood, plasma, serum and even zebrafish, a challenging positive real sample. Based on the micelle-biomacromolecule interaction, the phase-separation feature of surfactant micelles and ultrasound cavitation, UAMC possessed an impressive matrix cleanup capability and could rapidly reach distribution equilibrium (approximately 2 min), which enabled simultaneous sample cleanup and analyte extraction within 8 min. Due to the high cleanup efficiency of UAMC, large volume of pretreated samples could be injected for analysis without peak broadening, impurity interference and column degradation. Thus, online analyte enrichment could be automatically performed to significantly improve method sensitivity by the column-switching LVI-HPLC system, a commercial HPLC system with small modifications. The UAMC-LVI-HPLC method creatively integrated sample cleanup, analyte extraction and on-column enrichment into simple operation. In addition, the UAMC-LVI-HPLC method enabled non-matrix-matched analysis of cefathiamidine in complex biological samples. This feature was helpful to address the problems caused by conventional matrix-matched or internal standard calibration methods, such as matrix bias, increased workload, limited availability of suitable blank matrices and the use of expensive internal standards. The method had low limits of detections (e.g., 0.0051 mg/L and 0.038 μg/g), wide linear ranges (0.030-100 mg/L and 0.15-489 μg/g), good linear correlation (R2 = 0.9999), satisfactory accuracy (97.6-109.7%) and excellent intra- and interday precision (0.5-4.9%). Thus, UAMC-LVI-HPLC is expected to be a promising candidate for bioanalysis in therapeutic drug monitoring or pharmacokinetic and toxicology studies in the future.


Effect of the FXa inhibitors Rivaroxaban and Apixaban on platelet activation in patients with atrial fibrillation.
Rivaroxaban and Apixaban, increasingly used for stroke prevention in non-valvular atrial fibrillation (AF), might impact platelet reactivity directly or indirectly. By inhibition of Factor Xa (FXa) they preclude not only generation of relevant thrombin amounts but also block signalling of FXa via protease activated receptors. However, weather FXa-inhibition affects platelet haemostasis remains incompletely known. One hundred and twenty-eight patients with AF on chronic anticoagulation with either Rivaroxaban or Apixaban for at least 4 weeks were included in the study. In a time course group (25 on Rivaroxaban, 13 on Apixaban) venous blood samples were taken before NOAC medication intake in the morning as well as 2 and 6 h afterwards. In 90 patients (Rivaroxaban n = 73, Apixaban n = 17) blood samples were drawn during left atrial RFA procedures before as well as 10 and 60 min after the first heparin application (RFA group). Platelet reactivity analyzed by whole blood aggregometry (Multiplate Analyzer, Roche) in response to ADP, Collagen, TRAP and ASPI (arachidonic acid) was not altered by Rivaroxaban or Apixaban neither in the time course nor in the RFA group. Moreover, soluble P-selectin, Thrombospondin, von Willebrand Factor and beta thromboglobulin plasma levels, measured by ELISA, showed no statistically significant changes in both clinical settings for either FXa-inhibitor. The present study fails to demonstrate any significant changes on platelet reactivity in patients with AF under chronic Rivaroxaban or Apixaban medication, neither for trough or peak levels nor in case of a haemostatic activation in vivo as depicted by RFA procedures.


[On the best strategies on the best results for surgery of frontal epilepsy].
Frontal lobe epilepsy surgery is the second most common surgery performed for drug-resistant partial epilepsy. We investigated the longitudinal outcome in a cohort of patients investigated since 1990 with SEEG and modern diagnostic techniques. We reviewed 105 patients who underwent surgery between 1990 and 2005 (mean follow-up, six years; range: one to 17 years) and analyzed the year-per-year follow-up according to Engel's classification. Favorable outcome (Class I) was observed for 70% and this result was stable at least five years after surgery. More than 90% of patients with lesion-related epilepsies (focal cortical dysplasia and dysembryoplastic neuroepithelial tumors) became seizure-free. Less than 50% of patients classified as having cryptogenic epilepsy (defined as normal imaging and neuropathology on surgical specimen) had a favorable outcome. Permanent neurological sequelae were subtle and rare, especially after surgery for dysplasia in eloquent cortex (primary motor cortex). Our data indicate that frontal surgery is a successful treatment in patients when electrophysiological and morphological investigations demonstrate a well-defined epileptogenic zone or lesion to be surgically resected. Progress in electrophysiological and brain-imaging techniques will further improve the selection of frontal lobe epilepsy surgery candidates.


Do static or time-varying magnetic fields in magnetic resonance imaging (3.0 T) alter protein-gene expression?-A study on human embryonic lung fibroblasts.
To evaluate the influence of magnetic resonance imaging (MRI) on gene expression in embryonic human lung fibroblasts (Hel 299). The cells were exposed to the static magnetic field and to a turbo spin-echo sequence of an MR scanner at 3.0 Tesla. An MR group (exposed) and a control group (sham-exposed) were set up using a special MR-compatible incubation system. The exposure time was two hours. Gene expression profiles were studied using a complementary deoxyribonucleic acid (cDNA) microarray containing 498 known genes involved in transcription, intracellular transport, structure/junction/adhesion or extracellular matrix, signaling, host defense, energetics, metabolism, cell shape, and death. No changes in gene expression were found in either group (exposed or sham-exposed cells) at the end of a two-hour exposure for any of the 498 tested protein genes. The results suggest that MRI has no influence on protein-gene expression in eugenic human lung cells.


Conditioned aversions to an intravascular odorant.
The odorant allyl sulfide (essence of garlic) dissolved in a corn oil vehicle was injected into rats to induce a conditioned aversion. In subsequent two-choice drinking tests, rats injected with odorant and lithium chloride, and rats injected with odorant and saline avoided drinking from a water bottle paired with the odorant. Because allyl sulfide and saline injections produced symptoms of malaise, we suspect that the odorant served as its own unconditioned stimulus. Rats injected with vehicle and saline showed no differential behavior. In a second experiment, gas chromatography indicated that allyl sulfide was present on the rat's breath within 3 minutes of injection, and was detectable for up to 5 hours post-injection. We conclude that conditioned aversions can be obtained to an intravascular odorant and that one route by which such odorants reach the nose is the breath.


Prevalence of coal workers' pneumoconiosis in China: a systematic analysis of 2001-2011 studies.
Nowadays, coal workers' pneumoconiosis (CWP) is still believed to be the main occupational disease in China. However, information on the exact prevalence of the disease is not available. Therefore, the aims of our investigation were to provide the missing information in China by conducting a systematic evaluation of published data from 2001 to 2011 and to compare the prevalence of CWP with those in other countries. Published reports about the prevalence of CWP were searched from PudMed(English language databases), Foreign Medical Journal Full-Text Service Database (FMJS, English language databases), Chinese Journal Full-Text Database (CJFD, Chinese language databases), Chongqing VIP Chinese Science and Technology Journals Database (VIP, Chinese language databases), Chinese Biomedical Literature Database (CBM, Chinese language databases) and Chinese Medical Association Journals Database (CMAJ, Chinese language databases). The quality of identified reports was strictly evaluated using predetermined inclusion and exclusion criteria. Based on these criteria, 11 reports were selected. Then, the content of these reports were reviewed and the needed information was extracted. Meta-analysis was performed on the extracted data. The R2.15.1 software was applied for statistical analysis. The total populations from these reports were 173,646 and 10,821 for dust-exposed coal workers and patients with CWP, respectively. The pooled prevalence of CWP was 6.02% (95% CI: 3.43-9.26%) and the pooled rate of CWP patients combined with tuberculosis was 10.82% (95% CI: 8.26-13.66%). The prevalence was analyzed according to the geographic areas of the study, years of the investigation, duration of dust exposure, coal rank, stages of CWP, types of work and coal-mining categories, etc. Among them, the prevalence of CWP in locally owned mines (9.86%; 95% CI: 1.25-25.17%) was significantly higher than that of state-owned mines (4.83%; 95% CI: 2.35-8.13%) (P<0.05). Publication bias was assessed by the Egger's test which showed insignificant results (P>0.05). It was concluded that the prevalence of CWP were still high in China compared to UK (0.8%, during 1998-2000) and USA (3.2% in 2000s). In addition, the conditions in locally owned mines had caused more CWP than that of state-owned mines. Our data clearly show that regulatory agencies in China need to step up their effort in implementing more rigorous policies to protect coal miners, especially those in locally owned mines.


Effect of selenium on rat thioredoxin reductase activity: increase by supranutritional selenium and decrease by selenium deficiency.
Thioredoxin reductase is a newly identified selenocysteine-containing enzyme that catalyzes the NADPH-dependent reduction of the redox protein thioredoxin. Thioredoxin stimulates cell growth, is found in dividing normal cells, and is over-expressed in a number of human cancers. Redox activity is essential for the growth effects of thioredoxin; thus, thioredoxin reductase could be involved in regulating cell growth through its reduction of thioredoxin. In rats fed a selenium-deficient diet (<0.01 ppm) for up to 98 days, thioredoxin reductase activity was decreased, compared with that of rats fed a normal selenium diet (0.1 ppm), in lung, liver, and kidney, while thioredoxin reductase activity in the spleen and prostate was unaltered. Rats fed a high selenium diet (1.0 ppm) exhibited a 1.5-fold increase in kidney and a 2.0-fold increase in lung thioredoxin reductase activity that began to return to control values after 20 and 69 days, respectively. Liver showed a 2.1-fold increase in thioredoxin reductase activity at 20 days only. Thioredoxin reductase protein levels measured by western blotting using an antibody to human thioredoxin reductase were decreased in rats fed the selenium-deficient diet and did not increase in rats fed the high selenium diet. Rat thioredoxin reductase was shown to incorporate 75Selenium. Thus, in some tissues at least, the increase in thioredoxin reductase activity of rats fed a high selenium diet appears to be due to an increase in the specific activity of the enzyme, possibly caused by increased selenocysteine incorporation without an increase in thioredoxin reductase protein synthesis.


The efficacy of preanesthetic proton pump inhibitor treatment for patients on long-term H2 antagonist therapy.
We previously reported that H2-antagonist medication given for longer than 4 wk may produce complete tolerance to preanesthetic H2 antagonist therapy. In this study, we evaluated the efficacy of preanesthetic proton pump inhibitor (PPI; oral rabeprazol) use in patients receiving regular H2-antagonist (oral famotidine) therapy for more than 4 wk. Forty-eight patients with assumed complete tolerance to H2 antagonists undergoing elective surgery were recruited and randomly assigned to receive either a preanesthetic PPI (rabeprazol 20 mg; n = 24) or H2-antagonist (H2 group; roxatidine 75 mg; n = 24) at 9:00 pm on the day before surgery and 2 h before the induction of anesthesia. Volume of gastric contents and pH values were measured after the induction of anesthesia. Gastric pH value in the PPI group (5.38 +/- 2.42) was significantly higher than in the H2 group (3.27 +/- 1.98; P < 0.01). Gastric volume in the PPI group (8.6 +/- 1.5 mL) was significantly smaller than in the H2 group (15.4 +/- 2.8 mL; P < 0.05; cf. PPI). Fourteen patients in the H2 group were at risk of acid aspiration pneumonia (gastric pH <2.5 or volume >25 mL), whereas only four patients in the PPI group (P < 0.05) were at risk. These data suggest that in patients receiving H2-antagonist therapy for longer than 4 wk, prophylaxis for acid aspiration pneumonia should include preanesthetic PPI medication. We previously reported that more than 4 wk of administration of H2-antagonists may produce a full tolerance to preanesthetic H2-antagonists. The present study suggests that a proton pump inhibitor may be effective for prophylaxis of acid aspiration pneumonia in patients showing the full tolerance to H2 antagonists.


Anatomical localization of cortical beta rhythms in cat.
Beta electrocorticographic rhythms (40 Hz) develop during motionless focused attention in two distinct cortical foci in cats. A cytoarchitectonic study was performed to determine the precise location of these foci. Electrode tips recording beta rhythms were found: (i) in motor areas 4 gamma and 6a beta, in a band extending from the postcruciate cortex to the walls of the presylvian sulcus, crossing the frontal pole (anterior beta focus); (ii) in the posterior parietal associative area 5a, along the divisions of the ansate sulcus, extending to the mesial aspect of the hemispheres (posterior beta focus). The two foci are separated by areas 3, 2 and 1, where beta rhythms were never recorded. The fact that both these areas, containing giant pyramidal cells, develop a specific type of activity during immobility may have a functional meaning: area 5 may be involved in the cat as it is in the monkey in the control of motor behaviour.


Proteasome activities in the rectus abdominis muscle of young and older individuals.
Sarcopenia is one of the most striking effects of age, the causes and the pathogenic mechanisms being largely unknown. Unfortunately, there is limited information on the effect of aging on muscle protein breakdown in basal conditions. The present study aimed at investigating if skeletal muscle ubiquitn mRNA levels and proteasome activities vary with age in healthy individuals. Ub mRNA levels were measured by northern blot analysis whereas proteasome activities were determined by evaluating the cleavage of specific fluorogenic substrates in the rectus abdominis muscle of 14 healthy male individuals. Patients were divided in three groups according to the age: (1) 20-30 years (N = 3); (2) 31-64 years (N = 5); (3) > or = 65 years (N = 6). Quantitation of the ubiquitin mRNA levels (expressed in arbitrary units) (mean (SD) showed no differences among the three groups of age (20-30 years: 1352 +/- 441; 31-64 years: 1324 +/- 439; > or = 65 years: 884 +/- 400; P = 0.33). The correlation between age and muscle ubiquitin mRNA levels was not statistically significant (r = -0.4, P = 0.26). The three proteasome activities, chymotrypsin-like (CTL), trypsin-like (TL) and peptidyl-gutamyl-peptidase (PGP), expressed as nkatal x 10(-3)/mg protein, were similar in the three groups of patients stratified according to the age. There was no correlation between age with either CTL (r = 0.22, P = 0.4), PGP (r = 0.002, P = 0.9), and TL (r = 0.28, P = 0.33) activities. In conclusion, the present study shows that the skeletal muscle proteasome activities do not differ with age in healthy male individuals.


Achieving universal electrification of rural healthcare facilities in sub-Saharan Africa with decentralized renewable energy technologies.
A potential response to the COVID-19 pandemic in sub-Saharan Africa (SSA) with long-term benefits is to provide electricity for medical equipment in rural health centers and communities. This study identifies a large gap in the electrification of healthcare facilities in SSA, and it shows that decentralized photovoltaic systems can offer a clean, reliable, quick, and cost-effective solution. The cost of providing renewable electricity to each health facility by a stand-alone PV system is analyzed for a given location (incorporating operational costs). The upfront investment cost for providing electricity with PV to >50,000 facilities (mostly primary health posts) currently without electricity is estimated at EUR 484 million. Analysis of the accessibility and population distribution shows that 281 million people could reduce their travel time to healthcare facilities (by an average of 50 min) if all facilities were electrified.


Post-coital gross hematuria: an unusual presentation of benign prostatic hyperplasia.
To describe an unusual symptom of benign prostatic hyperplasia (BPH). A patient presented to our urology clinic having experienced post-coital gross hematuria for 2 years. He had not experienced lower urinary tract symptoms (LUTS). A series of examinations were performed to determine the source of bleeding. The prostate was defined as the active bleeding source responsible for the patient's post-coital hematuria. Endoscopic fulguration did not alleviate the symptom. The use of dutasteride, a dual inhibitor of 5alpha-reductase, solved the problem. This study reports for the first time that post-coital gross hematuria is one of the clinical presentations of BPH, which can be successfully treated with 5alpha-reductase inhibitor.


Lower extremity infections by vibrio vulnificus.
Vibrio vulnificus is a Gram-negative pathogen which is found in seawater and shellfish during warm months and can cause local infections in healthy individuals or septicemia in patients with chronic liver disease. Clinical and laboratory records of four complicated cases are presented, with a 4.2 mean year follow-up. Three patients underwent urgent leg amputation because of of irreversible necrotic changes with septic complications and failure of incisional drainage to control the infection. Another one patient underwent only excision of necrotic soft tissue but he developed calcaneus osteomyelitis after three years of the initial fish bone injury. Clinicians must maintain a high index of suspicion, especially in regions endemic for vibrio necrotising fasciitis and antibiotic prophylaxis must be given to swimmers before or during bathing.


"Satellite" haemodialysis.
Thirty of the 39 patients treated at the Blacktown Dialysis Centre, the first "satellite" dialysis centre in the greater metropolitan Sydney, had been referred from four Sydney renal units for long-term dialysis therapy. The move save approximately 150 kilometres in travelling and eight hours time each week for each of these patients. The cost of running the unit was approximately $10,000 per patient per year in the first year--no greater than that of home dialysis, and less than that of dialysis in a teaching hospital. The advantages of establishing satellite dialysis centre, the method of operation, and the results of the first year of operation of the Blacktown Dialysis Centre are described.


AlGaN/GaN Metal-Oxide-Semiconductor High-Electron-Mobility Transistor with Polarized P(VDF-TrFE) Ferroelectric Polymer Gating.
Effect of a polarized P(VDF-TrFE) ferroelectric polymer gating on AlGaN/GaN metal-oxide-semiconductor high-electron-mobility transistors (MOS-HEMTs) was investigated. The P(VDF-TrFE) gating in the source/drain access regions of AlGaN/GaN MOS-HEMTs was positively polarized (i.e., partially positively charged hydrogen were aligned to the AlGaN surface) by an applied electric field, resulting in a shift-down of the conduction band at the AlGaN/GaN interface. This increases the 2-dimensional electron gas (2-DEG) density in the source/drain access region of the AlGaN/GaN heterostructure, and thereby reduces the source/drain series resistance. Detailed material characterization of the P(VDF-TrFE) ferroelectric film was also carried out using the atomic force microscopy (AFM), X-ray Diffraction (XRD), and ferroelectric hysteresis loop measurement.


The influence of aging on the fracture load of milled monolithic crowns.
This in-vitro study was conducted to assess the effect of aging on the fracture load of molar crowns fabricated with monolithic CAD/CAM materials. The crown restorations were produced from Cerasmart, Vita Enamic, and IPS e.max CAD blocks. Aging was applied to the 10 samples each of monolithic CAD/CAM materials (n = 10). Dual-axis chewing simulator (50 N, 1.1 Hz, lateral movement: 1 mm, mouth opening: 2 mm, 1,200,000 cycles) and thermocycling (± 5-55 °C, 6000 cycles) were applied as an aging procedure. 10 samples each of monolithic CAD/CAM materials without aging (n = 10) were considered the control group. 6 tested groups were obtained. Then, all samples were evaluated in a universal testing machine to determine the fracture loading values'. There was not a statistically significant difference between the fracture load values before and after aging for all samples of Cerasmart, Vita Enamic, and IPS e.max CAD (p > 0.005). In a comparison of the monolithic materials together, a statistically significant difference was found between the fracture load values of IPS e.max CAD and Vita Enamic crowns before aging (p = 0.02). Also, Vita Enamic crowns (1978,71 ± 364,05 N) were found different from the IPS e.max CAD (p = 0.005) and Cerasmart crowns (p = 0.041) after aging. Dynamic aging with 1.200.000 cycles was found to have no effect to fracture loading on milled Cerasmart, Vita Enamic, and IPS e.max CAD monolithic crowns.


Promotion of cystine uptake and its utilization for glutathione biosynthesis induced by cysteamine and N-acetylcysteine.
Chinese hamster ovary (CHO) cells obtain a high capacity to utilize cystine from the growth medium by exposure to cysteamine (2-mercaptoethylamine, MEA) or N-acetylcysteine (NAC). For uptake studies a modified McCoy's 5A medium supplemented with 0.1 mM [35S]cystine was used. The uptake of cystine was dependent on the time of exposure (0-60 min) and the concentrations of MEA or NAC (0-8 mM). At high concentrations of MEA or NAC, the uptake of cystine became saturated. Half-maximal uptake of cysteine was observed at concentrations of 0.12 mM MEA and 0.66 mM NAC, respectively. Increase in temperature (37-44 degrees) or pH (6.0-8.0) during MEA or NAC exposure further increased the cystine uptake. The increased uptake of cystine was not affected in the presence of glutamate or homocysteate which both inhibited the cystine uptake of control cells. Determination of both reduced (GSH) and oxidized (GSSG) cellular glutathione showed a twofold increase in MEA- or NAC-treated CHO cells. DL-buthionine-S,R-sulfoximine (BSO), an inhibitor of GSH biosynthesis completely blocked the promotion of cystine uptake by MEA and NAC. By further analysis using reversed-phase HPLC of cell extracts, more than 90% of the [35S] radioactive cystine taken up by the cells could be recovered within the pool of GSH. The results demonstrate that exposure of CHO cells with MEA and NAC leads to a promoted uptake of cystine from the culture medium and its rapid utilization for cellular GSH biosynthesis.


TP53-mediated miR-2861 promotes osteogenic differentiation of BMSCs by targeting Smad7.
Bone defect seriously affects the quality of life. Meanwhile, osteogenic differentiation in BMSCs could regulate the progression of bone defect. Transcription factors are known to regulate the osteogenic differentiation in BMSCs. The study aimed to investigate the detailed mechanism by which TP53 regulates the osteogenic differentiation. To study bone defect in vitro, BMSCs were isolated from spinal cord injury rats. CCK-8 assay was applied to test the cell viability. The mineralized nodules in BMSCs was tested by alizarin red staining. Meanwhile, TUNEL staining and flow cytometry were performed to test the cell apoptosis. mRNA expression was tested by qRT-PCR. Starbase and dual-luciferase reporter assay were used to predict the downstream mRNA of miR-2861. Moreover, western blot was applied to detect the protein expressions (TP53 and Smad7). BMSCs were successfully isolated from rats. The expressions of miR-2861 were significantly upregulated in osteogenic medium, compared with growth medium. MiR-2861 inhibitor significantly decreased the levels of OCN, ALP, BSP, and Runx2 in BMSCs. In addition, miR-2861 inhibitor notably inhibited the mineralized nodules, viability, and induced the apoptosis of BMSCs. Smad7 was identified to be the downstream target of miR-2861, and knockdown of Smad7 notably reversed miR-2861 inhibitor-induced inhibition of osteogenic differentiation and promotion of apoptosis in BMSCs. Moreover, miR-2861 was transcriptionally regulated by TP53 in BMSCs. TP53-meidiated miR-2861 promotes osteogenic differentiation of BMSCs by targeting Smad7. Thereby, our research might provide new methods for bone defect treatment.


Oxymatrine Inhibits Bocavirus MVC Replication, Reduces Viral Gene Expression and Decreases Apoptosis Induced by Viral Infection.
Oxymatrine (OMT), as the main active component of Sophoraflavescens, exhibits a variety of pharmacological properties, including anti-oxidative, anti-inflammatory, anti-tumor, and anti-viral activities, and currently is extensively employed to treat viral hepatitis; however, its effects on parvovirus infection have yet to be reported. In the present study, we investigated the effects of OMT on cell viability, virus DNA replication, viral gene expression, cell cycle, and apoptosis in Walter Reed canine cells/3873D infected with minute virus of canines (MVC). OMT, at concentrations below 4 mmol/L(no cellular toxicity), was found to inhibit MVC DNA replication and reduce viral gene expression at both mRNA and protein levels, which was associated with the inhibition of cell cycle S-phase arrest in early-stage of MVC infection. Furthermore, OMT significantly increased cell viability, decreased MVC-infected cell apoptosis, and reduced the expression of activated caspase 3. Our results suggest that OMT has potential application in combating parvovirus infection.


A rare anatomical variation of the Berrettini anastomosis and third common palmar digital branch of the median nerve.
Variations in the origin and distribution of Berrettini anastomosis between the digital branches of the ulnar and median nerves exist and are well described in the literature. During regular dissections by medical students, we encountered a rare variation in the left hand of an approximately 50-year-old male cadaver. Berrettini anastomosis connecting the third common palmar digital branch of the median nerve with the fourth common palmar and proper palmar digital branches of the ulnar nerve presented a plexiform nature. This communicating branch and the third common palmar digital branch of the median nerve were perforated by the superficial palmar arch. Further, the superficial palmar arch was incomplete, and it was solely formed by the superficial branch of the ulnar artery. The unusual relationship of Berrettini anastomosis with the superficial palmar arch is very rare, and knowledge about such a variation is important when performing carpal tunnel release, flexor tendon surgery, and Dupuytren's fasciectomy and when dealing with arterial repairs and vascular graft applications in the hand.


Cross-reactive cellular, but not humoral, immunity is detected between OC43 and SARS-CoV-2 NPs in people not infected with SARS-CoV-2: Possible role of cTFH cells.
Multiple questions about SARS-CoV-2 humoral and cellular immunity remain unanswered. One key question is whether preexisting memory T or B cells, specific for related coronaviruses in SARS-CoV-2-unexposed individuals, can recognize and suppress COVID-19, but this issue remains unclear. Here, we demonstrate that antibody responses to SARS-CoV-2 antigens are restricted to serum samples from COVID-19 convalescent individuals. In contrast, cross-reactive T cell proliferation and IFN-γ production responses were detected in PBMCs of around 30% of donor samples collected prepandemic, although we found that these prepandemic T cell responses only elicited weak cTFH activation upon stimulation with either HCoV-OC43 or SARS-CoV-2 NP protein. Overall, these observations confirm that T cell cross-reactive with SARS-CoV-2 antigens are present in unexposed people, but suggest that the T cell response to HCoV-OC43 could be deficient in some important aspects, like TFH expansion, that might compromise the generation of cross-reactive TFH cells and antibodies. Understanding these differences in cellular responses may be of critical importance to advance in our knowledge of immunity against SARS-CoV-2.


Machine learning-based muscle mass estimation using gait parameters in community-dwelling older adults: A cross-sectional study.
Loss of skeletal muscle mass is associated with numerous factors such as metabolic diseases, lack of independence, and mortality in older adults. Therefore, developing simple, safe, and reliable tools for assessing skeletal muscle mass is needed. Some studies recently reported that the risks of the incidence of geriatric conditions could be estimated by analyzing older adults' gait; however, no studies have assessed the association between gait parameters and skeletal muscle loss in older adults. In this study, we applied machine learning approach to the gait parameters derived from three-dimensional skeletal models to distinguish older adults' low skeletal muscle mass. We also identified the most important gait parameters for detecting low muscle mass. Sixty-six community-dwelling older adults were recruited. Thirty-two gait parameters were created using a three-dimensional skeletal model involving 10-meter comfortable walking. After skeletal muscle mass measurement using a bioimpedance analyzer, low muscle mass was judged in accordance with the guideline of the Asia Working Group for Sarcopenia. The eXtreme gradient boosting (XGBoost) model was applied to discriminate between low and high skeletal muscle mass. Eleven subjects had a low muscle mass. The c-statistics, sensitivity, specificity, precision of the final model were 0.7, 59.5%, 81.4%, and 70.5%, respectively. The top three dominant gait parameters were, in order of strongest effect, stride length, hip dynamic range of motion, and trunk rotation variability. Machine learning-based gait analysis is a useful approach to determine the low skeletal muscle mass of community-dwelling older adults.


Rapid homeostatic modulation of transsynaptic nanocolumn rings.
Robust neural information transfer relies on a delicate molecular nano-architecture of chemical synapses. Neurotransmitter release is controlled by a specific arrangement of proteins within presynaptic active zones. How the specific presynaptic molecular architecture relates to postsynaptic organization and how synaptic nano-architecture is transsynaptically regulated to enable stable synaptic transmission remain enigmatic. Using time-gated stimulated emission-depletion microscopy at the Drosophila neuromuscular junction, we found that presynaptic nanorings formed by the active-zone scaffold Bruchpilot (Brp) align with postsynaptic glutamate receptor (GluR) rings. Individual rings harbor approximately four transsynaptically aligned Brp-GluR nanocolumns. Similar nanocolumn rings are formed by the presynaptic protein Unc13A and GluRs. Intriguingly, acute GluR impairment triggers transsynaptic nanocolumn formation on the minute timescale during homeostatic plasticity. We reveal distinct phases of structural transsynaptic homeostatic plasticity, with postsynaptic GluR reorganization preceding presynaptic Brp modulation. Finally, homeostatic control of transsynaptic nano-architecture and neurotransmitter release requires the auxiliary GluR subunit Neto. Thus, transsynaptic nanocolumn rings provide a substrate for rapid homeostatic stabilization of synaptic efficacy.


[Action of lysosomotropic modulators on the thyroid cells of rats].
Hydrocortisone, ammonium chloride, pepstatin and contrykal have been studied for their effect on incubated and cultured fragments of rat thyroid gland. It is found that the radioactive iodine uptake by thyroid gland cells is inhibited by hydrocortisone, ammonium chloride and pepstatin. Pepstatin induces formation of vacuoles with nonhydrolyzed thyroglobulin in thyrocytes.


The evolution of reproductive modes and life cycles in amphibians.
Amphibians have undergone important evolutionary transitions in reproductive modes and life-cycles. We compare large-scale macroevolutionary patterns in these transitions across the three major amphibian clades: frogs, salamanders, and caecilians. We analyse matching reproductive and phylogenetic data for 4025 species. We find that having aquatic larvae is ancestral for all three groups and is retained by many extant species (33-44%). The most frequent transitions in each group are to relatively uncommon states: live-bearing in caecilians, paedomorphosis in salamanders, and semi-terrestriality in frogs. All three groups show transitions to more terrestrial reproductive modes, but only in caecilians have these evolved sequentially from most-to-least aquatic. Diversification rates are largely independent of reproductive modes. However, in salamanders direct development accelerates diversification whereas paedomorphosis decreases it. Overall, we find a widespread retention of ancestral modes, decoupling of trait transition rates from patterns of species richness, and the general independence of reproductive modes and diversification.


(2E)-1-[5-Methyl-1-(4-methyl-phen-yl)-1H-1,2,3-triazol-4-yl]-3-[4-(piperidin-1-yl)phen-yl]prop-2-en-1-one.
Two independent mol-ecules comprise the asymmetric unit of the title compound, C24H26N4O. The major difference between them is found in the relative orientation of the triazole-bound p-tolyl group which have the opposite sense of twist [N-N-C-C torsion angles = 55.8 (3) and -49.8 (3)°]. The chalcone residue is almost coplanar with the triazole ring [N-C-C-O and C-C-C-C torsion angles = -178.9 (2) and -178.5 (2)°, respectively; cf. 177.9 (3) and 168.5 (3)°, respectively, in the second mol-ecule]. The conformation about each C=C double bond is E and in each case the triazole methyl group is syn to the carbonyl O atom. In the crystal, mol-ecules aggregate into layers parallel to (-113). The first independent mol-ecule self-associates into a layer via C-H⋯O and C-H⋯π inter-actions. By contrast, layers comprising the second independent mol-ecule do not feature specific inter-actions between mol-ecules. The global crystal packing comprises alternating layers.


Intracranial fibromuscular dysplasia and stroke in children.
Fibromuscular dysplasia (FMD) is an arterial lesion of unknown origin which may sometimes affect intracranial arteries. In recent years a few rare cases, mostly involving younger people, have been described. The present case concerns a child of 8 years in whom the finding of hemiplegia led to a diagnosis of intracranial fibrodysplasia which was proven by arteriography and biopsy. This arterial lesion is described within the context of stroke in children.


Temporary or removable directing groups enable activation of unstrained C-C bonds.
Carbon-carbon (C-C) bonds constitute basic skeletons in most organic molecules. One can imagine that selective manipulation of C-C bonds would provide a direct approach to edit or alter molecular scaffolds but has been an ongoing challenge. Due to the kinetic inertness of C-C bonds, the common strategies of activating these bonds by transition metals rely on either the use of highly strained substrates or the assistance of a permanent directing group (DG), in which strain relief or formation of stable metallocycles becomes the driving force. To allow more common and less strained compounds utilized as substrates for C-C activation, the use of temporary and removable DGs has emerged as an attractive strategy in the past two decades. A variety of C-C bonds in unstrained or less strained organic molecules now can be converted to more reactive metal-carbon bonds, and further downstream transformations have led to diverse synthetic methods. This review highlights the development of catalytic approaches that can activate unstrained C-C bonds enabled by temporary or removable DGs. The content is mainly divided based on the nature of the DGs: temporary and removable. Applications of these methods in syntheses of natural products or bioactive molecules are also discussed.


In vitro regulation of neuronal morphogenesis and polarity by astrocyte-derived factors.
Mesencephalic neurons were cultured from 2 to 5 days in mesencephalic (CM Gmes) or striatal (CM Gstr) astrocyte conditioned media or in the soluble (S100) and insoluble (P100) fractions prepared from these media by ultracentrifugation. CM Gmes as well as all soluble fractions induced dendritic and axonal elongation, whereas CM Gstr and the insoluble fractions promoted axonal growth only. The study of the shape of the neuronal cell bodies and the measurement of their adhesion to the substratum revealed that axons elongated under low adhesion conditions, but that dendrite growth was highly dependent upon adhesion and spreading of the neuronal soma. This different dependency of axonal and dendritic elongation upon spreading is explained by a model in which we consider the respective viscosities of axons and dendrites. From these observations and speculations we propose that axons and dendrites have different modes of elongation and that the primary effect of the astrocyte-derived factors capable of regulating neuronal polarity is to modify the adhesion of the neurons to their culture substratum.


Insensitivity of paediatric HIV-1 subtype C viruses to broadly neutralising monoclonal antibodies raised against subtype B.
A Phase I clinical trial has been proposed that uses neutralising monoclonal antibodies (MAbs) as passive immunoprophylaxis to prevent mother-to-child transmission of HIV-1 in South Africa. To assess the suitability of such an approach, we determined the sensitivity of paediatric HIV-1 subtype C viruses to the broadly neutralising MAbs IgG1b12, 2G12, 2F5, and 4E10. The gp160 envelope genes from seven children with HIV-1 subtype C infection were cloned and used to construct Env-pseudotyped viruses that were tested in a single-cycle neutralisation assay. The epitopes defining three of these MAbs were determined from sequence analysis of the envelope genes. None of the seven HIV-1 subtype C pseudovirions was sensitive to 2G12 or 2F5, which correlated with the absence of crucial N-linked glycans that define the 2G12 epitope and substitutions of residues integral to the 2F5 epitope. Four viruses were sensitive to IgG1b12, and all seven viruses were sensitive to 4E10. Only 4E10 showed significant activity against HIV-1 subtype C isolates, while 2G12 and 2F5 MAbs were ineffective and IgG1b12 was partly effective. It is therefore recommended that 2G12 and 2F5 MAbs not be used for passive immunization experiments in southern Africa and other regions where HIV-1 subtype C viruses predominate.


Assessment of stratified inhomogeneity within distal alveolar space with respect to oxygen uptake.
Investigations were made as to whether or not there is a limitation of oxygen transport by stratified inhomogeneity in distal alveolar gas. Experiments were performed on 2 subjects. Single breath manoeuvres were carried out with similar phases of inspiration and expiration but varying breath-hold times. The inspiratory gas contained a small amount of oxygen labeled carbon dioxide, C18O2. End-expiratory gas was analysed on its residual C18O2 partial pressure by mass spectrometry. For evaluating a stratificational conductance, compartment model analysis was applied on the breath-hold data. Stratificational conductance has been found to be higher than 553 ml.mmHg-1. min-1. When transferred to oxygen transport, this means that stratificational conductance is more than 10 times higher than oxygen diffusing capacity. It can be concluded that (i) stratified inhomogeneity in distal alveolar space does not exhibit a limiting factor of oxygen uptake in lungs, (ii) a contribution of stratificational effects to sloping alveolar plateau is expected to be of minor importance.


Peeking into the sleeping brain: Using in vivo imaging in rodents to understand the relationship between sleep and cognition.
Sleep is well known to benefit cognitive function. In particular, sleep has been shown to enhance learning and memory in both humans and animals. While the underlying mechanisms are not fully understood, it has been suggested that brain activity during sleep modulates neuronal communication through synaptic plasticity. These insights were mostly gained using electrophysiology to monitor ongoing large scale and single cell activity. While these efforts were instrumental in the characterisation of important network and cellular activity during sleep, several aspects underlying cognition are beyond the reach of this technology. Neuronal circuit activity is dynamically regulated via the precise interaction of different neuronal and non-neuronal cell types and relies on subtle modifications of individual synapses. In contrast to established electrophysiological approaches, recent advances in imaging techniques, mainly applied in rodents, provide unprecedented access to these aspects of neuronal function in vivo. In this review, we describe various techniques currently available for in vivo brain imaging, from single synapse to large scale network activity. We discuss the advantages and limitations of these approaches in the context of sleep research and describe which particular aspects related to cognition lend themselves to this kind of investigation. Finally, we review the few studies that used in vivo imaging in rodents to investigate the sleeping brain and discuss how the results have already significantly contributed to a better understanding on the complex relation between sleep and plasticity across development and adulthood.


Human acute toxicity prediction of the first 50 MEIC chemicals by a battery of ecotoxicological tests and physicochemical properties.
Five acute bioassays consisting of three cyst-based tests (with Artemia salina, Streptocephalus proboscideus and Brachionus calyciflorus), the Daphnia magna test and the bacterial luminescence inhibition test (Photobacterium phosphoreum) are used to determine the acute toxicity of the 50 priority chemicals of the Multicentre Evaluation of In Vitro Cytotoxicity (MEIC) programme. These tests and five physiocochemical properties (n-octanol-water partition coefficient, molecular weight, melting point, boiling point and density) are evaluated either singly or in combination to predict human acute toxicity. Acute toxicity in human is expressed both as oral lethal doses (HLD) and as lethal concentrations (HLC) derived from clinical cases. A comparison has also been made between the individual tests and the conventional rodent tests, as well as between rodent tests and the batteries resulting from partial least squares (PLS), with regard to their predictive power for acute toxicity in humans. Results from univariate regression show that the predictive potential of bioassays (both ecotoxicological and rodent tests) is generally superior to that of individual physicochemical properties for HLD. For HLC prediction, however, no consistent trend could be discerned that indicated whether bioassays are better estimators than physicochemical parameters. Generally, the batteries resulting from PLS regression seem to be more predictive than rodent tests or any of the individual tests. Prediction of HLD appears to be dependent on the phylogeny of the test species: cructaceans, for example, appear to be more important components in the test battery than rotifers and bacteria. For HLC prediction, one anostracan and one cladoceran crustacean are considered to be important. When considering both ecotoxicological tests and physicochemical properties, the battery based on the molecular weight and the cladoceran crustacean predicts HLC substantially better than any other combination.


Trabecular and retrocorneal proliferation of melanocytes and secondary glaucoma.
A 59-year-old woman with no evidence of glaucoma developed secondary open-angle glaucoma after an intracapsular cataract extraction complicated by vitreous and iris incarceration. Histopathologic and scanning and electron microscopic studies of the enucleated eye 22 years later revealed extensive proliferation of iris melanocytes across the trabecular meshwork and posterior surface of the cornea. Proliferation of iris stromal melanocytes over the trabecular meshwork may have caused secondary open-angle glaucoma.


Increasing potassium intake to prevent kidney damage: a new population strategy?
Reducing dietary sodium consumption and increasing potassium intake are effective approaches in reducing the prevalence of cardiovascular diseases. Whether this is also true for chronic kidney disease (CKD) is still debated. Elfassy et al. have examined associations between urinary sodium and potassium excretion and the incidence of CKD in young, 30-year-old subjects followed for 20 years. Although they failed to find an association between sodium intake and CKD incidence, there was an inverse association between high potassium intake and the development of albuminuria.


Analysis of survival in 300 high-risk patients up to 2.5 years after transapical aortic valve implantation.
Midterm results after transapical aortic valve implantation are still unknown in a large group of patients. We report our institutional experience in 300 high-risk patients. Since April 2008, transapical aortic valve implantation was performed in 300 patients (mean age, 80 ± 8 years). The mean logistic EuroSCORE (European System for Cardiac Operative Risk Evaluation) was 39% ± 19% and the mean Society of Thoracic Surgeons (STS) score was 19% ± 16%. Eighteen patients were in cardiogenic shock preoperatively. Follow-up was up to 31 months with a total of 3,500 months of follow-up. Technical success of the procedure was 99.7% (299 of 300 patients). The 30-day mortality rate in all patients without cardiogenic shock was 3.9%. The overall 30-day mortality for the whole group of 300 patients was 4.7%. The mortality of the last 100 patients dropped to 2.0%. The cumulative survival was 83% at 1 year, 76% at 1.5 years, and 65% at 2 years and beyond. In patients with lower risk scores, cumulative survival reached 78% at 2 years and beyond. The outcome of transapical aortic valve implantation in very high-risk patients was very favorable not only early after the procedure but also later on. Preoperative risk scores were not indicators for early mortality but were for later mortality. Survival was mainly influenced by noncardiac (renal, pulmonary, and vascular) comorbidities as well as by signs of advanced cardiac failure.


Effect of lysozyme on ionic forms of spores of Clostridium perfringens type A.
H spores of Clostridium perfringens type A (two strains) were more sensitive to germination by lysozyme than native spores. Resistance to lysozyme of H spores was restored by calcium loading.


Functional characterization of the Candida albicans CRZ1 gene encoding a calcineurin-regulated transcription factor.
Calcineurin is a phosphoprotein phosphatase devoted to the transduction of Ca(2+)-signals in eukaryotes. In the human pathogen Candida albicans, calcineurin function is required for cell morphogenesis, azole tolerance, membrane stress responses, survival in serum and virulence in mice. Molecular mechanisms as well as targets downstream C. albicans calcineurin involved in all these processes are still uncharacterized. Here we report the characterization of a C. albicans Crz1 calcineurin-regulated transcription factor using a Saccharomyces cerevisiae crz1Delta defective strain as heterologous host. CaCrz1p fulfils the function of its S. cerevisiae homolog protein to control the expression of several Ca(2+)/calcineurin-responsive genes acting on the CDRE sequence in promoters. In the model yeast, CaCrz1p activity and localization are regulated by calcineurin. Deletion of CRZ1 gene renders C. albicans hypersensitive to alkaline cations and membrane stress conditions, including that elicited by SDS and antifungal azoles. Our findings indicate that CaCrz1p is member of a calcium-regulated pathway required for the maintenance of membrane integrity.


Venice as a paradigm of coastal flooding under multiple compound drivers.
Full comprehension of the dynamics of hazardous sea levels is indispensable for assessing and managing coastal flood risk, especially under a changing climate. The 12 November 2019 devastating flood in the historical city of Venice (Italy) stimulated new investigations of the coastal flooding problem from different perspectives and timescales. Here Venice is used as a paradigm for coastal flood risk, due to the complexity of its flood dynamics facing those of many other locations worldwide. Spectral decomposition was applied to the long-term 1872-2019 sea-level time series in order to investigate the relative importance of different drivers of coastal flooding and their temporal changes. Moreover, a multivariate analysis via copulas provided statistical models indispensable for correctly understanding and reproducing the interactions between the variables at play. While storm surges are the main drivers of the most extreme events, tides and long-term forcings associated with planetary atmospheric waves and seasonal to inter-annual oscillations are predominant in determining recurrent nuisance flooding. The non-stationary analysis revealed a positive trend in the intensity of the non-tidal contribution to extreme sea levels in the last three decades, which, along with relative sea-level rise, contributed to an increase in the frequency of floods in Venice.


Treatment of scars and keloids with a cream containing silicone oil.
The clinical effect of silicone cream containing 20% of silicone oil was tested on 47 patients with hypertrophic scars and keloids. A silicone cream/occlusive dressing technique, quite similar in manner to silicone gel treatment, resulted in a remarkable improvement of scars and keloids in 9 of 11 cases (82%) whereas the simple application of the cream onto the scars and keloids of 36 cases resulted in only mild improvement in 8 (22%). Using the chi-square test, a statistically significant difference was seen between these two treatments (p less than 0.01). From these findings, we suggest that occlusion and hydration are the principal modes of action of the silicone gel sheet method and our silicone cream/occlusive dressing technique.


Oncocytoma of the eyelid: an aggressive benign tumor.
The authors report the case of an 83-year-old patient with a benign oncocytoma of the inferior eyelid. INTERVENTIONal case report. Treatment consisted of a large orbital exenteration followed by reconstruction with a pedicled temporalis muscle flap. Histologic evaluation and clinical follow-up were measured. After a year of follow-up, there was no sign of local recurrence. Oncocytomas, even if benign, must be considered as very aggressive tumors and treated accordingly.


Resistance of 3'-phosphoglycolate DNA ends to digestion by mammalian DNase III.
An essential step in the repair of free radical-mediated DNA strand breaks is the removal of sugar fragments such as phosphoglycolate from the 3' termini. While the abasic endonuclease Ape1 can remove phosphoglycolate from single-strand breaks in double-stranded DNA, an enzyme capable of removing it from 3' overhangs of double-strand breaks has yet to be identified. We therefore tested DNase III, the predominant 3' --> 5' exonuclease in mammalian cell extracts, for possible 3'-phosphoglycolate-removing activity. However, all 3'-phosphoglycolate substrates, as well as a 3'-phosphate substrate, were resistant to DNase III under conditions in which the analogous 3'-hydroxyl substrates were extensively degraded. The DNA end-binding protein Ku (an equimolar mixture of Ku70, now known as G22P1, and Ku86, now known as XRCC5) did not alter the resistance of the 3'-phosphoglycolate substrates, but the protein modulated the susceptibility of 3'-hydroxyl substrates, allowing DNase III to remove a 3' overhang but inhibiting digestion of the double-stranded portion of the substrate.


Chylous ascites in sibs from a consanguineous marriage.
We report a brother and sister with congenital chylous ascites. Parents were first cousins, and autosomal recessive inheritance may be the cause of the condition in these sibs.


Functions of antioxidant enzyme activities on the membrane bound total sialic acid and lipid peroxidation level in F. equiseti and F. acuminatum.
The variations of membrane bound total sialic acid (TSA) and lipid peroxidation level dependent on the antioxidant enzyme activities such as Superoxide Dismutase (SOD), Catalase (CAT), Glutathione peroxidase (GSH-Px) have been studied in yeast extract supplemented medium. The maximum SOD and CAT activities of F. equiseti tended to increase with raises of yeast extract concentration up to 25 g/L where they were determined to be 78.6 +/- 0.96 and 312.7 +/- 5.6 IU/mg. On the other hand, SOD and CAT activities in F. acuminatum significantly increased with the rise of yeast extract concentration up to 10 g/L (p < 0.01) and maximum activities were observed at this concentration as 36.3 +/- 0.54 and 115.3 +/- 2.19 IU/mg on the 12th day incubation. Other H2O2 scavenger enzyme, GSH-Px activities of F. equiseti and F. acuminatum were reached the maximum at 5 and 25g/L yeast extract and determined as 5.06 +/- 0.04 and 4.74 +/- 0.09 IU/mg, respectively. TSA level showed positive correlation with SOD and CAT activities while LPO levels variations negatively correlated. The results may indicate that these antioxidant enzymes also appeared to be involved in protecting membrane bound sialic acids as well as membrane lipid of the fungus from exogenous reactive oxygen species.


The mitochondrial transport protein superfamily.
The ADP/ATP, phosphate, and oxoglutarate/malate carrier proteins found in the inner membranes of mitochondria, and the uncoupling protein from mitochondria in mammalian brown adipose tissue, belong to the same protein superfamily. Established members of this superfamily have polypeptide chains approximately 300 amino acids long that consist of three tandem related sequences of about 100 amino acids. The tandem repeats from the different proteins are interrelated, and probably have similar secondary structures. The common features of this superfamily are also present in nine proteins of unknown functions characterized by DNA sequencing in various species, most notably in Caenorhabditis elegans and Saccharomyces cerevisiae. The high level expression in Escherichia coli of the bovine oxoglutarate/malate carrier, and the reconstitution of active carrier from the expressed protein, offers encouragement that the identity of superfamily members of known sequence but unknown function may be uncovered by a similar route.


Sepsis-induced Autoimmune Hemolytic Anemia: A Case Report.
Sepsis commonly brings patients to the emergency department (ED). Patient outcomes can vary widely. In some cases, rare complications of sepsis such as autoimmune hemolytic anemia can occur. A 68-year-old female presented with sepsis secondary to infected nephrolithiasis. The patient had signs and symptoms consistent with hemolysis upon arrival to the ED. Her hemolysis progressively worsened over a two-day period leading to a diagnosis of warm autoimmune hemolytic anemia. She responded well to treatment; however, her condition began to worsen due to a new infection caused by perforated colonic diverticula. The patient ultimately expired from complications of her perforated colonic diverticula. It is crucial that emergency physicians understand the risk factors, symptoms, pathophysiology, and treatment of this rare complication of sepsis so that favorable patient outcomes can be achieved.


A novel stimulus artifact removal technique for high-rate electrical stimulation.
Electrical stimulus artifact corrupting electrophysiological recordings often makes the subsequent analysis of the underlying neural response difficult. This is particularly evident when investigating short-latency neural activity in response to high-rate electrical stimulation. We developed and evaluated an off-line technique for the removal of stimulus artifact from electrophysiological recordings. Pulsatile electrical stimulation was presented at rates of up to 5000 pulses/s during extracellular recordings of guinea pig auditory nerve fibers. Stimulus artifact was removed by replacing the sample points at each stimulus artifact event with values interpolated along a straight line, computed from neighbouring sample points. This technique required only that artifact events be identifiable and that the artifact duration remained less than both the inter-stimulus interval and the time course of the action potential. We have demonstrated that this computationally efficient sample-and-interpolate technique removes the stimulus artifact with minimal distortion of the action potential waveform. We suggest that this technique may have potential applications in a range of electrophysiological recording systems.


Doxorubicin Cytotoxicity in Differentiated H9c2 Cardiomyocytes: Evidence for Acute Mitochondrial Superoxide Generation.
Although a mitochondrial redox-cycling superoxide-generating mechanism for the cardiotoxicity of doxorubicin was suggested from experiments with isolated mitochondria, its occurrence and contribution to cytotoxicity in intact cardiomyocytes is not fully established. Therefore, we determined the immediate and delayed effects of doxorubicin on the generation of reactive oxygen species (ROS) and cytotoxicity in differentiated H9c2 cardiomyocytes. Although relatively short incubations (3 or 6 h) with 1 or 5 µM doxorubicin did not acutely decrease cell survival, exposure to 5 µM doxorubicin for 3 h was sufficient to cause a significant delayed decrease in cell survival after an additional 24 h without doxorubicin. Mitochondrial superoxide generation was observed to increase within 30 min of incubation with 5 µM doxorubicin. Increased intracellular ROS generation, decreased mitochondrial metabolic activity, and decreased mitochondrial membrane potential (MMP) were observed after more extended periods (6-12 h). Overall, these observations support that the toxicity of doxorubicin to differentiated cardiomyocytes involves acute mitochondrial superoxide generation with subsequent intracellular ROS generation, mitochondrial dysfunction, and cell death.


Relation between age, education, and time to respond to questions in a computer-based medical interview.
The time required for 458 women volunteers to respond to questions in a computer-based medical interview was related both to their age and to their formal education. When the analysis was restricted to the 220 women with a college degree, older women responded more slowly than their younger counterparts, and when the analysis was restricted to the 265 women between 18 and 30 years of age, women with less formal education took longer to respond. By contrast, the time required for the volunteers to record their responses was related only to age.


Phosphatidylserine metabolism modification precedes manganese-induced apoptosis and phosphatidylserine exposure in PC12 cells.
Long-term exposure to high manganese (Mn) levels can lead to Parkinson-like neurological disorders. Molecular mechanisms underlying Mn cytotoxicity have been not defined. It is known that Mn induces apoptosis in PC12 cells and that this involves the activation of some signal transduction pathways. Although the role of phospholipids in apoptosis and signal transduction is well-known, the membrane phospholipid component in Mn-related damage has not yet been investigated. Phosphatidylserine (PS) facilitates protein translocation from cytosol to plasma membrane and PS exposure on the cell surface allows macrophage recognition of apoptotic cells. This study investigates the effects of MnCl2 on PS metabolism in PC12 cells, relating them to those on cell apoptosis. Apoptosis induction decreased PS radioactivity of PC12 cells incubated with radioactive serine. MnCl2 reduced PS radioactivity even under conditions that did not affect cell viability or PS exposure, suggesting that the effects on PS metabolism may represent an early event in cell apoptosis. Thus the latter conditions that also induced a greater PS decarboxylation were utilized for further investigating on the effects on PS synthesis, by measuring the activity and expression of PS-synthesizing enzymes, in cell lysates and in total cellular membranes (TM). Compared with corresponding controls, enzyme activity of MnCl2-treated cells was lower in cell lysates and greater in TM. Evaluating the expression of two isoforms of PS-synthesizing enzyme (PSS), PSSII was increased both in cell lysate and TM, while PSSI was unchanged. MnCl2 addition to control cell lysate reduced enzyme activity. These results suggest Mn plays a dual role on PS synthesis. Once inside the cell, Mn inhibits the enzyme/s, thus accounting for reduced PS synthesis in lysates and intact cells. On the other hand, it increases PSSII expression in cell membranes. The possibility that this occurs to counteract the direct effects of Mn ions on enzyme activity cannot be excluded. The effects on membrane enzyme activity and expression may also participate to PS exposure, observed at longer periods of treatment, by increasing membrane PS content.


Electrochemiluminescent detection of metal cations using a ruthenium(II) bipyridyl complex containing a crown ether moiety.
The effects of metal ions on the electrochemiluminescence (ECL) properties of (bpy)2Ru(AZA-bpy) (bpy = 2,2'-bipyridine; AZA-bpy = 4-(N-aza-18-crown-6-methyl-2,2'-bipyridine) have been investigated. The electrochemistry, photophysics and ECL of Ru(bpy)3(2+) in the presence of Pb2+, Hg2+, Cu2+, and K+ are reported. The anodic oxidation of Ru(bpy)3(2+) produces ECL in the presence of tri-n-propylamine (TPrA) in 50:50 (v/v) CH3CN:H2O solution. Increases in ECL efficiency (photons generated per redox event) up to 20-fold that depend on both the concentration and nature of the metal ion have been observed, making this an interesting system for electrochemiluminescence metal ion sensing.


Aurignacian structural features and burials at Cueva Morín (Santander, Spain).
The discovery of what seems to be the foundation of a hut, an alignment of six post holes, and two graves, one of which contains human remains in a remarkable state of preservation, provides important new information about the earliest Aurignacian occupation of northern Spain.


Integrated transcriptomic response to cardiac chronic hypoxia: translation regulators and response to stress in cell survival.
Complementary deoxyribonucleic acid microarray data from 36 mice subjected for 1, 2, or 4 weeks of their early life to normal atmospheric conditions (normoxia) or chronic intermittent (CIH) or constant (CCH) hypoxia were analyzed to extract organizational principles of the developing heart transcriptome and determine the integrated response to oxygen deprivation. Although both CCH and CIH regulated numerous genes involved in a wide diversity of processes, the changes in maturational profile, expression stability, and coordination were vastly different between the two treatments, indicating the activation of distinct regulatory mechanisms of gene transcription. The analysis focused on the main regulators of translation and response to stress because of their role in the cardiac hypertrophy and cell survival in hypoxia. On average, the expression of each heart gene was tied to the expression of about 20% of other genes in normoxia but to only 8% in CCH and 9% in CIH, indicating a strong decoupling effect of hypoxia. In contrast to the general tendency, the interlinkages among components of the translational machinery and response to stress increased significantly in CIH and much more in CCH, suggesting a coordinated response to the hypoxic stress. Moreover, the transcriptomic networks were profoundly and differently remodeled by CCH and CIH.


Epidemiology of heart failure in a community-based study of subjects aged > or = 57 years: incidence and long-term survival.
Survival data from hospital-based or clinical trial studies of patients with chronic heart failure (CHF) do not represent survival in community-based settings. To determine the incidence of CHF and the associated long-term survival in a community-based sample aged > or = 57 years and to assess the mortality risk associated with sex and age. This study was part of the Groningen Longitudinal Aging Study. Annual incidence of CHF per 1000 ranged from 2.5 in middle aged adults (57-60 years) up to 22.4 in older females (> or = 80 years) and 28.2 in older males (> or = 80 years). The 1, 2, 5 and 7-year survival rates were 74%, 65%, 45%, 32% for patients with CHF, compared to 97%, 94%, 80% and 70% in a matched reference group without CHF. Higher age (> or = 76 years) was a risk factor for mortality (OR = 2.1) and male sex was a risk factor in those aged < or = 75 years (OR = 1.9) but not for older patients. Long-term survival rates for patients with CHF in the community were worse than the known survival rates from clinical trials. There is a need for studies describing the care of patients with CHF in the community, including the type of care, the provider, the quality of care and the outcome.


Flock size and habitat-dependent food and energy intake of foraging Goldfinches.
During the breeding season Goldfinches (Carduelis carduelis L.) feed on milky ripe seeds of about 20 food plants. Individual Goldfinches joining a flock reduce the time spent vigilant with increasing flock size. Therefore birds feeding in flocks get an increased intake of kernels per time unit. This was measured for five different food plants (Dactylis glomerata (Gramineae), Knautia arvensis (Dipsacaceae), Senecio vulgaris, Taraxacum officinale, Tragopogon pratensis (Compositae)). In large-sized flocks, birds fed up to 2.3 times more kernels, than when feeding solitarily. In addition, visibility in the vegetation leads to a further increase of kernel intake. Thus feeding under good conditions as in recently mown areas, can raise kernel intake to the seven fold per time unit as compared to solitary feeding. The maximum ingestion rate of kernels was 98 per min which implies a head up-and-down movement every 0.6 s. The calculated energy intake of birds per time unit is lowest in Senecio and highest in Tragopogon. Thus the birds, when feeding on Tragopogon in larger flocks, can gain an energy intake 16 times higher than that reached when feeding on Senecio, despite of a higher kernel intake rate. The energy intake individual Goldfinches gain at the particular plant species is markedly increased with flock sizes up to eight birds, with larger flocks the intake increases only slightly.


Development and evaluation of a new polymeric material for small caliber vascular prostheses.
Polyethylene oxide (PEO), because of its low levels of protein and cellular adsorption, may provide a suitable coating for synthetic small caliber vascular prostheses. PEO/polysiloxane networks were synthesized via an acid-catalyzed epoxy/hydroxyl crosslinking reaction and used to produce conduits with a 4-mm internal diameter. Three networks with nominal PEO molecular weights of 2000, 8000, and 20,000 and all 65% PEO by weight were studied. Blood compatibility was assessed by measuring 111In-platelet and 125I-fibrinogen deposition in a baboon ex vivo shunt, over a 1-hr time period and at a flow rate of 50 ml/min. Differences in material performance were noted particularly after the initial 30-min blood contact period. Materials in the mid and high PEO molecular weight range (8000 and 20,000) had significantly lower levels of platelet adsorption than networks of low PEO molecular weight (2000) at 30 min (P less than 0.005) and 60 min (P less than 0.05). The lowest level of platelet deposition was noted on networks of high PEO molecular weight (20,000). During the observation period, platelet accumulation on this surface was less than one platelet per 1000 microns. Platelet deposition on Gore-Tex was two and three orders of magnitude greater than that on the high molecular weight PEO material at 30 and 60 min, respectively (P less than 0.001). Fibrinogen adsorption was also lower on materials of mid and high PEO molecular weights, when compared with low molecular weight networks (P less than 0.05) and Gore-Tex (P less than 0.05). Scanning electron micrographs confirmed these observations. Overall, platelet and fibrinogen depositions are low for PEO networks, particularly for materials of high PEO molecular weight. This latter observation may be related to increased surface molecular mobility and a relative enhancement of PEO content at the blood-material interface.


Physical, psychological and sexual effects in multi-ethnic Malaysian women who have undergone hysterectomy.
The postoperative effects on Asian women after hysterectomy have not been fully explored. This study was undertaken to investigate the physical, psychological and sexual functioning effects in multi-ethnic Malaysian women who have undergone hysterectomy. A cross-sectional questionnaire-based study was conducted on women who underwent hysterectomy at the Gynecological Outpatient Clinic, University of Malaya Medical Center between November 2008 and October 2009. Postoperative physical and psychological effects were common. Participants with higher household income had a significantly lower number of physical and psychological problems. Young women were more likely to experience psychological effects. There were significant differences between ethnic groups in physical and psychological symptoms. A multivariate model to determine factors associated with sexual functioning identified the importance of sexual relationship, spouse or partner's attitudes, and ethnic groups as significant covariates. The findings underscore the importance of ethnic-based approaches to counseling to mitigate the psychological effects of hysterectomy and to focus on young women with low socioeconomic status.


Crystallization of human c-H-ras oncogene products.
There is compelling evidence that cancer develops as a consequence of genetic changes (probably multiple) in some members of a selected set of cellular genes. DNA isolated from a variety of tumors, but not normal tissues, possesses the ability to malignantly transform non-tumorigenic cells. Many oncogenes responsible for such transformation have been isolated from transformed cell lines and animal and human tumors induced spontaneously, by virus, by chemical, or by radiation. The most commonly found transforming genes isolated from human tumor cells by DNA transfection assay are the ras gene family (c-H-ras, c-K-ras and N-ras). We report crystallization of several human c-H-ras oncogene proteins.


Anticoagulation. Current approach to heparin and warfarin therapy.
Anticoagulant therapy is required for a variety of indications. Heparin, usually administered intravenously, is the drug of choice for acute anticoagulation, with the infusion monitored by partial thromboplastin time. For long-term therapy the standard regimen includes heparin given via intravenous infusion for 7 to 14 days followed by oral warfarin therapy, monitored by prothrombin time. The duration of anticoagulant therapy depends on the indication for its use. The most serious complication with the anticoagulants is bleeding. Physicians should be aware of the risk factors for bleeding and of the measures capable of reversing the effects of the drugs.


Repeated ingestion of aspartame-sweetened beverage: effect on plasma amino acid concentrations in normal adults.
Aspartame (APM) is a dipeptide sweetener (L-aspartyl-L-phenylalanine methyl ester). It has been suggested that excessive use of the product might elevate plasma aspartate and phenylalanine concentrations. Eight normal adults (four male, four female) ingested three successive 12-oz servings of APM-sweetened beverage at two-hour intervals. The study was carried out in two parts in a randomized cross-over design. In one study the beverage was not sweetened. In the other, the beverage provided 10 mg APM/kg body weight per serving. Plasma amino acid concentrations were measured throughout the six-hour study period. The addition of APM to the beverage had no significant effect on plasma aspartate concentration. APM addition did increase plasma phenylalanine levels 1.64 to 2.05 mumol/dL above baseline values (5.09 +/- 0.82 mumol/dL) 30 to 45 minutes after each dose. However, plasma phenylalanine levels did not exceed normal postprandial values at any time. The data indicate ready metabolism of APM's amino acid content when administered at levels likely to be ingested by individuals who are heavy users of such beverages.


Noradrenaline deficiency in brain increases beta-amyloid plaque burden in an animal model of Alzheimer's disease.
Loss of Locus coeruleus (LC) noradrenergic (NA) neurons occurs in several neurodegenerative conditions including Alzheimer's disease (AD). In vitro and in vivo studies have shown that NA influences several features of AD disease including inflammation, neurodegeneration, and cognitive function. In the current study we tested if LC loss influenced beta amyloid (Abeta) plaque deposition. LC neuronal degeneration was induced in transgenic mice expressing mutant V717F human amyloid precursor protein (APP) by treatment with the selective neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine DSP4 (5mg/kg every 2 weeks beginning at age 3 months). At 9 months of age, when control mice show low amyloid load, DSP4-treated mice showed an approximately 5-fold increase in the average number of Abeta plaques. This was accompanied by an increase in the levels of APP C-terminal cleavage fragments. DSP4-treatment increased both microglial and astroglial activation. In vivo, DSP4-treatment decreased expression and activity of the Abeta degrading enzyme neprilysin, while in vitro NA increased phagocytosis of Abeta1-42 by microglia. These findings suggest that noradrenergic innervation from LC are needed to maintain adequate Abeta clearance, and therefore that LC degeneration could contribute to AD pathogenesis.


Significance of MRI Guided Focused Ultrasound Thalamotomy for Parkinson's Disease: A Review.
Magnetic-Resonance guided Focused Ultrasound (FUS) thalamotomy is a new and less invasive surgical technique for treating Parkinson's disease (PD). During therapy, the required part of the cerebral (as STN, Internal Globus Pallidus, and Ventral Intermediate Nucleus) is ablated with less possibility of infection and brain hemorrhage as it normally happens in invasive procedures. New advancement in the technique enables it for transcranial transportation of US. Nowadays, US coupling with MRI confirms the accurate energy transferring and monitoring. So, MRI guided FUS lesioning is discovered for various psychiatric and brain disorders. A technical overview of non-invasive MRI-FUS thalamotomy to treat various tremors is described here. Research, review articles, and book chapters are extracted from online resources using related search strings from the year 1994-2020. MRgFUS is concluded a non-invasive, satisfactory, and safe technique to reduce the tremor. Conlusion: MRgFUS is comparatively a new method that is being explored as a non-invasive cerebral ablation to solve the problems of movement disorder.