[Oxidative damage effects induced by CdTe quantum dots in mice liver].
To investigate oxidative damage effects induced by CdTe quantum dots (QDs) in mice liver. 40 ICR mice were randomly divided into 5 groups, one control group (normal saline), four CdTe QDs (exposed by intravenous injection of 0.2 ml CdTe QDs at the concentration of 0, 0.5, 5, 50 and 500 nmol/ml respectively). All mice were decapitated 24h after the injection. Concentration of MDA and the activities of SOD, CAT, 8-OHdG expression were examined by immunohistochemistry and hepatocellular apoptosis was measured with TUNEL resperctively. The results showed in 500 nmol/ml CdTe QDs group, MDA concentration in the liver tissue were significantly higher than those of control group (P < 0.05). The activities of SOD in 50 and 500 nmol/ml and CAT in 5, 50 and 500 nmol/ml CdTe QDs groups were significantly lower than those of control group (P < 0.01). Positive staining for 8-OHdG appeared in 50 and 500 nmol/ml CdTe QDs groups and the apoptosis of liver cells was observed in 500 nmol/ml CdTe QDs group by TUNEL technique. It was suggested that CdTe QDs at certain doses could induce oxidative damage effects of the mice liver in the condition of this experiment.


Cartilage resorption and endochondral bone formation during the development of long bones in chick embryos.
Cartilage resorption during long bone development in the chick embryo varies in several crucial aspects from that in mammals. Cartilage does not calcify prior to resorption, the pattern of vascular tunnelling is not as regular as that in mammals and no distinct growth plate or secondary ossification centre is apparent. Primary cartilage resorption is preceded by diffusion of substances which produce a change in the cartilage matrix and necrosis of adjacent chondrocytes. Mononuclear phagocytes resorb the bulk of uncalcified cartilage, but resorption is slowed down by the formation of an osteoid band along the walls of the marrow tunnels. This prevents resorbing cells from gaining access to the cartilage matrix. If this osteoid band is in alignment with the trabecular structure, it may contribute to structural bone. In some areas chondrocytes transform into, or are replaced by, bone-producing cells and osteoid is observed within the chondrocyte lacunae. Some calcification of cartilage is observed after 16 days in ovo, but this is independent of cartilage resorption. Remnants of calcified cartilage frequently persist in the marrow cavity and multinucleated chondroclasts are required to resorb these remnants.


Dietary exposure of juvenile female mice to polyhalogenated seafood contaminants (HBCD, BDE-47, PCB-153, TCDD): comparative assessment of effects in potential target tissues.
Fish represents source of nutrients and major dietary vehicle of lipophilic persistent contaminants. The study compared the effects of two legacy and two emerging fish pollutants (Hexabromocyclododecane HBCD; 2,2',4,4'-Tetrabromodiphenyl ether BDE-47; 2,2',4,4',5,5'-Hexachlorobiphenyl PCB-153; 2,3,7,8-Tetrachlorodibenzo-p-doxin TCDD) in juvenile female mice exposed through a salmon based rodent diet for 28 days (dietary doses: HBCD 199 mg/kg bw/day; BDE-47 450 μg/kg bw/day; PCB-153 195 μg/kg bw/day; TCDD 90 ng/kg bw/day). Dose levels were comparable to previously reported developmental Lowest Observed Adverse Effect Levels. None of the treatments elicited signs of overt toxicity, but HBCD increased relative liver weight. All compounds caused changes in liver, thymus and thyroid; spleen was affected by BDE-47 and PCB-153; no effects were seen in uterus and adrenals. Strongest effects in thyroid follicles were elicited by PCB-153, in thymus and liver by BDE-47. HBCD and BDE-47 induced liver fatty changes, but appeared to be less potent in the other tissues. HBCD, BDE-47 and TCDD increased serum testosterone levels and the testosterone/estradiol ratio, suggesting a potential involvement of pathways related to sex steroid biosynthesis and/or metabolism. The results support the role of toxicological studies on juvenile rodents in the hazard characterization of chemicals, due to endocrine and/or immune effects.


Positions of disulfide bonds and N-glycosylation site in juvenile hormone binding protein.
The juvenile hormone binding protein (JHBP) from Galleria mellonella hemolymph is a glycoprotein composed of 225 amino acid residues. It contains four Cys residues forming two disulfide bridges. In this study, the topography of the disulfide bonds as well as the site of glycan attachment in the JHBP molecule from G. mellonella was determined, using electrospray mass spectrometry. The MS analysis was performed on tryptic digests of JHBP. Our results show that the disulfide bridges link Cys10 and Cys17, and Cys151 and Cys195. Of the two potential N-glycosylation sites in JHBP, Asn4, and Asn94, only Asn94 is glycosylated. This site of glycosylation is also found in the fully biologically active recombinant JHBP expressed in the yeast Pichia pastoris.


Children punish third parties to satisfy both consequentialist and retributive motives.
Adults punish moral transgressions to satisfy both retributive motives (such as wanting antisocial others to receive their 'just deserts') and consequentialist motives (such as teaching transgressors that their behaviour is inappropriate). Here, we investigated whether retributive and consequentialist motives for punishment are present in children approximately between the ages of five and seven. In two preregistered studies (N = 251), children were given the opportunity to punish a transgressor at a cost to themselves. Punishment either exclusively satisfied retributive motives by only inflicting harm on the transgressor, or additionally satisfied consequentialist motives by teaching the transgressor a lesson. We found that children punished when doing so satisfied only retributive motives, and punished considerably more when doing so also satisfied consequentialist motives. Together, these findings provide evidence for the presence of both retributive and consequentialist motives in young children.


Identification of a ubiquitin-protein ligase subunit within the CCR4-NOT transcription repressor complex.
The RING finger protein CNOT4 is a component of the CCR4-NOT complex. This complex is implicated in repression of RNA polymerase II transcription. Here we demonstrate that CNOT4 functions as a ubiquitin-protein ligase (E3). We show that the unique C4C4 RING domain of CNOT4 interacts with a subset of ubiquitin-conjugating enzymes (E2s). Using NMR spectroscopy, we detail the interaction of CNOT4 with UbcH5B and characterize RING residues that are critical for this interaction. CNOT4 acts as a potent E3 ligase in vitro. Mutations that destabilize the E2-E3 interface abolish this activity. Based on these results, we present a model of how E3 ligase function within the CCR4-NOT complex relates to transcriptional regulation.


Genetic evidence and integration of various data sources for classifying uncertain variants into a single model.
Genetic testing often results in the finding of a variant whose clinical significance is unknown. A number of different approaches have been employed in the attempt to classify such variants. For some variants, case-control, segregation, family history, or other statistical studies can provide strong evidence of direct association with cancer risk. For most variants, other evidence is available that relates to properties of the protein or gene sequence. In this work we propose a Bayesian method for assessing the likelihood that a variant is pathogenic. We discuss the assessment of prior probability, and how to combine the various sources of data into a statistically valid integrated assessment with a posterior probability of pathogenicity. In particular, we propose the use of a two-component mixture model to integrate these various sources of data and to estimate the parameters related to sensitivity and specificity of specific kinds of evidence. Further, we discuss some of the issues involved in this process and the assumptions that underpin many of the methods used in the evaluation process.


Attenuated c-fos mRNA induction after middle cerebral artery occlusion in CREB knockout mice does not modulate focal ischemic injury.
To elucidate the mechanism of ischemia-induced signal transduction in vivo, we investigated the effect of the targeted disruption of the alpha and delta isoforms of the cAMP-responsive element-binding protein (CREB) on c-fos and heatshock protein (hsp) 72 gene induction. Permanent focal ischemia was induced by occlusion of the middle cerebral artery of the CREB mutant mice (CREB(-/-), n = 5) and the wild-type mice (n = 6). Three hours after onset of ischemia, the neurologic score was assessed and pictorial measurements of ATP and cerebral protein synthesis (CPS) were carried out to differentiate between the ischemic core (where ATP is depleted), the ischemic penumbra (where ATP is preserved but CPS is inhibited), and the intact tissue (where both ATP and CPS are preserved). There were no significant differences in neurologic score or in ATP, pH, and CPS between the two groups, suggesting that the sensitivity of both strains to ischemia is the same. Targeted disruption of the CREB gene significantly attenuated c-fos gene induction in the periischemic ipsilateral hemisphere but had no effect on either c-fos or hsp72 mRNA expression in the penumbra. The observations demonstrate that CREB expression, despite its differential effect on c-fos, does not modulate acute focal ischemic injury.


Prompt gamma ray activation analysis for determining chemical composition of 3D printing and casting materials used in biomedical applications.
Three-dimensional printing and casting materials were analyzed by prompt gamma-ray activation analysis (PGAA) to determine their suitability as human tissue surrogates for the fabrication of phantoms for medical imaging and radiation dosimetry applications. Measured elemental compositions and densities of five surrogate materials simulating soft tissue and bone were used to determine radiological properties (x-ray mass attenuation coefficient and electron stopping power). When compared with radiological properties of International Commission on Radiation Units and Measurements (ICRU) materials, it was determined that urethane rubber and PLA plastic yielded the best match for soft tissue, while silicone rubber and urethane resin best simulated the properties of bone.


A novel approach to the synthesis of oligodeoxyribonucleotide boranophosphates.
Deoxyribonucleoside 3'-boranophosphate derivatives including adenine, cytosine, guanine, and thymine bases were synthesized in good yields by the use of a new boranophosphorylation reaction. The reaction was found to be effective for the formation of internucleotidic boranophosphate linkages.


Grassland biodiversity bounces back from long-term nitrogen addition.
The negative effect of increasing atmospheric nitrogen (N) pollution on grassland biodiversity is now incontrovertible. However, the recent introduction of cleaner technologies in the UK has led to reductions in the emissions of nitrogen oxides, with concomitant decreases in N deposition. The degree to which grassland biodiversity can be expected to 'bounce back' in response to these improvements in air quality is uncertain, with a suggestion that long-term chronic N addition may lead to an alternative low biodiversity state. Here we present evidence from the 160-year-old Park Grass Experiment at Rothamsted Research, UK, that shows a positive response of biodiversity to reducing N addition from either atmospheric pollution or fertilizers. The proportion of legumes, species richness and diversity increased across the experiment between 1991 and 2012 as both wet and dry N deposition declined. Plots that stopped receiving inorganic N fertilizer in 1989 recovered much of the diversity that had been lost, especially if limed. There was no evidence that chronic N addition has resulted in an alternative low biodiversity state on the Park Grass plots, except where there has been extreme acidification, although it is likely that the recovery of plant communities has been facilitated by the twice-yearly mowing and removal of biomass. This may also explain why a comparable response of plant communities to reduced N inputs has yet to be observed in the wider landscape.


An updated review on advancement in fermentative production strategies for biobutanol using Clostridium spp.
A significant concern of our fuel-dependent era is the unceasing exhaustion of petroleum fuel supplies. In parallel to this, environmental issues such as the greenhouse effect, change in global climate, and increasing global temperature must be addressed on a priority basis. Biobutanol, which has fuel characteristics comparable to gasoline, has attracted global attention as a viable green fuel alternative among the many biofuel alternatives. Renewable biomass could be used for the sustainable production of biobutanol by the acetone-butanol-ethanol (ABE) pathway. Non-extinguishable resources, such as algal and lignocellulosic biomass, and starch are some of the most commonly used feedstock for fermentative production of biobutanol, and each has its particular set of advantages. Clostridium, a gram-positive endospore-forming bacterium that can produce a range of compounds, along with n-butanol is traditionally known for its biobutanol production capabilities. Clostridium fermentation produces biobased n-butanol through ABE fermentation. However, low butanol titer, a lack of suitable feedstock, and product inhibition are the primary difficulties in biobutanol synthesis. Critical issues that are essential for sustainable production of biobutanol include (i) developing high butanol titer producing strains utilizing genetic and metabolic engineering approaches, (ii) renewable biomass that could be used for biobutanol production at a larger scale, and (iii) addressing the limits of traditional batch fermentation by integrated bioprocessing technologies with effective product recovery procedures that have increased the efficiency of biobutanol synthesis. Our paper reviews the current progress in all three aspects of butanol production and presents recent data on current practices in fermentative biobutanol production technology.


Variability among the neuraminidase, non-structural 1 and PB1-F2 proteins in the influenza A virus genome.
Influenza A viruses infect a large number of mammals and birds resulting in sporadic infections, seasonal epidemics, epizootics and pandemics. The segmented genome of the virus encodes 10 or 11 proteins depending on the strain. The neuraminidase, non-structural 1 and the PB1-F2 proteins are known to be variable in their length due to very specific deletions, truncations and elongations. This review presents an update on what is currently known about these three proteins and discusses their length variations in relation to virulence and host adaptation in addition to identifying possible areas of future research.


Diaphragm Pacing without Tracheostomy in Congenital Central Hypoventilation Syndrome Patients.
Congenital central hypoventilation syndrome (CCHS) is a rare disorder affecting central control of breathing. Thus, patients require lifelong assisted ventilation. Diaphragm pacing (DP) may permit decannulation in those who are ventilator dependent only during sleep. The purpose of this study is to determine if patients with CCHS can be successfully ventilated by DP without tracheostomy. We reviewed the records of 18 CCHS patients (mean age 19.5 ± 10.1 years; 44% female) who were ventilated by DP only during sleep. Prior to diaphragm pacer implantation surgery, 14 CCHS patients had been using home portable positive pressure ventilation (PPV) via tracheostomy, 1 had been on PPV via endotracheal tube, and 3 had been using noninvasive PPV (NPPV). Of the patients with tracheostomy prior to DP (n = 15), 11 (73%) were decannulated and ventilated successfully by DP without tracheostomy. Of all the patients reviewed (n = 18), 13 (72%) were successfully ventilated by DP without tracheostomy. Obesity prevented successful DP without tracheostomy in 1 patient, and upper airway obstruction prevented success in another patient. Snoring and/or obstructive apneas were present in some patients, but they were improved by diaphragm pacer changes, adenotonsillectomy, and/or use of nasal steroids. DP without tracheostomy can be successfully achieved in patients with CCHS. Snoring and obstructive apneas, when present, can be managed by diaphragm pacer changes and medical therapies. Obesity can pose a challenge to successful DP.


Presence of HPV DNA in convalescent salivary rinses is an adverse prognostic marker in head and neck squamous cell carcinoma.
Human papillomavirus (HPV) 16 is present in up to 60% of patients with head and neck squamous cell carcinoma (HNSCC) and confers a favorable prognosis in terms of recurrence and mortality. Previous reports demonstrated that HPV-16 DNA can be detected in the initial salivary rinses from these patients. In this study, we assessed the feasibility of post-treatment HPV DNA shed from the oral mucosa as a prognostic marker for persistent/recurrent head and neck cancer. Fresh tumor samples and pre- and post-treatment salivary rinses were collected from 59 patients with HNSCC. HPV-16 E6 and E7 DNA copy number in these samples were quantified by real time PCR. Twenty of 59 patients (33.9%) were HPV-16 positive in their tumors before treatment. Four of 20 HPV tumor positive patients ultimately developed recurrence, and two of these four patients were HPV-16 positive in surveillance salivary rinses (sensitivity=50%). Of the 39 (66.1%) HPV-16 negative patients on initial clinical presentation and the 16 HPV-16 positive patients who did not recur, none were HPV-16 positive in salivary rinses after treatment (specificity=100%). HPV-16 presence in follow-up salivary rinses preceded clinical detection of disease recurrence by an average of 3.5 months. Patients with presence of HPV-16 DNA in surveillance salivary rinses are at significant risk for recurrence. Quantitative measurement of salivary HPV-16 DNA has promise for surveillance and early detection of recurrence.


Postpartum thyroid dysfunction and HLA status.
Nine-hundred-and-one women presenting in an antenatal clinic at the 60th week of pregnancy were tested for antithyroid antibodies. A group of 113 antibody-positive women and 108 antibody-negative age-matched controls were HLA typed and followed prospectively at 6-weekly intervals through pregnancy and for 12 months postpartum. Forty-five of the women developed biochemical evidence of postpartum thyroid dysfunction (PPTD) of whom 36 were antibody positive. Compared with a local control population (n = 600), and using multiplex analysis, there was a significant increase in the combinations HLA B8, DR3 and HLA A1, B8, DR3 from 22.5% to 40.0% (P less than 0.02) and from 18.6% to 35.6% (P less than 0.01) respectively in the women who developed PPTD. The well-recognized association of these haplotypes with other organ-specific autoimmune diseases provides further support for autoimmune events being implicated in the development of PPTD.


Behavioral and Psychological Symptoms of Dementia (BPSD): Clinical Characterization and Genetic Correlates in an Italian Alzheimer's Disease Cohort.
The occurrence of Behavioral and Psychological Symptoms of Dementia (BPSD) in Alzheimer's Disease (AD) patients hampers the clinical management and exacerbates the burden for caregivers. The definition of the clinical distribution of BPSD symptoms, and the extent to which symptoms are genetically determined, are still open to debate. Moreover, genetic factors that underline BPSD symptoms still need to be identified. To characterize our Italian AD cohort according to specific BPSD symptoms as well as to endophenotypes. To evaluate the associations between the considered BPSD traits and COMT, MTHFR, and APOE genetic variants. AD patients (n = 362) underwent neuropsychological examination and genotyping. BPSD were assessed with the Neuropsychiatric Inventory scale. APOE and MTHFR variants were significantly associated with specific single BPSD symptoms. Furthermore, "Psychosis" and "Hyperactivity" resulted in the most severe endophenotypes, with APOE and MTHFR implicated as both single risk factors and "genexgene" interactions. We strongly suggest the combined use of both BPSD single symptoms/endophenotypes and the "genexgene" interactions as valid strategies for expanding the knowledge about the BPSD aetiopathogenetic mechanisms.


Changing seroepidemiological patterns of cytomegalovirus infection in children in Taiwan from 1984 to 1989.
The prevalence of cytomegalovirus (CMV) antibody was studied in 966 children in 1984 and 927 children in 1989. The overall prevalence rate of CMV antibody was 59% for children in 1984 and 46% for children in 1989 (P less than 0.05). In both study years, the prevalence rate of CMV antibody was about 70% in infants under 6 months of age, declined to a trough between the ages of 6 and 12 months, and then increased to 40-50% between 1 and 4 years of age. The rate of CMV antibody for children above 4 years in 1984 increased steadily with age and reached 82% by 12 years. In contrast, the prevalence rate in 1989 remained at the level of 40-50% from age 4 to 10 years. It was followed by a sharp increase after 10 years of age and reached 84% at 12 years old. The seropositive rate in each of the 5-, 6-, 8-, 9-, and 10-year-old groups was higher in 1984 than that in 1989. These observations indicated that the prevalence rate of CMV antibody is decreasing in children. This change may be related to various socioeconomic factors, especially the less crowded family conditions in recent years.


Improvement of the Physicochemical Limitations of Rhapontigenin, a Cytotoxic Analogue of Resveratrol against Colon Cancer.
It has been argued that methoxylated stilbenes are better candidates for oral administration than hydroxylated stilbenes, including resveratrol, as they share many biological activities but have better bioavailability. By contrast, they have a disadvantage to consider, i.e., their lower hydrophilic character that leads to precipitation issues in the final product. In this work, we analysed and compared the growth inhibition of colorectal cancer cells of the methoxylated stilbene rhapontigenin and some analogues and overcame potential problems in the development of fortified products by designing inclusion complexes. Among several cyclodextrins, we found the one that best fit the molecule by physicochemical and bioinformatics assays. The stoichiometry and the encapsulation constants with natural and modified cyclodextrins were determined by fluorescence spectroscopy. The most promising complexes were analysed at different temperature and pH conditions, determining the thermodynamic parameters, to discover the optimal conditions for the preparation and storage of the products. The results showed that rhapontigenin solubility and stability were significantly improved, achieving a sevenfold increase in water solubility and maintaining more than 73% of the stilbene after three months. These findings could be of great interest for industries that aim to deliver novel bioactive compounds with higher solubility and lower degradation.


The use of the Port-A-Cath in children with haemophilia--a review.
Port-A-Caths have been used increasingly in children with severe haemophilia. In non-inhibitor patients where Port-a-Caths were used to facilitate long-term prophylaxis, the infection rate is rather low and ranges in the various studies from 0 to 29%, with a median follow-up time of about 27 months. Patients that received the Port-A-Cath for the induction of immune tolerance (inhibitor patients) have a high infection rate of 50% to 83%. Although this percentage is high, good venous access is extremely important, especially in this group. The number of both inhibitor and non-inhibitor patients in the studies are very small, and a prospective survey is important to obtain more adequate data.


Refolding of metacaspase 5 from Trypanosoma cruzi, structural characterization and the influence of c-terminal in protein recombinant production.
Metacaspases are known to have a fundamental role in apoptosis-like, a programmed cellular death (PCD) in plants, fungi, and protozoans. The last includes several parasites that cause diseases of great interest to public health, mostly without adequate treatment and included in the neglected tropical diseases category. One of them is Trypanosoma cruzi which causes Chagas disease and has two metacaspases involved in its PCD: TcMCA3 and TcMCA5. Their roles seemed different in PCD, TcMCA5 appears as a proapoptotic protein negatively regulated by its C-terminal sequence, while TcMCA3 is described as a cell cycle regulator. Despite this, the precise role of TcMCA3 and TcMCA5 and their atomic structures remain elusive. Therefore, developing methodologies to allow investigations of those metacaspases is relevant. Herein, we produced full-length and truncated versions of TcMCA5 and applied different strategies for their folded recombinant production from E. coli inclusion bodies. Biophysical assays probed the efficacy of the production method in providing a high yield of folded recombinant TcMCA5. Moreover, we modeled the TcMCA5 protein structure using experimental restraints obtained by XLMS. The experimental design for novel methods and the final protocol provided here can guide studies with other metacaspases. The production of TcMCA5 allows further investigations as protein crystallography, HTS drug discovery to create potential therapeutic in the treatment of Chagas' disease and in the way to clarify how the PCD works in the parasite.


Short-Term Safety and Plasma Concentrations of Edoxaban in Japanese Patients With Non-Valvular Atrial Fibrillation and Severe Renal Impairment.
The short-term safety and plasma concentrations of edoxaban 15 mg once daily in Japanese patients with non-valvular atrial fibrillation (NVAF) and severe renal impairment (SRI; creatinine clearance [CL<inf>CR</inf>] ≥15 to <30 ml/min) were compared with those in NVAF patients with normal renal function or mild renal impairment (normal/MiRI; CL<inf>CR</inf>≥50 ml/min) treated with edoxaban 30 or 60 mg. In this Phase 3 multicenter open-label 3 parallel-group study, SRI patients received once-daily edoxaban 15 mg (n=50), whereas normal/MiRI patients were randomized to receive either once-daily edoxaban 30 or 60 mg (n=22 and 21, respectively) for 12 weeks. Plasma edoxaban concentrations and biomarkers of blood coagulation and fibrinolysis were measured. Adverse events and thromboembolic events were recorded throughout the study. Rates of any bleeding were comparable between SRI patients receiving edoxaban 15 mg (20.0%) and normal/MiRI patients receiving edoxaban 30 or 60 mg (22.7% and 23.8%, respectively). No major bleeding or thromboembolic events occurred in any treatment group. Similar plasma concentrations and biomarker profiles were observed in SRI patients receiving edoxaban 15 mg and normal/MiRI patients receiving edoxaban 30 or 60 mg. In this 12-week short-term study in Japanese NVAF patients with SRI, edoxaban 15 mg once daily exhibited similar safety, plasma concentration, and biomarker profiles as did the 30-mg and 60-mg doses in patients with normal/MiRI.


An inference upon the neural network finding binocular correspondence.
Previously, the authors proposed a model of neural network extracting binocular parallax (Hirai and Fukushima, 1975). It is a multilayered network whose final layers consist of neural elements corresponding to "binocular depth neurons" found in monkey's visual cortex. The binocular depth neuron is selectively sensitive to a binocular stimulus with a specific amount of binocular parallax and does not respond to a monocular one. As described in the last chapter of the previous article (Hirai and Fukushima, 1975), when a binocular pair of input patterns consist of, for example, many vertical bars placed very closely to each other, the binocular depth neurons might respond not only to correct binocular pairs, but also to incorrect ones. Our present study is concentrated upon how the visual system finds correct binocular pairs or binocular correspondence. It is assumed that some neural network is cascaded after the binocular depth neurons and finds out correct binocular correspondence by eliminating the incorrect binocular pairs. In this article a model of such neural network is proposed. The performance of the model has been simulated on a digital computer. The results of the computer simulation show that this model finds binocular correspondence satisfactorily. It has been demonstrated by the computer simulation that this model also explains the mechanism of the hysteresis in the binocular depth perception reported by Fender and Julesz (1967).


Novel synaptic potentials in cerebellar Purkinje cells: probable mediation by metabotropic glutamate receptors.
Glutamate receptors of both the ionotropic (ion channel-linked) and metabotropic (enzyme-linked) categories are abundantly expressed by Purkinje cells in the cerebellum but the functional significance of the latter receptors is unknown. We have tested the possibility that they are activated by the parallel fibre input by recording from Purkinje cells within a biplanar cerebellar slice preparation using the grease-gap technique. Under conditions where ionotropic (NMDA and non-NMDA) glutamate and GABA receptors were blocked pharmacologically, electrical stimulation of parallel fibres gave rise to two very slow potentials. The first peaked about 400 msec from the start of stimulation and was depolarising. It was not evident with single stimuli but reached maximum amplitude after 6 shocks delivered at 50 Hz. The wave was abolished when the slices were perfused with Ca(2+)-free solution or with drugs that inhibit synaptic transmission, but it was resistant to blockade of GABAB receptors, acetylcholine receptors and adrenergic receptors. Next came a slow hyperpolarising potential that peaked about 30 sec after stimulation and which was also Ca(2+)-dependent. The sequence of potentials was replicated by perfusion of an exogenous agonist acting selectively on metabotropic glutamate receptors. We conclude that parallel fibre-to-Purkinje cell synaptic transmission involves not only fast signals generated through ionotropic non-NMDA receptors but also much slower potentials that are likely to be mediated by metabotropic glutamate receptors. These potentials are likely to be significant both for shorter-term (seconds to minutes) Purkinje cell excitability as well as for the induction of longer-term synaptic plasticity.


Physical fitness of lower limb amputees.
To investigate the cardiorespiratory endurance of the physical fitness of amputees and able-bodied subjects of the same ages and to demonstrate deterioration of the physical fitness of the amputees. The test subjects were 31 amputees. Eighteen able-bodied persons served as controls. The incremental exercise test was performed to evaluate physical fitness. Sixteen of 31 amputees underwent endurance training by using a cycle ergometer driven by the intact leg, and their physical fitness was evaluated after completion of the endurance training program. The Vo2max, anaerobic threshold, and maximum workload for the amputees were significantly lower than those of the able-bodied group. The equivalent values for the endurance training group before exercise treatment were 18.0, 12.1, and 63.9, respectively. After exercise treatment, these values significantly increased, and there was no significant difference from the able-bodied subjects. This study showed that the physical fitness of amputees was clearly lower than that of the able-bodied subjects and that the amputees were able to recover from a poorly conditioned status after endurance training.


Glycosylation in cancer: its application as a biomarker and recent advances of analytical techniques.
Despite significant worldwide investment in research, cancer remains one of the most common cause of death in the world. Early detection and reliable diagnosis are the keys to effectively treating cancer and improving the long-term survival of cancer patients. Therefore, there is an urgent need to develop a single, non-invasive biomarker with high sensitivity and specificity. Aberrant glycosylation is well defined as a hallmark of cancer and represents a promising source of potential biomarkers. Tumor-associated carbohydrate epitopes have long been detected by using monoclonal antibodies and lectins. Recent advances in analytical technologies allow us to analyze cancer-specific glycoforms on a target protein in a variety of clinical samples. A number of glycan analysis techniques, such as lectin-based detection methods and mass spectrometry combined with various types of chromatography, have been developed to establish novel glycoform-specific cancer biomarkers. Several glycan-based cancer biomarkers are already in clinical use. The aim of this review is to outline the role of glycan as a cancer biomarker and to summarize the current status and the potential for contribution of the serum glycoproteome to cancer diagnostics, monitoring, and prognostics.


A homochiral nanotubular crystalline framework of metallomacrocycles for enantioselective recognition and separation.
A highly ordered homochiral nanotubular crystalline framework was assembled from a hexameric Zn6L6metallaycle that was built from metallosalen ZnL units (H2L = (R,R)-(-)-N,N'-Bis(3-tert-butyl-5-(4- pyridyl) salicylidene)-1,2-diaminocyclohexane) by the complementary coordination of the pyridyl groups to the metal centers. Chiral channels and hydrophobic functionality presented by this structure make it an excellent host to recognize and separate racemic alcohols with high enantioselectivity (up to 99.5%). The crystalline solid can be easily recycled and reused five times without loss of crystallinity and enantioselectivity.


Calretinin-immunoreactive systems in the cerebellum and cerebellum-related lateral-line medullary nuclei of an elasmobranch, Scyliorhinus canicula.
Calretinin immunohistochemistry was used to study the organization of some cerebellar structures and lateral line medullary nuclei of an elasmobranch, the lesser-spotted dogfish Scyliorhinus canicula. In the cerebellar molecular layer, stellate cells are strongly calretinin-immunoreactive (CR-ir). Perikarya and dendrites of Purkinje cells are contacted by numerous stellate cell small CR-ir boutons. Some Purkinje cell perikarya are contacted by CR-ir climbing fibers forming complex axo-somatic contacts. In the granular layer, numerous CR-ir mossy fibers exhibited large swellings. Notable differences in density and diameter of mossy fibers are observed between the auricles and cerebellar body. Thin beaded CR-ir fibers are also present in the granular layer of the body. The lateral line nuclei of the octavolateralis region are comprised of a molecular-like cerebellar crest that covers the dorsal (electroreceptive) and the medial octavolateralis nuclei (mechanoreceptive). The cerebellar crest exhibited numerous CR-ir stellate cells. In the dorsal octavolateralis nucleus, the presence of conspicuous CR-ir cells and neuropil closely associated to the region of primary fiber terminals distinguishes it clearly from the medial nucleus, revealing major differences between the electroreceptive and mechanoreceptive primary nuclei of elasmobranchs. Moreover, CR distribution in the dogfish cerebellum showed interesting differences with those reported in cerebella of other vertebrates, indicating a high variability of cerebellar CR expression in phylogeny.


[Nosocomial urinary tract infections in the geriatric hospital - pathogen spectrum and resistancies].
We examined 834 isolates of urinary cultures (26 fungi and 808 isolates from 28 bacteria) in an academic geriatric teaching hospital for microbial spectrum and resistance analysis. Of the bacteria, 90% were associated to ten species. Detection rate of MRSA and ESBL was 1%, detection rate for pseudomonas aeruginosa, proteus species, coagulase negative staphylococci and klebsiella species were higher than in an university clinic (p < 0.001). Resistency rates were high for the 10 most frequent bacteria: 53.3% of cross-tabulations between bacterium and antibiotic agent (sulfamethoxazol-trimethoprim, amoxicillin-clavulanate, ciprofloxacin, moxifloxacin, cefuroxim, imipenem) showed resistency rate higher than 10%. We assume that specific factors of geriatric sample taking have an impact to our 2-year resistogram results. It is necessary to combine data analysis from comprehensive geriatric assessment and microbiological methods.


Development of an ethyl laurate-based microemulsion for rapid-onset intranasal delivery of diazepam.
An ethyl laurate-based microemulsion system with Tween 80 as surfactant, propylene glycol and ethanol as cosolvents was developed for intranasal delivery of diazepam. Phase behavior and solubilization capacity of the microemulsion system were characterized and in vivo nasal absorption of diazepam from microemulsion formulations was investigated in rabbits. A single isotropic region, which is considered as a bicontinuous microemulsion, was found in the pseudo-ternary phase diagrams developed at various Tween 80: propylene glycol: ethanol ratios. With the increase of Tween 80 concentration, the microemulsion region area, microemulsion viscosity, and the amount of H(2)O and ethyl laurate solubilized into the microemulsion system increased; however, the increase of ethanol percentage produced opposite effects. Diazepam, a practically water-insoluble drug, displayed a high solubility of 41 mg/ml in a microemulsion consisting of 15% ethyl laurate, 15% H(2)O, and 70% (w/w) surfactant/cosurfactant (Tween 80:propylene glycol:ethanol at 1:1:1 weight ratio). Nasal absorption of diazepam from this microemulsion was found to be fairly rapid. At 2 mg/kg dose, the maximum drug plasma concentration was arrived within 2-3 min, and the bioavailability (0-2 h) after nasal spray compared with intravenous injection was about 50%. These results suggest that this ethyl laurate-based microemulsion may be a useful approach for the rapid-onset delivery of diazepam during the emergency treatment of status epilepticus.


Ultrasound signs in threatened abortion and their prognostic significance.
During the first and early second trimesters of pregnancy in 244 consecutive patients with uterine bleeding, ultrasound studies were conducted to determine the cause of bleeding. In 165 of the patients the fetus was alive, and the outcome of pregnancy was successful in 143 (87%) despite the fact that ultrasound scanning revealed a total of 60 abnormalities. In the 22 patients whose pregnancy outcome was unfavorable, the number of abnormalities was significantly higher (P less than .05). The most common ultrasound abnormalities were placenta covering the internal os, fetal growth delay, multiple gestation, and intrauterine hematoma. At ultrasound examination, the presence of one or more abnormalities plus bleeding for three days or more significantly increased the risk to the pregnancy. When the duration of bleeding was less than three days and the ultrasound examination was normal, the risk to the pregnancy was lower (7%) than that of patients who had bled for three days or more and had at least one abnormality on ultrasound examination (24%) (P less than .05).


Membrane-less hydrogen bromine flow battery.
In order for the widely discussed benefits of flow batteries for electrochemical energy storage to be applied at large scale, the cost of the electrochemical stack must come down substantially. One promising avenue for reducing stack cost is to increase the system power density while maintaining efficiency, enabling smaller stacks. Here we report on a membrane-less hydrogen bromine laminar flow battery as a potential high-power density solution. The membrane-less design enables power densities of 0.795 W cm(-2) at room temperature and atmospheric pressure, with a round-trip voltage efficiency of 92% at 25% of peak power. Theoretical solutions are also presented to guide the design of future laminar flow batteries. The high-power density achieved by the hydrogen bromine laminar flow battery, along with the potential for rechargeable operation, will translate into smaller, inexpensive systems that could revolutionize the fields of large-scale energy storage and portable power systems.


The adverse outcome pathway concept: a pragmatic tool in toxicology.
Adverse outcome pathways (AOPs) are novel tools in toxicology and human risk assessment with broad potential. AOPs are designed to provide a clear-cut mechanistic representation of critical toxicological effects that span over different layers of biological organization. AOPs share a common structure consisting of a molecular initiating event, a series of intermediate steps and key events, and an adverse outcome. Development of AOPs ideally complies with OECD guidelines. This also holds true for AOP evaluation, which includes consideration of the Bradford Hill criteria for weight-of-evidence assessment and meeting a set of key questions defined by the OECD. Elaborate AOP frameworks have yet been proposed for chemical-induced skin sensitization, cholestasis, liver fibrosis and liver steatosis. These newly postulated AOPs can serve a number of ubiquitous purposes, including the establishment of (quantitative) structure-activity relationships, the development of novel in vitro toxicity screening tests and the elaboration of prioritization strategies.


Screening and validation of reference genes for qRT-PCR of bovine skeletal muscle-derived satellite cells.
The accuracy of sixteen commonly used internal reference genes was assessed in skeletal muscle-derived satellite cells of Qinchuan cattle at different stages of proliferation and induction of differentiation to determine the most suitable ones. Quantitative real-time PCR and three commonly used algorithmic programs, GeNorm, NormFinder and BestKeeper, were used to evaluate the stability of expression of the candidate internal reference genes (GAPDH, ACTB, PPIA, LRP10, HPRT1, YWHAZ, B2M, TBP, EIF3K , RPS9, UXT, 18S rRNA, RPLP0, MARVELD, EMD and RPS15A) in skeletal muscle-derived satellite cells at 0, 12, 24, 36 and 48 h of growth and after differentiation for 0, 2, 4, 6 and 8 days. The expression of two satellite cell marker genes, CCNA2 and MYF5, was used for validation analysis. The results of the software analyses showed that GAPDH and RPS15A were the most stable reference gene combinations during in vitro proliferation of bovine skeletal muscle-derived satellite cells, RPS15A and RPS9 were the most stable reference gene combinations during in vitro induction of differentiation of the cells, and PPIA was the least stable reference gene during proliferation and differentiation and was not recommended. This study lays the foundation for the selection of reference genes for qRT-PCR during the proliferation and induction of differentiation of bovine skeletal muscle-derived satellite cells.


Improving motorcycle conspicuity through innovative headlight configurations.
Most motorcycle crashes involve another vehicle that violated the motorcycle's right-of-way at an intersection. Two kinds of perceptual failures of other road users are often the cause of such accidents: motorcycle-detection failures and motion-perception errors. The aim of this study is to investigate the effect of different headlight configurations on motorcycle detectability when the motorcycle is in visual competition with cars. Three innovative headlight configurations were tested: (1) standard yellow (central yellow headlight), (2) vertical white (one white light on the motorcyclist's helmet and two white lights on the fork in addition to the central white headlight), and (3) vertical yellow (same configuration as (2) with yellow lights instead of white). These three headlight configurations were evaluated in comparison to the standard configuration (central white headlight) in three environments containing visual distractors formed by car lights: (1) daytime running lights (DRLs), (2) low beams, or (3) DRLs and low beams. Video clips of computer-generated traffic situations were displayed briefly (250ms) to 57 drivers. The results revealed a beneficial effect of standard yellow configuration and the vertical yellow configuration on motorcycle detectability. However, this effect was modulated by the car-DRL environment. Findings and practical recommendations are discussed with regard to possible applications for motorcycles.


Effect of aspirin on HIV disease progression among HIV-infected individuals initiating antiretroviral therapy: study protocol for a randomised controlled trial.
An increase in cardiovascular disease (CVD) among people living with HIV infection is linked to platelet and immune activation, a phenomenon unabolished by antiretroviral (ARV) drugs alone. In small studies, aspirin (acetylsalicylic acid [ASA]) has been shown to control immune activation, increase CD4+ count, halt HIV disease progression and reduce HIV viral load (HVL). We present a protocol for a larger ongoing randomised placebo controlled trial on the effect of an addition of ASA to ARV drugs on HIV disease progression. A single-centre phase IIA double-blind, parallel-group randomised controlled trial intends to recruit 454 consenting ARV drug-naïve, HIV-infected adults initiating ART. Participants are randomised in blocks of 10 in a 1:1 ratio to receive, in addition to ARV drugs, 75 mg ASA or placebo for 6 months. The primary outcome is the proportion of participants attaining HVL of <50 copies/mL by 8, 12 and 24 weeks. Secondary outcomes include proportions of participants with HVL of >1000 copies/mL at week 24, attaining a >30% rise of CD4 count from baseline value at week 12, experiencing adverse events, with normal levels of biomarkers of platelet and immune activation at weeks 12 and 24 and rates of morbidity and all-cause mortality. Intention-to-treat analysis will be done for all study outcomes. Ethical approval has been obtained from institutional and national ethics review committees. Findings will be submitted to peer-reviewed journals and presented in scientific conferences. PACTR202003522049711.


Towards a label-free optical porous silicon DNA sensor.
We report on the fabrication of an optical silicon-based label-free DNA sensor. n-Type crystalline silicon wafers have been electrochemically etched to form porous silicon layers and characterized in terms of porosity, pore distribution, surface composition and photoluminescence. Samples (0.25 cm(2)) have been cut and properly derivatized using trimethoxy-3-bromoacetamidopropylsilane in order to link single strand DNA (ss-DNA). Such a molecule is not commercially available and has been ad-hoc prepared by reacting hydrobromic acid and 3-aminopropyltrimethoxysilane in presence of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide as coupling agent. Trimethoxy-3-bromoacetamidopropylsilane acts as a bridge anchored to the porous silicon surface through the silane group while immobilizing ss-DNA by means of the bromoacetamido moiety. We have found that derivatized samples exhibit a photoluminescence that is stable in time and is not modified after exposure to non-complementary DNA strand. On the other hand, a sensible enhancement of the light emission has been observed when the derivatized samples react with the complementary strand, showing that the specific ss-DNA/complementary DNA (c-DNA) interaction can be optically sensed without using further labeling steps. This strongly strengthens the possible role of silicon as a material for biosensors.


Identification of prior dengue-naïve Dengvaxia recipients with an increased risk for symptomatic dengue during fever surveillance in the Philippines.
Dengue virus (DENV) is the leading cause of mosquito-borne viral diseases in humans. Dengvaxia, the first licensed dengue vaccine, is recommended for DENV-seropositive individuals aged 9-45 years. In the Philippines, Dengvaxia was administered to more than 830,000 children without prior serological testing in 2016-2017. Subsequently, it was revealed that DENV-seronegative children who received Dengvaxia developed severe disease following breakthrough DENV infection. As a result, thousands of children participating in the mass vaccination campaign were at higher risk of severe dengue disease. It is vital that an assay that identifies baseline DENV-naïve Dengvaxia recipients be developed and validated. This would permit more frequent and extensive assessments and timely treatment of breakthrough DENV infections. We evaluated the performance of a candidate assay, the DENV1-4 nonstructural protein 1 (NS1) IgG enzyme-linked immunosorbent assay (ELISA), developed by the University of Hawaii (UH), using well-documented serum/plasma samples including those >20 years post-DENV infection, and tested samples from 199 study participants including 100 Dengvaxia recipients from the fever surveillance programs in the Philippines. The sensitivity and specificity of the assay were 96.6% and 99.4%, respectively, which are higher than those reported for pre-vaccination screening. A significantly higher rate of symptomatic breakthrough DENV infection was found among children that were DENV-naïve (10/23) than among those that were DENV-immune (7/53) when vaccinated with Dengvaxia (p=0.004, Fisher's exact test), demonstrating the feasibility of the assay and algorithms in clinical practice. The UH DENV1-4 NS1 IgG ELISA can determine baseline DENV serostatus among Dengvaxia recipients not only during non-acute dengue but also during breakthrough DENV infection, and has implications for assessing the long-term safety and effectiveness of Dengvaxia in the post-licensure period.


Assortative marriage for cognitive abilities.
One hundred and twenty-three spouse pairs gathered as part of a family study of the genetics of special abilities were examined on a battery of ability tests. Four principal components were interpreted after rotation: Spatial, Verbal, Perceptual Speed, and Memory. In addition, the first factor from a common factor analysis (unrotated) was taken as an estimate of g. Assortive marriage was measured by the spouse correlations on the test and factor scores. Three multiple regression models were designed to determine whether phenotypic convergence during marriage occurs and whether resemblance between spouses in cognitive ability is related to fertility. The following independent variables were partialed out in the models: (1) sex and age; (2) sex, age, and length of marriage; and (3) sex, age, and number of children. Model 1 (age and sex) accounted for part of the correlation between spouses on the spatial tests, the verbal tests and the spatial and general factors. The perceptual speed and memory tests and factors were largely unaffected by partialing out the independent variables. No evidence of phenotypic convergence over years of marriage or of a relationship between fertility and resemblance in abilities was found.


A predicted three-dimensional dose sequence based treatment planning optimization method for gynecologic IMRT.
In knowledge-based treatment planning (KBTP) for intensity-modulated radiation therapy (IMRT), the quality of the plan is dependent on the sophistication of the predicted dosimetric information and its application. In this paper, we propose a KBTP method that based on the effective and reasonable utilization of a three-dimensional (3D) dose prediction on planning optimization. We used an organs-at-risk (OARs) dose distribution prediction model to create a voxel-based dose sequence based optimization objective for OARs doses. This objective was used to reformulate a traditional fluence map optimization model, which involves a tolerable spatial re-assignment of the predicted dose distribution to the OAR voxels based on their current doses' positions at a sorted dose sequencing. The feasibility of this method was evaluated with ten gynecology (GYN) cancer IMRT cases by comparing its generated plan quality with the original clinical plan. Results showed feasible plan by proposed method, with comparable planning target volume (PTV) dose coverage and greater dose sparing of the OARs. Among ten GYN cases, the average V30 and V45 of rectum were decreased by 4%±4% (p = 0.02) and 4%±3% (p<0.01), respectively. V30 and V45 of bladder were decreased by 8%±2% (p<0.01) and 3%±2% (p<0.01), respectively. Our predicted dose sequence-based planning optimization method for GYN IMRT offered a flexible use of predicted 3D doses while ensuring the output plan consistency.


Basal ganglia-thalamocortical circuits: parallel substrates for motor, oculomotor, "prefrontal" and "limbic" functions.
The central theme of the "segregated circuits" hypothesis is that structural convergence and functional integration occurs within, rather than between, each of the identified circuits. Admittedly, the anatomical evidence upon which this scheme is based remains incomplete. The hypothesis continues to be predicated largely on comparisons of anterograde and retrograde labeling studies carried out in different sets of animals. Only in the case of the "motor" circuit has evidence for the continuity of the loop been demonstrated directly in individual subjects; for the other circuits, such continuity is inferred from comparisons of data on different components of each circuit obtained in separate experiments. Because of the marked compression of pathways leading from cortex through basal ganglia to thalamus, comparisons of projection topography across experimental subjects may be hazardous. Definitive tests of the hypothesis of maintained segregation await additional double- and multiple-label tract-tracing experiments wherein the continuity of one circuit, or the segregation of adjacent circuits, can be examined directly in individual subjects. It is worthy of note, however, that the few studies to date that have employed this methodology have generated results consistent with the segregated circuits hypothesis. Moreover, single cell recordings in behaving animals have shown striking preservation of functional specificity at the level of individual neurons throughout the "motor" and "oculomotor" circuits. It is difficult to imagine how such functional specificity could be maintained in the absence of strict topographic specificity within the sequential projections that comprise these two circuits. This is not to say, however, that we expect the internal structure of functional channels (e.g., the "arm" channel within the "motor" circuit) to have cable-like, point-to-point topography. When the grain of analysis is sufficiently fine, anatomical studies have shown repeatedly that the terminal fields of internuclear projections (e.g., to striatum, pallidum, nigra, thalamus, etc.) often appear patchy and highly divergent, suggesting that neighboring groups of projection cells tend to influence interdigitating clusters of postsynaptic neurons. While more intricate and complex than simple point-to-point topography, however, this type arrangement should also be capable of maintaining functional specificity. As discussed briefly above, it is not yet clear to what extent the inputs to the "motor" circuit from the different precentral motor fields (e.g., MC, SMA, APA) are integrated in their passage through the circuit. It now appears that at the level of the putamen such inputs remain segregated.(ABSTRACT TRUNCATED AT 400 WORDS)


Therapeutic Path to Double Knockout: Investigating the Selective Dual-Inhibitory Mechanisms of Adenosine Receptors A1 and A2 by a Novel Methoxy-Substituted Benzofuran Derivative in the Treatment of Parkinson's Disease.
The dual inhibition of adenosine receptors A1 (A1 AR) and A2 (A2A AR) has been considered as an efficient strategy in the treatment of Parkinson's disease (PD). This led to the recent development of a series of methoxy-substituted benzofuran derivatives among which compound 3j exhibited dual-inhibitory potencies in the micromolar range. Therefore, in this study, we seek to resolve the mechanisms by which this novel compound elicits its selective dual targeting against A1 AR and A2A AR. Unique to the binding of 3j in both proteins, from our findings, is the ring-ring interaction elicited by A1Phe275 (→ A2Phe170) with the benzofuran ring of the compound. As observed, this π-stacking interaction contributes notably to the stability of 3j at the active sites of A1 and A2A AR. Besides, conserved active site residues in the proteins such as A1Ala170 (→ A2Ala65), A1Ile173 (→ A2Ile68), A1Val191 (→ A2Val86), A1Leu192 (→ A2Leu87), A1Ala195 (→ A2Ala90), A1Met284 (→ A2Met179), A1Tyr375 (→ A2Tyr369), A1Ile378 (→ A2Ile372), and A1His382 (→ A2His376) were commonly involved with other ring substituents which further complement the dual binding and stability of 3j. This reflects a similar interaction mechanism that involved aromatic (π) interactions. Consequentially, vdW energies contributed immensely to the dual binding of the compound, which culminated in high ΔGbinds that were homogenous in both proteins. Furthermore, 3j commonly disrupted the stable and compact conformation of A1 and A2A AR, coupled with their active sites where Cα deviations were relatively high. Ligand mobility analysis also revealed that both compounds exhibited a similar motion pattern at the active site of the proteins relative to their optimal dual binding. We believe that findings from this study with significantly aid the structure-based design of highly selective dual-inhibitors of A1 and A2A AR.


Ready, steady, go! A sugar hit starts the race to shoot branching.
In the classical theory of apical dominance, auxin depletion from the stem releases bud dormancy. Recent studies have revealed a poor correlation between the initial bud release and auxin depletion from the stem after decapitation. Sucrose mobility in plants and its accumulation in buds correlates well with the onset of bud release and is able to trigger bud outgrowth. The diversion of sugars away from axillary buds decreases bud release even where hormones are at levels generally considered conducive to bud release. This impact of sugars on bud outgrowth may be mediated by specific sugar and hormonal signalling pathways.


In vitro inhibitory effects of Kampo medicines on metabolic reactions catalyzed by human liver microsomes.
Although it is well known that drug-drug interactions may lead to toxicity and therapeutic failure, little is known about the incidence and consequences of herb-drug interactions in patients receiving Kampo medicines. We evaluated the frequency of the combined use of Kampo medicines and Western drugs at Osaka University Hospital, and investigated the effects of these formulae on the metabolic activity of different cytochrome P450 (CYP) isoforms using pooled microsomes obtained from human liver. Twenty-two Kampo formulae were used together with 40 Western drugs catalyzed by the CYP isoforms CYP3A4, CYP2C9, CYP2D6 and CYP1A2. Among the Kampo medicines, HOCHUEKKI-TO, SHOSAIKO-TO, NINJINYOUEI-TO, SAIREI-TO and KAKKON-TO were most frequently used during the study period (1996-2000). These were co-administered with 11 categories of drugs, which are substrates for CYP3A4. HOCHUEKKI-TO and SAIREI-TO were competitive inhibitors of CYP3A4 with Ki values of 0.65 and 0.1 mg/mL, respectively. HOCHUEKKI-TO, SHOSAIKO-TO and SAIREI-TO inhibited the metabolic activities of CYP2C9, but had no effect on CYP2D6. HOCHUEKKI-TO and SAIREI-TO exhibited non-competitive inhibition of the metabolic activity of CYP2C9 with a similar Ki value (0.7-0.8 mg/mL). SAIRE-TO (0.25 mg/mL) was a potent inhibitor of CYP1A2 (inhibition > 68%). Frequently used Kampo medicines may interact with Western drugs, which are substrates for CYP3A4, CYP2C9 and CYP1A2. Their co-administration should be undertaken with care.


Heart rate estimation in PPG signals using Convolutional-Recurrent Regressor.
Heart rate monitoring using PPG signal has emerged as an attractive as well as an applied research problem which enjoys a renewed interest in the recent years. Spectral analysis of PPG for heart rate monitoring, though effective when the subject is at rest, suffers from performance degradation in case of motion artifacts which mask the peak related with the actual heart rate. Leveraging the recent advancements in deep (machine) learning and exploiting the signal, spectral and time-frequency perspectives, we introduce an effective method for heart rate estimation from PPG signals acquired from subjects performing different exercises. We extract a set of features characterizing the signal and feed these feature sequences to a hybrid convolutional-recurrent neural network (C-RNN) in a regression framework. Experimental study on the benchmark IEEE signal processing cup dataset reports low error rates reading 2.41 ± 2.90 bpm for subject-dependent and 3.8 ± 2.3 bpm for subject-independent protocol thus, validating the ideas put forward in this study.


Associations between the chemical exposome and pregnancy induced hypertension.
Exposure to environmental chemicals has been linked to an increased risk of pregnancy-induced hypertension (PIH). This prospective cohort study examined the associations between PIH and maternal chemical exposure to four classes of chemicals (i.e., phthalates, bisphenols, perfluoroalkyl acids, non-essential metals and trace minerals). Participants included 420 pregnant women from the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort who had data available on diagnosed PIH and environmental chemical exposure. Twelve phthalate metabolites, two bisphenols, eight perfluoroalkyl acids and eleven non-essential metals or trace minerals were quantified in maternal urine or blood samples collected in the second trimester of pregnancy. Associations between the urinary and blood concentrations of these chemicals and PIH were assessed using multiple logistic and LASSO regression analyses in single- and multi-chemical exposure models, respectively. Thirty-five (8.3%) participants were diagnosed with PIH. In single chemical exposure models, two phthalate metabolites, mono-methyl phthalate (MMP) and monoethyl phthalate (MEP), three perfluoroalkyl acids, perfluoroheptanoic acid (PFHpA), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA), and one metal, manganese, were associated with increased odds of PIH. The metabolites of di (2-ethylhexyl) phthalate (DEHP) and the molar sum of these metabolites, as well as antimony, displayed trend associations (p < 0.10). In multi-chemical exposure models using LASSO penalized regressions and double-LASSO regressions, MEP (AOR: 1.43, 95% CI: 1.09-1.88, p = 0.009) and PFNA (AOR: 2.03, 95% CI: 1.01-4.07, p = 0.04) were selected as the chemicals most highly associated with PIH. These findings suggest that maternal levels of phthalates and perfluoroalkyl acids may be associated with the diagnosis on PIH. Future research should consider both individual and multi-chemical exposures when examining predictors of PIH and other maternal cardiometabolic health disorders, such as preeclampsia, eclampsia, HELLP syndrome, and gestational diabetes.


EBV-positive mucocutaneous ulcer presenting as a nasopharyngeal tumor in an immune suppressed patient.
We describe an unusual presentation of EBV-associated mucocutaneous ulcer presenting as a large tumor of the nasopharynx in an immune suppressed child. This condition is newly characterized and has not been well-studied in the otolaryngology literature. Our patient is a 12-year-old female undergoing chemotherapy for T-cell acute lymphoblastic leukemia who presented with progressively severe headaches, nasal obstruction, facial pain/pressure, photophobia, fever and otalgia associated with neutropenia and refractory to empiric antibiotic therapy. Bedside nasal endoscopy and imaging revealed signs of acute sinusitis and a large nasopharyngeal mass suspicious for neoplasm. The mass was eccentric to the right and distending the right fossa of Rosenmuller. She underwent endoscopic sinus surgery and biopsy of her nasopharyngeal mass. Pathologic analysis of the nasopharyngeal mass revealed EBV-positive mucocutaneous ulcer. This is an unusual presentation of a rare entity. EBV-positive mucocutaneous ulcer warrants awareness among otolaryngologists and is not well-described in our literature.


Usefulness of cardiac computed tomography in prosthetic heart valve dysfunction.
Prosthetic heart valve (PHV) dysfunction is a serious complication. Echocardiography remains the first-line imaging investigation to assess PHV dysfunction. However, the role of Computed Tomography (CT) scanning in this type of case has not been thoroughly studied yet. The objective of our study was to determine if cardiac Computed Tomography (CT) had a potentially complementary role to play alongside echocardiography in diagnosing the mechanism of prosthetic valve dysfunction. This prospective cohort study was conducted on 54 patients with suspected PHV dysfunction. All patients underwent routine diagnosis work-up (transthoracic and transesophageal echocardiography) and additional cardiac CT. Cardiac CT showed findings that were not detected by echocardiography in seven patients (12%) namely aortic pannus (5) and pseudoaneurysm (2). An underlying thrombus was detected by echocardiography and missed by cardiac CT in 15 patients (27%). However, in these thrombotic cases, cardiac CT contributed to the functional evaluation of leaflets. This study demonstrates that an integrated approach including transthoracic, transesophageal echocardiography and computed tomography is useful in patients with suspected PHV dysfunction. While computed tomography is more accurate in the diagnosis of pannus formation and periannular complications, echocardiography is superior at detecting thrombus.


Overexpression of Wld(S) or Nmnat2 in mauthner cells by single-cell electroporation delays axon degeneration in live zebrafish.
Axon degeneration is supposed to be a therapeutic target for treating neurodegenerative diseases. Mauthner cells (M-cells) are ideal for studying axons in vivo because of their limited numbers, large size, and long axons. In this study, we labeled M-cells by single-cell electroporation with plasmids expressing DsRed2 or EGFP. Injury-induced axon degeneration in labeled M-cell was imaged under a confocal microscope, and we found that the Mauthner axons started to degenerate about 24 hr after lesion. The Wld(S) protein containing full-length Nmnat1 is well-known for its axon-protective function in many systems. Overexpression of Wld(S) in M-cells also greatly delayed axon degeneration in live zebrafish. Nmnat2 is the only Nmnat highly expressed in brain. Here we demonstrated that overexpression of Nmnat2 in M-cells significantly delayed axon degeneration in vivo, and disruption of the NAD synthesis activity of Nmnat2 markedly attenuated its axon-protective function. All these data show that injury-induced axon degeneration of M-cell has a mechanism similar to that in mammalians and would be a valuable model for studying axon degeneration in vivo.


The I260Q variant of DNA polymerase beta extends mispaired primer termini due to its increased affinity for deoxynucleotide triphosphate substrates.
DNA polymerase beta plays a key role in base excision repair. We have previously shown that the hydrophobic hinge region of polymerase beta, which is distant from its active site, plays a critical role in the fidelity of DNA synthesis by this enzyme. The I260Q hinge variant of polymerase beta misincorporates nucleotides with a significantly higher catalytic efficiency than the wild-type enzyme. In the study described here, we show that I260Q extends mispaired primer termini. The kinetic basis for extension of mispairs is defective discrimination by I260Q at the level of ground-state binding of the dNTP substrate. Our results suggest that the hydrophobic hinge region influences the geometry of the dNTP binding pocket exclusively. Because the DNA forms part of the binding pocket, our data are also consistent with the interpretation that the mispaired primer terminus affects the geometry of the dNTP binding pocket such that the I260Q variant has a higher affinity for the incoming dNTP than wild-type polymerase beta.


Transcriptional network of androgen receptor in prostate cancer progression.
The androgen receptor belongs to the nuclear receptor superfamily and functions as a ligand-dependent transcription factor. It binds to the androgen responsive element and recruits coregulatory factors to modulate gene transcription. In addition, the androgen receptor interacts with other transcription factors, such as forkhead box A1, and other oncogenic signaling pathway molecules that bind deoxyribonucleic acid and regulate transcription. Androgen receptor signaling plays an important role in the development of prostate cancer. Prostate cancer cells proliferate in an androgen-dependent manner, and androgen receptor blockade is effective in prostate cancer therapy. However, patients often progress to castration-resistant prostate cancer with elevated androgen receptor expression and hypersensitivity to androgen. Recently, comprehensive analysis tools, such as complementary DNA microarray, chromatin immunoprecipitation-on-chip and chromatin immunoprecipitation-sequence, have described the androgen-mediated diverse transcriptional program and gene networks in prostate cancer. Furthermore, functional and clinical studies have shown that some of the androgen receptor-regulated genes could be prognostic markers and potential therapeutic targets for the treatment of prostate cancer, particularly castration-resistant prostate cancer. Thus, identifying androgen receptor downstream signaling events and investigating the regulation of androgen receptor activity is critical for understanding the mechanism of carcinogenesis and progression to castration-resistant prostate cancer.


Hypertension in childhood from renal vein thrombosis.
A case is presented of a 1-year-old boy with hypertension resulting from abnormal renin production by the right kidney. The kidney had undergone infarction and atrophy secondary to renal vein thrombosis. The left kidney remained normal despite inferior vena cava thrombosis because of the development of collateral venous circulation. The hypertension was cured by right nephrectomy. The child remains normotensive and with a normal serum creatinine at 1-year followup.


Identification by genetic algorithm optimized back propagation artificial neural network and validation of a four-gene signature for diagnosis and prognosis of pancreatic cancer.
Although some improvements in the management of pancreatic cancer (PC) have been made, no major breakthroughs in terms of biomarker discovery or effective treatment have emerged. Here, we applied artificial intelligence (AI)-based methods to develop a model to diagnose PC and predict survival outcome. Multiple bioinformatics methods, including Limma Package, were performed to identify differentially expressed genes (DEGs) in PC. A Back Propagation (BP) model was constructed, followed by Genetic Algorithm (GA) filtering and verification of its prognosis capacity in the TCGA cohort. Furthermore, we validated the protein expression of the selected DEGs in 92 clinical PC tissues using immunohistochemistry. Finally, intro studies were performed to assess the function of SLC6A14 and SPOCK1 on pancreatic ductal adenocarcinoma (PDAC) cells proliferation and apoptosis. Four candidate genes (LCN2, SLC6A14, SPOCK1, and VCAN) were selected to establish a four-gene signature for PC. The gene signature was validated in the TCGA PC cohort, and found to show satisfactory discrimination and prognostic power. Areas under the curve (AUC) values of overall survival were both greater than 0.60 in the TCGA training cohort, test cohort, and the entire cohort. Kaplan-Meier analyses showed that high-risk group had a significantly shorter overall survival and disease-free survival than the low-risk group. Further, the elevated expression of SLC6A14 and SPOCK1 in PC tissues was validated in the TCGA + GETx datasets and 92 clinical PC tissues, and was significantly associated with poor survival in PC. In PDAC cell line, SLC6A14 or SPOCK1 knockdown inhibited cells proliferation, migration and promoted cells apoptosis. Using Limma Package and GA-ANN, we developed and validated a diagnostic and prognostic gene signature that yielded excellent predictive capacity for PC patients' survival. In vitro studies were further conducted to verify the functions of SLC6A14 and SPOCK1 in PC progression.


When histologic diagnosis of pulmonary adenocarcinoma becomes difficult.
The differential diagnosis between pulmonary adenocarcinoma and several benign mimics can be a formidable challenge for the surgical pathologist, particularly in frozen sections and in small biopsies but sometimes in surgical specimens as well. In this review we will provide a practical guide to help the pathologist facing these problematic cases.


[Education interventions in heart failure using m-Health: Systematic review].
To provide the best scientific evidence available on the effectiveness of therapeutic education programs through digital health in patients with heart failure. Systematic review of randomized clinical trials. Six databases were included due to their relevance in Health Sciences: PubMed, EMBASE, Scielo, Cochrane, CINAHL, and Web of Science. In English and Spanish, studies carried out between 2018 and 2023 were selected. After evaluating the methodological quality of the studies, the Jadad tool was used to discriminate those that did not meet said quality. In total, 8 articles from 6 different countries were included. The review and analysis of the documents were carried out by independent pairs. The Cochrane tool for RoB 2 randomized clinical trials was used to assess the risk of bias. All the applications had therapeutic education, it was also assessed that they had monitoring, evaluation of signs and symptoms, drug titration, and professional follow-up through the application. This review reveals the significant impact of therapeutic education in increasing patient knowledge, reducing hospital readmissions, and improving functional status and self-care. This makes digital health a valuable tool to complement nursing care in patients with heart failure.


Learning Analytics and the Community of Inquiry: Indicators to Analyze and Visualize Online-Based Learning.
The Community of Inquiry (CoI) describes success factors for online-based learning. To develop approaches for automatic analysis of CoI to be visualized within student and teacher dashboards. Extending indicators from social network analysis and linguistics; evaluation within a case study. The project is just starting. Results will help to better understand and improve cooperative online-based learning in higher education.


Color vision impairment in workers exposed to neurotoxic chemicals.
Recent research shows that occupational exposure to several solvents, metals and other industrial chemicals can impair color vision in exposed workers. Occupation-related color vision impairment usually results in blue-yellow color discrimination loss or, less frequently, a combination of blue-yellow and red-green loss. The eyes may be unequally involved, and the course is variable depending on exposure and other factors. The pathogenesis of occupational color vision loss has not been elucidated; it may be due to, e.g. a direct action of neurotoxins on receptors, possibly on the cone's membrane metabolism, and/or to an interference with neurotransmitters within the retina. Other possible pathogenetic mechanisms, such as a direct effect to the optic nerve, have also been suggested. Occupational color vision loss is usually sub-clinical, and workers are unaware of any deficit. It can be assessed using sensitive tests, such as the Farnsworth-Munsell 100 Hue (FM-100) or the Lanthony D-15 desaturated panel (D-15 d). The latter is the most widely used for studies in groups of exposed workers, and offers the possibility of a quantitative evaluation of the results by calculation of the Bowman's Color Confusion Index (CCI), or of the Vingrys' and King Smith's Confusion Index (CI). Other advantages of D-15 d are the possibility to perform the test directly at the workplace, and the reproducibility when performed in standardized conditions. In most cases, occupation-related color vision impairment is correlated to exposure levels, and has often been observed in workers exposed to environmental concentrations below the current occupational limit proposed by the ACGIH. Progression with increasing cumulative exposure has been reported, while reversibility is still discussed. Acquired color vision impairment related to occupational exposure to styrene, perchloroethylene (PCE), toluene, carbon disulfide, n-hexane, solvent mixtures, mercury and some other chemicals are discussed. Results show that color vision testing should be included in the evaluation of early neurotoxicity of chemicals in exposed workers. The D-15 d would be useful in the surveillance of workers exposed to solvents and other chemicals toxic to the visual system.


Root growth in the teeth of 46,XY females.
The subjects of this study are women with a male sex chromosome complement or 46,XY females who show the complete form of the testicular feminization syndrome (CTF). The basic endocrine defect is end organ insensitivity to androgens. They are on average tall individuals and also show an increase in head and face dimensions relative to normal females. A size increase is likewise evident in permanent tooth crowns and here we report permanent tooth root lengths in eight 46,XY females, their five female relatives and population control females and males. Measurements were made from panoramic radiographs by a digital calliper according to established procedures on both sides of the jaws. The results show increased root lengths of 46,XY females relative to control females with values similar to those in population control males. The root and crown findings point to evident irreversible growth excesses in 46,XY females beginning 3 years after birth up to the age of 14 years expressing an effect which apparently is influencing in a continuous way. Excess root growth conceivably would develop independently of the possible androgen influence, and it is suggested that the increase results from the direct effect of the genes on the Y chromosome. It is possible that these genes on the Y chromosome are the same that promote tooth crown growth.


Changes in photoelectron transport of chloroplasts isolated from dark stressed leaves of maize seedlings.
Transfer of light-grown maize seedlings to dark causes a loss in the the contents of chlorophyll, protein and RNA of leaves, and a decline in DCPIP photoreduction by isolated chloroplasts. The loss in DCPIP-Hill reaction is attributed to the dark stress-induced damage of O2 evolving system of thylakoid membranes.


The potential for complex computational models of aging.
The gradual accumulation of damage and dysregulation during the aging of living organisms can be quantified. Even so, the aging process is complex and has multiple interacting physiological scales - from the molecular to cellular to whole tissues. In the face of this complexity, we can significantly advance our understanding of aging with the use of computational models that simulate realistic individual trajectories of health as well as mortality. To do so, they must be systems-level models that incorporate interactions between measurable aspects of age-associated changes. To incorporate individual variability in the aging process, models must be stochastic. To be useful they should also be predictive, and so must be fit or parameterized by data from large populations of aging individuals. In this perspective, we outline where we have been, where we are, and where we hope to go with such computational models of aging. Our focus is on data-driven systems-level models, and on their great potential in aging research.


Impact of risk factors for recurrent ischemic stroke in Prasat Neurological Institute.
Recurrent strokes are more likely to be more disabling or fatal than first-even strokes. The high frequency of recurrences underscores the importance ofsecondary prevention. Investigate risk factors of recurrent ischemic stroke and to compare the outcomes after treatment following the Thai stroke guideline between patients with recurrent ischemic stroke and patients without recurrent ischemic stroke. Sixty-seven patients with recurrent ischemic stroke and 167 patients without recurrent ischemic stroke were included in the present study. All patients were evaluated for demographic data, modifiable risk factors, and treatment. Patients without recurrent ischemic stroke had better controlled level of systolic blood pressure, diastolic blood pressure, and higher high-density lipoprotein level than patients with recurrent ischemic stroke. Carotid stenosis was higher in patients with recurrent ischemic stroke (43.3% vs. 28.7%, p = 0.032). Patients with recurrent ischemic stroke received statin therapy (67.2% vs. 86.8%, p = 0.001) and folic acid (61.2% vs. 78.4%, p = 0.007) less than patients without recurrent ischemic stroke. The multivariate analysis showed that well controlled diastolic blood pressure (p = 0.014), higher level of high-density lipoprotein (p = 0. 010), and receiving of statin (p = 0.002) were associated with decreased incidence of recurrent ischemic stroke. Well-controlled risk factors including blood pressure, fasting blood sugar, high-density lipoprotein, and low-density lipoprotein were crucial for the protection of recurrent ischemic stroke. Furthermore, the benefits of statin and folic acid therapies for the protection of recurrent ischemic stroke were emphasized


Retrovirus-Based Surrogate Systems for BSL-2 High-Throughput Screening of Antivirals Targeting BSL-3/4 Hemorrhagic Fever-Causing Viruses.
The majority of viruses causing hemorrhagic fever in humans are Risk Group 3 or 4 pathogens and, therefore, can only be handled in biosafety level 3 or 4 (BSL-3/4) containment laboratories. The restricted number of such laboratories, the substantial financial requirements to maintain them, and safety concerns for the laboratory workers pose formidable challenges for rapid medical countermeasure discovery and evaluation. BSL-2 surrogate systems are a less challenging, cheap, and fast alternative to the use of live high-consequence viruses for dissecting and targeting individual steps of viral lifecycles with a diminished threat to the laboratory worker. Typical surrogate systems are virion-like particles (VLPs), transcriptionally active ("infectious") VLPs, minigenome systems, recombinant heterotypic viruses encoding proteins of target viruses, and vesiculoviral or retroviral pseudotype systems. Here, we outline the use of retroviral pseudotypes for identification of antivirals against BSL-4 pathogens.


Sex and cognition: gender and cognitive functions.
Gender stereotypes hold that males outperform females in mathematics and spatial tests, and females outperform males on verbal tests. According to meta-analyses, however, among both children and adults, females perform equally to males on mathematics assessments. The gender difference in verbal skills is small and varies depending on the type of skill assessed (e.g., vocabulary, essay writing). The gender difference in 3D mental rotation shows a moderate advantage for males, but this gender difference occurs in the absence of a spatial curriculum in the schools. Meta-analyses of gender differences across a wide array of psychological qualities support the Gender Similarities Hypothesis, which states that males and females are quite similar on most-but not all-psychological variables.


Piperidine-based renin inhibitors: upper chain optimization.
The optimization of the 4-position of recently described new 3,4-disubstituted piperidine-based renin inhibitors is reported herein. The synthesis and characterization of compounds leading to the discovery of 11 (ACT-178882, MK-1597), a renin inhibitor with a suitable profile for development is described.


SIRT1 (rs3740051) role in pituitary adenoma development.
Our purpose was to determine if SIRT1 (rs4746720, rs3740051) genotypes have an influence on the development of pituitary adenoma (PA). The study group included 142 patients with pituitary adenoma (PA) and the control group consisted of 826 healthy people. The genotyping of SIRT1 (rs4746720, rs3740051) was carried out using the real-time polymerase chain reaction method. Statistically significant results were obtained in the analysis of SIRT1 rs3740051. Significant differences in genotype (G/G, G/A, A/A) distribution were obtained comparing patients with PA without recurrence and PA with recurrence (0, 17.9, 82.1% vs. 6.7, 6.7, 86.7%, respectively, p = 0.022). Also, statistically significant differences were observed when comparing the genotype (G/G, G/A, A/A) distribution in the non-invasive PA group and the invasive PA group (3.4, 25.9, 70.7% vs. 0, 8.3, 91.7%, respectively, p = 0.003), and allele G was less frequently observed in invasive PA, than in non-invasive PA (4.2% vs. 16.4%, p < 0,001). Further analysis revealed that G/A (OR = 0.261; 95% CI:0.099-0.689; p = 0.007) and each allele A (OR = 0.229; 95% CI:0.091-0.575; p = 0.002) were associated with lower odds of occurring an invasive PA. Our study revealed that SIRT1 rs3740051 is associated with PA recurrence and invasiveness. The haplotype containing alleles C-A in rs12778366-rs3740051 was found to be associated with increased odds of PA development as well.


Differences in coprophilous beetle communities structure in Sierra de Minas (Uruguay): a mosaic landscape.
Coprophilous beetles represent an abundant and rich group with critical importance in the functioning of terrestrial ecosystems. Most coprophagous beetles have a stenotopic distribution in relation to vegetation types. Because of this, they are usually very sensitive to environmental changes and are considered well suited as bioindicator organisms. The aim of this study was to analyze variations in coprophilous beetle assemblages in natural and anthropogenic habitats. Coprophilous beetle communities were sampled monthly for 1 year using pitfall traps baited with cow dung, in native xeric upland forests, 15-years-old plantations of Pinus elliottii and pastures in Sierra de Minas, Lavalleja, Uruguay. A total of 7,436 beetles were caught and identified to species or morphospecies level. The most abundant families were Aphodiidae, Scarabaeidae, and Staphylinidae. Differences in species richness, abundance, Shannon index, evenness, and dominance were detected between habitats. Abundances of most frequent families were significantly higher in both kinds of forests. Species richness and diversity of Aphodiidae and Staphylinidae were higher in forests, while Scarabaeidae showed the highest richness and diversity in pine plantations. Species composition significantly differed between habitats. Uroxys terminalis Waterhouse and Ataenius perforatus Harold typified the assemblages in native forests and pine plantations and also discriminated both communities because of their differential pattern of abundance between habitats. Typifying species in pastures were Onthophagus hirculus, Ateuchus robustus (Harold), and Ataenius platensis Blanchard. Habitat type had a strong effect on the coprophilous beetle community structure and composition.


Computerized tomography of ischemic myocardium: quantitation of extent and severity of edema in an in vitro canine model.
The capacity of computerized tomography to assess myocardial edema resulting from acute coronary occlusion was investigated in 19 arrested and 2 beating canine hearts. Edematous myocardium was consistently detected as areas of decreased attenuation values. The magnitude of the decrease in attenuation value was linearly related to the severity of the edema. The anatomic definition and tomographic information in the arrested hearts provided the capability for localization and quantitation of the extent of the lesion. The results of these in vitro investigations indicate that CT scanning is a technique which will contribute important pathophysiologic information about the evolution of myocardial ischemia.


Bimanual coordination in children: manipulation of object distance.
The performance of many everyday activities requires the coordination of the two upper limbs to achieve the goal of the task. Although bimanual performance has been studied in detail in adults, few studies have examined how children coordinate the movements of the two hands during symmetric and asymmetric bimanual prehension. With the current study, we asked younger (4-6 years, n = 14) and older (7-10 years, n = 16) children to complete a discrete bimanual task. Specifically, they reached to grasp cylinders located at near and far positions in either unimanual or bimanual condition. During bimanual symmetric conditions, participants performed movements with both hands toward two objects located at the same distance (both near or both far), while in the bimanual asymmetric conditions, they reached for objects at different distances. Results of the kinematic analyses indicated that the young children consistently experienced the "two target" effect, whereby bimanual movements were executed more slowly than unimanual movements to the same distance. Older children employed a hybrid strategy, exhibiting slower movements in bimanual congruent conditions, but larger non-dominant apertures in bimanual incongruent conditions. This hybrid strategy was hypothesized to stem from developmental changes occurring in the integration of sensory information around 8 years of age. While older children exhibited temporal and spatial coordination patterns that were similar to patterns reported in adults, large relative timing differences at the start and end of bimanual movements and considerably weaker spatial coupling were seen in the younger children.


Isolated torsion of the fallopian tube with hydrosalpinx mimicking a multiloculated ovarian cyst: whirlpool sign on preoperative sonography and MRI.
Isolated torsion of the fallopian tube is a rare case of lower abdominal pain. Early diagnosis of such cases is crucial because it allows for the possibility of salvage surgery and the prevention of irreversible vascular damage. However, diagnosis is rarely made before surgery due to nonspecific clinical and imaging features. We report a case of isolated tubal torsion with specific imaging findings on preoperative ultrasonography, color Doppler ultrasonography, and magnetic resonance imaging that was misdiagnosed as a multiloculated ovarian cyst at a local hospital.


[Functioning of the antioxidant system in epithelial cells of small intestine under the influence of ionizing radiation of low dose rate].
The investigations of the functional state of the antioxidant system in epithelial cells from rat small intestine in dynamics after X-ray irradiation (0.1; 0.5 and 1.0 Gy) at a low absorbed dose rate (55 mGy/min) were performed. The obtained results point out the ambiguity of the antioxidant system reaction to the activation of oxidative processes at different doses of irradiation. The multidirectional changes of these antioxidant enzymatic activities whose functioning is characterized by the early post-irradiation recovery depending on the value of the absorbed dose were observed. The sensitivity of superoxide dismutase, glutathione transferase and glutathione peroxidase in mitochondria of epithelial cells to the irradiation exposure in the investigated range of absorbed doses was shown.


The implications of increased mammographic breast density for breast screening in Jordan.
Mammographic breast density is associated with a four to six times increased risk for breast cancer. Mammographic breast density varies by ethnicity, geographical region and age. The aim of this study was to document for the first time the mammographic breast density of Jordanian women and to explore its relationship with age. Mammograms completed at King Abdullah University Hospital (Irbid, Jordan) between January 2016 and August 2018 were retrospectively reviewed and classified for breast density using the American College of Radiology (ACR) Breast Imaging-Reporting and Data System (BI-RADS). Descriptive analyses and Kurskal-Wallis test were used to examine the association between age and mammographic breast density. A total of 659 mammograms were reviewed. A significant inverse relationship was observed between age and breast density (P < 0.001). In women aged 40-49 years, 83.2% had dense breasts (ACR BI-RADS (c) and (d)). This percentage decreased to 59.8% of women aged 50-59 years; 38.4% of women in their 60s and 37.9% of women aged 70 years or older (ACR BI-RADS (c) only). The mammographic breast density of Jordanian women has been shown to be high across all age groups. Increased mammographic breast density is associated with increased breast cancer risk and renders mammography a less effective technique for the early detection of breast cancer. Breast cancer screening of Jordanian women should be individualised to develop screening protocols and include additional adjunct imaging to best manage women at high risk.


Impact of the introduction of a standardised ICD programming protocol: real-world data from a single centre.
Randomised trials have shown that empiric ICD programming, using long detection times and high detection zones, reduces device therapy in ICD recipients. However, there is less data on its effectiveness in a "real-world" setting, especially secondary prevention patients. Our aim was to evaluate the introduction of a standardised programming protocol in a real-world setting of unselected ICD recipients. We analysed 270 consecutive ICD recipients implanted in a single centre-135 implanted prior to protocol implementation (physician-led group) and 135 after (standardised group). The protocol included long arrhythmia detection times (30/40 or equivalent) and high rate detection zones (primary prevention lower treatment zone 200 bpm). Programming in the physician-led group was at the discretion of the implanter. The primary endpoint was time-to-any therapy (ATP or shocks). Secondary endpoints were time-to-inappropriate therapy and time-to-appropriate therapy. The safety endpoints were syncopal episodes, hospital admissions and death. At 12 months follow-up, 47 patients had received any ICD therapy (physician-led group, n = 31 vs. standardised group, n = 16). There was a 47 % risk reduction in any device therapy (p = 0.04) and an 86 % risk reduction in inappropriate therapy (p = 0.009) in the standardised compared to the physician-led group. There was a non-significant 30 % risk reduction in appropriate therapy (p = 0.32). Results were consistent across primary and secondary prevention patients. There were no significant differences in the rates of syncope, hospitalisation, and death. In unselected patients in a real-world setting, introduction of a standardised programming protocol, using long detection times and high detection zones, significantly reduces the burden of ICD therapy without an increase in adverse outcomes.


Health care policies/economics of the geriatric renal population.
The end-stage renal disease (ESRD) program is the only Medicare program for which entitlement is based on the presence of a medical diagnosis. In addition, entitlement is nearly universal. Over 90% of persons with ESRD receive Medicare benefits. Because of these unique characteristics, the ESRD program has been the subject of continuing debates about the role of the Federal government in the categorical funding of high-cost illnesses, reimbursement policies, and the ethical issues of treatment of terminal, or near terminal, patients. This report presents descriptive data from the Medicare ESRD Program Management and Medical Information System (PMMIS) concerning trends in program expenditures, incidence and prevalence of ESRD, and mortality. The purpose is to provide background material for informed discussions of these issues. Expenditures for the ESRD program have grown from $240 million in 1974 to $3.3 billion in 1987. During that same time, total Medicare expenditures increased at a comparable rate so that ESRD costs have remained a relatively constant proportion of Medicare costs for the last decade. The ESRD population is rapidly changing. Between 1978 and 1987, enrollment nearly tripled, from 44,000 to 124,000. Much of this change has occurred in the elderly population. Persons over 65 accounted for 20% of total enrollment in 1978 and 29% of total enrollment in 1987. Census projections show that the "graying" of the ESRD population will continue into the foreseeable future. Transplantation has had a marked effect on the ESRD population. Persons with a functioning kidney graft have increased from 11% of the total population in 1978 to 22% in 1987.(ABSTRACT TRUNCATED AT 250 WORDS)


A grey-DEMATEL approach for analyzing factors critical to the implementation of reverse logistics in the pharmaceutical care process.
There is an increasing interest in product recovery, closed-loop supply chains, and reverse logistics (RL) for mitigating environmental impairment. Although RL is becoming a mandatory policy in developed countries, it is still in an embryonic stage in some industrial sectors of emerging economies. The purpose of this study is twofold: (1) identify the critical factors to the successful implementation of RL in the Brazilian pharmaceutical care process (PCP) and (2) determine the cause-and-effect relationships among them. We use snowball sampling to select the relevant RL studies and deductive reasoning and classification to identify the critical factors and a grey decision-making trial and evaluation laboratory (DEMATEL) to evaluate the cause-and-effect relationships among them. The study revealed management, collaboration, information technology, infrastructure, policy, financial and economic, end-of-life management practices, and logistic performance factors as the most relevant factors to the successful implementation of RL in the Brazilian PCP. The end-of-life management practices were identified as the most critical factor, and information technology was identified as the least critical factor. We further determined the end-of-life management practices and policy have the strongest casual relationship. The municipal PCP coordinators can use the findings of this study to formulate mitigating strategies to identify and eliminate barriers to the successful implementation of RL in the Brazilian PCP.