A Discrete Choice Experiment to Elicit General Population Preferences Around the Factors Influencing the Choice to Make Clinical Negligence Claims.
This article determines public stated preferences around different factors that influence the choice to make clinical negligence claims against a national healthcare system. A large online survey was conducted using a discrete choice experiment (DCE) with the UK general population (N = 1013). DCE tasks involved a single profile and participants chose whether to make a claim for compensation (yes/no) after one of 3 randomly allocated patient safety incident (PSI) "scenarios" of different severities (mild, moderate, severe). DCE attributes described the actions of the healthcare system after a PSI and characteristics of the clinical negligence claims process. The data were modeled separately for each scenario (mild, moderate, severe) using logistic regression. Marginal effects and the probability of making a claim in a baseline case were estimated. Probability of choosing to claim was reduced by receipt of an apology, investigation and prevention of recurrence of the PSI, and longer time until claim decision and increased by an easy and straightforward claims process and high chance of compensation and for the mild scenario higher compensation amounts. Marginal effects and baseline case probabilities differed by scenario severity. The results suggest the actions of the healthcare system after a PSI and characteristics of the claims process have a larger impact on the probability of making a claim for milder PSIs. For more severe PSIs, a larger probability of making a claim was observed, and the choice was less influenced by the actions of the healthcare system after the PSI and characteristics of the claims process.


Inadvertent amniocenteses occurring during unrelated invasive diagnostic procedures in the third trimester.
Two cases of inadvertent third trimester amniocenteses occurring during attempted spinal tap and culdocentesis are presented. These hitherto undescribed occurrences stress potential complications of these invasive diagnostic procedures in the gravid woman.


Advanced granulomatous lesions in Mycobacterium bovis-infected cattle are associated with increased expression of type I procollagen, gammadelta (WC1+) T cells and CD 68+ cells.
The pathognomonic characteristic of tuberculosis (TB) is the formation of a tuberculous granuloma. The objective of this study was to classify lymph node granulomas from experimentally infected calves into different histopathological stages and characterize them further by studying cell types and markers of fibrosis associated with each of the stages. Four stages of granuloma were identified and mRNA and protein expression for cell markers, cytokines and pro-fibrotic markers were studied by immunohistochemistry (IHC) and in-situ hybridization (ISH). In advanced stage granulomas, there was an increase in the expression of TGF-beta, and of type I procollagen as demonstrated by IHC and ISH. As the granulomas advanced, there were fewer CD3+T cells and they tended to be more prominent towards the periphery of the lesions, with a steady increase in the number of CD68+ cells and gammadelta (WC1+) T cells. Granuloma classification and application of cell cytokine markers will assist in improving understanding of the pathogenesis of bovine TB and may help to identify the immunopathology of active disease versus contained or inactive disease. Such disease correlates may help to inform the development of improved diagnostic methods and support vaccine development programmes.


Cost-effectiveness analysis of vaginal misoprostol versus dinoprostone pessary: A non-inferiority large randomized controlled trial in France.
To assess the cost-effectiveness of vaginal misoprostol (PGE1; 25 μg) compared with a slow-release dinoprostone (PGE2) pessary (10 μg) for labor induction due to an unfavorable cervix at term. We used data from an open-label multicenter, randomized non-inferiority trial that recruited women for whom labor was induced for medical reasons. The incremental cost-effectiveness ratio was assessed from the payer's perspective, with the focus on inpatient care costs and using the cesarean deliveries avoided (CDA) rate as the primary analysis and the rate of vaginal delivery within 24 h (VD24) as the secondary analysis. Analyses were based on 790 women in each group. Differences between treatment arms were the mean cost per patient of €4410 and €4399, a CDA rate of 80.1% and 77.9% and a VD24 rate of 46.1% and 59.4% for dinoprostone and misoprostol, respectively. Dinoprostone is not cost-effective according to the CDA rate and misoprostol was either a cost-effective or a dominant strategy according to the VD24. Misoprostol and dinoprostone have equal cost management with mixed efficacy according to the clinical outcome used. Finally, misoprostol may be an attractive option for hospitals as the price is lower and it is easier to use. ClinicalTrials.gov: NCT01765881. URL: https://clinicaltrials.gov/ct2/show/NCT01765881. ClinicalTrialRegistrer.eu: 2011-000933-35. URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2011-000933-35/FR.


Early Fluid and Nutritional Management of Extremely Preterm Newborns During the Fetal-To-Neonatal Transition.
During the fetal-to-neonatal transitional period, extremely preterm newborns undergo significant intrabody fluid shifts and resulting weight loss due to increased insensible fluid losses due to immature skin, kidneys, among other factors. These ongoing physiologic changes make fluid and nutritional management complex in the neonatal-to-fetal transitional time period for extremely premature newborns. However, limited literature exists to guide optimal practices for providers caring for this population. Here, we review the evidence on optimal fluid and nutritional management during the fetal-to-neonatal transition of extremely preterm newborns.


Assessment of transmissibility and measures effectiveness of SARS in 8 regions, China, 2002-2003.
Severe acute respiratory syndrome (SARS) is a form of atypical pneumonia which took hundreds of lives when it swept the world two decades ago. The pathogen of SARS was identified as SARS-coronavirus (SARS-CoV) and it was mainly transmitted in China during the SARS epidemic in 2002-2003. SARS-CoV and SARS-CoV-2 have emerged from the SARS metapopulation of viruses. However, they gave rise to two different disease dynamics, a limited epidemic, and an uncontrolled pandemic, respectively. The characteristics of its spread in China are particularly noteworthy. In this paper, the unique characteristics of time, space, population distribution and transmissibility of SARS for the epidemic were discussed in detail. We adopted sliding average method to process the number of reported cases per day. An SEIAR transmission dynamics model, which was the first to take asymptomatic group into consideration and applied indicators of R 0, Reff, Rt to evaluate the transmissibility of SARS, and further illustrated the control effectiveness of interventions for SARS in 8 Chinese cities. The R 0 for SARS in descending order was: Tianjin city (R 0 = 8.249), Inner Mongolia Autonomous Region, Shanxi Province, Hebei Province, Beijing City, Guangdong Province, Taiwan Province, and Hong Kong. R 0 of the SARS epidemic was generally higher in Mainland China than in Hong Kong and Taiwan Province (Mainland China: R 0 = 6.058 ± 1.703, Hong Kong: R 0 = 2.159, Taiwan: R 0 = 3.223). All cities included in this study controlled the epidemic successfully (Reff<1) with differences in duration. Rt in all regions showed a downward trend, but there were significant fluctuations in Guangdong Province, Hong Kong and Taiwan Province compared to other areas. The SARS epidemic in China showed a trend of spreading from south to north, i.e., Guangdong Province and Beijing City being the central regions, respectively, and from there to the surrounding areas. In contrast, the SARS epidemic in the central region did not stir a large-scale transmission. There were also significant differences in transmissibility among eight regions, with R0 significantly higher in the northern region than that in the southern region. Different regions were able to control the outbreak successfully in differences time.


EEG vigilance regulation patterns and their discriminative power to separate patients with major depression from healthy controls.
Recently, a framework has been presented that links vigilance regulation, i.e. tonic brain arousal, with clinical symptoms of affective disorders. Against this background, the aim of this study was to deepen the knowledge of vigilance regulation by (1) identifying different patterns of vigilance regulation at rest in healthy subjects (n = 141) and (2) comparing the frequency distribution of these patterns between unmedicated patients with major depression (MD; n = 30) and healthy controls (HCs; n = 30). Each 1-second segment of 15-min resting EEGs from 141 healthy subjects was classified as 1 of 7 different vigilance stages using the Vigilance Algorithm Leipzig. K-means clustering was used to distinguish different patterns of EEG vigilance regulation. The frequency distribution of these patterns was analyzed in independent data of 30 unmedicated MD patients and 30 matched HCs using a χ² test. The 3-cluster solution with a stable, a slowly declining and an unstable vigilance regulation pattern yielded the highest mathematical quality and performed best for separation of MD patients and HCs (χ² = 13.34; p < 0.001). Patterns with stable vigilance regulation were found significantly more often in patients with MD than in HCs. A stable vigilance regulation pattern, derived from a large sample of HCs, characterizes most patients with MD and separates them from matched HCs with a sensitivity between 67 and 73% and a specificity between 67 and 80%. The pattern of vigilance regulation might be a useful biomarker for delineating MD subgroups, e.g. for treatment prediction.


Vesicouterine Fistula and Fetus in Bladder: A Case Report.
Vesicouterine fistulas are the rarest of all urogenital fistulas, with most cases occurring after cesarean section. A 38-year-old woman in rural Zimbabwe presented at 20 weeks gestation with a suspected fetus in the urinary bladder by transabdominal ultrasonography. This finding was confirmed intraoperatively together with a vesicouterine fistula. Cesarean section 20 years earlier was the only risk factor. Diagnosis was delayed for lack of access to appropriate imaging and a tertiary facility. A vesicouterine fistula is a rare presentation in the context of an advanced health care system. To our knowledge, this is the fourth case report of a fetus in the bladder secondary to vesicouterine fistula. Patient morbidity in this case possibly could have been avoided with earlier diagnosis and access to care.


Inhibition of surfactant production by insulin in fetal rabbit lung slices.
Incorporation of labeled glucose and fatty acid residues into saturated phosphatidylcholine was significantly reduced in lung slices from 27.5 days of gestation fetal rabbits during 90 min incubation in the presence of 100 microU/ml insulin. When 14C-glucose was used as substrate, incorporation into both phosphatidylcholine and saturated phosphatidylcholine was reduced by insulin. This occurred despite an increase in overall glucose utilization by the lung from 11.3 +/- 3.9 to 16.3 +/- 5.2 nmole/g tissue in the presence of insulin (P less than 0.05). A decrease in incorporation of fatty acid residues into saturated phosphatidylcholine was also observed when 14C-palmitate was used as substrate, from 102 +/- 4 to 90 +/- 5 nmole palmitate/g tissue (P less than 0.01). In the presence of insulin, there were significant reductions of both substrates appearing in lysophosphatidylcholine, a precursor of saturated phosphatidylcholine. There was no significant change in incorporation of glucose residues into glycogen or lactate under these conditions.


The myosin chaperone UNC-45 is organized in tandem modules to support myofilament formation in C. elegans.
The UCS (UNC-45/CRO1/She4) chaperones play an evolutionarily conserved role in promoting myosin-dependent processes, including cytokinesis, endocytosis, RNA transport, and muscle development. To investigate the protein machinery orchestrating myosin folding and assembly, we performed a comprehensive analysis of Caenorhabditis elegans UNC-45. Our structural and biochemical data demonstrate that UNC-45 forms linear protein chains that offer multiple binding sites for cooperating chaperones and client proteins. Accordingly, Hsp70 and Hsp90, which bind to the TPR domain of UNC-45, could act in concert and with defined periodicity on captured myosin molecules. In vivo analyses reveal the elongated canyon of the UCS domain as a myosin-binding site and show that multimeric UNC-45 chains support organization of sarcomeric repeats. In fact, expression of transgenes blocking UNC-45 chain formation induces dominant-negative defects in the sarcomere structure and function of wild-type worms. Together, these findings uncover a filament assembly factor that directly couples myosin folding with myofilament formation.


Evaluating construct validity of computable acute respiratory distress syndrome definitions in adults hospitalized with COVID-19: an electronic health records based approach.
Evolving ARDS epidemiology and management during COVID-19 have prompted calls to reexamine the construct validity of Berlin criteria, which have been rarely evaluated in real-world data. We developed a Berlin ARDS definition (EHR-Berlin) computable in electronic health records (EHR) to (1) assess its construct validity, and (2) assess how expanding its criteria affected validity. We performed a retrospective cohort study at two tertiary care hospitals with one EHR, among adults hospitalized with COVID-19 February 2020-March 2021. We assessed five candidate definitions for ARDS: the EHR-Berlin definition modeled on Berlin criteria, and four alternatives informed by recent proposals to expand criteria and include patients on high-flow oxygen (EHR-Alternative 1), relax imaging criteria (EHR-Alternatives 2-3), and extend timing windows (EHR-Alternative 4). We evaluated two aspects of construct validity for the EHR-Berlin definition: (1) criterion validity: agreement with manual ARDS classification by experts, available in 175 patients; (2) predictive validity: relationships with hospital mortality, assessed by Pearson r and by area under the receiver operating curve (AUROC). We assessed predictive validity and timing of identification of EHR-Berlin definition compared to alternative definitions. Among 765 patients, mean (SD) age was 57 (18) years and 471 (62%) were male. The EHR-Berlin definition classified 171 (22%) patients as ARDS, which had high agreement with manual classification (kappa 0.85), and was associated with mortality (Pearson r = 0.39; AUROC 0.72, 95% CI 0.68, 0.77). In comparison, EHR-Alternative 1 classified 219 (29%) patients as ARDS, maintained similar relationships to mortality (r = 0.40; AUROC 0.74, 95% CI 0.70, 0.79, Delong test P = 0.14), and identified patients earlier in their hospitalization (median 13 vs. 15 h from admission, Wilcoxon signed-rank test P < 0.001). EHR-Alternative 3, which removed imaging criteria, had similar correlation (r = 0.41) but better discrimination for mortality (AUROC 0.76, 95% CI 0.72, 0.80; P = 0.036), and identified patients median 2 h (P < 0.001) from admission. The EHR-Berlin definition can enable ARDS identification with high criterion validity, supporting large-scale study and surveillance. There are opportunities to expand the Berlin criteria that preserve predictive validity and facilitate earlier identification.


Effects of neurohypophyseal and adenohypophyseal hormones, steroids, eicosanoids, and extrafollicular tissue on ovulation in vitro of guppy (Poecilia reticulata) embryos.
In the viviparous guppy, oocyte maturation is followed by intrafollicular fertilization and gestation. The fully developed embryos are ovulated at term just prior to parturition. Various agents were tested in vitro for their effects on ovulation of embryos in isolated follicles of the guppy. Arachidonic acid (10 and 100 microM), PGE2, PGF2 alpha, and 6-keto-PGF1 alpha (0.1 microgram/ml) induced ovulation, while PGE1, 15-keto-PGF2 alpha, leukotriene B4, 5-, 12-, and 15-HETEs (0.01 to 0.1 microgram/ml), cortisol, 11-deoxycortisol (25 and 250 ng/ml), estradiol-17 beta, testosterone, 17 alpha,20 beta-P, progesterone (5 and 50 ng/ml), isotocin, vasotocin (0.02 to 2 microgram/ml), and guppy pituitary extract (one and two glands per fish) did not. Extrafollicular (EF) ovarian tissue cocultured with isolated follicles induced ovulation, and the medium levels of PGE and PGF in such incubations were higher than those in the control. Indomethacin, the cyclooxygenase inhibitor, did not inhibit ovulation induced by arachidonic acid and EF tissue, although it inhibited PGE and PGF production. NDGA, the lipoxygenase inhibitor, did not inhibit ovulation induced by arachidonic acid or EF tissue. A combination of eicosanoids synthesized by follicles and EF tissue may be involved in the induction of ovulation. Dibutyryl cAMP inhibited ovulation induced by PGE2, PGF2 alpha, 6-keto-PGF1 alpha, and EF tissue suggesting that a low level of cAMP may be associated with ovulation in the guppy.


Attitudes to smoke-free outdoor regulations in the USA and Canada: a review of 89 surveys.
To review the published survey data on public support for smoke-free outdoor regulations in the USA and Canada (two countries at the forefront of such policies). We searched for English language articles and reports using Medline, Google Scholar and Google for the period to December 2014. We retained population-based surveys of the adult general population in jurisdictions in the USA and Canada, with a minimum survey sample of 500. The analysis focused on assessing levels and trends in public support for different types of places and also explored how support varied between population groups. Relevant data were found from 89 cross-sectional surveys between 1993 and 2014. Support for smoke-free regulations in outdoor places tended to be highest for smoke-free school grounds (range: 57-95%) playgrounds (89-91%), and building entrances (45-89%) and lowest for smoke-free outdoor workplaces (12-46%) and sidewalks (31-49%). Support was lower among smokers, though for some types of places there was majority smoker support (eg, school grounds with at least 77% support in US state surveys after 2004). Trend data involving the same questions and the same surveyed populations suggested increased general public and smoker support for smoke-free regulations over time (eg, from 67% to 78% during 2002-2008 for smoke-free school grounds in the USA). Higher support was typically seen from women and some ethnic groups (eg, African-Americans). Outdoor smoke-free regulations can achieve majority public support, including from smokers.


Prevention of viral infections after bone marrow transplantation.
After bone marrow transplantation, a number of viral infections contribute to the morbidity and mortality of the procedure. Established preventive measures to avoid primary infection and reactivation of herpes-and cytomegaloviruses are outlined. Possible future strategies against these viruses (e. g., monoclonal antibodies, transfer of T-lymphocytes) and the possible role of improved diagnostic tools are briefly discussed.


Detection of characteristic distributions of phospholipid head groups and fatty acids on neurite surface by time-of-flight secondary ion mass spectrometry.
Neurons have a large surface because of their long and thin neurites. This surface is composed of a lipid bilayer. Lipids have not been actively investigated so far because of some technical difficulties, although evidence from cell biology is emerging that lipids contain valuable information about their roles in the central nervous system. Recent progress in techniques, e.g., mass spectrometry, opens a new epoch of lipid research. We show herein the characteristic localization of phospholipid components in neurites by means of time-of-flight secondary ion mass spectrometry. We used explant cultures of mouse superior cervical ganglia, which are widely used by neurite investigation research. In a positive-ion detection mode, phospholipid head group molecules were predominantly detected. The ions of m/z 206.1 [phosphocholine, a common component of phosphatidylcholine (PC) and sphingomyelin (SM)] were evenly distributed throughout the neurites, whereas the ions of m/z 224.1, 246.1 (glycerophosphocholine, a part of PC, but not SM) showed relatively strong intensity on neurites adjacent to soma. In a negative-ion detection mode, fatty acids such as oleic and palmitic acids were mainly detected, showing high intensity on neurites adjacent to soma. Our results suggest that lipid components on the neuritic surface show characteristic distributions depending on neurite region.


Peripartum findings and blood gas analysis in newborn foals born after spontaneous or induced parturition.
Induction of parturition in horses is still not well accepted due to the potential peripartum complications for mares and newborn foals. We assessed differences after spontaneous and induced parturition with low doses of oxytocin (OX) in 1) incidence of peripartum complications in mares; 2) viability, behavioral, physical, and venous blood gas analyses in foals. In this study 61 mares were included; 45/61 were enrolled in the spontaneous foaling group (SF) and 16/61 in the induced foaling group (IF). In the IF group, when the calcium in mammary secretion reached concentrations of ≥250 ppm, mares received a single injection of 2.5 IU of oxytocin IV once a day until foaling. Mares' breed, age, parity, gestational and stage II length, and peripartum complications were recorded. Foal maturity, vital (Apgar score), behavioral and physical parameters were assessed at birth, and the foal clinical condition was monitored for one week. A jugular venous blood sample was collected at birth for blood gas analysis, acid-base status, and lactate assessment. The median gestational length was within the reference interval in all the mares included and did not differ between the two groups. No statistical differences in the II stage length nor in incidence of peripartum complications were observed between the two groups. All the foals were born alive and showed no signs of prematurity/dysmaturity. No statistical differences were found in foal viability between the two groups. Time to stand and nurse from the mare, and body temperature were significantly higher in the IF compared to the SF group. Venous blood pH, SO2% and BE were lower, while pCO2 and lactate were higher in the IF than in the SF group. All the foals in both groups remained clinically healthy during the observation period. In conclusion, at term induction of parturition with a low dose of oxytocin does not have adverse effects on peripartum in mares. Our findings suggest that at term induced foals suffer slightly greater, but not clinically significant, hypoxia, hypercapnia and acidosis than spontaneously delivered foals.


Sutureless renal repair after low-velocity ballistic trauma.
The tissue adhesive butyl cyanoacrylate was evaluated in the repair of injured porcine kidneys following low-velocity ballistic trauma. This technique was compared to the classic renal repair using chromic suture and a patch of perirenal fat. The repair with butyl cyanoacrylate was less time consuming (four minutes vs. 28 minutes for the controls) and decreased blood loss (67 cc vs. 180 cc for the controls). Ten days post injury the kidneys repaired with tissue adhesive showed minimal intraparenchymal hemorrhage or perirenal bleeding, while two of the four (50%) suture-repaired kidneys showed intrarenal microhemorrhages and one (25%) developed a perirenal hematoma. Perirenal adhesions were noted in both groups. Vital signs, IVP's, creatinine clearance, and serum and urine chemistries were nearly identical in the two groups. The results show that low-velocity ballistic injuries of renal tissue can be repaired effectively and more efficiently with the use of butyl cyanoacrylate when compared to conventional suturing methods.


Visual evoked responses to light emitting diode (LED) photostimulation in newborn infants.
The use of a Xenon discharge stroboscope to elicit VERs in a neonatal intensive care unit has several disadvantages. To overcome these a photostimulator has been developed which consists of an array of 25 red light emitting diodes (LEDs). The LEDs are driven by pulses of fixed length and current and the output intensity is controlled by the pulse repetition rate. Such a photostimulator is compact and can be hand-held inside a cot or incubator. Using this method VERs have been recorded in healthy full-term and pre-term infants which are comparable in wave form and latency to those elicited by a stroboscope.


Diarrheic syndrome as a clinical sign of intestinal infiltration in progressive B-cell chronic lymphocytic leukemia.
Gastrointestinal involvement is a rare event in patients with B-cell chronic lymphocytic leukemia (B-CLL) and is usually associated to lymphomatous transformation. However, in autopsy studies the reported incidence of microscopic infiltration can reach up to 50% of cases. Seven B-CLL patients in advanced stage/progressive disease were evaluated by colonoscopy because of continuous diarrhea. Five out of seven patients (71%) presented histological evidence of colonic infiltration. Persistent diarrhea in patients with progressive/advanced B-CLL can be a clinical sign of intestinal infiltration and justifies endoscopic examinations.


A sample size program for "proving the null hypothesis".
A flexible APL computer program is presented for assistance in planning clinical trials designed to test the equivalence of two therapies. It is a substitute for the sample size graphs of Blackwelder and Chang and provides the option to calculate any of the six characteristics--sample size, significance level, power, success probability of standard therapy, success probability of experimental therapy, and minimum difference of interest--if five of them are prespecified.


Porous PdWM (M = Nb, Mo and Ta) Trimetallene for High C1 Selectivity in Alkaline Ethanol Oxidation Reaction.
Direct ethanol fuel cells are among the most efficient and environmentally friendly energy-conversion devices and have been widely focused. The ethanol oxidation reaction (EOR) is a multielectron process with slow kinetics. The large amount of by-product generated by incomplete oxidation greatly reduces the efficiency of energy conversion through the EOR. In this study, a novel type of trimetallene called porous PdWM (M = Nb, Mo and Ta) is synthesized by a facile method. The mass activity (15.6 A mgPd -1 ) and C1 selectivity (55.5%) of Pd50 W27 Nb23 /C trimetallene, obtained after optimizing the compositions and proportions of porous PdWM, outperform those of commercial Pt/C (1.3 A mgPt -1 , 5.9%), Pd/C (5.0 A mgPd -1 , 7.2%), and Pd97 W3 /C bimetallene (9.5 A mgPd -1 , 14.1%). The mechanism by which Pd50 W27 Nb23 /C enhances the EOR performance is evaluated by in situ Fourier transform infrared spectroscopy and density functional theory calculations. It is found that W and Nb enhance the adsorption of CH3 CH2 OH and oxophilic high-valence Nb accelerates the subsequent oxidation of CO and CHx species. Moreover, Nb promotes the cleavage of CC bonds and increases the C1 selectivity. Pd60 W28 Mo12 /C and Pd64 W27 Ta9 /C trimetallene synthesized by the same method also exhibit excellent EOR performance.


First report of spontaneous hepatic fibrosarcoma in a white-tufted marmoset (Callithrix jacchus) kept in captivity.
Reports of sarcomas in nonhuman primates are scarce and, specifically, primary hepatic sarcomas are rare, as in humans. This is the first report of an aggressive hepatic fibrosarcoma in a young adult Callithrix jacchus. The final postmortem diagnosis was obtained by means of immunohistochemical analysis, which confirmed the tumor histogenesis.


Molecular mechanisms underlying anticancer effects of myricetin.
Dietary guidelines published in the past two decades have acknowledged the beneficial effects of myricetin, an important and common type of herbal flavonoid, against several human diseases such as inflammation, cardiovascular pathologies, and cancer. An increasing number of studies have shown the beneficial effects of myricetin against different types of cancer by modifying several cancer hallmarks including aberrant cell proliferation, signaling pathways, apoptosis, angiogenesis, and tumor metastasis. Most importantly, myricetin interacts with oncoproteins such as protein kinase B (PKB) (Akt), Fyn, MEK1, and JAK1-STAT3 (Janus kinase-signal transducer and activator of transcription 3), and it attenuates the neoplastic transformation of cancer cells. In addition, myricetin exerts antimitotic effects by targeting the overexpression of cyclin-dependent kinase 1 (CDK1) in liver cancer. Moreover, it also targets the mitochondria and promotes different kinds of cell death in various cancer cells. In the present paper, a critical review of the available literature is presented to identify the molecular targets underlying the anticancer effects of myricetin.


Nucleus-specific modulation of phasic and tonic inhibition by endogenous neurosteroidogenesis in the murine thalamus.
Neurosteroids are potent allosteric modulators of GABAA receptors (GABAA Rs). Although the effects of exogenous neurosteroids on GABAA R function are well documented, less is known about effects of neurosteroids produced by local endogenous biosynthesis. The neurosteroidogenic enzymes 5α-reductase and 3α-hydroxysteroid dehydrogenase are expressed in two nuclei of somatosensory thalamus, the thalamic reticular nucleus (nRT) and ventrobasal nucleus (VB). Here, the effects of acute blockade of neurosteroidogenesis by the 5α-reductase inhibitor finasteride on phasic and tonic GABAA R-mediated currents were examined in nRT and VB of mice. In nRT, finasteride altered the decay and amplitude, but not the frequency, of phasic currents, with no effect on tonic inhibition. In VB neurons, by contrast, finasteride reduced both the size and frequency of phasic currents, and also reduced the degree of tonic inhibition. These studies thus provide novel evidence for endogenous modulation of GABAA R function by 5α-reduced neurosteroids in the mature thalamus.


Overexpression of hsp70i facilitates reactivation of intracellular proteins in neurones and protects them from denaturing stress.
Transfection of neurones with an adenoviral vector (Ad) expressing high levels of hsp70i was shown to protect primary hippocampal cultures from heat stress. To investigate one of the molecular mechanisms which may underlie hsp70i's neuroprotective effects we measured luciferase activity in the presence and absence of hsp70i following heat or chemical inactivation. Luciferase activity was recovered to 80% of control levels in the presence of recombinant hsp70i in vitro. Luciferase activity was also maintained in primary hippocampal neurones exposed to a denaturing stress if transfected with Ad-hsp70i. These results support the hypothesis that hsp70i protects neurones from stress by interacting with cytosolic proteins and thereby protecting them from inactivation.


In situ observation of dense-body release from hydrated human platelets.
Human-platelet dense bodies (secretory granules) have been visualized by electron microscopy in cells maintained in a hydrated state, and their sequential release after stimulation by thrombin has been observed in situ. The pattern of dense body release from individual platelets suggests that a a portion of the dense body complement of a single cell can be extruded without appreciable change in the position of the remaining dense bodies.


Characterization of two GH5 endoglucanases from termite microbiome using synthetic metagenomics.
Here, we characterize two novel GH5 endoglucanases (GH5CelA and GH5CelB) from an uncultured bacterium identified in termite gut microbiomes. Both genes were codon-optimized, synthetized, cloned, and expressed as recombinant proteins in Escherichia coli for subsequent purification. Both enzymes showed activity on the pNPC and barley β-glucan substrates, whereas GH5CelB also showed low activity on carboxymethyl cellulose. The optimum conditions for both enzymes were an acid pH (5) and moderate temperature (35 to 50 °C). The enzymes differed in the kinetic profiles and patterns of the generated hydrolysis products. A structural-based modeling analysis indicated that both enzymes possess a typical (β/α)8-barrel fold characteristic of GH5 family, with some differential features in the active site cleft. Also, GH5CelB presents a putative secondary binding site. Furthermore, adjacent to the active site of GH5CelA and GH5CelB, a whole subdomain rarely found in GH5 family may participate in substrate binding and thermal stability.Therefore, GH5CelA may be a good candidate for the production of cello-oligosaccharides of different degrees of polymerization applicable for feed and food industries, including prebiotics. On the other hand, GH5CelB could be useful in an enzymatic cocktail for the production of lignocellulosic bioethanol, because of the production of glucose as a hydrolysis product. Key Points • Synthetic metagenomics is a powerful approach for discovering novel enzymes. • Two novel GH5 endoglucanases from nonculturable microorganisms were characterized. • Structural differences between them and other GH5 endoglucanases were observed. • The enzymes may be good candidates for feed, food, and/or bioethanol industries.


Importance and pitfalls of molecular analysis to parasite epidemiology.
Molecular tools are increasingly being used to address questions about parasite epidemiology. Parasites represent a diverse group and they might not fit traditional population genetic models. Testing hypotheses depends equally on correct sampling, appropriate tool and/or marker choice, appropriate analysis and careful interpretation. All methods of analysis make assumptions which, if violated, make the results invalid. Some guidelines to avoid common pitfalls are offered here.


A secret(ly) aging man who has no time to die: The spectre of aging in the James Bond franchise.
Aging is not a phenomenon commonly associated with the James Bond franchise, which relies on the successful template of a more agile and youthful hero. While Bond's adversaries used to be older than him (at least in the classic Bond movies of the 1960s and 1970s), with their deficient 'Otherness' underlining the idea that they are 'bad' and impotent patriarchs, more recent Bond films have turned to different age constellations. Even though the films rarely comment on the hero's age or adjust the material to it, there are various ways in which Bond's age is highlighted in these films, depending, for instance, on whether he has to fight 'bad fathers', 'treacherous brothers', or 'disobedient sons'. This article runs the parameter of Bond's age against other parameters like the age of his adversaries and the number of his sexual conquests. It looks into two non-canonical Bond films, Casino Royale (1967) and Never Say Never Again (1983), to demonstrate that the topic of aging has seen more diverse and candid treatments outside of the jurisdiction of the official Eon series. This includes aspects like the hero's virility in the face of old age (at the intersection of senex and eros) and the meta-textual qualities of these films, which resonate with their subtexts on aging. The final section turns to Daniel Craig's swansong as Bond, No Time to Die (2021), which addresses the theme of mortality more directly than any other previous Bond outing.


Comparison of Retrograde Intrarenal Surgery and Micro-Percutaneous Nephrolithotomy for Kidney Stones: A Meta-Analysis.
Advances in micro-percutaneous nephrolithotomy (PCNL) for kidney stones have made it an alternative approach to the retrograde intrarenal surgery (RIRS) approach. Nevertheless, the superiority of micro-PCNL over RIRS is still under debate. The results are controversial. The purpose of this study was to systematically evaluate the clinical results in patients presenting with kidney stones treated with micro-PCNL or RIRS. A literature search was done for electronic databases to identify researches that compared micro-PCNL and RIRS till December 2019. The clinical outcome included complications, stone-free rates (SFRs), hemoglobin reduction, length of hospital stay, and operative time. Five articles were included in our study. The pooled results revealed no statistical difference in the rate of complications (OR = 0.99, 95% CI = 0.57-1.74, p = 0.99), length of hospital stay (MD = -0.29, 95% CI = -0.82 to 0.24, p = 0.28), and operative time (MD = -6.63, 95% CI = -27.34 to 14.08, p = 0.53) between the 2 groups. However, significant difference was present in hemoglobin reduction (MD = -0.43, 95% CI = -0.55 to 0.30, p < 0.001) and the SFRs (OR = 0.59, 95% CI = 0.36-0.98, p = 0.04) when comparing RIRS with micro-PCNL. Compared with micro-PCNL to treat kidney stones, RIRS is associated with better stone clearance and bearing higher hemoglobin loss. As the advantages of both technologies have been shown in some fields, the continuation of well-designed clinical trials may be necessary.


Electron acceptors associated with P-700 in Triton solubilized photosystem I particles from spinach chloroplasts.
Flash-induced absorption changes of Triton-solubilized Photosystem I particles from spinach were studied under reducing and/or illumination conditions that serve to alter the state of bound electron acceptors. By monitoring the decay of P-700 following each of a train of flashes, we found that P-430 or components resembling it can hold 2 equivalents of electrons transferred upon successive illuminations. This requires the presence of a good electron donor, reduced phenazine methosulfate or neutral red, otherwise the back reaction of P-700+ with P-430 occurs in about 30 ms. If the two P-430 sites, designated Centers A and B, are first reduced by preilluminating flashes or chemically by dithionite under anaerobic conditions, then subsequent laser flashes generate a 250 microseconds back reaction of P-700+, which we associate with a more primary electron acceptor A2. In turn, when A2 is reduced by background (continuous) illumination in presence of neutral red and under strongly reducing conditions, laser flashes then produce a much faster (3 microseconds) back reaction at wavelengths characteristic of P-700. We associate this with another more primary electron acceptor, A1, which functions very close to P-700. The organization of these components probably corresponds to the sequence P-700-A1-A2-P-430[AB]. The relation of the optical components to acceptor species detected by EPR, by electron-spin polarization or in terms of peptide components of Photosystem I is discussed. Preliminary experiments with broken chloroplasts suggest that an analogous situation occurs there, as well.


The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling.
A cDNA clone encoding a novel, widely expressed protein (called growth factor receptor-bound protein 2 or GRB2) containing one src homology 2 (SH2) domain and two SH3 domains was isolated. Immunoblotting experiments indicate that GRB2 associates with tyrosine-phosphorylated epidermal growth factor receptors (EGFRs) and platelet-derived growth factor receptors (PDGFRs) via its SH2 domain. Interestingly, GRB2 exhibits striking structural and functional homology to the C. elegans protein sem-5. It has been shown that sem-5 and two other genes called let-23 (EGFR like) and let-60 (ras like) lie along the same signal transduction pathway controlling C. elegans vulval induction. To examine whether GRB2 is also a component of ras signaling in mammalian cells, microinjection studies were performed. While injection of GRB2 or H-ras proteins alone into quiescent rat fibroblasts did not have mitogenic effect, microinjection of GRB2 together with H-ras protein stimulated DNA synthesis. These results suggest that GRB2/sem-5 plays a crucial role in a highly conserved mechanism for growth factor control of ras signaling.


Reference material development for detection of human respiratory syncytial virus using digital PCR.
Nucleic acid testing is a powerful tool for the detection of various pathogens. Respiratory syncytial virus (RSV) is a major cause of acute respiratory infection, especially in young children and infants. To improve the confidence and reliability of nucleic acid testing results for RSV, reference materials (RMs) of both type A and B of RSV were developed by the National Institute of Metrology, China, code numbers NIM-RM 4057 and 4058. The reference material was composed of in vitro transcribed RNA containing the nucleocapsid (N) gene, matrix (M) gene, and partial polymerase (L) gene of RSV. A duplex reverse transcription digital PCR method was established with limit of blank (LoB), limit of detection (LoD) and limit of quantification (LoQ) of 2, 5, and 23 copies per reaction for RSV-A and 4, 8, and 20 copies per reaction for RSV-B. The certified value and expanded uncertainty (U, k = 2) of the two RMs were determined to be (6.1 ± 1.4) × 104 copies/μL for RSV-A and (5.3 ± 1.2) × 104 copies/μL for RSV-B. The developed RMs can be used as standards to evaluate the performance of RSV detection assays.


Dorsal horn synaptosomal content of aspartate, glutamate, glycine and GABA are differentially altered following chronic constriction injury to the rat sciatic nerve.
The present study directly examined the axon terminal (synaptosomal) level of amino acid neurotransmitters in rats following chronic constriction injury (CCI) to the sciatic nerve. Dorsal horn, synaptosomal content of aspartate (Asp), glutamate (Glu), glycine and gamma-aminobutyric acid (GABA) was assessed in these rats, and in normal age-matched and younger rats. The synaptosomal content of Asp and Glu in CCI rats was increased by 44-46% compared with control rats (P<0.016). The synaptosomal content of GABA in younger rats was 33% lower than that observed in control rats (P<0.005). Altered axon terminal levels of amino acid neurotransmitters accompany the painful symptoms of neuropathy. The lower axon terminal level of GABA in younger rats may help to explain the age-dependency of pain development in animal models of nerve injury.


Hypertrophy and functional alterations in hyperdynamic phospholamban-knockout mouse hearts under chronic aortic stenosis.
To determine whether the hyperdynamic phospholamban-knockout hearts are capable of withstanding a chronic aortic stenosis. The transverse section of the aorta was banded in phospholamban-knockout and their isogenic wild-type mice, which were followed with echocardiography in parallel, along with sham-operated mice, before and at 2.5, 5 and 10 weeks after surgery. Cardiac decompensation was evidenced by the presence of lung congestion in some banded knockouts and wild-types, giving rise to a subset of non-failing and failing hearts within each group. The incidence of heart failure was not genotype-dependent but rather associated with higher heart rates before surgery. The development of left ventricular hypertrophy was similar between knockouts and wild-types and longitudinal assessment of end-diastolic dimension indicated progressive increases after banding, with a greater dilation in failing mice. Fractional shortening was reduced in failing knockouts and wild-types to a similar degree, with an earlier onset in the knockouts. In addition, fractional shortening was decreased in non-failing knockouts but not wild-types. Ejection times shortened after aortic banding particularly for failing hearts. Assessment of the SR Ca(2+)-ATPase protein levels indicated similar downregulation for failing knockouts and wild-types, while the phospholamban levels were not significantly altered in wild-types. The hyperdynamic phospholamban-knockout hearts are able to compensate against a sustained aortic stenosis similar to wild-types.


Efficacy of propranolol therapy after acute myocardial infarction related to coronary arterial anatomy and left ventricular function.
The effect of the beta-adrenergic blocking agent propranolol on morbidity and mortality risk after acute myocardial infarction was studied relative to coronary anatomy and left ventricular (LV) ejection fraction in a subset of 406 patients participating in a randomized study of 3,837 patients in the Beta Blocker Heart Attack Trial (BHAT). Median follow-up for this subset of patients was 28 months. The mortality rate was 2% (2 of 100) in patients with 2- and 3-vessel coronary artery disease taking propranolol and 10% (12 of 126) in those taking placebo (p less than 0.02). In patients with 2- and 3-vessel coronary artery disease with decreased LV function (defined as ejection fraction less than 50%), no patient taking propranolol died, whereas 17% (7 of 42) taking placebo died (p less than 0.04). The salutary effect of propranolol on mortality in the larger BHAT after acute myocardial infarction also was evident in this population studied in regard to their coronary and LV anatomy and function.


A comparison of real-time ultrasonography with intravenous urography in the follow-up of patients with spinal cord injury.
Patients with spinal cord damage require an expert urological assessment at regular intervals. Seventy-five patients with neurogenic bladder dysfunction associated with spinal paralysis attending for routine assessment of the upper urinary tract had both intravenous urography (IVU) and renal ultrasonography. The combination of a plain radiography of the abdomen and an ultrasound scan of the kidneys was found to be a cheap, safe and reliable alternative to intravenous urography for the regular follow-up of these patients.


Endothelin receptors in the human coronary artery, ventricle and atrium. A quantitative autoradiographic analysis.
In the present experiments we investigated endothelin (ET) receptors in the human coronary artery, and in ventricular and atrial muscle using quantitative receptor autoradiography. Displacement of [125I]Sf6b (Sarafotoxin S6b) (30 pM)- and [125I]ET-1 (30 pM)-labeled binding sites was studied using ET-1, the ETA receptor selective ligand BQ-123 (cyclo[D-Asp-L-Pro-D-Val-L-Leu-D-Trp-]), and the ETB receptor selective ligand [Ala1, 3, 11, 15]ET-1. Specific binding was more dense in atrium and coronary artery (relative optical density (r.o.d.): 0.14 +/- 0.01 and 0.16 +/- 0.01, respectively) than in ventricular muscle (r.o.d.: 0.10 +/- 0.01). In the coronary artery, binding was especially dense in the media. ET-1 displaced [125I]ET-1 and [125I]Sf6b monophasically in atrium, ventricle and coronary artery. [Ala1,3,11,15]ET-1 and BQ-123 displaced [125I]ET-1 and [125I]Sf6b-labeled sites biphasically in the ventricle and in the atrium. In the human coronary artery, [Ala1,3,11,15]ET-1 and BQ-123 displaced [125I]ET-1-labeled sites monophasically (pIC50: ET-1 (9.72 +/- 0.12) > BQ-123 (6.84 +/- 0.08) > [Ala1,3,11,15]ET-1 (6.40 +/- 0.12). In contrast, [Ala1,3,11,15]ET-1 and BQ-123 displaced [125I]Sf6b-labeled coronary artery sites biphasically (high affinity pIC50: BQ-123, 9.03 +/- 0.25; [Ala1,3,11,15]ET-1, 8.40 +/- 0.14; low affinity pIC50: BQ-123, 7.24 +/- 0.14; [Ala1,3,11,15]ET-1, 6.99 +/- 0.09). These data indicate that both [125I]ET-1 and [125I] Sf6b-labeled ETA and ETB binding sites in human ventricular and atrial muscle.(ABSTRACT TRUNCATED AT 250 WORDS)


Brain volume reductions within multiple cognitive systems in male preterm children at age twelve.
To more precisely examine regional and subregional microstructural brain changes associated with preterm birth. We obtained brain volumes from 29 preterm children, age 12 years, with no ultrasound scanning evidence of intraventricular hemorrhage or cystic periventricular leukomalacia in the newborn period, and 22 age- and sex-matched term control subjects. Preterm male subjects demonstrated significantly lower white matter volumes in bilateral cingulum, corpus callosum, corticospinal tract, prefrontal cortex, superior and inferior longitudinal fasciculi compared with term male subjects. Gray matter volumes in prefrontal cortex, basal ganglia, and temporal lobe also were significantly reduced in preterm male subjects. Brain volumes of preterm female subjects were not significantly different from those of term female control subjects. Voxel-based morphometry results were not correlated with perinatal variables or cognitive outcome. Higher maternal education was associated with higher cognitive performance in preterm male subjects. Preterm male children continue to demonstrate abnormal neurodevelopment at 12 years of age. However, brain morphology in preterm female children may no longer differ from that of term female children. The neurodevelopmental abnormalities we detected in preterm male subjects appear to be relatively diffuse, involving multiple neural systems. The relationship between aberrant neurodevelopment and perinatal variables may be mediated by genetic factors, environmental factors, or both reflected in maternal education level.


Benzodiazepine misuse in adults with alcohol use disorder: Prevalence, motives and patterns of use.
Benzodiazepines are among the most commonly misused drugs. Despite the known risks of combining benzodiazepines and alcohol, little is known about misuse among people with alcohol use disorder (AUD). Our aim was to characterize the prevalence, correlates, and patterns of misuse of benzodiazepines in adults with AUD. Adults receiving treatment for AUD (N = 258) completed a battery of questionnaires. We used descriptive statistics to characterize the prevalence and patterns of misuse and we used logistic regression models to identify correlates of misuse. Almost half of the sample reported a history of benzodiazepine prescription and 30% reported a history of misuse. Younger age, female sex, anxiety, and other substance use were associated with misuse. Coping was the most commonly reported reason for misuse. All participants who had misused a benzodiazepine in the past year used concurrently with another substance. Benzodiazepine misuse was common in this study, and risky patterns of use, such a co-use with other substances, were prevalent. Coping was the most common reason for misusing benzodiazepines, suggesting that un- or under-treated psychiatric symptoms may contribute to misuse.


Prevalence of musculoskeletal discomfort among female cabin crew in Taiwan.
This study investigated the prevalence of musculoskeletal discomfort among female cabin crew through cabin tasks and demographic factors, including age and seniority. This study conducted an online questionnaire survey targeted at female cabin crew in Taiwan and ensured that the sample size was with a statistical power of 0.95. This study evaluated the work intensity by ranking six common cabin tasks and examined musculoskeletal discomfort with Cornell Musculoskeletal Discomfort Questionnaire. Descriptive statistics were used to learn the work intensity and discomfort conditions. In addition, the Chi-square test of independence and multivariate adjustment were applied to clarify the impact of age and occupation on musculoskeletal discomfort in the neck, shoulders, and lower back. This study enrolled 88 female cabin crew members. Handling carry-on baggage was voted as the highest intensity cabin task (40%), which was also ranked as the strongest intensity on shoulders. Meanwhile, the upper trunk was more prevalent in musculoskeletal discomfort. Moreover, after multivariate adjustment with controlling the effect of age, this study found a marginal significant association (p = .09) between seniority and right shoulder discomfort for younger staff. This study found that handling carry-on baggage was associated with musculoskeletal complaints in the shoulders. Therefore, this study suggested that shoulders, especially for the right side might be related to the occupational injury, which was prevalent along with seniority among the younger crew. Overall, this study provided the preliminary findings to improve occupational training for preventive health.


Failure to modify scrapie in mice by administration of interferon or anti-interferon globulin.
Administration of potent mouse interferon preparations or anti-mouse interferon globulin did not influence the evolution of scrapie in mice after intraperitoneal injection of the agent. We conclude that the interferon system is probably not involved in scrapie.


Quantitative assessment of regional lung ventilation in emphysematous mice using hyperpolarized 129Xe MRI with a continuous flow hyperpolarizing system.
Lung ventilation function in small animals can be assessed by using hyperpolarized gas MRI. For these experiments a free breathing protocol is generally preferred to mechanical ventilation as mechanical ventilation can often lead to ventilation lung injury, while the need to maintain a gas reservoir may lead to a partial reduction of the polarization. To evaluate regional lung ventilation of mice by a simple but fast method under free breathing and give evidence for effectiveness with an elastase instilled emphysematous mice. Emphysematous mice. A Look-Locker based saturation recovery sequence was developed for continuous flow hyperpolarized (CF-HP) 129Xe gas experiments, and the apparent gas-exchange rate, k', was measured by the analysis of the saturation recovery curve. In mice with elastase-induced mild emphysema, reductions of 15-30% in k' values were observed as the results of lesion-induced changes in the lung. The proposed method was applied to an emphysematous model mice and ventilation dysfunctions have been approved as a definite decrease in k' values, supporting the usefulness for a non-invasive assessment of the lung functions in preclinical study by the CF-HP 129Xe experiments.


Specific binding modes of Cu(I) and Ag(I) with neurotoxic domain of the human prion protein.
Prion diseases are neurodegenerative disorders associated with a conformational change of the normal cellular isoform of the prion protein (PrP(C)) to an abnormal scrapie isoform (PrP(Sc)). human prion protein (hPrP(C)) is able to bind up to six Cu(II) ions. Four of them are distributed in the octarepeat domain, containing four tandem-repetitions of the sequence PHGGGWGQ. Immediately outside the octarepeat domain, in so called PrP amyloidogenic region, two additional and independent Cu(II) binding sites, encompassing His96 and His111 residues, respectively, are present. Considering the potential involvement of PrP in cellular redox homeostasis, investigations on Cu(I)-PrP interaction might be also biologically relevant. Interestingly, the amyloidogenic fragment of PrP contains a -M(X)nM- motif, known to act as Cu(I) binding site in different proteins. In order to shed more light on this issue, copper(I) and silver(I) interactions with model peptides derived from that region were analyzed. The results of our studies reveal that both metal ions are anchored to two thioether sulfurs of Met109 and Met112, respectively. Subsequent metal interaction and coordination to His96 and His111 imidazoles are primarily found for Cu(I) at physiological pH. Metal binding was also investigated in the presence of negatively charged micelles formed by the anionic surfactant, sodium dodecyl sulfate (SDS). Our results strongly support that metal binding mode strongly depends on the protein backbone structure. In particular we show that α-helix structuring of the amyloid PrP domain influences both the metal coordination sphere and the binding affinity.


Lysosomal Enzyme Glucocerebrosidase Protects against Aβ1-42 Oligomer-Induced Neurotoxicity.
Glucocerebrosidase (GCase) functions as a lysosomal enzyme and its mutations are known to be related to many neurodegenerative diseases, including Gaucher's disease (GD), Parkinson's disease (PD), and Dementia with Lewy Bodies (DLB). However, there is little information about the role of GCase in the pathogenesis of Alzheimer's disease (AD). Here we demonstrate that GCase protein levels and enzyme activity are significantly decreased in sporadic AD. Moreover, Aβ1-42 oligomer treatment results in neuronal cell death that is concomitant with decreased GCase protein levels and enzyme activity, as well as impairment in lysosomal biogenesis and acidification. Importantly, overexpression of GCase promotes the lysosomal degradation of Aβ1-42 oligomers, restores the lysosomal impairment, and protects against the toxicity in neurons treated with Aβ1-42 oligomers. Our findings indicate that a deficiency of GCase could be involved in progression of AD pathology and suggest that augmentation of GCase activity may be a potential therapeutic option for the treatment of AD.


The Non-Steady State Growth of Pearlite outside the Hultgren Extrapolation.
The goal of this paper is to analyse the effect of adding Al on the non-steady pearlite growth occurring in a Fe-C-Mn system. The results are discussed in terms of the partitioning of elements across the austenite/ferrite and austenite/cementite interfaces, and the modification of the pearlite driving force related to the change in carbon activity in austenite.


The different effects of breaking an object at different time points.
Whether the Object-based Correspondence Effect caused by task-irrelevant handles of graspable objects is attributed to the spatial-based or motor-based accounts, or both, has been controversial thus far. In this study, we investigated this question from the time dynamic perspective with the modified stimulus-response (S-R) compatibility paradigm. Specifically, we used three different types of objects in three behavioral experiments: objects with a handle, symmetrical objects, and objects with unilateral protrusion. The objects were broken or remained intact at three different time points (i.e., 50 ms, 150 ms, and 250 ms). The results showed that the object with an intact handle had the correspondence effect at 150 ms, while the correspondence effect disappeared when the handle was broken (Experiment 1). However, no similar pattern was found for symmetric objects (Experiment 2) and objects with unilateral protrusion (Experiment 3). Meanwhile, similar compatibility effects were found in all three experiments when the breakage occurred at 50 ms, which suggests that spatial-based, attention-related factors play a key role in early visual information representation. Our findings suggest that both early spatial-based and later motor-based mechanisms are necessary for the object-based correspondence effect, corroborating the development of visual information representation over time.


Cognitive testing (delayed non-match to sample) during oral treatment of female adolescent monkeys with the estrogenic pesticide methoxychlor.
This report presents preliminary data from a study of endocrine disruption in adolescence. A delayed non-match to sample (DNMS) task was used to assess the effects of the endocrine-active agent methoxychlor (MXC; 0, 25, or 50 mg/kg/day oral administration) in adolescent female monkeys 24-36 months of age (n=7-8/group). The testing utilized an automated touchscreen operant system (Cambridge Neuropsychological Test Automated Batteries [CANTAB]) with abstract, trial-unique visual stimuli. Basic performance of the task was established prior to dosing, training with simultaneous presentation of sample and choice stimuli continued during dosing, and delays (1/2, 1 or 2 s) were introduced near the end of the dosing period. The MXC50 group performed more poorly than controls during delay testing at the end of the dosing period, as well early in training with simultaneous presentation. No interaction between treatment group and delay interval was found. No significant differences from controls were observed at the lower dose (MXC25). Thus, MXC at a daily dose of 50 mg/kg appeared to interfere in a general way with performance of this visual discrimination and memory task. Further investigation will be needed to identify the impairment leading to this performance deficit.


Scleral Flap-Everting Suture for Glaucoma-filtering Surgery.
Most filtering surgery failures develop in the early postoperative period. The possibility to apply an everting suture to lift the flap in the postoperative period and reduce the possibility of an early failure is reported. Surgical technique description. An everting suture may be applied to the scleral flap in all types of ab externo anterior filtering surgeries. It could allow the surgeon to lift the scleral flap after the removal of the releasable sutures. The use of an everting suture would eliminate the need to use procedures for lifting the flap that involve puncturing the conjunctiva and may cause hemorrhages and leakage and promote scarring.


Thrombotic microangiopathy associated with Valproic acid toxicity.
Thrombotic microangiopathy (TMA) is a serious, sometimes life-threatening disorder marked by the presence of endothelial injury and microvascular thrombi. Drug-induced thrombotic microangiopathy (DI-TMA) is one specific TMA syndrome that occurs following drug exposure via drug-dependent antibodies or direct tissue toxicity. Common examples include calcineurin inhibitors Tacrolimus and Cyclosporine and antineoplastics Gemcitabine and Mitomycin. Valproic acid has not been implicated in DI-TMA. We present the first case of a patient meeting clinical criteria for DI-TMA following admission for valproic acid toxicity. An adolescent male with difficult to control epilepsy was admitted for impaired hepatic function while on valproic acid therapy. On the third hospital day, he developed severe metabolic lactic acidosis and multiorgan failure, prompting transfer to the pediatric intensive care unit. Progressive anemia and thrombocytopenia instigated an evaluation for thrombotic microangiopathy, where confirmed by concomitant hemolysis, elevated lactate dehydrogenase (LDH), low haptoglobin, and concurrent oliguric acute kidney injury. Thrombotic thrombocytopenic purpura was less likely with adequate ADAMTS13. Discontinuing valproic acid reversed the anemia, thrombocytopenia, and normalized the LDH and haptoglobin, supporting a drug-induced cause for the TMA. To the best of our knowledge, this is the first report of drug-induced TMA from valproic acid toxicity.


Infectious agents associated with epizootic rabbit enteropathy: isolation and attempts to reproduce the syndrome.
Epizootic rabbit enteropathy (ERE), a highly lethal (30-80% mortality) disease of broiler rabbits aged 6-14 weeks, first appeared in 1997 in French intensive enclosed rabbitries and is of unknown aetiology. Bacteriological, virological and parasitical examination of the intestinal contents of rabbits that had died either in spontaneous field cases or after experimental reproduction of ERE, were undertaken in an attempt to identify infectious agents that may play a role in the disease. Two bacterial strains, Clostridium perfringens and non-enteropathogenic Escherichia coli were repeatedly isolated at high faecal counts from naturally infected animals. In field cases, a correlation between typical gross lesions of epizootic enteropathy and the presence of the alpha toxin of Cl. perfringens was observed (P<0.0001; Chi-squared test). Although attempts to reproduce the disease by inoculation with different pools of cultivable bacterial strains failed, the disease was successfully reproduced by inoculation with one French and two Belgian samples of caecal contents.


E-cadherin cytoplasmic domain inhibits cell surface localization of endogenous cadherins and fusion of C2C12 myoblasts.
Myoblast fusion is a highly regulated process that is essential for skeletal muscle formation during muscle development and regeneration in mammals. Much remains to be elucidated about the molecular mechanism of myoblast fusion although cadherins, which are Ca(2+)-dependent cell-cell adhesion molecules, are thought to play a critical role in this process. Mouse myoblasts lacking either N-cadherin or M-cadherin can still fuse to form myotubes, indicating that they have no specific function in this process and may be functionally replaced by either M-cadherin or N-cadherin, respectively. In this study, we show that expressing the E-cadherin cytoplasmic domain ectopically in C2C12 myoblasts inhibits cell surface localization of endogenous M-cadherin and N-cadherin, as well as cell-cell fusion. This domain, however, does not inhibit myoblast differentiation according to microarray-based gene expression analysis. In contrast, expressing a dominant-negative β-catenin mutant ectopically, which suppresses Wnt/β-catenin signaling, did not inhibit cell-cell fusion. Therefore, the E-cadherin cytoplasmic domain inhibits cell-cell fusion by inhibiting cell surface localization of endogenous cadherins and not by inhibiting Wnt/β-catenin signaling.


Role of KCC2 in the Regulation of Brain-Derived Neurotrophic Factor on Ethanol Consumption in Rats.
Alcohol use disorder (AUD) is a common and complex disorder resulting from repetitive alcohol drinking. The mesocorticolimbic dopamine (DA) system, originating from the ventral tegmental area (VTA) in the midbrain, is involved in the rewarding effect of ethanol. The γ-aminobutyric acid (GABA) neurons in VTA appear to be key substrates of acute and chronic ethanol, which regulates DA neurotransmission indirectly in the mesocorticolimbic system. Despite significant research on the relationship between brain-derived neurotrophic factor (BDNF) and reduced alcohol consumption in male rats involving tropomyosin-related kinase B (TrkB), the mechanisms of BDNF-TrkB regulating alcohol behavior remain scarce. K+-Cl- cotransporter 2 (KCC2) plays a crucial role in synaptic function in GABAergic neurons by modulating intracellular chlorine homeostasis. Here, we found that 4-week intermittent alcohol exposure impaired the function of KCC2 in VTA, evidenced by a lower expression level of phosphorylated KCC2 and decreased ratio of phosphorylated KCC2 to total KCC2, especially 72 h after withdrawal from 4-week ethanol exposure in male rats. CLP290 (a KCC2 activator) reduced excessive alcohol consumption after alcohol withdrawal, whereas VU0240551 (a specific KCC2 inhibitor) further enhanced alcohol intake. Importantly, VU0240551 reversed the attenuating effects of BDNF and 7,8-dihydroxyflavone (7,8-DHF) on alcohol consumption after withdrawal. Moreover, intraperitoneal injection of 7,8-DHF upregulated KCC2 expression and phosphorylated KCC2 in VTA 72 h after withdrawal from ethanol exposure in male rats. Collectively, our data indicate that KCC2 may be critical in the regulating action of BDNF-TrkB on ethanol consumption in AUD.


Dependence of mammalian DNA replication on DNA supercoiling. II. Effects of novobiocin on DNA synthesis in Chinese hamster ovary cells.
Novobiocin, an inhibitor of gyrase-induced DNA supercoiling and DNA replication in prokaryotes, inhibited the incorporation of DNA precursors into DNA in both intact and permeable Chinese hamster ovary cells; much higher concentrations were required for permeable cells, in which no new replicons were initiated. Nucleoids were prepared from cells that were incubated for 60 min with 200 micrograms/ml novobiocin, made permeable, and incubated with 0--50 micrograms/ml ethidium bromide. Sedimentation of the nucleoids in neutral sucrose gradients suggested that the number of supercoils in the average nucleoid had been reduced by prior incubation with novobiocin. In intact cells, novobiocin is required inside the cell for continued inhibition of DNA synthesis, suggesting that it does not act directly on the DNA. Alkaline sucrose gradient profiles of DNA synthesized in the presence of novobiocin in intact cells indicated that the drug inhibited replicon initiation while having little if any effect on chain elongation. These data are consistent with the idea that an activity similar to the bacterial gyrase generates supercoils in mammalian DNA and produces the proper conformation for the initiation of DNA replication.


Synthesis and structural characterization of raffinosyl-oligofructosides upon transfructosylation by Lactobacillus gasseri DSM 20604 inulosucrase.
A new process based on enzymatic synthesis of a series of raffinose-derived oligosaccharides or raffinosyl-oligofructosides (RFOS) with degree of polymerization (DP) from 4 to 8 was developed in the presence of raffinose. This process involves a transfructosylation reaction catalyzed by an inulosucrase from Lactobacillus gasseri DSM 20604 (IS). The main synthesized RFOS were structurally characterized by nuclear magnetic resonance (NMR). According to the elucidated structures, RFOS consist of β-2,1-linked fructose unit(s) to raffinose: α-D-galactopyranosyl-(1 → 6)-α-D-glucopyranosyl-(1↔2)-β-D-fructofuranosyl-((1 ← 2)-β-D-fructofuranoside)n (where n refers to the number of transferred fructose moieties). The maximum yield of RFOS was 33.4 % (in weight respect to the initial amount of raffinose) and was obtained at the time interval of 8-24 h of transfructosylation reaction initiated with 50 % (w/v) of raffinose. Results revealed the high acceptor and donor affinity of IS towards raffinose, being fairly comparable with that of sucrose for the production of fructooligosaccharides (FOS), including when both carbohydrates coexisted (sucrose/raffinose mixture, 250 g L(-1) each). The production of RFOS was also attempted in the presence of sucrose/melibiose mixtures; in this case, the predominant acceptor-product formed was raffinose followed by a minor production of a series of oligosaccharides with varying DP. The easiness of RFOS synthesis and the structural similarities with both raffinose and fructan series of oligosaccharides warrant the further study of the potential bioactive properties of these unexplored oligosaccharides.


Evaluation of the effects of subject thickness on the exposure index in digital radiography.
The exposure index (EI) was proposed as a new X-ray dose index by the International Electrotechnical Commission (IEC) and has since been implemented as an international standard. The EI is calculated by use of an approximation equation under IEC-specified calibration conditions. However, several factors encountered in clinical practice, including the patient's body thickness and the tube voltage, differ with regard to these calibration conditions. We, therefore, require a solid water phantom-based function that can incorporate the IEC-specified conditions and different subject thicknesses to evaluate the effects of subject thickness on the EI. Here, we assumed average thicknesses of 10 cm for a child, 15 cm for slender patients, and 21 cm for an average adult abdomen and we evaluated errors, that are included in the EI, which were calculated by use of the function. Our results suggested that the EI depends on the subject thickness. At the 21-cm thickness (average adult abdomen), the display EI exhibited a small error level. In contrast, EI values calculated from the calibration conditions exhibited maximum errors that were as high as 34 % at the lower subject thicknesses (10 and 15 cm), suggesting a significant influence of the subject thickness on the EI. In conclusion, the EI should be used cautiously during the examination of children and thin patients, with a complete understanding of the discrepancy revealed by our study results.


Bare sclera closure in retinal detachment surgery.
Our modification of the limbal peritomy technique in retinal detachment surgery involved recession of the confunctiva 3 mm posterior to the corneoscleral limbus as the conjunctiva was closed. This recession offered some advantages over the standard nonrecessed method: fewer sutures were required; postoperative ophthalmoscopy was not impaired by conjunctiva swelling over the cornea; the eye was comfortable and quiet in appearance because there was no suture material or inflamed conjunctiva adjacent to the corneoscleral limbus. We have not encountered any disadvantages in several hundred cases.


The utility of adjunctive electroencephalography while performing transcarotid artery revascularization.
Transcarotid artery revascularization (TCAR) has been used as an alternative to carotid endarterectomy and transfemoral carotid artery stenting. Although TCAR has been associated with a decrease in perioperative strokes compared with transfemoral carotid artery stenting, little is known about the safety of cerebral blood during flow reversal or the value of adjunctive electroencephalography (EEG) monitoring in performing TCAR. We describe two cases of EEG changes in patients undergoing TCAR. These cases highlight the use of adjunctive EEG and provide examples of test clamping to assess for compromised collateral cerebral blood flow in patients undergoing TCAR.


Increased expression of long non-coding RNA SBDSP1 correlates with poor survival in colorectal cancer.
Long non-coding RNA SBDSP1 (SBDSP1) had been reported to be increased in colorectal cancer (CRC), but its effects on prognosis were still unclear. The aim of this study was to investigate the clinical significance and prognostic value of the SBDSP1 expression in CRC. The expression levels of SBDSP1 in CRC tissues and adjacent normal tissues were detected using quantitative Real-time PCR (qRT-PCR). The association between SBDSP1 expression and clinicopathological factors as well as survival rates were analyzed. To determine the prognostic value of SBDSP1, univariate and multivariate analysis were performed using the Cox proportional hazard analysis. The relative expression levels of SBDSP1 were significantly higher in CRC tissues than in the matched normal colon tissues (p < 0.01). SBDSP1 expression was significantly associated with differentiation (p = 0.002), depth of invasion (p = 0.007) and TNM stage (p= 0.004). Additionally, patients with higher SBDSP1 expression have significantly shorter disease-free survival (p = 0.006) and overall survival (p = 0.001) compared to those with lower expression. Moreover, univariate and multivariate analysis identified high SBDSP1 expression as an unfavorable prognostic factor for both overall survival and disease-free survival. The present study provides the first evidence that SBDSP1 may be a useful indicator of prognosis in patients with CRC.


Retromandibular Vein, Digastric Muscle, and Greater Auricular Nerve in Superficial Parotidectomies for Patients with Pleomorphic Adenoma-A Surgical Experience.
Retromandibular vein (RMV) and posterior belly of digastric muscle are among the landmarks used to identify facial nerve in parotid surgery. This observational cross-sectional study was done in the Department of ENT &HNS at a tertiary care teaching hospital for a period of 8 years with the aim to aware young otorhinolaryngologist about the relationship of posterior belly of digastric muscle & retromandibular vein with facial nerve and share our experience about preservation of posterior branch of greater auricular nerve. A total of 34 cases of superficial parotidectomies done for pleomorphic adenoma were included in this study. Relationship of facial nerve with retromandibular vein and posterior belly of digastric muscle was noted. Greater auricular nerve was identified, and every attempt was made to preserve its posterior branch. Retromandibular vein was medial to the trunks of facial nerve in 33 (97%) patients. It was lateral to lower division and medial to upper division in one case. Greater auricular nerve was seen to bifurcate into two branches (Anterior and posterior) in 21 (62%) cases while in one case(3%) three branches were seen emerging from main trunk and in another case(3%) first two branches were seen emerging and then anterior branch was further dividing into two. Preservation of posterior branch of greater auricular nerve was possible in 23 (68%) of patients. Posterior belly of digastric muscle was seen as a reliable and constant landmark. Facial nerve was seen superior to upper border of posterior belly of digastric muscle in all cases (100%). No anatomical variation of posterior belly was seen. Retromandibular vein is invariably seen medial to the trunks of facial nerve. Facial nerve is always seen superior to upper border of posterior belly of digastric muscle in almost all cases. Preservation of posterior branch of greater auricular nerve is possible in majority of the cases.


The impact of vaccine failure rate on epidemic dynamics in responsive networks.
An SIS model based on the microscopic Markov-chain approximation is considered in this paper. It is assumed that the individual vaccination behavior depends on the contact awareness, local and global information of an epidemic. To better simulate the real situation, the vaccine failure rate is also taken into consideration. Our main conclusions are given in the following. First, we show that if the vaccine failure rate α is zero, then the epidemic eventually dies out regardless of what the network structure is or how large the effective spreading rate and the immunization response rates of an epidemic are. Second, we show that for any positive α, there exists a positive epidemic threshold depending on an adjusted network structure, which is only determined by the structure of the original network, the positive vaccine failure rate and the immunization response rate for contact awareness. Moreover, the epidemic threshold increases with respect to the strength of the immunization response rate for contact awareness. Finally, if the vaccine failure rate and the immunization response rate for contact awareness are positive, then there exists a critical vaccine failure rate αc > 0 so that the disease free equilibrium (DFE) is stable (resp., unstable) if α < αc (resp., α > αc). Numerical simulations to see the effectiveness of our theoretical results are also provided.


Modified Halsted's operation for inguinal hernia repair: A new technique.
Inguinal hernia is a frequent problem presented to surgical clinic in Iraq. Surgical treatment options for inguinal hernia are numerous, selecting the appropriate method or technique depends on different factors. To find a new technique for open inguinal hernia repair with no recurrence even in recurrent cases, without major complications during or after surgery, and can be used even by new surgeons with little experience. A retrospective cross sectional study conducted in the Medical City teaching hospital and Private Hospitals in Baghdad, during the period from January 1, 2000, to December 30, 2016 on convenient sample of 408 Iraqi patients with inguinal hernia. The patients were treated by modified Halsted's technique by open surgery applying polypropylene mesh. The patients were followed up through frequent visits and phone calls to assess the recurrence and complications. No recurrence of inguinal hernia was reported after 5-10 years follow up, while 94.9% of patients reported postoperative complications commonly oedema of spermatic cord. There was a highly significant association between male gender hernia patients and post Modified Halsted operation complications (p < 0.001). A highly significant association was observed between direct hernia and post Modified Halsted operation complications (p < 0.001). The significant risk factors related to complications were anemia and collagen disease. The modified Halsted's operation for inguinal hernia repair is effective in treatment of inguinal hernia with low recurrence and complications rate.


Positive parental praise: increasing reactivity and accuracy of self-observation.
The parents of a 6-year-old disruptive boy were observed interacting with their son during 20 assessment-oriented, 10-minute experimental sessions. An experimental design consisting of alternately arranged baseline and self-monitoring conditions was utilized. Following the reversal-to-baseline phase, parents were given specialized training in self-recording positive parental praise. Results indicated that (a) self-monitoring of positive verbalizations was an effective means of producing reactive changes in parental behavior, and (b) training in self-monitoring increased parent-observer accuracy scores to more than acceptable levels of agreement. These findings were discussed with regard to the simplicity of a parental self-observational intervention and recommendations were made for continuing investigations in the area.


The diagnostic implications of routine ultrasound examination in histologically confirmed early molar pregnancies.
Early ultrasound examination is being used increasingly in the diagnosis of molar pregnancy. The aim of this study was to examine the diagnostic implications of routine ultrasound examination for histologically confirmed molar pregnancies. This was a retrospective review of sonographic and histological findings in a series of consecutive cases referred to the National Trophoblastic Disease Surveillance Centre with suspected molar pregnancies. In 194 cases referred to the center over a 6-month period in whom results of a preceding ultrasound examination were documented, review of ultrasound findings and final histological diagnosis was carried out. There were 155 cases with a reviewed histological diagnosis of complete or partial hydatidiform mole. In 131 (67%) cases, the sonographic diagnosis was that of a missed miscarriage/anembryonic pregnancy with no documented suspicion of molar pregnancy, referral being on the basis of histological examination of products of conception. In 63 cases, ultrasound examination suggested molar pregnancy; in 53 (84%) of these, the diagnosis of molar pregnancy was correct. Overall, 37 of 64 (58%) complete moles had sonographic evidence of molar pregnancy compared to 16 of 91 (17%) partial moles. Of 155 histologically confirmed complete or partial hydatidiform moles, only 53 (34%) were suspected as molar sonographically. The majority of cases of molar pregnancy now present as missed miscarriage/anembryonic pregnancy sonographically, highlighting the importance of histological examination to diagnose gestational trophoblastic disease.


What Predicts a Mayoral Official's Opinion about the Role of Stress in Health Disparities?
High stress is a public health issue in the United States (US), that disproportionately affects socially-marginalized group members, including racial and ethnic minorities and those of low socioeconomic status. While city governments have the potential to reduce stress exposure and health disparities through municipal policies, very little is known about factors that are associated with mayor officials' beliefs about stress as a determinant of disparities. This information is important because it can inform the design of interventions to educate city policymakers about evidence related to stress and health disparities. Using data from a 2016 survey of 230 mayor officials (101 mayors, 129 senior staff), multivariable logistic regression was used to determine the extent to which respondents' individual characteristics (e.g., ideology, highest level of education) and the characteristics of their city's population (e.g., percentage of residents non-white) were associated with their identification of stress as a factor that has a "very strong effect" on health disparities. Forty-four percent of respondents identified stress as having a very strong effect on health disparities. In the fully adjusted model, every percentage point increase in the proportion of a respondent's city population that was non-White increased the odds of identifying stress as having a very strong effect on health disparities by 2% [adjusted odds ratio (aOR) = 1.02; 95% CI = 1.00,1.04]. Interventions are needed to increase city policymakers' knowledge about the role of stress in the production of health disparities, which could, in turn, help cultivate political will for city policies that reduce disparities.


Further evaluation of prompting tactics for establishing intraverbal responding in children with autism.
We compared prompting tactics to establish intraverbal responding (question answering) in four boys with autism. Based on the results of intraverbal, textual, echoic, and tact pretests, we compared vocal and picture prompts with three participants, and textual, vocal, and picture prompts with one participant. We also evaluated repeated acquisition with different question sets, and included a concurrent-chains arrangement, in which initial link selections determined which prompting procedure occurred in the terminal link. All the prompting procedures were effective in establishing intraverbal responding, but vocal prompts resulted in the fewest trials to criterion for all four participants during the initial prompt comparison. However, the results were less consistent for the second comparison. The concurrent chains arrangement revealed a clear preference for picture prompts for one participant, but the results for the others were inconclusive.


Stability, aggregation, and sedimentation behaviors of typical nano metal oxide particles in aqueous environment.
The wide use of nano metal oxide particles (NMOPs) brings about their inevitable release into the water environment, affecting the environment and human health. Therefore, the stability, aggregation, and sedimentation process of four typical NMOPs (ZnO NPs, CeO2 NPs, TiO2 NPs, and CuO NPs) were investigated in artificial water and real municipal sewage to reveal their complicated behavior. Results showed that NMOPs aggregated at the pH of zero-charge point, and their hydrodynamic diameters and aggregation rates could reach the maximum values. The hydrodynamic diameters and aggregation rates of ZnO NPs, CeO2 NPs, TiO2 NPs, and CuO NPs at the zero-charge point were 617, 1760, 870, 1502 nm, and 31.7, 1158.1, 48.3, 115.7 nm/min, respectively. In addition, the dissolution of NMOPs led to the sedimentation rates under acidic conditions being much lower than those under neutral and alkaline conditions. The aggregation and sedimentation performance of NMOPs were affected by not only pH but also ionic strength (IS) and species. The aggregation rates of NMOPs increased with the increase of IS (0-10 mM), and the maximum aggregation rate of CeO2 NPs was 470.1 nm/min (pH = 7 and CaCl2 = 10 mM). According to Coulomb's law, divalent cations (Mg2+, Ca2+) were more competitively adsorbed on the surface of NMOPs than monovalent cations (K+, Na+), which increased the zeta potential and aggregation rate of NMOPs. Furthermore, the NMOPs were easier to aggregate in municipal sewage because of the homogeneous aggregation between nanoparticles and heterogeneous aggregation with natural colloids. The total interaction energy between NMOPs was calculated by the classical Derjaguin-Landau-Verwey-Overbeek (DLVO) theoretical formula, which was consistent with the experimental results.


Age and evolution of language area functions. A study on adult stroke patients.
This study attempted to verify some of the hypotheses advanced to explain the repeatedly reported finding that non-fluent aphasics are younger than fluent aphasics. One hundred and ninety eight vascular patients with cerebral infarcts documented by CT-scan were investigated. Also in this sample fluent patients were older than non-fluent patients. Age was found not to differ according to lesion site (anterior versus posterior). Patients with extensive lesions were, on average, younger than those with more restricted damage. The most interesting finding was that more than half patients with anterior lesion had fluent aphasia and that were remarkably older than anterior patients presenting with the classical non-fluent picture. It is inferred that anterior language areas undergo some kind of progressive functional evolution with age, though not in the sense postulated by Brown and Jaffe.


Endogenous human skin equivalent promotes in vitro morphogenesis of follicle-like structures.
Three-dimensional constructs formed by cells embedded in an exogenous scaffold could not represent a faithful in vitro replica of native and functional tissues. In this work we produced an endogenous human skin equivalent by means of a tissue engineering process that induces the full morphogenesis of functional dermal and epidermal compartments. In such an organotypic context we demonstrated that -by using adult human skin cells-it is possible to generate follicle-like structures in vitro resembling what occurs in vivo in the fetal skin. Immunotypization evidences an inward-oriented differentiation of the follicular-like structures through immunopositivity for epithelial stem cell markers such as p63 and K19. Moreover we detected the presence of versican within the intricate network of the dermal compartment, suggesting its role as an inductive factor for the morphogenesis of appendage-like structures. These results support the importance of the repository and regulatory role of the endogenous extra cellular matrix in guiding tissue morphogenesis. The microenvironment provided by the endogenous human skin equivalent preserves p63 and K19 positive cells and could finally be involved in: (i) triggering the arrangement of the keratinocytes in follicle-like structures; (ii) promoting the convolute profile of the derma-epidermal junction and (iii) improving epidermis barrier function. We argue that the nature of dermal compartment plays a role in directing epithelial cell fate and function in vitro.


Thermodynamics studies on tyrosine-hydantoin drug-cetyltrimethylammonium bromide mixed micellar system.
In the present paper, we report the micellization, aggregation behavior and thermodynamics of a cationic surfactant viz. cetyltrimethylammonium bromide (CTAB) in absence and presence of tyrosine-hydantoin (TH) drug. The solution behavior of the mixture of CTAB and TH drug has been determined using conductivity, surface tension, UV-visible and fluorescence spectroscopic methods. A strong interaction between the two amphiphiles is indicated from the above measurements. The critical micelle concentration (cmc) of CTAB is found to decrease with increase in the amount of TH in the mixture. The cmc values obtained by these methods are in good agreement with each other. The critical micelle concentration, aggregation number and standard free energy changes of aggregation of the surfactant (CTAB) in aqueous solution in absence and presence of TH are evaluated at different temperatures (294, 303 and 318K). The aggregation number is obtained by the steady-state fluorescence spectroscopic method. Thermodynamic parameters (the standard Gibbs energy change of micellization, ΔG°(m), the standard enthalpy change of micellization, ΔH°(m), the standard entropy change of micellization, ΔS°(m), the standard Gibbs (transfer) energy, (ΔG°(m))(tr)' , and the excess free energy change of micellization, ΔG(ex)) have been evaluated. The negative values of standard Gibbs energy change indicate spontaneous micellization and synergism. The interaction parameter, β(m), activity coefficients (f(1), f(2)) have been evaluated, and using these data we evaluated excess Gibbs energies, which indicate the spontaneity and the stability of the mixed micelles.


Automatic initialisation of buffer composition estimation for on-line analysis of unknown buffer solutions.
An automatic initialisation procedure for extracting useful information about buffer composition from a titration experiment is presented in this paper. The initialisation procedure identifies which buffering components are present in the sample from a relatively long list of buffers expected in the system monitored. The procedure determines approximate pKa values of the buffers and evaluates their maximum and minimum concentrations. This information is then used to start an optimisation procedure to fit the model of the buffer components to the titration data and to accurately determine buffer concentrations and pKa values. The procedure has been integrated as a software layer around the buffer capacity optimum model builder (BOMB) that fits a buffer-capacity model to a measured buffer-capacity curve to estimate model properties (pKa values and concentrations). The reliability and robustness of the resulting buffer capacity software (BCS) were tested using a titrimetric analyser simulator (TAS). The BCS was then validated off-line and on-line.


A quantitative structure property relationship for prediction of solubilization of hazardous compounds using GA-based MLR in CTAB micellar media.
QSPR studies for estimating the incorporation organic hazardous compounds in cationic surfactant (CTAB) were developed by application of the structural descriptors and multiple linear regression (MLR) method. Various structure-related descriptors were studied in order to derive information on hydrophobic, electronic and steric properties of solute molecules. Theoretical molecular descriptors selected by genetic algorithms-procedure were followed to predict logKs values by a stepwise-MLR method. A simple model with low standard errors and high correlation coefficients was selected. It was also found that MLR method could model the relationship between solubility and structural descriptors perfectly. The proposed methodology was validated using full cross validation and external validation using division of the available data set into training and test sets. The squared regression coefficient of prediction for the MLR model was 0.9624. The results illustrated that the linear techniques such as MLR combined with a successful variable selection procedure are capable to generate an efficient QSPR model for predicting the solubility of different compounds. The proposed model can be used adequately for the prediction and description of the solubility of organic compounds in micellar solutions.


N-substituted 2-aminobiphenylpalladium methanesulfonate precatalysts and their use in C-C and C-N cross-couplings.
A series of phosphine-ligated palladium precatalysts based on N-methyl- and N-phenyl-2-aminobiphenyl have been developed. Substitution at the nitrogen center prevents the presence of traces of aminobiphenyls that contain a free -NH2 group from contaminating cross-coupling products. These precatalysts produce N-substituted carbazoles upon activation, which cannot consume starting materials. These precatalysts were efficiently generated from 2-aminobiphenyl with minimal purification and found to be highly effective in Suzuki-Miyaura and C-N cross-coupling reactions.


Drug interventions for prevention of COVID-19 progression to severe disease in outpatients: a systematic review with meta-analyses and trial sequential analyses (The LIVING Project).
To assess the effects of interventions authorised by the European Medicines Agency (EMA) or the US Food and Drug Administration (FDA) for prevention of COVID-19 progression to severe disease in outpatients. Outpatient treatment. Participants with a diagnosis of COVID-19 and the associated SARS-CoV-2 virus irrespective of age, sex and comorbidities. Drug interventions authorised by EMA or FDA. Primary outcomes were all-cause mortality and serious adverse events. We included 17 clinical trials randomising 16 257 participants to 8 different interventions authorised by EMA or FDA. 15/17 of the included trials (88.2%) were assessed at high risk of bias. Only molnupiravir and ritonavir-boosted nirmatrelvir seemed to improve both our primary outcomes. Meta-analyses showed that molnupiravir reduced the risk of death (relative risk (RR) 0.11, 95% CI 0.02 to 0.64; p=0.0145, 2 trials; very low certainty of evidence) and serious adverse events (RR 0.63, 95% CI 0.47 to 0.84; p=0.0018, 5 trials; very low certainty of evidence). Fisher's exact test showed that ritonavir-boosted nirmatrelvir reduced the risk of death (p=0.0002, 1 trial; very low certainty of evidence) and serious adverse events (p<0.0001, 1 trial; very low certainty of evidence) in 1 trial including 2246 patients, while another trial including 1140 patients reported 0 deaths in both groups. The certainty of the evidence was very low, but, from the results of this study, molnupiravir showed the most consistent benefit and ranked highest among the approved interventions for prevention of COVID-19 progression to severe disease in outpatients. The lack of certain evidence should be considered when treating patients with COVID-19 for prevention of disease progression. CRD42020178787.


Publication of European Union research on infectious diseases (1991-2001): a bibliometric evaluation.
The study presented here analyzed the contents of 36 international infectious diseases journals from 1991 to 2001 to determine the number of reports prepared by authors in the European Union and to compare the per country scientific productivity. Articles included in the study were identified using the PubMed website. The number of publications in infectious disease journals produced by authors in the European Union experienced an exponential growth from 461 (19.2% of world production) in 1991 to 2,401 (35.9%) in 2001. The mean impact factor increased from 2.259 in 1991 to 3.001 in 2001. The leading countries in the total number of publications were the UK, France, and Germany. After taking population figures into account, Sweden, Denmark, and Finland headed the list, and after correcting for gross domestic product, the greatest producers were Sweden, Finland, and the UK. Overall, the scientific production and repercussion index of European Union research on infectious diseases experienced a notable rise during the last decade of the 20th century.


A comparative neutron activation analysis study of common generic manipulated and reference medicines commercialized in Brazil.
In this work, a comparative study of neutron activation analysis (NAA) was performed by the nuclear institutes: CDTN/CNEN-Brazil, CCHEN-Chile and the SCK.CEN-Belgium aiming to investigate some generic, manipulated and reference medicines largely commercialized in Brazil. Some impurities such as: As, Ba, Br, Ce, Co, Cr, Eu, Fe, Hf, Sb, Sc, Sm, Ti and Zn were found, and the heterogeneity of the samples pointed out the lack of an efficient public system of quality control.